(Topics in Organometallic Chemistry Vol.2) Shu Kobayashi - Lanthanides - Chemistry and Use in Organic Synthesis - Springer (1999)

Preface
While the lanthanides (strictly defined as the 14 elements following lanthanum

in the periodic table, but as normally used also include lanthanum itself) have
several unique characteristics compared to other elements, their appearance in
the history of the development of organometallic chemistry is rather recent.
Since the f orbitals are filled gradually from lanthanum ([Xe]4f0) to lutetium
([Xe]4f14), they are regarded as the f-block elements, which are discriminated
from the d-block transition elements.
This book was edited as the second volume of “Topics in Organometallic
Chemistry”, aiming at an overview of recent advances of chemistry and organic
synthesis of lanthanides. Since scandium (Sc) and yttrium (Y) (which lie above
the lanthanides and have similar characteristics) are also included, this book
covers rare earth chemistry. Recently, especially in this decade, the chemistry
and organic synthesis of lanthanides have developed rapidly as one of the most
exciting areas. An international team of authors has been brought together in
order to provide a timely and concise review of current research efforts such as
lanthanide catalysis in small molecule organic synthesis especially focused on
carbon-carbon bond-forming reactions, chemistry and organic synthesis using
low-valent lanthanides such as diiodosamarium, asymmetric catalysis, lantha-
nide-catalyzed polymer synthesis, and polymer-supported lanthanide catalysts
used in organic synthesis. Principles of organolanthanide chemistry are summa-
rized in the first chapter. I am sincerely grateful to Drs. R. Anwander, E. C. Dow-
dy, H. Gröger, Z. Hou, H. Kagan, G. Molander, J. L. Namy, M. Shibasaki, Y. Waka-
tsuki, and H. Yasuda for participating in this volume. J. Richmond, J. Sterritt-
Brunner, and B. Benner (Springer) are also acknowledged for encouraging me
to organize this work.
Finally, I hope that this volume is helpful to many researchers and students
who are or will be involved in or interested in this truly exciting and hot field.
Tokyo, December 1998 Shu Kobayashi

Principles in Organolanthanide Chemistry
Reiner Anwander
Anorganisch-chemisches Institut, Technische Universität München, Lichten-

bergstraße 4, D-85747 Garching, Germany
e-mail: [email protected]
During the last decade, the rare earth elements have given enormous stimulus to the field
of organic synthesis including stereoselective catalysis. This article outlines both the basic
and advanced principles of their organometallic chemistry. The intrinsic electronic features
of this 17-element series are reviewed in order to better understand the structural chemis-
try of their complexes and the resulting structure–activity relationships. Particular empha-
sis is placed on synthetic aspects, i.e. optimization of established procedures and alternative
methods with better access to catalytically relevant species. Accordingly, tailor-made ancil-
lary ligands are reported in detail and the reactivity pattern of lanthanide compounds is ex-
amined with representative examples.
Keywords: Lanthanides, Intrinsic properties, Reactivity, Synthesis, Ligands
List of Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Intrinsic Properties of the Lanthanide Elements . . . . . . . . . . 4
2.1 Electronic Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2.2 Steric Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3 Synthesis of Organolanthanide Compounds . . . . . . . . . . . . . 8
3.1 Thermodynamic and Kinetic Guidelines . . . . . . . . . . . . . . . 9

3.2 Inorganic Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.3 Metalorganic Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.4 Thermal Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4 Ligand Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4.1 Steric Bulk and Donor Functionalization . . . . . . . . . . . . . . . 24

4.2 Ancillary Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
4.3 Immobilization – “Supported Ligands” . . . . . . . . . . . . . . . . 31
2 Reiner Anwander
5 Reactivity Pattern of Organolanthanide Complexes . . . . . . . . . 32
5.1 Donor-Acceptor Interactions . . . . . . . . . . . . . . . . . . . . . . . 32

5.2 Complex Agglomerization . . . . . . . . . . . . . . . . . . . . . . . . 37
5.3 Ligand Exchange and Redistribution Reactions . . . . . . . . . . . . 39
5.4 Insertion Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
5.5 Elimination Reactions– Ligand Degradation . . . . . . . . . . . . . . 42
5.6 Redox Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.7 Reaction Sequences – Catalytic Cycles . . . . . . . . . . . . . . . . . 46
5.8 Side Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
6 Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
7 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
List of Abbreviations
Ar aromatic residue
BINOL binaphthol
CN coordination number
COT cyclooctatetraenyl
Cp η5-cyclopentadienyl
Cp* η5-pentamethylcyclopentadienyl
DME 1,2-dimethoxyethane
HMPA hexamethylphosphoric triamide
HSAB hard soft acid base
L ligand
Ln lanthanide (Sc, Y, La, Ce-Lu)
MMA methylmethacrylate
OTf trifluoromethanesulfonato (“triflate”), CF3SO3
Ph phenyl
PMDETA N, N, N’,N’’,N’’-pentamethyldiethylenetriamine
Py pyridine
R residue
salen N,N’-bis(3,5-di-tert-butylsalicylidene)ethylenediamine
Tp tris(pyrazolyl)borate
THF tetrahydrofuran
TMEDA tetramethylethylenediamine
X ligand
Z nuclear charge
Principles in Organolanthanide Chemistry 3
1
Introduction
The rare earth elements constitute an integral part of modern organic synthesis [1].
It was about 30 years ago that the peculiar redox behavior of several inorganic rea-
gents was discovered for selective reductive and oxidative conversions [2]. In the in-
terim period fine chemicals and polymer synthesis have increasingly benefited
from the application of highly efficient organolanthanide precatalysts [3]. Due to
their intrinsic electronic properties expressed in the “lanthanide contraction”, the
rare earth elements comprising the group 3 metals Sc, Y, La and the inner transition
metals Ce-Lu provide new structural and reactivity patterns, emerging in struc-
ture-activity relationships unprecedented in main group and d-transition metal
chemistry. It is also their low toxicity and availability at a moderate price which
makes this “17-element series” attractive for organic synthesis. The spectrum of
rare earth reagents ranges from inorganic to organometallic compounds as sche-
matically redrawn in Fig. 1 with representative examples.
While highly efficient inorganic reagents such as SmI2(thf)2 and Sc(OTf)3 are
already commercially available, the more sophisticated organometallic reagents
are as a rule prepared on a laboratory scale, often under rigorous exclusion of
moisture using inert gas techniques [4]. In particular, the latter class of com-
pounds offers access to tailor-made, well-defined molecular species via ligand
fine-tuning. The consideration of the intrinsic properties of the lanthanide cati-
Cp*2Sm(thf)2 Yb(metal)
Cp*2LnCH(SiMe3)2 SmI2(thf)x
Organometallics Inorganics
"CeCl3/LiCH3" (NH4)2Ce(NO3)6
Ln[N(SiMe3)2]3 pseudo - pseudo- Ln(OTf)3

Organometallics Inorganics
Ln(fod)3 Ln(NTf2)3(H2O)
Na3[La(S)-BINOL]3(thf)6(H2O) Ln[(-)BNP]3
Fig. 1. Rare earth metal reagents in organic synthesis (NTf2=bis[trifluoromethyl)sulfonyl]amide,

(–)BNP=(R)-(–)-1,1’-binaphthyl-2,2’-diylphosphato)
4 Reiner Anwander
ons as well as thermodynamic and kinetic factors are crucial in designing and
synthesizing novel molecular compounds. This article also includes reference to
highly reactive metalorganic compounds, pseudo-organometallics, containing
no direct metal carbon linkage; containing, however, otherwise readily hydro-
lyzable Ln-X bonds. For example, lanthanide compounds such as amide and
alkoxide derivatives not only display important synthetic precursors but also ex-
hibit excellent catalytic behavior in organic transformations [5,6]. Macrocyclic
ligands exhibiting Ln–N and Ln-O bonds are not considered in this survey [7].
The last 20 years have witnessed a rapid development in organolanthanide
chemistry and numerous review articles have been published, emphasizing var-
ious aspects including their use in organic transformations. A comprehensive
list of relevant articles has been given recently [8]. The purpose of this article is
not to give a comprehensive survey of organolanthanide compounds but rather
to address the principles of their chemistry.
2
Intrinsic Properties of the Lanthanide Elements
The rare earth elements represent the largest subgroup in the periodic table and
offer a unique, gradual variation of those properties which provide the driving
force for various catalytic processes. Their peculiar electronic configuration and
the concomitant unique physicochemical properties also have to be consulted
for the purpose of synthetic considerations. The highly electropositive character
of the lanthanide metals, which is comparable to that of the alkali and alkaline
earth metals, leads as a rule to the formation of predominantly ionic com-
pounds, Ln(III) being the most stable oxidation state [9]. This and other intrin-
sic properties are outlined in Scheme 1 which will serve as a point of reference
in this section [10–13].
2.1
Electronic Features
The Ln(III) cations of the series Ce–Lu exhibit the extended Xe-core electronic
configuration [Xe]4fn (n=1–14), a symbol which perfectly pictures the limited
radial extension of the f-orbitals: The 4f shell is embedded in the interior of the
ion, well-shielded by the 5s2 and 5p6 orbitals [14]. A plot of the radial charge den-
sities for the 4f, 5s, 5p and 6s electrons for Gd+ visually explains why Ln(III) cat-
ions are commonly thought of as a “triple-positively charged closed shell inert gas
electron cloud” (Fig. 2) [14].
Ionization energies of the elements [15], optical properties [16], and magnet-
ic moments of numerous complexes [17] prove that the f-orbitals are perfectly
shielded from ligand effects. Consequently, only minimal perturbation of the f-
electronic transitions results from the complexation of dipolar molecules. In
contrast to the broad d→d absorption bands of the outer transition elements,
the f→f bands of the lanthanides are almost as narrow in solid and in solution as
Ln4+ [E0 (M4+/M3+), V] 1.74 3.2 3.1
Ln3+ [10] Sc Y La Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Lu
Ln2+ [E0 (M2+/M3+), V] -1.55 -0.36 -2.1 -1.15
Cation Size (Å) [11] 0.745 1.032 1.01 0.938 0.861

(Ln3+, 6-coordination)
Electronic Configuration [Ar] [Kr] [Xe] [Xe]4f1 [Xe]4f14

(Ln3+)
Lewis Acidity
(Ln3+, relative)
Oxophilicity [12] 165 170 190 188 167 – 136 112 170 144 122 95 159
[D0(LnO), (± 5 kcalmol-1)]
Electronegativity [13] 1.3 1.2 1.1 1.1 1.1
(Pauling)
Scheme 1. Trends within intrinsic properties of the lanthanide elements
Fig. 2. Plot of the radial charge densities for the 4f-, 5s-, 5p-, and 6s-electrons of Gd+ from
[14]
6 Reiner Anwander
they are for gaseous ions. These transitions are “LaPorte-forbidden” and result
in weak intensities which are responsible for the pale color of the trivalent spe-
cies. General principles of d-transiton metal ligand bonding such as σ-donor/π-
acceptor interaction, the “18-electron rule”, and the formation of classic
carbene, carbyne, or carbon monoxide complexes are not observed in lantha-
nide chemistry, neither do they form Ln=O or Ln≡N multiple bonds. However,
the lack of orbital restrictions, e.g. the necessity to maximize orbital overlap as
in d-transition metal chemistry, allows “orbitally forbidden” reactions. Because
of very small crystal-field splitting and very large spin-orbit coupling (high Z)
the energy states of the 4fn electronic configurations are usually approximated
by the Russel–Saunders coupling scheme [18]. The peculiar electronic proper-
ties of the f-elements have proved attractive for numerous intriguing opto- and
magneto-chemical applications (“probes in life”) [15].
The inert gas-core electronic configuration also implies a conform chemical
behavior of all of the Ln(III) derivatives including Sc(III), Y(III) and La(III). The
contracted nature of the 4f-orbitals and concomitant poor overlap with the lig-
and orbitals contribute to the predominantly ionic character of organolantha-
nide complexes. The existing electrostatic metal ligand interactions are reflected
in molecular structures of irregular geometry and varying coordination num-
bers. According to the HSAB terminology of Pearson [19], lanthanide cations are
considered as hard acids being located between Sr(II) and Ti(IV). As a conse-
quence, “hard ligands” such as alkoxides and amides, and also cyclopentadienyl
ligands show almost constant effective ligand anion radii (alkoxide: 2.21±0.03 Å;
amide: 1.46±0.02; cyclopentadienyl: 1.61±0.03) [20] and therefore fit the evalua-
tion criteria of ionic compounds according to Eigenbroth and Raymond [21].
The ionic bonding contributions in combination with the high Lewis acidity
cause the strong oxophilicity of the lanthanide cations which can be expressed in
terms of the dissociation energy of LnO [12]. The interaction of the oxophilic
metal center with substrate molecules is often an important factor in governing
chemo-, regio- and stereoselectivities in organolanthanide-catalyzed transfor-
mations [22]. Complexation of the “softer” phosphorus and sulfur counterions
is applied to detect extended covalency in these molecular systems [23,24].
Scheme 1 further indicates the tendency of the Ln(III) cations to form the
more unusual oxidation states in solution [25]. Hitherto, organometallic com-
pounds of Ce(IV), Eu(II), Yb(II) and Sm(II) have been described in detail [4].
More sophisticated synthetic approaches involving metal vapor co-condensa-
tion give access to lower oxidation states of other lanthanide elements [26].
Charge dependent properties such as cation radii and Lewis acidity significantly
differ from those of the trivalent species. Ln(II) and Ce(IV) ions show very in-
tense and ligand-dependent colors attributable to “LaPorte-allowed” 4f→5d
transitions [16b]. Complexes of Ce(IV) and Sm(II) have achieved considerable
importance in organic synthesis due to their strongly oxidizing and reducing be-
havior, respectively [1,27]. Catalytic amounts of compounds containing the “hot
oxidation states” also initiate substrate transformations. As a rule this implies a
switch to the more stable, catalytically acting Ln(III) species [28].
2.2
Steric Features
Structural changes in homologous rare earth compounds arise from the lantha-
nide contraction [29], i.e. the monotonically decreasing ionic radii with increas-
ing atomic number. The 4f-electrons added along the lanthanide series from lan-
thanum to lutetium do not shield each other efficiently from the growing nuclear
charge, resulting in the contraction phenomenon. It is often this varying cation-
ic size which has a tremendous effect on the formation, coordination geometry
(coordination numbers) and reactivity of their complexes. Reports have accu-
mulated where organic substrates seem to discriminate not only between ligand
environments but also between single lanthanide elements [22]. Successful ex-
planations of these phenomena are based on the systematic theoretical investi-
gation and structural characterization of organolanthanide compounds [4].
Scheme 1 gives the trend of ionic radii of these “large” cations which prefer
formal coordination numbers in the range of 8–12 [30]. For example, consider-
ing the effective Ln(III) radii for 6-coordination, a discrepancy of 0.171 Å be-
tween Lu(III) and La(III) allows the steric fine-tuning of the metal center [11].
The structural implications of the lanthanide contraction are illustrated in Fig. 3
with the well-examined homoleptic cyclopentadienyl derivatives [31]. Three
structure types are observed depending on the size of the central metal atom: A,
[(η5-Cp)2Ln(µ-η5:ηx-Cp)]∞ 1≤x≤2; B, Ln(η5-Cp)3; C, [(η5-Cp)2Ln(µ-η1:η1-
Cp)]∞; these exhibit coordination numbers of 11 (10), 9, and 8, respectively. In
Ln Ln Ln
oligomeric, A (sym., P21/c) monomeric, B (P212121)
CN = 11 CN = 9
decreasing
La Pr Nd Pm Sm Gd Tb Ho Y Er Tm Yb Lu Sc ionic radius
a a a b b,c b b b d d d
CN = 10-11 CN = 8
Ln Ln Ln Ln
oligomeric, A (asym., P21, Pna21) oligomeric, C (Pbc21)
Fig. 3. Coordination modes in homoleptic, ionic LnCp3 derivatives (a belong to space group
P21; b indication from powder diffraction pattern; c show additional modifications Pbcm
and P21/n (contact dimer – effect of crystallization conditions [31b]); d belong to space
group Pna21 and exhibit lengthened intermolecular Ln-C contacts)
8 Reiner Anwander
accord with ionic bonding, small changes in ligand substitution lead to changed
coordination behavior and number (CN=10), as found in the tetranuclear ring
structure of the “MeCp” derivative. Monomeric type B is preferentially formed
with ligands bearing bulky substituents.
High coordination numbers can usually be accomplished in oligomeric struc-
tures or highly solvated complexes. However, both forms are undesirable for
synthesizing highly reactive compounds. The reactivity and stability, respective-
ly, of lanthanide complexes is correlated with the steric situation at the metal
center. Evaluation criteria as the principle of “steric saturation/unsatura-
tion/oversaturation” have been developed to explain the differences in reactivity
[32]. Hence, the main synthetic efforts as in d-metalorganic chemistry are put
into the fine-tuning of the ligand sphere to obtain tractable (volatile, catalytical-
ly reactive, etc.) compounds. Because of the importance of steric factors, ligand
environments have been numerically registrated, e.g. by the “cone-packing
model” [33], which represents a 3-D extension of Tolman’s “cone-angle model”
[34]. In this model, solid angles are calculated from structural data employing
van der Waals radii [35] and considering effects of second order packing. The in-
troduction of steric coordination numbers for various types of ligands based on
solid angle ratios further emphasizes the importance of steric considerations in
organo-f-element chemistry [36].
The Lewis acidity which is affected by the charge density (Z/r) is less distinct
in complexes derived from the large Ln(III) cations. Hence, these systems are of-
ten reported as mild Lewis acidic catalysts in organic synthesis [1]. However,
Sc(III) as by far the smallest Ln(III) cation is located in a “pole position” not only
with respect to Lewis acidity. Its “aluminum/lanthanide/early transition metal
hybrid character” [37] has revealed its superiority in many catalytic applications
[37,38]. Based on their relative preferences for pyridine, Lappert suggested a rel-
ative Lewis acidity scale: Cp2ScMe>AlMe3>Cp2YMe≈Cp2LnMe (here: Ln=large
lanthanide elements) [39]. Maximum electrostatic metal/ligand interaction and
ionic bond strength (enhanced complex stability) is also expected for scandium,
the smallest element. The Ln(III) charge density and the concomitant complex-
ation tendency also prove useful when studying the nature of Ca2+ binding in bi-
ological macromolecules exploiting the lanthanide elements as spectroscopic
and magnetic probes [15].
3
Synthesis of Organolanthanide Compounds
The availability of pure and well-defined starting materials is crucial for
straightforward and high-yield syntheses of organometallic rare earth com-
pounds. The suitability of both synthetic and catalyst precursors can be judged
by the consideration of thermodynamic and kinetic factors. For example, the
knowledge of metal–ligand bond strengths can assist in a better analysis of the
thermodynamics of archetypical ligand exchange reactions and to elaborate the
mechanistic scenarios of catalytic transformations [40].
3.1
Thermodynamic and Kinetic Guidelines
Marks and co-workers provided a most valuable examination of absolute bond

disruption enthalpies of various relevant metalorganic ligands X in Cp*2Sm–X.
The data were obtained by anionic titration calorimetry in toluene (Fig. 4) [41].
Although the Ln–X bonds seem to be thermodynamically very stable, they usu-
ally display kinetic lability due to high ligand exchange ability, chelating and sol-
ubility effects.
Scheme 2 encompasses important synthetic building blocks and preferred
synthetic strategies in organolanthanide chemistry. As acid/base-type exchange
reactions are fundamental, the ligands are depicted according to their increasing
pKa values (in water). This also correlates with the tendency to hydrolyze (orga-
nometallics) or with the competition between solvation and complexation on
the basis of the HSAB concept (inorganics).
The central point in this consideration is the Ln–OH moiety, the preferred
formation of which is called a “dilemma in organolanthanide chemistry”. Orga-
nolanthanide and pseudo-organolanthanide compounds readily hydrolyze
when exposed to air and moisture, with the formation of hydroxide and oxo-
centered ligand cluster intermediates. Lanthanide complexes with Ln–C linkag-
es are considered as “oversensitive” compounds [42]. Even ligands with lower
pKa values than water, as exemplified by substituted phenol ligands, tend to hy-
drolyze in organic solvents because the insoluble hydroxides formed act as a
driving force. However, the presence of hard donor functionalities or multiply
charged anions which are capable of chelation, can afford moisture-stable alkox-
ide and amide complexes, as has been shown for BINOL [43], polypyrazolylbo-
rate [44] and porphyrin-like complexes [45]. Nevertheless, all of the organolan-
thanide complexes should routinely be handled under an inert gas atmosphere
by application of high vacuum and glove-box techniques [46].
Sm—SiH(SiMe3)2
Sm—CH(SiMe3)2
Sm—η3-C3H5
Sm—SnPr
Sm—NMe2
Sm—OtBu
Sm—PEt2
Sm—Br
Sm—Cl
≡
Sm—H
Sm—I
33(2) 43(5) 45(2) 47(1) 48(2) 52(2) 69(2)73(2) 81(1) 84(2) 93 97(3)
D(Ln—TTB) [D(Cp*2Sm-R), (kcalmol-1)]

47(2) [Dy] - 72(2) [Y]
Fig. 4. Bond disruption enthalpies of organolanthanide(III) complexes. The gray area indi-
cates the bond disruption enthalpies of organolanthanide(0) arene species (TTB=η6-
C6H3tBu3-1,3,5)
10 Reiner Anwander
pKa (HL / H2O)
Inorganics Organometallics
Ln–CR3
+50
Ln–H
Ln–NR2
Ln–OR Ln–Cp Ln–

N=R
Ln–OH
15.7 D
A
Ln–acac C
Ln–OAr
Ln–NO3
B
-10
Ln–Hal
Ln–OTf
Scheme 2. Synthetic strategies towards organolanthanide compounds [A: amine elimina-

tion reactions, e.g. silylamide route; B: alkylation via alkoxide precursor, e.g. aryloxide
route; C: alkylation via amide precursor; D: hydrogenolysis of alkyl moieties]
3.2
Inorganic Reagents
Lanthanide halides, nitrates and triflates are not only common reagents in or-
ganic synthesis (Fig. 1) but also represent, in dehydrated form, key precursor
compounds for the more reactive organometallics (Scheme 2). As a rule, in com-
pounds of strong monobasic acids or even superacids, cation solvation competes
with anion complexation, which is revealed by fully or partially separated anions
and solvated cations in their solid state structures. The tendency to form outer
sphere complexation in coordinating solvents [47] is used as a criterion of the
reactivity of inorganic salt precursors in organometallic transformations.
Ln-Halides
Anhydrous lanthanide halides are ionic substances with high melting points
which take up water immediately when exposed to air to form hydrates (I–>Br–
>Cl–) [48]. Straightforward synthetic access and a favorable complexation/solva-
tion behavior make the lanthanide halides the most common precursors in orga-
nolanthanide chemistry. Many important Ln–X bonds (X=C, Si, Ge, Sn, N, P, As,
Sb, Bi, O, S, Se, Te) can be generated via simple salt metathesis reactions [4,8]. The
so-called ammonium chloride route either starting from the lanthanide oxides or
NH4Cl THF
LnCl3(H2O)x LnCl3 LnCl3(thf)x
≈150 °C/10-4 torr, -H2O soxhlet
x = 6,7 ≈ 350 °C/10-4 torr, - NH4Cl x = 1.33-3.5
≈150 °C/10-2 torr, -H2O

[CeCl3(H2O)]n
> 350 °C/10-2 torr, -H2O

"LnOX"
SOCl2, THF
HCl(aq.) - SO2, - HCl
Sc2O3 ScCl3(H2O)6 ScCl3(thf)3
80 °C
Scheme 3. Laboratory procedures for the preparation of lanthanide chloride precursors
the hydrated halides is the most popular laboratory procedure (upscaling is pos-
sible) to anhydrous lanthanide(III) chlorides (Scheme 3) [49]. Simple thermal de-
hydration which works well for lanthanide triflates leads to the formation of un-
desired lanthanide oxychlorides. Evans and co-workers have shown that the
standard recipe for dehydrating CeCl3(H2O)7 to make CeCl3/RLi will produce
[CeCl3(H2O)]n [50]. “CeCl3/RLi” is a popular Grignard-type reagent in organic
synthesis [51] which, for example, increasingly tolerates functional groups.
A coordinating solvent such as tetrahydrofuran (THF) is often necessary to
react the otherwise insoluble lanthanide halides via salt metathesis. These reac-
tions proceed via initial formation of the more soluble compounds LnX3(thf)x,
which are obtained via Soxhlet extraction and are popular, well-defined starting
reagents [52]. The extent of THF coordination depends on both the structural
type of the anhydrous lanthanide halide and the prevailing crystallization con-
ditions, and affects its solubility and hence its reactivity [53]. “ScCl3(thf)3” is
best synthesized by an alternative procedure utilizing SOCl2 as a dehydrating
agent [54]. Neutral donor ligands such as caprolactone [53a], 2,6-dimethyl-4-py-
rone [55] or chelating ligands such as DME [56] and crown ethers [57,58] also
reveal unforeseen and intriguing coordination chemistry.
Other small-scale laboratory procedures have been developed for the direct
synthesis of the more reactive THF adducts, avoiding “inconvenient” high tem-
perature treatment [59–62]. For example, the preparation of “LnCl3(thf)x” from
metal powder and hexachloroethane is facilitated by sonication [Eq. (1)] [59].
Additional metal-based synthetic routes include the redox transmetallation
with mercury(II) halides [Eq. (2)] [60] and the reaction with trimethylsilyl chlo-
ride and anhydrous methanol [Eq. (3)] [61]. Ammonia has been employed as an
alternative donating solvent in the synthesis of lanthanide alkoxides starting
from lanthanide chlorides [63].
THF
2 Ln + C2Cl6 2 LnCl3(thf)x + C2Cl4 (1)
)))
12 Reiner Anwander
+ ICH2CH2I, THF
LnI3(thf)3.5 Ln = Nd, Tm
- CH2CH2
+ 1.5 HgI2, THF

Ln LnI3(thf)3 Ln = Sm, Yb
- 1.5 Hg
+1.5 I2, HOiPr

LnI3(HOiPr)4 Ln = La, Ce, Nd
Scheme 4. Small-scale synthesis of solvated Ln(III) iodides
THF
2 Ln + 3 HgCl2 2 LnCl3(thf)x + 3 Hg
∆
(2)
Ln = Yb (x = 3); Er (x = 3.5); Sm (x = 2); Nd (x = 1.5)
THF
2 Ln + 6 Me3SiCl + 6 MeOH 2 LnCl3(thf)x +
∆
(3)
+ 6 Me3SiOMe + 3 H2
Scheme 4 shows small-scale syntheses of solvated iodides [64–66]. Strongly

donating solvents such as N-methylimidazole (N-MeIm) can accomplish com-
plete anion/cation separation as shown for [Sm(N-MeIm)8]I3 under anaerobic
conditions [67]. The chief factors which affect the often enhanced reactivity of
the higher homologous halides are their higher solubility [48a], a thermody-
namically more labile Ln–X bond (Fig. 4), the soft Lewis basicity of the iodide
anion, and different solubility properties of the eliminated alkali metal salt.
Lanthanide(II) halides, in particular iodides, are prominent synthetic precur-
sors to the corresponding Ln(II) organometallics [32,68,69]. SmI2 is a well-es-
tablished reducing reagent in organic synthesis and is commercially available as
a THF solution and in solid form [27]. Its THF solvate was synthesized according
to Eq. (4) and was structurally characterized as a 7-coordinate SmI2(thf)5 [70].
The less soluble YbI2(thf)2 can be obtained analogously [27] and the ammonia
complex is readily formed according to Eq. (5) [69]. TmI2(dme)3 is the only sol-
uble Tm(II) compound synthesized so far [Eq. (6)] [71]. A large-scale synthesis
of SmBr2 avoiding the expensive metal precursor has been accomplished accord-
ing to the reaction sequence shown in Eq. (7) [68].
THF
Sm + ICH2CH2I SmI2(thf)x + CH2=CH2 (4)
NH3(liq)
Yb + 2 NH4I YbI2(NH3)x + H2 (5)
DME
TmI3 + Tm 2 TmI2(dme)3 (6)
∆
HBraq. methyl orthoformate

Sm2O3 SmBr3x6H2O SmBr3
(7)
Li, THF
SmBr3 SmBr2(thf)x
The complex (pyH)2(CeCl6) has been discussed as an alternative Ce(IV) pre-

cursor [72]. Pseudohalides such as thiocyanates should receive some attention
as specific synthetic precursors due to their dual ligation mode [73]. Like the hal-
ides [74], their Ln(III) derivatives have been successfully employed as catalysts
in organic transformations [75].
Other Inorganic Salts

Alternative inorganic precursors which are referred to in Scheme 2 are also
available by treatment of lanthanide oxides Ln2O3 with the corresponding acid
[76,77]. Nitrate ligands coordinate slightly stronger to the lanthanide centers
compared to halides, but are reported to yield coarse precipitates of alkali ni-
trates in salt metathesis reactions [78]. Nitrates are also preferred as precursors
in macrocyclic chemistry where they preferentially occupy the outer ligation
sphere [7]. Strong complexation of doubly charged anions (CO32–>SO42–) causes
a considerable decrease in solubility of the corresponding Ln2X3 and hence pre-
cludes their broad use as synthetic precursors [77]. Ln-fluorides [79] and phos-
phates are totally insoluble in solvents suitable for organometallics [4,15]. Pseu-
do-inorganic salts derived from superacids, in particular derivatives of triflate,
contain weakly coordinating anions and were often found to be superior to lan-
thanide halides in salt metathesis reactions [80]. Anhydrous Ln(OTf)3 can be
easily obtained by thermal dehydration [Eq. (8)] [81]. Lanthanide triflates have
attracted considerable attention as reuseable Lewis acidic catalysts in numerous
carbon–carbon bond-forming reactions [82].
CF3SO3H, H2O 180-200 °C
Ln2O3 [Ln(H2O)9][CF3SO3]3 Ln(CF3SO3)3 (8)
100 °C, 1h 48h
Rare earth borohydrides obtained from the chlorides [Eq. (9)] [83] have been
used in salt metathesis reactions and were found to be attractive for the genera-
tion of cationic species [84]. The presence of more weakly coordinated BF4– an-
ions in [Eu(MeCN)3(BF4)3]x which can be synthesized according to Eq. (10) pro-
motes several catalytic transformations of non-heteroatom-substituted organic
substrates, including the polymerization of styrene [85].
THF, - 3 NaCl
NdCl3 + 3.3 NaBH4 Nd(BH4)3 (thf)2 (9)
60 °C, 48 h
CH3CN
Eu + 3 NOBF4 [Eu(CH3CN)3(BF4)3]x + 3 NO (10)
rt, 1d
Cerium ammonium nitrate [(NH4)2Ce(NO3)6, CAN], a key oxidizing agent, is the

most common Ce(IV) precursor [86]. The use of acetylacetonates of cerium(IV) has
been discussed [87] and Ce(OTf)4 should also prove to be a valuable precursor [88].
14 Reiner Anwander
Metals
Lanthanide metals which are conveniently prepared from the metal halides are
commercially available in the form of ingots, chips (filings), foils and powders and
are also handled as prominent synthetic precursors. For example, alkoxide com-
plexes derived from cheap and low boiling alcohols are alternatively synthesized
from metals under HgCl2 catalysis [89]. Representative examples for transmetal-
lation and transmetallation/ligand exchange reactions are given in Eqs. (11)–(13)
[90]. Ammonia solutions of ytterbium and europium react with a variety of Brøn-
sted acidic reagents according to Eq. (14) [91]. Metal oxidation/ligand transfer oc-
curs in THF in the presence of catalytic [Eq. (15)] and stoichiometric amounts of
iodine [Eq. (16)] [92]. “Lanthanide Grignard” reagents, formulated as “RLnI” are
prepared in situ from the metal and the alkyl(aryl)halide in THF [Eq. (17)] [93].
Utilization of an extremely bulky alkyl ligand allowed the isolation of
{Yb[C(SiMe3)3]I(OEt2)}2 according to a salt metathesis reaction [94].
THF
Ln + 3 TlCp LnCp3(thf) + 3 Tl (11)
80 °C, 20h
THF
Sm + Hg(C6F5)2 + 2 HNR2 Sm(NR2)2(thf)4 +
12h
(12)
+ Hg + 2 HC6F5
THF
Yb + Sn[N(SiMe3)2]2 Yb[N(SiMe3)2]2(thf)2 + Sn (13)
80 °C, 8h
NH3(liq) HR
Eu Eu2+(NH3)6x2e-(NH3)n EuR2(NH3)m (14)
- H2, -NH3
I2(!), THF, Py
Ln + 1.5 ArSSAr Ln(SAr)3(py)3 (15)
50 °C, 48 h
LaI2(thf)2
THF
2 Ln + Ph + 2 I2 (16)
Ph 50 °C, 48h Ph Ph
LaI2(thf)2
THF
Yb + CH3I CH3YbI (17)
-30 °C
The co-condensation of electron-beam vaporized lanthanide metals with

neutral (hetero-)aromatic molecules or 2,2-dimethylpropylidynephosphine
(tBuCP) affords deeply colored compounds. The isolated, crystalline sandwich
P tBu
P tBu
tBu tBu P
tBu P P
tBu tBu P ScI
tBu
tBu tBu
tBu tBu
tBu Gd0 tBu Ho0 tBu ScII
tBu tBu
tBu tBu tBu I
P Sc P P
tBu tBu P tBu
P tBu
P
tBu
Fig. 5. Arene complexes of low-valent lanthanide elements obtained by co-condensation
methods
and triple-decker complexes are thermally stable and exhibit lanthanide centers
in the formal oxidation states Ln(0), Sc(I) and Sc(II) (Fig. 5) [95].
3.3
Metalorganic Reagents
According to Scheme 2, inorganics and pseudo-inorganics are suitable precur-

sors for a variety of organometallic compounds. However, incorporation of al-
kali metal salts and ate complex formation according to the traditional metathesis
route are often observed. As this is usually an undesired feature and particularly
pronounced in rare earth alkyl [96], amide [97] and alkoxide chemistry [98]
(Sect. 5.1), new synthetic routes involving well-defined metalorganic precursor
compounds have been developed. Considering the (pseudo-)organometallic
side of Scheme 2 (right), usually all of the compounds on this side are able to
produce the neighboring systems on their left by Brønsted acid/base-type reac-
tions, e.g. alkyls might readily react with amines, cyclopentadienes and alcohols
to yield amide, alkoxide and cyclopentadienyl complexes, respectively. Lantha-
nide silylamide and aryloxide moieties qualify as versatile synthetic precursors
due to high-yield and high-purity synthetic procedures. The preparation of their
homoleptic derivatives is shown in Eqs. (18) and (19) [99,100].
1. THF, -3 KCl, 20 °C
LnCl3 + 3 K[N(SiMe3)2] Ln[N(SiMe3)2]3
2. sublimation (18)
pure
1. THF, -3 KCl, 70 °C
LnCl3 + 3 KOAr Ln(OAr)3
2. sublimation (19)
pure
OAr = OC6H3tBu2-2,6; OC6H2tBu2-2,6-Me-4
The Silylamide Route

Rare earth silylamide complexes have not only attracted enormous attention for
the synthesis of precatalyst systems but also for the isolation of well-defined
16 Reiner Anwander
Ln – C≡CR
Ln – Cp
Ln – SnR3
Ln – NR2
Ln – N(SiMe3)2 + HL Ln – PR2 + HN(SiMe3)2
Ln – OR
Ln – SR
Ln – SeR
Ln – TeR
Ln – Cl
Scheme 5. The silylamide route
compounds of relevance in precursor chemistry of ceramic and electronic ma-

terials, such as pure alkoxides [101,102]. The general redox stability of the lan-
thanide cations and the chemical robustness of the silylamide ligand has result-
ed in numerous ligand exchange reactions with substrate molecules of increased
Brønsted acidity such as alcohols, phenols, cyclopentadienyls, acetylenes, phos-
phanes, and thiols as listed in Scheme 5 [103–113].
Factors which often make the silylamide route superior to traditional salt me-
tathesis reactions are (i) the reaction in non-coordinating solvents due to the
high solubility of the monomeric metal amides, (ii) mild reaction conditions of-
ten at ambient temperature, (iii) avoidance of halide contamination, (iv) ease of
product purification [removal of the released amine along with the solvent un-
der vacuum (bp HN(SiMe3)2: 125 °C)], (v) base-free products (coordination of
the sterically demanding, released amine is disfavored), (vi) “quantitative yield”,
and (vii) the facile availability of mono- and heterobimetallic amide precursors.
A limiting factor of this specific amine elimination route is the steric bulk of
the [N(SiMe3)2] ligand, obvious in incomplete exchange reactions with similarly
bulky ligands such as Cp*H [104], HOCtBu3 [114] or highly substituted phos-
phanes [108]. In order to better cope with such sterically suppressed ligand ex-
change reactions the alternative silylamide precursor Ln[N(SiHMe2)2]3(thf)2,
which can be prepared in high yield for all of the lanthanide elements [yttrium:
Eq. (20)] [115], has been introduced.
n-hexane, - LiCl
YCl3(thf)3.5 + 2.9 LiN(SiHMe2)2 Y[N(SiHMe2)2]3(thf)2 (20)
rt, 16h
The bis(dimethylsilylamide) ligand [N(SiHMe2)2] not only favors the attack

of protic reagents by decreased steric bulk, but amine elimination is also affected
by a decreased silylamide basicity, easier workup procedures (bp HN(SiHMe2)2:
93–99 °C) and the presence of an excellent spectroscopic probe (“Si-H”). Ac-
cording to this “extended silylamide route”, catalytically relevant complexes with
salen [116], (substituted) linked-indenyl [117], and sulfonamide ligands [118]
have been synthesized (Fig. 6). Such controlled ligand associations, which are
tBu iPr
iPr
O
S
tBu iPr
O
N O N
N(SiHMe2)2 N(SiHMe2)2
Me2Si Ln N(SiHMe2)2 Ln Ln
thf thf
N N
O
tBu iPr O
S
O
iPr
tBu iPr
Fig. 6. C2-symmetric rare earth complexes according to the extended silylamide route
+ 3 LiCH2SiMe3, + H2L, NMe2

n-hexane, - 3 LiCl - 2SiMe4
ScCl3(thf)3 Sc(CH2SiMe3)3(thf)2 Me2Si Sc
0 °C, 1h rt, 30min
N CH2SiMe3
tBu
Scheme 6. In situ generation of a reactive alkyl precursor
proposed as proceeding via THF dissociation, are not obtained with the
Ln[N(SiMe3)2]3 system.
The application of the more basic Ln(NiPr2)3(thf) as a metalorganic precur-
sor compound is controversial [119] because its availability is hampered by ate
complexation [Sect. 5.1, LiLn(NiPr2)4] and enhanced thermal instability (de-
composition at 100 °C/10–4 Torr) [120]. An efficient alkane elimination reaction
utilizing the in situ formed alkyl species Ln(CH2SiMe3)(thf)2 produced com-
plexes with linked amido cyclopentadienyl ligands (Scheme 6) [121]. However,
the thermal instability of Ln(CH2SiMe3)(thf)2 and ate complex formation seem
to be limiting factors [122].
The silylamide route can also be applied to lanthanide(II) chemistry
(Scheme 7). Although the well-characterized complexes Ln[N(SiMe3)2]2(thf)2
exhibit enhanced steric flexibility [123], the scope of exchange reactions is now
limited by the reductive properties of Sm(II). For example, Sm(II) amides tend
to get oxidized by enolizable alcohols [124]. However, aryloxides of type
Sm(OAr)2(thf)x have been isolated and ate complexation as evidenced in
[KSm(OC6H3-2,6-tBu2)3(thf)]n proves to be a stabilizing factor [125]. According
to this latter approach, mixed metallic complexes can be obtained by retention
of the original metal ligand composition. Partially exchanged heteroleptic com-
plexes such as {KSmCp*2[N(SiMe3)2](thf)2}n are available due to steric restric-
tions [126]. Eu(II) and Yb(II) silylamides are accessible to all of the exchange re-
actions listed in Scheme 5 [127].
18 Reiner Anwander
+ 3n HOAr,
n-hexane
[KSm(OC6H2tBu2-2,6-Me-4)3]n
- 3n HN(SiMe3)2
{KSm[N(SiMe3)2]3}n
(thf)2 (thf)2
K K
+ 3n HCp*,
toluene/THF
Sm Sm
- 2n HN(SiMe3)2,
- HCp*
N(SiMe3)2 N(SiMe3)2 n/2
Scheme 7. Heterobimetallic Sm(II) complexes according to the silylamide route
Organometallic derivatives of europium and ytterbium are also readily

formed via reactions in liquid ammonia. The active species in these reactions are
the hexaammine complexes and the only byproducts are hydrogen and ammo-
nia [Eq. (21a-c)]. According to this procedure, the compounds EuCp2 [128], Yb-
Cp*2(NH3)x [91], Ln(COT) (Ln=Eu,Yb) [129, 130], Eu(C≡CMe)2 [131], Eu(Ph2)2
[132], Yb(OC6H2tBu2-2,6-Me-4)2(thf)3 [90c], LnX2 (Ln=Eu, Yb; X=Cl, Br, I)
[133] and decaborates, e.g. (NH3)xYb(B10H14) [134] have been synthesized.
Ln + m NH3(liq) Ln2+(NH3)6x2e–(NH3)n (21a)
2 HR + 2 e–(NH3)n 2 R– + H2 + n NH3 (21b)
Ln2+(NH3)6 + 2 R– LnR2 + 6 NH3 (21c)
Generation of Lanthanide Alkyl Bonds

Lanthanide alkyl compounds are important alkyl transfer reagents and initiate
a variety of catalytic reactions. The transformation of lanthanide alkoxide bonds
to lanthanide alkyl bonds seems to be an attractive alternative to the alkylation
of lanthanide halides with alkali metal alkyl compounds. For example, the ary-
loxide route affords homoleptic lanthanide alkyls in good yield [Eq. (22)] [135].
n-hexane, - 3 LiOAr
Ln(OC6H2tBu2-2,6)3 + 3 LiCH(SiMe3)2 Ln[CH(SiMe3)2]3 (22)
rt, 30min
Due to the high solubility of the starting and the resulting rare earth complex-
es, the reaction can be conducted in nonpolar solvents from which the insoluble
alkali aryloxides can easily be separated. However, this type of kinetically con-
trolled metathesis reaction is very sensitive towards the reaction conditions in-
cluding the type of alkoxide (aryloxide) ligand, type of metal, number and type
of co-ligands, stability and solubility of the eliminated alkali metal alkoxide
(aryloxide), solvent, temperature, etc. As a result, incomplete ligand exchange,
exchange of the co-ligand, ate complexation, exchange equilibria and ligand re-
distribution can occur. Scheme 8 gives an idea of the complexity of these alkox-
ide-derived alkylation reactions [136–139]. Acetylacetonate complexes have
been discussed as alternative alkyl precursors [87].
Aluminum alkyls, in particular trimethylaluminum, produce chelating alkyl
alkoxide moieties, [(µ-OtBu)AlMe2(µ-Me)], via Lewis acid/base-pair formation
[140,141]. In the reaction with Y3(OtBu)7Cl2(thf)2, AlMe3 simultaneously acts as
a powerful denucleation reagent tolerating ethereal solvents such as THF at the
lanthanide center (Scheme 9). Reaction products such as LnCl3(dme)2 arise from
ligand redistributions (Sect. 5.3). The homoleptic complex Ln[(µ-OtBu)AlMe2
SiMe3
Ar Ar
O O
toluene Sm
Sm(OC6H3iPr2-2,6)3(thf)2 + 3 LiCH2SiMe3 (thf)Li Li(thf)
- LiCH2SiMe3 O
Ar
SiMe3
pentane
Cp*Ce(OAr)2 + 2 LiCH(SiMe3)2 Cp*Ce[CH(SiMe3)2]2 + 2 Li(OAr)
hexane
Cp*Ce(OAr)2 + exc. KCH(SiMe3)2 Cp*Ce(OAr)[CH(SiMe3)2] +
- K(OAr)
approx. 10 % Cp*Ce(OAr)2
hexane
Cp*Y(OAr)2 + 2 MCH(SiMe3)2 Cp*Y(OAr)[CH(SiMe3)2] + M(OAr)
M = Li, K (better yield) + MCH(SiMe3)2
+ 1.6 LiMe,
n-hexane,
- LiOAr Li(OAr)(OEt2) / toluene
Cp*Y(OAr)2 [Cp*Y(µ-Me)2]3 [Cp*Y(OAr)(µ-Me)]2
- 40 °C LiMe / hexane
CpR OtBu CpR

hexane
Y Y + LiCH2SiMe3 “Y(OtBu)3-x(CH2SiMe3)x" + LiCpR
tBuO OtBu OtBu
R=H R = SiMe3
R = Ind
OtBu {[µ-η5:η5-C5H4(SiMe3)]Li}n
tBuO OtBu
Y Li(thf) CH2SiMe3
Li
OtBu tBuO OtBu
O Y
tBuO O (thf)2Li Li(thf)2
Li Li H 2C CH2
Li Si structurally characterized products
OtBu O = OC2H4OMe Me2
Scheme 8. Reaction behavior of lanthanide aryloxide and alkoxide complexes towards alkali
metal alkyl reagents (OAr=C6H3tBu2-2,6)
20 Reiner Anwander
Al thf
RO CH3
CH3 OR
+
R Y
CH3 Y O Al
O OR
CH3 Al R
Al OR CH3
Cl Al
OtBu
Y
tBuO OtBu 3 AlMe3, hexane extract
OtBu Cl hexane
products
Y Y rt, 12h
tBuO THF extract
OtBu OtBu (DME)
thf thf thf
Y3(OtBu)7(Cl)2(thf)2 Cl
Cl R O O
O
Y Al + Y
O O
RO O
R Cl
Cl
thf
Scheme 9. Reaction of AlMe3 with a mixed alkoxide halide cluster
4 MMe3,
- 3 LiCl
Ln[(µ-Me)2MMe2][(µ-Me)(µ-NMe2)MMe2]2 + 0.5 [Me2NMMe2]2
Ln(NMe2)3(LiCl)3 hexane, rt
M
excess MMe3,
H 3C CH3
- 3LiCl
CH3 Ln CH3 + 1.5 [Me2NMMe2]2
M CH3 M
CH3
Ln[(µ-Me)2MMe2]3
Scheme 10. Alkylation of lanthanide amide complexes with group 13 metal alkyls (M=Al, Ga)
(µ-Me)]3 can be obtained as the sole product from the reaction of AlMe3 with
Ln3(OtBu)9 [142].
Extended alkylation is observed when lanthanide amide complexes are used
as synthetic precursors [107,143]. The formation of a strong group 13 metal–
N(amide) bond promotes this type of alkylation reaction. Depending on the sto-
ichiometry, the reaction of MMe3 (M=Al, Ga) with Ln(NMe2)3(LiCl)3 yields
partially or peralkylated species (Scheme 10). Again, the reactivity is
determined by steric factors. For example, the sterically encumbered
La[N(SiMe3)2]3 does not show any tendency to form a Lewis acid/base adduct
with group 13 metal alkyls, a prerequisite for subsequent alkylation under these
conditions [115]. However, peralkylated products are obtained from

Ln[N(SiHMe2)2]3(thf)2, Sm[N(SiMe3)2]2(thf)2, and KSm[N(SiMe3)2]3 [8,115].
Generation of Lanthanide Hydride Bonds

Organolanthanide hydride complexes are also key reagents in rare earth cataly-
sis. The highly reactive lanthanide hydride bonds not only serve as catalytic in-
itiators but are also often assumed key intermediates in catalytic reactions such
as the hydrosilylation [144] and olefin polymerization reaction (β-H elimina-
tion) [145]. The hydrogenolysis of alkyl complexes is a favorable route for syn-
thesizing lanthanide hydride bonds [Eq. (23)] [146]. However, small changes in
the size of the metal, the size of the alkyl group, solvent, degree of association of
the complex, or type of co-ligand cause substantial changes in reactivity
[137,146].
n-hexane
Cp2LnCH(SiMe3)2 + H2 (1 atm) [Cp2Ln(µ-H)]2 + H2C(SiMe3)2 (23)
0 °C, 3h
Although solid state structures of these complexes exclusively display bridg-

ing “Ln(µ-H)nLn” moieties [4], a fluxional behavior in solution with terminal
Ln–H bonds as the reactive species has been suggested [147]. LiAlH4 acts as an
elegant hydride transfer reagent and depending on the nature of the metal and
donor ligand, as well as the cyclopentadienyl substitution, dinuclear species are
formed (Scheme 11) [148]. Similar unsolvated dinuclear species were obtained
from the reduction of alane by Sm(II) organometallics [Eq. (24)] [149]. Lantha-
nide hydride species can also be generated by thermal treatment of lanthanide
alkyl complexes such as Cp2LntBu [150] or by salt metathesis reactions employ-
ing NaH [151]. The thermal decomposition of the sterically crowded lanthanide
alkoxide complex Ln(OCtBu3)3 produced a bridged hydride species as a side
product (Scheme 12) [109].
TMEDA - AlH3(tmeda)
[(C5H4tBu2-1,3)2SmCl]2 + 2 LiAlH4 [(C5H4tBu2-1,3)2SmAlH4]2(tmeda)
- 2 LiCl
+ TMEDA, - AlH3(tmeda)
[(C5H4tBu2-1,3)2Sm]2H[AlH4(tmeda)] [(C5H4tBu2-1,3)2Sm(µ-H)] 2
Scheme 11. Generation of lanthanide hydride bonds via a salt metathesis reaction
90%
0.5 [Ce(OCHtBu2)3]2 + 3 i-C4H8
Ce(OCtBu3)3
150 °C, vacuum 10%
(1/n) [Ce(OCHtBu2)2H]n + 3 i-C4H8 + tBu2CO
Scheme 12. Generation of lanthanide hydride bonds via thermal degradation

22 Reiner Anwander
Et2O,
- 2 Al, - 2 H2
2 (C5H4tBu2-1,3)2Sm(thf) + 2 AlH3(NEt3) (24)
[(C5H4tBu2-1,3)2Sm(µ-H)] 2
Generation of Cationic Organolanthanide Species

Several routes are currently applied to synthesize cationic organolanthanide
species, including the halide abstraction from heteroleptic Ln(III) compounds
[Eq. (25)] [152], the oxidation of divalent metallocenes [Eqs. (26) and (27)]
[153], the protolysis of lanthanide alkyl and amide moieties [Eqs. (28) and (29)]
[154,155], and anion exchange [Eqs. (30) and (31)] [84,156]. In the absence of a
coordinating solvent such extremely electrophilic species attain stabilization via
arene interactions with the BPh4– anion (Sect. 5.1) [153b]. Cationic rare earth
species have been considered as promising candidates for Lewis acid catalysis
[157].
THF, - AgI
[C5H3(SiMe3)2-1,3]2CeI(NCMe)2 + AgBF4
rt (25)
{[C5H3(SiMe3)2-1,3]2Ce(NCMe)2}[BF4]
THF
Cp*2Sm(thf)2 + AgBPh4 [(Cp*2Sm(thf)2][BPh4] + Ag (26)
toluene
Cp*2Sm + AgBPh4 [Cp*2Sm][BPh4] + “black solids” (27)
toluene,
- CH2(SiMe3)2
Cp*La[CH(SiMe3)2]2 + [NHPhMe2]BPh4
(28)
[Cp*LaCH(SiMe3)2][BPh4]
THF, - NMe3
- HN(SiHMe2)2
(salen)Y[N(SiHMe2)2](thf) + [NHMe3]BPh4
rt (29)
[(salen)Y(thf)3][BPh4]
THF
(COT)Nd(BH4)(thf)2 + [NHEt3]BPh4 [(COT)Nd(thf)4][BPh4] +
rt
(30)
+ "[NHEt3]BH4"
1. KL/MeOH, - 2 KCl
SmCl3(H2O)6 [SmL2][BPh4]
2. NaBPh4/H2O, - NaCl (31)
L = tris[3-(2-pyridyl)-pyrazol-1-yl]hydroborate
3.4
Thermal Stability
Despite the kinetic lability of the Ln–X σ-bonds (even the thermodynamically
very stable Ln–OR bond undergoes rapid ligand exchange reactions [158]), or-
ganolanthanide compounds are thermally robust over a wide range of tempera-
ture [99,100,102,104,159–165]. Thermal stability is important for conducting
ligand exchange reactions and catalytic transformations at elevated tempera-
tures [1,22]. The sublimation behavior is a criterion of thermal stability, and is
frequently consulted to judge the suitability of volatile molecular precursors for
chemical vapor deposition techniques (Fig. 7).
Bulky ligands affect the ionic nature of the polarized Ln–X bond by minimiz-
ing polar interactions (intra- and intermolecular) and optimizing volatility by
the concept of steric shielding. The detection of isolated molecules instead of
salt-like arrangements in the solid state confirms this trend. The polarizing ef-
fect can also be reduced by introduction of donor-functionlized ligands which
can bring about charge transfer to the metal cation. Decomposition pathways
can be sterically blocked by filling the coordination sphere of the metal with
large ligands. However, sterically overcrowded ligands may degradate at elevat-
ed temperature as illustrated for the Ln(OCtBu3)3 system [109].
4
Ligand Concepts
Ligand design occupies a pivotal role in organolanthanide chemistry. The nature
of the ligand, including its size, basicity, and functionalization, promptly affects
complex features such as (mono)nuclearity, cation size and electrophilicity. Pro-
lific metal cation/ligand synergisms impart novel reactivity patterns which can
[Y(OCMe2CH2CH2NMe2)3]2
Nd(C5H4CH2CH2NMe2)2Cl
Sm(OC6H3tBu2-2,6)3
Ce(C5H4SiMe3)3
[Nd(OCHtBu2)3]2
[Nd(C5H4Me)3]4
[CeCp*2(µ-Cl)]2
(OEP)Sc(acac)
Ln[N(SiMe3)2]3
"La(OtBu)3"
YbCp2
100 200 300 sublimation temperature
Fig. 7. Sublimation behavior of various lanthanide complexes at 10–3 mbar (OEP 2,3,7,8,12,
13,17,18-octa(ethyl)porphyrin; acac acetylacetonate)
24 Reiner Anwander
R R Do
Do R (L)xMI MI(L)x Do R R
Ln R Ln R Do R Ln R Ln MI
R R R
R R
R R
Do Do Do
MI(L)x
e-homoleptic d-homoleptic ate-e-homoleptic ate-d-homoleptic
Fig. 8. Modes of homoleptic Ln(III) coordination (Do donor functionality)
be of interest in, for example, ligand-enhanced stereoselective catalysis [166].

Therefore, ligand classification and adaptation deserve particular attention.
Assuming the ligand interaction to be of electrostatic origin, optimal charge
balance of the lanthanide(III) cations should be achieved by three stable anionic
ligands. Identical anions accomplish so-called homoleptic systems which can be
of neutral type (MRn)x or ate type [MRn]z–[Xm]z+ [167]. Homoleptic compounds
can be further classified as to whether the ligands are coordinatively equally (e-
homoleptic) or differently (d-homoleptic) attached to the metal center (Fig. 8).
The d-homoleptic mode is found in oligomeric systems where both terminal and
bridging ligands are present; however, they are also found in monomeric com-
plexes which contain functionalized ligands. Here, steric oversaturation can pre-
vent the formation of e-homoleptic coordination [31,168].
Heteroleptic organolanthanide complexes containing reactive Ln–X bonds
and stabilizing ancillary ligands are key precursor compounds in catalytic trans-
formations. Mononuclearity is usually a prerequisite for both good solubility
and reactivity. Utilization of bulky ligands, ate complexation, and donor func-
tionalization are applicable procedures for generating mononuclear complexes.
4.1
Steric Bulk and Donor Functionalization
Scheme 13 emphasizes the effect of sterically demanding groups on the genera-

tion of homoleptic mononuclear complexes. This modification often gives ac-
cess to classes of compounds which are not isolable/defined in the presence of
correspondingly small ligands. Various examples feature both different Ln–X
bonds and different oxidation states [169]. Structurally characterized Ln–C
bonded homoleptic systems include alkyl [94,135], cyclopentadienyl [31,170],
pentadienyl [171], pentamethylcyclopentadienyl [172], indenyl [173], cycloocta-
tetraenyl [80e], (aza)allyl [174] and arene derivatives [26]. Representative exam-
ples of pseudo-organometallics containing Ln–N bonds comprise silylamide,
azabutadiene, benzamidinate and porphyrin complexes [114,175–178]. Aryloxide,
alkoxide, β-diketonate and Schiff base ligands can stabilize homoleptic mono-
nuclear Ln–O derived complexes [101, 179–182]. Derivatives featuring phospho-
rus and sulfur bonds include alkyl phosphides [183] and aryl and alkyl sulfides
[90c,184].
[(η5-C5H5)2Sm(µ-η5:η2-Cp)]∞ Sm[η5-C5(CH3)5]3
[Ln(CH3)3]a Ln{CH[Si(CH3)3]2}3
[Yb(CH3)2]a Yb{C[Si(CH3)3]3}2
[Ln(NMe2)3]a Ln{N[Si(CH3)3]2}3
[Ln(OC6H5)3]b Ln{OC6H2[C(CH3)3]2-2,6-CH3-4}3
[Ln(SC6H5)3]b Ln{SC6H2[C(CH3)3]2-2,4,6}3
Scheme 13. Tractable, mononuclear species via steric cally bulky ligands (acompound not
known/ not stable; bdegree of agglomerization not determined)
The attachment of potentially coordinating groups produces donor-function-

alized ligands and is a popular approach to fine-tuned ancillary ligands. This is
particularly appealing in organolanthanide chemistry [185], considering the
large size of the lanthanide cations and their preference for high coordination
numbers. Intramolecular ring formation via “dative bonds” [186] according to
the HSAB concept stabilizes mononuclear complexes via the effect of chelation
and entropy. Ligand-bonded donor groups successfully compete with donating
solvent molecules for coordination sites, implying improved thermal behavior
by suppressing oligomerization during heating and sublimation. The presence
of intramolecularly active donor functionalities affects the polarity of the lan-
thanide–counterion bond by more or less pushing electron density into the met-
al. As a result strong donor groups will significantly decrease the reactivity of an
adjacent, kinetically labile Ln–X bond, but on the other hand enhance its stabil-
ity against hydrolysis. Hence, the balance of donor strength is important for the
production of a flexible coordination mode, revealed by “arm on – arm off ”
processes. Such hemilabile ligands are proposed as directing the approach of or-
ganic substrates in catalytic transformations [187]. In the absence of ring strain
the bond strength of such an intramolecular coordination resembles that of the
corresponding intermolecular one [188]. For example, the strength of an in-
tramolecular hard “←OR2” coordination will be in the range of 5–7 kcal/mol as
determined for intermolecular THF coordination [41].
Figure 9 outlines general strategies of donor functionalization applied in lan-
thanide alkyl [189–193], amide [194–196] and alkoxide chemistry [180,197,198].
Hard donor functionalities such as NMe2 and OMe dominate this scenario and
it is often the combination of steric bulk and donor ligation which leads to the
envisaged mononuclear species. Donor functionalization of alkyl ligands proved
to be successful even in stabilizing lanthanide alkyl bonds in a low-valent Sm(II)
species [191]. Allylic moieties are also very effective in stabilizing low aggregated
organolanthanide species as evidenced in mononuclear homoleptic phosphi-
26 Reiner Anwander
Me2N
PMe2
SiMe3
Ln–C–R Ln SiMe3 Ln SiMe3
Ln
Si CH3
PMe2
tBuO Me2N
CH3
Me2P CH3 MeO

Si
CH3
Ln–N(P)–R Ln N Ln N Ln P
CH3
Si
Me2N Me2P CH3 MeO
NMe2
– –
Ln–O–R Ln O Ln O Ln O
Si
MeO Me2N
Me2N
Fig. 9. Donor functionalization of monovalent rare earth complexes
PPh2
NMe2
OCH2Ph
H3C
N Si Si
H3C
N
NMe2
MeO
Fig. 10. Functionalization of cyclopentadienyl ligands
nomethanide [199], benzamidinate [200] and azaallyl complexes [177]. Multiple

functionalization displays another option. As revealed in aryl [193] and silylamide
derivatives [195], donor moieties flank the central bonding unit in a potentially
tridentate chelating array.
Not surprisingly, donor functionalization has been extensively applied to tai-

lor cyclopentadienyl ligands (Fig. 10). In addition to the attachment of one pen-
dant donor arm [160, 201], functionalization via donor-linked bis(cyclopentadi-
enyl) ligands [202], including donor-tethered silicon bridges [203], and donor
functionalized chiral side chains are found [204]. Only a few examples feature
soft donor functionalities such as phosphines [205] and arenes [206].
4.2
Ancillary Ligands
Various terms including “spectator ligand”,“auxiliary ligand” or “ancillary ligand”

are used to characterize the portion of the ligand sphere which is not directly in-
volved in basic reactivity steps such as insertion or ligand exchange reactions.
Primarily, ancillary ligands serve to prevent oligomerization or polymerization
of electronically and coordinatively unsaturated derivatives, and to impart ki-
netic stability for otherwise highly reactive species. The mononuclearity, chem-
ical robustness and rigidity anticipated are common attributes of a well-defined
precatalyst system. Furthermore, ancillary ligands can direct catalytic processes
if their bulkiness causes metal shielding and steric constraints, if differently po-
larized Ln–X bonds affect the electrophilicity of the metal center, or if they ex-
hibit a reservoir for chirality and additional flexible coordination sites.
Hence, synthetic organolanthanide chemistry puts the main emphasis on the
adaption of prevailing precatalyst types to the requirements of highly enantiose-
lective catalysis. This is impressively demonstrated by tied-back cyclopentadi-
enyl complexes [207], even water-stable BINOL systems [43], and fluorinated β-
diketonate complexes (Fig. 11) [208].
Cp2Ln(CH3) Ln5(O)(OiPr)13 Ln(thd)3
(thf)2
Na F3CF2CF2C
SiMe3
O O O
Ln N
Me2Si O
SiMe3 O La Eu
H O Na(thf)2 O
(thf)2Na 2 O
O
3
[Me2Si(C5Me4)(C5H3R*)]LnN(SiMe3)2 Na3La[(S)-BINOL)]3(thf)6(H2O) Eu(hfc)3
Fig. 11. Development of sophisticated ligand environments for enantioselective catalysis

[thd 2,2,6,6-tetramethyl-3,5-heptanedione, hfc 3-(heptafluoropropylhydroxymethylene)-d-
camphorato]
28 Reiner Anwander
R R R
N O
Ln Ln Ln
Fig. 12. Amide and alkoxide moieties as cyclopentadienyl-analogous ligands
Cyclopentadienyl derivatives and related systems such as indenyl and fluore-

nyl still play a dominant role in ligand fine-tuning. However, ligand design has
gradually reached a high level of variety and sophistication, e.g. as presented by
the new generation of group 4 metal “non-metallocene” catalysts (for olefin po-
lymerization) [209,210]. In particular, chelating nitrogen-containing counter
ligands have become the focus of much attention [209]. Similar to the related
alkoxide ligands [210], they offer a lower formal electron count, thus rendering
a more electrophilic and therefore potentially more active catalyst fragment
(Fig. 12) [37]. Ancillary ligands, reported for Ln(III) species, can be classified ac-
cording to their charge (valency) and coordination mode (Figures 13–15).
Monovalent Ligands
Numerous mono-charged cyclopentadienyl substitutes have been discussed in rel-
evance to the catalysis topic. The attachment of one or two of such ligands is easily
perfomed and may render two or one reactive sites, respectively. The resulting lig-
and sphere offers enhanced steric flexibility, and kinetic inertness of the monova-
lent ancillary ligand is often achieved via chelation through charge delocalization
or donor functionalization. The stability of the resulting complexes, however, can
be affected by ligand redistribution (disproportionation) and formation of the ho-
moleptic system (Sect. 5.3). A representative selection of this ligand type is shown
(Fig. 13), comprising N,N’-bis(tert-butyl)glyoxaldiimine [(dad)Li]– [211], N-iso-
propyl-2-(isopropylamino)troponimine [(iPr)2ati] [212], substituted benzamidi-
nates [213], substituted tris(pyrazolyl)borates Tp-Rx [214], (N,O-bis(tert-butyl)
(alkoxydimethylsilyl)amide [215], tri(tert-butyl)methoxide (tritox) [102], substi-
tuted aryloxides [137], tri(tert-butyl)siloxide (silox) [102,216] and functionalized
siloxide ligands [217].
Divalent Ligands
Heteroleptic complexes derived from doubly charged, “linked” ligands consti-
tute a class of well-defined metallocene-analogous precatalyst species. Various
C1- and C2-symmetric members of the bis(cyclopentadienyl) fragment have
been reported [218], including linked amido-cyclopentadienyl [219] and dihy-
droanthracene-cyclopentadienyl ligands [220] (Fig. 14). Such divalent ligands
when coordinated in a chelating fashion provide a strongly bonded, rigid back-
bone which not only imparts kinetic stability but is also a prerequisite for asym-
metric induction at the metal center. By nature, the synthesis of these ancillary
ligands is more costly/lengthy and subsequent complex preparations may re-
SiMe3
N N N
N N
LnR2 Li R' N N
H B
N N N N N
SiMe3
Me2N
Me O
Si C O O Si O Si O
Me N
NMe2
Fig. 13. Monovalent ancillary ligands
SiMe3
B
C B
Me3Si C
B
B
Si Ln R C Si (THF)Li
N B
B
Me3Si C
C B
B
SiMe3
Me3Si PhH2C SiPh3

N N
B C Me
BB Si O O O
CH2Ph Me
BB C
Me Si
BB N O O O
B B Me N
Me3Si
SiPh3
N
N N O O
N
N N
Fig. 14. Divalent ancillary ligands

30 Reiner Anwander
quire alternative routes to avoid oligomerization by ligand bridging [116–118].

The remaining Ln(III)–R bond, typically an alkyl, hydride or amide moiety, dis-
plays a reactive site whose kinetic profile can be stabilized upon variation of the
bite angle and chelate ring size of the ancillary ligand, respectively [37]. Together
with diamide [221,222], biphenol or BINOL ligands [223,224], salen [116] and
sulfonamide ligands [118] have been discussed as alternative spectator environ-
ments. The latter can easily be obtained in enantiomerically pure form. Tem-
plate-type ligands such as cyclooctatetraenyl [225] and porphyrin [226] have
been shown to be very effective in stabilizing mononuclear complexes. In par-
ticular, porphyrin–metal moieties are rather robust and less moisture-sensitive.
Carborane derivatives have been employed both in the form of “lithium”-linked
[227] and template-type ligands [228].
Trivalent Ligands
Complexes derived from triply charged ligands formally correspond to the ho-
moleptic tris(cyclopentadienyl) complexes LnCp3. These compounds can be of
relevance in Lewis acid catalysis where their activity is directed by the formation
of Lewis acid (catalyst)/base (substrate) pairs [229]. Hence, metal–ligand bond
disruption and formation processes are pushed into the background. Linked cy-
clopentadienyl-carborane ligands form mononuclear commo (sandwiched)
metallacarborane complexes [230]. Highly functionalized podate ligands such
as triamidoamine (“azatrane”) [231] and tribenzyltrifluoroacetoacetate [232]
produce formally 4- and 6-coordinated complexes, respectively (Fig. 15). A di-
nuclear composition has been proven for Ln(III) complexes of the trivalent oli-
gosilsesquioxane ligand, T7(OH)3 [233]. These incompletely condensed ligands
SiMe2tBu
tBuMe2Si
N
Si N
Ln
C B N
B C
B B B B
B N
B
B B
SiMe2tBu
O
Si
O O
O O
Si O Si
O Si O
Si O
O O O
O O O
O
Si Si F3C O
O CF3
CF3
Fig. 15. Trivalent ancillary ligands

appear to be highly electron withdrawing and are currently being studied as

models for silica surfaces [234].
4.3
Immobilization – “Supported Ligands”
The ligand sphere can also be manipulated by immobilization (grafting) tech-

niques. The surface of an inorganic oxide or an organic polymer then acts as an
alternative ligand environment imposing steric and electronic constraints. The
so-called heterogenization of homogeneous catalysts is a popular method for
the generation of hybrid catalysts, featuring both the advantages of homogene-
ous and heterogeneous catalysis [235]. Figure 16 shows various types of such su-
pramolecular entities which have been successfully employed in catalytic trans-
formations. Neodymium centers bonded to a carboxylated divinylbenzene
crosslinked polystyrene matrix mediate the polymerization of butadiene to cis-
1,4-polybutadiene in the presence of organoaluminum reagents [236]. Polymer-
supported scandium triflate has been employed as a reusable catalyst in several
fundamental Lewis acid catalyzed carbon–carbon bond-forming reactions such
as aldol, Michael, and Friedel–Crafts acylation reactions [237] and the prepara-
tion of diverse quinoline derivatives according to a three-component coupling
reaction [238]. Immobilization techniques such as chemisorbed polyacryloni-
trile derivatives [PA-Sc-TAD, polyallyl scandium trifylamide ditriflate] and mi-
croencapsulated scandium triflate [MC-Sc(OTf)3] have been used. In the latter
hybrid system the Sc(III) is probably stabilized by π-interactions with the poly-
PS CH2 CH Al(iBu)3/AlEt2Cl CH2 CH

x x PA-Sc-TAD
C O CH2NTf
O
Nd1/3 Sc(OTf)2
C3F7
OiPr
C
O Me2HSi Nd
O Eu1/3
O O O
O O O
CH3 Si Si Si
O Si O Si
MCM-41
CH3 CH3
m n
Fig. 16. Heterogenized homogeneous catalysts

32 Reiner Anwander
styrene backbone. Chiral polysiloxane-fixed europium β-diketonates were

found to be reusable catalysts in the Danishefsky hetero-Diels–Alder reaction
[239].
Mesoporous silicates of type MCM-41 display versatile, rigid and thermally
and chemically robust host materials for the grafting of pseudo-organometallic
compounds such as silylamides and alkoxides (Fig. 16) [115,240]. These materi-
als effectively catalyze carbon–carbon bond-forming reactions and functional
group transformations, as shown for the Meerwein–Ponndorf–Verley reduction
[241]. Heterogeneous reactions of lanthanide metals dissolved in liquid ammo-
nia with free hydroxy groups of silica and alumina [242] or zeolites [243] yielded
supported lanthanide species which exhibit catalytic activity in (de-)hydrogen-
ation, isomerization and Michael reactions. Lanthanide amide and imide moie-
ties have been discussed as catalytically active surface species.
5
Reactivity Pattern of Organolanthanide Complexes
The intrinsic properties of the rare earth cations as revealed by their oxophilici-
ty, “hardness”, and large size govern the reactivity of organolanthanide com-
plexes. Hence, parallels to the chemistry of aluminum, the group 2 and group 4
elements, and the actinides are often detected. In this section the most impor-
tant reaction pathways of these highly reactive complexes are surveyed with rep-
resentative examples. The stoichiometric reactions outlined also represent the
elementary steps in catalytic reaction sequences.
5.1
Donor–Acceptor Interactions
The interaction of the hard, Lewis acidic Ln(III) centers with neutral electron-
donating moieties is a ubiquitous feature of organolanthanide complexes. In ad-
dition to the electron deficiency of the lanthanide center, steric unsaturation di-
rects this stabilization of the complexes via adduct formation.
Simple Lewis Acid/Base-Type Interactions

Solvent complexation usually results from salt metathesis reactions which have
been carried out in ethereal solvents such as THF or DME. Solvent coordination
as a rule decreases the reactivity of Ln–R bonds by depolarization, steric satura-
tion, and competition reactions. On the other hand, donor coordination leads to
an enhanced reducing ability of Ln(II) compounds (e.g. HMPA coordination
[244]). Lewis base coordination often forces crystallization (e.g. OCPh2, OPPh3,
TMEDA) [Eq. (32)] [245,246] and strongly donating ligands such as acetonitrile
or pyridine were shown to act as denucleating agents in cyclopentadienyl and
alkoxide chemistry [Eq. (33)] [20,247]. Substituted imidazol-2-ylidenes,
carbene-type ligands, form strong adduct complexes with Ln(II) and Ln(III)
metal centers as indicated by THF displacement [Eq. (34)] [248]. However, coor-
dination of soft Lewis bases was observed in the case of terminally bonded PMe3
in a highly electrophilic scandium complex [Eq. (35)] [249]. Even water com-
plexes could be trapped as the initial step of the hydrolysis reaction [250]. The
vast majority of organic transformations mediated by lanthanide centers de-
pend on pre-coordination of a neutral, functionalized substrate and subsequent
formation of an activated species.
hexane (32)
Ln[N(SiMe3)2]3 + O=CPh2 Ln[N(SiMe3)2]3(O=CPh2)
hexane
[Dy(OCHtBu)3]2 + 4 CH3CN 2 Dy(OCHtBu)3(CH3CN)2 (33)
N
THF
(C5Me4Et)2Yb(thf) + : (C5Me4Et)2Yb(carbene) + THF (34)
N
"carbene"
H2, PMe3,
n-hexane
5 1
2 [(η -C5Me4)SiMe2(η -NtBu)]ScCH(SiMe3)2
-CH2(SiMe3)2
(35)
PMe3
H SiMe2
Me2Si Sc Sc
N H PMe3 N
tBu tBu
The reverse process, desolvation, is often more difficult to achieve. Thermal

treatment (toluene method) [Eq. (36)] [251], intermetallic Lewis acid/base compe-
tition reactions [Eq. (37)] [252,253], and SiMe3I-mediated ring opening [Eq. (38)]
[254] have been applied for THF removal. The two latter variants have been
probed both homogeneously and heterogeneously. Depending on the desolvating
reagent, donor solvent removal is favorably accomplished at an early stage of a
multistep synthesis (Scheme 14) [254].
toluene, - THF
Ce[C5H3(SiMe3)2-1,3]3(thf) Ce[C5H3(SiMe3)2-1,3]3 (36)
∆, vacuum
n-hexane
Ln[N(SiHMe2)2]3(thf)2 + AlMe3 Ln[N(SiHMe2)2]3(thf) + AlMe3(thf) (37)
toluene
Cp*La[CH(SiMe3)2]2(thf) + [Merrifield polymer]-CH2SiMe2I
(38)
Cp*La[CH(SiMe3)2]2 + [Merrifield polymer]-CH2SiMe2O(CH2)4I
34 Reiner Anwander
route A
toluene
Cp*LaI2(thf)3 + excess Me3SiI [Cp*LaI2]n + 3 Me3SiO(CH2)4I
+ 2 K[CH(SiMe3)2], OEt2
Cp*La[CH(SiMe3)2]2
route B
hexane/OEt2
Cp*LaI2(thf)3 + 2 K[CH(SiMe3)2] Cp*La[CH(SiMe3)2]2(thf) + 2 KI
excess Me3SiI, toluene

- Me3SiO(CH2)4I
Cp*La[CH(SiMe3)2]2 [Cp*LaI2]n + 2 Me3SiCH(SiMe3)2
0 °C
Scheme 14. Solvent-free rare earth alkyl species – THF removal at an early stage
Ate Complexation
The formation of anionic rare earth metal ligand moieties or ate complexation
are commonly observed features of salt metathesis reactions when alkali metal
cyclopentadienyl [147], alkyl [96], amide [97,255] and alkoxide derivatives are
employed [Eqs. (39)-(42)] [256].
1. THF
NdCl3 + 2 LiCp* Cp*2 Nd(µ-Cl)2Li(OEt2)2 + LiCl (39)
2. OEt2
THF, PMDETA,
- 2 LiCl
LaCl3 + 3 LiCH(SiMe3)2 La[CH(SiMe3)2]3(µ-Cl)Li(pmdeta) (40)
rt
THF/TMEDA
SmCl3(thf)3 + 2 LiNiPr2 (NiPr2)2Sm(µ-Cl)3Li2(tmeda) (41)
rt, 3h
Me2N
THF, O
- 2 NaCl
LuCl3 + 3 NaO Cl Lu Na (42)
O
Me2N
O
Ate complexation, as main product or as contamination, occurs via coordina-

tion of additional counter ligands or alkali metal halide incorporation. The remov-
al of alkali metal halides can often only be achieved by tedious extraction experi-
ments [257] or in the case of thermally stable compounds via sublimation [258].
Due to the additional electronic and steric saturation of the metal environment,
the reactivity of ate complexes is significantly decreased. Ate complexation can be
(tmeda)
Li (tmeda)
CH3 Li S
CH3 N N S
H3C S
Er Li (tmeda) Nd Li(thf) Yb Li (tmeda)
H 3C CH3 S S
N N
CH3
Li S
Li (tmeda)
(tmeda)
SiMe3
Me3Si
La Y
SiMe3
Me3Si
[Li(µ-C4H8O2)1.5]+ {(Me3SiCH2)x(OtBu)1-xY(µ-OtBu)4[Li(thf)]4(µ4-Cl)}+
Fig. 17. Stabilization of reactive homoleptic complexes via ate complexation
avoided by the application of alternative synthetic procedures such as the silyl-

amide route (Sect. 3.3). Although ate complexation is considered a nuisance for
the preparation of highly reactive lanthanide species, promising synthetic and cat-
alytic behavior has been ascribed. For example, ligand exchange reactions involv-
ing heterobimetallic ate systems can proceed via retention of the metal composi-
tion [125]. Their potential for cation exchange reactions still has to be examined.
Rare earth binolate complexes of the type Na3La[(S)-BINOL]3(thf)6(H2O) effec-
tively catalyze enantioselective carbon–carbon bond-forming reactions [43] and
heterobimetallic complexes containing linked amido-cyclopentadienyl ligands,
Li[Ln(η5:η1-C5Me4SiMe2NCH2CH2NMe2)2], have been reported to be active in the
ring-opening polymerization of lactones and lactides [219].
The stabilization of otherwise labile homoleptic complexes is another useful
option of ate complexation. This can occur via ion pair formation [174,259] or
entrapment of the cationic moieties in the ligand sphere (Fig. 17) [120,184,260].
Neutral π-Donor Ligation – Arene and Olefin Coordination

The coordination of an alkene to an electron-deficient metal center is the pro-
posed preceding step to the insertion into Ln–C, Ln–H and Ln–N bonds
[22,145]. η2-Olefin and alkyne complexes of the lanthanide elements are partic-
ularly unstable due to the lack of dπ-pπ back-bonding to the coordinated alkene
[261–268]. However, tailoring of the olefin environment by maximization of the
Lewis basicity of the alkene [262] or utilizing chelation effects [263] has led to
complexes indentified by structure analysis and NMR spectroscopy, respectively
(Fig. 18). η6-Arene coordination is considerably more stable than η2-olefin co-
ordination and can occur in a mono(arene) [265], bis(arene) (Sect. 3.2) [26] and
intermolecular fashion [247]. Lanthanide π-donor ligation is observed in the ab-
36 Reiner Anwander
CH3
Yb Pt(PPh3)2 Y Yb
CH3
iPr
ArO O Sm
ArO
Cl Cl Sm Cl Cl La
Al iPr N
Al Cl iPr La N
Cl Cl Cl OAr
Cl O
Cl OAr
iPr Sm
Al
Cl Cl
Fig. 18. π-Donor interactions in organolanthanide chemistry
sence of coordinating solvent molecules only. Pseudo-η2-π-bonded complexes

involving hydrogen [266] and nitrogen [267] also show reversible coordination
with Ln(II) fragments. In contrast, the reaction of SmCp*2 with hydrazine pro-
duces a dinuclear Sm(III) complex featuring a bridging (NHNH)2- moiety [268].
Agostic Interactions
The term “agostic” bonding, originally proposed for the formation of two-elec-
tron three-center bonds of the type C–H→M [269], is now often used in lantha-
nide chemistry to describe the interaction of a highly electron-deficient, sterical-
ly unsaturated metal center with “CH”, “SiMe”, and “SiH” ligand fragments.
These intramolecular, chelate-type interactions are of predominantly electro-
static nature (Fig. 19) [270]. Although the agostic bonding is weak and usually
not observed in solution [271], it can have significant implications for the mo-
lecular and electronic structure and hence reactivity of the molecule. The solid
state structures often reveal quite remarkable angle distortions within the agos-
tically interacting fragment. Detailed studies performed on complexes which
are active in olefin polymerization propose that α-C-H agostic interactions as-
sist chain propagation (transition state) [272], while β-C-H interactions retard
ethylene insertion (ground state) [273]. Strong β-Si-H diagostic interactions can
be formed even in the presence of a coordinating solvent. Such potentially tri-
dentate chelating arrays direct the rac/meso ratio in ansa-lanthanidocene com-
plexes [117]. The intramolecular agostic approach is routinely observed in elec-
tron-deficient complexes of the bulky ligand CH(SiMe3)2 [274]. The presence of a
H H tBuH2C
HH C AlMe2 RO OR
Me2Al C O
H H La La
H O
H R
CH2 Nd C tBuH2C
C
Sc H H H O RO O CH2tBu
CH2 H OR
H H R
H C HH C O
H H La La
RO O OR
AlMe2 CH2tBu
Me3Si SiMe3
H
N N SiMe2 SiMe2
H H Me2Si
Me3Si SiMe3
C La C H3C Yb CH3 Me2Si Y N
Me2Si SiMe2 P P SiMe2

CH3 H3C H
Fig. 19. Agostic interactions in organolanthanide chemistry
multi-agostic interaction was proposed in permethylated complexes Ln(AlMe4)3,

yielding formal coordination numbers as high as 18 [275]. The formation of ago-
stic interactions is not restricted to compounds containing metal–carbon bonds,
as evidenced by the ring structure of [La(OCH2tBu)3]4 [276]. Bulky amide and
aryloxide (sulfide) ligands such as N(SiMe3)2 [277], N(SiHMe2)2 [117], and NiPr2
[120] offer another agostic reservoir as emphasized in the important synthetic
precursors Ln[N(SiMe3)2]3 [114] and Ln(OC6H3tBu2-2,6)3 [101].
5.2
Complex Agglomerization
Steric and electronic factors often force the stabilization of monometallic species
via agglomerization. As a rule, the formation of di- and multinuclear species is
achieved by intermolecular bridging of the smallest, most reactive and labile
Ln–X bond and, hence, leads to decreased reactivity.
Dinuclear Complexes
The formation of dinuclear complexes is routinely observed along with the im-
portant class of lanthanidocene complexes of type Cp2LnR when R is a sterically
less demanding ligand such as H, Me or a small alkoxide group [4]. Depending
on the metal and ligand size, bridging can also occur in an asymmetric fashion
as evidenced in [Cp*2Lu(CH3)]2 [Eq. (43)] [145]. The formation of dinuclear lig-
and bridged species is also observed in organo-Ln(II) chemistry. Two represent-
ative examples are given in Eqs. (44) und (45) [127,278]. Rare earth amide and
38 Reiner Anwander
alkoxide complexes show an even more pronounced tendency of agglomeriza-

tion [Eq. (46)] [159].
1. OEt2, - AlMe3(OEt2)
-40°C CH3
Cp*2Lu(µ-CH3)2AlMe2 Cp*2Lu LuCp*2 (43)
2. NEt3, vacuum
CH3
THF I
2 SmI2(thf)2 + 2 KCp* (thf)2Cp*Sm SmCp*(thf)2 (44)
I
+ 2 HOCtBu3,
hexane, CtBu3
- 2 HN(SiMe3)2 O
{Yb[N(SiMe3)2]2}2 (Me3Si)2N–Yb Yb–N(SiMe3)2 (45)
rt, 16h O
Bu3Ct
n-hexane,
- 6 HN(SiMe3)2
2 Lu[N(SiMe3)2]3 + 6 HOCMe2CH2OMe
rt, 16h (46)
(η2-OR)Lu(µ,η2-OR)3Lu(η1-OR)2
Self Assembly – Rings and Clusters

In the absence of strongly coordinating donor molecules, specific ligand ar-
rangements can direct the formation of higher agglomerated systems (Fig. 20).
Depending on the Ln/Cp ratio, the formation of rings (Cp/Ln=2) and clusters
(Cp/Ln<2) can be observed in cyclopentadienyl (pseudo-)halide complexes
[279]. [Cp*2Sm(µ-CN)]6 obtained by a thermal hetero-ligand degradation reac-
tion involving N(SiMe3)CH(Ph)(N=CHPh) is composed of a 18-membered ring,
exhibiting a S6-symmetric chair conformation [280]. In the presence of coordi-
nating isonitrile ligands [Cp*2Sm(µ-CN)(CNc-C6H11)] is formed featuring a 9-
membered ring [281]. Lower Cp/Ln ratios inevitably create further coordination
sites at the metal center and lead to cluster formation. [Cp*6Yb(µ-F)4] (Cp/Ln=
1.2) is a rare example of a ring-cluster hybrid molecule [282]. A highly symmet-
ric icosaeder arrangement of the metal centers was observed in [Cp12Sm12(µ-
Cl)24] (Cp/Ln=1) containing a centered Cl4 tetrahedron [283]. Ring formation is
less predictable in alkoxide chemistry, as revealed by the decameric constitution
of [Y(OCH2CH2OMe)3]10 [284]. In the presence of small charge densities such as
Cl, OH, and O alkoxide, cluster formation is the preferred agglomerization path-
way [285]. A few cluster compounds featuring only amide ligands have been re-
ported [97].
Fig. 20. Self assembly of cyclopentadienyl derivatives – rings and clusters
5.3
Ligand Exchange and Redistribution Reactions
The vast majority of ligand exchange reactions such as salt metathesis, amine
elimination, and hydrogenolysis have already been addressed to in the previous
sections. The high ligand exchange ability is a peculiar feature of lanthanide
complexes and of fundamental importance for their catalytic application. Even
the thermodynamically very strong lanthanide alkoxide and amide bonds are
kinetically labile as found in transamination and transalcoholysis reactions
[158]. Donor ligand exchange as a rule occurs via dissociation processes and the
exchange rate of water has been studied in detail in the context of biologically
and medically relevant processes [286]. Counter ligand exchange proceeds via
40 Reiner Anwander
δ+ δ-
+ HSiPh3 Ln C
pentane - CH2(SiMe3)2
Cp*2LnCH(SiMe3)2 Cp*2LnSiPh3
H Si
δ- δ+
Scheme 15. Ln-C/Si-H transposition in the σ-bond metathesis reaction
H2, c-hexane
[Me2Si(NtBu)(OtBu)]2YCH(SiMe3)2 {[Me2Si(NtBu)(OtBu)]2Y(µ-H)}2
50 °C, 3d
Y[Me2Si(NtBu)(OtBu)]3
Scheme 16. Ligand redistribution (disproportionation) in a heteroleptic alkyl complex
THF hexane extract

{[C5H4(SiMe3)]Y(OtBu)2}2 + 2 LiN(SiMe3)2
[C5H4(SiMe3)]2Y(OtBu)2Li(thf)2 + Y[N(SiMe3)2]3
Scheme 17. Ligand redistribution in a heteroleptic cyclopentadienyl complex
σ-bond metathesis involving four-centered transition states. Such converted

processes are often the proposed key intermediates (turnover-limiting steps) in
hydrogenolysis reactions, and are shown in Scheme 15 for the Si-H/Ln-C trans-
position of the catalytic hydrosilylation reaction [144]. The pronounced elec-
trophilicity of the lanthanide centers mediates the activation of C–H bonds of a
range of hydrocarbons including methane [Eq. (47)] [287]. C-H activation of
propene by organolanthanide hydride systems leads to allyl complexes, an im-
portant deactivation step in organolanthanide-catalyzed propene polymeriza-
tion [Eq. (48)] [147,288]. Thermal treatment of Cp*2LaCH(SiMe3)2 led to ag-
glomerization via intramolecular C-H activation [Eq. (49)] (cf. Sect. 5.5) [289].
benzene
Cp*2LuCH3 + 13CH
4 Cp*2Lu13CH3 + CH4 (47)
pentane
[Cp*2Nd(µ-H)]2 + 3
0 °C, 16h
2 Cp*2Nd + CH3CH2CH3 (48)
c-hexane,
- 4 CH2(SiMe3)2
4 Cp*2CeCH(SiMe3)2 {Cp*3Ce2[µ3-η5,η1,η1-C5Me3(CH2)2]}2 (49)
125 °C, 24h
Ligand redistribution (scrambling, disproportionation) can occur in hetereo-

leptic compounds, the formation of the most stable homoleptic derivatives be-
ing the driving force [Schemes 16 and 17, Eq. (50)] [139,215,290].
toluene (50)
1.5 {Eu[N(SiMe3)2]2(µ-Cl)(thf)}2 2 Eu[N(SiMe3)2]3 + EuCl3(thf)x
5.4
Insertion Reactions
The formal insertion of double and triple bonds into reactive Ln–H, Ln–C, and
Ln–N bonds is of fundamental significance in a large number of catalytic reac-
tions. Direct insertion of olefins such as propene into a Lu–Me bond has been
detected as part of the “lanthanide model for Ziegler–Natta polymerization”
[Eq. (51)] [291]. Alkene and alkyne insertion is also a key step in the hydroami-
nation/cyclization reaction of N-unprotected aminoolefins [292]. Insertion of
polarized double bonds such as carbon monoxide and acetonitrile often leads to
highly functionalized reaction products. Carbon monoxide insertion into lan-
thanide alkyl bonds can occur in a single and multiple fashion with the forma-
tion of η2-acyl and enedione diolate moieties, respectively (Scheme 18) [293].
The insertion of the metal-bonded carbonyl of CpCo(CO)2 into a Sc–Me bond
led to a heterobimetallic system [Eq. (52)] [294]. A non-classical carbocation
species was isolated from the insertion of CO into one cyclopentadienyl moiety
of the sterically crowded complex SmCp*3 [Eq. (53)] [295]. This is a remarkable
reaction promoted by steric constraints. A “Sc-Si(SiMe3)3” moiety mediates the
insertion and coupling of the isocyanide CN(Xyl) (Scheme 19) [296]. The subse-
quent rapid intramolecular rearrangement reactions probably proceed via a re-
active silene intermediate.
CH3
H
c-hexane CH
Lu CH3 + H2C C Lu (51)
CH3 CH2 CH3
C O
toluene
Cp*2Sc–CH3 + CpCo(CO)2 Co Sc (52)
rt, 12h
C O
H 3C
toluene O
Cp*3Sm + 2 CO Sm (53)
rt, 5min
O
42 Reiner Anwander
Lu
O O
tBu O tBu
CO excess CO
Lu Lu C tBu
toluene toluene tBu
THF O
O
Lu
Scheme 18. Single and multiple carbon monoxide insertion into a lutetium alkyl bond
Xyl
CNXyl, N CNXyl,
benzene benzene
Cp2Sc[Si(SiMe3)3](thf) Cp2Sc C
Si(SiMe3)3
Xyl Xyl Xyl
N N SiMe3 N SiMe3
C Cp2Sc
Cp2Sc
Cp2Sc C N Si(SiMe3)2 N
SiMe3 Si(SiMe3)2
N Si
SiMe3
Xyl SiMe3
Scheme 19. Double insertion of CN(Xyl) into a scandium silicon bond (Xyl=C6H3Me2-2,6)
5.5
Elimination Reactions – Ligand Degradation
β-H and β-alkyl elimination have been reported as major decomposition routes
of lanthanide alkyl bonds. These extrusion reactions were initially observed in
Cp*2Ln-R catalysts and can be considered as models for chain termination oc-
curing during propene polymerization [Eqs. (54) and (55)] [297]. The intramo-
lecular ligand metallation and concomitant hydrocarbon extrusion found in
amide templated complexes depend on the metal size and alkyl ligand
(Scheme 20) [298]. Silylamine fragmentation has been observed along with the
synthesis of the alkoxide complexe Tm(OCtBu3)3 according to the silylamide
route [Eq. (56)] [114]. In corresponding exchange reactions with excess of fluor-
inated alcohols HORF, ammonia is the final degradation product of the si-
THF, toluene,
- MCl -RH
LnCl[N(SiMe2CH2PMe2)2]2 + MR LnR[N(SiMe2CH2PMe2)2]2
rt, 20min ∆
MR = PhLi, PhCH2K; Ln = La, Y, Lu

Me2 Me2
Si Si
N
CH
Me2P
Y PMe2
Me2P PMe2
N
Si
Si Me2
Me2
Scheme 20. Thermally induced intramolecular alkane (benzene) elimination
lylamine, trapped as an ammine complex. The bulkiness and the basicity of the
alkoxide ligand, and the type of solvent, effect the ammonia formation [299].
Due to its relevance to the conversion of oxofunctionalized substrates the unex-
pected cleavage of acetylacetone in the presence of an yttrium alkoxide is shown
in Eq. (57) [300].
c-hexane
Cp*2LuCH2CH(CH3)2 Cp*2LuH + CH2=C(CH3)2 (54)
c-hexane
Cp*2LuCH2CH(CH3)2 Cp*2LuCH3 + CH2=CH(CH3) (55)
- HN(SiMe3)2
2 Tm[N(SiMe3)2]3 + 6 HOCtBu3
(tBu3CO)3Tm (56)
SiMe2
H 2N CH2 NH2
SiMe2
Tm(OCtBu3)3
toluene
Y5O(OiPr)13 + excess Hacac
20 °C, 24 h
CH3
H 3C CH3
O OH2
O O CH3
H3C (57)
O O O
Y Y
O O O
H3C O O O CH3
H2O
H 3C CH3
H 3C
44 Reiner Anwander
5.6
Redox Chemistry
Kagan and co-workers pioneered the work on the reductive behavior of the low
oxidation states of the lanthanide elements in organic synthesis [2b]. Ln metals
and Ln(II) derivatives were subsequently found to promote a number of impor-
tant individual reactions [301]. “The combination of one- and two-electron
chemistry sets SmI2 apart from virtually every other reductive coupling agent
currently available” and exhibits exceptional properties for sequential conver-
sions tolerating unprotected functional groups [1b].
Evans and co-workers have worked out the peculiar reducing ability of Sm(II)
with the corresponding organometallic reagents, in particular Cp*2Sm(thf)x,
and characterized many metal-bonded products by X-ray crystallography [32].
Their standard reagent is readily oxidized by oxygen to form an oxo-bridged
dimer [Eq. (58)] [302]. In contrast, the tris(3,5-dimethylpyrazole)hydroborate
ligand produces a superoxo complex under an atmosphere of oxygen [Eq. (59)]
[303]. Again, steric and electronic constraints at the metal center, induced by the
ligand environment, seem to force this different reaction behavior. Examples of
the unique reductive potential of Cp*2Sm include the functionalization of un-
saturated hydrocarbon substrates with carbon monoxide (Scheme 21) [304, 305].
toluene
Cp*2Sm(thf)2 + O2(g) Cp*2Sm O SmCp*2 (58)
rt
toluene O
Sm(TpMe2-3,5)2 + O2(g) (TpMe2-3,5)Sm (59)
-78 °C → rt
O
Ph Cp*2SmO H
CH CH
Ph
CO (90 psi), hexane, 24 h
thf H OSmCp*2
Sm
thf Ph
Ph
N N O N
Ph C
Cp*2Sm
CO (90 psi), THF, 24 h SmCp*2
C
N O
Ph
Scheme 21. The reductive potential of Cp*2Sm(thf)2

The reaction of one-electron reducing agents with ketones yields radical ani-
ons (ketyls) which are key intermediates in a variety of carbonyl group transfor-
mations. Reduction of aromatic ketones by low-valent samarium and ytterbium
compounds [Ln metal and Ln(II)] allowed the first trapping of these radicals in
the coordination sphere of a metal [306]. The isolation of an Yb(II) benzophe-
none dianion [Eq. (60)] [307], a lanthanoid-imine azametallacyclopropane
complex [Eq. (61)] [308], and a heteroleptic fluorenone ketyl organosamar-
ium(III) complex [Eq. (62)] [309] by Hou and co-workers emphasize the useful-
ness of hexamethylphosphoramide (HMPA) and sterically demanding groups as
stabilizing ligands. The reaction of La[η5-C5H3(SiMe3)2-1,3] with a potassium
mirror in dimethoxyethane produced a lanthanocene(III) methoxide complex
via persistent paramagnetic La(II) intermediates (Scheme 22) [310].
Ph
Ph
O O
THF/HMPA
2 Yb + 2 C (hmpa)2Yb Yb(hmpa)2 (60)
rt, 1h
Ph Ph O
Ph Ph
Ph
Ph
N N
THF/HMPA
Yb + C Yb(hmpa)3 (61)
rt, 4h
Ph Ph
Ph Ph
THF O (62)
Cp*2Sm(thf)2 + Sm
rt, 2h
thf
O
K(mirror), DME
LaCp''3 [K(dme)x][LaCp''3] [LaCp''2(dme)y] + [KCp''(dme)z]
1. -40 °C, 3h
2. rt, 45h
[LaCp''2(µ-OMe)]2 + ?
- KCp''
Scheme 22. Generation of low-valent lanthanum reaction intermediates [Cp''=C5H3(SiMe3)2-1,3]

46 Reiner Anwander
Only a few complexes containing Ce(IV)–carbon bonds have been structural-

ly characterized so far. Salt metathesis reactions utilizing mixed alkoxide nitrate
Ce(IV) precursors [Eq. (63)] [311], as well as the oxidative salt elimination of
K[Ce(COT)]2 ate complexes with silver iodide, led to isolable organocerium(IV)
species [Eq. (64)] [80e]. The oxidation of the homoleptic Ce(III) alkoxide
Ce(OCtBu3)3 with benzoquinone yielded a dinuclear heteroleptic Ce(IV) com-
plex [Eq. (65)] [312].
THF
2 Ce(OtBu)(NO3)3(thf)2 + 6 NaCp Cp2Ce(OtBu)2 +
+ 6 NaNO3
+ other products
(63)
+ Ce
OtBu
THF,
- Ag, - KI
K{Ce[C8H5(SiMe3)3-1,3,6]2} + excess AgI
rt, 1h
SiMe3
Me3Si
(64)
SiMe3
Ce
Me3Si
SiMe3
Me3Si
benzene
2 Ce(OCtBu3)3 + C6H4O2
rt, 30min
Ce(OCtBu3)3 (65)
O O
(Bu3CtO)3Ce
5.7
Reaction Sequences – Catalytic Cycles
The vast majority of the reaction pathways outlined in the preceding sections
can be rediscovered as basic steps in many organolanthanide-mediated organic
transformations. The well-examined mechanistic scenarios shown as follows
Cp'2Ln N(SiMe3)2
R R
H2N
HN(SiMe3)2
R
R
H2
N
H R R
N
* Cp'2Ln
H 2N
HN
R R
R R
R R
NH2
R R
R R
H2 H2
N N
H H
Cp'2Ln N Cp'2Ln N R
*
R
R
R
Scheme 23. Organolanthanide-catalyzed hydroamination
with the hydroamination (Scheme 23) [218a,292], Michael addition (Scheme 24)
[313], and MMA polymerization reactions (Schemes 25 and 26) [314,315] sum-
marize this section.
5.8
Side Reactions
The intrinsic properties and concomitant high reactivity of organolanthanide

moieties often lead to unforeseen and undesired products under the prevailing
reaction and storage conditions and, finally, some of these cause accidental re-
actions such as ether cleavage [Eqs. (66)–(68)] [94, 177,316–318], carbon diox-
ide insertion [Eq. (69)] [319], or partial hydrolysis [Eq. (70)] [320]. Cluster for-
mation [285] of complexes containing small alkoxide ligands is often observed
in the presence of traces of water and proceeds via hydrolysis/dehydration/
dealkoxylation processes [Eq. (71)] [321]. In these systems the oxo and hydroxo
moieties occupy central cluster positions where they can accomplish high metal
coordination (CN=6).
48 Reiner Anwander
O
O (thf)2
Na
O
O O +
H OMe O O
O Ln O
OMe MeO OMe
(thf)2Na H2O O Na(thf)2
O O
MeO
(thf)2Na (thf)2Na
O
* O
* O
O O
O Na(thf)2 O Na
O OMe
* Ln O
* Ln O
O OH O OH
O O
(thf)2Na H (thf)2Na
* O O
*
MeO OMe
Scheme 24. Heterobimetallic multifunctional catalysis of a Michael reaction by Na3[La(S)-

BINOL]3(thf)6(H2O)
OMe OMe
O C O C Me
MMA
Sm Me Sm Me CH2R
R CH2
C CH2
O C
R = H, Me OMe
OMe OMe
Me O C Me
O C
CH2R
MMA
Sm CH2 Sm
CH2
Me Me
O C O C
COOMe
C C C
Me
H2 CH2R
OMe OMe
Scheme 25. Organolanthanide(III)-catalyzed methylmethacrylate polymerization

O
2 MMA
2 Sm(II) 2 OMe Cp*2Sm(III)
MeO Sm
O
2n-2 MMA
O
Sm OMe
CO2Me Sm
MeO O
n n
O MeO2C OMe
Sm
"link"-functionalized polymers
Scheme 26. Organosamarium(II)-initiated methylmethacrylate polymerization
benzene,
- HC(SiMe3)3, - C2H4
Yb[C(SiMe3)3]2 + 2 Et2O 0.5 [C(SiMe3)3Yb(µ-OEt)(OEt2)]2 (66)
20 °C
toluene, - THF
Cp2Yb(CH3)(thf) / LiCl(thf)x [Cp2Yb(µ-OCH=CH2)]2 (67)
reflux , 72 h
O
Me2Si SiMe2 THF
[Cp*2Sm(µ-H)]2 +
O O Me2 Me2
Si O Si Si O (68)
Me2 O
Cp*2Sm SmCp*2
thf thf
THF / CO2 (dry ice)

- 2 NaCl, - 2 LiCl
YCl3 + 2 NaCp + Li(CH2)3NMe2 (69)
O
NMe2
Cp2Y
O
50 Reiner Anwander
crystallization
hexane / H2O (traces)
2 (C5H4tBu)3Ln [(C5H4tBu)2Ln(µ-OH)]2 + 2 HCptBu (70)
-35 °C
toluene, -THF
3 Ce(OtBu)4(thf)2 Ce3(OtBu)10O (71)
rt, 2-3d
6
Perspectives
Examples of the exceptional and intriguing potential of rare earth reagents in or-
ganic synthesis will be treated in comprehensive form in the following chapters
of this volume. The text of this chapter on “Principles in Organolanthanide
Chemistry” has been directed towards a basic understanding of the chemistry of
the most reactive members of this family. Improved and alternative synthetic
procedures ensure the availability of both inorganic and organometallic rea-
gents in pure and well-defined form. Each of the important areas of reactivity of
organolanthanide compounds which have been addressed to in this survey
should prove fertile for further development. Examination of such highly reac-
tive species will provide important details to explain the reaction pathways of
the inorganic reagents in organic synthesis by means of spectroscopy and struc-
ture determination. So far, the vast majority of active components and reaction in-
termediates is under-determined due to the application of in situ reaction se-
quences. The operating system is often a “black-box” and process optimization
is achieved by empirical methods. This dearth of data of the active components
should further stimulate the interaction between organic synthesis and organo-
metallic chemistry. On the other hand, chiral organometallic and pseudo-orga-
nometallic reagents challenge the field of enantioselective catalysis. For this rel-
atively young branch of lanthanide chemistry, ligand design has become indis-
pensable. Since rare earth ligand interactions are ruled by simple principles such
as ionic bonding and the HSAB theory, combinatorial chemistry could prove a
valuable tool for ligand fine-tuning. In addition to the evaluation of novel ancil-
lary ligand sets, detailed studies on supramolecular rare earth chemistry are to
be expected, tackling host-guest interactions [322], the topic of immobilization
[235], and dendrimer chemistry [323]. Clearly, organolanthanide chemistry has
much to offer to the field of organic synthesis.
7
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Lanthanide- and Group 3 Metallocene Catalysis in
Small Molecule Synthesis
Gary A. Molander* and Eric D. Dowdy
Department of Chemistry and Biochemistry, University of Colorado at Boulder,

Boulder, CO 80309–0215 USA
* e-mail: [email protected]
Although the polymerization prowess of organolanthanide complexes has been known for
some time, efforts to apply these catalysts to small molecule synthesis have only recently be-
gun. The selectivity of these metallocenes is predominantly steric in nature, and they are
compatible with a wide variety of organic functional groups. A review of their use in olefin
hydrogenation, hydrosilylation, and polyene cyclization with emphasis on chemoselectivity
and diastereoselectivity is presented here. The various ways in which the catalysts and rea-
gents can be tuned to produce the desired products is also discussed.
Keywords: Metallocenes, Catalysis, Cyclization, Hydrogenation, Silylation
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
2 General Features of the Catalytic Systems and the

Olefin Insertion Reaction . . . . . . . . . . . . . . . . . . . . . . . . 121
3 Catalytic Hydrogenation Reactions . . . . . . . . . . . . . . . . . . 123
4 Catalytic Hydrosilylation Reactions . . . . . . . . . . . . . . . . . . 127
4.1 Silylation of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

4.2 Silylation of Alkynes . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
5 Catalytic Cyclization Reactions . . . . . . . . . . . . . . . . . . . . . 133
5.1 Termination by β-Hydride Elimination . . . . . . . . . . . . . . . . 134

5.2 Termination by Hydrogenation . . . . . . . . . . . . . . . . . . . . . 135
5.3 Termination by Silylation . . . . . . . . . . . . . . . . . . . . . . . . 136
5.3.1 Cyclization/Silylation of Terminal Dienes and Trienes . . . . . . . . 137
5.3.2 Cyclization/Silylation of Hindered Dienes and Trienes. . . . . . . . 145
5.3.3 Cyclization/Silylation of Enynes and Dienynes . . . . . . . . . . . . 147
6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
7 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
120 Gary A. Molander, Eric D. Dowdy
1
Introduction
Carbon-carbon bond-forming reactions constitute the heart and soul of syn-
thetic organic chemistry. Nowhere are these reactions more prolific than in com-
mercial polymerization reactions, where worldwide production of polyethylene
and polypropylene is carried out on enormous scale. The polymerization of α-
olefins employing Ziegler-Natta catalysts [1], organolanthanides and group 3 or-
ganometallics [2], palladium and nickel cationic complexes [3], and related cat-
alysts [4] have revolutionized the controlled synthesis of polymers derived from
terminal alkenes. Group 3 organometallics and organolanthanides in particular
are among the most active known catalysts in olefin polymerization chemistry
[5]. However, in spite of the spectacular ability of these complexes to generate
new carbon-carbon bonds in polymerization reactions, relatively little effort has
been made in applying these catalytic systems to small molecule synthesis
through cyclization reactions of dienes, enynes, and related substrates
LnCp*2 FG
cat. "Cp*2LnH"
n( ) (1)
n( ) n( )
To be sure, the extrapolation of reactivity from ethylene and propylene to

highly functionalized organic molecules is daunting, and many questions arise
concerning the suitability of the aforementioned catalysts within this context.
For example, only recently have available catalysts been able to polymerize any-
thing but monosubstituted alkenes. Even allylic substitution of such alkenes has
presented difficulties for the sterically sensitive organometallic complexes [6].
To be broadly applicable, catalysts would have to be developed that would allow
insertion of more highly substituted alkenes. Functional group compatibility
was also of concern. Most polar functional groups (even ethers) were reported
to either react with the organometallics [7] or irreversibly bind so as to inhibit
catalysis [8]. Again, to be considered as part of a general synthetic method it was
imperative that organometallic catalysts be developed that could tolerate a wide
range of common organic functionality. Many of the complexes, particularly the
organolanthanides and group 3 organometallics, are extraordinarily air-sensi-
tive and require glove-box or Schlenk-line techniques for their handling. The
synthesis of reasonably air-stable complexes would facilitate the introduction of
these catalysts to a broader range of applications. Finally, several issues of selec-
tivity would have to be addressed. First, chemoselectivity in the insertion of a
single alkene or alkyne in a polyunsaturated system would be required. A high
degree of regioselectivity in this insertion is also essential. Diastereoselectivity
in reactions of chiral substrates and prochiral unsaturated systems would neces-
sitate examination. Finally, chiral, nonracemic complexes would have to be de-
veloped in order to meet the challenges of modern synthetic organic chemistry.
Lanthanide- and Group 3 Metallocene Catalysis in Small Molecule Synthesis 121
This contribution is not intended to be a comprehensive review of the appli-

cation of group 3 metal and lanthanide metallocenes to selective organic synthe-
sis, but rather seeks to highlight some of the general characteristics of these cat-
alysts and to provide a critical discussion of the reactions to which they have
been applied. Emphasis has been placed upon the means by which some of the
potential problems delineated above have been addressed and upon the applica-
tion of these catalytic species to novel methods in synthetic organic chemistry.
2
General Features of the Catalytic Systems and the Olefin Insertion Reaction
The key step in nearly all of the catalytic processes to be discussed is olefin in-
sertion into a metal hydride [Eq. (2)] or organometallic species [Eq. (3)]. These
hydrometallation and carbometallation processes also form the basis for the po-
lymerization of alkenes. Olefin insertions generally occur with the same regiose-
lectivity as hydroboration reactions [9], with the bulky metal and associated lig-
ands residing at the least hindered site of the two carbon reactive unit.
"Cp*2LnH" + CH2=CHR Cp*2LnCH2CH2R (2)
Cp*2LnR + CH2=CHR' Cp*2LnCH2CHRR' (3)
In most instances these reactions are extremely exothermic and effectively ir-
reversible under reasonable reaction conditions [10]. Even tert-butyl-substitut-
ed organolanthanides (prepared by other methods) exhibit significant kinetic
stability [11].
The organolanthanide- and group 3 organometallic catalysts are highly elec-
trophilic species. Although there is a significant electronic driving force in the
olefin insertion process, for the most part steric factors predominate. Much of
this can be attributed to the effects of coordinative unsaturation at the metal
center. High reactivity is associated with free coordination sites and terminal
(non-bridging) ligands [12]. The requirement for free coordination sites dictates
that noncoordinating solvents be utilized for the catalytic reactions. Thus com-
mon ether solvents lead to low catalytic turnover rates [10] and can even deacti-
vate catalysts via ether cleavage reactions [7, 13]. Consequently, hydrocarbon
solvents are used exclusively in the catalytic reactions.
Although it would seem logical to utilize the most sterically unhindered lig-
ands about the metal to achieve maximum reactivity with hindered alkenes, in
fact there is a delicate balance that must be achieved between the “openness” of
the metal center and the tendency for the organometallic hydrides to undergo a
deactivating ligand redistribution [14] or to dimerize, forming hydride-bridged
dimers [Eq. (4)] [10].
H
2 Cp2LnH Cp2Ln LnCp2 (4)
H
These dimers are less reactive or unreactive in catalytic reactions of interest,

and thus some substitution on the cyclopentadienyl ligands is necessary to pre-
vent dimer formation through steric hindrance to association. Pentamethylcy-
clopentadienyl (Cp*) ligands are useful for this, and lead to catalytic systems
that are highly reactive and yet exquisitely selective in the insertion of mono-
substituted alkenes. One such precatalyst system is the yttrium complex
Cp*2YMe•THF. Although Lewis bases normally depress catalytic activity be-
cause they compete for empty coordination sites on the catalyst, in this precata-
lyst the single THF of solvation appears to catalyze the hydrometallation process
[Eq. (5)] [15] in the same manner that Lewis bases catalyze the hydroboration of
olefins with 9-BBN [16]:
H
Cp*2Y YCp*2 + 2 THF 2 Cp*2YH•THF (5)
H
A related complex lacking a THF of association, Cp*2YCH(TMS)2, is orders of

magnitude less reactive than Cp*2YMe•THF in reactions with monosubstituted
alkenes. Addition of one molar equivalent of THF per equivalent of
Cp*2YCH(TMS)2 restores catalytic activity to the level of the methyl complex
[17]. Apparently, this THF also depresses the rate of σ-bond metathesis (see be-
low) relative to olefin insertion [10], with important ramifications for cycliza-
tion/termination processes to be discussed later. Curiously, this THF effect ap-
pears unique to the Cp*2YR system.
Unfortunately, the yttrium hydride complex Cp*2YH is very hindered about
the reactive metal center and does not react readily with 1,1-disubstituted
alkenes and more highly hindered olefins. Three general catalyst modifications
have been utilized to overcome this difficulty. The first is the incorporation of
lanthanide metals with larger ionic radii. Because of the lanthanide contraction,
early lanthanides have a larger ionic radius than the late lanthanides. Placement
of one of the larger metal ions into the ligand system has the effect of opening it
up, allowing access to more hindered alkenes. This strategy has its limits, and to
create even more accessible metal centers the ligand system itself must be
changed. Incorporation of a single bulky substituent onto the cyclopentadienyl
units has been utilized to open the reactive metal center. Substituents such as
tert-butyl groups and trimethylsilyl groups appear to prevent extensive hydride
dimer formation, but at the same time leave the metal center relatively open for
interaction with olefins. An example of such a precatalyst is displayed in Fig. 1.
Although the methyl precatalyst is a dimer, the active hydride catalyst is most
likely a monomer, and is capable of rapid olefin insertion of most 1,1-disubsti-
tuted alkenes [18]. Another interesting feature of the catalyst is its unusual sta-
bility. Members of this class of precatalysts have been weighed in the air and uti-
lized in hydrosilylation reactions performed with normal procedures for the
benchtop handling of air-sensitive materials [9, 19].
The third strategy that has been utilized to provide more open access to the
metal is to utilize “hinged” cyclopentadienyl ligands. A one atom bridge between
two cyclopentadienyl units serves to increase the angle between them, and again
TMS TMS
Me
Ln Ln = [(CpTMS)2LnMe]2
Me
TMS TMS
Ln = Sm, Y, Lu
Fig. 1. Unhindered catalyst systems for reaction with hindered alkenes
Me2Si SmCH(TMS)2
Fig. 2. Hinged catalyst system for reaction with hindered alkenes
provides more facile approach of substrate to the metal. Figure 2 depicts one
such precatalyst [20].
With a wide range of metals and ligands available [2a, 21], organolanthanide
and group 3 organometallic catalysts are readily “tuned” to provide the desired
reactivity and selectivity patterns in reactions of interest.
3
Catalytic Hydrogenation Reactions
Organolanthanides and group 3 organometallics are extraordinarily reactive hy-
drogenation catalysts [22]. They are also relatively challenging to prepare and
handle. This, combined with their lack of tolerance to reactive functional
groups, makes them less attractive than many transition metal-based catalysts
in standard hydrogenation reactions. It is instructive, however, to examine the
catalytic cycle of hydrogenation reactions because it serves as a useful model for
the other catalytic reactions to be discussed subsequently. Additionally, useful
information concerning selectivity has been derived from studies of the hydro-
genation reaction.
Transition metal-based hydrogenation reactions most often operate on a cat-
alytic cycle that involves oxidative addition, olefin insertion, and reductive elim-
ination. The mechanistic basis for organolanthanide hydrogenation is quite dif-
ferent, and involves olefin insertion and σ-bond metathesis (Fig. 3).
A σ-bond metathesis initiates the process, converting an organometallic pre-
catalyst into the catalytic hydride species through a four-centered exchange of
Cp*2LnR'
H2
- R'H
H
"Cp*2LnH"
H
R R
H2 H
LnCp*2
R
Fig. 3. Catalytic cycle for hydrogenation
ligands [Eq. (6)] [23]. Olefin insertion is the product-determining step of the
process, and is generally irreversible under optimal conditions for hydrogena-
tion [10]. A σ-bond metathesis reaction constitutes the final step of the process,
wherein the organometallic reacts with hydrogen to release the hydrocarbon
and regenerate the active catalyst.
Cp*2Ln R
Cp*2LnR + H2 Cp*2LnH + RH (6)
H H
Detailed kinetic studies for organolanthanide-catalyzed hydrogenations have

been performed [22]. Although there are some exceptions, for reactive olefins
the rate of the reaction is proportional to the product of the catalyst concentra-
tion and hydrogen concentration, indicating a rapid olefin insertion and rate
limiting σ-bond metathesis. With the exception of cyclohexene, the relative rate
constants for hydrogenation of monosubstituted alkenes and a variety of 1,2-
disubstituted alkenes are remarkably similar. Nevertheless, synthetically useful
selectivities can be achieved with a highly discriminating catalyst (Eqs. 7–9)
[24]. For most diene substrates wherein the two alkenes exhibit different reac-
tivities, hydrogen uptake need not be monitored. Even with a highly reactive,
strained alkene such as is found in the bicyclo[2.2.1] system, the monosubstitut-
ed alkene is so much more reactive that a single equivalent of hydrogen is uti-
lized even in the presence of a vast excess of hydrogen (Eq. 7). Perhaps even
more impressive is the selectivity displayed in Eq. (8), wherein substitution at
one allylic position of a diene system is sufficient to permit virtually complete
selectivity. Most common alcohol protecting groups are tolerated (Eq. 9), but al-
lylic acetate and allylic halide functionalities inhibit catalytic turnover.
5% Cp*2YMe•THF
1 atm H2, benzene (7)

rt, 1 h, 72%
OTr 5% Cp*2YMe•THF OTr

1 atm H2, benzene
(8)
rt, 1 h, 96%
Me Me 2% Cp*2YMe·THF Me Me
R R
1 atm H2, benzene, rt, 1 h (9)
R = OTBS, OMe, OBn; yield = 74-99%
R = OAc, Cl; yield = 0%
More hindered, less reactive alkenes such as 1,1-disubstituted alkenes require

a more open catalyst [25]. For the hydrogenation reaction, the simple alternative
of utilizing a samarium- or ytterbium-based catalyst permits these substrates to
react effectively, often with high diastereoselectivities (Eqs. 10–12). A variety of
alkyl and aryl substituents are tolerated, including a tertiary amine (Eq. 11). Al-
lylic ether substitution, however, inhibits the reaction, even under more vigor-
ous conditions. After initial insertion of the olefin, the Lewis acidic metal center
can form a stable five-membered ring chelate with the oxygen, preventing fur-
ther reaction. In general, the diastereoselectivity of the olefin insertion dimin-
ishes when the existing stereogenic center occupies a position that causes less in-
teraction with the bulky organometallic reagent (Eq. 12). The stereochemistry
of the products is that predicted by the approach of the bulky organometallic to
the less hindered face of the exo-methylene unit.
10% Cp*2SmCH(TMS)2
1 atm H2 (10)
cyclopentane, rt
84%
3% Cp*2SmCH(TMS)2
R R
1 atm H2, cyclopentane
R = Ph, (CH2)3NMe2, 50 ˚C (11)
76-96%, >10 : 1 ds
R = OMe, 70 ˚C, 0%
3% Cp*2YbCH(TMS)2
1 atm H2 (12)
cyclopentane, -20 ˚C
t-Bu 73%, 3.3 : 1 ds t-Bu
Enantioselective catalytic hydrogenation reactions have been reported and

appear to offer synthetically useful results, although for a very limited set of
alkenes [10, 26]. Thus deuteration of styrene and hydrogenation of substituted
styrenes, molecules with essentially no functional group available to serve as a
stereochemical control element, can be accomplished with modest to high

asymmetric induction using a series of elegantly designed chiral, nonracemic
catalysts (Eq. 13).
0.7% cat. H
1 atm. H2
heptane, rt, <1 h
95%, 71% ee
(13)
cat. = (TMS)2CHSm SiMe2 R* =

)
R*
Although a model was proposed in which olefin insertion occurred to place

the metal on the terminus of the alkene (“1,2-addition”) [10, 26], based upon
subsequent mechanistic and synthetic studies of the hydrosilylation reaction of
styrenes (see below), this model would appear to be incorrect [27]. Thus an ir-
reversible, stereochemically determinant “2,1-insertion” probably initiates the
reaction, with subsequent σ-bond metathesis completing the process. Most re-
markable is the fact that, if correct, this model demands that the olefin insertion
takes place to orient the highly hindered metal center at a tertiary carbon center,
and that apparently little, if any, β-hydride elimination occurs from the resultant
organometallic.
A “frontal trajectory” has been suggested to explain the sense of asymmetric
induction in these reactions (Fig. 4), and seems most valid based on steric ef-
fects. However, a “lateral trajectory” cannot be ruled out based upon the evi-
dence available to date [10, 26].
Alkynes also undergo selective hydrogenation to generate cis-alkenes [22,
28]. The process has not been developed, however, and at any rate it is unlikely
to compete with more established methods.
Sm H
Me2Si Sm H
R* Ph
Ph
R*
Lateral trajectory model Frontal trajectory model
Fig. 4. Models for asymmetric induction in hydrogenation of styrene derivatives

4
Catalytic Hydrosilylation Reactions
Metal catalyzed hydrosilylation reactions provide the most efficient and eco-
nomical route to organosilanes [29]. Organosilanes can be readily oxidized to
the corresponding alcohols utilizing a Tamao procedure or related reactions
[30]. The overall process thus constitutes the synthetic equivalent of a catalytic
hydroboration/oxidation sequence [31]. One advantage of the silylation/oxida-
tion protocol is the stability of the intermediate silane which allows the unmask-
ing of the alcohol to be performed at a synthetically convenient time. In spite of
the potential of hydrosilylation reactions in selective organic synthesis, relative-
ly little effort has been made to develop procedures for the selective hydrosilyla-
tion of polyfunctional alkenes and alkynes, especially when compared to the
analogous hydroboration reaction.
Organolanthanide and group 3 organometallic catalysts provide an alterna-
tive to the more traditional platinum-based catalysts for the selective hydrosi-
lylation of alkenes and alkynes. Mechanistically, the transformation is analo-
gous to the catalytic hydrogenation reaction detailed previously [22]. When si-
lane is utilized in place of hydrogen, the σ-bond metathesis occurs to place the
silane moiety on the alkyl unit, and the organometallic hydride is again regen-
erated (Fig. 5). In the overall process a rapid, exothermic, and essentially irre-
versible olefin insertion is followed by the slower, rate-determining σ-bond me-
tathesis. Because the group 3 metallocenes and organolanthanides are highly ef-
fective catalysts for dehydrogenative polysilylation [32], the desired process de-
mands that olefin insertion and σ-bond metathesis occur much more rapidly
than the generation of polysilanes.
Cp*2LnR'
R3SiH
- R'SiR3
H
SiR3 "Cp*2LnH"
R"
R"
R3SiH H
LnCp*2
R"
Fig. 5. Catalytic cycle for hydrosilylation

4.1
Silylation of Alkenes
The earliest reported examples of group 3 or organolanthanide catalyzed hy-

drosilylation reactions emphasized reactions with simple alkenes (e.g., 1-oc-
tene) (Eq. 14) [33]. The lutetium- and neodymium-based catalysts utilized for
these studies typically required 2 d at high temperatures (80–90 ˚C) to react and
provided modest to good yields of the desired terminal (linear) organosilanes.
Styrene provided mixtures of linear and branched organosilanes [Eq. (15)].
5% Cp2LuC6H4CH3•THF
PhMeHSi
n-C6H13 n-C6H13 +
MePhSiH2, 90 ˚C, 2 d
75%, 28 : 1
(14)
SiHMePh
+
n-C6H13
4% Cp*2NdCH(TMS)2 SiH2Ph
+ PhH2Si
Ph Ph
PhSiH3, 80 ˚C, 2 d Ph (15)
88%, 4.5 : 1
The regioselectivity of olefin insertion varies with the complex used in the re-
action [27, 34]. In the hydrosilylation of a monosubstituted olefin, the use of
complexes with larger metals and more open ligands provide increased yields of
the product derived from reversed (“2,1”) insertion (Eq. 16). These results re-
veal that a variety of complexes give excellent selectivity for terminal insertion,
but the conditions to elevate the amount of “2,1” insertion remain elusive.
5% catalyst SiH2Ph
PhH2Si
n-C8H17 n-C8H17 +
PhSiH3, rt, 1-24 h n-C8H17
Catalyst Yield (% isolated) ds
Cp*2LuMe•THF 98 100 : 0
Cp*2YbCH(TMS)2 91 100 : 0 (16)
Cp*2YMe•THF 84 100 : 0
Cp*2SmCH(TMS)2 90 11 : 1
Cp*2NdCH(TMS)2 85 3.2 : 1
Cp*2LaCH(TMS) 2 90 1.9 : 1
Me 2SiCp"2YCH(TMS)2 84 31 : 1
Me 2SiCp"2SmCH(TMS) 2 98 1:2
Me 2SiCp"2NdCH(TMS)2 89 1:2
The development of organoyttrium catalysts provided a major breakthrough

in terms of efficiency and selectivity in the synthesis of organosilanes [35].
These catalysts reacted with monosubstituted alkenes and reactive disubstituted
alkenes within hours at room temperature, providing high yields of the desired
organosilanes (Eq. 17). It was also demonstrated that common organic func-
tional groups (halides, ethers, and acetals) could be tolerated under the reaction
conditions (Eq. 18).
3% Cp*2YCH(TMS)2
SiH2Ph (17)
PhSiH3, benzene
rt, 3.5 h, 85% H
3% Cp*2YCH(TMS)2
SiH2Ph
X X
PhSiH3, benzene (18)
rt, 83-96%
X = Cl, OBn, OTBDMS, OTHP
In the same study, remarkable steric selectivity was demonstrated in the hy-
drosilylation of dienes with varying substitution patterns [35]. Virtually com-
plete selectivity was observed for the reaction of monosubstituted olefins in the
presence of disubstituted alkenes (Eqs. 19, 20) and for the silylation of a 1,1-di-
substituted olefin in preference to a trisubstituted double bond (Eq. 21).
3% Cp*2YCH(TMS)2
PhSiH3, benzene, rt SiH2Ph (19)

92 h, 91%
3% Cp*2YCH(TMS)2 SiH2Ph
PhSiH3, toluene, rt (20)
18 h, 97%
3% Cp*2YCH(TMS)2 SiH2Ph
PhSiH3, benzene, rt (21)
96 h, 61%, 2:1 ds
The yttrium catalysts are less effective for more sterically hindered olefins,
but the flexibility afforded by being able to alter both the metal and the ligand
system provides a means to adjust reactivity in a manner that allows hydrosilyla-
tion of more highly substituted alkenes. The simple modification of increasing
the ionic radius of the metal permits the hydrosilylation of 1,1-disubstituted
alkenes (Eq. 22) [25]. This effect dominates over slight ligand modifications, as
a complex with more hindered ligands (C5Me4i-Pr) (Eq. 23) shows similar reac-
tivity to the C5Me5-derived yttrium complex (Eq. 21) [36]. A silicon-hinged cat-
alyst further increases turnover frequency over nonbridged systems by a factor
of eight (Eq. 24) [27]. Unfortunately, there is a trade-off with the more open cat-
alysts. Although increased reactivity with more highly substituted alkenes is ob-
served, monosubstituted alkenes react with poor regioselectivity.
SiH2Ph
5% Cp*2SmCH(TMS)2
R
R
PhSiH3, cyclohexane (22)
70 ˚C, 12 h
63-92%, 9 : 1 ds
R = Me, i-Bu, Bn, (CH2)3NMe2
5% (C5Me4i-Pr)2SmCH(TMS)2 SiH2Ph
rt, 96 h, 82%
cat. Me2SiCp'2SmCH(TMS)2 SiH2Ph
PhSiH3, benzene-d6 (24)

60 ˚C, 98%
Cp' = C5Me4
Styrene derivatives react with “2,1-” regioselectivity [27]. This reversal of se-
lectivity varies considerably with the metal ionic radius and the ligand array
present, with larger metals and bridged ligands giving higher ratios of the “2,1”
product. As with the catalytic hydrogenation of styrene derivatives discussed
previously, the olefin insertion reaction defines the regiochemistry and stereo-
chemistry of the final product. Thus the olefin insertion is essentially irreversi-
ble under the reaction conditions, and the σ-bond metathesis presumably oc-
curs with retention of configuration to provide the observed products with re-
markably high ee’s considering the overall nature of the transformation (Eq. 25).
0.5% cat. SiH2Ph

PhSiH3, benzene-d6
rt, 98%, 68% ee
(25)
cat. = (TMS)2CHSm SiMe2 R* =

)
R*
4.2
Silylation of Alkynes
Although terminal alkynes are metallated with organolanthanide hydrides and

therefore cannot be hydrometallated [37], internal alkynes do undergo effective
hydrosilylation [38]. As expected, cis-addition of the organometallic hydride to
the alkyne is observed (Eq. 26). Branching at one of the propargyl positions is
necessary for high regioselectivity in unsymmetrical alkynes. A variety of
branched substituents are suitable for use (Eqs. 27–31) widening the possibili-
ties of subsequent synthetic steps. Placing a tertiary group on the alkyne (Eq. 30)
slows the reaction, allowing the competitive dehydrogenative polymerization of
silane to lower the yield of the desired product.
5% (C5Me4i-Pr)2YCH(TMS)2 n-C6H13
n-C6H13 +
PhSiH3, 50 ˚C
12 h, 78%, 4 : 1 PhH2Si H
(26)
n-C6H13
+
H SiH2Ph
5% Cp*2YMe•THF
PhSiH3, cyclohexane
50 ˚C, 24 h, 80%
(27)
SiH2Ph
O
O 5% Cp*2YMe·THF O (28)
n-C5H11 n-C5H11
O PhSiH3, 50 ˚C
24 h, 85% H SiH2Ph
TBDMSO 5% Cp*2YMe•THF
n-C10H21 PhSiH3, cyclohexane
90 ˚C, 24 h, 89%
(29)
TBDMSO n-C10H21
SiH2Ph
5% Cp*2YMe·THF t-Bu n-C10H21

t-Bu n-C10H21
PhSiH3, 55 ˚C H SiH2Ph (30)
48 h, 28%
5% Cp*2YMe·THF
(31)
PhSiH3, 90 ˚C
7 d, 50% H SiH2Ph
Equation (31) illustrates an interesting facet of this regioselectivity [38]. Al-

though both substituents are branched, the phenyl group is effectively smaller
than the cyclohexyl moiety, allowing good selectivity. The steric preference is
likely buttressed by the same electronic directing effects of aryl groups observed
for styrene derivatives [27].
The critical and in fact rate-limiting step of alkyne hydrosilylation is the σ-
bond metathesis [38]. Both the increased strength of a Csp2-metal bond and the
geometric requirements for the σ-bond metathesis combine to require the reac-
tions to be heated overnight to achieve high yields of the desired alkenylsilanes.
The hydrosilylation of alkynes is tolerant of a wide variety of functional groups
(Eq. 32) including halides, amines, and several alcohol protecting groups [38]. A
collection of substrates that were unreactive at temperatures up to 90 ˚C is pic-
tured in Fig. 6. The strongly Lewis acidic complexes probably cause catalyst-de-
activating ionization of the propargylic acetals.
5% Cp*2YMe•THF
X
PhSiH3, cyclohexane
50 ˚C, 24 h, 73-84%
X = Cl, OTHP, NMe2
(32)
SiH2Ph
The chemoselectivity of the catalyst for alkynes over alkenes is of interest. Ex-
cellent discrimination is achieved in substrates containing an alkyne paired with
a hindered olefin (Eqs. 27, 33) [38]. When offered a monosubstituted olefin
(Eq. 34) the catalyst is less selective, producing mixtures of alkyl- and vinylsi-
lanes. As previously noted for the hydrogenation of dienes, the addition of a
group allylic to the alkene sterically shields the double bond and can electroni-
O S O
n-C8H10 n-C8H10 n-C8H10
O S O
Fig. 6. Alkynes that are unreactive to catalytic hydrosilylation conditions

cally deactivate it as well (Eq. 35). This allows virtually complete selectivity for
alkyne insertion.
5% Cp*2YMe·THF
(33)
PhSiH3, 50 ˚C
24 h, 90% H SiH2Ph
5% Cp*2YMe·THF
( ) 0.5 equiv. PhSiH3
6
50 ˚C, 12 h
(34)
SiH2Ph SiH2Ph
( ) ( )
6 + + 6
( )
H SiH2Ph 6 H SiH2Ph
OTBDMS
5% Cp*2YMe·THF
TBDMSO
PhSiH3, rt
(35)
21 h, 93%
H SiH2Ph
5
Catalytic Cyclization Reactions
The propensity for organolanthanides and group 3 organometallics to undergo
olefin insertion reactions leading to the polymerization of α-olefins provides the
possibility of cyclizing dienes and other polyunsaturated substrates. A reasona-
ble catalytic cycle for such a transformation is depicted in Fig. 7. There are sev-
eral requirements for successful cyclization. In an unsymmetrical diene, selec-
tive reaction at a single alkene is necessary to avoid a mixture of regioisomeric
products. As noted previously, this requirement has been met with organoyt-
trium catalysts (Eq. 8) [24]. If the reactions are carried out under a hydrogen at-
mosphere, intramolecular olefin insertion must occur more rapidly than σ-
bond metathesis of the newly formed organometallic with hydrogen. Diastereo-
selectivity is established in the cyclization, and should be predictable based
upon a simple chair transition structure for the cyclization. Finally, in the ab-
sence of hydrogen the catalytic cycle can be completed by β-hydride elimination
to afford the exomethylene-substituted cycloalkane.
Cp*2LnR'
H2
- R'H
H H
CH3
"Cp*2LnH"
R R
n( ) n( )
H2
H H
LnCp*2
R R LnCp*2
n( ) n( )
- Cp*2LnH
H
R
n( )
Fig. 7. Catalytic cycle for the cyclization of dienes
5.1
Termination by β-Hydride Elimination
Carbocycles and heterocycles ranging from five-membered to nine-membered

have been synthesized utilizing organoscandium catalysts (Eqs. 36–39) [8].
These reactions are carried out in the absence of hydrogen or other “chain ter-
minators”. Consequently, the organometallic generated after initial olefin inser-
tion is more persistent, and is therefore provided the time to cyclize to ring sizes
that are normally inaccessible. Diastereoselectivity issues were not addressed in
this study, nor was the tolerance of the catalysts for a wide range of functional
groups. From the reported studies it is clear that discrimination of the catalysts
for a monosubstituted alkene in the presence of an allylically substituted mono-
substituted alkene is not high (Eq. 39).
9% [DpScH]2
( )5 rt, 3 d
85%
(36)
t-Bu
DpScH = Me2Si ScH
t-Bu
5% [DpScH]2
80 ˚C, 10 min
(37)
quant
4% Me2SiCp'2Sc(H)(PMe3)
N N
80 ˚C, 10 min
(38)
93%
6% [DpScH]2
80 ˚C, 10 min
+ (39)
99%, 2 : 1
5.2
Termination by Hydrogenation
Organoyttrium catalysts have been utilized to effect the cyclization of dienes un-
der reductive conditions [39]. Excellent selectivity is achieved in these reactions
between two monosubstituted alkenes leading to a single regioisomeric product
(Eq. 40), and the diastereoselectivity is consistent with the simple chair transi-
tion structure model (Fig. 7). Both acetals and thioacetals are tolerated (Eq. 41),
whereas nitriles, esters, and sulfones preclude product formation (Eq. 42).
5% Cp*2YMe•THF
OTr
OTr 1 atm H2 (40)
benzene, rt, <1 h
99%, 21 : 1 ds
X 5% Cp*2YMe•THF X
X 1 atm H2, benzene

X
(41)
rt, <1 h
X = O, 85%
X = S, 97%
R 5% Cp*2YMe·THF
no reaction
R 1 atm H2, benzene (42)
R = CN, CO2Me, SO2Ph
A reduced yield of the cyclized product accompanied by reduced uncyclized

material is obtained in the reaction of 1,2-divinylbenzene (Eq. 43) [39]. This
could be caused by the rigid aryl group skewing the geometry of the transition
state, making cyclization more difficult. Additionally, it seems likely that a sub-
stantial amount of inverse (“2,1”) addition occurs. The failure of the secondary
benzylic organometallic thus formed to cyclize would lead to formation of the
uncyclized hydrogenated product.
5% Cp*2YMe·THF
+
1 atm H2, benzene (43)
rt, 1 h
53% 26%
Fully reduced uncyclized material is also obtained in the hydrogenation of di-

allyldimethylsilane (Eq. 44) [39]. This is undoubtedly because the relatively long
Si-C bonds perturb the cyclization transition state.
Me 5% Cp*22YMe·THF Me
Si Si (44)
Me 1 atm H22, benzene Me
rt, 1 h, 64%
More highly hindered (e.g., 1,1-disubstituted) alkenes cannot be accommo-

dated by the Cp*2YH catalysts. However, more sterically open catalysts permit
rapid cyclization under extraordinarily mild conditions (Eq. 45) [10].
0.5% cat.
1 atm H2
neat, rt, 2 h
(45)
TMS
cat. = (TMS)2CHY SiMe2 R* =

)
R*
5.3
Termination by Silylation
Although the cyclization reactions described above represent a potentially pow-

erful means for carbon-carbon bond formation, under reductive (hydrogenoly-
sis) conditions the method utilizes a highly functionalized diene substrate and
leaves an essentially unfunctionalized product in its wake. The utilization of si-
lylation as a chain terminating event provides a way to place functionality back
into the molecule after the cyclization (Fig. 8).
Cp*2LnR'
R3SiH
- R3SiR'
H H
CH2SiR3
"Cp*2LnH" R
R
n( ) n( )
R3SiH
H H
LnCp*2
R R
LnCp*2
n( ) n( )
Fig. 8. Catalytic cycle for the cyclization/silylation of dienes
5.3.1
Cyclization/Silylation of Terminal Dienes and Trienes
Early studies centered on the utilization of organolutetiums (Eq. 46) [32a], orga-
noneodymiums [33c], and organosamariums [27] for the cyclization of 1,5-hex-
adiene and homologs. The early studies of the cyclization/silylation process in-
cluded only unsubstituted dienes, leaving questions of regioselection, diastere-
oselection, and functional group toleration unanswered. A more thorough study
of this chemistry that focused on the application to small molecule synthesis was
performed utilizing organoyttrium complexes [40]. The organoyttrium-cata-
lyzed process employed on monosubstituted dienes appears to be quite general
for the synthesis of both five- and six-membered rings. For the synthesis of five-
membered rings, phenylsilane is a convenient “chain terminator.” It provides
high yields of cyclized/silylated products with no stereocenters introduced as a
result of the incorporation of the silicon atom. High diastereoselectivities are
achieved in many instances (Eq. 47).
cat. Cp*2LuMe
SiH2Ph
PhSiH3, pentane
(46)
30 min, quant.
OCPh3
5% Cp*2YMe•THF
OCPh3 PhSiH3, cyclohexane
(47)
SiH2Ph
rt, 1 h, 71%, 24 : 1 ds
Noteworthy in all of these metallocene-catalyzed reactions is the fact that they

proceed with complete “atom economy” [41], i.e., all of the atoms from the sub-
strates and reagents are incorporated into the desired product and there are no
byproducts produced. Many of these reactions are so clean, in fact, that pouring
the reaction mixture through a short bed of Florisil to remove the catalyst, fol-
lowed by evaporation of the solvent and bulb-to-bulb distillation, leads to essen-
tially quantitative yields of analytically pure product.
The synthetic equivalency of the silane and an alcohol can be easily demon-
strated by subjecting the crude silane product to any of a variety of available ox-
idizing conditions (Eq. 48) [30, 40].
5% Cp*2YMe•THF Ph
PhSiH3
Ph cyclohexane, rt, 1 h SiH2Ph
1. HBF4•OEt2 (48)
CHCl3, 0 ˚C, 1 h Ph
2. KF, KHCO3, H2O2
THF, MeOH OH
heat, 18 h
74% overall yield
9 : 1 ds
Cyclohexane formation is entropically less favorable than cyclopentane gen-

eration, and treatment of 1,6-dienes under the conditions listed in Eq. (47) leads
to the production of uncyclized, disilylated products (Eq. 49) [35] or silicon
bridged dimers [40]. To avoid these problems, phenylmethylsilane can be em-
ployed as the chain terminator. Utilizing this more hindered silane slows the σ-
bond metathesis sufficiently to prevent dimerization (Eq. 50). The trapping step
can be retarded even further by the use of diphenylsilane (Eq. 51). Thus, not only
can the metal and the ligand array be manipulated to bring about the desired re-
sult in the catalytic process, but the properties of the silane reagent itself can also
be adjusted to meet the demands of the synthesis at hand.
3% Cp*2YCH(TMS)2
PhH2Si SiH2Ph
PhSiH3, benzene, rt (49)
26 h, 96%
OTBDMS
OTBDMS 5% Cp*2YMe·THF
(50)
MePhSiH2, cyclohexane SiHMePh
rt, 2 h, 99%, 1.5 : 1 ds
t-Bu
5% Cp*2YMe·THF N
MePhSiH2, cyclohexane SiHMePh
t-Bu rt, 2 h, 97%
N (51)
t-Bu
5% Cp*2YMe·THF N
Ph2SiH2, cyclohexane SiHPh2
rt, 20 h, 65%
The functional group compatibility of this process is similar to that described

previously [40]. Protected alcohols (Eq. 50), tertiary amines (Eq. 51), and pro-
tected ketones (Eq. 52) are all inert to the reaction conditions.
S S 5% Cp*2YMe•THF S S
PhMeSiH2
(52)
cyclohexane, rt, 1 h SiHMePh
99%
In the reaction of triallylamine (Eq. 53) [40], after the first ring forming event
the organometallic is trapped by σ−bond metathesis with the silane instead of
undergoing an entropically unfavorable intramolecular olefin insertion to yield
a bridged bicyclic structure. The remaining double bond then competes effec-
tively for the catalyst, making the isolation of monocyclic silylated product bear-
ing a free allyl group impossible.
SiHMePh
5% Cp*2YMe·THF
N (53)
N MePhSiH2, cyclohexane
rt, 1 h, 90% SiHMePh
Monosubstituted diene systems have been employed for the synthesis of bicy-
clic systems as well as monocyclics [17]. The simplest way to accomplish this is
to construct a second ring onto an existing structure (Eq. 54). This cyclization
process is initiated at the alkene lacking allylic substitution. The formation of
the six-membered ring necessitates the use of methylphenylsilane as the silylat-
ing reagent. Because the silane itself comprises a new stereocenter, it must be re-
moved by oxidation to assess accurately the diastereoselectivity of cyclization.
Fluxionality of the five-membered ring results in a mixture of diastereomers at
the silylmethyl-substituted stereocenter.
OTBDMS
OTBDMS
5% Cp*2YCH3·THF
cyclohexane H
PhMeSiH2, rt,1 h
92%, 1.7:1 ds SiHMePh
(54)
OTBDMS
t-BuOOH, KH
DMF, 50 °C, 12 h H
86%, 1:1 ds
OH
Because the stereochemistry at the ring juncture is passed undisturbed from

the substrate, by generating substrates with a fixed relationship between the ole-
fin bearing substituents either ring fusion may be produced at will (Eq. 55) [17].
After oxidation of the silane product and deprotection to the corresponding di-
ol, the stereochemistry of the single isomer was determined by X-ray crystal
analysis. In this case the high diastereoselectivity observed may be explained by
the transition structures shown in Fig. 9. The bulky organometallic prefers to be
away from the existing ring, leading to the observed cis-decalin product.
SiHMePh
5% Cp*2YMe•THF H
PhMeSiH2
(55)
OTBS cyclohexane, rt, 1 h
86% OTBS
‡
Y
Y H
Olefin
Insertion
OR OR
Favored
‡
Olefin
Y Insertion Y
Disfavored
OR OR
Fig. 9. Steric factors governing cis-decalin formation

‡
Y
Olefin
Y
Insertion
OR H
Favored OR H
H
H ‡ Olefin
OR Y Insertion
OR
Disfavored Y
Fig. 10. Steric factors governing trans-decalin formation
A trans-decalin system can be produced by using a substrate with the oppo-

site diastereomeric relationship (Eq. 56 and Fig. 10) [17]. Of interest is the
heightened stereoselectivity observed when the relatively rigid cyclohexane unit
is substituted for the fluxional cyclopentane moiety (Eq. 54). This rigidity accen-
tuates the steric interactions governing the stereochemical course of the reac-
tion.
SiHMePh
5% Cp*2YMe•THF H
PhMeSiH2
(56)
OTMS cyclohexane, rt, 1 h
89% OTMS
If the substituents are arranged to form a trans-decalin with complementary

substitution, no cyclization occurs (Eq. 57) [17]. The slower six-membered ring
formation at the hindered alkene is interrupted by silylation. This allows im-
pressive chemoselectivity in polyene substrates. When presented with a sub-
strate possessing three monosubstituted olefins with varying steric environ-
ments, the catalyst can select the least hindered alkene for initial insertion and
will only cyclize onto the less hindered of the two remaining double bonds
(Eq. 58). A mechanistic outline and depiction of the steric environments is given
in Fig. 11.
THPO 5% Cp*2YCH3·THF THPO
cyclohexane (57)
PhMeSiH2, rt, 1 h SiHMePh
98%
Cp*2YMe·THF
PhMeSiH2
TBDMSO Cp*2YH·THF TBDMSO

SiHMePh
PhMeSiH2
YCp*2
TBDMSO TBDMSO
YCp*2
Fig. 11. Catalytic cycle for the selective reaction of a triene
TBSO
TBSO
5% Cp*2YMe•THF
PhMeSiH2
(58)
cyclohexane, rt, 1 h H
86% SiHMePh
The failure to insert quaternary vinyl groups in a cyclization process is limit-

ed to 1,6-diene systems [17]. When a similar competition for selective insertion
is attempted on a 1,5-diene, cyclization occurs because of the inherent entropic
advantage of five-membered ring formation (Eq. 59). The close approach of the
bulky organometallic to the axial alkoxy substituent in the chair-like transition
structure (Fig. 12b) causes the reaction to proceed through the less hindered
boat formation (Fig. 12a).
OTMS SiHMePh
5% Cp*2YMe•THF TMSO
PhMeSiH2 (59)
cyclohexane, rt, 6 h
80% H
In addition to their ability to assemble bicyclic structures on a monocyclic

scaffold, the organoyttrium catalysts can also convert trienes to bicyclics in a se-
quential process (Eqs. 60, 61) [17]. Both five- and six-membered rings can be
constructed at will. In these cases the stereochemistry at the bridgeheads is a re-
sult of the chair-like transition structures operative during the intramolecular
olefin insertions (Schemes 1, 2). There are two notable features of this reaction.
The first is that after the initial olefin insertion a 5-exo cyclization at the allyli-
OTMS OTMS
H ‡ Olefin H
(a)
Insertion
Y Y
Favored
‡
OTMS
Olefin OTMS
Y
Y (b)
Insertion
H
H
Disfavored
Fig. 12. Steric factors governing bicyclic product formation
cally substituted alkene is chosen over a 6-exo cyclization at an unhindered

alkene. The second is the formation of the trans-bicyclo[3.3.0] ring system. Cur-
rently, the number of methods available to prepare this highly strained system is
quite limited [42]. The formation of single product isomers attests to the high
chemo- and stereoselectivity of each individual reaction step.
TMSO 5% Cp*2YMe•THF t-BuOOH, KH

PhSiH3 DMF, 50 ˚C, 12 h
OH (60)
OH
H
73%
H
5% Cp*2YMe•THF SiHMePh
PhMeSiH2 (61)
cyclohexane, rt, 1 h H
68%
The chemoselectivity of these catalysts allows the selective construction of bi-

cyclic systems bearing additional substitution (Eqs. 62, 63) [17]. By varying the
stereochemistry of the substituents, the three-dimensional structure of the
product can be altered as desired.
first OTMS
OTMS OTMS YCp*2
"Cp*2YH" cyclization
YCp*2
H
second
cyclization
H OTMS PhSiH3 H OTMS
σ-bond
PhH2Si H metathesis Cp*2Y H
Scheme 1
"Cp*2YH"
YCp*2
first
cyclization
SiHMePh YCp*2
YCp*2
PhMeSiH2 second
σ-bond cyclization
metathesis
Scheme 2
H
5% Cp*2YCH3·THF
cyclohexane SiH2Ph (62)

OTBDMS PhSiH3, rt, 1 h OTBDMS
72%, 2.1:1 ds
H
5% Cp*2YCH3·THF
cyclohexane SiH2Ph (63)

OTBDMS PhSiH3, rt, 1 h OTBDMS
78%, 7.2:1 ds
In spite of their recognized Lewis acidity and the propensity to complex with
Lewis bases (particularly in an intramolecular chelate) [8], the organoyttrium
complexes can be utilized for the synthesis of nitrogen heterocycles. The proto-
col has been employed in a concise synthesis of (±)-epilupinine (Scheme 3) [43].
4 steps cat. Cp*2YMe•THF

OH
NH N PhMeSiH2
SiHMePh OH
t-BuOOH, KH, CsF
DMF, 45 ˚C, 12 h
N N
(±) - Epilupinine
51-62%, two steps
Scheme 3
5.3.2
Cyclization/Silylation of Hindered Dienes and Trienes
As mentioned previously, more highly hindered alkene systems cannot be ac-

commodated by the relatively closed organoyttrium catalysts, and thus more
open ligand arrays have been enlisted to allow incorporation of 1,1-disubstitut-
ed alkenes. A first generation catalyst was developed that worked quite well in
these systems, albeit at somewhat elevated temperatures and protracted reac-
tion times [44]. The ligand possessed a silicon hinge that served to open the
clamshell comprised of the cyclopentadienyl rings, and the rings themselves
possessed a single trimethylsilyl group to prevent hydride dimer formation.
Monosubstituted alkenes reacted in preference to 1,1-disubstituted alkenes
(Eq. 64). Remarkably, both alkenes can be disubstituted, generating a quater-
nary center with complete stereochemical control (Eq. 65). Trienes reacted in a
sequential process, in one case leading to a spirocyclic system (Eq. 66).
SiH2Ph
cat. Me2Si(CpTMS)2YCH(TMS)2
(64)
PhSiH3, cyclohexane
90 ˚C, 16 h, 79%
5% Me2Si(CpTMS)2YCH(TMS)2 SiH2Ph
PhSiH3, cyclohexane
(65)
90 ˚C, 16 h, 57%
5% Me2Si(CpTMS)2YCH(TMS)2
PhSiH3, cyclohexane
90 ˚C, 24 h, 64% (66)
SiH2Ph
Recognizing the need to carry out these reactions under milder conditions, a
second generation catalyst was tested in similar systems [44]. This new system,
lacking the silicon hinge, proved to be extraordinarily reactive, in fact orders of
magnitude more reactive than any other neutral catalyst tested to date in similar
substrates (compare Eqs. 66, 67). As described previously, the precatalyst has
modest air stability, and yet the catalyst itself is remarkably reactive. Catalyst
loadings as low as 0.5 mol% have been employed in reasonably large scale reac-
tions (10–20 mmol), and the catalyst also supports the presence of the standard
functional groups for this general class of catalysts (Eq. 68). One problem with
the catalyst is that it apparently becomes deactivated over time because of hy-
dride dimer formation. Ideal reaction conditions for slow-reacting substrates
thus involve addition of smaller portions of the catalyst at fixed intervals to
maintain an active concentration of the catalyst.
5% [(CpTMS)2YMe]2 SiH2Ph
(67)
PhSiH3, cyclohexane
rt, 1 h, 88%
OTBDPS OTBDPS
Me (68)
PhSiH3, cyclohexane
rt,16 h, 74%
The expanded capabilities of this catalyst allowed the construction of addi-

tional ring systems [44]. A transannular olefin insertion formed a bicyc-
lo[3.3.1]nonane structure (Eq. 69). Multiple insertion steps can selectively
transform a monocyclic substrate into a propellane derivative (Eq. 70). The cat-
alytic cycle begins at the monosubstituted olefin, followed by the insertion of the
remaining double bonds to form five membered rings.
(69)
PhSiH3, cyclohexane
rt, 20 h, 50%
5% [(CpTMS)2YMe]2
+
PhSiH3, cyclohexane
SiH2Ph
rt, 1 h
75%
(70)
SiH2Ph
+
14%
This catalyst is surprisingly intolerant of branching on the hindered olefin

(Eq. 71) [44]. The addition of two methylene units between the alkene and the
branch point is required to provide good yields of cyclized product. Another
limitation is the inability of the complex to insert an endocyclic olefin (Eq. 72).
5% [(CpTMS)2LnMe]2 SiH2Ph
( )n ( )n +
PhSiH3, cyclohexane
rt, 1 h
n = 0, Ln = Lu 0%
n = 2, Ln = Y 84%
(71)
PhH2Si
+ ( )n
84%
0%
5% [(CpTMS)2LuMe]2
SiH2Ph
rt,1 h, 93%
5.3.3
Cyclization/Silylation of Enynes and Dienynes
Enynes have been found to be excellent substrates for the cyclization/silylation

sequential reaction [45]. The electron rich alkyne undergoes preferential reac-
tion, thus requiring propargyl branching to direct the regiochemistry of the in-
itial insertion. Although sp2 hybridized, the organometallic originally formed is
converted smoothly via the cyclization/silylation process to afford the desired
products. A variety of functional groups can be tolerated at key positions in

these substrates (Eqs. 73, 74). The diastereoselection varies reliably with the size
of the substituent, as would be expected from the chair-like transition structure
for insertion. Six-membered rings can also be generated in high yields and with
modest diastereoselection when phenylmethylsilane is employed (Eq. 75). In
this case varying the silylating reagent causes a drastic change in the outcome of
the reaction (compare with Eq. 35).
O
O OCPh3 5% Cp*2YMe•THF O
(73)
O PhSiH3
88%, 35 : 1 ds OCPh3
PhH2Si
R 5% Cp*2YMe·THF
+
PhSiH3 R
cyclohexane, rt, 2h
SiH2Ph
+
R
SiH2Ph (74)
R % Yield ds
OTBDMS 93 6.5 : 1
OTIPS 93 12 : 1
OTr 84 24 : 1
Et 88 >50 : 1
CH2OMe (100 ˚C) 80 20 : 1
CH2OTBDMS 76 >50 : 1
N 91 40 : 1
TBDMSO 12% Cp*2YMe•THF

(75)
MePhSiH2
cyclohexane, 50 ˚C, 8 h
quant., 4 : 1 ds PhMeHSi OTBDMS
The cyclization protocol can be carried a step further by judiciously placing

another olefin in the substrate [38]. The incorporation of an additional allylic
group only results in low yields of bicyclic products (Eq. 76). The reduced yield
is undoubtedly because of the poor chemoselectivity between the alkyne and the
allylic olefin. Alkyl substitution on the allyl group gives complete selectivity for
initial alkyne insertion, but the hindered olefin prevents bicyclic product forma-
tion (Eq. 77). Geminal dimethyl substitution at the allylic position, however,
provides selectivity in the initial insertion without stopping the second intramo-
lecular insertion from taking place (Eq. 78). This dienyne cyclization allows an-
other entry into the strained trans-bicyclo[3.3.0]octane system, and contains an
additional handle for further functionalization.
5% Cp*2YMe•THF
SiH2Ph (76)
benzene-d6, PhSiH3
rt, 2.5 h, 33%
5% Cp*2YMe•THF
SiH2Ph (77)
benzene-d6, PhSiH3
rt, 24 h, 84%
H
5% Cp*2YMe•THF
benzene-d6, PhSiH3, rt SiH2Ph (78)

18 h, 76%, 3.9 : 1 ds
A single substituent allylic to the monosubstituted olefin is sterically large

enough to make the initial insertion selective (Eqs. 79, 80) [38]. Either substrate
diastereomer can be prepared, leading to different steric interactions in the
transition states (Figs. 13, 14), and different product stereochemistry patterns.
O OTr
O 5% Cp*2YMe•THF
(79)
SiH2Ph
benzene-d6, PhSiH3 O H
OTr rt, 90%, >40 : 1 ds
O
M H
R' R'
H M
R R H
R' H
R' M conformation leading to the formation

cat. of the major product
H
R M
R H
R' M R'
H R
H H
R
conformation leading to the formation
of the minor product
Fig. 13. Steric factors governing dienyne bicyclization
M H
H H
R' M
R R R'
R' H
H M conformation leading to the formation

cat. of the minor product
R'
R M
R H
H M H
R' R
H R'
R
conformation leading to the formation
of the major product
Fig. 14. Steric factors governing dienyne bicyclization
O Bn
O 5% Cp*2YMe•THF
SiH2Ph (80)
Bn benzene-d6, PhSiH3 O H
rt, 89%, 30 : 1 ds
O
If the alkyl chain is shortened by one carbon, a substrate is generated that has
the possibility for bicyclo[2.2.1]heptane generation (Eq. 81) [38]. After the ini-
tial alkyne insertion, the catalyst must choose between cyclobutane and cy-
clopentane formation. The five-membered ring is formed because of the lower
strain involved, but the remaining olefin is not inserted because the lowest ener-
gy conformation of the organometallic intermediate places the olefin out of
reach of the carbon-metal bond (Eq. 82).
SiH2Ph
OTBDMS
5% Cp*2YMe•THF
OTBDMS (81)
benzene-d6, PhSiH3
rt, 2h, 70%
SiH2Ph
H OTBDMS H
H
H (82)
R
R OTBDMS
YCp*2
YCp*2
6
Conclusions
The lanthanide- and group 3 metallocenes exhibit a rich chemistry that can be
exploited for the selective synthesis of small molecules. At least one class of cat-
alysts that are easily synthesized in a single pot exhibit reasonable stability in the
air. Consequently, they should be readily accessible to practicing synthetic or-
ganic chemists. Catalysts have been developed that permit reactions of mono-
substituted and 1,1-disubstituted alkenes, as well as internal alkynes. Practical
solutions for the inability of more highly substituted alkenes to insert have yet
to be reduced to practice. Terminal alkynes are rapidly metallated by these cat-
alysts, and are unlikely to be adaptable to many of the processes outlined in this
contribution. A variety of functional groups are tolerated by the catalysts (hali-
des, acetals, thioacetals, ethers, and amines), and thus highly functionalized
substrates of interest in complex molecule synthesis should be amenable to uti-
lization in selected processes. A high degree of chemoselectivity can be achieved
in polyunsaturated systems, and regiochemistry in the olefin insertion reactions
can also be controlled. Both of these conspire to provide an effective means to
control the direction of cyclization in unsymmetrical systems. Excellent diaster-
eoselectivity can often be achieved, taking advantage of both the inherent selec-
tivity of the catalysts themselves as well as the highly ordered transition struc-
tures involved in the intramolecular processes they promote. Finally, elegant
asymmetric catalysts have been synthesized and utilized in selective reactions.
Further developments in this arena are certain to produce a class of readily avail-
able catalysts that provide rapid and efficient entry to a wide range of complex
structures in enantiopure form.
Acknowledgments
Our work in this area was supported by a research grant from the National Insti-
tutes of Health (GM48580). The authors thank a very talented group of cowork-
ers whose names appear in the references below for their dedicated effort to this
chemistry.
7
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Influence of Solvents or Additives on the Organic Chemistry
Mediated by Diiodosamarium
Henri B. Kagan*, Jean-Louis Namy
Laboratoire de Synthèse Asymétrique, Institut de Chimie Moléculaire d’Orsay,

Bat. 420, Université Paris Sud, 91405 Orsay, France
*e-mail: [email protected]
The reactivity of diiodosamarium in solvents other than THF or in mixtures of solvents are
discussed. The influence of additives able to coordinate to samarium are then considered
(amides, amines or ethers). Proton donors sometimes drastically modify the selectivity of
reactions induced by diiodosamarium; some metal salts [such as Fe(III) or Ni(II)] in cata-
lytic amounts may also strongly accelerate or modify reactions induced by diiodosamar-
ium. Thanks to the above tuning of the diiodosamarium reactivity, rich and diversified or-
ganic transformations have been performed, some examples of which are presented.
Keywords: Samarium diiodide, Electron transfer, Organosamarium, Radicals, Selectivity
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
2 Influence of Solvents . . . . . . . . . . . . . . . . . . . . . . . . . . 156
2.1 Tetrahydrofuran . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

2.2 Tetrahydropyran . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
2.3 Ethers Other Than THF or THP . . . . . . . . . . . . . . . . . . . . 160
2.4 Nitriles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
2.5 Benzene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
3 Influence of Additives . . . . . . . . . . . . . . . . . . . . . . . . . 163
3.1 Electron-Rich Additives . . . . . . . . . . . . . . . . . . . . . . . . 163

3.1.1 Hexamethylphosphoramide . . . . . . . . . . . . . . . . . . . . . . 163
3.1.2 N,N'-Dimethylpropyleneurea . . . . . . . . . . . . . . . . . . . . . 175
3.1.3 Other Nitrogen Ligands . . . . . . . . . . . . . . . . . . . . . . . . 177
3.1.4 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
3.2 Proton Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
3.2.1 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
3.2.2 Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
3.2.2.1 Reduction of Carbonyl and C=N Groups . . . . . . . . . . . . . . 181
3.2.2.2 Pinacol Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
3.2.2.3 Carbonyl-Ene Couplings . . . . . . . . . . . . . . . . . . . . . . . . 182
156 Henri B. Kagan, Jean-Louis Namy
3.2.2.4 Cleavage of Carbon–Heteroatom Bonds . . . . . . . . . . . . . . . 185

3.2.2.5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
3.2.3 Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
3.3 Metal Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
3.3.1 Iron Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
3.3.2 Nickel Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
3.3.3 Cobalt Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
3.3.4 Copper Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
3.3.5 Chromium Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
3.3.6 Palladium Complexes . . . . . . . . . . . . . . . . . . . . . . . . . 192
3.3.7 Lithium Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
5 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
1
Introduction
Diiodosamarium was prepared for the first time by Matignon and Cazes in 1906
by heating triiodosamarium at high temperature under an atmosphere of hydro-
gen [1]. For a long time, subsequent preparations used high temperature tech-
nology and solid state chemistry (for example, see [2]).
In 1977 we described the mild preparation of diiodosamarium at room tem-
perature by reaction between samarium powder and 1,2-diiodoethane in THF
[3]. The dark-green solution of SmI2 in THF (0.1 M) was used as a convenient
reducing agent. We reported in 1980 the basic organic transformations induced
by this new reagent [4]. Since that time we, as well as many other groups, have
discovered plenty of new reactions, often performed under smooth conditions
and with a high selectivity, through a combination of radical and organometallic
chemistry. Diiodosamarium is becoming a major reagent in organic chemistry,
many reviews on its reactivity are available (for example, see [5–12]). In this ar-
ticle we shall discuss the various ways to tune the reducing properties of diio-
dosamarium by changing THF to another solvent or by introduction of various
additives which can coordinate to samarium or act as catalysts (for a short re-
view, see [13]).
2
Influence of Solvents
2.1
Tetrahydrofuran (THF)
The chemistry of diiodosamarium has been developed in THF mainly because

the mild preparation of SmI2 from samarium powder and 1,2-diiodosamarium
Influence of Solvents or Additives on the Organic Chemistry Mediated by Diiodosamarium 157
is performed in THF to give stable solutions (under inert atmosphere) of the re-
agent [3,4,14]. During the period 1977–1986, the basic organic transformations
induced by SmI2 involved reactions in THF. In 1987 Inanaga et al. described the
acceleration of SmI2-mediated reactions by addition of some HMPA (usually
5%) in THF [15,16]. This effect is discussed in Sect. 3. It involves the coordinat-
ing properties of HMPA towards Sm(II) and Sm(III) ions. Another way to alter
the redox properties of the Sm(II)/Sm(III) couple is to replace THF by another
solvent. One method is to evaporate THF and to add the desired solvent. This ap-
proach has been used to prepare SmI2 complexed by various nitriles (vide infra).
The difficulty comes from the necessity to fully remove the last THF molecules
which remain bound to SmI2, and which may influence its reactivity [17]. The
best strategy, therefore, is to try to generate SmI2 directly in the desired solvent.
This has been achieved successfully in nitriles, in tetrahydropyran (THP), in tet-
raglyme and even in benzene. There are several incentives for performing SmI2-
induced chemistry in various solvents. One can expect some of the following
consequences:
1. Acceleration of some reactions,
2. An improved selectivity,
3. New reactions, and
4. Elimination of by-products generated from competitive reactions with THF
(H-abstraction, ring opening, etc.).
2.2
Tetrahydropyran (THP)
In 1992, Ito et al. reported the possibility of replacing THF by tetrahydropyran

(THP) in some reactions induced by SmI2 [19,20]. These authors wanted to pre-
pare carbanions α to an amino nitrogen, through the strategy depicted in
Scheme 1. The reactions were performed in the mixture THP/HMPA, since the
Scheme 1
yields were slightly better than in THF which acts as an intermolecular hydrogen
donor to the aryl radical. The appended orthoiodobenzyl in 1 thus generated or-
ganosamarium 2 which then produced N-benzyl amines 3 by reaction with var-
ious electrophiles. SmI2 was directly prepared in THP. Undheim et al. applied
this reaction to the alkylation of saturated heterocycles α to nitrogen [21].
In 1994 we set up independently a preparation of SmI2 in THP from samar-
ium metal and 1,2-diodoethane [22]. We wanted to explore the possibility of im-
proving the yields of the acid chloride chemistry, where by-products arise by
ring opening of THF. Indeed there was a complete absence of the above by-prod-
ucts. Interestingly, acid chlorides with a branched α-carbon react with SmI2 to
give stable THP solutions of acylsamariums 4 which can then react with an alde-
hyde or ketone to give the mixed α-ketols 5 (Scheme 2). This two-step process
avoids the competitive pinacol formation, especially fast when an aldehyde is in
the presence of SmI2. Some examples are indicated in Scheme 2. The acylsamar-
ium structure 4 is well supported by the formation of deuterated aldehyde 8, by
reduction of acid chloride 7 and by reaction with D2O.
Scheme 2
Acid chlorides with an α-carbon with at least one hydrogen are prone to give
self-coupling to symmetrical α-ketols 6. However, the Barbier procedure in THP
allows the preparation of mixed α-ketols 5 in good yields even when using alde-
hydes.
Recently we discovered that allylic and benzylic samarium compounds could
be generated in THP [23]. For example, allylic iodide 9 treated at –15 °C with a
THP solution of SmI2 (2 equiv) followed by addition of butanone at the same
temperature gave in 90% isolated yield homoallylic alcohol 10 devoid of the usu-
al branched isomer (Scheme 3). Treatment of the allylic organosamarium with
D2O provided a fair yield of deuterated alkene. Allylsamarium itself is smoothly
prepared at 0 °C and reacts with various types of substrates. Especially interest-
ing is the high endo stereoselectivity of addition to camphor, the allylation of im-
ine 11 and the addition on β-keto ester 12 which is easily enolizable. Diiodoben-
zylsamarium may be prepared at –15 °C from benzyl bromide and reacts with 2-
octanone to give the tertiary alcohol in good yield.
In conclusion, THP may in many cases improve the efficiency of reactions in-
itially performed in THF and stabilize organosamarium species which are gen-
erated and which may subsequently react with various electrophiles.
Scheme 3
2.3
Ethers Other Than THF or THP
There are almost no reports of preparation of SmI2 in ethers other than THF or
THP. Inanaga et al. prepared SmI2 in 1,3-dioxolane and then added 10% ace-
tonitrile to produce a clear solution. This solution was used in the masked
formylation of aldehydes or ketones in the presence of iodobenzene [24]. Iodo-
benzene is transformed into the benzene radical which generates the 1,3-diox-
olanyl radical. The latter is presumably reduced to the corresponding organosa-
marium which then adds on the carbonyl. This process is illustrated in Scheme 4
for cyclododecanone. It is essential to avoid the presence of THF which will com-
pete with 1,3-dioxolane as a hydrogen donor to the benzene radical.
Tetraglyme (2,5,8,11,14-pentaoxapentadecane) has been used in the hy-
droxymethylation of aldehydes via addition of benzyl chloromethyl ether in the
presence of SmI2. Addition of tetraglyme suppresses the competitive pinacol for-
mation, presumably by a complex formation with SmI2 as evidenced by a purple
color [25]. Tetraglyme has also been used as a cosolvent in an intramolecular
Barbier reaction involving an iodoaldehyde and a THF solution of diiodosamar-
ium [26].
2.4
Nitriles
Diiodosamarium in THF induces a reductive coupling of acid chlorides to form

α-ketols 6 (Scheme 5) [27]. A mixed coupling between an acid chloride and a ke-
tone may also give ketols 13. We found that the by-product 14 was produced in
many cases by the classical acylation of THF which involves a ring opening cat-
alyzed by a Lewis acid [here the Sm(III) species]. Ruder discovered that SmI2
Scheme 4
Scheme 5
could be readily prepared in acetonitrile [28]. This author claimed that mixed α-
ketols 13 were produced by a two-step procedure and in good yields in ace-
tonitrile. We reinvestigated this work and found that it gave a mixture of prod-
ucts where the pinacol derived from the ketone was the major product [29]. Re-
activity of SmI2 in acetonitrile towards acid chlorides is roughly the same as in
THF. Many by-products are formed involving some reactions with acetonitrile.
In order to avoid the C-H acidity in the α of the nitrile group we investigated the
use of pivalonitrile. It is possible to prepare SmI2 (as a slurry) in pivalonitrile
from samarium powder and 1,2-diiodoethane [29]. An X-ray crystal structure of
SmI2-(NCCMe3)2 was performed by Sen et al. and shows a distorted octahedron
around samarium with a bent Sm-N=C structure [30].The cross-coupling be-
tween acid chlorides and ketones gave α-ketols 2 in moderate yields. Barbier re-
actions are slower in acetonitrile than in THF; however, the regioselectivity of
the reactions between allylic halides and ketones is significantly improved (in fa-
vor of the unbranched isomer). Surprisingly, HMPA does not enhance the reac-
tivity of SmI2 in nitriles (Barbier reactions or pinacolization of ketones). Reac-
tions are accelerated by catalytic amounts of some transition-metal salts (see
Sect. 3.3.6). Diiodosamarium may be prepared in propanenitrile or octaneni-
trile, but these solvents do not offer special advantages over pivalonitrile.
It is worth pointing out that acetonitrile was used as a cosolvent by Inanaga et
al. in 1987 [4]. These authors later studied SmI2-promoted aryl radical cycliza-
tion with olefins and obtained quite good yields in acetonitrile [31].
SmI2 in acetonitrile has been used for the preparation in good yields of 1,3-
diketones 15 [32]. The authors first added the α-halo ketone to the SmI2 solution
and subsequently added the desired acid chloride or anhydride. No comparisons
were given between reactions run in THF or acetonitrile.
Scheme 6
Ishii et al. prepared an Sm(II) reagent in acetonitrile from NaI, ClSiMe3 and
samarium grain. A soluble species was produced with the deep-green color of
SmI2 but its structure was not established [33]. At –40 °C this Sm(II) reagent is
able to dehalogenate α-chloro or α-bromo ketones or esters, if methanol is
present as the proton source. Acetonitrile was superior to THF or DME for this
reaction. The reagent gave a faster reaction compared to SmI2/THF for the for-
mation of pinacols of acetophenone [34]. Curiously, benzaldehyde did not pro-
duce hydrobenzoin unless HMPA was added. A lactone formation was the result
of the coupling of methyl acrylate and a ketone or imine (Scheme 6). Reformat-
sky-type reactions between ethyl α-bromoacetate and ketones gave satisfactory
yields of β-hydroxy esters, without showing any special improvement with re-
spect to the SmI2/THF system. However, it is interesting to note that some Refor-
matsky or Barbier reactions have been achieved in good yields with octanal,
without perturbation by pinacol formation.
2.5
Benzene
It is not possible to prepare SmI2 in benzene from samarium and 1,2-diio-

doethane or iodine. However, it was discovered that addition of 10% HMPA as a
cosolvent to benzene promoted the reaction of samarium and 1,2-diiodoethane
[35]. The reagent reduced various 1,1-dibromoalkenes to the corresponding re-
arranged alkynes, presumably through the generation of alkylidenecarbenes
(Scheme 7). The use of benzene instead of THF avoided the formation of re-
duced products obtained by hydrogen abstraction. This process was extended to
the synthesis of cyclopentenes by C-H insertion on the intermediate carbene
[36]. The reaction works especially well from 1,1-diiodoalkenes (Scheme 7). The
same authors also used the benzene/HMPA solvent to achieve some SmI2-in-
duced Wittig rearrangements via 1,5-hydrogen transfer of vinyl radicals [37]
(Scheme 7). Here again, it is crucial to avoid THF which will induce a competi-
tive intermolecular hydrogen abstraction.
Scheme 7
3
Influence of Additives
3.1
Electron-Rich Additives
3.1.1
Hexamethylphosphoramide (HMPA)
The highly promoted effect of HMPA on reactions of SmI2 was reported for the
first time in 1986 by Inanaga et al. [38] for the reductive cross-coupling of carb-
onyl compounds with α,β-unsaturated esters (Scheme 8). HMPA was used as a
cosolvent with THF (ca. 5%). Enhancement of the coupling rates and yields were
quite remarkable; however, the diastereoselectivity was sometimes diminished
in the presence of HMPA.
Independently, Fukuzawa and co-workers [39] reported intramolecular reac-
tions leading to bicyclic γ-lactones from keto or aldo α,β-unsaturated esters
(Scheme 9). The reaction was mediated by SmI2 in the presence of HMPA
(THF/HMPA=10/1) but the beneficial effect of HMPA was less obvious in that
case.
Scheme 8
Scheme 9
Scheme 10
Inanaga et al. have developed the use of HMPA for the highly regioselective
reduction of α,β-epoxy esters and δ,γ-epoxy α,β-unsaturated esters [40]
(Scheme 10).
The best results were obtained when HMPA (5 equiv) and dimethylamino
ethanol (DMAE, 2 equiv) were used as additives. The authors also reported the
reductive cross-coupling of 1,3-dioxolane with carbonyl compounds to yield α-
hydroxy derivatives [24]; the reaction was performed in the presence of HMPA
(ca. 5% of the solvent) and was complete within 5 min at room temperature
(Scheme 11).
A remarkable effect by HMPA was observed in the reduction of organic hali-
des with SmI2 in THF [41] (Scheme 12).
As mentioned in Sect. 2.3, Inanaga and co-workers have demonstrated that
Barbier-type reactions of organic halides with carbonyl compounds are promot-
ed by addition of HMPA [16]. They reported a mild convenient method for the
direct synthesis of lactones from bromo esters and ketones or aldehydes by using
a HMPA-promoted Barbier-type reaction with SmI2 (Scheme 13). They also
found that the SmI2/THF-HMPA system was highly useful for the generation of
Scheme 11
Scheme 12
Scheme 13
Scheme 14
ketyls and their intramolecular addition to a variety of activated olefins [42]

(Scheme 14). In addition, this system has been used to successfully reduce orga-
no heteroatom oxides including triphenyl phosphine oxide [43].
Thus the most popular way to increase the rate of reactions of diiodosamar-
ium has become the use of a mixture of THF–HMPA (90–95:10–5) as solvent. Al-
though the coordination of HMPA to the Sm(II) ion was thought to be responsi-
ble for this effect, the role played by HMPA remained unclear until 1994.
In order to clarify this problem, Hou and Wakatsuki [44] prepared SmI2/HMPA
complexes by addition of HMPA to a blue solution of SmI2 in THF. The resulting
Scheme 15
purple solution was concentrated and toluene was added. After a few days at
room temperature, black-purple blocks of SmI2(HMPA)4 were deposited in 90%
yield, and they were structurally characterized. It appears that the Sm(II) ion sits
on an inversion center and is bonded by two I– anions and four HMPA ligands
in a distorted octahedron. The central Sm(II) ion and the four HMPA ligands are
exactly coplanar and the two iodide anions are mutually trans (Scheme 15).
In a recent work, electrochemical studies of the reducing power of SmI2 in
THF and the effect of HMPA cosolvent as a function of concentration have been
reported [45]. This effect was studied by recording a linear sweep voltamogram
for each cosolvent addition. The oxidation potential vs. the Ag/AgNO3 reference
electrode for 0 to 6 equiv of HMPA cosolvent was measured. The addition of
3 equiv of HMPA to SmI2 had a drastic effect on the redox potential, increasing
the oxidation potential from –1.33 to –1.95 V. The addition of 4 equiv of HMPA
to SmI2 increased the potential even further to –2.05. Further addition of HMPA
showed no effect on the redox potential.
These observations are consistent with the structure determined by Hou et
al.; the complex SmI2(HMPA)4 should be the reactive intermediate responsible
for the unique reactivity of the SmI2/THF–HMPA system.
Preparation, structural characterization and reactivity studies of SmI3–
HMPA complexes have also been performed [46]. The composition of the dried
complex was found to be SmI3(HMPA)4. The reactivity of this complex was ex-
amined in comparison with that of SmI3 in THF only. In contrast to the latter
complex, the HMPA complex was not reduced to low-valent samarium species
by n-butyl lithium or sec-butyl lithium. These results might be interpreted by
considering that this Sm(III) complex is well stabilized by the coordination of
HMPA which could be one of the driving forces for the facile electron transfer
from SmI2–HMPA complexes.
Molander et al. [47] suggested that other factors could be involved in the ef-
fective role of this additive: disaggregation of SmI2, f-orbital perturbation due to
the ligand field effect in the presence of the strong donor ligand HMPA raising
the energy of the HOMO (electron-donating orbital). A combination of these ef-
fects might also be considered.
The effect of HMPA on the spectroscopic properties of SmI2 has also been ex-
amined [48].
We wish to review here some studies that stress the specific role played by
HMPA in samarium diiodide reactions.
Reduction of 1-iodo-5-hexene with SmI2/THF–HMPA has been studied by

Curran and co-workers [49] (Scheme 16). They found that reaction is slow with-
out HMPA. A reasonable reaction time (<10 min) is attained with 2 equiv of
HMPA per SmI2. In the range from 1.3 to 4.4 equiv, the ratio of directly reduced
product to the rearranged product increases dramatically (from 8:92 to 54:46).
Increasing the amount of HMPA beyond 5 equiv results in a very slow decrease
in the ratio. These results are consistent with the above results concerning the
structure of the complex SmI2–HMPA [44] and the electrochemical studies [45].
The easier the reduction of the 5-hexenyl radical to organosamarium species,
the less the cyclopentyl-carbinyl radical is formed.
Curran et al. demonstrated that reduction of aryl halides to radicals is also
strongly accelerated in the presence of HMPA, as well as reduction of alkyl rad-
icals to alkyl samarium [50,51] (Scheme 17).
HMPA is also necessary for the in situ preparation of the organosamarium
species from alkyl halides and SmI2 in THF [52]. A similar effect was also ob-
served in the case of reactions performed in tetrahydropyran [23].
Molander et al. studied the intramolecular coupling of unactivated olefinic
ketones by a reductive ketyl-olefin radical cyclization, mediated by SmI2 in the
presence of HMPA [47] (Scheme 18).
HMPA was required to promote efficient ketyl-olefin cyclization in the de-
sired manner. It seems that factors other than reduction potentials also play a
Scheme 16
Scheme 17
role in the efficiency of HMPA as an additive in SmI2-promoted reactions: ketyl

radical anions appear to have greater persistence when generated in the pres-
ence of HMPA than without additives. By progressively increasing the amount of
HMPA, from 0 to 8 equiv, the percentage of 20 (generated by hydrogen abstrac-
tion from the solvent) decreased and the stereoselectivity of 19 increased. These
enhanced diastereoselectivities were attributed to an added steric component in
the cyclization transition states. As an application, SmI2 in the presence of
HMPA has been used to promote 8-endo cyclization of various keto olefins af-
fording a variety of eight-membered ring products in fair to excellent yields
[53]. This success was in part attributed to the formation of ketyls exhibiting re-
markable persistence in the presence of HMPA perhaps because the HMPA ex-
cludes the proton source (t-BuOH) from the coordination sphere of the Sm(III)
ion.
The successful intramolecular coupling between vinyl oxiranes and ketones
mediated by SmI2 in the presence of HMPA as a cosolvent has been reported [54]
(Scheme 19). The use of HMPA as a cosolvent allowed the couplings to be per-
formed at lower temperatures and improved the regioselectivity of the process
as the 1,5-diols were then the only products isolated; the E/Z ratio was also af-
fected.
Scheme 18
Scheme 19
Studies by Molander et al. have demonstrated that samarium diiodide effi-

ciently promotes the intramolecular coupling of ketones with distal epoxy ole-
fins in the presence of HMPA, in good yields and often with high diastereoselec-
tivity (Scheme 20). When tetramethylguanidine was used instead of HMPA, the
desired carbocycle was obtained in good yield but the diastereoselectivity was
diminished [55]. Evidence has been presented that suggests that the reaction
proceeds via an initial radical cyclization route although reaction via an allyl sa-
marium species cannot be ruled out.
In order to achieve the total synthesis of (–)-anastrephin, a D-glucose-derived
α,β-unsaturated ester, was subjected to an SmI2-mediated intramolecular re-
ductive coupling reaction with the SmI2/THF–HMPA system. The reaction pro-
ceeded with moderate stereoselectivity leading to a diastereomeric mixture of
hexahydro benzofuran-2(3H)-ones in which a cis-fused product was the major
isomer [56] (Scheme 21). The presence of HMPA was essential for smooth cou-
pling; significant reduction of the aldehyde to a hydroxymethyl group occurred
without HMPA.
The use of HMPA can modify the course of a reaction. It is well known that
aromatic aldehydes or aromatic ketones readily couple to pinacols 21 on treat-
ment with SmI2 in THF, but addition of 2.8 equiv of HMPA leads to the forma-
tion of product 22 that results from connecting a para carbon with the carbonyl
of another molecule (Scheme 22).
It is proposed that HMPA molecules coordinate with samarium ions through
their oxygen atom because the ketyls and ortho carbons are hindered by the
HMPA ligands; coupling at the para position with a second molecule of benzal-
dehyde would be favored [57,58].
Scheme 20
Scheme 21
Scheme 22
Scheme 23
Scheme 24
Similarly, methyl thiophenecarboxylate reacts at the C5 position with a series

of substituted benzaldehydes and acetophenone in the presence of the
SmI2/THF–HMPA system to give a samarium enediolate which can be trapped
by a second electrophile [59] (Scheme 23). The samarium-bonded ketyl anion
radical does not trap the hydrogen atom or undergo acyloin coupling, presum-
ably due to the hindrance of the ligated HMPA molecules.
Very interesting chemistry has been developed with sulfones and samarium
diiodide.
Neither deoxygenation nor desulfonylation occurs upon treatment of various
phenylsulfones with SmI2/THF. However, in the presence of HMPA, reductive
desulfonylation was achieved [60]. Thus a series of substituted glycosyl phenyl-
sulfones was converted into the corresponding glycals with SmI2/THF–HMPA
[61] (Scheme 24).
Scheme 25
Scheme 26
Scheme 27
The Julia alkylidenation was improved using SmI2/THF-HMPA instead of

Na(Hg) for the reductive elimination step. In contrast, a poor result was reported
without HMPA [62] (Scheme 25).
In the presence of HMPA, allylic sulfones react with SmI2 and ketones to give
a Barbier-type reaction (Scheme 26). Much lower yields are obtained if the rea-
gents are not thoroughly degassed, and in the absence of HMPA [63].
Completely stereoselective cyclizations using formyl allyl sulfides and sul-
fones have been described. Optimum conditions involved the slow addition of a
solution of the starting material in THF to a 0.1 M solution of SmI2 containing
8 equiv of HMPA in THF at –10 and –78 °C, respectively [64].
It has also been reported that SmI2 mediates the in situ reductive addition of
geminal bis-phenyl sulfones to ketones in THF. In the presence of HMPA
(10 equiv), addition to the carbonyl is completely suppressed, but not desulfo-
nylation [65] (Scheme 27).
Reaction of β-hydroxy or β-acetoxy sulfones with SmI2 in the presence of

HMPA caused effective reductive elimination to provide olefins [66]. In contrast,
Kende recorded a poor result in the reductive elimination of the β-hydroxy phe-
nyl sulfones with SmI2 without HMPA [67]. Finally, it has been reported that
contrary to phenyl sulfones, 2-pyridyl sulfones are instantaneously reduced in
the presence of SmI2 without additives [68].
Samarium(II) triflate, a promising reagent for selective organic synthesis, has
been prepared by treatment of a THF solution of Sm(OTf)3 with 1 equiv of an or-
ganolithium (or organomagnesium) reagent at room tempeature [69,70]
(Scheme 28). Generation of the samarium(II) was unsuccessful in the presence
of HMPA.
The Sm(OTf)3 reagent mediates the Grignard-type reaction in THF–HMPA.
Alkylation, allylation and benzylation of ketones and aldehydes with alkyl, allyl
or benzyl halides proceeded via stable organosamarium intermediates [69]
(Scheme 29).
Matsuda et al. have studied the hydroxyl group directed intermolecular ke-
tone-olefin coupling reactions, induced by SmI2, between α-hydroxy ketones
and α,β-unsaturated esters or nitriles (Scheme 30). It was noted that reactions
Scheme 28
Scheme 29
Scheme 30
run in the presence of HMPA resulted in all cases in some depression in the di-
astereoselection [71–73]. Various other reactions have been reported which ex-
emplify the crucial role of the solvent HMPA.
Inanaga et al. achieved the hydrodimerization of conjugated esters and
amides with the SmI2/THF–HMPA system in the presence of a proton source
[74].(Scheme 31). However, inexplicably, Alper et al. achieved reductions (not
reductive dimerization) of the double bond of α,β-unsaturated esters and
amides with the same system [75]. In the latter paper, however, the presence of
a proton donor is not mentioned.
The reductive coupling of α-bromoacetate to succinic acid diesters mediated
by SmI2 in the presence of HMPA has been reported [76] (Scheme 32).
In contrast, reactions performed without HMPA as additive do not lead to
dimerization but to β-keto esters [77] (Scheme 33). Obviously, the intermediate
samarium enolate which is formed behaves in a different way according to the
presence or the absence of HMPA.
The reductive dimerization of cyclopropane-1,1-dicarboxylic esters using
SmI2/THF has also been reported (Scheme 34). In this case, the addition of
Scheme 31
Scheme 32
Scheme 33
Scheme 34
HMPA did not improve yields of the dimer. On the contrary, yields were higher
in the absence of HMPA [78].
A new intramolecular reductive carbon–carbon bond formation has been
noted in reactions of 1-(2-formyloxyethyl)-3-formyl-oxycycloalkene with SmI2
giving a spiro hemiacetal (Scheme 35). The absence of HMPA caused a consid-
erable decrease in the yield of the hemiacetal [79].
Coupling reactions of indoles and carbonyl compounds (either intra- or
intermolecularly) have been described. This is a new method for hydroxylation
at the C2 position of indole (Scheme 36). The role of HMPA is crucial to prevent
reduction or pinacolic coupling of aromatic carbonyl compounds [80].
Stereocontrolled decalin ring annulation reactions through the hydroxyl
group directed pinacol coupling using SmI2 have been reported by Matsuda and
et al. Stereocomplementarity was observed depending on the presence or ab-
sence of HMPA [81] (Scheme 37). The authors propose that without HMPA only
the aldehyde of the substrate is reduced to the ketyl radical during the initial re-
Scheme 35
Scheme 36
Scheme 37
duction by SmI2, whereas in the presence of HMPA a ketyl radical pair is gener-
ated through a single electron transfer from SmI2.
Katritzky et al. have prepared α-amino carbanions from tosyl methyl amines.
The transformation was achieved by treatment with 2 equiv of SmI2 [82] in the
presence of an electrophile (Scheme 38). In the absence of HMPA the use of iso-
butyraldehyde as the electrophile gave only the amine dimer (98%). However,
the addition of 5% of HMPA resulted in a 67% yield of the desired product (62%)
with a minor amount of diamine (17%). The formation of the hydroxy amine
probably involves a carbanion intermediate whereas coupling gives the diamine.
Samarium diiodide has also been used for the intramolecular coupling of al-
dehydes and ketones with O-benzyl formaldoxime [83], for the corresponding
intermolecular coupling with diphenylhydrazone [84,85] and for the intra-
molecular coupling of an α,β-unsaturated ester with an oxime ether [86]
(Scheme 39). In all these cases the addition of HMPA was found to be essential
for a successful reaction.
3.1.2
N,N'-Dimethylpropyleneurea (DMPU)
Because of the toxicity of HMPA, studies on other samarium(II) additives have

been carried out by several researchers. DMPU, a well-known and less toxic al-
ternative to HMPA, has sometimes been used as a cosolvent for SmI2 reactions.
Addition of DMPU to a THF solution of SmI2 results in an immediate color
change from blue to purple.
Scheme 38
Scheme 39
Curran et al. were the first to use SmI2/THF–DMPU. This system promoted a
tandem radical cyclization [87] (Scheme 40). Reduction of 23 with SmI2/THF
produced 24, 25 and 26 in low yield; addition of HMPA accelerated the reaction
and gave 24 in 91% yield. DMPU as additive gave similar results to HMPA with
respect to reaction rate and yield but 25 and 26 were also formed albeit in low
yield (9 and 4%). In addition, the cyclization in THF–HMPA required less than
2 equiv of SmI2 (1.3 equiv) but when DMPU was used, a larger excess of SmI2
was needed, perhaps because the reaction mixture was heterogeneous.
Ring scission of cyclic β-halogeno ethers to olefinic alcohols mediated by
SmI2 has been studied. Scission in the tetrahydrofuran series could be accelerat-
ed by addition of HMPA or DMPU with only a small deterioration in diastereo-
selectivity, but in the tetrahydropyran series there was a drastic change in the
stereochemistry of the product when DMPU was used. Obviously, DMPU has a
substantial effect on the formation and conformation of complexes in solution
[88,89].
A mixture of THF and DMPU has been used as a solvent for SmI2 in various
reactions such as cyclization of alkynyl halides [90,91], tandem iodo-enone cy-
clization/samarium enolate aldol reaction [92], coupling of β-silylacrylic esters
[93], deprotection of arenesulfonamides [94] and pyridine-2-sulfonamides [95],
radical ring-opening reactions of cyclopropyl ketones and the trapping of the re-
sulting samarium(III) enolates by a variety of electrophiles [96] (Scheme 41).
From the above studies, the SmI2/THF–DMPU combination emerges as the
most useful, in particular because in this case the problem of second electron de-
livery is avoided.
Scheme 40
Scheme 41
Scheme 42
The SmI2/THF–DMPU system has also been used as an alternative to the

Na(Hg) amalgam in the Julia–Lythgoe olefination [97] (Scheme 42). It was found
that this system gave a positive rate enhancement (from 95% in 5 d with
SmI2/THF to 95% in 35 min). The DMPU reaction also gave considerably higher
stereoselectivity (E/Z=9:1) than was observed using HMPA. Further studies to
optimize the reactions have led to the use of 10 to 20 equiv each of DMPU and
MeOH, respectively, which gives reasonable reaction times (35 min) and high
selectivity for the E olefin (99:1).
The role of DMPU has been studied by Curran et al. in the reduction of an o-
(allyloxy) iodobenzene. It was found that DMPU is much more efficient in MeCN
than in THF [98]. The reduced effectiveness of DMPU in THF may be due in part
to formation of an insoluble SmI2/DMPU complex.
3.1.3
Other Nitrogen Ligands
Various other commercially available nitrogen ligands have been screened to in-
crease the reducing power of SmI2 in THF.
Inanaga et al. have studied the selective conjugate reduction of α,β-unsaturat-
ed esters and amides with SmI2. While the reductive dimerization was promoted
by HMPA [74], the use of dimethylformamide (DMF), dimethylacetamide
(DMA), tetramethylurea (TMU) and bidentate ligands such as N,N,N',N'-tetram-
ethylethylenediamine (TMEDA)and N,N,N'N'-tetramethylpropylenediamine
(TMPDA) were effective for the conjugate reduction of the substrate. DMA was
found to be the most promising. In contrast, in the presence of the tridentate
chelating agent N,N,N'N''N''-pentamethyldiethylenetriamine, no reaction took
place. This result might be due to the complete occupancy of the coordination
sphere of samarium [99].
The formation of an aryl radical from the corresponding aryl iodide or aryl
bromide using SmI2 has been carried out in the presence of various other nitro-
gen ligands (Scheme 43). The results obtained with Et3N, DBU or TMG were sat-
isfactory or even superior to the ones obtained with HMPA (27+28: 71%; 4 h;
27/28=81:29). It is worth noting that the ligand/SmI2 molar ratio has practically
no effect on the reaction course if more than 2 equiv of ligand are present [100].
TMEDA has sometimes been used as an additive in the reduction of α,β-
epoxy esters. In this case it was associated with HMPA and isopropanol [40], as,
Scheme 43
Scheme 44
Scheme 45
for example, in the intermolecular aldol-type reactions of phenacyl bromides

with carbonyl compounds [101] and for the reduction of cyclopropyl lactones
[102] (Scheme 44).
TMG has been used for the cyclization of a keto vinyl epoxide (Scheme 45).
Better yields were achieved than with HMPA; unfortunately, a 1:1 mixture of di-
astereomers was obtained [55].
The effect of cosolvents (TMP, DBU, PMP, TMU, NMP, DMPU) on the oxida-
tion potential of SmI2 in THF has been studied. The change in the reducing power
of SmI2 is dependent on the nature and concentration of these cosolvents. For ex-
ample, the SmI2/TMU reducing species was determined to have an Eox of –1.99V
(vs. an Ag/AgNO3 electrode) at 30 equiv of cosolvent while the SmI2/DMPU
complex displayed an Eox of –2.21 V at the same cosolvent concentration. The ef-
fect of water on the Eox of SmI2 was also determined; it was found that 55 equiv
of water increased the oxidation potential to –1.74 V [103].
3.1.4
Miscellaneous
Kamochi and Kudo found that the reducing ability of SmI2 is enhanced by addi-
tion of a base (KOH, LiNH2 or LiOMe), allowing the fast reduction of carboxylic
acids to alcohols [104]. Reduction of nitriles to primary amines has also been re-
alized by the system SmI2/50% KOH (1:2) in a few minutes at room temperature
[105].
BINAPO (the bis-oxide of BINAP) can complex samarium and gives some
stereocontrol in the formation of γ-butyrolactones by reaction of ketones with
α,β-unsaturated esters and SmI2 in THF. Enantiomeric excesses (ee's) of up to
90% were obtained [106].
3.2
Proton Sources
All the reactions induced by SmI2 start with a one-electron transfer giving rise
to an anion radical which evolves in various ways: radical chemistry, cleavage
into a carbanion and a radical, further reduction to a dianion, etc. Very often
marked differences in the product distribution are observed when SmI2-in-
duced transformations are performed in aprotic or protic conditions, because in
the latter case in situ protonation of key intermediates may occur. Kinetic stabil-
ity of SmI2/THF solutions in the presence of some water or alcohols have been
reported [15,107]. It is then possible to use these solutions for in situ protonation
of end products or intermediates. For example, it has been firmly established
that the samarium Barbier reaction between an organic halide RI and a ketone
involves a reactive organosamarium intermediate RSmI2 since the reaction per-
formed in the presence of SmI2/THF–t-BuOD or EtOD leads to the formation of
some RD. Under the same conditions, and in the absence of ketones, the deuter-
ation of RI into RD was also achieved in good yield [108,109].
Apart from its usefulness for some mechanistic investigations the presence of
protic additives may disturb the course of a reaction and change the product dis-
tribution. It is this aspect which will be considered here.
3.2.1
Water
In 1980, we established that water was the additive of choice for the SmI2 reduc-
tion of ketones and aldehydes [15]. In fact, there is growing evidence that water
serves not only as a proton source but can also accelerate certain classes of sa-
marium reductions. Addition of water to THF solutions of SmI2 induces a color
change from the original deep blue to a wine-red similar to the one encountered
in a THF–HMPA mixture. The color persists for a few hours if pure and thor-
oughly deaerated water is used. It appears that water acting as a coordinating lig-
and (as well as a proton source) greatly increases the reducing ability of SmI2
(see Sect. 3.1.3 and [103]) and THF–H2O can thus be considered to be in some
reactions a good substitute for THF–HMPA.
Curran et al. have studied reductions of 1,3-diphenylpropanone, ethyl cinna-
mate, diphenyl sulfoxide, 1-iodododecane, and o-allyloxyiodobenzene with
SmI2 in the presence of water [98] (Scheme 46). The accelerating role of water in
the reduction of alkyl and aryl iodide has been readily demonstrated [99].
Inanaga et al. reported the use of a 37% aqueous solution of formaldehyde for
the reductive cross-coupling of carbonyl compounds with α,β-unsaturated es-
ters with the SmI2/THF–H2O system [38] (Scheme 47).
Ohgo et al. have achieved a cross-coupling reaction of aldehydes with α-dike-
tones to give the corresponding adducts [110] (Scheme 48); reactions without
HMPA gave better results compared with the reactions using HMPA as additive.
Scheme 46
Scheme 47
Scheme 48
Unprotected tetrono- and pentonolactone undergo an α-deoxygenation reac-

tion mediated by SmI2 in THF–H2O [111] (Scheme 49). The NO reductive cleav-
age reaction is also accelerated by addition of water [86].
Kamochi and Kudo have reported the use of the SmI2/THF–H2O system to re-
duce aromatic carboxylic acids to alcohols (Scheme 50). Furthermore, aromatic
esters amides and nitriles were similarly reduced by this system in good yield
[104]. As indicated above, reduction of carboxylic acids to primary alcohols is
also effective with SmI2 in a THF–H2O–NaOH mixture [105]. In contrast, with-
out water these substrates remain unchanged. With the SmI2/THF–H2O system,
pyridine was rapidly reduced to piperidine; in similar reactions with pyridine
derivatives bearing chloro, amino and cyano substituents, these functionalities
were partly eliminated to afford pyridine or piperidine [107].
Curran and Studer transformed in good yields some aromatic dimethylacetals
to methylbenzylacetals, by an overall process of reductive demethoxylation [112].
This reaction works by addition of 4 equiv of H2O at room temperature.
The reduction of allylic halides (in the cepham family) by SmI2/THF in the
presence of some water gave a very fast transformation into exomethylene ce-
phams [113]. The authors made the hypothesis that an intramolecular protona-
tion occurs in a σ-allylsamarium by H2O coordinated to samarium.
3.2.2
Alcohols
3.2.2.1
Reduction of Carbonyl and C=N Groups
We have shown that THF–MeOH solutions of SmI2 are excellent reducing agents
of ketones or aldehydes to the corresponding alcohols [15]. A mechanistic study
Scheme 49
Scheme 50
with MeOD established that 2-octanone was transformed into 2-D-octanol, pre-
sumably through the intermediate formation of the carbanion obtained by the
reduction of the hydroxy radical issued from the ketyl protonation [114]. Reduc-
tion of a mixture of aldehyde and ketone gave a high preference for the aldehyde
reduction [15].
The combination of SmI2 and trimethylsilyl chloride (in replacement of t-
BuOH) in THF–HMPA was found to accelerate the reduction of sterically hin-
dered or enolizable ketones such as 6-keto- or 20-keto-steroids and 5-cholesten-
one [115].
Isocyanates R–N=C=S have been transformed by SmI2 in good yields into thio-
formamides RNH–(H)C=S in THF–HMPA in the presence of t-BuOH at –78 °C
[116]. The use of t-BuOD gave the C-deuterated thioformamide, establishing
that the reaction occurs by two successive one-electron transfers giving this car-
banion which is trapped by in situ protonation.
3.2.2.2
Pinacol Formation
In 1983 we recognized that aprotic THF solutions of SmI2 gave pinacol forma-
tion from aldehydes or ketones; the reaction being quite fast with aldehydes or
aromatic ketones [117]. However, aromatic carbonyl compounds were coupled
in THF by the samarium/I2/MeOH system, SmI2 being formed in situ [118].
Hanessian et al. discovered that the intramolecular reductive coupling of var-
ious 1,6- and 1,5-dialdehydes gave mainly cis-diols [119]. This useful methodol-
ogy involves the presence of an alcohol (t-BuOH or MeOH) acting as an in situ
protonating agent for the reaction intermediate. For example, the myo-inositol
derivative 29 [120] and 30, an intermediate in the total synthesis of forskolin
[121], have been synthesized (Scheme 51). An intramolecular coupling of α-keto
aldehyde was also successful, giving a bicyclic system 31 which may be a relay in
the total synthesis of taxoids [122].
3.2.2.3
Carbonyl-Ene Couplings
The reductive coupling of ketones or aldehydes with electrophilic alkenes such

as conjugated esters (Scheme 52) has been described independently by Inanaga
et al. [38] and Fukuzawa et al. [123,124]. The reaction was performed in THF ei-
ther in the presence of HMPA [38] or an alcohol [123,124]. The mechanistic as-
pects of this reaction have been discussed [124]. Presumably, the ketyl radical or
its protonated form adds to ethyl acrylate with formation of the C–C bond. An
efficient enantioselective synthesis of γ-butyrolactones has been derived by us-
ing N-methylephedrinyl acrylate or crotonate [125]. One example (synthesis of
33) is indicated in Scheme 52.
The intramolecular reductive ketone-olefin coupling was realized by Molan-
der et al. by the combination SmI2/THF–t-BuOH [126]. For example, the spiro-
Scheme 51
Scheme 52
cyclic lactone 34 was obtained with high diastereoselectivity because of chela-

tion of oxygens on Sm3+ (Scheme 52). The protic conditions prevented a retro-
aldol process occurring, as observed under aprotic conditions.
Iminium salt 35 was reduced in anhydrous acetonitrile in the presence of at
least 1 equiv of camphorsulfonic acid (CSA) (Scheme 52) [127]. In this way, pyr-
rolidine 36 was obtained in good yield. The cyclization presumably involves a N-
protonated unsaturated α-amino radical, while the non-protonated form gives
less cyclization and more reduction of the C=N bond.
Triple bonds may also undergo coupling reactions to a carbonyl. Inanaga et
al. found that the reduction system SmI2/THF–HMPA–t–BuOH efficiently pro-
motes the carbonyl addition on the triple bond, generating allyl alcohol 37 [128]
(Scheme 53). A similar procedure was used for the intramolecular coupling re-
action [129]. The highest yields were observed for compounds with electron-
withdrawing groups on the terminal site of the alkyne, as for the reactions de-
scribed in Scheme 53.
Scheme 53
Intramolecular reductive coupling of aldehydes and allenic esters has also

been described [130]. For example, aldehyde 38 was transformed into cyclopen-
tanols 40a and 40b (Scheme 53). Presumably ketyl 39 is an intermediate in the
reaction. Although being nucleophilic in character it adds to the carbon adjacent
to the ester group because of the chelation on samarium, which explains the
good diastereoselectivity. The use of homologous aldehydes of 38 should gener-
ate rings of larger size than cyclopentane; however, the cyclizations are difficult
and need adjustments to the experimental conditions. A six-membered ring an-
alog of 40 was obtained by using methanol instead of tert-butanol. The seven-
membered homolog 42 was produced in acetonitrile containing 10 equiv of wa-
ter. Aldehyde 41 was transformed into different products 43 and 44 by minor
changes in the experimental conditions.
3.2.2.4
Cleavage of Carbon–Heteroatom Bonds
α-Heterosubstituted ketones are a very widely represented class of compounds

amongst organic compounds. Reduction of α-heterosubstituted ketones to ke-
tones is a useful synthetic operation. In 1986 it was shown that SmI2 is a good rea-
gent for this transformation, which was achieved under mild conditions (–78 °C)
in THF–MeOH [131]. For example, α-substituted ketones 45 (Scheme 54) were
reduced in 2-dodecanone in good yield for various X groups. Only X=OH gave
a poor yield of the desired ketone. The authors envisioned that the initial step of
the reaction is formation of an α-ketyl which is rapidly protonated by methanol.
A second electron transfer should produce a carbanion which generates an enol
by β-elimination. Finally, the enol tautomerizes into the ketone. Under the above
experimental conditions α-acetoxy esters were not reduced, a different result to
that with α-bromo esters or α-bromo ketones.
The reduction of cyanophosphates 46, readily prepared from ketones or alde-
hydes with diethyl phosphorocyanidate and lithium cyanide, led to nitriles in
excellent yields [132] (Scheme 54). This reductive cyanation process has also
Scheme 54
been applied to conjugated enones or enals, giving β,γ-unsaturated nitriles with-

out products from the migration of the double bond.
Aliphatic α-epoxy ketones were also successfully converted into the corre-
sponding β-hydroxy ketones by SmI2 in THF–methanol solution [133]. The pro-
tonation of the intermediate ketyls is the key step in the process. Radical •C(OH)
generated vicinal to an epoxide induces α C–O bond cleavage with ring opening
of the epoxide. The alkoxy radical is finally reduced to an alcoholate. Aliphatic
α-epoxy ketones have also been treated with diiodosamarium in the presence or
absence of methanol [134]. A large excess of methanol (or water) favored the for-
mation of the β-hydroxy ketone, which is absent under aprotic conditions (in
this case a small amount of α,β-diketone may be detected).
Deoxygenation reactions have been developed for the preparation of some
deoxy sugars. A convenient procedure is to use SmI2 in THF in the presence of
anhydrous ethylene glycol as the proton source (Scheme 55).
Peracetylated aldonolactones gave mixtures of the unsaturated aldonolactone
and the deoxy analog [135]. However, good control of the nature of the leaving
group and the addition or non-addition of HMPA may fully control the selectiv-
ity of the reaction in the direction of the saturated or the unsaturated sugars
[136]. Some examples are indicated in Scheme 55. A similar procedure has been
used for the anomeric deoxygenation of peracetylated 2-ulosonic acids (as me-
thyl esters) [137]. Deoxygenation in position α to a ketone has been successfully
performed in the taxoid family [138].
Reduction of epoxy esters was not selective in the presence of methanol or
ethanol but gave good yields of β-hydroxy esters by using N,N-dimethyleth-
anolamine (DMEA) [40]. DMEA seems to play the role of a proton source and
also acts as a chelator of samarium species, increasing the reduction power of
SmI2 and decreasing the Lewis acidity of Sm(III). See Scheme 56 for some exam-
ples.
Scheme 55
Scheme 56
The reduction of 2,3-epoxycycloalkanone hydrazones by SmI2 in THF in the

presence of t-BuOH has been investigated by Kang et al. [139]. 2-Acylaziridines
were converted into β-amino carboxyl compounds (Scheme 56) by a reaction
very similar to the reduction of α,β-epoxy ketones [140]. The main problems
were the unselective ring opening of the aziridine ring and the formation of
over-reduced amino alcohols. These difficulties were overcome by using 2.5 equiv
of SmI2 in THF at 0°C in the presence of a suitable proton source. In the case of
2-acylaziridines, methanol was preferred, while for aziridine-2-carboxylates
and aziridine-2-carboxamides, DMEA was the best additive. The usefulness of
DMEA may be related to several factors, as already pointed out by Inanaga et al.
for the reduction of epoxy esters [40] (vide supra).
3.2.2.5
Conclusions
Protic additives other than water strongly modify the course of the reactions
mediated by diiodosamarium. As discussed above, the additives protonate some
anionic intermediates to new intermediates, driving the reaction in the desired
direction. In some specific cases it may coordinate to samarium and modify the
redox and Lewis acid properties of some of the samarium complexes. Chiral pro-
tic additives may also act as asymmetric protonating agents of prochiral inter-
mediates. For example, Takeuchi et al. reduced benzil to the corresponding sa-
marium enediolate and treated it with various chiral amino alcohols. The result-
ing benzoin could be obtained with ee's up to 91% by using quinidine as the pro-
ton source [141]. The catalytic use of a C2-symmetric diol for asymmetric pro-
tonation of some samarium enolates was achieved in the presence of trityl alco-
hol (an achiral proton source for regeneration of the catalyst). In this way ee's up
to 93% were observed [142]. Enantioselective protonation of samarium enolates
generated from 2-methoxy-2-substituted cyclohexanones by SmI2 in the pres-

ence of some chelating chiral diols gave up to 94% ee of 2-substituted cyclohex-
anones [143,144]. The in situ asymmetric protonation of allenylsamariums ob-
tained by reduction of propargylic esters has recently been described (see
Sect. 3.3.6).
3.2.3
Acids
The combination of SmI2 with a protic or aprotic acid (POCl3, HCl, H2SO4 or
H3PO4) has been investigated by Kamochi and Kudo for the reduction of aro-
matic acids and derivatives [145]. Excellent results were obtained by the addi-
tion of an amount of 85% H3PO4. Thus, at room temperature, acids or esters gave
primary alcohols, while amides ArCONH2 were transformed into aldehydes and
aromatic nitriles into primary amines. All these reactions were performed in
THF in a few minutes. In some cases there were some differences to the corre-
sponding reduction in the presence of a base which was described in Sect. 3.1.4.
A mechanism was proposed by the authors to explain the influence of acids, in-
volving protonation of various intermediates.
Curran and Studer recently used 1 equiv of trifluoroacetic acid or BF3–OEt2
as a useful additive to promote the reductive coupling of aromatic dimethyla-
cetals to 1,2-diaryl-1,2-dimethoxyethanes [112]. If the acids were replaced by
water, a reductive demethoxylation occurred (see Sect. 3.2.1). The added acid
may activate the acetal, giving formation of an oxocarbenium ion which is then
reduced by SmI2 to a radical which couples or is further reduced. It is interesting
to note that a Lewis acid such as BF3–OEt2 is compatible with the use of SmI2.
3.3
Metal Salts
3.3.1
Iron Salts
In 1980 we noticed that a samarium Barbier reaction between n-butyl iodide and
2-octanone which needed 8 h at 65 °C could be run in 3 h at room temperature
in the presence of a catalytic amount (2 mol%) of ferric chloride [15]. This ex-
periment was inspired by the known catalytic effect of the Fe3+ ion on the
Ln2+/Ln3+ conversion [146]. The beneficial influence of the Fe(III) derivative in
reactions mediated by SmI2 has been used by several authors in various process-
es. Thus, Molander et al. described a general procedure for five- and six-mem-
bered ring annulation starting from 2-(ω-iodoalkyl) cycloalkanones [147].
Diiodosamarium induced an intramolecular Barbier reaction, under mild
conditions (room temperature), in the presence of a catalytic amount of iron
tris(dibenzoylomethane [Fe(DBM)3]. In this way many bicyclic tertiary alco-
hols were prepared. These conditions were also convenient for the cyclization
Scheme 57
of ω-iodoalkyl acyl derivatives (esters, lactones or amides) into ketones [148].

A comparison was made between addition of HMPA or of a catalytic amount
of Fe(DBM)3 or Fe(acac)3. Both methods are often of the same efficiency. This
type of reaction was named intramolecular nucleophilic acyl substitution of
halo-substituted esters or lactones. One example is shown in Scheme 57. A
similar cyclization involving N-iodoalkyl cyclic imides was later described by
Ha et al. (see Scheme 57) [149] using SmI2/t-BuOH. Iron(III) catalysis was also
useful in the reductive cleavage of cyclopropanes activated by ester functions
[150]. This cleavage may also be realized in the presence of an aliphatic ketone
which traps the intermediate samarium homoenolate, one example is depicted
in Scheme 57.
Iron(III) catalysis may be considered as a good alternative to HMPA activa-
tion in many reactions induced by SmI2. Recently, we reinvestigated this area to
discover whether other metal salts could be equivalent or superior. Diiodonickel
was the result of this investigation (vide infra).
3.3.2
Nickel Salts
We screened the catalytic behavior of various transition-metal salts or complex-

es in the classical Barbier reaction between 2-octanone and 1-iodobutane in the
presence of 2 equiv of SmI2 in THF at room temperature [151]. Many metal hal-
ides significantly improved the yield (compared to the blank reaction): FeX3 (X=
Br, Cl, I), CuCl2, CuI, NiX2 (X=Br, I), AgX (X=Br, I), CoBr2. Amongst them NiI2
proved to be a superior catalyst allowing an almost quantitative reaction in less
than 10 min. Surprisingly, acetylacetonates of Ni, Fe, Co and Cu are quite ineffi-
cient in this reaction.
Diiodonickel (1 mol%) accelerated significantly many of the reductions per-

formed by SmI2 in THF. For example, some epoxides were deoxygenated in good
yields to the corresponding alkenes at room temperature in 20 min, 2-octanone
gave the pinacol in 10 min (instead of 24 h without catalyst) at room tempera-
ture, and cyclohexane carbonyl chloride coupled quantitatively into 2-hydroxy-
1,2-dicyclohexylethanone in 1 min (reaction performed in THP).
An unexpected feature of the SmI2/NiI2 system is the high reactivity of esters
under intermolecular Barbier conditions. As for Grignard reagents, the reaction
gives tertiary alcohols; one example is mentioned in Scheme 58. The coupling
between a ketone and a conjugated ester, which is promoted by HMPA [38], may
be easily obtained by NiI2 catalysis (Scheme 58). Nucleophilic acylation of esters
by acid chlorides has been realized by the Barbier procedure (Scheme 58) [152].
The reaction intermediate A can be either hydrolyzed into mixed α-ketols or
quenched by other electrophiles (aldehydes or anhydrides). Recently, NiI2 catal-
ysis has been successfully applied to the cyclization of iodoalkyl α,β-unsaturat-
ed esters or amides (for one example, see Scheme 58); iron(III) catalysts were
equally efficient [153]. NiI2 has also been used to selectively activate 1-iodo-3-
chloropropane for the Barbier condensation on various keto esters, the reaction
occurring on the carbon bearing the iodine [154].
Scheme 58
3.3.3
Cobalt Salts
In 1991, Inanaga et al. described the reduction at room temperature of some dis-
ubstituted alkynes by the combination SmI2/proton source in the presence of
some transition-metal catalysts (3% equiv) in THF [155]. By a good choice of
catalyst (CoCl2, 4 PPh3) and proton source (MeOH, i-PrOH or AcOH) it was pos-
sible to orientate the reaction towards the exclusive formation of the Z-alkene.
When the same reaction was performed in the presence of HMPA then the E-
alkene was produced. Iron(III) and Ni(II) catalysts were found to be less effi-
cient. It was assumed that the reactive species were the corresponding transi-
tion-metal hydrides obtained by reduction of the initial complexes.
3.3.4
Copper Salts
When copper salts were added to organosamarium species produced in situ

from an organic halide and SmI2, a transmetallation process gave organocop-
pers able to react in catalyzed conjugate additions [156,157].
The cross-coupling of alkylsamarium reagents with alkyl halides may be cat-
alyzed by copper salts such as CuX (X=Br, Cl or I) or Li2CuCl4 [158]. The most
effective catalyst for the desired cross-coupling was CuBr or Li2CuCl4. The reac-
tion was performed at room temperature in THF with 8 equiv of HMPA. Some
examples are listed in Scheme 59. In order to optimize cross-coupling products
R1–R2, the reaction was performed in two steps, with initial formation of the or-
ganosamarium from R1X and then addition of the catalyst and of R2X.
3.3.5
Chromium Salts
Alkylation of ketones by gem-dibromoalkanes in the presence of a stoichiomet-

ric amount of SmI2/Sm (1:1) and a catalytic amount of CrCl3 (10% equiv) was
studied by Utimoto et al. [159]. It gave in moderate yields (40–70%) various
Scheme 59
alkenes as E/Z mixtures. The reaction presumably involves a gem-dimetallic re-

agent [C(SmX2)2 or C(SmX2)(CrX2)]. The reaction can be applied to easily eno-
lizable ketones such as β-tetralone.
3.3.6
Palladium Complexes
In 1986 Inanaga et al. found that allylic or propargylic acetates could be reduced
in THF by diiodosamarium in the presence of a catalytic amount of a Pd(0) com-
plex and 1 equiv of 2-propanol [160,161]. Some examples are indicated in
Scheme 60. The mechanism of the reaction likely involves π-allyl (or σ-allenyl)
palladium intermediates which are reduced first to radicals and then to carban-
ions (see Scheme 60). A final protonation by the alcohol generates the products.
Scheme 60
Some limitations to this reaction have been noticed [162]. The reductive cou-
pling of allylic acetates with carbonyl compounds (which act as electrophiles in
replacement of a proton donor) provided homoallylic alcohols [163]. Similarly,
coupling of propargylic esters to carbonyl compounds gave allenyl alcohols or
acetylenic alcohols according to the structure of the reactants [164,165]. Some
examples can be found in Scheme 60. The intramolecular coupling reaction us-
ing ω-keto-alkynyl esters allowed the synthesis of five- or six-membered ring
systems [166]. A highly regio- and stereoselective synthesis of allylsilanes was
achieved by reductive silylation of allylic phosphates with a SmI2/HMPA/Pd(0)
system and TMSCl [167].
A regiodivergent reduction of allylic esters with SmI2 in the presence or ab-
sence of a Pd(0) catalyst gave either α- or γ-protonated products by tuning the
proton source (alcohols, H2O) and the ester functionality (Scheme 61) [168].
A changeover of regioselectivity was observed by Mikami et al. in the reduc-
tion of secondary propargylic phosphates by the SmI2/Pd(0)/proton source sys-
tem [169]. tert-Butanol and dimethyl (R,R)-tartrate gave allene and acetylene,
respectively (Scheme 61). This process was modified in an asymmetric synthesis
of chiral allenes [170].
2,3-Naphthoquinodimethanes were easily generated from ortho-bis(α-ace-
toxypropargyl) benzene derivatives by the SmI2/Pd(0)/proton donor system
[171]. The reduction occurs by a 6π-electron cyclization of an O-diallenylben-
zene intermediate.
3.3.7
Lithium Salts
The Barbier reaction discussed in Sect. 3.3.2 was not accelerated by addition of
LiCl. In the literature there are only a few examples where lithium salts are ben-
Scheme 61
Scheme 62
eficial for reactions mediated by SmI2. However, it is worth mentioning that a re-
ductive dialkylation of isoindigo by cis-1,4-dichloro-2-butene only works in the
presence of an excess of LiCl (KCl is inefficient) as indicated in Scheme 62 [172].
The mechanism was not elucidated; a chelate may be involved.
Recently, Flowers et al. initiated a study on the influence of additives on the
reactivity of SmI2, in parallel with electrochemical investigations (see
Sect. 3.1.1). These authors found that the oxidation potentials of SmI2 in THF
containing 12 or more equivalents of LiBr or LiCl were, respectively, –1.98 and –
2.11 V (instead of –1.33 V). They established that the corresponding molecular
species were not SmBr2 and SmCl2. These new reagents are highly reactive and
facilitate the pinacol coupling of cyclohexanone at room temperature in a few
minutes at room temperature [173].
4
Conclusions
In this chapter we have tried to present the main changes which occur for reac-
tions mediated by diiodosamarium when THF is replaced by other solvents or
when some additives are introduced into the THF solution. Many useful organic
transformations have been achieved by this approach but, due to lack of space,
this area has not been covered extensively. However, we hope to have demon-
strated that introduction into THF of various additives in stoichiometric or cat-
alytic amounts or replacement of THF by another solvent may drastically mod-
ify the behavior of SmI2. The most promising approach involves the use of mo-
lecular catalysts since one may expect a wide range of chemo- or stereoselectiv-
ities by suitable changes in the structure of the catalysts.
5
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Chiral Heterobimetallic Lanthanoid Complexes:
Highly Efficient Multifunctional Catalysts for the
Asymmetric Formation of C-C, C-O, and C-P Bonds
Masakatsu Shibasaki* and Harald Gröger
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo,

Bunkyo-ku, Tokyo 113, Japan
* e-mail: [email protected]
The use of alkali metal-containing, heterobimetallic lanthanoid complexes as catalysts in
asymmetric synthesis is reviewed. This new and innovative type of chiral catalyst, which
was recently developed by Shibasaki et al., contains a Lewis acid as well as a Brønsted base
moiety, thereupon showing a similar mechanistic effect as observed in enzyme chemistry.
The heterobimetallic complexes have been successfully applied as highly stereoinducing
catalysts in many different types of asymmetric reactions, including the stereoselective for-
mation of C-C, C-O, and C-P bonds.
Keywords: Heterobimetallic catalysts, Lanthanoid complexes, Asymmetric synthesis, Ho-

mogenous catalysis
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
2 Structural Requirements for an Efficient Bimetallic Catalyst:

What does the Catalysts Look Like? . . . . . . . . . . . . . . . . . . 201
3 Asymmetric Catalytic C-C Bond Formation Using

Heterobimetallic Lanthanoid Complexes . . . . . . . . . . . . . . . 203
3.1 Nitroaldol Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . 203

3.1.1 Development of an Efficient Catalysis in Model Reactions . . . . . 203
3.1.2 Enantioselective Catalytic Nitroaldol Reaction: Adducts with
One Stereogenic Center . . . . . . . . . . . . . . . . . . . . . . . . . 206
3.1.3 Diastereoselective Catalytic Nitroaldol Reaction Starting
from Chiral Aldehydes . . . . . . . . . . . . . . . . . . . . . . . . . . 207
3.1.4 Diastereoselective and Enantioselective Nitroaldol Reaction . . . . 209
3.1.5 Tandem Inter-Intramolecular Catalytic Asymmetric
Nitroaldol Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
3.1.6 Recent Improvements (Second Generation of LnLB Catalyst)
and Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
3.2 Direct Asymmetric Aldol Reaction . . . . . . . . . . . . . . . . . . . 213
3.3 Michael Addition Reaction . . . . . . . . . . . . . . . . . . . . . . . 213
3.4 Diels-Alder Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
200 Masakatsu Shibasaki, Harald Gröger
4 Catalytic Asymmetric C-O Bond Formation Using

Heterobimetallic Lanthanoid Complexes: Epoxidation . . . . . . . . 218
5 Catalytic Asymmetric C-P Bond Formation Using

Heterobimetallic Lanthanoid Complexes . . . . . . . . . . . . . . . . 220
5.1 Hydrophosphonylation of Aldehydes . . . . . . . . . . . . . . . . . . 220

5.2 Hydrophosphonylation of Imines . . . . . . . . . . . . . . . . . . . . 223
5.2.1 Hydrophosphonylation of Acyclic Imines . . . . . . . . . . . . . . . . 223
5.2.2 Hydrophosphonylation of Cyclic Imines . . . . . . . . . . . . . . . . 225
6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
7 References and Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
Abbreviations
Ln lanthanoid metal ion (III)
M alkali metal ion
L lithium
S sodium
P potassium
B 1,1'-binaphthol (BINOL)
LnMB lanthanoid-alkali metal-binaphthoxide complex of type LnM3tris(bi-
naphthoxide)
LLB lanthanum-lithium-binaphthoxide complex LaLi3tris(binaphthoxide)
1
Introduction
One of the most fascinating aspects in the history of asymmetric catalysis with
its countless successful applications in the stereoselective synthesis of a broad
variety of functional groups is the structural variety of the complexes which are
able to be used as catalysts [1, 2]. Many catalysts have been developed based on
different ideas and concepts of mechanistic effect. However, in spite of the abun-
dance of such catalysts which have been successfully applied in asymmetric ca-
talysis, not a handful of them possess multifunctional abilities catalyzing differ-
ent type of enantioselective reactions. The development of such a type of chiral
catalyst, the catalytic effect of which is not limited to one reaction but to differ-
ent types of asymmetric synthetic organic transformations, remained an attrac-
tive challenge for a long time.
In the following, such a desired new and innovative multifunctional catalytic
system is reviewed: The chiral heterobimetallic lanthanoid complexes, devel-
oped by Shibasaki et al., have recently been shown to catalyze a broad spectra of
organic reactions including many “classical” carbon-carbon bond formations
Chiral Heterobimetallic Lanthanoid Complexes 201
like the nitroaldol reaction, Michael addition, aldol reaction and so on, but also
an oxidation reaction as well as the asymmetric formation of carbon-phospho-
rus bonds with excellent stereoselectivity in all cases (Fig. 1) [3–5]. This new
concept for catalytic asymmetric reactions, based on the idea of using chiral het-
erobimetallic lanthanoid complexes which function as both Brønsted base and
Lewis acid, just like an enzyme, makes possible a variety of efficient catalytic
asymmetric reactions.
2
Structural Requirements for an Efficient Bimetallic Catalyst:
What does the Catalysts Look Like?
For a better understanding of many successful applications of the rare earth-al-
kali metal containing LnM3tris(binaphthoxide) complexes (LnMB, Ln=rare
earth, M=alkali metal) to catalytic asymmetric synthesis, intense investigations
also focused on the determination of the structure. It has been shown that these
complexes, which can be readily prepared from the corresponding rare earth
trichlorides and/or rare earth isopropoxides [5], possess a structure as present-
ed in Fig. 2. This structure was supported by various NMR spectroscopic, MS
spectrometric, X-ray crystallographic and other analytic investigations of a va-
riety of LnMB complexes.
Beginning with LDI-TOF mass spectral analysis, these investigations revealed
that the structure was in fact a heterobimetallic complex consisting of one lan-
thanum, three lithium and three BINOL moieties [6]. Although LDI-TOF mass
Asymmetric C-O bond Asymmetric C-C bond

formation: formation:
• Epoxidation of enones • Nitroaldol reaction
• Aldol reaction
• Michael addition reaction
• Diels-Alder reaction
Chiral
Heterobimetallic
Lanthanoid Catalysts
LnMB
Asymmetric C-P bond formation:

• Hydrophosphonylation of aldehydes
• Hydrophosphonylation of imines
Figure 1. Applications of heterobimetallic lanthanoid complexes in asymetric catalysis

M O O M
O Ln O
O O
M
(R)-LnMB
Figure 2. The structure of (R)-LnMB. (M=alkali metal, Ln=lanthanoid metal)
spectrometry has a mass accuracy of about ±0.1%, the proposed structural

framework was strongly supported by the similarity of the mass spectra of var-
ious other rare earth complexes, since rare earth elements have their own atomic
weights and isotope abundance distributions. Successful attempts have also
been made to obtain X-ray grade crystals of rare earth complexes of type LnLB
and LnSB [6–8]. Several rare earth-sodium-BINOL complexes (LnSB, S=sodi-
um) could be crystallized from THF starting from rare earth trichlorides includ-
ing LaCl3, disodium (R)-binaphthoxide, NaOtBu, and H2O. The elemental anal-
yses suggested a stoichiometry of LnNa3tris(binaphthoxide)-6THF-2H2O, which
was confirmed by X-ray crystallographic analyses of La, Pr, Nd, and Eu complex-
es as being correct. The X-ray crystallographic analyses showed that these crys-
tals had almost the same structure (Fig. 2), with the differences being in the dis-
tance of the atoms around the center from the central rare earth metal [6, 7].
Each rare earth (S)-BINOL complex has a chiral center at the rare earth metal so
that the (S)-BINOL complex can exist as a diastereomer. Nevertheless, it is inter-
esting to note that La, Pr, Nd, and Eu complexes starting from (S)-BINOL exist
only in the Λ-configuration, perhaps due to the greater thermodynamic stability
of this configuration compared to the ∆-form.
All the above-mentioned LnSB crystals showed similar mass patterns com-
pared to those of Ln-Li-BINOL complexes, though they contained sodium in-
stead of lithium. The oligomeric structure of the catalysts in the reaction mix-
ture was supported by a slightly positive asymmetric amplification in the asym-
metric nitroaldol reaction [9]. In addition, quite recently Shibasaki et al. report-
ed the first X-ray crystallographic structure of a lithium-containing heterobime-
tallic catalyst of type LnLB, namely the SmLi3tris(binaphthoxide) complex
SmLB [8].
Concerning the heterobimetallic potassium lanthanoid catalysts (R)-LnPB, a
very recent NMR spectroscopic as well as FAB and ESI mass spectrometric study
of isolated (R)-YbPB complexes provided a clear insight into the assembly of this
heterobimetallic complex in solution. At first, the assumption that the proposed
structure of (R)-YbPB (according to Fig. 2) corresponds with those of isolated

crystals (R)-YbPB was confirmed [10]. Moreover, the application of these isolat-
ed crystals (R)-YbPB in an asymmetric hydrophosphonylation reaction (see also
Sect. 5.2.2.) gave (nearly) the same good result as the corresponding catalyst so-
lution, indicating that the determined structure of the crystals corresponds with
the actual catalytically active species. Such a knowledge of the composition of
the heterobimetallic catalysts, namely the potassium derivative (R)-YbPB, in so-
lution represents one of the rare cases in catalytic asymmetric synthesis in which
the “real catalytically active species” could be isolated, applied, and analyzed by
NMR spectroscopical and mass spectrometrical methods.
In summary, it is noteworthy that all of these heterobimetallic asymmetric
complexes of type LnMB are stable in organic solvents such as THF, CH2Cl2 and
toluene which contain small amounts of water, and also are insensitive to oxy-
gen. Using a catalytic amount of LnMB complexes various kinds of asymmetric
C-C bond formation reactions, an asymmetric epoxidation, and asymmetric hy-
drophosphonylations of either imines or aldehydes (catalyzed by LnPB, P=po-
tassium) proceed efficiently to give the corresponding desired products in high
stereoselectivity. In detail, these asymmetric reactions will be discussed in the
following sections.
3
Asymmetric Catalytic C-C Bond Formation Using Heterobimetallic Lanthanoid
Complexes
3.1
Nitroaldol Reaction
3.1.1
Development of an Efficient Catalysis in Model Reactions
In 1992, Shibasaki et al. reported for the time an application of chiral heterobi-
metallic lanthanoid complexes (LnLB) as chiral catalysts in asymmetric cataly-
sis, namely the catalytic asymmetric nitroaldol reaction (Henry reaction),
which is one of the most classical C-C bond forming processes [11]. Additional-
ly, this work represents the first enantioselective synthesis of β-nitroalcohol
compounds by the way of enantioselective addition of nitroalkanes to aldehydes
in the presence of a chiral catalyst. The chiral BINOL based catalyst was prepared
starting from anhydrous LaCl3 and an equimolar amount of the dialkali metal
salt of BINOL in the presence of a small amount of water [9].
Starting from prochiral aldehydes 1–3, the desired products b were obtained
in good chemical yields and with enantioselectivities up to 90% ee (Scheme 1)
[11]. The amount of the catalyst is not shown in Scheme 1 due to the unknown
structure of the catalyst (at this time).
Investigations concerning the influence of the rare earth metal component
showed pronounced differences both in the reactivity and in the enantioselec-
La-Li-(S)-BINOL complex OH
RCHO + CH3NO2 NO2
THF, -42 °C, 18 h R
(10 equiv)
1: R = PhCH2CH2 4: 79% (73% ee), R = PhCH2CH2

2: R = iPr 5: 80% (85% ee), R = iPr
3: R = cyclohexyl 6: 91% (90% ee), R = cyclohexyl
Scheme 1. The first catalytic asymmetric nitroaldol reaction catalyzed by chiral lanthanoid
complexes.
ee (%) 100 OH
NO2
6
80 OH
NO2
Ph
60 4
OH
40 NO2
Ph
7
20
Eu
Gd Pr
Yb Y Tb Sm Nd La
0
0.8 0.9 1.0 1.1
+3 Ionic radius of rare earth elements (Å)
Figure 3. Effects of the ionic radii of rare earth elements on the enantioselectivity.
tivity among the various rare earth metals used [12]. When benzaldehyde and
nitromethane were used as starting materials, the corresponding Eu complex
gave 7 in 72% ee (91%) in contrast to 37% ee (81%) in the case of the La complex
(–40 ˚C, 40 h). The unique relationship between the ionic radii of rare earth met-
als and the enantioselectivities of several nitroaldols 4, 6, 7 are depicted in Fig. 3.
Consequently, small changes in the structure of the catalyst (ca. 0.1 Å in ionic
radius of the rare earth cation) cause drastic changes in the optical purity of the
produced nitroaldols. Although in general nitroaldol reactions are regarded as
equilibrium processes, no detectable retro-nitroaldol reaction was observed in
the Ln-BINOL complex catalyzed asymmetric nitroaldol reactions.
The proposed mechanism for the asymmetric nitroaldol reaction catalyzed
by heterobimetallic lanthanoid complexes is shown in Scheme 2 [5]. In the ini-
tial step, the nitroalkane component is deprotonated and the resulting lithium
nitronate coordinates to the lanthanoid complex under formation of the inter-
Li *
O
O O OH
* La Li NO2
CH3NO2 O O R'
O
Li *
(R)-LLB
Li Li
* * * *
O O O O
O La O O La O H
Li O O H+ Li O O
R'
O N CH O O
Li 2 + H
* O— * Li N CH2
I O—
II
R'CHO
Scheme 2. A possible mechanism for catalytic asymmetric nitroaldol reactions with nitro-
methane.
mediate I. [13] Subsequent addition of the aldehyde by coordination of the C=O

double bond to the lanthanoid (III) center ion leads to intermediate II, in which
the carbonyl function should be attacked by the nitronate via a six-membered
transition state (in an asymmetric environment). A proton exchange reaction
step will then generate the desired optically active nitroalkanol adduct with re-
generation of the “free” rare earth complex LnLB.
In addition to the early results of the general and effective catalytic asymmet-
ric nitroaldol reaction (Scheme 1), which proceeds efficiently in the presence of
3.3 mol% of LLB, the knowledge of the structure of the LnLB complexes (see
Sect. 2) led to an extension of this catalytic method to a wide range of further ap-
plications which are described below.
The structural modification of the BINOL ligand system also plays an impor-
tant role concerning stereoselection in the asymmetric Henry reaction. Im-
proved enantioselectivites were obtained using a number of (R)-BINOL deriva-
tives in which the 6,6'-positions were substituted [14]. Their utility as asymmet-
ric catalysts was assessed with enantioselectivities up to 88% ee accompanied by
chemical yields up to 85% in the nitroaldol reaction of nitromethane with hy-
drocinnamaldehyde 1. Whereas the substitution at the 6,6'-position of BINOL
proved to be effective in obtaining superior asymmetric catalysts, the use of
complexes derived from 3,3'-disubstituted BINOL derivatives [15, 16] gave ra-
cemic 4 and BIPOL derived catalyst [17] gave 4 in only 39% ee.
Recently, Okamoto et al. showed that the reactivity and selectivity also de-
pends on the alkali metal component in the heterobimetallic catalysts [18]. Us-
ing the bulkier 2-nitropropane as starting material in a model reaction with ben-
zaldehyde, almost no reaction occurred at –30 ˚C in the presence of the lithium
containing catalyst LLB, whereas higher temperatures as well as the use of
HMPA as a co-solvent only led to racemic product. However, in the presence of
the corresponding potassium-containing catalyst LPB the desired reaction pro-
ceeded with 46% ee. In contrast, the use of LLB was connected with superior
enanioselectivity and chemical yield (compared to LPB) when replacing 2-nitro-
propane by the less bulkier nitromethane (LLB: 91% yield; 48% ee; LPB: 71%
yield; 6% ee) [18].
3.1.2
Enantioselective Catalytic Nitroaldol Reaction: Adducts with One Stereogenic Center
A first example of an efficient application of the LnLB catalyzed nitroaldol reac-

tion as key step in a multi-step syntheses was presented by Shibasaki et al. in the
asymmetric approach to three kinds of optically active β-blockers 10, 13, and 16
(Scheme 3) [12, 19–21].
Using 14 and 10 mol equiv of nitromethane at –50 ˚C in the presence of
3.3 mol% of (R)-LLB catalyst, a 76% yield of nitroaldol 15 in 92% ee was ob-
tained. Reductive alkylation of the nitroaldol 15 to 16 was accomplished by a
PtO2 catalyzed hydrogenation. Thus, (S)-(–)-pindolol 16 was synthesized in only
four steps from 4-hydroxyindole [20]. Interestingly, the nitroaldols 9, 12, and 15
were found to have (S)-configuration when (R)-LLB was used. The nitronates
thus appear to react preferentially with the Si face of the aldehydes, in the oppo-
CH3NO2 (10-50 equiv)

(R)-LLB (3.3 mol %) Ar
Ar O NO2
O CHO
-50 °C, THF OH
8 9: 90% yield; 94% ee
11 12: 80% yield; 92% ee
14 15: 76% yield; 92% ee
H2, PtO2, CH3OH 10: 80% (S)-metoprolol

Ar
O N 13: 90% (S)-propranolol
acetone, 50 °C H 16: 88% (S)-pindolol
OH
8, 9, 10: Ar = 11, 12, 13: Ar = 14, 15, 16: Ar =

N
H3CO H
Scheme 3. Catalytic asymmetric synthesis of β-blockers using (R)-LLB as a catalyst.

site sense to the enantiofacial selectivity which might have been expected on the
basis of the previous results (cf. Scheme 1). These results suggested that the pres-
ence of an oxygen atom at the β-position had a pronounced influence on the
enantiofacial selectivity.
The LLB type catalysts were also successfully applied in the asymmetric ni-
troaldol reaction of quite unreactive α,α-difluoro aldehydes. However, catalytic
asymmetric nitroaldol reaction of a broad variety of α,α-difluoro aldehydes
proceeded satisfactorily when using the heterobimetallic asymmetric catalysts
with modified, 6,6'-disubstituted BINOL ligands [22]. The best results were ob-
tained with the samarium (III) complex (5 mol%) generated from 6,6'-bis{(tri-
ethylsilyl)ethynyl}BINOL with enantioselectivities up to 95% ee. The (S)-config-
uration of one representative nitroaldol adduct showed that the nitronate react-
ed preferentially on the Si face of aldehyde in the presence of (R)-LLB (20 mol%;
74% yield; 55% ee). It is noteworthy that the enantiotopic face selection for α,α-
difluoro aldehydes is reverse to that for nonfluorinated aldehydes. The stereose-
lectivity for α,α -difluoro aldehydes is identical with that of β-oxa-aldehydes,
suggesting that the fluorine atoms at the α-position have a great influence on
enantioface selection.
3.1.3
Diastereoselective Catalytic Nitroaldol Reaction Starting from Chiral Aldehydes
The diastereoselective catalytic nitroaldol reaction has been investigated start-

ing from optically active α-amino aldehyde, e.g. 17. The adducts of type 18 are
attractive intermediates for the synthesis of unnatural erythro-amino-2-hy-
droxy acids, which are important components of several biologically active com-
pounds. For example, the promising HIV-protease inhibitor KNI-272 [23, 24]
contains (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid (erythro-AHPA,
19) as a subunit. A conventional diastereoselective synthesis in the presence of
achiral bases led to limited internal induction with erythro/threo ratios of 18 in
the range between 62:38 and 74:26. The use of the achiral complex La(OiPr)3
gave the product 18 in an 89:11 erythro/threo ratio [25]. However, this limitation
of diastereoselection has been overcome using catalytic amounts of lithium-
containing heterobimetallic complexes LnLB (Scheme 4).
In the presence of (R)-LLB (3.3 mol%), the treatment of N-phthaloyl-L-phe-
nylalanal 17 with nitromethane at –40 ˚C gave practically a single stereoisomer
of (2R,3S)-2-hydroxy-4-phenyl-3-phthaloylamino-1-nitrobutane 18 in 92%
yield (>99:1 erythro-selectivity) [25]. Interestingly, reaction of the (S)-aldehyde
17 with nitromethane, using the (S)-LLB complex as a catalyst, led to a reduced
diastereo- and enantioselectivity (96% yield; erythro/threo 74:26; 90% ee(eryth-
ro)). The conversion of the nitroaldol adduct 18 into 19 was achieved in one pot
(80% yield).
A further example of a diastereoselective nitroaldol reaction using heterobi-
metallic lanthanoid complexes as catalysts was recently reported by Okamoto et
al. [18] in connection with a novel approach to 1α,24(R)-dihydroxyvitamin D3
208
OH OH
LLB catalyst (3.3 mol %) 12N HCl
CHO + NO2
Ph CH3NO2 Ph Ph COOH
THF, -40 °C, 72 h 100 °C, 46 h
NPhth (20 equiv) NPhth NH2
17 18 19
(R)-LLB: 92% yield;
>99:1 erythro/threo;
erythro: 96% ee
(S)-LLB: 96% yield;
74:26 erythro/threo;
erythro: 90% ee
Scheme 4. Diastereoselective nitroaldol reaction as key step in the synthesis of erythro-AHPA 19.
Masakatsu Shibasaki, Harald Gröger

OH
CHO
(S)-LPB type catalyst (R)
(20 mol %) NO2
+ (CH3)2CHNO2
THF, -30 or -50 °C
(50 equiv)
H H
PhC(O)O PhC(O)O
20 21
dr(R:S) up to 94:6
up to 71% yield
Scheme 5. Catalytic diastereoselective nitroaldol reaction promoted by the LPB type catalyst.
[26], which is an active analogue of vitamin D3 and induces keratinocyte differ-

entiation [27, 28]. Herein, several rare earth metal complexes were used to cata-
lyze the nitroaldol reaction of the CD-ring 24-aldehyde precursor 20 with 2-ni-
tropropane (Scheme 5). In accordance with the results of the corresponding
model reaction with benzaldehyde when using 2-nitropropane as starting mate-
rial (see Sect. 3.1.1.), the best results were achieved in the presence of the potas-
sium containing lanthanoid complex of type LPB with (S)-6,6'-{(triethylsi-
lyl)ethynyl}BINOL as ligand. The desired nitroaldol adduct 21 was formed in
yields up to 71% and with diastereomeric ratios dr up to 94:6 (Scheme 5). It is
noteworthy, that a conjugate double bond in the aldehyde component was need-
ed for good asymmetric induction.
3.1.4
Diastereoselective and Enantioselective Nitroaldol Reaction
LnLB type catalysts are also able to promote diastereoselective and enantioselec-
tive nitroaldol reactions starting from prochiral materials. In preliminary work,
LLB gave unsatisfactory results in terms of both diastereoselectivity (syn/anti
ratio 63 : 37 to 77 : 23) and enantioselectivity (<78% ee) [19]. However, an effec-
tive asymmetric induction was obtained in the presence of LL(B-a) type cata-
lysts containing 6,6'-substituted BINOL (Scheme 6; for the structure of B-a, see
Scheme 7).
The application of the catalysts of type LL(B-a) (3.3 mol%) to diastereoselec-
tive nitroaldol reactions led to high syn-selectivity and enantioselectivity [29].
In all cases, much higher syn-selectivity (syn/anti ratio up to 94:6) and enanti-
catalyst OH OH
(3.3 mol %) R' R'
RCHO + R'CH2NO2 R + R
THF, -40 °C syn NO2 anti NO2
1: R = PhCH2CH2 23: R' = Et 25(syn), 26 (anti): R = PhCH2CH2, R' = Et
22: R = CH3(CH2)4 24: R' = CH2OH 27(syn), 28 (anti): R = PhCH2CH2, R' = CH2OH
29(syn), 30 (anti): R = CH3(CH2)4, R' = CH2OH
Reagent Catalyst Time Product Yield syn/anti ee (syn)

[h] [%] [%]
1 + 23 LLB 138 25 + 26 89 85 : 15 87
1 + 23 LL(B-a) 138 25 + 26 85 93 : 7 95
1 + 24 LLB 111 27 + 28 62 84 : 16 66
1 + 24 LL(B-a) 111 27 + 28 97 92 : 8 97
22 + 24 LLB 93 29 + 30 79 87 : 13 78
22 + 24 LL(B-a) 93 29 + 30 96 92 : 8 95
Scheme 6. Diastereoselective and enantioselective nitroaldol reaction.

OH
catalyst (10 mol %)
CH3(CH2)14CHO OH CH3(CH2)14
+ O2N OH
-40 °C, 163 h
32 NO2
33 + anti-adduct
OH
Et3SiC≡C LL(B-a) catalyst:
H2, Pd-C 6
CH3(CH2)14 OH 78% (syn/anti = 91:9),
EtOH OH syn: 97% ee
NH2
OH
syn-dihydrosphingosine 31 LLB catalyst:
6'
Et3SiC≡C 31% (syn/anti =
86:14),
B-a syn: 83% ee
Scheme 7. Catalytic asymmetric synthesis of syn-dihydrosphingosine.
oselectivity (up to 97% ee) was obtained using the catalysts with 6,6'-substituted
BINOL instead of LLB (for comparison representative results are given in
Scheme 6). The optical purities of the minor anti-adducts 26, 28, and 30 were
lower than those of the syn-adducts 25, 27, and 29, indicating that the former
were not generated by epimerization of the nitro group. In fact, treatment of the
syn-adducts with catalysts such as LLB and its derivatives resulted in near-quan-
titative recovery of the starting materials with unchanged optical purities.
The syn-selective asymmetric nitroaldol reaction was successfully applied to
the catalytic asymmetric synthesis of threo-dihydrosphingosine 31, which elicits
a variety of cellular responses by inhibiting protein kinase C (Scheme 7) [30]. Ni-
troaldol reaction of hexadecanal 32 with 3 equiv of nitroethanol catalyzed by
LL(B-a) gave the corresponding nitroaldol adduct 33 in high syn-selectivity
(91:9) and 78% yield, with the syn-adduct 33 being obtained with up to 97% ee
[29]. In this case, under similar conditions the LLB-catalyzed reaction proceed-
ed only slowly to give an 86:14 ratio of the syn and anti-adducts in 31% yield
(with lower optical purity: 83% ee). The hydrogenation of 33 in the presence of
10% Pd on charcoal afforded threo-dihydrosphingosine 31 in 71% yield.
3.1.5
Tandem Inter-Intramolecular Catalytic Asymmetric Nitroaldol Reaction
The asymmetric catalytic nitroaldol reaction was furthermore successfully ex-

tended to the field of asymmetric tandem reactions [31]. Tandem reactions are
especially useful to construct compounds with several chiral centers in a one-pot
synthesis starting from simple achiral components in the presence of a chiral
catalyst. The first tandem inter-intramolecular catalytic asymmetric nitroaldol
reaction has been realized in the reaction of the cyclopentanedione derivative
34 with nitromethane using a catalytic amount of LnLB according to Scheme 8
[31].
O
OH O
O CH3NO2 (10 equiv)
(R)-PrLB (5 or 10 mol %) O2N *
OHC
* O2N * O*
THF, -40 °C OH
O
O
34 (S)-35a 35b
O O
room temperature
HO HO
OH OH
O2N O2N
36a 36b
up to 45% yield (cryst. product)
up to 65% ee (crude product)
up to 79% ee (cryst. product)
Scheme 8. Tandem inter-intramolecular catalytic asymmetric nitroaldol reaction.
In addition to temperature effects, the optical purity of the product 36b

strongly depends on the lanthanoid center ion. In the presence of (R)-PrLB com-
plex (5 mol%) as the most efficient catalyst, the hexahydro-1-indanone deriva-
tive 36b was formed with enantioselectivities up to 65% ee (for comparison: LLB
(10 mol%; –20 ˚C): 39% ee; YbLB (10 mol%; –20 ˚C): 7% ee) [31]. After crystal-
lization, 36b was isolated with up to 79% ee and 41% yield.
3.1.6
Recent Improvements (Second Generation of LnLB Catalyst) and Summary
The catalytic asymmetric nitroaldol reactions promoted by LLB or its deriva-

tives require at least 3.3 mol% of asymmetric catalysts for efficient conversion.
However, even in the case of 3.3 mol% of catalyst, reactions are rather slow. At-
tempts were made to reduce the required catalytic amount and accelerate the re-
actions, which led to a second-generation heterobimetallic lanthanoid catalyst
(LLB-II), prepared from LLB, 1 mol equiv of H2O, and 0.9 mol equiv of butyllith-
ium. The use of only 1 mol% of LLB-II efficiently promoted catalytic asymmetric
nitroaldol reactions and additionally LLB-II (3.3 mol%) accelerated these reac-
tions [32]. A comparison of the efficiency of LLB (or LL(B-a)) and the second-
generation catalysts LLB-II (or LL(B-a)-II) is given in Scheme 9. The structure
of LLB-II has not yet been unequivocally determined. However, it appears that it
is a complex of LLB and LiOH.
Using a second-generation LnLB catalyst consisting of 6,6'-bis{(trimethylsi-
lyl)ethynyl}BINOL and Sm, an efficient catalytic asymmetric synthesis of arb-
OH
catalyst (1 mol %) R'
RCHO + R'CH2NO2 R
NO2
3: R = C6H11 37: R' = H 6: R = C6H11, R' = H
1: R = PhCH2CH2 38: R' = CH3 39: R = PhCH2CH2, R' = CH3
23: R' = Et 25: R = PhCH2CH2, R' = Et
Reagent Catalyst Time Temp. Product Yield syn/anti ee (syn)

[h] [°C] [%] [%]
3 + 37 LLB 24 –50 6 5.6 – 88
3 + 37 LLB-II 24 –50 6 73 – 89
1 + 38 LL(B-a) 113 –30 39 25 70 : 30 62
1 + 38 LL(B-a)-II 113 –30 39 83 89 : 11 94
1 + 23 LL(B-a) 166 –40 25 trace – –
1 + 23 LL(B-a)-II 166 –40 25 84 95 : 5 95
Scheme 9. Comparison of the catalytic activity of LLB and second-generation LLB (LLB-II)
or LL(B-a) and LL (B-a)-II. [LLB-II: LLB + H2O (1 mol equiv) + BuLi (0.9 mol equiv.);
LL(B-a)-II: LL(B-a) + H2O (1 mol equiv) + BuLi (0.9 mol equiv)]; For the structure of the
BINOL derivative ligand B-a, see Scheme 7
CH3NO2 (10 equiv) OH

TBSO CHO
SmLB*-II (3.3 mol %) TBSO NO2
TBSO THF,-50 °C, 67 h

TBSO
41 42
93%, 92% ee
OH
H
HO N
HO OH
40: arbutamine
64% overall yield
Scheme 10. A catalytic asymmetric synthesis of arbutamine. [SmLB*-II = SmLi3tris(R)-6,6‘-

bis(trimethylsilylethynyl)binaphthoxide) + H2O (1.0 mol equiv to Sm) + BuLi (0.6 mol
equiv to Sm)].
utamine 40, which is a useful β-agonist [33, 34], was achieved (Scheme 10) [8]. In
the key step, the nitroaldol adduct 42 was formed in 93% yield and with 92% ee [8].
In conclusion, since the first example of a catalytic asymmetric nitroaldol re-
action (Henry reaction) was reported in 1992 by Shibasaki et al., this reaction
has been developed into a highly efficient synthetic method for the stereoselec-
tive synthesis of nitroalkanols. Using alkali metal-containing heterobimetallic
lanthanoid complexes as catalysts, a broad variety of nitroalkanol derivatives

containing one, two, or more stereogenic centers have been constructed in a
highly stereoselective manner. Until now, this new and innovative catalytic con-
cept has been applied to the synthesis of several biologically active and pharma-
ceutically interesting compounds (or their precursors).
3.2
Direct Asymmetric Aldol Reaction
Although the development of a range of catalytic asymmetric aldol-type reac-

tions has proven to be a valuable contribution to asymmetric synthesis [35–37],
in all of these reactions pre-conversion of the ketone moiety to a more reactive
species such as an enol silyl ether, enol methyl ether, or ketene silyl acetal has
been an unavoidable necessity. However, quite recently Shibasaki et al. reported
that a direct catalytic asymmetric aldol reaction, which is known in enzyme
chemistry, is also possible in the presence of heterobimetallic lanthanoid cata-
lysts [38]. Using (R)-LLB (20 mol%), which shows both Lewis acidity and Brøn-
sted basicity similar to the corresponding aldolases, the desired optically active
aldol adducts were obtained with up to 94% ee. A variety of aldehydes and un-
modified ketones can be used as starting materials (Scheme 11).
Moreover, although it is known that aldol reactions that utilize acetone as a
starting material are generally difficult to control, this reaction proceeds well in
the presence of LLB (20 mol%) and 10 equiv of acetone to give the aldol adduct
with up to 74% ee and in 82% yield. The postulated mechanism of this direct cat-
alytic aldol reaction is presented in Scheme 12.
Therein, the lanthanum center ion (III) should function as a Lewis acid acti-
vating the aldehyde, whereas the lithium binaphthoxide moiety act as Brønsted
base moiety. The synergetic effect of both groups, as can be seen in intermediate
III, appeared to be responsible that the reaction proceeds without any activation
of the starting materials, especially the ketone component.
3.3
Michael Addition Reaction
Catalytic asymmetric Michael reactions are one of the most important synthetic
methods for obtaining asymmetric centers by enantioselective construction of
carbon-carbon bonds [39, 40]. The first lanthanoid complex catalyzed Michael
(R)-LLB OH O
O (20 mol %)
R1CHO + R1 R2
H 3C R2 -20 °C, THF
yields up to 90%
ee up to 94%
Scheme 11. LLB-catalyzed direct aldol reaction.

R2
O M O O
O H
*
1
2 O LA R H
R II
R2
O M O M O
H
H
*
*
O LA I O LA O III
R1
R2
OH O
O LA : Lewis acid
1 O M
R R2 M : Metal of Brønsted
H base
O
*
O LA R1 O
IV : Chiral ligand
*
O
Scheme 12. Catalytic Cycle of Direct Catalytic Asymmetric Aldol Reactions.
O
O LSB
1
COOR (10 mol %)
+ R2 COOR1
( )n
( )n COOR1 THF
R2 COOR1
n = 1,2 R1 = Et, Me, Bn 43
R2 = H, CH3 up to 98% yield
up to 92% ee
O LnSB O Ph
COOCH3 (10 mol %) H
+ COOCH3
Ph Ph COOCH3 toluene, Ph
-50°C COOCH3
44 45
Ln=La: 93% yield; 77% ee
Ln=Pr: 96% yield; 56% ee
Ln=Gd: 54% yield; 6% ee
Scheme 13. LnSB-catalyzed asymmetric Michael addition.
addition reaction was realized using malonates as Michael donor in the catalytic
asymmetric Michael reaction of various enones [41, 42]. Although ineffective as
an asymmetric catalyst for nitroaldol reactions, LSB (L=lanthanum, S=sodium)
was found to be effective in this case, giving Michael adducts 43 in up to 92% ee
and almost quantitative yield (Scheme 13) [41]. In general, the use of THF as a
solvent led to the best results, whereas in the case of the corresponding LSB-cat-
alyzed reaction of trans-chalcone 44 the use of toluene was essential to give the
product in good enantiomeric excess. Center metal effects were also investigated
for this Michael reaction, indicating that LSB was the best catalyst for catalytic
asymmetric Michael reactions.
In order to clarify the nature of the interaction between the enone and the
asymmetric catalyst, the complexation was studied by 1H-NMR spectroscopy af-
ter mixing cyclohexenone and the asymmetric bimetallic complexes and ob-
serving the chemical shift of the α-proton of cyclohexenone [41]. Interestingly,
it was found that complexation with LSB induced a small downfield shift on the
α-proton of cyclohexenone whereas PrSB, a moderately effective asymmetric
catalyst for Michael reactions, induced a large upfield shift. In strong contrast,
in the case of either EuSB or LLB, which gave only near-racemic Michael ad-
ducts, the 1H-NMR spectra showed no changes in chemical shift of the α-proton
of cyclohexenone. These NMR studies indicated that the carbonyl group of the
enone coordinated to lanthanum and/or praseodymium metal in the LnSB mol-
ecule, while the enone did not coordinate to either LLB and/or EuSB. These
changes of chemical shift were observed even in the presence of dimethyl
malonate. The chemical phenomena described above might be understood by
considering the differing dihedral angles of binding of the BINOL moiety to the
center metal in each case.
Additionally, computational simulations of the enantioselection process us-
ing Rappé's universal force field (UFF) [43–45] were carried out which clearly in-
dicated that the (R)-LSB complex complexes better as a pro-(R) adduct than as
pro-(S) adduct (∆E=4.9 kcal/mol) [41]. The proposed catalytic cycle is shown in
Scheme 14. Thus, the basic LSB complex also acts as a Lewis acid, controlling the
orientation of the carbonyl function and so activating the enone to attack. It ap-
O
O
COOCH3 Na *
+ O
O O COOCH3
COOCH3 * La Na
O O COOCH3
Na O *
LSB
Na *
OCH3 O O
* O O Na
Na * La O
O Na O
O O O OCH3
* La O Na O OH
O OH * OH O
Na O
* OCHOCH
3 3
I II
Scheme 14. Proposed catalytic cycle for the asymmetric Michael reaction promoted by LSB.
pears that the multifunctional nature of the LSB catalyst makes possible the for-
mation of Michael adducts with high ees even at room temperature. As final step
the resultant sodium enolates II of the optically active Michael adducts appear
to abstract a proton from an acidic OH so as to regenerate the LSB catalyst. In
both catalytic asymmetric Michael reactions and nitroaldol reactions, enones
and/or aldehydes appear to coordinate to the rare earth metal. The reason why
LSB is more effective for catalytic asymmetric Michael reactions whereas LLB is
more effective for catalytic asymmetric nitroaldol reactions is still unclear at
present. However, it seems that slight differences in bond lengths in chelate
structures such as I and II, as well as slight differences in “bite” angle for the BI-
NOL moiety caused by varying the alkali metal component may be responsible
for this effect.
Another type of an LSB catalyzed asymmetric Michael reaction, in which the
asymmetric center is induced on the side of the adduct originating from the
Michael donor, was also reported by Shibasaki et al. (Scheme 15) [46]. In a pre-
liminary study, it was found that the reaction of 46 with 3-buten-2-one in THF
using 10 mol% of LSB gave 47 with 23% ee, while carrying out the reaction in tol-
uene afforded 47 with 75% ee. However, when the amount of LSB was reduced to
5 mol%, the enantiomeric excess of 47 declined to a more modest 25% ee. To off-
set this decline while still maintaining the lower level of catalyst slow addition of
46 was essential. Accordingly, the use of syringe pump methods gave 47 with
high enantiomeric excess (89% ee). The reaction was further improved when us-
ing CH2Cl2 as a solvent. Thus, the asymmetric Michael reaction catalyzed by
5 mol% of LSB in CH2Cl2 gave 47 in 89% yield and with 91% ee, without the need
for slow addition previously encountered (Scheme 15). In addition, in this case
the catalytic asymmetric Michael reaction for 47 was not so affected by the
choice of rare earth metal.
In conclusion, as shown in Scheme 15, slow addition of β-keto ester and the
use of CH2Cl2 as solvent are generally quite effective methods for preventing re-
duction of enantiomeric excess for the various Michael adducts. On the other
solvent yield ee
toluene 83% 25%
toluenea) 76% 89%
CH2Cl2 89% 91%
a) Slow addition of nucleophile with
syringe-pump methods over 8h
Scheme 15. LSB-catalyzed Michael addition of 46 with methyl vinyl ketone.

hand, malonates give the adducts with high ees regardless of the solvent used
[41]. These results can be rationalized by comparison of the pKa of a β-keto ester
with that of a malonate; the former is significantly more acidic than the latter.
Thus, the concentration of the resulting Na-enolate can be expected to be greater
in the case of the β-keto ester, and moreover this Na-enolate will react with an
enone more slowly than the Na-enolate derived from a malonate. We suggest
that this combination of more rapid formation and longer lifetime increases the
likelihood of dissociation of the Na-enolate from the chelated ensemble, thus
giving a product of lower ee. On the other hand, in less polar CH2Cl2 the Na-eno-
late would, even in this case, remain part of the ensemble, thereby affording the
product with high ee (Fig. 4). Furthermore, it appears that slow addition of the
β-keto ester also acts to limit undesired ligand exchange between BINOL moie-
ties and the Michael donor.
In both types of catalytic asymmetric Michael reactions, the use of either sec-
ond-generation LSB or 6,6'-substituted BINOL derived LSB type catalysts did
not result in significantly improved results.
3.4
Diels-Alder Reaction
A further application of the heterobimetallic lanthanoid catalysts of the LLB

type to the field of catalytic asymmetric Diels-Alder reactions [47, 48] was also
achieved by Shibasaki et al. [49]. In general, LLB type complexes are multifunc-
tional asymmetric catalysts, showing both Brønsted basicity and Lewis acidity.
Nevertheless, in this study the use of LLB type catalysts acting as asymmetric
Lewis acids alone was examined and led to the development of an LLB (type) cat-
alyzed asymmetric Diels-Alder reaction [49]. Representative results for the cat-
alytic asymmetric Diels-Alder reactions using 48 and cyclopentadiene in tolu-
ene as a solvent are shown in Scheme 16.
in CH2Cl2 in THF
Na * O O
Na * O O
O Na O O Na
O O O OEt * La O
La O O O
* O OH
O OH O
O OEt
Na *
Na *
high ee low ee
Figure 4. Proposed mechanism for the catalytic asymmetric Michael reaction promoted by
LSB.
O O catalyst
(10 mol %) H
N O + N
—20 °C, 20 h O
O
48 O
49
(R)-LLB (R)-LLB*a)
yield: 82% 100%
endo/exo: 15:1 36:1
ee: 63% 86%
a) LLB*=LaL3tris(6,6’-dibromobinaphth-
oxide)
Scheme 16. Catalytic asymmetric Diels-Alder reaction.
Compared to the result with LLB, the use of a 6,6'-dibromosubstituted BINOL

derived LLB type catalyst LLB* led to significantly improved yield, endo:exo ra-
tio and enantioselectivity (86% ee). Interestingly, the addition of 12-crown-4 to
the reaction medium resulted in the formation of the adduct 49 with much lower
enantiomeric excess. This result appears to suggest that the lithium cation(s)
play a key role in activation of the dienophile.
4
Catalytic Asymmetric C-O Bond Formation Using Heterobimetallic
Lanthanoid Complexes: Epoxidation
Catalytic asymmetric epoxidations are one of the most important asymmetric
processes [1]. In addition to previous successful achievements of other groups
with allylic alcohols [50, 51] and unfunctionalized olefins [52–55], the first effi-
cient catalytic asymmetric epoxidation of a variety of enones with broad gener-
ality has been developed when using chiral lanthanoid complexes [56].
In the presence of the sodium-containing heterobimetallic catalyst (R)-LSB
(10 mol%), the reaction of enone 52 with TBHP (2 equiv) was found to give the
desired epoxide with 83% ee and in 92% yield [56]. Unfortunately LSB as well as
other bimetallic catalysts were not useful for many other enones. Interestingly,
in marked contrast to LSB an alkali metal free lanthanoid BINOL complex,
which was prepared from Ln(O-i-Pr)3 and (R)-BINOL or a derivative thereof (1
or 1.25 molar equiv) in the presence of MS 4A (Scheme 17), was found to be ap-
plicable to a range of enone substrates. Regarding enones with an aryl-substitu-
ent in the α-keto position, the most effective catalytic system was revealed when
using a lanthanum-(R)-3-hydroxymethyl-BINOL complex La-51 (1–5 mol%)
and cumene hydroperoxide (CMHP) as oxidant. The asymmetric epoxidation
proceeded with excellent enantioselectivities (ees between 85 and 94%) and
yields up to 95%.
R
50: R = H
OH (1 equiv)
Ln(O-i-Pr)3 + OH 51: R = CH2OH
Ln = La or Yb (1.25 equiv)
MS 4A
THF, rt
La-BINOL cat. (R)-La-50

La-3-hydroxymethyl-BINOL cat. (R)-La-51
Yb-BINOL cat. (R)-Yb-50
Yb-3-hydroxymethyl-BINOL cat. (R)-Yb-51
(1-8 mol % catalytic amount)

O O
O
R1 R2 MS 4A, rt, THF R1 R2
52 ROOH (1.5 equiv; 53
CHMP or TBHP)
R1 = Ph, i-Pr, Ph(CH2)2, (R)-La-51 and CHMP:
CH3(CH2)4 up to 95% yield;
up to 94% ee
R2 = Ph, CH3, i-Pr, (R)-Yb-51 and TBHP:
o-MOMOC6H4 up to 91% yield;
up to 94% ee
Scheme 17. Catalytic asymmetric epoxidation of enones.
In contrast to this result, the enones with an alkyl moiety in the α-keto posi-
tion were best converted to the corresponding epoxides when replacing lantha-
num by ytterbium in the corresponding catalytically active complex of the above
mentioned type. Using TBHP (1.5 equiv) as oxidant in the presence of 5 mol%
of Yb-51 gave enantioselectivities up to 94%. However, the use of either Yb-50
catalyst or a La-CMHP system afforded the product of type 53 with less satisfac-
tory results. It seems likely that the difference in ionic radius between lanthanum
and ytterbium, as well as the difference in Lewis acidities, accounts for the ob-
served center metal effects.
Although the structure of the catalytically active species could not have been
unequivocally determined, it was found that an almost 1:1 ratio of Ln(O-i-Pr)3
(Ln=La or Yb) and BINOL gave the maximum enantiomeric excesses. In addi-
tion, an asymmetric amplification of the catalytic asymmetric epoxidation has
been obtained (Fig. 5) [56], which led to the conclusion that an oligomeric struc-
ture of these lanthanoid-BINOL catalysts may play a key role in these catalytic
asymmetric epoxidations of enones. Regarding the mechanism, a Ln-alkoxide
moiety in the catalysts appears to act as a Brønsted base, activating a hydroper-
oxide moiety so as to make possible a Michael reaction. At the same time anoth-
er Ln metal ion seems to act as a Lewis acid, both activating and controlling the
orientation of the enone. Furthermore, it is noteworthy that this catalytic asym-
metric epoxidation can be carried out at room temperature using 1–8 mol% of
an asymmetric catalyst to give epoxides with good enantiomeric excesses.
100
ee of 53a (%)
80
O
60 O
Ph CH3
40
53a
20
0
0 20 40 60 80 100
ee of 50 (%)
Figure 5. Asymmetric amplification in the Yb-50 catalyzed epoxidation reaction to 50a.
5
Catalytic Asymmetric C-P Bond Formation Using Heterobimetallic Lanthanoid
Complexes
The application of the heterobimetallic lanthanoid complexes of the LnMB type
led to a breakthrough in establishing a highly efficient asymmetric catalytic
route to α-hydroxy as well as α-amino phosphonic acid esters, which have at-
tracted much attention due to their wide ranging biological activity [57–64]. The
heterobimetallic catalysis described below represents the first and until now the
only highly efficient asymmetric catalytic approach to both α-hydroxy and α-
amino phosphonates by the attractive way of asymmetric catalytic hydrophos-
phonylation.
5.1
Hydrophosphonylation of Aldehydes
For the first time an LLB catalyzed enantioselective hydrophosphonylation of al-

dehydes has been independently reported by Shibuya et al. and Rath and Spilling
in the early 1990s [65, 66]. Due to the unknown catalyst structure of LLB at this
time, and to the fact that the purity of LLB catalyst utilized by this groups ap-
peared to be rather low, only low to modest ees have been achieved using LLB.
According to Shibuya et al. and Rath and Spilling, the hydrophosphonylation of
benzaldehyde gave the corresponding α-hydroxy phosphonates in less than 30%
ee [65, 66]. However, under similar conditions Shibasaki et al.'s reinvestigation
of the catalytic asymmetric hydrophosphonylation of benzaldehyde and cin-
namaldehyde with 1.3 equiv of dimethyl phosphite in the presence of 10 mol%
of LLB gave the corresponding α-hydroxy phosphonates in strongly improved
76% ee (79% yield) and in 72% ee (78% yield), respectively [67]. It is noteworthy
that with slow addition of the aldehydes, the enantiomeric excesses of both
products rose up to 83% ee (73% yield) and 79% ee (88% yield) respectively.
The reaction strongly depends on the solvent, increasing the ee from 4 to 16

to 79% ee when changing the solvent from diethyl ether to dichloromethane to
THF, which has been shown to be the solvent of choice. The LLB catalyzed hy-
drophosphonylation was most efficient in the case of aromatic aldehydes of low
reactivity or arylated α,β-unsaturated aldehydes as starting materials, with
enantioselectivities in the range of 84–95% ee (Scheme 18). A comparison of the
catalytic ability of LLB with its relative aluminum complex ALB showed that LLB
is superior for most of the aldehyde systems. Interestingly, however, for electron-
deficient aromatic aldehydes the aluminum-lithium-complex ALB gave better
results (e.g. in the case of p-nitrobenzaldehyde: 36% ee vs 71% ee). Thus, LLB
and ALB can be used in a complementary manner for the catalytic asymmetric
hydrophosphonylation of aldehydes. In contrast to other reactions, herein the
use of neither 6,6'-bis((triethylsilyl)ethynyl)BINOL nor the second-generation
LLB catalyst gave a significant improvement in the results.
The above-mentioned effects of slow addition of the aldehydes on the enanti-
oselection can be best explained as follows. Heterobimetallic catalysts such as
LLB are believed to activate both nucleophiles and electrophiles. For the hydro-
phosphonylation of comparatively unreactive aldehydes the activated phosphite
can react only with aldehydes which are pre-coordinated to lanthanum. Howev-
er, in the case of reactive aldehydes such as benzaldehyde and cinnamaldehyde,
the Li-activated phosphite may be able to undergo a competing reaction with the
unactivated aldehyde. If such aldehydes are added in one portion, the ee of the
product will be reduced. Slow addition of aldehyde, in contrast, has the effect of
maximizing the ratio of activated to unactivated aldehyde present in solution, by
allowing time for the catalytic cycle to complete and regenerate the catalyst,
thereby facilitating aldehyde activation. Reactive aldehydes should, therefore, be
added slowly in order to avoid the side reaction which proceeds without activa-
tion of the aldehyde by LLB (Scheme 19).
A detailed investigation into the hydrophosphonylation of substituted ben-
zaldehydes as well as heteroaromatic aldehydes has been recently reported by
Shibuya et al. [68] Therein this group found an interesting effect of the p-substit-
uent on enantioselectivity. In agreement with the results reported by Shibasaki
O OH
O (R)-LLB (10 mol %)
+ H P(OCH3)2 R P(OCH3)2
R H THF, -78 °C
O
R = Ph, p-R’C6H4,
(E)-R’CH=CR’’, 54
up to 94% yield
alkyl up to 95% ee
Scheme 18. LLB-catalyzed asymmetric hydrophosphonylation of aldehydes.

Li *
O
O O
O * La Li
O O OH
HP(OCH3)2 O
Li * R P(OCH3)2
LLB
O
Li Li
* * * *
O O O O
O La O O La O H R
Li H Li O O
O OO
OO H
P(OCH3)2
* Li * Li P(OCH3)2
RCHO
Scheme 19. A proposed catalytic cycle for asymmetric hydrophosphonylation.
et al. [67], good results were obtained when using p-methoxybenzaldehyde in

the presence of LLB with up to 82% ee and excellent yields [68]. A significant in-
fluence of the lanthanoid metal center ion and the alkali metal component was
also found, underlining that the choice of the rare earth metal and alkali metal
component in the Shibasaki catalyst is a crucial factor in inducing good enanti-
oselectivity. Interestingly, compared to LLB the use of either EuLB or SmLB as
asymmetric catalyst gave the reverse enantioselection (in case of p-methoxy
benzaldehyde), although with low ee (8 and 9%, respectively).
The role of the aromatic ring within a substrate was investigated in the LLB-
catalyzed hydrophosphonylation of a range of heteroaromatic aldehydes 55 (X=
O,S) with diethyl phosphite. Good yields were obtained for all products 56, al-
though enantioselectivities strongly varied from 18 to 73% ee (Scheme 20). The
enantioselectivities obtained from the reactions with aldehydes bearing a thi-
ophene nucleus were found to be higher than those of the corresponding furan-
carboxaldehyde derivatives. Regarding the series of reactions with aldehydes
which possess the same heterocycle, the numerical value of the ee of the prod-
ucts increased with an increase in the numerical value of the super-delocaliza-
bility Sr(E) [69, 70] at the carbonyl oxygen within the substrates (see Scheme 20).
These results reveal that the electrophilic coordination of the lanthanum atom in
a presumed LLB-phosphite complex to the carbonyl atom of the aldehyde might
be one critical factor governing the enantioselectivity.
Scheme 20. LLB-catalyzed asymmetric hydrophosphonylation of heteroaromatic aldehydes.
5.2
Hydrophosphonylation of Imines
5.2.1
Hydrophosphonylation of Acyclic Imines
α-Amino phosphonic acids are interesting compounds for the use in the design
of enzyme inhibitors [59, 60]. As in the case of α-hydroxy phosphonic acids, the
absolute configuration of the α-carbon strongly influences the biological prop-
erties. Although several (especially diastereoselective) methods for the synthesis
of optically active α-amino phosphonic acids have been known for a long time
[71, 72], the first catalytic asymmetric hydrophosphonylation of imines has
been reported recently by Shibasaki et al. [73] using potassium-containing
LnK3tris(binaphthoxide) complexes (LnPB) as most efficient catalysts.
Interestingly, almost the first results in asymmetric hydrophosphonylation
with acyclic imines revealed that the lanthanum-potassium-BINOL catalyst LPB
was more effective than the analog sodium and lithium complexes LSB and LLB,
both of which have been shown to be highly efficient in asymmetric C-C bond
formations (see Sect. 3). As a representative example, in the presence of LPB
(20 mol%) and 5 equiv of dimethyl phosphite the hydrophosphonylation of im-
ine 57a proceeds at room temperature under formation of the desired product
in 91% ee, whereas the use of LLB and LSB gave decreased enantioselectivities
(LSB: 49% ee; LLB: 38% ee) and yields. Moreover, attempts to improve the effi-
ciency of this asymmetric catalysis were successful. In the presence of only 5 or
10 mol% catalytic amount of LPB and 1.5 equiv of phosphite, another α-amino
phosphonate (bearing a benzhydryl group as N-substituent) was obtained in ex-
cellent 92 or 96% ee and good yields up to 82% when using 57b as imine compo-
nent (Scheme 21).
The broad generality of this asymmetric hydrophosphonylation method us-
ing catalytic amounts of LPB was shown by the effective conversion of several
types of imines to the corresponding optically active α-amino phosphonates in
satisfactory to excellent enantioselectivities up to 96% ee and yields up to 87%.
Concerning the substitution pattern of the imine component, the authors fo-
cused on the use of alkyl and alkenyl groups as C-substituents, whereas the ben-
zhydryl group was used as N-substituent in most of the cases due to the possibil-
ity to cleave this group from the products in order to obtain the pure α-amino
phosphonic acids with a primary amino function. In case of two imines, the use
of GdPB or PrPB gave the best results. Once again, these results confirm impres-
sively the ability of the LnMB type catalysts as a flexible asymmetric catalytic
system which can be easily modified and “designed” according to the needs for
the desired reaction by changing lanthanoid center ion, alkali metal component
and/or BINOL derivative. However, in this reaction neither the use of second-
generation LPB catalyst nor of LPB derivatives derived from modified BINOLs
gave improved results.
The proposed mechanism of this catalytic asymmetric hydrophosphonyla-
tion is shown in Scheme 22. The first step of this reaction is the deprotonation of
dimethyl phosphite by LPB to generate the potassium dimethyl phosphite. This
potassium phosphite immediately coordinates to a rare earth to give I due to the
strong oxophilicity of rare earth metals [74]. I then reacts with an imine to give
an optically active potassium salt of the α-amino phosphonate, which leads via
proton-exchange reaction to an α-amino phosphonate and LPB, thereby com-
pleting the catalytic cycle and giving the desired asymmetric hydrophospho-
nylation.
O R
R HN
N H P(OCH3)2
(R)-LPB P(OCH3)2
H (5 - 20 mol %)
O
57 58
a: R = CH(p-CH3OC6H4)2 up to 82% yield
b: R = CHPh2 up to 96% ee
Scheme 21. Asymmetric hydrophosphonylation of acyclic imines catalyzed by (R)-LnPB.

* O
O K O O K R1 * P(OCH3)2
HP(OCH3)2 O La O
HNR2
* O O *
K
LPB complex
* *
K
K O O K O O K
O O
O La O * La *
O O
* O O * O K
O H HNR2
KP(OCH3)2 P(OCH3)2
R1*
I III
*
2
N R K
O O K
O O
R1 H * La
O O *
OH
KNR2
P(OCH3)2
R1 *
II
Scheme 22. Proposed catalytic cycle.
In conclusion, the lanthanoid complex catalyzed hydrophosphonylation of

acyclic imines represents an efficient method to produce optically active α-ami-
no phosphonates in modest to high enantiomeric excess.
5.2.2
Hydrophosphonylation of Cyclic Imines
In spite of the high level of interest in the asymmetric synthesis of α-amino

phosphonic acids, less is known in the case of cyclic α-amino phosphonates. Al-
though in recent years descriptions of promising pharmaceutical applications
for cyclic compounds (and acylated derivatives thereof) have been published
[61–64], until now no efficient general asymmetric route has been available to
prepare this class of α-amino phosphonates. Several attempts at a diastereose-
lective synthetic route which were made by the addition of a stoichiometric
amount of chiral phosphites to cyclic imines, namely thiazolines, gave only lim-
ited diastereoselection ratios of dr=2:1 or below [75, 76].
The first efficient enantioselective synthetic route to cyclic α-amino phospho-
nates, namely the pharmaceutically interesting heterocyclic phosphonates of
type 1 [63, 64], by an asymmetric addition reaction of dialkyl phosphites to het-
erocyclic imines was recently developed by Shibasaki et al. (Scheme 23) [10, 77].
O
(H3CO)2P
N (R)-LnPB (5 - 20 mol %) 4 NH
H3C 4 CH3 H 3C CH3
H3C S CH3 (H3CO)2PHO, H3C S CH3
THF/toluene (1:7)
59 (S)-60
up to 97% yield
up to 98% ee
Scheme 23. Enantioselective hydrophosphonylation catalyzed by (R)-LnPB complexes.
Therein, potassium-containing heterobimetallic lanthanoid complexes have

been chosen as catalysts and thiazolines of type 59 were used as the imine sub-
strates. To produce the optically active α-amino phosphonate (S)-60, the model
compound 2,2,5,5-tetramethyl-3-thiazoline 59 was treated with 5 equiv of dime-
thyl phosphite in the presence of several kinds of chiral lanthanoid-potassium-
binaphthoxide complexes [(R)-LnPB]. At first, 20 mol% of LaK3tris(binaphthox-
ide) ((R)-LPB) in THF/toluene (1:7) at room temperature was used, which has
been shown to be the most efficient catalytic system in the asymmetric hydro-
phosphonylation of acyclic imines (see Sect. 5.2.1). However, only a modest
enantioselectivity of 61% ee accompanied by a 53% chemical yield was observed
in the formation of (S)-60 using this method. The efficiency of the reaction was
improved by increasing the reaction temperature to 50 ˚C. Investigations of the
influence of further lanthanoid metal components in the catalyst structure re-
vealed that, in the presence of Sm, Gd, Dy, and Yb, the ee values rose to 97% ee
accompanied by good to high chemical yields [10, 77]. The characteristic rela-
tionship between the ionic radii of the rare earth metal ions (III) and the enan-
tioselectivity is summarized in Fig. 6. The functional course of this graph sup-
ports the idea that (R)-LnMB catalysts represent a multifunctional, highly flexi-
ble catalyst system by varying their incorporated components.
In contrast to the asymmetric hydrophosphonylation of acyclic imines, the
rare earth metals with lower ionic radii in the range of [Yb(III)] to [Gd(III)] were
connected with the highest enantioselectivities of approximately 95% ee (where-
as high optical purities with acyclic imines were achieved with La(III), a lantha-
noid metal with a relatively large ionic radii). The asymmetric hydrophospho-
nylation of 59 with (R)-LPB was found to be limited, with only 64% ee. In agree-
ment with the hydrophosphonylation of acyclic imines, potassium was needed
as the alkali metal component in the complex (R)-LnMB to obtain acceptable re-
sults. In order to identify a highly efficient catalytic system which could main-
tain a high ee and yield even in the presence of small catalytic amounts, the in-
fluence of reduced catalytic amounts has been investigated. In the case of the
(R)-SmPB catalyzed asymmetric hydrophosphonylation, a steady decrease in
chemical yields was observed with smaller catalytic amounts, whereas nearly
unchanged high chemical yields were obtained when reducing the concentra-
tion of the (R)-YbPB catalyst from 20 to 15 to 10 mol%. A further decrease in the
ee 100
(%)
80
60
40
20
Gd
Yb Dy Sm Pr La
0
0.8 0.9 1.0 1.1
+3 Ionic Radius (A)
Figure 6. Effect of Lanthanoid Ionic Radii on Enantioselectivity (corresponding to the reac-

tion shown in Scheme 23).
100
90
80
Yield (%); ee (%)
70
60
50
40
30
(R)-SmPB (% Yield)
20
(R)-SmPB (% ee)
(R)-YbPB (% Yield)
10 (R)-YbPB (% ee)
0
0 5 10 15 20
Catalytic Amount
(mol %)
Figure 7. Influence of the catalytic amount on asymmetric hydrophosphonylation of imine

59.
concentration of the catalyst to 5 mol% (R)-YbPB gave (S)-60 in a still satisfac-

tory 63% yield. In all cases the enantioselectivity of the (R)-YbPB-catalyzed re-
action was approximately 95% ee. The functional dependence of the chemical
yield and enantiomeric excess from the catalytic amount is shown schematically
in Fig. 7.
Considering the superior asymmetric catalysis properties of La-Li-6,6'-disub-

stituted BINOL complexes in the enantioselective nitroaldol reaction, investiga-
tions were carried out with corresponding ytterbium catalysts. The use of the
6,6'-bis(methoxy)binaphthoxide derivative as ligand gave (S)-60 in improved
81% chemical yield while maintaining high enantioselectivity (96% ee; catalyic
amount: 5 mol%) [10]. Moreover, the flexibility of the optimized catalytic con-
ditions with regard to other substituted thiazolines was investigated using
5 mol% catalytic amount of (R)-YbPB in connection with a reaction tempera-
ture of 50 ˚C and THF/toluene (1:7) as a solvent. After a 48 h reaction time all
corresponding α-amino phosphonates were synthesized with high enantioselec-
tivities (up to 96% ee) nearly independently of the substituents at the thiazoline
ring system. In addition, at these reaction conditions (48 h reaction time) hydro-
phosphonylation of the model component 59 gave the corresponding product in
further improved 88% chemical yield (compared to 63% after 40 h).
The proposed mechanistic course is shown in Scheme 24 [10]. As the first
step, an interaction between the P=O bond's oxygen and the Yb(III) center ion
might occur, which results in the formation of a lanthanoid/phosphite complex
I. The preferred coordination of phosphite (instead of the theoretically also pos-
sible imine bond at the nucleophile N-atom) to Yb(III) is due to the high ox-
ophilicity of lanthanide(III) ions. However, in structure I the phosphorus atom
doesn't show any nucleophilic abilities, which are necessary for a nucleophilic
attack on the C=N double bond. Consequently, a tautomeric rearrangement of
structure I should take place, leading to a Ln(III)-coordinated phosphite form
IIb. Therein, the λ3 phosphorus atom shows enhanced nucleophilic character
caused by the lone pair, which now allows a nucleophilic attack on the C=N dou-
ble bond of the thiazolines. The nucleophilicity of the phosphorus atom should
be further increased by (partial) deprotonation and an additional coordination
of the resulting anion to the potassium in the intermediate IIa. Consequently, the
P-nucleophile reacts (in a high enantioselective manner) with the C=N double
bond of the thiazoline 59 to form the chiral potassium salt of the 4-thiazolidinyl-
phosphonate III. A subsequent proton-exchange reaction step produces the α-
amino phosphonate (S)-60 and (R)-LnPB, which are connected to each other in
structure IV. The final step of the catalytic cycle is achieved by a dissociation of
the α-amino phosphonate (S)-60 from the rare earth complex IV, which regen-
erates the “free” catalyst (R)-LnPB.
As shown in Fig. 8, two possibilities are conceivable for the addition step of
the imine to the lanthanoid-phosphite complex IIa. To determine whether struc-
ture V or VI seems to be the more reasonable in the addition reaction of a dime-
thyl phosphite with the C=N double bond of cyclic imines, several hydrophos-
phonylation experiments using different types of phosphites were carried out in
the presence or absence of the Lewis acid boron trifluoride. As it was shown that
a high level of Lewis acid activation of the imine is required independently from
the nucleophilicity of the phosphorus nucleophile which was used, a transition
state of type VI appeared to exist as the dominant transition state structure.
Scheme 24. Proposed reaction mechanism (for graphical reasons, the substituents at the
thiazoline 59 are not shown in this scheme).
Figure 8. Two possibilities for coordination of imine in the addition step.

6
Summary
In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were
recently developed by Shibasaki et al., are highly efficient catalysts in stereose-
lective synthesis. This new and innovative type of chiral catalyst contains a Lewis
acid as well as a Brønsted base moiety and shows a similar mechanistic effect as
observed in enzyme chemistry. A broad variety of asymmetric transformations
were carried out using this catalysts, including asymmetric C-C bond forma-
tions like the nitroaldol reaction, direct aldol reaction, Michael addition and
Diels-Alder reaction, as well as C-O bond formations (epoxidation of enones).
Thereupon, asymmetric C-P bond formation can also be realized as has been
successfully shown in case of the asymmetric hydrophosphonylation of alde-
hydes and imines. It is noteworthy that all above-mentioned reactions proceed
with high stereoselectivity, resulting in the formation of the desired optically ac-
tive products in high to excellent optical purity.
7
References and Notes
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37:9291
Reactions of Ketones with Low-Valent Lanthanides:
Isolation and Reactivity of Lanthanide Ketyl and Ketone
Dianion Complexes
Zhaomin Hou* and Yasuo Wakatsuki
The Institute of Physical and Chemical Research (RIKEN), Hirosawa 2–1, Wako,
Saitama 351–0198, JapanYasuo Wakatsuki
*E-mail: [email protected]
Recent progress in the chemistry of structurally well-defined lanthanide ketyl and ketone
dianion complexes is reviewed, with particular emphasis on the ligand effects on the reac-
tivity of these complexes. It has been demonstrated that the stability and reactivity of the
ketyl radical and ketone dianion species strongly depend on the steric and electronic prop-
erties of the ancillary ligands, the structure of their parent ketones, as well as the nature of
the metals to which they are bound. Fine-tuning these factors can control the reactivity of
these species. Generation and reactions of dianionic thioketone and imine species are also
briefly described.
Keywords: Ketyl radicals, Ketone dianions, Lanthanides, pinacol coupling, Ligand effects
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
2 One-Electron Reduction of Ketones . . . . . . . . . . . . . . . . . . 234
2.1 Fluorenone Ketyl Complexes with an Aryloxide (ArO) Ligand . . . 235

2.2 Fluorenone Ketyl Complexes with a C5Me5 Ligand . . . . . . . . . . 237
2.3 Fluorenone Ketyl Complexes with an N(SiMe3)2 Ligand . . . . . . 238
2.4 Benzophenone Ketyl Complexes . . . . . . . . . . . . . . . . . . . . 240
2.5 Complexes Bearing Three Independent Ketyl Ligands . . . . . . . 241
2.6 Structure-Reactivity Relation of Lanthanide Ketyl Complexes . . . 243
3 Two-Electron Reduction of Ketones . . . . . . . . . . . . . . . . . . 243
3.1 Isolation of a Ytterbium(II) Benzophenone Dianion Complex . . . 244

3.2 Reactions of Ketone Dianions with Organic Electrophiles . . . . . 245
3.3 Reactions of Ketone Dianions with 2,6-Di-tert-Butylphenols . . . . 246
3.3.1 Benzophenone Dianion Species . . . . . . . . . . . . . . . . . . . . 246
3.3.2 Fluorenone Dianion Species . . . . . . . . . . . . . . . . . . . . . . 248
4 Ketone-Reduction Paths Based on Isolated Intermediates . . . . . 248
5 Dianionic Thioketone and Imine Species . . . . . . . . . . . . . . . 250
6 Conclusions and Perspectives . . . . . . . . . . . . . . . . . . . . . 251
7 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
Topics in Organometallic Chemistry, Vol. 2

Volume Editor: S. Kobayashi
© Springer-Verlag Berlin Heidelberg 1999
234 Zhaomin Hou, Yasuo Wakatsuki
1
Introduction
Reactions of ketones with low-valent lanthanides such as SmI2 and the Ln (Ln=
Sm, Yb) metals constitute one of the most useful reactions in lanthanide-medi-
ated organic synthesis, and occupy an important position in modern organic
chemistry [1, 2]. It is well known that one-electron reduction of ketones by low-
valent lanthanides easily produces the corresponding radical anion species, or
ketyls. In the case of diaryl ketones, further one-electron transfer is also achiev-
able to afford the corresponding ketone dianions. These highly reactive species
play a very important role, as key intermediates, in a variety of useful reactions
involving ketones, such as reductions, ketyl-olefin couplings, pinacol couplings,
intermolecular cross couplings, and the Barbier-type reactions. Although other
reducing metals such as alkali, alkaline earth, and low-valent titanium metals
can also produce similar ketyls or ketone dianions upon reaction with ketones
[3], the lanthanide species usually behave differently from those metal analogs
and in many cases show higher reactivity and chemo-, regio- and stereo-selec-
tivity.
Despite the extensive applications and importance of the lanthanide ketyl and
ketone dianion species in organic synthesis, very little was known about their
structures. Our understanding about the reactivity of this important class of
species had relied solely on the analysis of the organic products obtained by hy-
drolysis work-up of the final reaction mixtures. Attempts to isolate these species
were greatly hampered by their extremely high reactivity and air and moisture
sensitivity [4].
It was not until very recently that significant progress has been made in this
field. By using sterically demanding ancillary ligands under an extremely dry
and oxygen-free inert atmosphere, several different types of lanthanide ketyl
and ketone dianion complexes have been successfully isolated and many of them
structurally characterized. Detailed studies on the reactivity of these well-de-
fined complexes have offered unprecedented insights into the mechanistic as-
pects of the reactions of ketones with low-valent lanthanides, and also shed new
lights on similar reactions with other reducing agents. This article is intended to
highlight the recent progress in this area, with particular emphasis on the struc-
ture-reactivity relation of lanthanide ketyl and ketone dianion complexes.
2
One-Electron Reduction of Ketones
The most difficult problem in isolating a ketyl species generated in one-electron
reduction of ketones is due to its rapid hydrogen abstraction and/or coupling re-
actions. To suppress these decomposition reactions, it is essential to use sterical-
ly demanding reducing agents and highly conjugated ketones [5]. It has been
found that several types of lanthanide reducing agents are able to afford isolable
and structurally characterizable ketyl complexes in the reactions with benzo-
Reactions of Ketones with Low-Valent Lanthanides 235
phenone and fluorenone. The structures and reactivity (stability) of the lantha-
nide ketyl complexes are strongly dependent on the ancillary ligands, solvents,
and the structure of their parent ketones.
X-ray analyses have shown that the C-O bond distance of a ketyl unit is gen-
erally around 1.30 Å, which is longer than that of a free ketone (ca. 1.20 Å) and
shorter than that of an alkoxide (ca. 1.40 Å). The radical carbon atom of a ketyl
is still in a sp2-hybrid state.
2.1
Fluorenone Ketyl Complexes with an Aryloxide (ArO) Ligand
Reactions of the divalent lanthanide aryloxide complexes Ln(OAr)2(L)x (Ar=

C6H2-tBu2-2,6-Me-4; 1a: Ln=Sm, L=THF, x=3; 1b: Ln=Yb, L=THF, x=3; 1c: Ln=
Sm, L=HMPA, x=2; 1d: Ln=Yb, L=HMPA, x=2) with 1 equivalent of fluorenone
in THF at room temperature give the corresponding ketyl complexes 2a-d as
deeply-colored crystals in high yields (Scheme 1) [6, 7]. Complexes 2a-d all have
a similar structure in which one fluorenone ketyl and two ArO ligands are placed
at the equatorial and two L (L=THF or HMPA) ligands are located at the apical
positions of a distorted trigonal bipyramid.
When the THF-coordinated complex 2a is dissolved in hexane/ether, the two
THF ligands are substituted by one molecule of OEt2, and the ketyl radical
dimerizes into a pinacolate (3) (Scheme 2) [6, 7]. More remarkably, the newly
formed C-C bond in 3 (1.613(9) Å) can be easily broken to quantitatively regen-
erate the ketyl 2a when 3 is dissolved in THF (Scheme 2), which unequivocally
demonstrates that the pinacol coupling process of the ketyl radical is completely
reversible. Addition of 2 equivalents of HMPA (per Sm) to a THF solution of 2a
or 3 gives almost quantitatively the corresponding HMPA-coordinated ketyl
complex 2c (Scheme 2). Since the coordination ability of HMPA is much strong-
er than that of THF [8], complex 2c is much more stable than 2a, and no change
was observed when 2c was treated similarly with hexane/ether. These results
clearly demonstrate that the stability and reactivity of a ketyl species are strong-
Scheme 1
Scheme 2
OH OH
l
HC
2N nt.
ArO OAr qua 4
Sm THF O2
THF
quant.
O
1a O
2N
H
qu Cl
2a an
t.
H OH
Scheme 3
ly influenced by the ancillary ligands bound to the central metal, and HMPA is a
better ligand than THF for the stabilization of a ketyl species [5, 7, 9].
Reflecting the typical reactivity of a ketyl species, hydrolysis of 2a gives the
corresponding pinacol-coupling product 4, while air oxidation of 2a yields flu-
orenone almost quantitatively (Scheme 3). Reaction of 2a with one equivalent of
1a produced a THF-insoluble purple precipitate which upon hydrolysis afforded
fluorenol quantitatively, suggesting that a fluorenone dianion intermediate was
formed [7, 9].
2.2
Fluorenone Ketyl Complexes with a C5Me5 Ligand
The similar reactions of (C5Me5)2Ln(THF)2 (Ln=Sm, Yb) with 1 equivalent of

fluorenone in THF give the corresponding ketyl complexes 5a,b in 85–87% iso-
lated yields (Scheme 4) [7]. Reactions of 5a,b with 1 equivalent of HMPA afford
the HMPA-coordinated ketyl complexes 5c,d. In contrast with the ArO-ligated
ketyl complexes 2a–d which require two THF or HMPA ligands as an additional
stabilizing moiety, the C5Me5-ligated complexes 5a–d need only one THF or
HMPA ligand for the stabilization of the ketyl species. This difference apparently
results from the larger size of C5Me5 as compared to that of the ArO ligand. Ad-
dition of hexane/ether to the THF-coordinated ketyl complexes 5a,b did not
cause any further reaction (Scheme 4), showing that the C5Me5-supported 5a,b
are more stable and less reactive than the ArO-supported 2a,b (see also
Sect. 2.1).
C5Me5 O
THF hexane
(C5Me5)2Ln(THF)2 + Ln no reaction
Ln = Sm, Yb C5Me5 THF
O
5a: Ln = Sm, 87%
5b: Ln = Yb, 85%
HMPA
C5Me5 O
Ln
C5Me5 HMPA
5c: Ln = Sm, 85%
5d: Ln = Yb, 86%
Scheme 4
C5Me5 HMPA C5Me5

THF O
Sm + Sm
ArO 91%
HMPA ArO HMPA
O
Ar = C6H2 tBu 6
2-2,6-Me-4
dark-brown
Scheme 5
Reaction of (C5Me5)Sm(OAr)(HMPA)2 with 1 equivalent of fluorenone in

THF also gives the corresponding ketyl complex 6 (Scheme 5) [7], demonstrat-
ing that the heteroleptic C5Me5/OAr ligand set [10] is also able to stabilize a ketyl
species. It is also noteworthy that although the homoleptic analogs 2c and 5c are
isolable, ligand redistribution of 6 to give either of these complexes was not ob-
served. Complex 6 represents a rare example of a lanthanide complex which
bears all different ligands.
2.3
Fluorenone Ketyl Complexes with an N(SiMe3)2 Ligand
The ketyl species stabilized by N(SiMe3)2 behaves a little differently from those
by C5Me5 and the ArO ligand. Reaction of Sm(N(SiMe3)2)2(THF)2 with
1 equivalent of fluorenone in THF gave a brown solution whose UV-Vis spec-
trum was almost identical to that of the ArO-ligated ketyl complex 2a, suggest-
ing that the corresponding ketyl species 7a was formed [7]. However, attempts
to isolate the ketyl species 7a from THF were unsuccessful and always resulted
in the formation of the light yellow pinacolate 8a (Scheme 6).
The central C-C bond in 8a could also be cleaved by addition of a strongly co-
ordinative solvent. Dissolving the light yellow 8a in THF gave immediately a
brown solution whose UV-Vis spectrum was the same as that of the solution
originally obtained by the reaction of Sm(N(SiMe3)2)2(THF)2 with fluorenone in
THF (Scheme 6). Addition of 4 equivalents of HMPA to this THF solution afford-
ed the bis(HMPA)-coordinated ketyl complex 7b together with the mono(HM-
PA)-coordinated pinacolate complex 8b (Scheme 7) [7].
The isolation of the pinacolate 8a rather than the ketyl 7a from THF
(Scheme 6) and the isolation of the mono(HMPA)-coordinated pinacolate 8b to-
gether with the bis(HMPA)-coordinated ketyl 7b in the reaction of 8a or 7a with
HMPA (Scheme 7) contrast sharply with the similar reactions of the ArO-ligated
complex 2a or 3, in which only the bis(THF or HMPA)-coordinated ketyl com-
plexes were isolated (see also Sect. 2.1). These differences probably result from
the difference in electron-donating ability between N(SiMe3)2 and the ArO lig-
and. Since N(SiMe3)2 is more electron-donating than the ArO ligand, dissocia-
tion of a neutral L (L=THF or HMPA) ligand from the central Sm atom in the
(Me3Si)2N
THF
(Me3Si)2N N(SiMe3)2 (Me3Si)2N
Sm
THF Sm THF O
Sm(N(SiMe3)2)2(THF)2 + THF – THF
O +THF
O O
Sm
N(SiMe3)2
THF
7a N(SiMe3)2
brown in THF
8a, 79%
light-yellow
Scheme 6
(Me3Si)2N
HMPA
(Me3Si)2N Sm
(Me3Si)2N N(SiMe3)2
O
HMPA Sm HMPA
HMPA +
O O
Sm
N(SiMe3)2
HMPA
N(SiMe3)2
(Me3Si)2N 7b
8b
THF greenish-brown
(Me3Si)2N light-yellow
Sm 50% 20%
O
ArO OAr
O ArOH Sm
THF THF
Sm – HN(SiMe3)2
N(SiMe3)2 90% O
THF
N(SiMe3)2
8a
light-yellow 2a
purple-brown
ArO OAr
ArOH/HMPA
HMPA Sm HMPA
– HN(SiMe3)2
88% O
2c
dark-green
Scheme 7
(Me3Si)2N
THF
(Me3Si)2N
Sm (Me3Si)2N N(SiMe3)2 (Me3Si)2N N(SiMe3)2
O ∆H =11 kcal/mol Sm + THF Sm
THF THF
2 THF O 2
in toluene – THF O
O
Sm
N(SiMe3)2
THF 7c
N(SiMe3)2 7a
8a
Scheme 8
(Me3Si)2N-ligated complexes 7a,b would be easier than that in the ArO-ligated

complexes 2a,c, which thus causes pinacol-coupling of the ketyl radical in 7a,b
to occur more easily. In accord with this consideration, when 4 equivalents of
ArOH were added to a THF solution of 8a, the corresponding ArO-ligated ketyl
complex 2a was isolated in 90% yield with the release of HN(SiMe3)2 (Scheme 7).
The similar reaction of 8a with ArOH in THF/HMPA yielded selectively the cor-
responding bis(HMPA)-coordinated ketyl complex 2c (Scheme 7) [7].
To gain more information concerning the C-C bond cleavage of the pinacolate
8a, a variable-temperature UV-Vis spectroscopic study in toluene was carried
out. The derived dissociation enthalpy DHdiss for 8a to give 7c is 11 kcal/mol
(Scheme 8) [7]. This value is much smaller than that reported for silicon benzo-
pinacolate, Me3SiOC(Ph)2C(Ph)2OSiMe3 (31 kcal/mol) [11], but comparable

with that reported for the Ca-Cpara bonds in the trityl dimer [Ph3C]2 (11–
12 kcal/mol) [12] and that for the dimeric titanium(IV) alkoxide/enolate com-
plex [(tBu3SiO)3Ti(OCPh2)]2 (18 kcal/mol) [13]. Obviously the dissociation en-
thalpy for 8a to give the bis(THF)-coordinated ketyl complex 7a should be much
smaller than this value, since this process is accompanied by the formation of
two new Sm(III)-THF bonds (Scheme 8). Since the bond energy of a Sm(II)-THF
bond in (C5Me5)2Sm(THF)n (n=1 or 2) is about 5–7 kcal/mol [14], and a Sm(III)-
THF bond is generally stronger than a Sm(II)-THF bond, the formation of two
Sm(III)-THF bonds in the course of the transformation of 8a to 7a would release
more than 10 kcal/mol, which could well compensate the enthalpy (11 kcal/mol)
for the cleavage of the central C-C bond in 8a. It is thus not difficult to under-
stand that when a large excess of THF is present (e.g., in THF solution), the equi-
libria in Scheme 8 will be greatly shifted to the right, and complete dissociation
of 8a to 7a will be easily achieved.
2.4
Benzophenone Ketyl Complexes
Compared to the planar fluorenone ketyl, benzophenone ketyl is less conjugated

and thus more reactive [15]. Reactions of benzophenone with the lanthanide re-
ducing agents which were successfully used for the isolation of fluorenone ketyl
complexes did not give a structurally characterizable benzophenone ketyl spe-
cies, and in many cases yielded the corresponding hydrogen abstraction prod-
ucts. For example, reaction of 1d with 1 equivalent of benzophenone in THF gave
after a few weeks the colorless ytterbium(III) aryloxide/diphenylmethoxide
complex Yb(OCHPh2)2(OAr)(HMPA)2 (9) via hydrogen radical abstraction
from solvent by the initially generated ketyl radical species (Scheme 9) [7].
ArO OAr OAr

O solvent-H
THF Yb
Yb(OAr)2(HMPA)2 + C HMPA HMPA HMPA Yb HMPA + [Yb(OAr)3]
1d Ph Ph O O ?
O
C Ph C H C H
Ar = C6H2tBu2-2,6-Me-4 Ph Ph Ph Ph
Ph
9
66% based on Ph2CO
Scheme 9
O TpMe2 Ph
toluene Sm O C
Sm(TpMe2)2 + C
Ph 80% Ph
Ph TpMe2
TpMe2 = BH(3,5-dimethylpyrazolyl)3 10, purple
Scheme 10
Recently, Takats and coworkers have successfully isolated a structurally char-

acterizable lanthanide benzophenone ketyl complex (10) by using a further ster-
ically demanding reducing agent, Sm(TpMe2)2 (TpMe2=BH(3,5-dimethylpyra-
zolyl)3) (Scheme 10) [16a]. Izod and coworkers have isolated and structurally
characterized the corresponding benzophenone ketyl complex by using
Sm(C(SiMe3)2(SiMe2OMe))2(THF) as a rducing agent [16b]. These results again
demonstrate that the behavior of a ketyl species is greatly influenced by the an-
cillary ligands.
2.5
Complexes Bearing Three Independent Ketyl Ligands
In contrast with the divalent lanthanide complexes, which are one-electron

transfer agents and afford complexes consisting of one ketyl per metal ion upon
reaction with ketones, the zero valent lanthanide metals are three-electron
transfer agents, and their reactions with ketones, if straightforward, should yield
complexes bearing three independent ketyl ligands. However, compared to mo-
no(ketyl) complexes, the isolation of a multi(ketyl) metal species is generally
more difficult and challenging, since intramolecular pinacol-coupling of ketyl
radicals is also possible besides the common intermolecular reactions.
It has been found that the use of HMPA as a coordinating ligand can suffi-
ciently suppress coupling reactions of the ketyl radicals in multi(ketyl) metal
complexes to allow their isolation [5, 7, 15, 17]. Thus, reaction of Sm metal pow-
der with 3 equivalents of fluorenone and 3 equivalents of HMPA in THF afforded
the corresponding Sm(III) tris(fluorenone ketyl) complex 11a as black-green
blocks (Scheme 11) [7, 17]. An X-ray analysis has shown that this complex pos-
sesses an octahedral structure, in which the central Sm atom is coordinated in
mer-type fashion by three ketyls and three HMPA ligands. The similar reaction
of Yb metal with 3 equivalents of fluorenone gives the Yb(III) tris(ketyl) complex
11b (Scheme 11), which is isostructural and isomorphous with 11a [7].
Hydrolysis of 11a,b gives almost quantitatively the corresponding pinacol 4
(Scheme 11). Interestingly, the reaction of 11a with 0.5 equivalents of 4 yields the
dimeric samarium(III) fluorenoxide/pinacolate complex 12 and fluorenone
(Scheme 11) [7]. Further studies have confirmed that the formation of 12 is via
hydrogen atom abstraction from the pinacol by one ketyl, followed by pinacol-
coupling of the other two ketyls together with simultaneous release of two
HMPA ligands in 11a (Scheme 11). Homolytic C-C bond cleavage of the biradical
species 13, which is formed by dehydrogenation (–H.) of pinacol 4, affords flu-
orenone. It is noteworthy that the small steric change, which is caused by the
transformation of one of the three fluorenone ketyls to a fluorenoxy unit, has im-
posed crucial influence on the stability and reactivity of the other two ketyls.
In contrast with the case of fluorenone, similar reactions of Ln/HMPA (Ln=
Sm, Yb) with benzophenone did not give an isolable ketyl species and yielded fi-
nally decomposition products, demonstrating again that benzophenone ketyl is
more reactive than fluorenone ketyl [7]. These reactions are also in sharp con-
OH
242
OH
H+
O 4, 98%
HMPA HMPA
3 equiv HMPA
Ln + 3 Ln
THF O
HMPA
O O
(Ln = Sm) HMPA O H

O
+4 O
– fluorenone Sm Sm
O
11a: Ln = Sm, 65% O HMPA
or H O
11b: Ln = Yb, 60% + benzopinacol
black-green – benzophenone
+ 0.5 equiv 4
12, 60%
light-yellow
– HMPA
O O
1 HMPA
HMPA
2 HMPA
O Sm
O HMPA HMPA O
Sm O
O H O
13 HMPA
O
H
Scheme 11
Zhaomin Hou, Yasuo Wakatsuki
trast with those of Na/HMPA [5] or Ca/HMPA [5, 15] with benzophenone, in
which the corresponding benzophenone ketyl species have been successfully
isolated and structurally characterized. These results show that the nature of the
reducing metals also strongly influences on the reactivity and stability of a ketyl
species and the lanthanide ketyl species are more reactive than those of alkali
and alkaline earth metals.
2.6
Structure-Reactivity Relation of Lanthanide Ketyl Complexes
The results described above have demonstrated that the stability and reactivity
of a ketyl species are extremely susceptible to the environment around the cen-
tral metal ion. Both anionic and neutral (solvent) ligands play an important role
in determining the behavior of a ketyl species. The sterically demanding
bis(pentamethylcyclopentadienyl) ligand set (C5Me5)2 together with a neutral L
(L=THF or HMPA) ligand offers a good stabilizing environment for a lanthanide
fluorenone ketyl species, while the less bulky (ArO)2 or ((Me3Si)2N)2 ligand set
requires two L (L=THF or HMPA) ligands for the stabilization of the same ketyl
species. In the latter case, dissociation of one of the two L ligands from the cen-
tral metal ion easily occurs to cause pinacol-coupling of the ketyl, and this takes
place more easily for the (Me3Si)2N-ligated complexes than for the ArO-ligated
ones, due to the stronger electron-donating ability of N(SiMe3)2. Re-coordina-
tion of an L ligand to the metal atom of the resulting pinacolate easily cleaves the
central C-C bond and regenerates the ketyl, which thus makes the pinacol-cou-
pling process reversible. The relatively small dissociation enthalpy for the pina-
colate complexes (e.g., DHdiss=11 kcal/mol for 8a) could well account for this re-
versibility. HMPA, as a neutral and strongly coordinating ligand, offers an excel-
lent stabilizing moiety for both mono- and multi-ketyl complexes. The transfor-
mation of the tris(ketyl) complex 11a to the fluorenoxide/pinacolate complex 12
provides unprecedented insights into the elementary steps of the hydrogenation
and pinacol-coupling reactions of a ketyl species. Ketone-dependence of the sta-
bility of ketyls is also observed. In contrast to fluorenone ketyl complexes, the
isolation of a structurally characterizable benzophenone ketyl complex is more
difficult due to its less conjugated structure which makes it more reactive and
less stable. However, by choosing an appropriate ligand set such as bis(hydrot-
ris(3,5-dimethylpyrazolyl)borate), a structurally characterizable lanthanide
benzophenone ketyl species can indeed be isolated. It is obvious from these re-
sults that the stability and reactivity of a ketyl radical species can be controlled
through tuning the ancillary ligands bound to the central metal ion.
3
Two-Electron Reduction of Ketones
Among all low-valent lanthanides, the zero valent Sm and Yb metals are the most
often used reducing agents for the study of two-electron reduction of ketones.
Although earlier studies showed that the formation of a samarium ketone dian-
ion species was not as efficient as that of ytterbium [18–20], it was later found
that samarium ketone dianion species could be generated similarly if the metal
surface was sufficiently activated, e.g., by ICH2CH2I [21, 22]. Since the negatively
charged carbon and oxygen atoms in a ketone dianion species are adjacent, the
use of a sterically demanding lanthanide(II) reducing agent does not necessarily
give a good result for the isolation of such species because of the steric repulsion
between the resultant two closely located bulky metal moieties. Therefore, the
control of the reactivity or stability of a ketone dianion species through tuning
the ancillary ligands may not be as effective as in the case of ketyls. Moreover,
compared to the mono-anionic ketyls, ketone dianions are more difficult to gen-
erate. They are more sensitive to air and moisture, and thus more difficult to
handle. Probably due to these reasons, structurally characterized examples of
ketone dianion species remain very scarce [23–25], and only one lanthanide ke-
tone dianion complex, [Yb(m-h1,h2-OCPh2)(HMPA)2]2, has been isolated and
structurally characterized to date (see below) [24]. The known ketone dianions
are limited solely to those bearing two aromatic groups on the carbonyl carbon
atom.
Despite these limitations, it has been found that the lanthanide ketone dian-
ions are an interesting class of species which show unique reactivities. As de-
scribed below, in lanthanide ketone dianion species the carbonyl carbon atom is
completely changed from electrophilic to nucleophilic, and shows strong nucle-
ophilicity towards a variety of organic substrates. Due to the delocalization of
the negative charges in the aromatic groups, some reactions can also take place
at the aromatic ring.
3.1
Isolation of an Ytterbium(II) Benzophenone Dianion Complex
Reaction of Yb metal powder with 1 equivalent of benzophenone in THF/HMPA

gives the Yb(II) benzophenone dianion complex [Yb(m-h1,h2-OCPh2)(HM-
PA)2]2 (14) as purple crystals (Scheme 12) [21, 24]. X-ray analysis has revealed
that complex 14 possesses a dimeric structure, in which the two Yb atoms are
bridged by two benzophenone dianions. The bridge is built in such a manner
Scheme 12
O O
C C
...
Scheme 13
Scheme 14
that a benzophenone dianion uses its O atom to make a Yb-O bond with one
Yb(II) ion and its C atom to make a Yb-C bond with the other Yb(II) ion to which
the lone electron pair of the oxygen atom is also donated (Scheme 12). The C-O
bond of the benzophenone dianion (1.39(6) Å) is longer than that of benzophe-
none ketyl (1.31(2) Å) [15, 16] and that of free benzophenone (1.23(1) Å) [26].
Similar to benzophenone ketyl, the carbonyl carbon atom in benzophenone di-
anion is still in an sp2-hybrid state, which can thus allow good conjugation of the
negative charges with the phenyl rings.
Consistent with the above structural observations, the 1H NMR signals for the
phenyl groups in 14 in THF-d8 are greatly upfield shifted to as high as d 5.63–
7.04, demonstrating that the negative charges of the ketone dianion are indeed
highly delocalized into the phenyl rings, especially to the para-positions (d 5.63)
(Scheme 13) [21,22]. As described in Sect. 3.3, this delocalization of electrons
can have great influence on the reactivity of benzophenone dianion species.
3.2
Reactions of Ketone Dianions with Organic Electrophiles
It has been found that lanthanide ketone dianion species are excellent nucle-
ophiles, which react smoothly with a variety of organic substrates such as ke-
tones, nitriles, epoxides, CO2, etc. to give after hydrolysis the corresponding un-
symmetrical pinacols, a-hydroxy ketones, 1,3-diols, a-hydroxy carboxylic acids,
etc., in good yields, respectively (Scheme 14) [18–20]. Compared to alkali metal
ketone dianions, they are less basic and more nucleophilic, and selectively un-
dergo addition reactions even with substrates bearing active a-protons, such as
aliphatic ketones and nitriles.
3.3
Reactions of Ketone Dianions with 2,6-Di-tert-Butylphenols
Most of the reactions of ketone dianion species, including those of main group
and titanium metals, are known to occur at the carbonyl unit, as demonstrated
in Sect. 3.2. However, it was found that the protonation reactions of lanthanide
benzophenone dianion species with 2,6-di-tert-butylphenols can take place not
only at the carbonyl group but also at the phenyl ring, due to the delocalization
of the negative charges onto the aromatic groups. The selectivity between reac-
tions at the carbonyl group and those at the aromatic ring in lanthanide diaryl
ketone dianion species depends greatly on the nature of both metals and ke-
tones.
3.3.1
Benzophenone Dianion Species
Reaction of the Yb(II)-benzophenone dianion complex 14 with ArOH (Ar=

C6H2-tBu2-2,6-R-4, R=H, Me) gave the corresponding ytterbium(II) bis(ary-
loxide) complex Yb(OAr)2(HMPA)2 (1d) as a major product, which was formed
by the protonation of both the carbon and oxygen atoms of the carbonyl unit
with ArOH (Scheme 15) [22, 24]. Besides 1d, an ytterbium(III) enolate complex
(15) was also obtained as a minor product. In contrast, when the analogous
Sm(II) benzophenone dianion species was allowed to react with ArOH, the sa-
marium(III) enolate complex 16, which is analogous to 15, was formed as a ma-
jor product, while the samarium(II) bis(aryloxide) complex Sm(OAr)2(HMPA)2,
an analog of 1d, was not observed (Scheme 16) [22, 27]. The similar reaction of
the Sm(II) benzophenone dianion species with ArOD yielded the corresponding
C HMPA OAr
HMPA O ArO HMPA
ArOH
Yb Yb + HMPA Yb HMPA
HMPA Yb
O – Ph2CHOH
HMPA ArO O
C HMPA O
C C
1d, 80% H Ph Ph H
H
14 Ar = C6H2-tBu2-2,6 -Me-4 H
15, 5%
Scheme 15
OAr
O C HMPA
THF/HMPA HMPA O
Sm + Ph C Ph ArOH HMPA Sm HMPA
Sm Sm
O HMPA 60% O O
HMPA
C C C
H Ph Ph H
H H
16
Ar = C6H2-tBu2-2,6 -Me-4
Scheme 16
OAr
O
THF/HMPA ArOD HMPA Sm HMPA
Sm + Ph C Ph
60% O O
C C
H Ph Ph H
D D
17
Scheme 17
OAr toluene or OAr

toluene-d8
HMPA Sm HMPA HMPA Sm HMPA
180 °C
O O 80% H O O
C H
C C C
H Ph Ph H
Ph Ph Ph
H H Ph
16 18
Scheme 18
deuterated enolate 17 (Scheme 17), suggesting that the formation of 15 and 16 is

via the direct protonation of the para carbon atom of a phenyl group in the ben-
zophenone dianion unit.
The formation of the enolate complexes 15 and 16 is apparently due to the de-
localization of the negative charges in the phenyl groups of the benzophenone
dianion species (see Scheme 13). The difference in reactivities observed between
Sm(II) and Yb(II) benzophenone dianion species may result from differences in
the two divalent metal ions. Since Sm(II) is more electron-donating [28] and big-
ger in size than Yb(II) [29], the negative charges in the Sm(II) benzophenone di-
anion species must be more delocalized into its phenyl rings, which are thus
more easily protonated on the phenyl part and give a Sm(III) enolate species.
It is also interesting to note that the formation of the enolates 15 and 16 in the
above reactions resembles well the Birch reduction of aromatic compounds
bearing electron-withdrawing groups [30], in which metal enolate intermedi-
ates are believed to be formed via monoprotonation of dianionic species. How-
ever, such species have never been well characterized. Complexes 15 and 16 are
OAr OAr
toluene
HMPA Sm HMPA HMPA Sm HMPA
180 °C
O O O O H(D)
C C C
C H(D)
H Ph Ph H (D)H
D D
17 H(D)
19
Scheme 19
rare examples of structurally characterized metal enolate compounds which

model the enolate intermediates formed in the Birch reductions.
When the enolate complex 16 was heated in toluene or toluene-d8 at 180 ˚C
overnight, intramolecular hydrogen transfer reaction occurred to give the cor-
responding aryloxide/diphenylmethoxide complex Sm(OC(H)Ph2)2(OAr)(HM-
PA)2 (18) (Scheme 18) [22, 24]. The similar reaction of the deuterated enolate 17
yielded 19 selectively (Scheme 19); scrambling of deuterium at the phenyl ring
was not observed. These results suggest that the formation of 18 from 16 is a one-
step 1,5-hydrogen shift process. It is also noteworthy that even at high tempera-
tures (up to 180 ˚C) ligand redistribution in these heteroleptic lanthanide com-
plexes was not observed.
3.3.2
Fluorenone Dianion Species
The protonation reaction of the Yb(II) fluorenone dianion species with ArOH is
similar to the major reaction of the Yb(II) benzophenone dianion 14 with ArOH,
occurring at both the C and O atoms of the carbonyl unit to afford 1d and fluore-
nol (Scheme 20). However, the protonation reaction of the Sm(II) fluorenone di-
anion species with ArOH takes place only at the C atom and is accompanied by
the oxidation of the Sm(II) ion to give the corresponding samarium(III) ary-
loxide/fluorenoxide complex 20 (Scheme 20), which again demonstrates the
metal dependence of the reactivity of lanthanide ketone dianion species [22].
4
Ketone-Reduction Paths Based on Isolated Intermediates
As described above, with the combination of appropriate lanthanide reducing
agents, solvents, and substrates, almost all types of the key intermediates in-
volved in the reduction of ketones have been isolated and structurally character-
ized (Scheme 21), such as the one-electron reduction product (ketyl radical 21),
its reversible coupling product (pinacolate 24), hydrogen abstraction product
(alkoxide 23) and further one-electron reduction product (ketone dianion 22),
and the selective protonation products of the ketone anion (alkoxide 23 and eno-
(Ln = Yb)
ArO HMPA
ArOH
Yb
– fluorenol
ArO HMPA
O ArO 1d, 85%
Ln(HMPA)x Ln(HMPA)x
THF/HMPA ArOH
Ln + O H
O OAr
(Ln = Sm)
ArOH Sm HMPA
HMPA
– H2
ArO O H
Reactions of Ketones with Low-Valent Lanthanides
20, 64%
Scheme 20
249
O
Ar C H
Ar
23 H+
solvent-H
O O O OH
+e +e
C C E H+
–e –e C Ar C E
Ar Ar Ar Ar Ar Ar Ar
21 22 E = electrophiles or H+
H+
Ar = Ph H+
OH OH O O O
Ar H+ O
C C Ar Ar C C Ar C
Ph Ph C H
Ar Ar Ar Ar
H Ph
24 H
25
Scheme 21. Structurally characterized intermediates and their reactions
late 25). Structural and reactivity studies of these isolated intermediates have
given rise to an ever clearer picture of the reaction paths in the reaction of ke-
tones with low-valent lanthanides (Scheme 21), and thus offered unprecedented
insights into the mechanistic aspects of these and related reactions.
5
Dianionic Thioketone and Imine Species
Similar to diaryl ketones, aromatic thioketones and imines can also be reduced
to the corresponding dianionic species. Fujiwara and coworkers have reported
that the ytterbium diaryl thioketone dianion species, generated by reaction of Yb
metal with the thioketones in THF/HMPA at low temperature, show good nucle-
ophilicity towards organic substrates such as acetone and alkyl halides
(Scheme 22) [31]. The thioketone dianion species seemed to be less stable than
those of ketones. At room or higher temperatures, C-S bond cleavage reaction
took place.
Reaction of N-(diphenylmethylidene)aniline with 1 equivalent of Yb metal in
THF/HMPA gives the corresponding dianionic complex Yb(h2-Ph2CNPh)(HM-
PA)3 (26) whose structure has been crystallographically determined (Scheme 23)
[32]. The imine dianion complex 26 is more basic and less nucleophilic than ke-
tone- and thioketone-dianion species. It reacts with CO2 to give after hydrolysis
the corresponding Yb(III) amino acid derivative [33], but with acetone to release
SH OH
CH3COCH3
Ar C C CH3
72%
Ar CH3
S S
THF/HMPA Yb
C + Yb Ar C
Ar Ar 0 °C
Ar
Ar = Ph, C6H4Me-4 BrCH2(CH2)nCH2Br Ar
50-66% Ar ( )n
S
n = 1, 2
Scheme 22
CH3COCH3
Ph2CHNHPh
> 99%
Ph Ph
N
THF/HMPA N
+ Yb Yb(HMPA)3
C room temp. C
Ph Ph Ph
Ph
CO2 H 2O
26, red-black Ph2C(NHPh)COO)3Yb • 2HMPA •
45% 2H2O
92%
Scheme 23
Ph2CHNHPh almost quantitatively (Scheme 23) [32]. Isomerization of terminal

alkynes to internal alkynes by 26 was also reported [34].
6
Conclusions and Perspectives
The results described in this article have clearly demonstrated that the highly re-
active lanthanide ketyl and ketone dianion species can not only be isolated but
also their reactivity be controlled through adjusting the environment around the
central metals. For example, a ketyl species can be “deactivated” (stabilized) by
binding to a bulky metal moiety and “reactivated” by reducing the bulkiness
around the metal. Although the examples presented here are limited to those of
aromatic ketones, these data should be conceptually useful for the understand-
ing and design of reactions involving other organic carbonyl compounds. In
view of the versatile uses of ketyls in organic synthesis and the high nucle-
ophilicity of lanthanide ketone dianion species, if the “deactivation” and “reacti-
vation” of alkyl ketone and/or aldehyde ketyl species can be achieved in a con-
trollable way, and if alkyl ketone and/or aldehyde dianion species can also be
generated, numerous classical C-C bond formation processes will be substan-
tially improved and our capability to access a variety of new target compounds
will be dramatically enhanced. These topics remain to be challenged.
Acknowledgments. We are grateful to all our coworkers who have so effectively

participated in our work described here and whose names are shown in the list
of references. Our studies were financially supported by grants from the Ministry
of Education, Science, Sports, and Culture of Japan, and by the President’s Special
Research Grant of The Institute of Physical and Chemical Research (RIKEN).
7
References
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Organo Rare Earth Metal Catalysis for the Living
Polymerizations of Polar and Nonpolar Monomers
Hajime Yasuda
Department of Applied Chemistry, Faculty of Engineering, Hiroshima University,

Higashi-Hiroshima 739–8527, Japan
e-mail: [email protected]
This article deals with the rare earth metal initiated polymerization of polar and nonpolar
monomers in a living fashion. For example, [SmH(C5Me5)2]2 or LnMe(C5Me5)2(THF) (Ln=
Sm, Y and Lu) conducted the polymerization of methyl methacrylate(MMA) to give high
molecular weight syndiotactic polymers (Mn>500,000, syndiotacticity>95%) quantitative-
ly at low temperature (–95 °C). The initiation mechanism was discussed on the basis of X-
ray analysis of the 1:2 adduct of [SmH(C5Me5)2]2 with MMA. Synthesis of high molecular
weight isotactic poly(MMA) with very narrow molecular weight distribution was for the
first time realized by the efficient catalytic function of Yb[C(SiMe3)3]2. Living polymeriza-
tions of alkyl acrylates (methyl acrylate, ethyl acrylate, and butyl acrylate) were also possi-
ble by the excellent catalysis of LnMe(C5Me5)2(THF) (Ln=Sm, Y). By taking advantages of
the living polymerization ability, we attempted ABA triblock copolymerization of
MMA/butyl acrylate/MMA to obtain rubber-like elastic polymers. Organo rare earth metal
complexes such as LnOR(C5R5)2 or LnR(C5R5)2 conducted the living polymerizations of
various lactones such as β-propiolactone, δ-valerolactone and ε-caprolactone, and also
conducted the block copolymerizations of MMA with various lactones. Lanthanum alkox-
ide(III) has good catalytic activity for the polymerization of alkyl isocyanates. Monodis-
perse polymerizations of lactide and various oxiranes were also achieved by the use of rare
earth metal complexes. C1 symmetric bulky organolanthanide(III) complexes such as
SiMe2[2(3),4-(SiMe)2C5H2]2LnCH(SiMe3)2 (Ln=La, Sm, and Y) show high catalytic activity
towards linear polymerization of ethylene. Organolanthanide(II) complexes such as ra-
cemic SiMe2(2-SiMe3-4-tBu-C5H2)2Sm(THF)2 as well as C1 symmetric SiMe2[2(3),4-
(SiMe3)2C5H2]2Sm(THF)2 were found to have high activity for the polymerization of ethyl-
ene to give Mn>106 with Mw/Mn =1.6. Utilizing the high polymerization activity of rare
earth metal complexes towards both polar and nonpolar monomers, block copolymeriza-
tions of ethylene with polar monomers such as methyl methacrylate and lactones were for
the first time realized. 1,4-cis-Conjugated diene polymerization of 1,3-butadiene and iso-
prene became available by the efficient catalytic activity of NdCl(C5H5)2/AlR3 or Nd(oc-
tanoate)3/AlR3. The Ln(naphthenate)3/AliBu3 system allows selective polymerization of
acetylene in cis-fashion.
Keywords: Living polymerization, Living copolymerization, Rare earth metal complexes,

Alkyl methacrylate, Alkyl acrylates, Lactones, Ethylene, 1-Olefins, Conjugated dienes,
Acetylene
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
2 Highly Stereospecific Living Polymerization of
Alkyl Methacrylates . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
3 Living Polymerization of Alkyl Acrylates . . . . . . . . . . . . . . . 262
256 Hajime Yasuda
4 Block Copolymerization of Hydrophorbic and

Hydrophilic Acrylates . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
5 Polymerization of Alkyl Isocyanates . . . . . . . . . . . . . . . . . . 265
6 Living Polymerization of Lactones . . . . . . . . . . . . . . . . . . . 265
7 Stereospecific Polymerization of Oxiranes . . . . . . . . . . . . . . . 267
8 Polymerization of Lactide . . . . . . . . . . . . . . . . . . . . . . . . 269
9 Stereospecific Polymerization of Olefins . . . . . . . . . . . . . . . . 269
10 Block Copolymerization of Ethylene with Polar Monomers . . . . . 274
11 Polymerization of Styrene . . . . . . . . . . . . . . . . . . . . . . . . 276
12 Stereospecific Polymerization of Conjugated Dienes . . . . . . . . . 276
13 Stereospecific Polymerization of Acetylene Derivatives . . . . . . . 279
14 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
1
Introduction
Recent development of various living polymerizations of polar and nonpolar
monomers allows the synthesis of high molecular weight polymers with very
narrow molecular weight distribution. The indispensable conditions for the ide-
al living polymers are (1) number-average molecular weight Mn>100,000, (2)
polydispersity index Mw/Mn<1.05, (3)stereoregularity >95%, and (4) high con-
version in a short period of time >95%. Even the famous living polystyrene sys-
tem [1] and the Group Transfer system [2] do not simultaneously satisfy require-
ments (1) and (2). Recently, to satisfy a long desire of many polymer chemists,
all these four requirements were found to be met in the rare earth metal-initiated
polymerization of methyl methacrylate (MMA), which gave Mn>500,000 with
Mw/Mn=1.02–1.03 (syndiotacticity >95%) [3]. More recently, we have found iso-
tactic polymerization of MMA by the efficient catalysis of non-metallocene type
single component complex, Yb[C(SiMe3)3]2, to give the poly(MMA) of
Mn>200,000 with Mw/Mn=1.1 in high yield (isotacticity >97%).
Alkyl acrylates were for the first time polymerized in a living fashion with the
aid of the unique catalytic action of rare earth metal complexes [4]. Since these
monomers have an acidic α-H, termination and chain transfer reactions occur
so frequently that their polymerizations generally do not proceed in a living
manner. By taking advantages of the living polymerization ability of both MMA
and alkyl acrylate, ABA or ABC type tri-block copolymerization was performed
to obtain thermoplastic elastomers.
Living polymerization of lactones has been successfully performed by the ca-
talysis of rare earth metal complexes producing Mw/Mn values of 1.07–1.08 [5].
Polymerizations of acrylonitrile and alkyl isocyanates have been successfully re-
alized using La[CH(SiMe3)2]2(C5Me5) as initiator, and those of various oxiranes
have been made using Ln(acac)3/AlR3/H2O system [6].
Organo rare earth metal initiators also show good activity towards non-polar
monomers such as ethylene, 1-olefins, styrene, conjugated dienes, and acetylene
Organo Rare Earth Metal Catalysis for the Living Polymerizations of Polar and Nonpolar Monomers 257
derivatives. In fact, poly(ethylene) of Mn>1,000,000 with Mw/Mn=1.6 was

made available by the use of a C1 symmetric divalent complex, Me2Si[2(3),4-
(SiMe3)2C5H2]2Sm(THF)2. However, the magnitude of Mn for poly(olefin)s such
as poly(1-pentene), polystyrene, and poly(1,5-hexadiene) were not made high
enough even with the help of the characteristic catalytic action of rare earth
metal complexes. The maximum Mn of 60,000 obtained for poly(1-hexene) was
still far below the desired minimum of 400,000. Conjugated dienes and acetylene
derivatives were polymerized by the use of rather complex rare earth metal cat-
alysts, but the resulting Mw/Mn remained fairly large. The use of a mononuclear
single-site catalyst is required for the polymerization of these derivatives.
2
Highly Stereospecific Living Polymerization of Alkyl Methacrylates
Although various living polymerization systems have been proposed, any of an-
ionic [7], cationic [8], Group Transfer [2], and metal carbene initiated polymer-
izations [9] achieved no success in synthesizing living polymers of Mn>500,000
with Mw/Mn<1.05. On the other hand, high molecular weight poly(MMA) hav-
ing an unusually low polydispersity has been synthesized by utilizing the unique
initiating function of organolanthanide(III) complexes (Fig. 1) [3]. The relevant
complexes include lanthanide hydrides, bulky alkyl lanthanide, bis-Me-bridged
trimethylaluminum complexes of alkyllanthanides, and simple alkyl complexes
(Fig. 2). The results of the polymerization of MMA with [SmH(C5Me5)2]2 ini-
tiator at different temperatures are summarized in Table 1. The most striking is
very narrow molecular weight distributions, i.e. Mw/Mn=1.02–1.04 for
Mn>60×103. Remarkably, [SmH(C5Me5)2]2 complexes give high conversion (pol-
ymer yield) in a relatively short period, and allow the polymerization to proceed
over a wide range of reaction temperatures from –78 to 40 °C. Furthermore, syn-
diotacticity exceeding 95% is obtained when the polymerization temperature is
lowered to –95 °C.
The typical initiator systems reported so far for the synthesis of highly
syndiotactic poly(MMA) are bulky alkyllithium CH3(CH2)4CPh2Li [10], Grig-
nard reagent in THF [11], and some AlR3 complexes [12]. Although the
Fig. 1. Organolanthanide initiated syndiotactic polymerization of MMA

258 Hajime Yasuda
Fig. 2. X-ray analysis of Sm(C5Me5)2(MMA)2H
Table 1. Characterization of monodisperse poly(MMA) synthesized by [SmH(C5Me5)2]2

initiator
Polymerization MMA/initiator Mn × 103 Mw/Mn rr % Conversion/%
temperature(°C) charged(mol/mol) (react. time)
40 500 55 1.03 77.3 99 (1 h)
0 500 58 1.02 82.4 99 (1 h)
0 1500 215 1.03 82.9 93 (2 h)
0 3000 563 1.04 82.3 98 (3 h)
–78 500 82 1.04 93.1 97 (18 h)
–95 1000 187 1.05 95.3 82 (60 h)
Mn and Mw/Mn were determined by GPC using standard poly(MMA) with Mw measured by
light scattering method. Solvent, toluene; solvent /[M]0=5 (vol/vol).
CH3(CH2)4CPh2Li initiator in THF conducted the polymerization of MMA at

–78 °C, the Mn reached only 10,000 with Mw/Mn=1.18, while it gave isotactic
polymers in toluene. iBuMgBr and CH2=CHC6H4CH2MgBr in THF at lower
temperature also gave high syndiotactic poly(MMA) but Mn remained as low
as 14,000–18,000 and the yields were quite low. When iBuMgBr or tBuMgBr
was used in toluene instead of THF, the resulting poly(MMA) had a high iso-
tacticity of 96.7% with Mn=19,900 and Mw/Mn=1.08 [13]. AlEt3•PR3 complexes
gave high syndiotacticity, but not a high molecular weight.
Ketene silyl acetal/nucleophilic agent systems initiate the polymerization of
alkyl methacrylates. These well-known Group Transfer systems yielded living
polymers with atactic sequences at relatively high temperature [2]. Me2C=
C(OMe)OSiR3 and R2POSiMe3 can be used as initiators, and tris(dimethylami-
no)sulfonium bifluoride and Et4CN are frequently used as catalysts. For exam-
ple, the Mw/Mn of the resulting poly(MMA) was 1.06 for Mn=3800, and 1.15 for
Mn=6300. Thus, we conclude that organolanthanide-initiated polymerization is

superior to other catalysts in obtaining monodisperse high molecular weight
poly(MMA).
These findings motivated us to isolate the 1 : 1 or 1 : 2 adduct of
[SmH(C5Me5)2]2 with MMA in order to elucidate the initiation mechanism. Af-
ter expending much effort, we have obtained the desired 1:2 adduct as an air-
sensitive orange crystal (mp 132 °C). The X-ray analysis of the adduct indicates
that one of the MMA unit is linked to the metal in an enolate form while at the
other end the penultimate MMA unit is coordinated to the metal through its C=
O group. Thus an 8-membered cyclic intermediate was formed (Fig. 3).
Although similar cyclic intermediates have been proposed by Bawn and Led-
with [14] and Cram and Copecky [15] for the isotactic polymerization of MMA,
no isolation of such active species has succeeded. On the basis of the X-ray struc-
tural data as well as the observed mode of polymerization, we can propose a
coodination anionic mechanism involving an 8-membered transition state for
the present organo rare-earth metal initiated polymerization of MMA. In the in-
itiation step, the hydride attacks the CH2 group of MMA, and a transient
SmOC(OCH3)=C(CH3)2 species should be formed. Then the incoming MMA
molecule is supposed to participate in the 1,4-addition to produce an 8-mem-
bered cyclic intermediate. Further addition of MMA to the 1:2 addition com-
pound results in liberation of the coordinated ester group and the 8-membered
cyclic intermediate is again generated. The intermolecular repulsion between
C(7) and C(9) (or the polymer chain) should be the essential factor in determin-
ing the syndiotacticity. The addition of 100 molar amounts of MMA to the 1:2
adduct yielded poly(MMA) of Mn=ca. 110×103 and Mw/Mn=1.03, proving that
the 1:2 adduct is a real active species. Thus, initiation process occurs much faster
than the propagation process.
Fig. 3. Typical initiator used for the living polymerization of MMA

260 Hajime Yasuda
On the other hand, monodisperse isotactic poly(MMA) has been obtained with
tBuMgBr in toluene at –40 °C (Mn=10.1×103, Mw/Mn=1.08, isotacticity =96.7%)
[16] or secBuMgBr in toluene at –78 °C (Mn=4.9×103, Mw/Mn=1.29, isotacticity
=95.5%) [16]. Synthesis of isotactic poly(MMA) with much higher molecular
weight is required. Recently, high molecular weight isotactic poly(MMA) (mm=
97%, Mn=500,000, Mw/Mn=1.12) was first obtained quantitatively by the use of a
non-metallocene type rare earth complex [(Me3Si)3C]2Yb (Fig. 4) [17]. We pro-
pose here the initiation mechanism as noted below through noncyclic interme-
diate for this isotactic polymerization of MMA (Fig. 5). The polymerization
should proceed by the enantiomorphic site control in toluene. In contrast, syn-
diotactic polymer was obtained when THF was used as solvent (rr=87%, Mn=
3.2×104, Mw/Mn=1.76) presumably due to chain end control through cyclic in-
termediate. By utilizing the resulting isotactic polymer, we have prepared a ster-
eo-complex between isotactic and syndiotactic polymers by mixing these two
polymers in acetone in a 1:2 ratio (Fig. 6). The resulting stereo-complex shows
the intermediate physical property between the homo-isotactic and homo-syn-
dotactic polymers (Table 2). Isotactic polymerization of MMA has also been
achieved (mm=94%, Mn=134×103, Mw/Mn=6.7) by using Me2Si(C5Me4)[C5H3-
(1S),(2S),(5R)-neomenthyl]LaR (R=CH(SiMe3)2 or N(SiMe3)2) [18], while
Me2Si(C5Me4)[C5H3-(1S),(2S),(5R)-menthyl]LnR (Ln=Lu, Sm; R=CH(SiMe3)2
or N(SiMe3)2) complex produces syndiotactic poly(MMA) (rr=69%, Mn=177×
260103, Mw/Mn=15.7). Polydispersity is rather wide in these cases.
Fig. 4. Isotactic polymerization of MMA catalyzed by rare earth metal complex
Fig. 5. Proposed intermediates for syndiotactic and isotactic polymerization of MMA

Fig. 6. Preparation of stereo-complex between isotactic and syndiotactic poly(MMA)
Table 2. Mechanical properties of isotactic, syndiotactic poly(MMA) and the stereo-

complex
Tensile modulus Tensile strength Elongation
kgf/mm2 kgf/mm2 %
isotactic poly(MMA) 2.0 30.2 435
syndiotactic poly(MMA) 10.0 116.1 13
stereo-complex 4.6–5.8 86–121 20–30
Boffa and Novak found a divalent rare earth metal complex, Sm(C5Me5)2, to
be a good catalyst for polymerization of MMA [19]. The initiation started with
the coupling of two coordinated MMA molecules to form Sm(III) species. The
bis-allyl initiator, Sm(η3-CH2-CH-CH)2(C5Me5)2, was also effective for living
polymerization of MMA. In this case, MMA must add to both ends of the hexa-
diene group. In the polymerization of MMA initiated with methylaluminum tet-
raphenylporphyrine, crowded Lewis acid such as MeAl(ortho-substituted phe-
nolate)2 serves as a very effective accelerator without damaging the living char-
acter of polymerization [20]. Thus, the polymer produced has narrow polydis-
persity (Mw/Mn=1.09) and sufficiently high molecular weight, Mn=25,500, but
the stereoregularity is very poor. The use of a simple organoaluminum such as
trimethylaluminum causes the occurrence of preferred termination.
The organolanthanide initiators also allowed stereospecific polymerization
of ethyl, isopropyl, and tert-butyl methacrylates. The rate of polymerization and
syndiotacticity decreased with increasing bulkiness of the alkyl group in the or-
der Me>Et>iPr>>tBu. Butyl methacrylate was also polymerized using Nd(oc-
tanoate)3/AliBu3 (Al/Nd=7–10), but the molecular weight distribution and ster-
eoregularity were not reported [21].
In general, Ziegler-Natta catalysts such as TiCl4/MgCl2/AlR3 and Kamin-
sky catalysts such as Cp2ZrCl2/(AlMe2-O-)n do not catalyze the poly-
merization of polar monomers. However, a mixture of cationic species
Cp2ZrMe(THF)+ and Cp2ZrMe2 has been found to do so for MMA [17], al-
lowing syndiotactic poly(MMA) (rr=80%, Mn=120,000, Mw/Mn=1.2–1.3)
[22]. Recently, Soga et al. [23] reported the syndio rich polymerization of
MMA catalyzed by Cp2ZrMe2/Ph3CB(C6F5)4/ZnEt2 and also the isotactic po-
262 Hajime Yasuda
lymerization of MMA catalyzed by rac-Et(ind)2ZrMe2/Ph3CB(C6F5)4/ZnEt2

(mm=96.5%, Mn=39.3×104, Mw/Mn=1.43). The observed characteristic na-
ture of rare earth metal initiator may originate from large ionic radii (1.0–
1.17 Å) and low electronegativity (1.0–1.2). Their ionic radii are much larger
than those of main group metals (Li 0.73; Mg 0.71; Al 0.68 Å) and the elec-
tronegativities resemble those of Li (1.0) and Mg (1.2).
3
Living Polymerization of Alkyl Acrylates
Living polymerization of alkyl acrylates is usually very difficult because the
chain transfer or temination occurs preferentially, owing to a high sensitivity of
the acidic α-proton to the nucleophilic attack. Exceptions are the living polym-
erization of a bulky acrylic ester catalyzed by alkyllithium/inorganic salt (LiCl)
systems as well as the Group Transfer polymerizations of ethyl acrylate using
ZnI2 as the catalyst. Porphyrinatoaluminum initiator systems also induced the
living polymerization of tert-butyl acrylate [24], but the upper limit of molecu-
lar weight attained was ca. 20, 000. We have found the efficient initiating proper-
ties of SmMe(C5Me5)2(THF) and YMe(C5Me5)2(THF) for living polymerization
of acrylic esters (Table 3), i.e. methyl acrylate (MeA), ethyl acrylate (EtA), butyl
acrylate (Bu), and tert-butyl acrylate (tBuA), although the reactions were non-
stereospecific (Fig. 7) [25]. The initiator efficiency exceeded 90% except for
tBuA. We therefore concluded that the reactions occur in living fashion. In fact,
the Mn of poly(BuA) initiated by SmMe(C5Me5)2(THF) increased linearly in pro-
Table 3. Polymerization of alkyl acrylates initiated by organolanthanide complexes

Initiator Monomer Mn/103 Mw/Mn Tacticity/% Conversion
rr mr mm % Efficiency
%
[SmMe(C5Me5)2(THF)] MeA 48 1.04 30 50 20 99 89
EtA 55 1.04 51 49 94 86
nBuA 70 1.05 28 53 19 99 91
tBuA 15 1.03 27 47 26 99 79
Polymerization conditions: 0 °C in toluene, initiator concentration 0.2 mol%.
Fig. 7. Living polymerization of alkyl acrylates

portion to the conversion, while Mw/Mn remained unchanged, irrespective of

the initiator concentration. In order to establish the characteristic nature of
these initiation systems, the initiator concentration was decreased from 0.1 to
0.002 mol% of monomer and high molecular weight poly(EtA) of Mn=800,000
with narrow molecular weight distribution (Mw/Mn=1.05) was obtained.
ABA type triblock copolymerization of MMA/BuA/MMA should give rubber-
like elastic polymers. The resulting copolymers should have two vitreous outer
blocks, where the poly(MMA) moiety (hard segment) associates with the nod-
ules, and the central soft poly(BuA) elastomeric block provides rubber elasticity.
The first step polymerization of MMA gave Mn of 15,000 with Mw/Mn=1.04 and
then a mixture of MMA and BuA was added to this growing end to result in the
formation of desired ABA triblock copolymer (BuA polymerized more rapidly
than MMA) (Fig. 8). Table 4 shows the typical mechanical properties of the ABA
Table 4. Mechanical properties of triblock copolymers
Copolymer Tensile Tensile Elongation Izod impact Compression

modulus strength (%) strength set/%
(MPa) (MPa) (J/m) (70 °C, 22 h)
Poly(MMA) 610 80 21 18 100
poly(MMA/BuA/MMA) 75 27 83 383 (N.B) 101
(20:47:33)
poly(MMA/BuA/MMA) 46 22 8 390 (N.B) 103
(25:51:24)
poly(MMA/BuA/MMA) 0.8 0.7 163 400 (N.B) 58
(8:72:20)
poly(MMA/BuA/MMA) 0.2 0.1 246 410 (N.B) 97
(6:91:3)
poly(MMA/EtA/EtMA) 119 22 276 34 62
(26:48:26)
N.B.; not break. EtA; ethylacrylate. EtMA; ethyl methacrylate
Fig. 8. ABA type block copolymerization of MMA/BuA/MMA

264 Hajime Yasuda
type copolymers thus obtained. Homo-poly(MMA) has large tensile modulus

and large tensile strength, but is poor in elongation and shows very large com-
pression set. In contrast, the triblock copolymer (8:72:20) shows 58% compres-
sion set and large elongation (163%), indicating that this polymer is a thermo-
plastic elastomer. The triblock copolymer of MMA/EtA/EtMA in the ratio of
26:48:26 also showed large elongation and small compression set. Thus, elastic
copolymers of methacrylate with acrylate were for the first time obtained by us-
ing living polymerization ability of rare earth metal complexes.
4
Block Copolymerization of Hydrophobic and Hydrophilic Acrylates
Trimethylsilyl metacrylate (TMSMA) was found to proceed the living polymer-
ization using SmMe(C5Me5)2(THF) as initiator to give high molecular weight
syndiotactic polymer (Mn=56,000, rr=92%) with very low polydispersity
(Mw/Mn=1.09). By utilizing this nature, we have performed the block copolym-
erization of TMSMA with MMA or butyl acrylate to obtain the adhesive materi-
als upon hydrolysis of the resulting polymer [26]. The result is shown in Table 5.
Thus, block copolymerization of TMSMA with MMA (or BuA) gave thermally
stable adhesive materials for the first time (high thermal stability originates
from high syndiotacticity) (Fig. 9).
Fig. 9. Block copolymerization of MMA with TMSMA
Table 5. Block copolymerization of TMSMA with MMA or BuA

Feed ratio Mn (calcd) poly(TMSMA) poly(TMSMA/MMA Yield/%
or BuA)
TMSMA MMA Mn Mw/Mn Mn Mw/Mn
67 124 23,000 8,900 1.13 28,100 1.17 99
TMSMA BuA
30 42 10,100 52,000 1.11 10,500 1.16 98
67 93 22, 500 81,000 1.10 22,600 1.26 99
30 304 43,700 51,000 1.11 77,300 1.15 99
Solvent, toluene; Polymerization of TMSMA 2 min, Polymerization temp. 0 °C.
5
Polymerization of Alkyl Isocyanates
Polyisocyanates have attracted much attention owing to their liquid crystalline
properties, stiff-chain solution characteristics, and induced optical activities as-
sociated with the helical chain conformation. Pattern and Novak discovered that
such titanium complexes as TiCl3(OCH2CF3) and TiCl2(C5H5)(OCH2CF3) initi-
ate the living polymerization of isocyanates at ambient temperature, giving pol-
ymers with narrow molecular weight distribution [27]. When hexyl isocyanate
was added to TiCl3(OCH2CF3) the polymerization took place, to give Mn (Mw/Mn=
1.1–1.3) increasing linearly with the initial monomer-to-initiator mole ratio or
the monomer conversion over a wide range. Recently, Fukuwatari et al. found
lanthanum isopropoxide to serve as a novel anionic initiator for the polymeriza-
tion of hexyl isocyanate at low temperature (–78 °C), which led to very high mo-
lecular weight (Mn>106) and rather narrow molecular weight distribution
(Mw/Mn=2.08–3.16) [28]. Other lanthanide alkoxides such as Sm(OiPr)3,
Yb(OiPr)3, and Y(OiPr)3 also induced the polymerization of hexyl isocyanate.
Furthermore, it was shown that butyl, isobutyl, octyl and m-tolyl isocyanates
were polymerized using lanthanum isopropoxide as initiator. However, tert-
butyl and cyclohexyl isocyanates failed to polymerize with these initiators under
the same reaction conditions. When the reaction temperature was raised to am-
bient temperature, only cyclic trimers were produced at high yields. More re-
cently we have found that La(C5Me5)2[CH(SiMe3)]2 also initiates the polymeri-
zation of hexyl isocyanate in 90–96% yields in THF at –20 to –40 °C (Mn=59×104,
Mw/Mn=1.57–1.90) [29] (Fig. 10).
6
Living Polymerization of Lactones
AlEt3-H2O or AlEt3-catalyzed polymerizations of 3-methyl-β-propiolactone and
ε-caprolactone have been reported [30, 31] but this type of polymerization gen-
erally gives a broad molecular weight distribution. We have explored the polym-
erization of various lactones including β−propiolactone (PL), 3-methyl-β-propi-
olactone (MePL), δ-valerolactone (VL) and ε-caprolactone initiated by single
organolanthanides, and found that VL and CL led to the living polymerization
(Fig. 11) , yielding polymers with Mw/Mn=1.05–1.10 at quantitative yields
(Table 6). For ε-caprolactone, Mn obtained with the SmMe(C5Me5)2(THF) or
Fig. 10. Living polymerization of alkyl isocyanate

266 Hajime Yasuda
Fig. 11. Living polymerization of lactones
Table 6. Living polymerization of lactones with organolanthanide complexes

Initiator Monomer Mn/103 Mw/Mn Conversion/%
SmMe(C5Me5)2(THF) VL 75.2 1.07 80.1 (7 h)
CL 109.4 1.09 92.0 (7 h)
[SmH(C5Me5)2]2 VL 65.7 1.08 90.5 (7 h)
CL 71.1 1.19 88.7 (5 h)
[YOMe(C5H5)2]2 CL 162.2 1.10 87.5 (5 h)
PL 60.5 3 94.5 (5 h)
PL β-propiolactone, VL δ-varelolactone, CL ε-caprolactone. Polymerization, 0 °C in tolu-
ene.
[SmH(C5Me5)2]2 system increased with increasing conversion, but Mw/Mn re-

mained constant, irrespective of the conversion. For β-propiolactone, the use of
YOR(C5Me5)2 was more favorable. On the other hand, divalent organolantha-
nide complexes can initiate the polymerization of lactones, but the resulting pol-
ymers had rather broad molecular weight distributions.
At the early stage of the polymerization of lactone with Ln(OR)(C5Me5)2, one
mole of ε-caprolactone coordinates to the metal, as is the case for the reaction of
YCl3 with ε-caprolactone, giving the six-coordinate mer complex, YCl3•(ε-capro-
lactone)3, in which each caprolactone molecule is coordinated as a monodentate
ligand through its carbonyl oxygen [32]. The polymerization starts with the co-
ordination of ε-caprolactone to form the 1:1 complex, Ln(OR)(C5Me5)2 (ε-
caprolactone) (Fig. 12), and in its propagation step the alkoxide attacks the C=
O group to produce Ln[O(CH2)5C(O)OR](C5Me5)2 (ε-caprolactone) [5]. In the
SmMe(C5Me5)2 initiator system, the reaction is initiated by the attack of ε-
caprolactone or δ-valerolactone to result in the formation of an acetal without
ring opening. This process has been confirmed by 13C NMR studies on the stoi-
chiometric reaction products.
Anionic block copolymerizations of MMA with lactones proceeded smoothly
to give copolymers with Mw/Mn=1.11–1.23 when the monomers were added in
this order (Fig. 13).
However, when the order of addition was reversed, no copolymerization took
place, i.e. no addition of MMA to the polylactone active end occurred [5].
Fig. 12. Initiation mechanism for polymerization of lactones
Fig. 13. Copolymerization of MMA with lactones
7
Stereospecific Polymerization of Oxiranes
Organolanthanide(III) complexes such as LnMe(C5Me5)2 or LnH(C5Me5)2 do
not initiate the polymerization of oxirans, but more complex systems like
Ln(acac)3/AlR3/H2O and Ln(2-EP)3/AlR3/H2O (2-EP; di-2-ethylhexylphos-
phate) polymerize with good initiation activity [33]. High molecular weight
poly(ethylene oxide) is one of the common water-soluble polymers useful as
adhesives, surfactants, plasticizers, and dispersants as well as for sizing materi-
al. Poly(ethylene oxide) of Mn=2.85×106 was obtained with the Y(2-
EP)3/AliBu3/H2O system at the ratio of Y/Al/H2O=1/6/3. The initiator activity
varies with the molar ratio of the components. Polymerization of propylene ox-
ide was reported to proceed with the Ln(acac)3/AlEt3/H2O system, and light
rare earth elements (Y, La, Pr, Nd, Sm) produced very high molecular weight
poly(propylene oxide) at Al/Ln=6 in a short period of time (2 h) in toluene [34].
The Nd(acac-F3)3/AlR3/H2O (Ln=Y, Nd) systems [35] gave isotactic poly(pro-
pylene oxide), while the Cp2LnCl/AlR3/H2O, Sm(OiPr)3/AlR3/H2O or Y(2-ethyl-
hexanoate)3/AlR3/H2O system produced relatively low molecular weight isotac-
tic species of this polymer (Fig. 14).
268 Hajime Yasuda
Fig. 14. Rare earth metal initiated polymerization of oxirans
Fig. 15. Copolymerization of epichlorohydrine with CO2
Random copolymerization of propylene oxide with ethylene oxide proceeded

smoothly with the Nd(2-EP)3/AlEt3/H2O system at 80 °C [36]. From the copoly-
merization composition curve, the monomer reactivity ratios were evaluated to
be r1(EO)=1.60 and r2(PO)=0.45. The conversion increased with an increase in
the Al/Nd ratio and saturated at a molar ratio of 16. Since the Nd(2-
EP)3/AlEt3/H2O system generates a growing poly(propylene oxide) chain having
a very long life, block copolymerization with ethylene oxide can be achieved suc-
cessfully. The Ln(acac)3/AliBu3/H2O (1:8:4) systems, especially in the case of Nd
derivative, also initiated the polymerization of epichlorohydrin (EPH) to yield a
polymer of Mv =16.5×105 with 21% crystallinity. Toluene is used preferably but
aliphatic hydrocarbons is not suitable because poly(epichlorohydrin) precipi-
tates from the solvent during the polymerization. The relative monomer reactiv-
ities evaluated for the propylene oxide (PO)-allyl glycidylether(AGE) system
were r1(PO)=2.0 and r2(AGE)=0.5, and those for the epichlorohydrin-AGE sys-
tem were r1(EPH)=0.5 and r2(AGE)=0.4 [37]. This combination of monomer re-
activity ratios indicates that the polymerization with Ln(acac)3/AliBu3/H2O fol-
lows a coordination anionic mechanism, but that with the AliBu3/H2O system
does cationic polymerization mechanism.
Although the copolymerization of propylene oxide with CO2 takes place effec-
tively with the organozinc-additives or the (tetraphenyl)porphyrin-AlCl system
[38], the copolymerization of epichlorohydrine with CO2 hardly occurs with
these catalysts. Shen et al. [39] showed that a rare earth metal catalyst such as the
Nd(2-EP)3/AliBu3 (Al/Nd=8) system was very effective for the copolymerization
of epichlorohydrine with CO2 (30–40 atm) at 60 °C (Fig. 15). The content of CO2
in the copolymer reached 23–24 mol% when 1,4-dioxane was used as solvent.
The ZnEt2/H2O [40], AlEt3/H2O [41], and Cd salt [42] systems are well-known
initiators for the polymerization of propylene sulfide. Shen et al. [43] examined
this polymerization with the Ln(2-EP)3/AliBu3/H2O system and found that high
molecular weight polymers were produced at a low concentration of Nd
(6.04×10–3 mol/l) at the ratio of Nd/Al/H2O=1/8/4. The polymerization activity
decreased in the order Yb=La>Pr>Nd=Eu>Lu>Gd>Dy>Ho>Er. The 13C-NMR
spectrum indicated that β-cleavage occurs preferentially over the α-cleavage
and the ratio of these ring openings changes little with the initiator system and
the polymerization temperature. The polymers obtained were amorphous ac-
cording to DSC and XRD analyses.
8
Polymerization of Lactide
Shen et al. [44] succeeded ring opening polymerization of D,L-lactide (racemic
species) using Nd(naphthenate)3/AliBu3/H2O (1:5:2.5), Nd(P204)3/AliBu3/H2O
(P204=[CH3(CH2)3CH(CH2CH3)CH2O]2P(O)OH], and Nd(P507)3/AliBu3 /H2O
(P507=(iC8H17O)2P(O)OH) systems, obtaining the polymers whose molecular
weights were Mn=3.1–3.6×104 and the conversions larger than 94%. When the
Ln(naphthenate)3/AliBu3/H2O system was used, nearly the same results were
obtained irrespective of the metals used (La, Pr, Sm, Gd, Ho, Tm). Divalent (2,6-
tBu2-4-Me-phenyl)2Sm(THF)4 was also found to be active for the polymeriza-
tion of D,L-lactide at 80 °C in toluene, giving Mn of 1.5–3.5×104 [45]. A more re-
cent finding is that the Ln(O-2,6-tBu2-C6H3)3/iPrOH (1:1–1:3) system initiates a
smooth homo-polymerization of L-lactide, CL (caprolactone) and VL (valerol-
actone) to give relatively high molecular weights (Mn>24×103) with low polydis-
persity indices (Mw/Mn=1.2–1.3) (Fig. 16) [46]. Ring-opening polymerization of
D,L-lactide was also carried out by using Ln(OiPr3)3 as the catalyst at 90 °C in tol-
uene. The catalytic activity increased in the order La>Nd>Dy>Y and the molec-
ular weight reaches 4.27×104(conversion 80%) [47]. However, the molecular
weight distribution is not clear at present. The block copolymerization of CL
with L-lactide proceeded effectively and gave a polymer of very narrow molecu-
lar weight distribution (Mw/Mn=1.16). On the other hand the addition of CL to
the living poly(L-lactide) end led to no success.
9
Stereospecific Polymerization of Olefins
Bulky organolanthanide(III) complexes such as LnH(C5Me5)2 (Ln=La, Nd) were
found to catalyze with high efficiency the polymerization of ethylene. These hy-
drides are, however, thermally unstable and cannot be isolated as crystals.
Therefore, thermally more stable bulky organolanthanides were synthesized by
Fig. 16. Polymerization of D,L-lactide

270 Hajime Yasuda
introducing four trimethylsilyl groups into the Me2Si bridged Cp ligand, as

shown in Fig. 17. The reaction of the dilithium salt of this ligand with anhydrous
SmCl3 produced a mixture of two stereo-isomeric complexes. The respective
isomers were isolated by utilizing their different solubilities in hexane, and their
structures were determined by X-ray crystallography. One of them has a C2 sym-
metric (racemic) structure in which two trimethylsilyl groups are located at the
2,4-positions of the Cp rings, while the other has a C1 symmetric structure in
which two trimethylsilyl groups are located at 2,4- and 2,3-positions of each Cp
ring. Both were converted to alkyl derivatives when they were allowed to react
with bis(trimethylsilyl)methyllithium [48]. The Cp'-Sm-Cp' angle of the racemic
precursor is 107°, which is about 15° smaller than that of non-bridged
SmMe(C5Me5)2(THF).
Meso type ligands were synthesized by forcing two trimethylsilyl groups to be
located at the 4-position of the ligand with introduction of two bridges. Actually,
the complexation of this ligand with YCl3 yielded a meso type complex, and the
structure of the complex was determined by X-ray analysis. The meso type alkyl
complex was synthesized in a similar manner [49]. Table 7 summarizes the re-
sults of ethylene polymerization with these organolanthanide(III) complexes.
Interestingly, only C1 type complexes can initiate the polymerization, implying
that the catalytic activity varies with the structure of the complex. The X-ray
structure of the C1 symmetric complex is given in Fig. 18, where the Cp'-Sm-Cp'
angle is seen to be 108°, a very small dihedral angle. The polymerization of eth-
ylene with SmH(C5Me5)2 in the presence of PhSiH3 formed PhH2Si capped pol-
yethylene(Mn=9.8 x104, Mw/Mn=1.8), and the copolymerization of ethylene with
1-hexene or styrene gave PhH2Si capped copolymer (comonomer content 60
and 26 mol%, respectively; Mn=3.7×103, Mw/Mn=2.9 for ethylene-1-hexene co-
polymer, Mn=3.3×103 for ethylene-styrene copolymer) [50].
Fig. 17. Synthesis of organolanthanide(III) for polymerization of ethylene

Table 7. Ethylene polymerization by organolanthanide(III) complexes

Initiator Mn/104 Mw/Mn Activity
(g/mol•h)
(C5Me5)2SmCH(SiMe3)2 no polymerization
SiMe2[2,4-(SiMe3)2C5H2]2SmCH(SiMe3)2 no polymerization
(racemic)
SiMe2(Me2SiOSiMe2)(3-SiMe3- no polymerization
C5H2)YCH(SiMe3)2 (meso)
SiMe2[2(3),4-(SiMe3)2C5H2]2SmCH(SiMe3)2 41.3 2.19 3.3×104
(C1)
SiMe2[2(3),4-(SiMe3)2C5H2]2YCH(SiM3)2 (C1) 33.1 1.65 18.8×104
Initiator concentration, 0.2 mol%. Ethylene was introduced by bubbling at atmospheric
pressure.
Fig. 18. X-ray structure of C1 symmetric SiMe2[2(3),4-(SiMe3)2C5H2]2SmCH(SiMe3)2
Racemic, meso, and C1 symmetric divalent organolanthanide complexes can

be synthesized by allowing the dipotassium salt of the corresponding ligand to
react with SmI2 [51]. Figure 20 shows their structures determined by 1H NMR
and X-ray analyses. Table 8 shows the results of the ethylene polymerization
with divalent samarium complexes. It is seen that the meso type complex has the
272 Hajime Yasuda
Fig. 19. Initiation mechanism for polymerization of ethylene catalyzed by rare earth metal
(III) complexes
Fig. 20. X-ray and NMR analysis of racemic, meso and C1 symmetric complexes(II)
Fig. 21. Initiation mechanism for polymerization of ethylene catalyzed by rare earth meta
(II) complexes
highest activity for the polymerization of ethylene, but the molecular weights of
the resulting polymers are the lowest. On the other hand, the racemic and C1
symmetric complexes produce much higher molecular weight polyethylene but
the activity is rather low.
Particularly, the very high molecular weight polyethylene (Mn>100×104) ob-
tained with C1 complex deserves attention (Fig. 21). For the polymerization of
α-olefins, only the racemic divalent complex showed good activity at 0 °C in tol-
uene: poly(1-hexene) Mn=24,600, Mw/Mn=1.85; poly(1-pentene) Mn=8,700,
Mw/Mn=1.58. Thus, we see that the reactivity of divalent organolanthanide com-
plexes varies depending on their structure. The poly(1-alkene) obtained re-
vealed highly isotactic structure (>95%) when examined by 13C NMR (Fig. 22).
The dihedral angles of Cp'-Ln-Cp' of racemic and meso type divalent complexes
were 117 and 116.7°, respectively. These values are much smaller than those of
Fig. 22. 13C NMR spectrum of isotactic poly(1-hexene)
Table 8. Ethylene polymerization by divalent samarium complexes

Initiator Time Mn/104 Mw/Mn Activity
min (g/mol•h)
(C5Me5)2Sm(THF)2 1 2.28 1.25 43
2.46 2.28 41
Racemic 1 11.59 1.43 6
35.63 1.60 14
Meso 5 1.94 3.29 14
4.73 3.49 47
C1 Symmetry 5 100.8 1.60 1.6
>100.0 1.64 1.1
Sm(C5Me5)2(THF) (136.7°) [52] and Sm(C5Me5)2 (140.1°) [53]. Therefore, it can

be concluded that the complexes having smaller Cp'-Ln-Cp' angles are more ac-
tive for the polymerization of ethylene and α−olefins.
More recently, YR2[tris(pyrazoyl)borate] of trivalent state was found to have
excellent activity for the polymerization of ethylene (Fig. 23). When R is C6H5,
resulting Mw reaches 1.2×106 (Mw/Mn=4.10). However, the present initiator is
inactive for the polymerization of 1-olefins such as propylene and 1-hexene
[54].
274 Hajime Yasuda
Fig. 23. YR2[tris(pyrazoyl)borate] initiated polymerization of ethylene
Fig. 24. Block copolymerizations of ethylene with MMA
10
Block Copolymerization of Ethylene with Polar Monomers
Block copolymerization of ethylene or propylene with polar monomers is yet to
be attained in polyolefin engineering. The success of this type of block copoly-
merization should give hydrophobic polymeric materials having remarkably
high adhesive, dyeing, and moisture adsorbing properties. The following is the
first example of a well-controlled block copolymerization using the unique dual
catalytic function of LnR(C5Me5)2 (Ln=Sm, Yb, and Lu; R=H, Me) complexes
toward polar and nonpolar olefins [55]. Ethylene was copolymerized with
MMA first by the homopolymerization of ethylene (17–20 mmol) with
SmMe(C5Me5)2(THF) or [SmH(C5Me5)2]2(0.05 mmol) at 20 °C in toluene un-
der atmospheric pressure, and then sequential addition of MMA (10 mmol)
(Table 9). The initial step proceeded very rapidly, completed in 2 min, and gave
a polymer of Mn=ca. 10,100 and Mw/Mn=1.42–1.44. However, the second step
was rather slow, with the reaction taking 2 h at 20 °C (Fig. 24). The polymer ob-
tained was soluble in 1,2-dichlorobenzene and 1,2,4-trichlorobenzene at 100 °C
but insoluble in THF and CHCl3. This fact indicates quantitative conversion to
the desired linear block copolymer. Repeated fractionation in hot THF did not
change the molar ratio of the polyethylene and poly(MMA) blocks, though po-
ly(MMA) blended with polyethylene can easily be extracted with THF. With the
copolymerization, the elution maximum in GPC shifted to a higher molecular
Table 9. Block copolymerization of ethylene with polar monomers

Polar monomer Polyethylene blocka Polar polymer blockb Unit ratio
Mn/103 Mw/Mn Mn/103 Mw/Mn
MMA 10.3 1.42 24.2 1.37 100:103
1.39 12.8 1.37 100:13
MeA 6.6 1.40 15.0 1.36 100:71
2.01 3.0 1.66 100:4
EtA 10.1 1.44 30.8 2.74 100:85
1.97 18.2 3.84 100:21
VL 10.1 1.44 7.4 1.45 100:20
CL 6.6 1.40 23.9 1.76 100:89
a Determined by GPC using standard polystyrene
b Determined by 1H NMR
Polymerization was carried out at 0 °C.
weight region, with its initial unimodal pattern unchanged. The relative molar
ratio of the polyethylene and poly(MMA) blocks was controllable at will in the
range of 100:1 to 100:103 if the Mn of the initial polyethylene was fixed to ca.
10,300. 1H and 13C NMR spectra for the copolymers as well as their IR absorption
spectra were superimposable onto those of the physical mixtures of the respective
homopolymers. The molar ratio of the poly(MMA) and polyethylene blocks,
however, decreased as the Mn of the prepolymer increased, especially when Mn
exceeds over ca. 12,000 at which value polyethylene began precipitating as fine
colorless particles. It is noteworthy that smooth block copolymerization of ethyl
acrylate or methyl acrylate to the polyethylene growing chain (Mn=6600–24,800)
can be realized by the sequential addition of the two monomers.
We have extended the above work to the block copolymerization of ethylene
with lactones. δ-Valerolactone and ε-caprolactone were incorporated to the
growing polyethylene end at ambient temperature and the expected AB type co-
polymers (100:1 to 100:89) were obtained in high yield.
The treatment of the resulting block copoly(ethylene/MMA) (100:3, Mn=
35,000) and block copoly(ethylene/ε−caprolactone) (100:11, Mn=12,000) with
dispersed dyes (Dianix AC-E) made them deeply dye with three primary colors,
though polyethylene itself was inert to these dyes. Reversed addition of the mon-
omers (first MMA or lactones and then ethylene) induced no block copolymer-
ization at all, even in the presence of excess ethylene, and only homo-po-
ly(MMA) and homo-poly(lactone) were produced. Hence, these copolymers can
be said to have a very desirable chemical reactivity.
More recently, Yang et al. [56] have examined a new approach in which a reac-
tive functional group was introduced into polyolefins using methylenecyclopro-
pane. Thus, ethylene (1.0 atm) was copolymerized with methylenecyclopropane
(0.25–2.5 ml) using [LnH(C5Me5)2]2 (Ln=Sm, Lu) in toluene at 25 °C, and it was
shown that 10–65 of exo-methylenes were incorporated per 1000 -CH2- units.
The resulting polymer had a Mw of 66–92×103. Yet its Mw/Mn was larger than 4.
276 Hajime Yasuda
Fig. 25. Styrene polymerization by La(C5Me5)[CH(SiMe3)2]2
11
Polymerization of Styrene
Styrene polymerization was performed by using binary initiator systems such as
Nd(acac)3/AlR3 or Nd(P507)3/AlR3. Syndio-rich polystyrene was obtained at a ra-
tio of Al/Nd=10–12 [57]. More recently, it was shown that the
Gd(OCOR)3/iBu3Al/Et2AlCl catalytic system initiates the copolymerization of
styrene with butadiene, but gives only atactic polystyrene [58]. The
Sm(OiPr)3/AlR3 or Sm(OiPr)3/AlR2Cl (Sm/Al=1–15) catalytic system also initi-
ates the polymerization of styrene to give a high molecular weight polymer (Mn=
300,000), low in polydispersity but atactic in stereoregularity [59]. The cationic
polymerization of styrene using Ln(CH3CN)9(AlCl4)3(CH3CN) was also exam-
ined [60], with the finding that the activity increased in the order La (conversion
73%)>Tb=Ho>Pr=Gd>Nd>Sm=Yb>Eu (conversion 54%), while Mn decreased
with increasing the polymerization temperature from 0 (20×103) to 60 °C
(13×103). A more recent study showed that the single component initiator
[(tBuCp)2LnCH3]2 (Ln=Pr, Nd, Gd) initiated the polymerization of styrene at rel-
atively high temperature, 70 °C, with a conversion of 96% and the Mn of 3.3×104
for [(tBuCp)2NdCH3]2 [61], though stereoregularity was very poor. The activity
varied greatly with the lanthanide element; and catalytic activity increased in the
order Nd>Pr>Gd>>Sm=Y (the Sm and Y complexes showed practically no activ-
ity). Therefore, the reaction is supposed to follow the radical initiation me-
chanism. Styrene polymerization was also performed successfully using the
single component initiators, [(Me3Si)2N]2Sm(THF)2, [(Me3Si)2CH]3Sm, and
La(C5Me5)[CH(SiMe3)2]2(THF) at 50 °C in toluene without addition of any cocat-
alyst (Fig. 25). The resulting polymers had Mn=1.5–1.8×104 and Mw/Mn=1.5–1.8,
and show atactic properties [62].
Thus no success has yet been achieved in synthesizing syndiotactic polysty-
rene with rare earth metal complexes, in contrast to the synthesis of highly
syndiotactic polystyrene with TiCl3(C5Me5)/(AlMe-O-)n (syndiotacticity
>95%) [63,64].
12
Stereospecific Polymerization of Conjugated Dienes
Organolanthanide(III) based binary initiator systems were used by Yu et al. [65]
for stereospecific polymerization of butadiene and isoprene. Typically, the po-
lymerization of butadiene catalyzed by C5H5LnCl2•THF/AlR3 yielded polymers

with a cis-1,4-content as high as 98% (Fig. 26). The polymerization activity
decreased in the order Nd>Pr>Y>Ce>Gd and iBu2AlH>iBu3Al>Et3Al>Me3Al,
while the viscosity of the polymer decreased in the order Et3Al>iBu3Al>
iBu2AlH. Although the NdCl3/iBu3Al system exhibited practically no initiating
activity, the use of NdCl3/PrOH instead of the solvent-free metal chloride
brought about high polymerization activity and high stereoregularity in the cis-
1,4-polymerization of butadiene [66]. The Mn of the polymer increased linearly
with increasing conversion and reached 1530×103 at 85% conversion when
NdCl3•iPrOH/AlEt3 (1:10) was used in heptane at –70 °C, but Mw/Mn (1.8–2.5)
showed no change with conversion. The number N of polymer chains per metal
atom was 1.09–1.43 at –70 °C, and increased to 2.0–3.0 when the polymerization
temperature was raised to 0 °C. Most noteworthy is a very high cis-content real-
ized at –70 °C, which amounted to 99.4%.
This indicates the existence of the anti-π-allyl-Nd species rather than the syn-
π-allyl-Nd species in the polymerization system. The cis-1,4-content of po-
ly(butadiene) increased as the AlEt3 concentration was lowered [66].
The arene organolanthanide system, Nd(C6H6)(AlCl4)3/AliBu3 (Al/Nd=30),
also induces the catalytic polymerization of isoprene to give cis–1,4 polymers
in 92–93% selectivity at low conversion (17–36%). Neither of the
Nd(C6Me6)(AlCl4)3/AliBu3 (1:30) nor NdCl3/AlCl3/AliBu3 (1:3:30) systems
showed catalytic activity for the polymerization of isoprene [67]. The random
copolymerization of isoprene with butadiene went smoothly with the use of
the Nd(C6H6)(AlCl4)3/AliBu3 system and gave an isoprene/butadiene(1:4) co-
polymer at high yield, but no data for Mw/Mn and Mn were reported [68]. The
(β-CH3-π-allyl)2LnCl5Mg2(TMEDA)2/AlR3 and (allyl)4LnLi systems also initi-
ate the 1,4-polymerization of isoprene in 50% stereoregularity at high conver-
sion. Highly selective cis-1,4-polymerizations of conjugated dienes were ob-
tained by the use of homogeneous (CF3COO)2NdC1•EtOH/AlEt3 (1:7) initiator
Fig. 26. Rare earth metal initiated polymerizations of conjugated dienes

278 Hajime Yasuda
system, i.e. 97.5% cis-selectivity for butadiene and 96.7% for isoprene. Al-
though bimetallic species like (CF3COO)EtNd(µ-Cl)(µ-H)AlEt2 are proposed
as active one, their exact structures are still unknown [69]. The molecular
structure of dimer complexes, [(CF3C)(µ2-O)2(µ3-O)4YAlEt2(THF2)]2 and
[(CF3)( µ2-O)3(µ3-O)3NdAlEt2(THF2)]2, generated during the reaction be-
tween (CF3COO)2NdC1 and AlEt3, has recently been elucidated by X-ray anal-
ysis. However, these complexes are considered to be byproducts because they
give polymers of low stereoregularity only at low yield [70].
A remarkable solvent effect was observed on the activity of the Nd
(OCOC7H15)3/Et2AlCl/iBu3Al system, which initiates the cis-1,4-polymerization
of butadiene (>98%) and isoprene (>95%). Aliphatic compounds such as pen-
tane, 1-pentene, and 2-pentene behave as good solvents, while aromatic com-
pounds such as toluene and mesitylene act as inhibitors [71]. The coordination
of aromatic compounds to the metal center may be responsible for the remarka-
ble suppression of the polymerization, as was the case in the polymerization us-
ing cobalt catalysts [72]. A binary initiator system, LnCl3[(BuO)3PO]3/AliBu3,
and a ternary system, Ln(naphthenate)3/AliBu3/Al2Et3Cl3 (naphthenate;
C10H7COO), also behave as good initiators for the cis-1,4-polymerization of iso-
prene [73]. In both cases, the polymerization activity varies with the nature of the
metal in the order Nd>Pr>Ce>Gd>La>>Sm>Eu. Thus, the activity increases
with increasing electronegativity and does so with decreasing M3+ ionic radius,
except for Sm3+ and Eu3+ which can be easily converted to the M2+ species in the
presence of a reducing agent. No relationship was observed between the initiating
activity and the Ln-O or Ln-Cl bond energy determined by IR and laser Raman
spectroscopy.
Block copolymerization of butadiene with isoprene (32:68–67:33) giving high
cis-1,4-polymers have also been successfully made with the Ln(naphthen-
ate)3/AliBu3/Al2Et3Cl3 system at temperature –78 to 33 °C. Noteworthy is the rel-
atively long life time of this initiator. Thus, it was possible to copolymerize iso-
prene 1752 h after the polymerization of butadiene. The (iPrO)2HLn2Cl3HAlEt2
species (Ln=Gd, Dy, Er, Tm) [74] prepared from either Ln(iPrO)3/Et2AlCl/Et3Al
or (iPrO)2LnCl/Et3Al also can initiate the cis-1,4-polymerization of butadiene
and isoprene. The most probable structure of this complex as evidenced by X-
ray analysisis is (iPrO)HLnEt(Cl)AlHEt(Cl)LnCl(OiPr). The polymerization ac-
tivity decreased in the order Gd>Dy>Er>Tm and the cis-content ranged from 92
to 95% in the case of Gd derivatives. Random copolymerization of butadiene
with isoprene was also performed using Nd(C6H6)(AlCl4)3/AlR3 (Al/Nd=30) in
benzene. Both monomers were incorporated in the copolymer selectively with
cis–1,4-butadiene 96.1–96.4% and cis–1,4-isoprene 97.5–98.3%. The conversion
increased with increase in the polymerization temperature from 0 (10%) to
80 °C (80–100%) [75].
Some rare earth metal based initiators induce the trans-1,4-polymerization
of conjugated dienes at high yield. The Ce(acac)3/AlEt2Cl system as well as the
CeCl3/AlEt2Cl and GdCl3/AlEt3 systems were most effective catalyst system to
carry out this type of polymerization for isoprene with high selectivity (91–
97%) [76]. The marked difference in the selectivity between the Ce(acac)3/AlEt3
and the C5H5LnCl2/AlR3 or (iPrO)2LnCl/AlR3 initiator systems may be due to a
specific action of small amounts of water present in the system. Actually, metal
compound hydrates like NdCl3•6H2O, PrCl3•6H2O and UO2(C2H3O2)2•6H2O
can initiate the trans-polymerization in the presence of AlR3 [77]. Prolonged
aging of the initiator system decreased the activity significantly, presumably
owing to an irreversible self-reaction of the intermediate generated from the
organolanthanide and water. A precise recent study on the effect of water has
revealed that a maximum conversion was attainable at an H2O/AlEt2Cl ratio of
1.1–1.2, which produces (AlEt-O-)n(AlCl-O)m species. However, the molecular
weight was independent of the amount of water added to AlEt2Cl.
Butadiene-styrene copolymerization was attempted using the L3Ln-RX-AlR3
system [78]. Especially, (CF3COO)3Nd/C5H11Br/AliBu3 (1:3:15) was found to be
active for this type of copolymerization, with the cis-content of butadiene unit
amounting 97.8% and the styrene content to ca. 32%. However, for the system of
isoprene/styrene, the trans-1,4-polyisoprene copolymer was produced exclu-
sively.
13
Stereospecific Polymerization of Acetylene Derivatives
Polyacetylene (PA) is one of the simplest conjugated polymers, useful for man-
ufacturing lightweight high energy density plastics for storage batteries, solar
energy cells, etc. Acetylene can be polymerized to give high cis PA film with
Ti(OiBu)4/AlEt3 [79] or Co(NO3)2/NaBH4 [80] at temperatures lower than –
78 °C. Recently, it has been reported that Ln(naphthenate)3/AlR3/Donor (1:10:2–
3) (Donor=acetone, ether, ethyl acetate) systems also can initiate stereoregular
cis polymerization of acetylene at 30 °C, which leads to silvery metallic film [81,
82]. The polymer yield increased with increasing polymerization temperature
from –15 to 45 °C. A cis-polyacetylene with 95% selectivity was obtained when
the Al/Ln ratio was adjusted to ca. 5. The polymerization activity decreased in
the order Y=Ce>Nd=Tb>Pr>La>Lu>Gd>Tm=Er>Ho=Yb=Eu>Sm>Dy. The
trans content of the film amounted to 100% when the temperature was raised to
180 °C. The elements leading to PA film with a cis content exceeding 95% are La,
Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, and Y. The electrical conductivity of the films
was 294×10–8 Scm–1 for La, 181×10–8 Scm–1 for Nd, 194×10–8 Scm–1 for Gd,
490×10–8 Scm–1 for Tb, and 184×10–8 Scm–1 for Tm. Differential scanning calor-
imetry revealed two exothermic peaks at 200 and 380 °C and an endothermic
peak at 460 °C. These peaks were attributed to cis-trans isomerization, hydrogen
migration, and chain decomposition, respectively [82].
Sc(naphthenate)3/ROH/AlR3 (1/2/7) has been found to exhibit an activity
similar to the lanthanide series catalyst [83] (Fig. 27). The cis PA film obtained
with it showed an electrical conductivity of 14.4 Scm–1 when the polymer was
doped with I2 at a ratio of (CHI0.04)n, and the TEM measurement suggested the
formation of fibrils of about 20–30 nm in size.
280 Hajime Yasuda
The (P204)3Ln/AlR3 system also exhibited good activity for the polymeriza-
tion of acetylene when Al/Ln ratio was 5 [83]. The polymerization was conduct-
ed by the conventional method, and polymers with silver metallic appearance
were obtained. The addition of an oxygen-containing donor was effective for en-
hancing the polymerization rate and the cis-content. The effects were especially
marked for P204 (PO/Nd=1.1). The activity decreased in the order Nd=
Tb>Ce>Pr=Y>La>Er>Ho>Sm=Eu>Yb=Lu>Gd>Tm>Dy and the cis-content
decreased in the order Pr (95%)>Lu=Tb=Dy (92%)>Er=Y=Sm=Gd (87–89%).
The polymerization activities of Nd(P507)3, Nd(P204)3, and Nd(P215) were com-
pared and found to increase in this order, the result is consistent with the basic-
ities of the ligands (P507H=pKa 4.10, P204H=pKa 3.32, P215H=pKa 3.22). The M-
C bond is supposed to weaken as the electron donating ability of the ligand in-
creases. The Nd(iPrO)3/AlEt3 (Al/Nd=10) system [84] was also shown to be a
good initiator for the polymerization of acetylene. The soluble fraction obtained
was considered to be trans-polyacetylene, which was shown to have a molecular
weight of 277–540. Its 1H NMR spectrum revealed methyl groups at δ=
0.826 ppm and terminal vinyl groups at 4.95 ppm.
Phenylacetylene was polymerized to give a polymer of high cis configuration
by the use of the Ln(naphthenate)3/AlEt3 system [85, 86], with the activity de-
creasing in the order Gd>Lu>Nd=Ce>Ho>Sm>Dy=Eu>Er>Pr>La>Y=Tm>Yb,
and the cis-content exceeding 90%. It had Mn and Mw of 2×105 and 4×105, respec-
tively, and was crystalline according to XRD and SEM measurement. Its soften-
ing point was in the range 215–230 °C. Other terminal alkynes such as 1-hexyne,
1-pentyne, 3-methyl-1-pentyne, 4-methyl-1-pentyne, 3-methyl-1-butyne, and
phenylacetylene were found to polymerize quantitatively in the cis-fashion with
the Ln(naphthenate)3/AlR3/C2H5OH (Ln=Sc, Nd) or Ln(P204)3/ AlR3/C2H5OH
(1:7:3) system. The highest molecular Mn obtained was 16.8×104 for poly(1-pen-
tyne). Trimethylsilylacetylene was oligomerized to H(Me3SiC=CH)nCH2CHMe2
(n=2–3) by the use of LnX3(Donor)/AliBu3 (Ln=Gd, Pr, Nd, Tb, Dy, Lu; X=Cl, Br)
[87, 88]. The catalytic dimerization of terminal alkynes using
(C5Me5)2LnCH(SiMe3)2 (Ln=Y, La, Ce) has been reported recently. Here the
dimer was a mixture of 2,4-disubstituted 1-buten-3-yne and 1,4-disubstituted 1-
Fig. 27. Rare earth metal initiated polymerizations of acetylene derivatives

buten-3-yne for phenylacetylene and (trimethylsilyl)acetylene, but it was a 2,4-

disubstituted dimer for alkylacetylene [89]. Selective formation of 2,4-disubsti-
tuted 1-buten-3-ynes has already been achieved with the (C5Me5)2TiCl2/RMgX
catalyst [90].
14
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Polymer-Supported Rare Earth Catalysts Used in Organic
Synthesis
Shu Kobayashi

Bunkyo-ku, Tokyo 113– 0033, Japan
E-mail: [email protected]
Abstract. Three types of polymer-supported rare earth catalysts, Nafion-based rare earth
catalysts, polyacrylonitrile-based rare earth catalysts, and microencapsulated Lewis acids,
are discussed. Use of polymer-supported catalysts offers several advantages in preparative
procedures such as simplification of product work-up, separation, and isolation, as well as
the reuse of the catalyst including flow reaction systems leading to economical automation
processes. Although the use of immobilized homogeneous catalysts is of continuing inter-
est, few successful examples are known for polymer-supported Lewis acids. The unique
characteristics of rare earth Lewis acids have been utilized, and efficient polymer-support-
ed Lewis acids, which combine the advantages of immobilized catalysis and Lewis acid-me-
diated reactions, have been developed.
Keywords: Lewis acids, Polymer-supported catalysts, Rare earth triflate, Combinatorial syn-
thesis, Carbon–carbon bond-forming reactions
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
2 Nafion-Based Rare Earth Catalysts . . . . . . . . . . . . . . . . . . 286
3 Polyacrylonitrile-Based Rare Earth Catalysts . . . . . . . . . . . . 289
4 A Microencapsulated Rare Earth Lewis Acid.
(A New Type of Polymer-Supported Catalyst) . . . . . . . . . . . . 295
5 References and Notes . . . . . . . . . . . . . . . . . . . . . . . . . . 303
1
Introduction
Use of polymer-supported catalysts offers several advantages in preparative pro-
cedures. Simplification of product work-up, separation, and isolation as well as
reuse of the catalyst including use of flow reaction systems could lead to eco-
nomical automation processes. Although the use of immobilized homogeneous
catalysts is of continuing interest [1], few successful examples are known for pol-
ymer-supported Lewis acids [2,3]. This is probably due to the instability of most
Lewis acids to air (moisture) and water. During preparation of polymer-sup-
ported catalysts, many manipulations have to be carried out in air or in the pres-
ence of water. On the other hand, it was recently found that some rare earth
Lewis acids are stable in water [4]. Utilizing this very unique characteristic, sev-
eral efforts to develop efficient polymer-supported Lewis acids combining the
advantages of immobilized catalysis and Lewis acid-mediated reactions, have
286 Shu Kobayashi
been made. In this chapter, three types of polymer-supported rare earth cata-
lysts, Nafion-based rare earth catalysts, polyacrylonitrile-based rare earth cata-
lysts, and microencapsulated Lewis acids are discussed [5].
2
Nafion-Based Rare Earth Catalysts
Recently, scandium triflate [Sc(OTf)3] was found to be stable in water and suc-
cessful Lewis acid catalysis was carried out in both water and organic solvents
[6–8]. Sc(OTf)3 coordinates to Lewis bases under equilibrium conditions, and
thus activation of carbonyl compounds using a catalytic amount of the acid has
been achieved [6,7]. In addition, effective activation of nitrogen-containing
compounds such as imines, amino aldehydes, etc. has been performed success-
fully [8]. Encouraged by the characteristics and the usefulness of Sc(OTf)3 as a
Lewis acid catalyst, a polymer-supported scandium catalyst was prepared.
Nafion (NR-50, Du Pont) was chosen as the supporting framework [9]. Three
equivalents of Nafion were treated with ScCl3◊6H2O in acetonitrile under reflux
conditions [10]. After 40 h, 96% of the ScCl3◊6H2O was consumed and the poly-
mer thus prepared (Nafion-Sc) contained 1.3% Sc, according to ICP analysis.
Choice of solvent is important at this stage; only 27% of the ScCl3◊6H2O was con-
sumed when 1,2-dichloroethane was used as the solvent. This Nafion-Sc catalyst
was then tested in several synthetic reactions [11]. First, allylation reactions of
carbonyl compounds were investigated. Allylation reactions of carbonyl com-
pounds are among the most important carbon–carbon bond-forming reactions,
and the products, homoallylic alcohols having hydroxyl and double bond
groups, are synthetically useful intermediates [12]. Nafion-Sc was also found to
be effective in the allylation reactions of carbonyl compounds with tetraallyltin,
and selected examples are shown in Table 1 [13]. In all cases, the reactions pro-
ceeded smoothly in both organic and aqueous solvents to afford the desired ho-
moallylic alcohols in high yields. Not only aldehydes, but also ketones worked
well. Moreover, use of aqueous solvents enabled the reactions of non-protected
carbohydrates [14]. Non-protected sugars reacted directly with tetraallyltin to
give the adducts, which are useful intermediates for the synthesis of higher sug-
ars. Salicylaldehyde and 2-pyridinecarboxaldehyde reacted with tetraallyltin to
afford the corresponding homoallylic alcohols in good yields. These compounds
are known to react with the Lewis acids rather than the nucleophile under gen-
eral Lewis acidic conditions.
Nafion-Sc was also found to be effective in some other reactions (Schemes 1–
3). In typical Lewis acid-mediated reactions, such as Diels–Alder, Friedel–Crafts
acylation, and imino Diels–Alder reactions, Nafion-Sc worked efficiently to af-
ford the corresponding adducts in high yields.
It was also found that Nafion-Sc could be easily recovered and reused. The
catalyst was recovered simply by filtration and washing with a suitable solvent,
and the activity of the recovered Nafion-Sc was comparable to the fresh catalyst;
in the reaction of benzaldehyde with tetraallyltin in H2O/MeOH/toluene(1:7:4)
Polymer-Supported Rare Earth Catalysts Used in Organic Synthesis 287
Table 1. Sc-Nafion-catalyzed allylation reactions of carbonyl compounds with tetraallyltina

Carbonyl
Compound Product Solventb Yield (%)
OH A 91
PhCHO B 90
Ph C 91
OH
CHO A 83
Ph C 83
Ph
OH
CHO A 93
Ph C 98
Ph
N CHO OH
N A 78
O
OH
Ph A 57 c
Ph
O
OH A 64 c
Ph Ph
C 87 c
O OH A 95 c
Ph Ph
C 85 c
O MeO2C OH A 81 c
Ph CO2Me Ph
C 84 c
OAc OAc
D-arabinose AcO A 76 c,d,e
OAc OAc
OAc OAc
D-ribose AcO A 91 c,d,f
OAc OAc
OAc OAc OAc
D-glucose
AcO A 64 c,d,g
OAc OAc
a The reaction was carried out at rt unless otherwise noted.
b A: H O/THF (1:9); B: H O/MeOH/toluene (1:7:4); C: CH CN.
2 2 3
c The reaction was carried out at 60 °C.
d The products were isolated after acetylation.
e syn/anti=59:41.
f syn/anti=65:35.
g Diastereomeric ratio=68:32. Relative configuration assignment was not made.
288 Shu Kobayashi
O O
Nafion-Sc O
+
N O CH2Cl2, rt, 2 h
92% CO N O
H2O/MeOH/Toluene
(1:7:4), rt, 2 h
97%
Scheme 1
Nafion-Sc
MeO + Ac2O MeO COCH3
LiClO4-CH3NO2
50 °C, 6 h
68%
Scheme 2
NH2
PhCOCHO•H2O + +
MeO
H
Nafion-Sc MeO
H
H2O/MeOH/Toluene
(1:7:4), rt, 2 h N COPh
92% H
Scheme 3
[15] at rt; lst, 91% (15 h); 2nd, 81% (48 h); 3rd, 93% (40 h); in the reaction of 3-
acryloyl-1,3-oxazolidin-2-one with cyclopentadiene at rt; 1st, 92% (2 h); 2nd,
87% (2 h); 3rd, 91% (2 h).
Nafion-Sc was also used in a flow system. Nafion-Sc was packed in a glass tube
and substrates were passed through the column using a motor pump (Fig. 1)
[16]. Results of the reaction of benzaldehyde with tetraallyltin in aqueous solu-
tion are shown in Scheme 4. It is noted that even higher yields were obtained in
the 2nd, 3rd, and 4th runs than in the 1st run.
Nafion-Sc
pump
Fig. 1. A flow system using Nafion-Sc
Run Yield (%) Run Yield (%)

1 75 3 84
2 93 4 84
Scheme 4. Nafion-Sc-catalyzed allylation using a flow system
3
Polyacrylonitrile-Based Rare Earth Catalysts
One of the drawbacks of polymer-supported catalysts is their low reactivity.
Bearing in mind that the low reactivity might be ascribed to insolubility of the
catalysts, a new polymer-supported catalyst, which was partially soluble in an
appropriate solvent and is precipitated after completion of the reaction and re-
covered quantitatively by filtration, was searched. After several trials, a new
scandium catalyst, polyallylscandium trifylamide ditriflate (PA-Sc-TAD), was fi-
nally developed. PA-Sc-TAD was readily prepared according to Scheme 5. Poly-
acrylonitrile was treated with BH3◊SMe in diglyme for 36 h at 150 °C. The result-
ing amine (1) was reacted with Tf2O in the presence of Et3N in 1,2-dichlo-
290 Shu Kobayashi
CH2 CH BH3•SMe2 CH2 CH Tf2O/Et3N
CN n CH2NH2 n
1
CH2 CH 1. KH CH2 CH
CH2NH n 2. Sc(OTf)3 CH2NTf n
Tf
2 Sc(OTf)2
PA-Sc-TAD (3)
Scheme 5. Preparation of PA-Sc-TAD (3)
roethane for 10 h at 60 °C to afford sulfonamide 2 [17]. After compound 2 and

KH were combined, Sc(OTf)3 was added and the mixture was stirred in THF for
48 h at rt to give 3 [18]. PA-Sc-TAD (3) is gummy, but is dispersed and partially
soluble in a mixture of CH2Cl2/CH3CN. The dispersed catalyst assembles again
when hexane is added.
In the presence of PA-Sc-TAD (3), quinoline synthesis based on a three-com-
ponent coupling reaction [8b,c] was performed. An aldehyde, an aromatic
amine, and an alkene were mixed in CH2Cl2/CH3CN (2:1) at 60 °C for 12 h. Hex-
ane was then added and the catalyst was filtered off. The filtrate was concentrat-
ed in vacuo to afford a crude adduct. After purification by column chromatogra-
phy, the desired quinoline derivative was obtained in a high yield.
This method is especially useful for construction of a quinoline library
(Scheme 6) [19]. The procedure is very simple; it involves just mixing the cata-
lyst (PA-Sc-TAD), an aldehyde, an aromatic amine, and an alkene (alkyne). After
filtration, the filtrates are concentrated to give almost pure quinoline derivatives
in most cases. Dehydrating agents such as MS 4A, MgSO4, etc. are not necessary.
It is noted that PA-Sc-TAD is water-tolerant and that substrates having water of
crystallization can be used directly. PA-Sc-TAD can be easily recovered and con-
tinuous use is possible without any loss of activity (Scheme 7).
Combinatorial synthesis, a synthetic strategy which leads to large chemical li-
braries, is beginning to make a significant impact especially on the drug discov-
ery process. Although polymer-supported substrates (reagents) have often been
employed for library construction [20], there are some disadvantages to this
method. First, the reactions of polymer-supported reagents are sometimes slow,
and differences in reactivity between the substrates lead to lack of diversity of
the library in some cases. Secondly, the loading level of polymer-supported sub-
strates is generally low (<0.8 mmol/g), and large-scale preparation is difficult.
The present reactions using the polymer-supported catalysts provide a new
method for synthesizing a large number of structurally distinct compounds. In
addition, a characteristic feature of the present method compared with conven-
tional combinatorial synthetic technology using polymer-supported reagents is
NH2
R3 R5
R1CHO + +
R4 R6
R3 R4
R2
PA-Sc-TAD (3) R5
R6
N R1
R2 H
Ph O
Cl Cl
N Ph N Ph N Ph
H H H
75%, 90/10 80%, 86/14 83%, 62/38
SPh SBu
Cl Cl
H,H
N Ph N Ph HN
H H
Ph
65%, nd 84%a 92%, 95/5
Cl
HN OMe
MeO HN HN
Ph Ph
85%, 99/1 quant., 100/0 71%, 100/0
Cl
Cl Cl
HN
HN HN
S
Cl
70%, 100/0 96%, 100/0 91%, 100/0
Cl Cl
Cl
HN HN
HN
COPh
O
78%, 100/0 80%, 100/0 99%, 100/0
aButyl ethynyl sulfide was used as a dienophile.
Scheme 6. Synthesis of quinoline derivatives

292 Shu Kobayashi
NH2
PhCOCHO•H2O + +
PA-Sc-TAD (3)
CH2Cl2-CH3CN
(2:1) N COPh
H
1st use, 90%; 2nd use, 91%; 3rd use, 93% yield
Scheme 7
that more than 100-mg scale syntheses with a large array of diverse molecular
entries have been achieved with high purities (high yields and high selectivi-
ties). The number of commercially available aromatic aldehydes, aliphatic alde-
hydes, heterocyclic aldehydes, and glyoxals and glyoxylates that could be appli-
cable to this synthesis is more than 200, and more than 200 aromatic amines and
50 alkenes (and alkynes) [21] are commercially available. Therefore, a quinoline
library of more than a million compounds with high quantity and quality could
be prepared by using an automation system based on this method. Moreover, the
tetrahydroquinoline derivatives thus obtained are easily oxidized to dihydroqui-
noline or quinoline derivatives, which could double or triple the size of the li-
brary. Similarly, diverse amino ketone, amino ester, and amino nitrile deriva-
tives were synthesized using PA-Sc-TAD as a catalyst (Schemes 8 and 9) [22].
In addition to several advantages of polymer-supported catalysts in synthesis,
such as simplification of reaction procedures, easy separation of catalysts and
products, application to automation systems, etc., it is desirable to achieve high
selectivities by utilizing the bulkiness of polymers, the stability of polymer-co-
ordinated complexes, etc. [23]. Such examples have recently been reported using
a polymer-supported scandium catalyst (PA-Sc-TAD) [24]. It is well recognized
that aldimines are less reactive than aldehydes towards nucleophilic addition be-
cause of the difference in electronegativity between oxygen and nitrogen, the
steric hindrance of aldimines, etc. [25]. In fact, in the model competition reac-
tion of benzaldehyde and N-benzylideneaniline with propiophenone lithium
enolate, the enolate attacks the aldehyde exclusively in the coexistence of the ald-
imine. On the other hand, it was recently reported that in the presence of a cat-
alytic amount of Yb(OTf)3, aldimines react with silyl enolates selectively to af-
ford the corresponding adducts in high yields, even in the coexistence of alde-
hydes [26]. Scandium salts were then used in the same competition reactions.
Although both scandium and ytterbium elements belong to group 3, the compe-
tition reaction of benzaldehyde and N-benzylideneaniline with the silyl enol
ether of propiophenone in the presence of 20 mol% of Sc(OTf)3 gave a mixture
of aldehyde-adduct 4a (13%) and aldimine-adduct 5a (58%). Interestingly, when
OSiMe3
2
R1CHO + R NH2 + R3
R4
R2HN O
PA-Sc-TAD (3)
R1 R4
3
R
Scheme 8
PA-Sc-TAD (3) NHR2

2 Me3SiCN
R1 CHO + R NH2 +
R1 CN
Scheme 9
4a 5a
Catalyst Solvent Yield (%)

M 4a/5a
/equiv /temp(°C) 4a 5a
Li THF/-78 97 trace >99/1
TMS Sc(OTf) 3 /0.2 CH 2 Cl 2 /-23 13 58 18/82

CH 2 Cl 2 :CH 3 CN
TMS PA-Sc-TAD/0.06 (2:1)/rt 1 95 1/99
Scheme 10. A competition reaction between an aldehyde and an aldimine
a polymer-supported scandium catalyst (PA-Sc-TAD) was used, the aldimine se-

lectivity was improved dramatically, and the aldimine reacted with the silyl eno-
late to give the corresponding adduct in excellent selectivity (Scheme 10). Other
combinations of aldehydes, aldimines, and silyl enolates were then tested, and
the results are summarized in Scheme 11. In all cases, aldimines reacted with si-
lyl enolates selectively in the coexistence of aldehydes to afford the correspond-
ing adducts in high yields.
The unique selectivities obtained using the polymer-supported catalyst can
be explained by the following equations. A catalytic amount of a scandium Lewis
294 Shu Kobayashi
4 5
Yield (%)
R1 R2 R3 R4 4/5
4 5
Ph Ph Ph Me 1 97 1/99
c-C 6 H 11 Ph Ph Me trace 91 <1/>99
2-furyl Ph Ph Me trace >99 <1/>99
c-C 6 H 11 (p-Cl)Ph Ph Me trace 97 <1/>99
Ph Ph SEt H trace 58 <1/>99
Scheme 11. Aldimine-selective reaction using a polymer-supported catalyst
R2
ScX3 O N ScX3 R2
k1 + k2
O N
R1 H R1 H
R1 H R1 H
+ ScX3
6
Scheme 12
OSiMe3
R4 O OH
3
R
6 R3 R1
4
R
Scheme 13
OSiMe3
R2
R4 O HN
R3
6
R3 R1
R4
Scheme 14
Ph Ph
O OH O HN
O N OSiMe3 Catalyst
+
+ +
CH2Cl2, -23 °C Ph Ph Ph Ph
Ph H Ph H Ph
4a 5a
Catalyst Yield (%)

4a/5a
4a 5a
Sc(OTf)3 13 58 18/82
Sc(OTf) 2 (NTf 2 ) 16 77 17/83
Sc(NTf2 )3 3 77 4/96
ScCl 3 trace 43 <1/>99
Sc(PF 6 )3 2 76 3/97
Sc(SbF 6 )3 3 64 5/95
Sc(AsF 6 )3 26 49 35/65
Sc(ClO 4 )3 trace 87 <1/>99
Sc(BPh 4 )3 18 51 16/84
{[(3,5-CF3 )2 Ph] 4 B}3 Sc 10 66 13/87
Scheme 15
acid first coordinates an aldimine, but the coordination occurs under equilibri-
um conditions (Schemes 12–14). Aldehyde/Lewis acid or aldimine/Lewis acid
complexes should be stabilized by counter anions of scandium compounds
(Scheme 15), and the ratios of 4/5 shown in Scheme 15 could depend on the sta-
bility of the complexes influenced by the counter anions. On the other hand,
when the polymer-supported scandium catalyst (PA-Sc-TAD) was used, the cat-
alyst also coordinated aldimines first. In this case, however, the aldimine/poly-
mer-supported catalyst complexes are more stable than aldimine/nonpolymer
Lewis acid complexes due to the polymer effect. Hence, the aldimines activated
by the polymer-supported catalyst reacted with silyl enolates to afford aldimine
adducts exclusively.
These aldimine-selective reactions using the polymer-supported catalyst will
be applied to other nucleophilic addition reactions in organic chemistry.
4
A Microencapsulated Rare Earth Lewis Acid (A New Type of Polymer-
Supported Catalyst)
In Sects. 1 and 2, polymer-supported scandium Lewis acids based on Nafion and
a polyacrylonitrile derivative were discussed. While several useful reactions
296 Shu Kobayashi
Fig. 2. Scanning electron microscopy (SEM) micrograph (left) and scandium energy dis-
persive X-ray (EDX) map of MC Sc(Otf)3
have been developed, it was found that their reactivity, especially towards alde-
hydes and ketones, was lower than that of the nonpolymer Lewis acids. In gen-
eral, catalysts are immobilized on polymers via coordinate bonds or covalent
bonds. While the stability of polymer catalysts having coordinate bonds is often
low, preparation of polymer catalysts having covalent bonds can be troublesome
and their activities are generally lower than those of the nonpolymer catalysts
[27]. As an unprecedented polymer-supported Lewis acid, attention is focused
on a microencapsulated Lewis acid.
Microcapsules have been used for coating and isolating substances until such
time as their activity is needed, and their application to medicine and pharmacy
has been extensively studied [28]. Recently, much progress has been made in this
field, and, for example, the size of the microcapsules that can be achieved has
been reduced from a few µm to nanometers [28,29]. The idea is to apply this mi-
croencapsulation technique to the immobilization of Lewis acid catalysts onto
polymers. That is, Lewis acids would be physically enveloped by polymer thin
films and, at the same time, immobilized by the interaction between p electrons
of benzene rings of the polystyrene used as a polymer backbone and vacant or-
bitals of the Lewis acids [30]. Sc(OTf)3 was first chosen as a Lewis acid to be im-
mobilized [31]. Preparation of the microencapsulated Sc(OTf)3 [MC Sc(OTf)3]
was performed as follows: Polystyrene (1.000 g) was dissolved in cyclohexane
(20 ml) at 40 °C, and to this solution was added Sc(OTf)3 (0.200 g) as a core. The
mixture was stirred for 1 h at this temperature and then slowly cooled to 0 °C.
Coacervates were found to envelop the core dispersed in the medium, and hex-
ane (30 ml) was added to harden the capsule walls. The mixture was stirred at rt
for 1 h, and the capsules were washed with acetonitrile several times and dried
at 50 °C [32,33]. A scanning electron microscopy (SEM) micrograph and a scan-
dium energy dispersive X-ray (EDX) map of MC Sc(OTf)3 prepared are shown
in Fig. 2. It was found that small capsules of MC Sc(OTf)3 adhered to each other,
probably due to the small size of the core. Judging from the scandium mapping,
Ph
Ph OSiMe3 MC Sc(OTf)3 NH O
N
+
Ph CH3CN, rt, 3 h Ph Ph
Ph H
Use a Yield/%
1 90
2 90
3 88
4 89
5 89
6 88
7 90
a
Recovered catalyst was used
successfully (Runs 2,3,4...)
Scheme 16. Imino aldol reaction (flow system)
Sc(OTf)3 was located all over the polymer surface. The importance of the ben-
zene rings of the polystyrene in immobilizing Sc(OTf)3 was demonstrated by
control experiments using polybutadiene or polyethylene instead of polysty-
rene. While 43% of Sc(OTf)3 [100%=the amount of Sc(OTf)3 immobilized by
polystyrene] was bound using polybutadiene, no Sc(OTf)3 was observed in the
microcapsules prepared using polyethylene. These results demonstrate that the
interaction between Sc(OTf)3 and the benzene rings of polystyrene is a key to
immobilizing Sc(OTf)3. Steric factors (physical envelopment) would also con-
tribute to the remarkable immobilizing ability of polystyrene compared to poor
immobilization of polybutadiene and polyethylene.
MC Sc(OTf)3 was used in several fundamental and important Lewis acid cat-
alyzed carbon–carbon bond-forming reactions. All the reactions were carried
out on a 0.5 mmol scale in acetonitrile [34] using MC Sc(OTf)3 containing ca.
0.120 g Sc(OTf)3. The reactions were carried out in both batch (using normal
vessels) and flow systems (using circulating columns). It was found that
MC Sc(OTf)3 effectively activated aldimines. Imino aldol (Sheme 16), aza Diels–
Alder (Scheme 17), cyanation (Scheme 18), and allylation (Scheme 19) reactions
of aldimines proceeded smoothly using MC Sc(OTf)3 to afford, respectively, the
synthetically useful b-amino ester, tetrahydroquinoline, a-aminonitrile, and
homoallylic amine derivatives in high yields.
Although it is well known that most Lewis acids are trapped and sometimes
decomposed by basic aldimines, MC Sc(OTf)3 worked well in all cases. One of
the most remarkable and exciting points is that the activating ability of
298 Shu Kobayashi
Use Yield/%
1 80
2 78
3 78
Scheme 17. Aza-Diels–Alder reaction (flow system)
Use Yield/%
1 77
2 77
3 76
Scheme 18. Cyanation reaction (flow system)
Use Yield/%
1 85
2 87
3 83
Scheme 19. Allylation reaction of imine (flow system)
MC Sc(OTf)3 for aldimines was revealed to be superior to monomeric Sc(OTf)3

by preliminary kinetic studies (Fig. 3) [35].
The polymer catalyst was recovered quantitatively by simple filtration and
could be reused. The activity of the recovered catalyst did not decrease even after
seven uses (Scheme 16). MC Sc(OTf)3 could also be successfully used in three-
Fig. 3. Comparison of MC Sc(OTf)3 (O) and Sc(OTf)3 (") in the reaction of N-benzylide-
neaniline with (Z)-1-phenyl-1-trimethylsiloxypropene. The reaction was carried out using
N-benzylideneaniline (0.5 mmol), (Z)-1-phenyl-1-trimethylsiloxypropene (0.60 mmol),
and MC Sc(OTf)3 [1.167 g, containing Sc(OTf)3 0.120 g] or Sc(OTf)3 (0.120 g) in CH3CN
(5 ml) at rt
Use Yield/%
1 90
2 96
3 93
Scheme 20. Mannich-type reaction (flow system)
component reactions such as Mannich-type (Scheme 20), Strecker (Scheme 21),

and quinoline-forming reactions (Scheme 22). These reactions are known to be
useful for the synthesis of biologically interesting compound libraries [36].
It was also found that MC Sc(OTf)3 was effective for the activation of carbonyl
compounds. The polymer scandium catalysts such as Nafion-Sc, polyallylscan-
300 Shu Kobayashi
Use Yield/%
1 70
2 71
3 75
Scheme 21. Strecker reaction (flow system)
Use Yield/%
1 68
2 69
3 69
Scheme 22. Quinoline synthesis (flow system)
Use Yield/%
1 92
2 97
3 95
Scheme 23. Aldol reaction (batch system)
dium trifylamide ditriflate (PA-Sc-TAD) were found to have only a low ability to
activate aldehydes, as mentioned previously. On the other hand, MC Sc(OTf)3
efficiently activated aldehydes, and aldol (Scheme 23), cyanation (Scheme 24)
and allylation (Scheme 25) reactions of aldehydes proceeded smoothly to give
the corresponding aldol, cyanohydrin, and homoallylic alcohol derivatives in
high yields.
Use Yield/%
1 79
2 78
3 74
Scheme 24. Cyanation reaction of an aldehyde (batch system)
Use a Yield/%
1 92
2 91
3 90
Scheme 25. Allylation reaction of an aldehyde (batch system)
Use Yield/%
1 92
2 97
3 95
Scheme 26. Michael reaction (batch system)
Michael reaction of an a,b-unsaturated ketone with a silyl enol ether

(Scheme 26) and a Diels–Alder reaction of an oxazolidinone derivative with cy-
clopentadiene (Scheme 27) also worked well using MC Sc(OTf)3. Moreover, a
Friedel–Crafts acylation proceeded smoothly to produce an aromatic ketone in
a good yield (Scheme 28). Friedel–Crafts alkylation and acylation reactions are
fundamental and important processes in organic synthesis as well as in indus-
302 Shu Kobayashi
Use Yield/%
1 77
2 79
3 80
Scheme 27. Diels–Alder reaction (batch system)
Use Yield/%
1 76
2 76
3 81
Scheme 28. Friedel–Crafts acylation (batch system)
trial chemistry [37]. While the alkylation reaction proceeds in the presence of a
catalytic amount of a Lewis acid, the acylation reaction generally requires more
than a stoichiometric amount of a Lewis acid, usually aluminum chloride
(AlCl3), due to consumption of the Lewis acid by coordination to the aromatic
ketone products. It should be noted that MC Sc(OTf)3 has high activity in the
Friedel–Crafts acylation and can be recovered easily by simple filtration and re-
used without loss of activity.
Similarly, microencapsulated ytterbium triflate (MC Yb(OTf)3) has been pre-
pared [38]. MC Yb(OTf)3 was found to be effective in the aza-Diels–Alder reac-
tion using ethyl vinyl ether as a dienophile (Scheme 29). In the presence of
MC Yb(OTf)3, N-benzylideneaniline reacted with ethyl vinyl ether to afford the
corresponding tetrahydroquinoline derivative in a good yield. MC Yb(OTf)3
could also be recovered quantitatively and could be reused. The yield of the 2nd
and 3rd runs were comparable to that of the 1st run. In a similar reaction using
Sc(OTf)3 or MC Sc(OTf)3 as a catalyst, ethyl vinyl ether polymerized rapidly and
no desired adduct was obtained.
Use Yield/%
1 78
2 70
3 77
Scheme 29. Aza-Diels–Alder reaction using Yb(Otf)3 (batch system)
Thus, a microencapsulation technique has been shown to be quite effective

for binding catalysts to polymers. Utilizing this technique, unprecedented poly-
mer-supported, microencapsulated rare earth Lewis acids have been prepared.
The catalysts thus prepared have been successfully used in many useful carbon–
carbon bond-forming reactions. In all cases, the catalysts were recovered quan-
titatively by simple filtration and reused without loss of activity. This new tech-
nique for binding nonpolymer compounds to polymers will be applicable to the
preparation of many other polymer-supported catalysts and reagents.
Acknowledgments. Our work in this area was partially supported by CREST, Ja-
pan Science and Technology Corporation (JST), and a Grant-in-Aid for Scientif-
ic Research from the Ministry of Education, Science, Sports and Culture, Japan.
The author thanks and expresses his deep gratitude to his co-workers whose
names appear in the references.
5
1. (a) Bailey DC, Langer SH (1981) Chem Rev 81:109. (b) Akelah A, Sherrington DC (1981)
Chem Rev 81:557. (c) Frechet JM (1981) J Tetrahedron 37:663. (d) Smith K (ed) (1992)
Solid supports and catalysts in organic synthesis. Ellis Horwood, Chichester. (e) Sher-
rington DC, Hodge P (eds) (1988) Synthesis and separations using functional polymers.
John Wiley, New York. (f) Blazer HU, Pugin B (1995) In: Jannes G, Dubois J (eds) Chiral
reactions in heterogeneous catalysis. Plenum Press, New York
2. Recently, Lewis acid mediated reactions have been especially focused upon because of
their unique reactivities, selectivities, and mild conditions. Schinzer D (ed) (1989) Se-
lectivities in Lewis acid promoted reactions. Kluwer, Dordrecht; Santelli M, Pons J-M
(1995) Lewis acids and selectivity in organic synthesis. CRC Press, Boca Raton
3. Immobilization of AlCl3 onto polymers or inorganic support materials has been report-
ed. (a) Neckers DC, Kooistra DA, Green GW (1972) J Am Chem Soc 94:9284. (b) Krzy-
wicki A, Marczewski M (1980) J Chem Soc Faraday Trans 1:1311. (c) Drago RS, Getty EE
(1988) J Am Chem Soc 110:3311. (d) Clark JH, Martin K, Teasdale AJ, Barlow SJ (1995)
J Chem Soc Chem Commun 2037. Montmorillonite-supported zinc chloride. (e) Clark
JH, Cullen SR, Barlow SJ, Bastock TW (1994) J Chem Soc Perkin Trans 2 1117. Immobi-
304 Shu Kobayashi
lized trityl salts. (f) Mukaiyama T, Iwakiri H (1985) Chem Lett 1363. Polymer- or den-
drimer-bound Ti-TADDOLates. (g) Seebach D, Marti RE, Hintermann T (1996) Helv
Chim Acta 79:1710. (h) Rheiner PB, Sellner H, Seebach D (1997) Helv Chim Acta
80:2027. (i) Comina PJ, Beck AK, Seebach D (1998) Org Pro. Res Dev 2:18
4. (a) Kobayashi S (1991) Chem Lett 2187. (b) Kobayashi S, Hachiya I (1994) J Org Chem
59:3590. (c) Kobayashi S (1994) Synlett 689
5. Besides these examples, rare earth catalysts supported on ion-exchange resins have re-
cently been reported. Yu L, Chen D, Li J, Wang PG (1997) J Org Chem 62:3575
6. Kobayashi S, Hachiya I, Araki M, Ishitani H (1993) Tetrahedron Lett 34:3755
7. (a) Kobayashi S, Hachiya I, Ishitani H, Araki M (1993) Synlett 472. (b) Hachiya I, Koba-
yashi S (1993) J Org Chem 58:6958. (c) Hachiya I, Kobayashi S (1994) Tetrahedron Lett
35:3319. (d) Kawada A, Mitamura S, Kobayashi S (1994) Synlett 545. (e) Kobayashi S, Ar-
aki M, Hachiya I (1994) J Org Chem 59:3758. (f) Kobayashi S, Moriwaki M, Hachiya I
(1995) J Chem Soc Chem Commun 1527. (g) Kobayashi S, Moriwaki M, Hachiya I (1995)
Synlett 1153. (h) Kobayashi M, Hachiya I, Yasuda M (1996) Tetrahedron Lett 37:5569. (i)
Kobayashi S, Moriwaki M, Hachiya I (1997) Bull Chem Soc Jpn 70:267. (j) Kobayashi S,
Wakabayashi T, Nagayama S, Oyamada H (1997) Tetrahedron Lett 38:4559. (k) Koba-
yashi S, Wakabayashi T, Oyamada H (1997) Chem Lett 831
8. (a) Kobayashi S, Araki M, Ishitani H, Nagayama S, Hachiya I (1995) Synlett 233. (b)
Kobayashi S, Ishitani H, Nagayama S (1995) Chem Lett 423. (c) Kobayashi S, Ishitani H,
Nagayama S (1995) Synthesis 1195. (d) Kobayashi S, Hachiya I, Suzuki S, Moriwaki M
(1996) Tetrahedron Lett 37:2809. (e) Kobayashi S, Ishitani H, Komiyama S, Oniciu DC,
Katritzky AR (1996) Tetrahedron Lett 37:3731. (f) Kobayashi S, Moriwaki M, Akiyama
R, Suzuki S, Hachiya I (1996) Tetrahedron Lett 37:7783. (g) Kobayashi S, Ishitani H,
Ueno M (1997) Synlett 115. (h) Kobayashi S, Moriwaki M (1997) Tetrahedron Lett
38:4251. (i) Kobayashi S, Akiyama R, Moriwaki M (1997) Tetrahedron Lett 38:4819. (j)
Kobayashi S, Akiyama R, Kawamura M, Ishitani H (1997) Chem Lett 1039. (k) Koba-
yashi S, Busujima T, Nagayama S (1998) J Chem Soc Chem Commun 19. (l) Oyamada H,
Kobayashi S (1998) Synlett 249
9. As for metal Nafions, Hg: (a) Olah GA, Meidar D (1978) Synthesis 671. (b) Saimoto H, Hi-
yama T, Nozaki H (1985) Bull Chem Soc Jpn 56:3078. Si: (c) Murata S, Noyori R (1980)
Tetrahedron Lett 21:767. Cr, Ce: (d) Kanemoto S, Saimoto H, Oshima K, Nozaki H (1984)
ibid. 25:3317. Al,: (e) Waller FJ (1984) Br Polym J 16:239. Ta: (f) Olah GA, Gupta B, Farina
M, Felberg, JD, Ip WM, Husain A, Karpeles R, Lammertsma K, Melhotra AK, Trivedi NJ
(1985) J Am Chem Soc 107:7097. See also: (g) Waller F (1986) J Catal Rev Sci Eng 28:1
10. ScCl3◊6H2O (519 mg, 2.0 mmol) and Nafion (5 g, 1.2 meq/g) were combined in ace-
tonitrile (10 ml) under reflux for 40 h. After cooling to rt, the polymer was filtered,
washed with acetonitrile (20 ml¥3), and then dried under reduced pressure for 24 h. A
trial to prepare Nafion-Sc from Sc2O3 and Nafion failed (only 0.1% Sc was included in
the polymer (ICP analysis))
11. Kobayashi S, Nagayama S (1996) J Org Chem 61:2256
12. Yamamoto Y, Asao N (1993) Chem Rev 93:2207
13. Nafion 50 itself has much lower activity in this reaction. For example, only 19% yield of
the adduct was obtained in the reaction of acetophenone with tetraallyltin
14. (a) Schmid W, Whitesides GM (1991) J Am Chem Soc 113:6674. (b) Kim, E, Gordon DM,
Schmid W, Whitesides GM (1993) J Org Chem 58:5500. (c) Li C-J, Chan T-H (1997) Or-
ganic reactions in aqueous media. Wiley, New York
15. Kobayashi S, Hachiya I, Yamanoi Y (1994) Bull Chem Soc Jpn 67:2342
16. Nafion-Sc (2 g) and sea sand (2 g, 15–20 mesh) were combined and the mixture was
packed in a 6-mm glass tube. A carbonyl compound (0.5 mmol) and tetreallyltin
(0.5 mmol) were dissolved in acetonitrile (4 ml) and passed through the column using
a peristaltic pump (EYELA, MP-3)
17. (a) Takahashi H, Kawakita T, Ohno M, Yoshioka M, Kobayashi S (1992) Tetrahedron Lett
48:5691. (b) Corey EJ, Imwinkelried R, Pikul S, Xiang YB (1991) J Am Chem Soc 111:5493
18. PA-Sc-TAD (3) is fully characterized by elementary analysis. 3: C, 23.51; H, 3.62; N, 3.33;
F, 12.5; S, 6.74; Sc, 2.0%
20. Reviews: (a) Thompson LA, Ellman JA (1996) Chem Rev 96:555. (b) Früchtel JS, Jung G
(1996) Angew Chem Int Ed Engl 35:17. (c) Terrett NK, Gardner M, Gordon DW, Kobylecki
RJ, Steele J (1995) Tetrahedron 51:8135. (d) Lowe G (1995) Chem Soc Rev 37:309. (e) Gal-
lop MA, Barrett RW, Dower WJ, Fodor SPA, Gordon EM (1994) J Med Chem 37:1233. (f)
Gordon EM, Barrett RW, Dower WJ, Fodor SPA, Gallop MA (1994) J Med Chem 37:1385
21. Electron-deficient dienophiles will not work under the conditions, because the present
reactions are based on inverse electron-demand aza-Diels–Alder reactions
22. Kobayashi S, Nagayama S, Busujima T (1996) Tetrahedron Lett 37:9221
23. For example, (a) Bailar JC Jr (1974) Catal Rev Sci Eng 10:17. (b) Pittman CU, Jacobson
SE (1978) J Mol. Catal 3:293. (c) Dawans F, Morel D (1978) ibid. 3:403. (d) Carlini C,
Braca G, Ciardelli F, Sbrana G (1977) ibid. 2:379. (e) Capka M, Svoboda P, Cerny M, Het-
flejs J (1971) Tetrahedron Lett 3787. (f) Brown JM, Morinari H (1979) Tetrahedron Lett
2933. (g) Pinna F, Bonivento M, Strukul G, Graziani M, Cernia E, Palladino N (1976) J
Mol Catal 1:309
24. Kobayashi S, Nagayama S (1997) Synlett 653
25. For example, Yamaguchi M (1991) In: Trost BM (ed) Comprehensive organic synthesis,
vol 1. Pergamon, New York, chap 1.11
26. (a) Kobayashi S, Nagayama S (1997) J Org Chem 62:232. (b) Kobayashi S, Nagayama S
(1997) J Am Chem Soc 119:10049
27. Ciardelli F, Tsuchida E, Wöhrle D (eds) (1996) Macromolecule-metal complexes.
Springer, Berlin Heidelberg New York
28. Donbrow M (1992) Microcapsules and nanoparticles in medicine and pharmacy. CRC
Press, Boca Raton
29. Marty JJ, Oppenheim RC, Speiser P (1978) Pharm Acta Helv 53:17; Kreuter J (1978)
Pharm Acta Helv 53:33
30. (a) Greoffrey F, Cloke N (1995) In: Lappert MF (ed) Comprehensive organometallic
chemistry II. Pergamon, Oxford, vol 4, p 1. (b) Edelmann FT (1995) In: Lappert MF (ed)
Comprehensive organometallic chemistry II. Pergamon, Oxford, vol 4, p 11
32. Judging from the recovered Sc(OTf)3 (0.080 g), 0.120 g of Sc(OTf)3 was microencapsulat-
ed according to this procedure. The weight of the capsules was 1.167 g which contained
acetonitrile. MC Sc(OTf)3 thus prepared can be stored at rt for more than a few months
33. IR (KBr) 3062, 3030 (vCH), 1946, 1873, 1805 (dCH), 1601, 1493 (benzene rings). 1255
(vasSO2), 1029 (vsSO2), 756 (vC-S), 696 (vS-O) cm–l. Cf. Sc(OTf)3: 1259 (vasSO2), 1032
(vsSO2), 769 (vC-S), 647 (vS-O) cm–l; polystyrene: 3062, 3026 (vCH), 1944, 1873, 1803
(dCH), 1600, 1491 (benzene rings) cm–l
34. Nitromethane was used in Friedel–Crafts acylation (Scheme 28)
35. Although the origin of the high activity of MC Sc(OTf)3 is not clear at this stage, it was
reported that aldimine–Lewis acid complexes were stabilized by using a polymer-sup-
ported Lewis acid. Cf. [24]
36. Cf. Ugi I, Domling A, Hörl W (1994) Endeavour 18:115; Armstrong RW, Combs AP, Tem-
pest PA, Brown SD, Keating TA (1996) Acc Chem Res 29:123
37. For leading references on Friedel–Crafts acylation, Olah GA (1973) Friedel–Crafts
chemistry. Wiley-Interscience, New York; Heaney H (1991) In: Trost BM (ed) Compre-
hensive organic synthesis. Pergamon, Oxford, vol 2, p 733; Olah GA, Krishnamurti R,
Prakash GKS (1991) In: Trost BM (ed) Comprehensive organic synthesis. Pergamon,
Oxford, vol 3, p 293
38. Kobayashi S, Nagayama S, Endo M, unpublished results
Lanthanide Triflate-Catalyzed Carbon-Carbon
Bond-Forming Reactions in Organic Synthesis
Shu Kobayashi

Bunkyo-ku, Tokyo 113–0033, Japan E-mail: [email protected]
Versatile carbon-carbon bond-forming reactions using lanthanide triflates (Ln(OTf)3) as

catalysts are discussed. Lanthanide triflates are new types of Lewis acids different from typ-
ical Lewis acids such as AlCl3, BF3, SnCl4, etc. While most Lewis acids are decomposed or
deactivated in the presence of water, lanthanide triflates are stable and works as Lewis acids
in water solutions. Many nitrogen-containing compounds such as imines and hydrazones
are also successfully activated by using a small amount of Ln(OTf)3. Lanthanide triflates are
also excellent Lewis acid catalysts in organic solvents. A catalytic amount of Ln(OTf)3 is
enough to complete reactions in most cases. In addition, Ln(OTf)3 can be recovered after
reactions are completed and can be reused. Several chiral lanthanide catalysts for asymmet-
ric Diels-Alder, aza Diels-Alder, and 1,3-dipolar cycloaddition reactions are also described.
Keywords: Lanthanide triflate, Lewis acid, Carbon-carbon bond formation, Asymmetric

synthesis, Catalysis, Organic synthesis
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
2 Aldol Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
2.1 Aldol Reactions in Aqueous Media . . . . . . . . . . . . . . . . . . . 65

2.2 Recovery and Reuse of the Catalyst . . . . . . . . . . . . . . . . . . 72
2.3 Aldol Reactions in Organic Solvents . . . . . . . . . . . . . . . . . . 72
2.4 Aldol Reactions in Micellar Systems . . . . . . . . . . . . . . . . . . 75
3 Diels-Alder Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . 77
4 Allylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
5 Mannich-Type Reactions . . . . . . . . . . . . . . . . . . . . . . . . 81
5.1 Reactions of Imines with Silyl Enolates . . . . . . . . . . . . . . . . 81

5.2 One-Pot Synthesis of b-Amino Esters from Aldehydes . . . . . . . 83
5.3 Use of Acylhydrazones as Electrophiles
in Mannich-Type Reactions . . . . . . . . . . . . . . . . . . . . . . . 86
5.4 Aqueous Mannich-Type Reaction . . . . . . . . . . . . . . . . . . . 89
64 Shu Kobayashi
6 Aza Diels-Alder Reactions . . . . . . . . . . . . . . . . . . . . . . . . 91
6.1 Reactions of Imines with Dienes or Alkenes . . . . . . . . . . . . . . 91

6.2 Three-Components Coupling Reactions of Aldehydes,
Amines, and Dienes or Alkenes . . . . . . . . . . . . . . . . . . . . . 93
6.3 Reaction Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
7 Asymmetric Diels-Alder Reactions . . . . . . . . . . . . . . . . . . . 98
8 Asymmetric Aza Diels-Alder Reactions . . . . . . . . . . . . . . . . . 106
9 Catalytic Enantioselective 1,3-Dipolar Cycloadditions . . . . . . . . 109
10 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
11 References and Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
1
Introduction
Lewis acid-catalyzed carbon-carbon bond forming reactions have been of great
interest in organic synthesis because of their unique reactivities, selectivities,
and for the mild conditions used [1]. While various kinds of Lewis acid-promot-
ed reactions have been developed and many have been applied in industry, these
reactions must be carried out under strict anhydrous conditions. The presence
of even a small amount of water stops the reaction because most Lewis acids im-
mediately react with water rather than the substrates and decompose or deacti-
vate, and this has restricted the use of Lewis acids in organic synthesis.
On the other hand, lanthanide compounds were expected to act as strong
Lewis acids because of their hard character and to have strong affinity toward
carbonyl oxygens [2]. Among these compounds, lanthanide triflates (Ln(OTf)3)
were expected to be one of the strongest Lewis acids because of the electron-
withdrawing trifluoromethanesulfonyl group. Their hydrolysis was postulated
to be slow, based on their hydration energies and hydrolysis constants [3]. In
fact, while most metal triflates are prepared under strict anhydrous conditions,
Lanthanide triflates are reported to be prepared in aqueous solution [4, 5]. The
large radius and the specific coordination number of lanthanide(III) are also
unique, and many investigations using Ln(OTf)3 as Lewis acids have been per-
formed.
In this paper, use of Ln(OTf)3 as Lewis acid catalysts in carbon-carbon bond-
forming reactions in both aqueous and organic solvents is overviewed.
Lanthanide Triflate-Catalyzed Carbon-Carbon Bond-Forming Reactions in Organic Synthesis 65
2
Aldol Reactions
2.1
Aldol Reactions in Aqueous Media
The titanium tetrachloride-mediated aldol reaction of silyl enol ethers with al-
dehydes was first reported in 1973 [6]. The reaction is notably distinguished
from the conventional aldol reactions carried out under basic conditions; it pro-
ceeds in a highly regioselective manner to afford cross aldols in high yields [7].
Since this pioneering effort, several efficient activators such as trityl salts [8],
Cray montmorillonite [9], fluoride anions [10], etc. [11] have been developed to
realize high yields and selectivities, and now the reaction is considered to be one
of the most important carbon-carbon bond forming reactions in organic syn-
thesis. These reactions are usually carried out under strictly anhydrous condi-
tions. The presence of even a small amount of water causes lower yields, proba-
bly due to the rapid decomposition or deactivation of the promoters and the hy-
drolysis of the silyl enol ethers. Furthermore, the promoters cannot be recovered
and reused because they decompose under usual quenching conditions.
On the other hand, the water-promoted aldol reaction of silyl enol ethers with
aldehydes was reported in 1986 [12]. While the report that the aldol reactions
proceeded without catalyst in water was unique, the yields and the substrate
scope were not satisfactory. In 1991 the first example of Lewis acid catalysis in
aqueous media was reported; that is the hydroxymethylation reaction of silyl
enol ethers with commercial formaldehyde solution using Ln(OTf)3. Formalde-
hyde is a versatile reagent as one of the most highly reactive C1 electrophiles in
organic synthesis [13]. Dry gaseous formaldehyde required for many reactions
has some disadvantages because it must be generated before use from solid pol-
ymer paraformaldehyde by way of thermal depolymerization and it itself-po-
lymerizes easily [14]. On the other hand, commercial formaldehyde solution,
which is an aqueous solution containing 37% formaldehyde and 8–10% metha-
nol, is cheap, easy to handle, and stable even at room temperature. However, the
use of this reagent is strongly restricted due to the existence of a large amount of
water. For example, the titanium tetrachloride (TiCl4)-promoted hydroxymeth-
ylation reaction of silyl enol ethers was carried out by using trioxane as a HCHO
source under strict anhydrous conditions [6b, 15]. Formaldehyde water solution
could not be used because TiCl4 and the silyl enol ether reacted with water rather
than HCHO in that water solution.
The effects of Ln(OTf)3 in the reaction of 1-phenyl-1-trimethylsiloxypropene
(1) with commercial formaldehyde solution were examined [16]. In most cases
the reactions proceeded smoothly to give the corresponding adducts in high
yields. The reactions were most effectively carried out in commercial formalde-
hyde solution-THF media under the influence of a catalytic amount of Yb(OTf)3.
Several examples of the hydroxymethylation reaction of silyl enol ethers with
commercial formaldehyde solution are shown in Table 1, and the following char-
66 Shu Kobayashi
Table 1. Reaction of silyl enol ethers with commercial formaldehyde solution catalyzed by
Yb(OTf)3
Entry Silyl enol ether Product Yield/%
1 94
2 85
3 77
4 82
5 86
6 92
7 92
8 88
9 83
10 90
a Z/E=>98/2.
b Z/E=1/4.
c The mixture of the hydroxy thioester and the lactone (2:1) was obtained. The other dias-
tereomers were not observed.
d The mixture of the hydroxy thioester and lactone (3:1) was obtained. Less than 3% yield of
the other diastereomers was observed.
Table 2. Effect of Lanthanide Triflates

Ln(OTf ) 3 Yield/% Ln(OTf) 3 Yield/%
La(OTf) 3 8 Dy(OTf) 3 73
Pr(OTf) 3 28 Ho(OTf) 3 47
Nd(OTf) 3 83 Er(OTf) 3 52
Sm(OTf) 3 46 Tm(OTf) 3 20
Eu(OTf) 3 34 Yb(OTf) 3 91
Gd(OTf) 3 89 Lu(OTf) 3 88
acteristic features of this reaction are noted. (1) In every case, the reactions pro-
ceeded smoothly under extremely mild conditions (almost neutral) to give the
corresponding hydroxymethylated adducts in high yields. Sterically hindered
silyl enol ethers also worked well and the diastereoselectivities were high. (2) Di-
and poly-hydroxymethylated products were not observed [17]. (3) The absence
of equilibrium (double bond migration) in silyl enol ethers allowed for a re-
giospecific hydroxymethylation reaction. (4) Only a catalytic amount of
Yb(OTf)3 was required to complete the reaction. The amount of the catalyst was
examined by taking the reaction of 1 with commercial formaldehyde solution as
a model, and the reaction was found to be catalyzed by even 1 mol% of
Yb(OTf)3: 1 mol% (90% yield); 5 mol% (90% yield); 10 mol% (94% yield);
20 mol% (94% yield); 100 mol% (94% yield).
The use of Ln(OTf)3 in the activation of aldehydes other than formaldehyde
was also investigated [18]. The model reaction of 1-trimethylsiloxycyclohexene
(2) with benzaldehyde under the influence of a catalytic amount of Yb(OTf)3
(10 mol%) was examined. The reaction proceeded smoothly in H2O-THF (1:4),
but the yields were low when water or THF was used alone. Among several
Ln(OTf)3 screened, neodymium triflate (Nd(OTf)3), gadolinium triflate
(Gd(OTf)3), Yb(OTf)3, and lutetium triflate (Lu(OTf)3) were quite effective,
while the yield of the desired aldol adduct was lower in the presence of lantha-
num triflate (La(OTf)3), praseodymium triflate (Pr(OTf)3) or thulium triflate
(Tm(OTf)3) (Table 2).
Lanthanide triflates were found to be effective for the activation of formalde-
hyde water solution. The effect of ytterbium salts was also investigated (Table 3)
[19]. While the Yb salts with less nucleophilic counter anions such as OTf– or
ClO4– effectively catalyzed the reaction, only low yields of the product were ob-
tained when the Yb salts with more nucleophilic counter anions such as Cl–,
OAc–, NO3–, and SO42– were employed. The Yb salts with less nucleophilic coun-
68 Shu Kobayashi
Table 3. Effect of Yb salts

Yb salt Yield/%
Yb(OTf)3 91 a)
b)
Yb(ClO)4 88
YbCl3 3
Yb(OAc)3•8H2O 14
Yb(NO3)3•5H2O 7
Yb2(SO4)3•5H2O trace
a syn/anti = 73/27
b 76/24
ter anions are more cationic and the high Lewis acidity promotes the desired re-
action.
Several examples of the present aldol reaction of silyl enol ethers with alde-
hydes are listed in Table 4. In every case, the aldol adducts were obtained in high
yields in the presence of a catalytic amount of Yb(OTf)3, Gd(OTf)3, or Lu(OTf)3
in aqueous media. Diastereoselectivities were generally good to moderate. One
feature in the present reaction is that water soluble aldehydes, for instance,
acetaldehyde, acrolein, and chloroacetaldehyde, can be reacted with silyl enol
ethers to afford the corresponding cross aldol adducts in high yields (entries 5–
7). Some of these aldehydes are commercially supplied as water solutions and
are appropriate for direct use. Phenylglyoxal monohydrate also worked well
(entry 8). It is known that water often interferes with the aldol reactions of metal
enolates with aldehydes and that in the cases where such water soluble aldehydes
are employed, some troublesome purifications including dehydration are neces-
sary. Moreover, salicylaldehyde (entry 9) and 2-pyridinecarboxaldehyde
(entry 10) could be successfully employed. The former has a free hydroxy group
which is incompatible with metal enolates or Lewis acids, and the latter is gen-
erally difficult to use under the influence of Lewis acids because of the coordina-
tion of the nitrogen atom to the Lewis acids resulting in the deactivation of the
acids.
The aldol reactions of silyl enol ethers with aldehydes were also found to pro-
ceed smoothly in water-ethanol-toluene [20]. Some reactions proceeded much
faster in this solvent system than in THF-water. Furthermore, the new solvent
system realized continuous use of the catalyst by a very simple procedure.
Several water-organic solvent systems were examined in the model reaction
of 1-phenyl-1-trimethylsiloxypropene (1) with 2-pyridinecarboxaldehyde un-
Table 4. Lanthanide triflate-catalyzed aldol reactions in aqueous media

Entry Aldehyde Silyl Enol Ether Yield/%
1 91 a)
2 89 b)
3 93 c)
4 81 d)
5 93 e, f)
6 82 e, g)
7 95 h)
8 67 i)
9 81 j, k)
10 87 j, l)
a syn/anti=73/27. g syn/anti=60/40.
b syn/anti=63/37. h syn/anti=45/55.
c syn/anti=71/29. i syn/anti=27/73.
d syn/anti=53/47. j Lu(OTf) was used instead of Yb(OTf)3.
3
e Gd(OTf) was used instead of Yb(OTf)3. k syn/anti=55/45.
3
f syn/anti=46/54. l syn/anti=42/58.
70 Shu Kobayashi
OH O
CHO OSiMe3 Yb(OTf) 3 (10 mol%)
+ Ph
N Ph solvent, rt, 4 h
N
Table 5. Effect of solvents

Solvent Yield / % syn /anti
H 2 O / Toluene ( 1 : 4) 0
H 2 O / EtOH / Toluene (1 : 3 : 4) 30 37 / 63
(1 : 5 : 4) 41 39 / 61
(1 : 7 : 4) 70 41 / 59
(1 : 10 : 4) 96 40 / 60
H2 O / THF ( 1 : 4) 12 43 / 57
der the influence of 10 mol% Yb(OTf)3 (Table 5). While the reaction proceeded
sluggishly in a water-toluene system, the adduct was obtained in a good yield
when ethanol was added to this system. The yield increased in accordance with
the amount of ethanol, and it was noted that the reaction proceeded much faster
in the water-ethanol-toluene system than in the original water-THF system.
Although the water-ethanol-toluene (1:7:4) system was one phase, it easily be-
came two phases by adding toluene after the reaction was completed. The prod-
uct was isolated from the organic layer by a usual work up. On the other hand,
the catalyst remained in the aqueous layer, which was used directly in the next
reaction without removing water. It is noteworthy that the yields of the second,
third, and fourth runs were comparable to that of the first run (Eq. 1).
(1)
1st run: 86% (syn /anti = 38/62)
2nd run: 82% (syn /anti = 38/62)
3rd run: 90% (syn /anti = 38/62)
4th run: 82% (syn /anti = 39/61)
Several examples of the present aldol reactions of silyl enol ethers with alde-
hydes in water-ethanol-toluene are listed in Table 6. 3-Pyridinecarboxaldehyde
as well as 2-pyridinecarboxaldehyde, salicylaldehyde, and formaldehyde water
Table 6. b(OTf)3-catalyzed aldol reactions of silyl enol ethers with aldehydes in water-etha-
nol-toluene
Aldehyde Silyl Enol Ether Product Yield / %
a)
89
95
87
82
96
90
a syn/anti=74/26.
solution worked well. As for silyl enol ethers, not only ketone enol ethers but also
silyl enolates derived from thioesters were used. In every case, the adducts were
obtained in high yields in the presence of 10 mol% Yb(OTf)3.
72 Shu Kobayashi
reaction mixture
water (quench)
(extraction)
organic layer aqueous layer
(purification) (removal of water)
product Ln(OTf)3
Scheme 1
2.2
Recovery and Reuse of the Catalyst
While continuous use of Ln(OTf)3 is possible, it is also easy to recover Ln(OTf)3

themselves. Lanthanide triflates are more soluble in water than in organic sol-
vents such as dichloromethane. Almost 100% of Ln(OTf)3 was quite easily recov-
ered from the aqueous layer after the reaction was completed and it could be re-
used. For example, first use (20 mol% of Yb(OTf)3) in the reaction of 1 with for-
maldehyde water solution (94% yield); second use (91% yield); third use (93%
yield). The reactions are usually quenched with water and the products are ex-
tracted with an organic solvent (for example, dichloromethane). Lanthanide tri-
flate is in aqueous layer and only removal of water gives the catalyst which can
be used in the next reaction (Scheme 1). It is noteworthy that lanthanide triflates
are expected to solve some severe environmental problems induced by Lewis
acid-promoted reactions in industrial chemistry [21].
2.3
Aldol Reactions in Organic Solvents
Lanthanide triflates were found to be excellent Lewis acids not only in aqueous
media but also in organic solvents. The reaction of ketene silyl acetal 3 with ben-
zaldehyde proceeded smoothly in the presence of 10 mol% of Yb(OTf)3 in
dichloromethane at –78 °C, to afford the corresponding aldol-type adduct in a
94% yield. The same reaction at room temperature also went quite cleanly with-
out side reactions and the desired adduct was obtained in a 95% yield. No adduct
Ln(OTf)3 (10 mol%) OH O

R3 OSiMe3 CH2Cl2, rt, 16 h
1
R CHO +
75-100 % (1st run) R1 R2
R4 R2 77-100 % (2nd run) R3 R4
Ln(OTf)3 (10 mol%) OMe O

R3 OSiMe3 CH2Cl2, rt, 16 h
R1CH(OMe)2 +
88-94 % (1st run) R 1 R2
R4 R2 90-92 % (2nd run) 3
R R 4
Scheme 2
Table 7. Effect of catalysts

Entry Catalyst Yield/%
1 Sc(OTf) 3 81
2 Y(OTf) 3 trace
3 Yb(OTf) 3 trace
was obtained in THF-water or toluene-ethanol-water, because hydrolysis of the

ketene silyl acetal preceded the desired aldol reaction in such solvents. In other
organic solvents such as toluene, THF, acetonitrile, and DMF, Yb(OTf)3 worked
well, and it was found that other Ln(OTf)3 also catalyzed the above aldol reac-
tion effectively (85–95% yields).
Silyl enolates derived from not only esters but also thioesters and ketones re-
acted with aldehydes to give the corresponding adducts in high yields
(Scheme 2) [22]. Furthermore, acetals reacted smoothly with silyl enolates to af-
ford the corresponding aldol-type adducts in high yields. It should be noted that
the catalysts could be easily recovered from the aqueous layer after the reactions
were quenched with water and could be reused, and that the yields of the second
run were almost comparable to those of the first run in every case.
Scandium triflate (Sc(OTf)3) was found to be an effective catalyst in the aldol
reactions [23]. The activities of various triflate catalysts were evaluated in the al-
dol reaction of 1-trimethylsiloxycyclohexene (2) with benzaldehyde in dichlo-
romethane (Table 7). While the reaction scarcely proceeded at –78 °C in the
presence of Yb(OTf)3 or Y(OTf)3 [24], the aldol adduct was obtained in an 81%
74 Shu Kobayashi
Sc(OTf)3 (5 mol%) OH O
OSiMe3 CH2Cl2, -78 °C
CHO +
Ph Ph OMe
OMe 80%
3
Sc(OTf)3 (5 mol%)
OMe OSiMe3 CH2Cl2 OMe O
+
Ph OMe OMe -78 °C; 0% Ph OMe
3 0 °C to rt; 97%
Scheme 3
yield in the presence of Sc(OTf)3. Obviously Sc(OTf)3 is more active than

Y(OTf)3 or Yb(OTf)3 in this case.
Several examples of the Sc(OTf)3-catalyzed aldol reactions of silyl enolates
with aldehydes were examined, and it was found that silyl enolates derived from
ketones, thioesters, and esters reacted smoothly with aldehydes in the presence
of 5 mol% of Sc(OTf)3 to afford the aldol adducts in high yields. Sc(OTf)3 was
also found to be an effective catalyst in the aldol-type reaction of silyl enolates
with acetals. The reactions proceeded smoothly at –78 °C or room temperature
to give the corresponding aldol-type adducts in high yields without side reac-
tion products. It should be noted that aldehydes were more reactive than acetals
[25]. For example, while 3-phenylpropionaldehyde reacted with the ketene silyl
acetal of methyl 2-methylpropionate (3) at –78 °C to give the aldol adduct in an
80% yield, no reaction occurred at –78 °C in the reaction of the same ketene silyl
acetal with 3-phenylpropionaldehyde dimethylacetal. The acetal reacted with
the ketene silyl acetal at 0 °C to room temperature to give the aldol-type adduct
in a 97% yield (Scheme 3).
Sc(OTf)3 can behave as a Lewis acid catalyst even in aqueous media. Sc(OTf)3
was stable in water and was effective in the aldol reactions of silyl enolates with
aldehydes in aqueous media. The reactions of usual aromatic and aliphatic alde-
hydes such as benzaldehyde and 3-phenylpropionaldehyde with silyl enolates
were carried out in both aqueous and organic solvents, and water-soluble formal-
dehyde and chloroacetaldehyde were directly treated as water solutions with silyl
enolates to afford the aldol adducts in good yields. Moreover, the catalyst could
be recovered almost quantitatively from the aqueous layer after the reaction was
completed. The recovered catalyst was also effective in the second reaction, and
the yield of the second run was comparable to that of the first run (Eq. 2).
Sc(OTf)3 (5 mol%) OH O
OSiMe3 CH2Cl2, -78 °C, 1 h
PhCHO + (2)
88% (1st run) Ph OMe
OMe
3 89% (2nd run)
2.4
Aldol Reactions in Micellar Systems
Sc(OTf)3-catalyzed aldol reactions of silyl enol ethers with aldehydes were suc-
cessfully carried out in micellar systems. While the reactions proceeded sluggishly
in pure water, remarkable enhancement of the reactivity was observed in the pres-
ence of a small amount of a surfactant. In these systems, versatile carbon-carbon
bond-forming reactions proceeded in water without using any organic solvents.
Lewis acid catalysis in micellar systems was first found in the model reaction
of 1 with benzaldehyde (Table 8) [26]. While the reaction proceeded sluggishly
in the presence of 0.2 equiv. Yb(OTf)3 in water, remarkable enhancement of the
reactivity was observed when the reaction was carried out in the presence of
0.2 equiv. Yb(OTf)3 in an aqueous solution of sodium dodecylsulfate (SDS,
0.2 equiv., 35 mmol/l), and the corresponding aldol adduct was obtained in a
50% yield. In the absence of the Lewis acid and the surfactant (water-promoted
conditions), only 20% yield of the aldol adduct was isolated after 48 h, while a
33% yield of the aldol adduct was obtained after 48 h in the absence of the Lewis
acid in an aqueous solution of SDS. The amounts of the surfactant also influ-
Table 8. Effect of Ln(OTf)3 and surfactants

Ln(OTf)3 /eq. Surfactant/equiv. Time/h Yield/%
Yb(OTf) 3 /0.2 48 17
Yb(OTf) 3 /0.2 SDS/0.04 48 12
Yb(OTf) 3 /0.2 SDS/0.1 48 19
Yb(OTf) 3 /0.2 SDS/0.2 48 50
Yb(OTf) 3 /0.2 SDS/1.0 48 22
Sc(OTf) 3 /0.2 SDS/0.2 17 73
Sc(OTf) 3 /0.1 SDS/0.2 4 88
Sc(OTf) 3 /0.1 TritonX-100 a)/0.2 60 89
Sc(OTf) 3 /0.1 CTAB/0.2 4 trace
76 Shu Kobayashi
Table 9. Sc(OTf)3-catalyzed aldol reactions in micellar systems
Aldehyde Silyl Enol Ether Yield/%
88 a)
86 b)
88 c)
82 d)
88 e)
75 f,g)
94
84 g)
a syn/anti=50/50. e syn/anti=57/43.
b syn/anti=45/55. f Sc(OTf)3 (0.2 equiv.) was used.
c syn/anti=41/59. g Additional silyl enolate (1.5 equiv.) was
d Commercially available HCHO aq. (3 ml), charged after 6 h.
1 (0.5 mmol), Sc(OTf)3 (0.1 mmol), and
SDS (0.1 mmol) were combined.
enced the reactivity and the yield was improved when Sc(OTf)3 was used as a
Lewis acid catalyst. Judging from the critical micelle concentration, micelles
would be formed in these reactions, and it is noteworthy that the Lewis acid-cat-
alyzed reactions proceeded smoothly in micellar systems [27]. It was also found
that the surfactants influenced the yield, and that TritonX-100 was effective in
the aldol reaction (but required long reaction time), while only a trace amount
of the adduct was detected when using cetyltrimethylammonium bromide
(CTAB) as a surfactant [28].
Several examples of the Sc(OTf)3-catalyzed aldol reactions in micellar sys-

tems are shown in Table 9. Not only aromatic, but also aliphatic and a,b-unsatu-
rated aldehydes reacted with silyl enol ethers to afford the corresponding aldol
adducts in high yields. Formaldehyde water solution also worked well. Ketene si-
lyl acetal 3, which is known to hydrolyze very easily even in the presence of a
small amount of water, reacted with an aldehyde in the present micellar system
to afford the corresponding aldol adduct in a high yield.
It should be noted that the reactions were successfully carried out in water
without using any organic solvents. Use of the reusable scandium catalyst and
water as a solvent would result in clean and environmentally friendly systems.
3
Diels-Alder Reactions
Although many Diels-Alder reactions have been carried out at higher reaction
temperatures without catalysts, heat sensitive compounds in complex and mul-
tistep syntheses cannot be employed. While Lewis acid catalysts allow the reac-
tions to proceed at room temperature with satisfactory yields, they are often ac-
companied by diene polymerization and excess amounts of the catalyst are often
needed to catalyze carbonyl-containing dienophiles [29].
Lanthanide triflates were also found to be efficient catalysts in the Diels-Alder
reactions of carbonyl-containing dienophiles with cyclopentadiene [30]. A catalytic
amount of Yb(OTf)3 was enough to promote the reactions to give the correspond-
ing adducts in high yields, and the catalyst could be easily recovered and reused.
In the Diels-Alder reactions, Sc(OTf)3 was clearly the most effective among
Ln(OTf)3 as a catalyst [31]. While in the presence of 10 mol% of Y(OTf)3 or
Yb(OTf)3, only a trace amount of the adduct was obtained in the Diels-Alder re-
action of MVK with isoprene, and the reaction proceeded quite smoothly to give
the adduct in a 91% yield in the presence of 10 mol% of Sc(OTf)3.
Several examples of the Sc(OTf)3-catalyzed Diels-Alder reactions are shown
in Table 10. In every case, the Diels-Alder adducts were obtained in high yields
with endo selectivities.
The present Diels-Alder reactions proceeded even in aqueous media (Eq. 3)
[32]. Thus, naphthoquinone reacted with cyclopentadiene in THF-H2O (9:1) at
room temperature to give the corresponding adduct in a 93% yield (endo/exo=
100/0).
O
Sc(OTf)3 (10 mol%) O
+ (3)
THF : H2O ( 9 : 1 )
O O
93% yield, endo/exo = 100/ 0
Recovery and reuse of the catalyst were also possible in this reaction. After the
reaction was completed, the aqueous layer was concentrated to give the catalyst.
The recovered catalyst was effective in subsequent Diels-Alder reactions, and it
78 Shu Kobayashi
Table 10. Sc(OTf)3-catalyzed Diels-Alder reactions

Dienophile Diene Product Yield /% endo/ exo
O O
O
95 87 / 13
N O O
CON
O
89 100 / 0
CON O
O
90
CON O
O
86
CON O
O O
O
97 84 / 16
N O O
CON
O
96 89 / 11
O
83 >95 / 5
O
O
91
O
73
O
O
83 100 / 0
O
O
O
89 94 / 3
O
O
92
O
should be noted that the yields of the second and even the third runs were com-
parable to that of the first run.
4
Allylation Reactions
Synthesis of homoallylic alcohols by the reaction of allyl organometallics with

carbonyl compounds is one of the most important processes in organic synthe-
sis [33]. The allylation reactions of carbonyl compounds were found to proceed
smoothly under the influence of 5 mol% of Sc(OTf)3 [34] by using tetraallyltin
[35] as an allylating reagent [36]. Several examples are shown in Table 11. The
reactions proceeded smoothly in the presence of only a catalytic amount of
Sc(OTf)3 under extremely mild conditions [8], and the adducts, homoallylic al-
cohols, were obtained in high yields. Ketones could also be used in the reaction
(entries 4, 5). In most cases, the reactions were successfully carried out in aque-
ous media. It is noteworthy that unprotected sugars reacted directly to give the
adducts in high yields (entries 7–9). The allylated adducts are intermediates for
the synthesis of higher sugars [37]. Moreover, an aldehyde containing water of
crystallization such as phenylglyoxal monohydrate reacted with tetraallyltin to
give the di-allylated adduct in high yield (entry 10). Under the present reaction
conditions, salicylaldehyde and 2-pyridinecarboxaldehyde reacted with tetraal-
lyltin to afford the homoallylic alcohols in good yields (entries 11, 12). Under
general Lewis acid conditions, these compounds react with the Lewis acids rath-
er than the nucleophile. Furthermore, several kinds of solvents could be used.
The reactions also proceeded under non-aqueous conditions. Water-sensitive
substrates under Lewis acid conditions could be reacted in an appropriate or-
ganic solvent (entries 13, 14).
Yb(OTf)3 is also effective in the present allylation reactions. For example, 3-
phenylpropionaldehyde reacted with tetraallyltin in the presence of 5 mol% of
Yb(OTf)3 to afford the adduct in a 90% yield.
The water-ethanol-toluene system could be successfully applied to the
present allylation reactions. An example of the allylation reaction of tetraallyltin
with aldehyde is shown in Eq. (4), and in this case continuous use of the catalyst
was also realized.
OH
CHO Sn Yb(OTf)3 (10 mol%)
Ph +
4 Ph
H2O/EtOH/toluene
(1 : 7 : 4) (4)
rt, 8 h
1st run: 90%; 2nd run: 95%; 3rd run: 96%; 4th run: 89%
Furthermore, the Sc(OTf)3-catalyzed allylation reactions of aldehydes with

tetraallyltin proceeded smoothly in micellar systems to afford the correspond-
80 Shu Kobayashi
Table 11. Sc(OTf)3-catalyzed allylation reactions of carbonyl compounds with tetraallyltina)

Entry Carbonyl Compound Product Solvent Yield/%
1 92
96
96
86
94
2 94
82
3 98
94
4 78
5 87
6 82
c)
7 81
d)
89
e)
93
f)
8 89
9 88f)
g)
10 78
Table 11. (continued)

Entry Carbonyl Compound Product Solvent Yield/%
11 quant.
90
quant.
12
84
13 87
14
90
a Carried out at 25 °C except for entries 8 d syn/anti=27/73.

and 9 (60 °C). e syn/anti=26/74.
b The products were isolated after acetlyat- f syn/anti=50/50.
ion. g Diastereomer ratio=88/12. Relative
con-
c syn/anti=28/72. figuration assignment was not made.
ing homoallylic alcohols in high yields. The reactions were successfully carried
out in the presence of a small amount of a surfactant in water without using any
organic solvents.
5
Mannich-Type Reactions
5.1
Reactions of Imines with Silyl Enolates
The Mannich and related reactions provide one of the most fundamental and
useful methods for the synthesis of b-amino ketones or esters. Although the clas-
sical protocols include some severe side reactions, new modifications using pre-
formed iminium salts and imines have been developed [38]. Among them, reac-
tions of imines with enolate components, especially silyl enolates, provide useful
and promising methods leading to b-amino ketones or esters. The first report
using a stoichiometric amount of TiCl4 as a promoter appeared in 1977 [39], and
since then some efficient catalysts have been developed [40].
82 Shu Kobayashi
OSiMe3 Ln(OTf)3 R2
R2 (5 mol%) NH O
N R 3
+ R5
CH2Cl2, 0 °C R1 R5
R1 H R4 R3 R4
Table 12. Reactions of imines with silyl enolates

Imine Silyl enolate Ln Yield/%
Ph OSiMe3
N Yb 97 a)
3
OMe Y 81
Ph H
OSiMe3
Yb 95
SEt
N Ph Yb 86
3
Ph H Y 78
OSiMe3 Yb 65
SEt Sc 80
OSiMe3
Yb 80 b)
OBn
Ph
N
3 Yb 95
H
O OSiMe3
OBn
Yb 67 c)
N Ph
3 Yb 88
H
O
Ts
N
3 Yb 88
Ph H
Ph
N
Ph 3 Yb 60
H
O
N Ph
3 Yb 47
C4H9 H
a Second use=96% yield; third use=98% yield.
b syn/anti=18/82.
c syn/anti=21/79.
In aqueous media, water coordinates lanthanide triflates under equilibrium

conditions, and thus activation of carbonyl compounds using a catalytic amount
of the Lewis acid has been performed. It was expected that, based on the same
consideration, the catalytic activation of imines would be possible by using lan-
thanide triflates.
The reactions of imines with silyl enolates were tested in the presence of
5 mol% of Ln(OTf)3, and selected examples are shown in Table 12 [41]. In most
cases the reactions proceeded smoothly in the presence of 5 mol% of Yb(OTf)3
(a representative lanthanide triflate) to afford the corresponding b-amino ester
derivatives in good to high yields. Yttrium triflate (Y(OTf)3) was also effective,
and the yield was improved when Sc(OTf)3 was used instead of Yb(OTf)3 as a
catalyst. Not only silyl enolates derived from esters, but also that derived from a
thioester, worked well to give the desired b-amino esters and thioester in high
yields. In the reactions of the silyl enolate derived from benzyl propionate, anti
adducts were obtained in good selectivities. In addition, the catalyst could be re-
covered after the reaction was completed and could be reused.
5.2
One-Pot Synthesis of β-Amino Esters from Aldehydes
While the Lewis acid-catalyzed reactions of imines with silyl enolates are one of
the most efficient methods for the preparation of b-amino esters, many imines
are hygroscopic, unstable at high temperatures, and difficult to purify by distil-
lation or column chromatography. It is desirable from a synthetic point of view
that imines, generated in situ from aldehydes and amines, immediately react
with silyl enolates and provide b-amino esters in a one-pot reaction. However,
most Lewis acids cannot be used in this reaction because they decompose or de-
activate in the presence of the amines and water that exist during imine forma-
tion. Due to the unique properties of Ln(OTf)3, their use as catalysts for the
above one-pot preparation of b-amino esters from aldehydes was planned.
A general scheme of the one-pot synthesis of b-amino esters from aldehydes
is shown in Scheme 4 [42]. In the presence of a catalytic amount of Yb(OTf)3 and
an additive (a dehydrating reagent such as MS 4 A or MgSO4), an aldehyde was
treated with an amine and then with a silyl enolate in the same vessel. Several
examples are shown in Tables 13 and 14, and the following characteristic fea-
tures of this reaction are noted.
1. In every case, b-amino esters were obtained in high yields. Silyl enolates de-
rived from esters as well as thioesters reacted smoothly to give the adducts.
R2
R3 OSiMe3 Yb(OTf)3 (5-10 mol%) NH O
R1CHO + R2NH 2 +
R4 R5 Additive, CH2Cl2, rt R1 R5
R3 R4
Scheme 4
84 Shu Kobayashi
Table 13. One-pot synthesis of b-amino esters from aldehydes

Entry R1 R2 Silyl enolate Additive a) Yield/%
MS4A 90
1 Ph Ph
MgSO4 89
2 Ph Bn MS4A 85
3 Ph p-MeOPh MgSO4 91 b)
4 Ph o-MeOPh MS4A 96
5 Ph Ph MS4A 90
6 Ph Bn MS4A 62 b)
p-MeOPh 79
7 Ph MS4A
84,b) 87 b,c)
8 Ph C4H9 MS4A 89
9 PhCO d) Ph MgSO4 82
10 PhCO d) Ph MgSO4 87
11 PhCH=CH p-MeOPh MgSO4 92 e)
12 Ph(CH2)2 Bn MgSO4 83 f)
13 C4H9 Bn MgSO4 77 f)
14 C8H17 Bn MgSO4 81 f)
15 C8H17 Ph 2CH MgSO4 89 g)

a MS4A or MgSO4 was used. Almost compa- d Monohydrate.
rable yields were obtained in each case. e C H CN, –78 °C.
2 5
b CH CN was used as a solvent. f –78 to 0 °C.
3
c Sc(OTf) was used instead of Yb(OTf) . g 0 °C.
3 3
No adducts between aldehydes and the silyl enolates were observed in any re-
action.
2. A silyl enol ether derived from a ketone also worked well to afford the b-ami-
no ketone in a high yield (Table 13, entry 10).
3. Aliphatic aldehydes reacted with amines and silyl enolates to give the corre-
sponding b-amino esters in high yields. In some reactions of imines, it is
known that aliphatic enolizable imines prepared from aliphatic aldehydes
gave poor results.
R2
R3 OSiMe3 Yb(OTf)3 (5-10 mol%) NH O
1
R CHO + R 2NH
2
+
4 MS4A, C2H5CN, -78 °C
R R1 R4
R3
Table 14. Diastereoselective one-pot synthesis of b-amino esters from aldehydes

Entry R1 R2 Silyl enolate Yield/% syn / anti a
OSiMe3
1 Ph Bn 90 1 / 13.3
OMe
OTBS
2 Ph Bn 78 1 / 9.0
TBSO OMe
BnO OSiMe3
3 Ph(CH2) 2 Ph2CH 88 8.1 / 1
OMe
BnO OSiMe3
4 C4H9 Ph2CH 90 8.1 / 1
OMe
BnO OSiMe3
5 (CH3)2CHCH2 Ph2CH 86 7.3 / 1
OMe
a Determined by 1H NMR analysis.
4. Phenylglyoxal monohydrate also worked well in this reaction. The imine de-
rived from phenylglyoxal is unstable and a troublesome treatment is known
to be required for its use [43].
5. The catalyst could be recovered after the reaction was completed and could be
reused (first run, 91%; second run, 92%, in the reaction of benzaldehyde, p-
anisidine, and silyl enolate 3 (Table 13, entry 3)).
6. As for the diastereoselectivity of this reaction, good results were obtained af-
ter examination of the reaction conditions. While anti adducts were produced
preferentially in the reactions of benzaldehyde, syn adducts were obtained
with high selectivities in the reactions of aliphatic aldehydes (Table 14).
7. The high yields of the present one-pot reactions depend on the unique prop-
erties of Ln(OTf)3 as the Lewis acid catalysts. Although TiCl4 and TMSOTf are
known to be effective for the activation of imines [39, 44], the use of even sto-
ichiometric amounts of TiCl4 and TMSOTf instead of Ln(OTf)3 in the present
one-pot reactions gave only trace amounts of the product in both cases
(Table 15).
8. One-pot preparation of a b-lactam from an aldehyde, an amine, and a silyl
enolate has been achieved based on the present reaction (Scheme 5). The re-
action of the aldehyde, the amine, and 2 was carried out under the standard
conditions, and Hg(OCOCF3)2 was then added to the same pot. The desired
b-lactam was isolated in a 78% yield.
86 Shu Kobayashi
Table 15. Effect of catalysts

Entry Activator Yield/%
1 Yb(OTf) 3 10 mol% 89
2 TiCl 4 100 mol% trace
3 TMSOTf 100 mol% trace
1. Yb(OTf)3 (10 mol%) p-MeOPh O

OSiMe3 MS4A N
PhCHO + p-MeOPhNH2 +
SEt 2. Hg(OCOCF3)2
Ph
78%
Scheme 5
Thus, the one-pot synthesis of b-amino esters from aldehydes has been
achieved by using lanthanide triflate catalysis. The high efficiency using simple
starting materials and a catalytic amount of a reusable catalyst is especially note-
worthy.
5.3
Use of Acylhydrazones as Electrophiles in Mannich-Type Reactions
Hydrazones are aldehyde and ketone equivalents as well as imines. Their stabil-
ity is much higher than imines and actually hydrazones derived from aliphatic
aldehydes are often crystalline and can be isolated and stored at room tempera-
ture. However, their reactivity as electrophiles is known to be low, and there have
been many fewer reports on the reactions of hydrazones with nucleophiles than
those of imines [45, 46].
While 3-phenylpropionaldehyde phenylhydrazone did not react with ketene
silyl acetal 3b (R2=tBu) derived from methyl isobutyrate at all, 3-phenylpropion-
aldehyde acylhydrazones reacted with 3b in the presence of a catalytic amount
of Sc(OTf)3. Among the acylhydrazones tested, 4-trifluoromethylbenzoylhydra-
zone (4a, R1=CF3) gave the best yield (Table 16). It is noteworthy that the elec-
tronic effect of the benzoyl moieties influenced the yields dramatically. While
hydrazones with electron-donating groups gave lower yields, higher yields were
Table 16. Effect of R1 and Lewis acids

Entry Lewis Acid R1 R2 Temp/°C Yield/%
1 Sc(OTf)3 H t -20 37
2 Sc(OTf)3 MeO tBu -20 7
3 Sc(OTf)3 NO2 tBu -20 77
4 Sc(OTf)3 CF3 tBu -20 88
5 Sc(OTf)3 CF3 Me -20 97 (75a,b)
6 BF3•OEt 2 CF3 Me 0 4a
7 TiCl4 CF3 Me 0 13a
8 SnCl 4 CF3 Me 0 46a
a Dichloromethane was used as a solvent.
b 0 °C.
obtained using hydrazones with electron-withdrawing groups. As for Lewis ac-

ids, Sc(OTf)3 gave an excellent yield [47–49], and much lower yields were ob-
tained by using typical Lewis acids such as TiCl4, SnCl4, and BF3•OEt2 [50].
Several examples of the reactions of 4-trifluoromethylbenzoylhydrazones
with silyl enolates are shown in Table 17. Hydrazones derived from aromatic,
aliphatic, and a,b-unsaturated aldehydes reacted with silyl enolates smoothly to
afford the corresponding b-N'-acylhydrazinocarbonyl compounds in high
yields. It is noted that several aliphatic hydrazones, readily prepared from
aliphatic aldehydes, reacted with silyl enolates smoothly to afford the corre-
sponding adducts in high yields [51]. All aliphatic acylhydrazones tested were
crystalline and could be stored at room temperature. As for silyl enolates, the
enolates derived from both esters and thioesters worked well. 1-Phenyl-1-tri-
methylsiloxyethene (a ketone-derived silyl enolate) also reacted with an aliphat-
ic acylhydrazone to afford the corresponding adduct in a good yield.
Reductive cleavage of the nitrogen-nitrogen bond of the hydrazino com-
pound (6a) was successfully carried out using Raney Ni under H2 atmosphere
(Scheme 6) [52]. Thus, adduct 5 was treated with a catalytic amount of Raney Ni
(W-3) under H2 (1 atm) at ambient temperature. After cleavage of the nitrogen-
nitrogen bond, the resulting amine was protected as its t-butoxycarbonyl (Boc)
group (6). It was found that b-lactam 7 was obtained by treatment of 5 with n-
BuLi at –78 °C [53], while pyrazolone 8 was produced in the presence of NaOMe
88 Shu Kobayashi
Table 17. Reactions of acylhydrazones with silyl enolates

Entry R1 R2 R3 R4 Temp/°C Yield/%
1 Ph(CH2) 2 Me Me OMe -20 97
2 (CH3)2CHCH2 Me Me OMe rt 88
3 CH3(CH2)5 Me Me OMe 0 95
4 Ph Me Me OMe rt 73
5 CH3CH=CH Me Me OMe 0-rt 80
6 PhCH=CH Me Me OMe rt 75
7 Ph(CH2)2 H H SEt 0 79
8 CH3(CH2)5 H H SEt 0 80
9 (CH3)2CHCH2 H H SEt 0-rt 68
10 c-C6H11 H H SEt 0 68
11 (CH3) 2CHCH2 Me Me SEt 0-rt 83
12 Ph(CH2) 2 OBn H OiPr -78 90a,b
13 Ph(CH2) 2 H Me OPh -45-0 95a,c
14 Ph(CH2) 2 H H Ph rt 66
a Propionitrile was used as a solvent.
b syn/anti=75/25.
c syn/anti=64/36.
O
H Boc
N NH2 O NH O
HN O Raney Ni Boc2O
CF3 OMe OMe
OMe
5 6
71% (2 steps)
Scheme 6
at 70°C (Scheme 7). Since isomerization from 7 to 8 was observed under these
conditions (NaOMe), 7 and 8 were expected to be kinetic and thermodynamic
products, respectively. Moreover, pyrazolidinone 9 was obtained in the presence
of samarium diiodide (SmI2) [54] in THF-MeOH at 45°C.
O
H
N
n-BuLi, -78 °C N
CF3
93%
O
7
NaOMe, 70 °C (O2) N NH
5
99% O
8
SmI2, 45 °C HN NH
94% O
Scheme 7
5.4
Aqueous Mannich-Type Reaction
As mentioned in the previous sections, silyl enolates are excellent enolate com-
ponents in the Mannich-type reactions with imines. Alternatively, it was found
that vinyl ethers also reacted with imines smoothly in the presence of a catalytic
amount of Ln(OTf)3 to afford the corresponding b-amino ketones. In addition,
the reactions proceeded smoothly by the combination of aldehydes, amines, and
vinyl ethers in aqueous media [55].
A general scheme for the new Mannich-type reaction is shown below
(Scheme 8); the procedure is very simple. In the presence of 10 mol% of
Yb(OTf)3, an aldehyde, an amine, and a vinyl ether were combined in a solution
of THF-water (9:1) at room temperature to afford a b-amino ketone.
Selected examples of the present reaction are shown in Table 18. In all cases,
b-amino ketones were obtained in good yields. Several characteristic features
are noteworthy in this reaction. The procedure is very simple, consisting of sim-
ply mixing an aldehyde, an amine, a vinyl ether, and a small amount of Ln(OTf)3
in aqueous solution. The catalyst could be recovered after the reaction was com-
pleted and could be reused (first run, 93%; second run, 83%; third run, 87%, in
the reaction of phenylglyoxal•monohydrate, p-chloroaniline, and 2-methoxy-
propene). Commercially available formaldehyde and chloroacetaldehyde water
solutions were used directly and the corresponding b-amino ketones were ob-
tained in good yields. Phenylglyoxal•monohydrate, methyl glyoxylate, an
aliphatic aldehyde, and an a,b-unsaturated ketone also worked well to give the
corresponding b-amino esters in high yields. In some Mannich reactions with
preformed iminium salts and imines, it is known that yields are often low be-
cause of the instability of the imines derived from these aldehydes or trouble-
some treatments are known to be required for their use [43, 56].
90 Shu Kobayashi
OMe Yb(OTf)3 (10 mol%) R2

NH O
R1CHO + R2NH2 +
R3 THF - H2O (9:1)
R1 R3
Scheme 8
Table 18. Synthesis of b-amino ketones in aqueous media
R1 R2 R3 Yield/%
H p-ClPh Me 92
H p-Ans Me 76
H p-Ans Ph quant.
Ph p-ClPh Me 90
Ph p-Ans Me 74
Ph(CH2 )2 p-ClPh Me 55
ClCH2 p-ClPh Me 59
PhCH=CH p-ClPh Me 73
PhCO p-ClPh Me 93
PhCO Ph Me 90
PhCO p-Ans Me 75
PhCO p-Ans Ph 85
MeO2C p-Ans Me 67
MeO2C p-Ans Ph 58
p-Ans=p-Anisidine
OMe
R2NH R2 2 _ R2 R2
2
N R3 R N OMe
H2O
NH OMe NH O
R1CHO OH
-H2O R1 R1 + R3 R1 R1 R3
H R3
Scheme 9
A possible mechanism for the present reaction is shown in Scheme 9. It

should be noted that dehydration accompanied by imine formation and succes-
sive addition of a vinyl ether proceed smoothly in aqueous solution and that the
first aqueous Mannich-type reaction catalyzed by Ln(OTf)3 has been developed
[57]. Use of Ln(OTf)3, a water-tolerant Lewis acid, is key and essential in this re-
action.
6
Aza Diels-Alder Reactions
6.1
Reactions of Imines with Dienes or Alkenes
The imino Diels-Alder reaction is among the most powerful synthetic tools for
constructing N-containing six-membered heterocycles, such as pyridines and
quinolines [58]. Although Lewis acids often promote these reactions, more than
stoichiometric amounts of the acids are required due to the strong coordination
of the acids to nitrogen atoms [58]. Use of Ln(OTf)3 as a catalyst was investigated
in this reaction.
R1 R1
R4
R3
N N
or
R1
Ph O Ph R2
R2 cat. Ln(OTf)3 12 13
N + R4
R4 CH3CN, rt
Ph H R3 R2 H
R1 R3 R1
10
or H
N Ph N Ph
H H
14 15
Table 19. Syntheses of pyridine dereivatives catalyzed by Ln(OTf)3

Ln(OTf)3 Product Yield/%
R1 Diene
(mol%)
H (10a) OSiMe3 12a 93 (99) a)
Yb(OTf)3
OMe (10b) OMe 12b 82
(10)
Cl (10c) 11 12c 92
H (10a) 13a+14a 54b)
Sc(OTf)3
OMe (10b) 13b+14b 71c)
(20)
Cl (10c) 13c+14c 50d)
H (10a) 15a 69 (91) e,f)
Yb(OTf)3
OMe (10b) 15b 38f)
(10)
Cl (10c) 15c 85f)
a 10 mol% Sc(OTf)3 was used. The reaction d 13c 37%, 14c 13%.
was carried out at 0 °C. e 20 mol% Sc(OTf) was used.
3
b 13a 37%, 14a 17%. f cis/trans=94/6.
c 13b 8%, 14b 63%.
92 Shu Kobayashi
Table 20. Syntheses of quinoline derivatives catalyzed by Ln(OTf)3

R1 R2 Alkene Product Yield/% cis/trans
H H (10a) 16a 75 57/43
OMe H (10b) 16b 0
Cl H (10c) 16c quant. nda)
H OMe (10d) 16d 70 nda)
H H (10a) 17a 96 nda)

OMe H (10b) 17b 77 67/33
Cl H (10c) 17c 95 nda)
OMe H (10b) 18 quant. 83/17 b)
a Not determined.
b Relative configuration assignment was not made.
In the presence of 10 mol% of ytterbium triflate (Yb(OTf)3, a representative

lanthanide triflate), N-benzylideneaniline (10a) was treated with 2-trimethylsi-
loxy-4-methoxy-1,3-butadiene (Danishefsky's diene, 11) [59] in acetonitrile at
room temperature. The imino Diels-Alder reaction proceeded smoothly to af-
ford the corresponding tetrahydropyridine derivative in a 93% yield (Table 19).
The adduct was obtained quantitatively when Sc(OTf)3 was used as a catalyst.
Imines 10b and 10c also reacted smoothly with 11 to give the corresponding ad-
ducts in high yields. The reaction of 10a with cyclopentadiene was performed
under the same reaction conditions. It was found that the reaction course
changed in this case and that a tetrahydroquinoline derivative was obtained in a
69% yield. In this reaction, the imine worked as an azadiene toward one of the
double bonds of cyclopentadiene as a dienophile [43, 60]. In the reactions of 2,3-
dimethylbutadiene, mixtures of tetrahydropyridine and tetrahydroquinoline
derivatives were obtained.
Other examples and effects of Ln(OTf)3 are shown in Tables 20 and 21, re-
spectively [61]. A vinyl sulfide, a vinyl ether, and a silyl enol ether worked well
as dienophiles to afford tetrahydroquinoline derivatives in high yields [62, 63].
As for the Ln(OTf)3, heavy lanthanides such as Er, Tm, and Yb gave better re-
sults.
Table 21. Effects of Ln(OTf)3 (1)
Ln Yield/%
Sc 94
Y 60
La 45
Pr 57
Nd 60
Sm 63
Eu 63
Gd 76
Dy 63
Ho 64
Er 97
Tm 92
Yb 85
Lu 72
6.2
Three-Components Coupling Reactions of Aldehydes, Amines, and Dienes or Alkenes
One synthetic problem in the imino Diels-Alder reactions is the imines' stability
under the influence of Lewis acids. It is desirable that the imines activated by
Lewis acids are immediately trapped by dienes or dienophiles [57]. In 1989, Sis-
ko and Weinreb reported a convenient procedure for the imino Diels-Alder re-
action of an aldehyde and a 1,3-diene with N-sulfinyl p-toluenesulfonamide via
N-sulfonyl imine produced in situ, by using a stoichiometric amount of BF3•OEt2
as a promoter [64].
Bearing in mind the usefulness and efficiency of one-pot procedures, three-
component coupling reactions between aldehydes, amines, and alkenes via imi-
ne formation and imino Diels-Alder reactions were examined by using Ln(OTf)3
as a catalyst.
In the presence of 10 mol% of ytterbium triflate and magnesium sulfate, ben-
zaldehyde was treated with aniline and 11 successively in acetonitrile at room
94 Shu Kobayashi
R2 Yb(OTf)3
(5-20 mol%) pyridine or quinoline
R1 CHO + + diene or alkene
CH3CN, rt derivatives
H 2N
Table 22. One-pot synthesis of pyridine and quinoline derivatives

Diene or
R1 R2 Alkene Product Yield/% cis/trans
Ph H 11 12a 80
(83)a)
15a 56 94/ 6
SPh 16a 70 nd b)
Cl 16c quant. nd b)
H OEt 17a 60 79/21

O
PhCO H 11 76
N COPh
Ph
19
H
R2
H H 94 96/ 4
N R1 (97)c) (96/ 4)
H
20a
OMe 20b 94 94/ 6
Cl 20c quant. 96/ 4
MeO2C H 21a 82 99/ 1
Cl 21c 84 99/ 1
SPh
Cl
Cl SPh 65 ndb)
N CO2Me
H
22
H
Cl
Hd) Cl H 90c)
N
H
23
a Sc(OTf)3 (10 mol%) was used. d Commercial formaldehyde water solution
b Not determined. was used.
c The reactions were carried out in aqueous
solution (H2O:EtOH:toluene=1:9:4).
Table 23. Effects of Ln(OTf)3 (2)

Ln Yield/%
Sc 63
Y 77
La 88
Pr 75
Nd 97
Sm 91
Eu 87
Gd 91
Dy 87
Ho 76
Er 84
Tm 84
Yb 94
Lu 80
temperature. The three-component coupling reaction proceeded smoothly to af-

ford the corresponding tetrahydropyridine derivative in an 80% yield. It is note-
worthy that Yb(OTf)3 kept its activity and effectively catalyzed the reaction even
in the presence of water and the amine [65]. Use of Sc(OTf)3 slightly improved
the yield. Other examples of the three-component coupling reaction are shown
in Table 22. In the reaction between benzaldehyde, anisidine, and cyclopentadi-
ene under the same reaction conditions, the reaction course changed and the
tetrahydroquinoline derivative was obtained in a 56% yield. A vinyl sulfide, a vi-
nyl ether, and a silyl enol ether worked well as dienophiles to afford tetrahydro-
quinoline derivatives in high yields. Phenylglyoxal monohydrate reacted with
amines and 11 or cyclopentadiene to give the corresponding tetrahydropyridine
or quinoline derivatives in high yields. As mentioned in the previous section, the
imine derived from phenylglyoxal is known to be highly hygroscopic and its pu-
rification by distillation or chromatography is very difficult due to its instability
96 Shu Kobayashi
[43]. Moreover, the three-component coupling reactions proceeded smoothly in

aqueous solution, and commercial formaldehyde water solution could be used
directly. Most lanthanide triflates tested were effective in the three-component
coupling reactions (Table 23). These reactions provide very useful routes for the
synthesis of pyridine and quinoline derivatives.
6.3
Reaction Mechanism
In the reactions of 10a–10c with cyclopentadiene, a vinyl sulfide, or a vinyl ether

(10a–c work as azadienes), 10c gave the best yields, while the yields using 10b
were lowest. The HOMO and LUMO energies and coefficients of 10a–c and pro-
tonated 10a–c are summarized in Table 24. These data do not correspond to the
differences in reactivity between 10a–c if the reactions are postulated to proceed
via concerted [4+2] cycloaddition. On the other hand, the high reactivity of 4c
toward electrophiles compared to 10a and 10b may be accepted by assuming a
stepwise mechanism.
The reaction of 10a with 2-methoxypropene was tested in the presence of
Yb(OTf)3 (10 mol%). The main product was tetrahydroquinoline derivative 24a,
and small amounts of quinoline 25a and b-amino ketone dimethylacetal 26a
were also obtained (Eq. 5). On the other hand, the three components coupling
reaction between benzaldehyde, aniline, and 2-methoxypropene gave only a
small amount of tetrahydroquinoline derivative 24a, and the main products in
this case were b-amino ketone 27a and its dimethylacetal 26a (Eq. 6). Similar re-
sults were obtained in the reaction of 4b with 2-methoxypropene and the three
Table 24. HOMO and LUMO energies and coefficient of 10a–ca

HOMO Coefficient HOMO Coefficient
/eV C1 N2 C3 C4 /eV C1 N2 C3 C4
10a -8.97 0.32 0.35 -0.34 -0.24 -0.69 0.43 -0.38 -0.30 0.27
10b -8.68 0.32 0.29 -0.40 -0.24 -0.64 0.43 -0.38 -0.28 0.28
10c -8.93 0.30 0.31 -0.35 -0.22 -0.85 0.43 -0.35 -0.33 0.27
10a - H+ -13.19 0.15 0.31 -0.39 -0.19 -5.75 0.63 -0.48 -0.09 0.21
10b - H+ -12.53 0.20 0.18 -0.46 -0.08 -5.58 0.62 -0.49 -0.07 0.21
10c - H+ -12.58 0.16 0.15 -0.37 -0.10 -5.77 0.63 -0.47 -0.19 0.21
a Calculated with MOPAC Ver. 6.01 using the PM3 Hamiltonian. MOPAC Ver. 7: Stewart JJP
(1989) QCPE Bull 10:9. Revised as Ver. 6.01 by Tsuneo Hirano, University of Tokyo, for HI-
TAC and UNIX machines (1989) JCPE Newslett 10:1.
NH2 OMe
(TfO)3Ln Ph-R
Ln(OTf)3
PhCHO + N
Ph H
R
H 2O
R R-Ph
NH OMe
(TfO)3Ln OH 27
- Ph
N
OMe MeOH
+
Ph
28 26
MeOH
24 25
(oxidation)
Scheme 10
components coupling reaction between benzaldehyde, anisidine, and 2-methox-

ypropene (Eqs. 7 and 8).
A possible mechanism of these reactions is shown in Scheme 10. Intermediate
28 is quenched by water and methanol generated in situ to afford 26 and 27, re-
spectively. While 24 is predominantly formed from 28 under anhydrous condi-
tions, formation of 26 and 27 predominated in the presence of even a small
amount of water. It is noted that these results suggest a stepwise mechanism in
these types of imino Diels-Alder reactions [66].
Ph Yb(OTf)3
N OMe (10 mol%) Ph
NH OMe
+ HN + N + OMe
Ph H CH3CN, rt
Ph
OMe Ph (5)
10a Ph
24a 25a 26a
74% 5% 1%
OMe Yb(OTf)3 (10 mol%) Ph

PhCHO + PhNH2 + NH O
24a + 26a +
MgSO4, CH3CN, rt
Ph (6)
27a
7% 18% 27%
PMP OMe OMe

Yb(OTf)3
N PMP
OMe (10 mol%) NH OMe
+ HN + + OMe
CH3CN, rt N
Ph H Ph
OMe
10b Ph Ph (7)
24b 25b 26b
83% 3% 2%
PMP = p-MeO-Ph
98 Shu Kobayashi
NH2
OMe Yb(OTf)3 (10 mol%) PMP
NH O
PhCHO + + 26b +
MgSO4, CH3CN, rt
Ph
(8)
MeO 27b
PMP = p-MeO-Ph 34% 37%
Thus, a new type of Lewis acid, lanthanide triflates, is quite effective for the
catalytic activation of imines, and has achieved imino Diels-Alder reactions of
imines with dienes or alkenes. The unique reactivities of imines which work as
both dienophiles and azadienes under certain conditions were also revealed.
Three-component coupling reactions between aldehydes, amines, and dienes or
alkenes were successfully carried out by using Ln(OTf)3 as catalysts to afford py-
ridine and quinoline derivatives in high yields. The triflates were stable and kept
their activity even in the presence of water and amines. According to these reac-
tions, many substituted pyridines and quinolines can be prepared directly from
aldehydes, amines, and dienes or alkenes. A stepwise reaction mechanism in
these reactions was suggested from the experimental results.
7
Asymmetric Diels-Alder Reactions
Recently, some efficient asymmetric Diels-Alder reactions catalyzed by chiral

Lewis acids have been reported [67]. The chiral Lewis acids employed in these
reactions are generally based on traditional acids such as titanium, boron, or
aluminum reagents, and they are well modified to realize high enantioselectivi-
ties. Although lanthanide compounds were expected to be Lewis acid reagents,
only a few asymmetric reactions catalyzed by chiral lanthanide Lewis acids were
reported. Pioneering work by Danishefsky et al. demonstrated that Eu(hfc)3 (an
NMR shift reagent) catalyzed hetero-Diels-Alder reactions of aldehydes with si-
loxydienes, but enantiomeric excesses were moderate [68].
As shown in the previous section, lanthanide triflates were found to be good
catalysts in the Diels-Alder reaction of various dienophiles with cyclic and acy-
clic dienes. The reactions proceeded smoothly in the presence of a catalytic
amount of the triflate to give the corresponding adducts in high yields. Moreo-
ver, the catalyst was stable in water and was easily recovered from the aqueous
layer after the reaction was completed, and could be reused. These unique
properties were considered to be dependent on the specific characters of the
lanthanides(III) [69], and design of chiral lanthanide triflates which could
work as an efficient catalyst in the asymmetric Diels-Alder reaction was per-
formed.
First, Yb(OTf)3 was chosen as a representative of the lanthanide triflates. The
chiral Yb triflate was prepared in situ from Yb(OTf)3, (R)-(+)-binaphthol, and a
tertiary amine (Eq. 9) [70], and a model reaction of 3-(2-butenoyl)-1,3-oxazoli-

din-2-one (6) with cyclopentadiene was examined [71].
OH
1.2 eq
OH (9)
2.4 eq. amine
Yb(OTf)3 “chiral Yb triflate”
MS 4A 0 °C, 30 min
Thus, in the presence of a chiral Yb triflate prepared from Yb(OTf)3, (R)-(+)-

binaphthol, and triethylamine at 0 °C for 0.5 h in dichloromethane, 29 reacted
with cyclopentadiene at room temperature to afford the Diels-Alder adduct in
an 87% yield (endo/exo=76/24) and the enantiomeric excess of the endo adduct
was shown to be 33%. After screening several reaction conditions, it was found
that the amine employed at the stage of the preparation of the chiral ytterbium
triflate strongly influenced the diastereo- and enantioselectivities. In general,
bulky amines gave better results and 70%, 75%, and 71% ees were observed
when diisopropylethylamine, cis-2,6-dimethylpiperidine, and cis-1,2,6-trimeth-
ylpiperidine were used, respectively. In addition, a better result was obtained
when the amine was combined with molecular sieves 4 Å (cis-1,2,6-trimethyl-
piperidine, 91% yield, endo/exo=86/14, endo=90% ee), and the enantiomeric
excess was further improved to 95% when the reaction was carried out at 0 °C
[72].
At this stage, although the reaction conditions were optimized, aging of the
catalyst was found to take place. High selectivities (77% yield, endo/exo=89/11,
endo=95% ee) were obtained when the diene and the dienophile were added just
after Yb(OTf)3, (R)-(+)-binaphthol, and a tertiary amine were stirred at 0 °C for
0.5 h in dichloromethane (the original catalyst system). On the other hand, the
selectivities became lower in accordance with the stirring time of the catalyst so-
lution and the temperature. These results seemed to be ascribed to the aging of
the catalyst, but the best result (77% yield, endo/exo=89/11, endo=95% ee) was
obtained when the mixture (the substrates and 20 mol% of the catalyst) was
stirred at 0 °C for 20 h. It was suggested from this result that the substrates or the
product stabilized the catalyst. The effect of the substrates or the product on the
stabilization of the catalyst was then examined, and the dienophile (29) was
found to be effective in preventing the catalyst from aging. When 20 mol% of the
original catalyst system and 29 (additive) were stirred at 0 °C for 5.5 h in dichlo-
romethane, the product was obtained in a 66% yield, endo/exo=87/13, and the
enantiomeric excess of the endo adduct was 88%.
Moreover, after screening several additives other than 29, it was found that
some additives were effective not only in stabilizing the catalyst but also in con-
trolling the enantiofacial selectivities in the Diels-Alder reaction. Selected exam-
ples are shown in Table 25. When 3-acetyl-1,3-oxazolidin-2-one (30) was com-
bined with the original catalyst system (to form catalyst A), the endo adduct was
100 Shu Kobayashi
O O “chiral Yb catalyst” CO N O
+ additive (20 mol%) (2S, 3R)
N O +
MS4A, CH2Cl2, 0 °C
O
CO N O
(2R, 3S)
Table 25. Effect of additives

Additive Yield/% endo/exo 2S,3R /2R,3S (ee (%))a)
O O
N O 29 66 87/13 94.0/ 6.0 (88)
O O
N O 30 77 89/11 96.5/ 3.5 (93)
O O
80 88/12 22.5/77.5 (55)
O O
36 81/19 19.0/81.0 (62)
O O 15.5/84.5 (69)
69 88/12
Ph 83 93/ 7 9.5/90.5 (81) b)
a Enantiomer ratios of endo adducts.
b 1,2,2,6,6-Pentamethylpiperidine was used instead of cis-1,2,6-trimethylpiperidine.
Yb(OTf)3, MS4A, and the additive were stirred in dichloromethane at 40 °C for 3 h.
obtained in 93% ee and the absolute configuration of the product was 2 S, 3R. On
the other hand, when acetyl acetone derivatives were mixed with the catalyst, re-
verse enantiofacial selectivities were observed. The endo adduct with an absolute
configuration of 2R, 3S was obtained in 81% ee when 3-phenylacetylacetone
(PAA) was used as an additive (catalyst B). In these cases, the chiral source was
the same (R)-(+)-binaphthol. Therefore, the enantioselectivities were controlled
by the achiral ligands, 3-acetyl-1,3-oxazolidin-2-one and PAA [73].
As shown in Table 26, the same selectivities were observed in the reactions of
other 3-acyl-1,3-oxazolidin-2-ones. Thus, by using the same chiral source ((R)-
(+)-binaphthol), both enantiomers of the Diels-Alder adducts between 3-acyl-
1,3-oxazolidin-2-ones and cyclopentadiene were prepared. Traditional methods
have required both enantiomers of chiral sources in order to prepare both enan-
tiomers stereoselectively [74], but the counterparts of some chiral sources are of
poor quality or are hard to obtain (for example, sugars, amino acids, alkaloids,
etc.). It is noted that the chiral catalysts with reverse enantiofacial selectivities
could be prepared by using the same chiral source and a choice of achiral ligands.
Table 26. Synthesis of both enantiomers of the Diels-Alder adducts between cyclopentadi-
ene and dienophiles by use of catalysts A and B
Dienophile Catalyst A
Yield/% endo/exo 2S,3R/2R,3S (ee (%))b)
O O (93)
77 89/11 96.5/ 3.5
N O
77 89/11 97.5/ 2.5 (95)c)
O O
Ph N O 40 81/19 91.5/ 8.5 d) (83)
O O
34 80/20 93.0/ 7.0 (86)
n N
Pr O
81 80/20 91.5/ 8.5 (83)c)
Dienophile Catalyst Ba)

Yield/% endo/exo 2S,3R/2R,3S (ee (%))b)
O O
N O 83 93/ 7 9.5/90.5 (81)
O O 60 89/11 10.5/89.5d) (79)

Ph N O
51 89/11 8.5/91.5d) (83)
51 89/11 5.5/94.5d) (89)e)
O O 81 91/ 9 10.0/90.0 (80)

Prn N O 85 91/ 9 9.0/91.0 (82)e)
60 91/ 9 7.5/92.5 (85)f)
Catalyst A: Yb(OTf)3+(R)-(+)-binaphthol+cis-1,2,6-trimethylpiperidine+MS4A+3-acetyl-
1,3-oxazolidin-2-one (30)
Catalyst B: Yb(OTf)3+(R)-(+)-binaphthol+cis-1,2,6-trimethylpiperidine+MS4A+3-pheny-
lacetylacetone (PAA)
a 1,2,2,6,6-Pentamethylpiperidine was used instead of 1,2,6-trimethylpiperidine.
b Enantiomer ratios of endo adducts.
c Without additive.
d 2R,3R/2S,3S.
e Tm(OTf) .
3
f Er(OTf) was used instead of Yb(OTf) .
3 3
These exciting selectivities are believed to be strongly dependent on the spe-

cific coordination number of Yb(III) [69] (Scheme 11). Two binding sites for the
ligands are now postulated in the Yb catalysts. 29 or 30 coordinates in site A un-
der equilibrium conditions to stabilize the original catalyst system. When 29 co-
ordinates Yb(III), cyclopentadiene attacks from the si face of 29 (site A favors si
face attack). On the other hand, in catalyst B (the original catalyst system and
PAA), site A is occupied by PAA [75]. Since another coordination site still re-
mains in the Yb(III) catalyst owing to the specific coordination numbers, 29 co-
ordinates at site B and cyclopentadiene attacks from the re face (site B favors re
face attack).
102 Shu Kobayashi
NR'3
H
O R
Yb(OTf)3 O
O site A CO N O
H
NR'3 O O O O (2S, 3R)
or
R N O N O
30
R N O
NR'3 O O
H
O site B
R O
Yb(OTf)3
CO N O
O site A
H (2R, 3S)
O O
NR'3
Ph
Scheme 11
Table 27. Effect of Ln(OTf)3

Ln Catalyst A
Yield/% endo/exo 2S,3R / 2R,3S (ee(%))a)
Lu 60 89/11 96.5/3.5 (93)
Yb 77 89/11 96.5/3.5 (93)
Tm 46 86/14 87.5/12.5 (75)
Er 24 83/17 84.5/15.5 (69)
Ho 12 73/27 62.5/37.5 (25)
Y 6 70/30 60.0/40.0 (20)
Gd 0
Ln Catalyst B
Yield/% endo/exo 2S,3R /2R,3S (ee (%))a)
Lu 30 89/11 24.5/75.5 (51)
Yb 88 92/ 8 15.0/85.0 (70)
Tm 72 91/ 9 13.0/87.0 (74)
Er 59 90/10 13.0/87.0 (74)
Ho 70 84/16 21.0/79.0 (58)
Y 85 91/ 9 19.5/80.5 (61)
Gd 61 85/15 28.5/71.5 (43)
a
Enantiomer ratios of endo adducts.
The effect of other lanthanide triflates was also examined. As shown in

Table 27, lanthanide elements strongly influenced the yields and selectivities. A
slight difference between the two catalyst systems (catalysts A and B) on the ef-
Table 28. Enantioselective Diels-Alder reactions using a chiral scandium catalyst

Dienophile Catalyst/mol% Yield/% endo/exo ee/% (endo)
20 94 89/11 92 (2S,3R )
10 84 86/14 96 (2S,3R )
5 84 87/13 93 (2S,3R )
3 83 87/13 92 (2S,3R )
20 99 89/11 93 (2R,3R)
10 96 90/10 97 (2R,3R)
20 95 78/22 74 (2S,3R )
10 86 78/22 75 (2S,3R )
fect of the lanthanide elements was also observed. In catalyst A, lutetium triflate
(Lu(OTf)3) was also effective in generating the endo Diels-Alder adduct in 93%
ee. The yields and selectivities diminished rapidly in accordance with the en-
largement of the ionic radii. In catalyst B, on the other hand, the best results were
obtained when thulium triflate (Tm(OTf)3) or erbium triflate (Er(OTf)3) was
employed. Deviations to either larger or smaller ionic radii resulted in decreased
selectivities, although the Diels-Alder adduct was obtained in an 85% yield with
good selectivities (endo/exo=92/8, endo isomer=61% ee) even when holmium
triflate (Ho(OTf)3) was used.
Although Sc(OTf)3 has slightly different properties compared with other lan-
thanide triflates, the chiral Sc catalyst could be prepared from Sc(OTf)3, (R)-(+)-
binaphthol, and a tertiary amine in dichloromethane [76]. The catalyst was also
found to be effective in the Diels-Alder reactions of acyl-1,3-oxazolidin-2-ones
with dienes. The amines employed in the preparation of the catalyst influenced
the enantioselectivities strongly. For example, in the Diels-Alder reaction of 3-
(2-butenoyl)-1,3-oxazolidin-2-one with cyclopentadiene (CH2Cl2, 0 °C), the
enantiomeric excesses of the endo adduct depended crucially on the amines em-
ployed; aniline, 14% ee; lutidine, 46% ee; triethylamine, 51% ee; 2,2,6,6-tetram-
ethylpiperidine, 51% ee; diisopropylethylamine, 69% ee; 2,6-dimethylpiperid-
ine, 69% ee; 1,2,2,6,6-pentamethylpiperidine, 72% ee; and cis-1,2,6-trimethyl-
piperidine, 84% ee.
Several examples of the chiral Sc(III)-catalyzed Diels-Alder reactions are
shown in Table 28. The highest enantioselectivities were observed when cis-
1,2,6-trimethylpiperidine was employed as an amine. 3-(2-Butenoyl)-, 3-cin-
namoyl-, and 3-(2-hexenoyl)-1,3-oxazolidin-2-ones reacted with cyclopentadi-
104 Shu Kobayashi
N
H
O
Ln(OTf)3
O
H
N
Scheme 12
ene smoothly in the presence of the chiral Sc catalyst to afford the corresponding
Diels-Alder adducts in high yields and high selectivities. It should be noted that
even 3 mol% of the catalyst was enough to complete the reaction and the endo
adduct was obtained in a 92% ee.
The catalyst was also found to be effective for the Diels-Alder reactions of an
acrylic acid derivative [77]. 3-Acryloyl-1,3-oxazolidin-2-one reacted with 2,3-
dimethylbutadiene to afford the corresponding Diels-Alder adduct in a 78%
yield and a 73% ee, whereas the reaction of 3-acryloyl-1,3-oxazolidin-2-one with
cyclohexadiene gave a 72% ee for the endo adduct (88% yield, endo/exo=100/0).
Similar to the chiral Yb catalyst, aging was observed in the chiral Sc catalyst.
It was also found that 30 or 3-benzoyl-1,3-oxazolidin-2-one was a good additive
for stabilization of the catalyst, but that reverse enantioselectivities by additives
were not observed. This can be explained by the coordination numbers of
Yb(III) and Sc(III); while Sc(III) has up to seven ligands, specific coordination
numbers of Yb(III) allow up to twelve ligands [69, 78].
As for the chiral ytterbium and scandium catalysts, the following structures
were postulated. The unique structure shown in Scheme 12 was indicated by
13C NMR and IR spectra. The most characteristic point of the catalysts was the
existence of hydrogen bonds between the phenolic hydrogens of (R)-(+)-

binaphthol and the nitrogens of the tertiary amines. The 13C NMR spectra indi-
cated these interactions, and the existence of the hydrogen bonds was confirmed
by the IR spectra [79]. The coordination form of these catalysts may be similar
to that of the lanthanide(III)-water or -alcohol complex [78]. It is noted that the
structure is quite different from those of conventional chiral Lewis acids based
on aluminum [80], boron [81], or titanium [82]. In the present chiral catalysts,
the axial chirality of (R)-(+)-binaphthol is transferred via the hydrogen bonds
to the amine parts, which shield one side of the dienophile effectively [83]. This
is consistent with the experimental results showing that amines employed in the
preparation of the chiral catalysts strongly influenced the selectivities and that
bulky amines gave better selectivities.
Although the transition states of the chiral lanthanide(III)-catalyzed reac-
tions are rather complicated due to the specific coordination number and stere-
ochemistry of lanthanide(III), the sense of asymmetric induction in the chiral
O O
O H O
Sc N N
H
TfO O
N OTf
diene
Scheme 13
Yb Catalyst A: Yb(OTf)3 + (R)-(+)-binaphtol + TMP+30

Yb Catalyst B: Yb(OTf)3 + (R)-(+)-binaphtol + TMP+PAA
Sc Catalyst: Sc(OTf)3 + (R)-(+)-binaphtol + TMP
Fig. 1. Correlation between the ee of the Diels-Alder adduct and the ee of (R)-(+)-binaphthol
scandium-catalyzed reactions can be rationalized by assuming an intermediate

octahedral Sc(III)-dienophile complex (Scheme 13). The axial chirality of (R)-
(+)-binaphthol is transferred to the amine, the re face of the acyl-1,3-oxazolidin-
106 Shu Kobayashi
2-one is effectively shielded by the amine part, and a diene approaches the dien-
ophile from the si face to afford the adduct in a high enantioselectivity.
It was also suggested that aggregation of the catalysts influenced the selectiv-
ities in the Diels-Alder reactions, and the reaction of 3-(2-butenoyl)-1,3-oxazo-
lidin-2-one with cyclopentadiene using (R)-(+)-binaphthol in lower enantio-
meric excesses was examined [84]. The results are shown in Fig. 1. Very interest-
ingly, a positive nonlinear effect was observed in the chiral Sc catalyst. In the chi-
ral Yb catalysts, on the other hand, the effect was dependent on the additives.
The extent of asymmetric induction in catalyst A did not deviate from the enan-
tiomeric excesses of (R)-(+)-binaphthol in the range 60–100% ee [85], while a
negative nonlinear effect was observed in catalyst B. These results can be as-
cribed to a difference in aggregation between the Sc catalyst, Yb catalyst A, and
Yb catalyst B.
8
Asymmetric Aza Diels-Alder Reactions
While asymmetric reactions using chiral Lewis acids have been demonstrated to
achieve several highly enantioselective carbon-carbon bond-forming processes
using catalytic amounts of chiral sources [86], chiral Lewis acid-catalyzed asym-
metric reactions of nitrogen-containing substrates are rare, probably because
most chiral Lewis acids would be trapped by the basic nitrogen atoms to block
the catalytic cycle. For example, aza Diels-Alder reactions are one of the most
basic and versatile reactions for the synthesis of nitrogen-containing heterocy-
clic compounds [58, 87]. Although asymmetric versions using chiral auxiliaries
or a stoichiometric amount of a chiral Lewis acid have been reported [88], exam-
ples using a catalytic amount of a chiral source are unprecedented.
In the previous section, lanthanide triflates were shown to be excellent cata-
lysts for achiral aza Diels-Alder reactions. While stoichiometric amounts of
Lewis acids are required in many cases, a small amount of the triflate effectively
catalyzes the reactions. On the other hand, chiral lanthanide Lewis acids have
been developed to realize highly enantioselective Diels-Alder reactions of 2-ox-
azolidin-1-one with dienes [89]. The reaction of N-benzylideneaniline with cy-
clopentadiene was first performed under the influence of 20 mol% of a chiral yt-
terbium Lewis acid prepared from ytterbium triflate (Yb(OTf)3), (R)-(+)-1,1'-
bi-naphthol (BINOL), and trimethylpiperidine (TMP). The reaction proceeded
smoothly at room temperature to afford the desired tetrahydroquinoline deriv-
ative in a 53% yield, although no chiral induction was observed. At this stage, it
was indicated that bidentate coordination between a substrate and a chiral Lewis
acid would be necessary for reasonable chiral induction. N-Benzylidene-2-hy-
droxyaniline (31a) was then prepared, and the reaction with cyclopentadiene
(32a) was examined. It was found that the reaction proceeded smoothly to afford
the corresponding 8-hydroxyquinoline derivative (33a) [90] in a high yield. The
enantiomeric excess of the cis adduct in the first trial was only 6%; however, the
selectivity increased when diazabicyclo-[5,4,0]-undec-7-ene (DBU) was used in-
Table 29. Effect of additive

Additiveb/mol% Temp/°C Yield/% cis/trans ee/% (cis)
0 71 98 / 2 62
-15 to 0 48 99 / 1 68
MID (20) -15 to 0 21 98 / 2 91
DTBP (20) 0 49 95 / 5 31
DTBP (100) 0 67 99 / 1 61
DMP (100) 0 14 98 / 2 56
DTBMP (100) -15 82 >99 / 1 70
DTBP (100) -15 92 >99 / 1 71
a Prepared from Yb(OTf)3, (R)-(+)-BINOL, and DBU.
b MID: 1-Methylimidazole. DTBP: 2,6-di-t-butylpyridine. DMP: 2,6-dimethylpyridine. DT-
BMP: 2,6-di-t-butyl-4-methylpyridine.
stead of TMP (Table 29). It was also indicated that the phenolic hydrogen of 31a
would interact with DBU, which should interact with the hydrogen of (R)-(+)-
BINOL [91], to decrease the selectivity. Additives which interact with the phe-
nolic hydrogen of 31a were then examined. When 20 mol% of N-methylimida-
zole (MID) was used, 91% ee of the cis adduct was obtained; however, the chem-
ical yield was low. Other additives were screened and it was found that the de-
sired tetrahydroquinoline derivative was obtained in a 92% yield with high se-
lectivities (cis/trans>99/1, 71% ee), when 2,6-di-t-butyl-4-methylpyridine (DT-
BMP) was used.
Other substrates were tested, and the results are summarized in Table 30 [92].
Vinyl ethers (32b–32d) also worked well to afford the corresponding tetrahydro-
quinoline derivatives (33b–33e) in good to high yields with good to excellent di-
astereo- and enantioselectivities (entries 1–9). Use of 10 mol% of the chiral cat-
alyst also gave the adduct in high yields and selectivities (entries 2, 6). As for ad-
ditives, 2,6-di-t-butylpyridine (DTBP) gave the best result in the reaction of im-
ine 31a with ethyl vinyl ether (32b), while higher selectivities were obtained
when DTBMP or 2,6-diphenylpyridine (DPP) was used in the reaction of imine
31a with 32b. This could be explained by the slight difference in the asymmetric
environment created by Yb(OTf)3, (R)-(+)-BINOL, DBU, and the additive (see
below). While use of butyl vinyl ether (32c) decreased the selectivities (entry 7),
dihydrofurane (32d) reacted smoothly to achieve high levels of selectivity
(entries 8, 9). It was found that the imine (31c) prepared from cyclohexanecar-
108 Shu Kobayashi
Table 30. Asymmetric synthesis of tetrahydroquinoline derivatives
a See Table 29.

b 2,6-Diphenylpyridine.
c Sc(OTf)3 was used.
O R1
O H
t Yb
Bu N N N
H
N H O
tBu
N
N R2
R3
Scheme 14
boxaldehyde and 2-hydroxyaniline was unstable and difficult to purify. The

asymmetric aza Diels-Alder reaction was successfully carried out using the
three component coupling procedure (successively adding the aldehyde, the
amine, and cyclopentadiene) in the presence of Sc(OTf)3 (instead of Yb(OTf)3),
(R)-(+)-BINOL, DBU, and DTBMP.
Assumed transition state of this reaction is shown in Scheme 14. Yb(OTf)3,
(R)-(+)-BINOL, and DBU form a complex with two hydrogen bonds, and the ax-
ial chirality of (R)-(+)-BINOL is transferred via the hydrogen bonds to the
amine parts. The additive would interact with the phenolic hydrogen of the im-
ine, which is fixed by bidentate coordination to Yb(III). Since the top face of the
imine is shielded by the amine, the dienophiles approach from the bottom face
to achieve high levels of selectivity.
Thus, catalytic asymmetric aza Diels-Alder reactions of imines with alkenes
have been developed using a chiral lanthanide Lewis acid, to afford 8-hydroxy-
quinoline derivatives in high yields with high diastereo- and enantioselectivi-
ties. Characteristic points of this reaction are as follows.
i. Asymmetric aza Diels-Alder reactions between achiral azadienes and dien-
ophiles have been achieved using a catalytic amount of a chiral source.
ii. The unique reaction pathway in which the chiral Lewis acid activates not di-
enophiles but dienes, is revealed. In most asymmetric Diels-Alder reactions
reported using chiral Lewis acids, the Lewis acids activate dienophiles [86,
93].
iii. A unique lanthanide complex including an azadiene and an additive, which
is quite different from the conventional chiral Lewis acids, has been devel-
oped.
9
Catalytic Enantioselective 1,3-Dipolar Cycloadditions
1,3-Dipolar cycloadditions between nitrones and alkenes are most useful and
convenient for the preparation of isoxazolidine derivatives, which are readily
converted to 1,3-amino alcohol equivalents under mild reducing conditions
[94]. In spite of the importance of chiral amino alcohol units for the synthesis of
biologically important alkaloids, amino acids, b-lactams, and amino sugars, etc.
[95], catalytic enantioselective 1,3-dipolar cycloadditions remain relatively un-
explored [95, 96]. Catalytic enantioselective 1,3-dipolar cycloadditions of ni-
trones with alkenes using a chiral lanthanide catalyst were investigated [97, 98].
First, the 1,3-dipolar cycloaddition reaction of N-benzylidenebenzylamine N-
oxide with 3-(2-butenoyl)-1,3-oxazolidin-2-one was performed in the presence
of a chiral Yb(III) catalyst (20 mol%) prepared from Yb(OTf)3, (S)-1,1'-binaph-
thol ((S)-BINOL), and triethylamine (Et3N). The reaction proceeded smoothly
at room temperature to afford the corresponding isoxazolidine derivative in a
65% yield with high endo/exo selectivity (99/1), and a moderate ee of the endo
adduct was observed (Table 31). The enantiomeric excess was improved to 78%
when cis-1,2,6-trimethylpiperidine (TMP) was used instead of Et3N. Further-
110 Shu Kobayashi
endo exo
Table 31. Effect of amines
Amine Yield/% endo /exo ee/% b
Et 3 N 65 99/1 63
iPr2 NEt 73 >99/1 62
c
cis -1,2,6-TMP 73 99/1 78
(R )-MPEA d 92 >99/1 71
(S )-MPEA 80 97/3 35
e
(R )-MNEA 92 99/1 96
(S )-MNEA 87 99/1 62
a Chiral Yb(III)=Yb(OTf)3+(S)-BINOL+amine.
b Ee of the endo adducts.
c cis-1,2,6-Trimethylpiperidine.
more, it was found that use of chiral amines influenced the selectivity dramatical-
ly, and combination of the chirality of BINOL and the amine was crucial for the
selectivity. Namely, 71% ee of the endo adduct was obtained in the model reac-
tion using a catalyst prepared by the combination of (S)-BINOL and N-methyl-
bis[(R)-1-phenylethyl]amine ((R)-MPEA), while only 35% ee was observed by
the combination of (S)-BINOL and (S)-MPEA. Moreover, it was found that 96%
ee of the endo adduct was obtained with an excellent yield (92%) and diastereo-
selectivity (endo/exo=99/1) by the combination of (S)-BINOL and a newly-pre-
pared chiral amine, N-methyl-bis[(R)-1-(1-naphthyl)ethyl]amine ((R)-MNEA)
[99]. The chiral Yb(III) catalyst thus prepared has two independent chiralities
(hetero-chiral Yb(III) catalyst, see below) and it was found that the sense of the
chiral induction in these reactions was mainly determined by BINOL and that
the chiral amine increased or decreased the induction relatively.
Several examples of the 1,3-dipolar cycloadditions between nitrones and 3-
(2-alkenoyl)-1,3-oxazolidin-2-ones using the novel hetero-chiral Yb(III) catalyst
are shown in Table 32. In most cases, the desired isoxazolidine derivatives were
obtained in excellent yields with excellent diastereo- and enantioselectivities. It
is noted that high levels of selectivities were attained at room temperature. Ni-
trones derived from aromatic and heterocyclic aldehydes gave satisfactory re-
endo exo
Table 32. Catalytic enantioselective 1,3-dipolar cycloadditions
R1 R2 Yield/% endo/exo ee/%b
Ph CH3 92 99/1 96
p-Cl-Ph CH3 93 99/1 92
p-MeO-Ph CH3 82 95/5 90
2-furyl CH3 89 95/5 89
1-naphthyl CH3 88 98/2 85
Ph H 91 >99/1 79
Ph C 3H7 89 98/2 93
C2H5 CH3 88 53/47 96
a Chiral Yb(III)=Yb(OTf) +(S)-BINOL+(R)-MNEA.
3
b Ee of the endo adduts.
NMeR2
H
O
NMeR2
Yb(OTf)3
O
H
NMeR2
N
(R)-MNEA
Scheme 15
sults, and even in the reaction using the nitrone derived from an aliphatic alde-
hyde, the cycloaddition proceeded smoothly to give the endo adduct in an excel-
lent enantiomeric excess, albeit low endo/exo selectivity was observed. Moreo-
ver, it was found that alkenes which could be employed in the present 1,3-dipolar
cycloaddition were not limited to 3-(2-alkenoyl)-1,3-oxazolidin-2-one deriva-
tives. When N-phenylmaleimide was used as a dipolarophile, the desired isoxa-
zolidine derivative was obtained in a 70% yield with endo/exo>99/1, and the
enantiomeric excess of the endo adduct was 70% ee under the standard reaction
conditions [100, 101].
As for the structure of the hetero-chiral Yb(III) catalyst, the following struc-
ture was supported (Scheme 15). Actually, the existence of hydrogen bonds be-
tween the phenolic hydrogens of (S)-BINOL and the nitrogens of (R)-MNEA was
confirmed by the IR spectra of the catalyst [79, 102].
112 Shu Kobayashi
Bn O Bn O
N O MeOMgI N Pd/C, H2
(quant.) (65%)
Ph CON O Ph OMe
O
34
35
NH2 OR TBSO
H H
LDA (78%)
Ph Ph
CO2Me NH
O
TBSCl/imid. 36: R = H 38
(quant.) 37: R = TBS
Scheme 16
3-Hydroxyethyl-b-lactam derivative was synthesized using the present reac-

tions (Scheme 16). Isoxazolidine derivative 34, prepared via the catalytic enan-
tioselective 1,3-dipolar cycloaddition, was treated with methoxymagnesium io-
dide [103] to give methyl ester 35. Reductive N-O bond cleavage and deprotec-
tion of the N-benzyl part of 35 was performed in the same pot using Pd/C under
hydrogen atmosphere (10 kg/cm2) [104] to afford amino ester 36. After the re-
sulting alcohol moiety was protected as its t-butyldimethylsilyl (TBS) ether, cy-
clization of 37 proceeded smoothly using lithiumdiisopropylamide (LDA) [105]
to afford the corresponding b-lactam (38) [106] in a good yield.
10
Conclusions
Lanthanide triflates are new types of Lewis acids different from typical Lewis ac-
ids such as AlCl3, BF3, SnCl4, etc. While most Lewis acids are decomposed or de-
activated in the presence of water, lanthanide triflates are stable and works as
Lewis acids in water solutions. Many nitrogen-containing compounds such as
imines and hydrazones are also successfully activated by using a small amount
of Ln(OTf)3. Lanthanide triflates are also excellent Lewis acid catalysts in organ-
ic solvents. A catalytic amount of Ln(OTf)3 is enough to complete reactions in
most cases. In addition, Ln(OTf)3 can be recovered after reactions are completed
and can be reused.
Recently, polymer-supported lanthanide catalysts have beem of great interest,
and these topics are discussed elsewhere. Use of lanthanide catalysts in solid-
phase organic synthesis is now well-recognized [107]. There have also been
many transformations other than carbon-carbon bond-forming reactions in or-
ganic synthesis using lanthanide triflates as catalysts, and all these will be re-
viewed in the near future.
Acknowledgments. Our work in this area was partially supported by CREST, Ja-
pan Science and Technology Corporation (JST), and a Grant-in-Aid for Scientif-
ic Research from the Ministry of Education, Science, Sports, and Culture, Japan.
The author thanks and expresses his deep gratitude to his coworkers whose
names appear in the references.
11
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demic, Dordrecht
2. Molander GA (1992) Chem Rev 92:29
3. Baes CF Jr, Mesmer RE (1976) The hydrolysis of cations. Wiley, New York, p 129
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dron 44:6065
13. For example: (a) Hajos ZG, Parrish DR (1973) J Org Chem 38:3244; (b) Stork G, Isobe
M (1975) J Am Chem Soc 97:4745; (c) Lucast DH, Wemple J (1976) Synthesis 724; (d)
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Minami I (1986) Tetrahedron Lett 27:2483; (f) Larsen SD, Grieco PA, Fobare WF (1986)
J Am Chem Soc 108:3512
14. Snider BB and Yamamoto K respectively developed formaldehyde-organoaluminum
complex as formaldehyde source in several reactions: (a) Snider BB, Rodini DJ, Kirk
TC, Cordova R (1982) J Am Chem Soc 104:555; (b) Snider BB (1989) In: Schinzer D (ed)
Selectivities in Lewis acid promoted reactions. Kluwer Academic Publishers, London,
pp 147–167; (c) Maruoka K, Conception AB, Hirayama N, Yamamoto H (1990) J Am
Chem Soc 112:7422; (d) Maruoka K, Concepcion AB, Murase N, Oishi M, Yamamoto H
(1993) J Am Chem Soc 115:3943
15. Cf. TMSOTf-mediated aldol-type reaction of silyl enol ethers with dialkoxymethanes
was also reported: Murata S, Suzuki M, Noyori R (1980) Tetrahedron Lett 21:2527
16. Kobayashi S (1991) Chem Lett 2187
17. Gaut H, Skoda J (1946) Bull Soc Chim Fr 13:308
114 Shu Kobayashi
18. Kobayashi S, Hachiya I (1992) Tetrahedron Lett 33:1625

19. Kobayashi S, Hachiya I (1994) J Org Chem 59:3590.
20. Kobayashi S, Hachiya I, Yamanoi Y (1994) Bull Chem Soc Jpn 67:2342
21. Haggin J (1994) Chem Eng News Apr 18:22
22. Kobayashi S, Hachiya I, Takahori T (1993) Synthesis 371
23. Kobayashi S, Hachiya I, Ishitani H, Araki M (1993) Synlett 472
24. Y(OTf)3 and Yb(OTf)3 catalyzed the aldol reaction of 2 with benzaldehyde at room
temperature in dichloromethane to afford the aldol adduct in 58% (syn/anti=32/68)
and 81% yields (syn/anti=29/71), respectively
25. It was reported that TMSOTf selectively activated acetals rather than aldehydes in the
aldol-type reaction of silyl enolates: (a) Noyori R, Murata S, Suzuki M (1981) Tetrahe-
dron 37:3899; (b) Mukai C, Hashizume S, Nagami K, Hanaoka M (1990) Chem Pharm
Bull 38:1509. (c) Murata S, Suzuki M, Noyori R (1980) J Am Chem Soc 102:3248. Selec-
tive activation of acetals or aldehydes under certain non-basic conditions are now un-
der investigation in our group; cf. (d) Mukaiyama T, Ohno T, Han JS, Kobayashi S
(1991) Chem Lett 949
26. Kobayashi S, Wakabayashi T, Nagayama S, Oyamada H (1997) Tetrahedron Lett
38:4559
27. Although several organic reactions in micelles were reported, there was no report on
Lewis acid catalysis in micelles, to the best of our knowledge. In addition, judging
from the amount of the surfactant used in the present case, the aldol reaction would
not proceed not only in micelle. Precise reaction mechanism is now under investiga-
tions: (a) Fendler JH, Fendler EJ (1975) Catalysis in micellar and macromolecular sys-
tems. Academic Press, London; (b) Holland PM, Rubingh DN (eds) Mixed surfactant
systems. ACS, Washington, DC; (c) Cramer CJ, Truhlar DG (eds) (1994) Structure and
reactivity in aqueous solution. ACS, Washington, DC; (d) Sabatini DA, Knox RC, Har-
well JH (eds) (1995) Surfactant-enhanced subsurface remediation. ACS, Washington,
DC
28. Hydrolysis of silyl enol ether 1 took place when lower yields were observed as in
Table 8
29. (a) Yates D, Eaton PE (1960) J Am Chem Soc 82:4436; (b) Hollis TK, Robinson NP, Bos-
nich B (1992) J Am Chem Soc 114:5464; Review: (c) Carruthers W (1990) Cycloaddi-
tion reactions in organic synthesis. Pergamon, Oxford
30. Kobayashi S, Hachiya I, Takahori T, Araki M, Ishitani H (1992) Tetrahedron Lett 6815
31. Kobayashi S, Hachiya I, Araki M, Ishitani H (1993) Tetrahedron Lett 3755
32. Some Diels-Alder reactions in water without catalyst were reported. For example: (a)
Rideout DC, Breslow R (1980) J Am Chem Soc 102:7816; (b) Grieco PA, Garner P, He Z
(1983) Tetrahedron Lett 24:1897
33. Review: Yamamoto Y, Asao N (1993) Chem Rev 93:2207
34. Hachiya I, Kobayashi S (1993) J Org Chem 58:6958
35. For the reactions of carbonyl compounds with tetraallyltin: (a) Peet WG, Tam W (1983)
J Chem Soc, Chem Commun 853; (b) Daude G, Pereyre M (1980) J Organometal Chem
190:43; (c) Harpp DN, Gingras M (1988) J Am Chem Soc 110:7737. See also (d) Fuku-
zawa S, Sato K, Fujinami T, Sakai S (1983) J Chem Soc, Chem Commun 853. Quite re-
cently Yamamoto et al. has reported allylation reactions of aldehydes with tetraallyltin
in the presence of hydrochloric acid: (e) Yanagisawa A, Inoue H, Morodome M,
Yamamoto H (1993) J Am Chem Soc 115:10,356
36. Lewis acid-promoted allylation reactions of carbonyl compounds with allyltrialkyltin
were reported: (a) Yamamoto Y, Yatagai H, Naruta Y, Maruyama K (1980) J Am Chem
Soc 102:7107; (b) Pereyre M, Quintard J-P, Rahm A (1987) Tin in organic synthesis.
Butterworths, London, p 216
37. (a) Schmid W, Whitesides GM (1991) J Am Chem Soc 113:6674; (b) Kim E, Gordon DM,
Schmid W, Whitesides GM (1993) J Org Chem 58:5500
38. Kleinman EF (1991) In: Trost BM (ed) Comprehensive organic synthesis, vol 2. Perga-
mon, Oxford, p 893
39. Ojima I, Inaba S-I, Yoshida K (1977) Tetrahedron Lett 3643
40. (a) Ikeda K, Achiwa K, Sekiya M (1983) Tetrahedron Lett 24:4707; (b) Mukaiyama T,
Kashiwagi K, Matsui S (1989) Chem Lett 1397; (c) Mukaiyama T, Akamatsu H, Han JS
(1990) Chem Lett 889; (d) Onaka M, Ohno R, Yanagiya N, Izumi Y (1993) Synlett 141.
For a stoichiometric use: (e) Dubois J-E, Axiotis G (1984) Tetrahedron Lett 25:2143; (f)
Colvin EW, McGarry DG (1985) J Chem Soc, Chem Commun 539; (g) Shimada S, Saigo
K, Abe M, Sudo A, Hasegawa M (1992) Chem Lett 1445. For an enantioselective ver-
sion: (h) Hattori K, Yamamoto H (1994) Tetrahedron 50:2785
41. Kobayashi S, Araki M, Ishitani H, Nagayama S, Hachiya I (1995) Synlett 233
42. Kobayashi S, Araki M, Yasuda M (1995) Tetrahedron Lett 36:5773
43. Lucchini V, Prato M, Scorrano G, Tecilla P (1988) J Org Chem 53:2251
44. Guanti G, Narisano E, Banfi L (1987) Tetrahedron Lett 28:4331
45. Selected examples using hydrazones as electrophiles or equivalents are as follows. As
far as we know, there have been no examples of Lewis acid-mediated reactions of hy-
drazones with nucleophiles: (a) Kodata I, Park J-Y, Yamamoto Y (1996) J Chem Soc,
Chem Commun 841; (b) Enders D, Ward D, Adam J, Raabe G (1996) Angew Chem, Int
Ed Engl 35:981; (c) Denmark SE, Weber T, Piotrowski DW (1987) J Am Chem Soc
109:2224; (d) Enders D, Schubert H, Nubling C (1986) Angew Chem, Int Ed Engl
25:1109; (e) Claremon DA, Lumma PK, Phillips BT (1986) J Am Chem Soc 108:8265; (f)
Takahashi H, Tomita K, Otomasu H (1979) J Chem Soc, Chem Commun 668
46. In pioneering work, rhodium-catalyzed enantioselective hydrogenation of acylhydra-
zones derived from ketones was reported: Burk MJ, Feaster JE (1992) J Am Chem Soc
114:6266
47. Oyamada H, Kobayashi S (1998) Synlett 249
48. Kobayashi S, Furuta T, Sugita K, Oyamada H (1998) Synlett (in press)
49. It has been shown that lanthanide triflates are excellent catalysts for the catalytic acti-
vation of imine and related compounds, while most Lewis acids are decomposed or
deactivated in the presence of basic nitrogen atoms. For example, (a) Kobayashi S, Bu-
sujima T, Nagayama S (1998) J Chem Soc, Chem Commun 19; (b) Kobayashi S, Na-
gayama S (1997) J Am Chem Soc 119:10,049; (c) Kobayashi S, Akiyama R, Kawamura
M, Ishitani H (1997) Chem Lett 1039; (d) Kobayashi S, Ishitani H, Ueno M (1997) Syn-
lett 115
50. Yb(OTf)3 was effective for the activation of the acylhydrazone, although the yield was
ca. 10% lower than that using Sc(OTf)3 in a preliminary experiment
51. It is also known that the imines derived from a,b-unsaturated aldehydes are often dif-
ficult to prepare due to their instability
52. Alexakis A, Lensen N, Mangeney P (1991) Synlett 625. Cf. Seebach D, Wykypiel W
(1979) Synthesis 423. See also [45]
53. The structure was confirmed by X-ray analysis of the corresponding N-benzoyl deriv-
ative
54. Cf. Overman LE, Rogers BN, Tellew JE, Trenkle WC (1997) J Am Chem Soc 119:7159
55. Kobayashi S, Ishitani H (1995) J Chem Soc, Chem Commun 1379
56. Other lanthanide triflates can also be used. In the reaction of phenylglyoxal•monohy-
drate, p-chloroaniline, and 2-methoxypropene, 90% (Sm(OTf)3), 94% (Tm(OTf)3),
and 91% (Sc(OTf)3) yields were obtained
57. Grieco et al. reported in situ generation and trapping of ammonium salts under Man-
nich-like conditions: (a) Larsen SD, Grieco PA (1985) J Am Chem Soc 107:1768; (b)
Grieco PA, Parker DT (1988) J Org Chem 53:3325 and references cited therein
58. (a) Weinreb SM (1991) In: Trost BM (ed) Comprehensive organic synthesis, vol 5. Per-
gamon, Oxford, p 401; (b) Boger DL, Weinreb SM (1987) Hetero Diels-Alder method-
ology in organic synthesis. Academic Press, San Diego, chaps 2 and 9
116 Shu Kobayashi
59. Danishefsky S, Kitahara T (1974) J Am Chem Soc 96:7807

60. (a) Boger DL (1983) Tetrahedron 39:2869; (b) Grieco PA, Bahsas A (1988) Tetrahedron
Lett 29:5855 and references cited therein
61. (a) Kobayashi S, Ishitani H, Nagayama S (1995) Chem Lett 423; (b) Kobayashi S, Ishi-
tani H, Nagayama S (1995) Synthesis 1195
62. As for the reactions of vinyl ethers, see (a) Joh T, Hagihara N (1967) Tetrahedron Lett
4199; (b) Povarov LS (1967) Russian Chem Rev 36:656; (c) Worth DF, Perricine SC,
Elslager EF (1970) J Heterocyclic Chem 7:1353; (d) Kametani T, Takeda H, Suzuki Y,
Kasai H, Honda T (1986) Heterocycles 24:3385; (e) Cheng YS, Ho E, Mariano PS, Am-
mon HL (1985) J Org Chem 56:5678 and references cited therein. As for the reactions
of vinyl sulfides, see Narasaka K, Shibata T (1993) Heterocycles 35:1039
63. Fujiwara et al. reported a similar type of reaction: Makioka Y, Shindo T, Taniguchi Y,
Takaki K, Fujiwara Y (1995) Synthesis 801
64. Sisko J, Weinreb SM (1989) Tetrahedron Lett 30:3037
65. When typical Lewis acids such as BF3•OEt2 and ZnCl2 (100 mol%) were used instead of
the lanthanide triflates under the same reaction conditions, lower yields were ob-
served (23 and 12%, respectively)
66. Nomura Y, Kimura M, Takeuchi Y, Tomoda S (1978) Chem Lett 267
67. (a) Hashimoto S, Komeshita N, Koga K (1979) J Chem Soc, Chem Commun 437; (b)
Narasaka K, Iwasawa N, Inoue M, Yamada T, Nakashima M, Sugimori J (1989) J Am
Chem Soc 111:5340; (c) Chapuis C, Jurczak J (1987) Helv Chim Acta 70:436; (d)
Maruoka K, Itoh T, Shirasaki T, Yamamoto H (1988) J Am Chem Soc 110:310; (e) Co-
rey EJ, Imwinkelried R, Pikul S, Xiang YB (1989) J Am Chem Soc 111:5493; (f)
Kaufmann D, Boese R (1990) Angew Chem, Int Ed Engl 29:545; (g) Corey EJ, Imai
N, Zhang HY (1991) J Am Chem Soc 113:728; (h) Sartor D, Saffrich J, Helmchen G,
Richard CJ, Lambert H (1991) Tetrahedron Asym 2:639; (i) Mikami K, Terada M,
Motoyama Y, Nakai T (1991) Tetrahedron Asym 2:643; (j) Evans DA, Miller SJ, Lect-
ka T (1993) J Am Chem Soc 115:6460; (k) Ishihara K, Gao Q, Yamamoto H (1993) J
Am Chem Soc 115:10,412; (l) Maruoka K, Murase N, Yamamoto H (1993) J Org
Chem 58:2938; (m) Seerden JG, Scheeren HW (1993) Tetrahedron Lett 34:2669. Re-
view: (n) Narasaka K (1991) Synthesis 1; (o) Kagan HB, Riant O (1992) Chem Rev
92:1007
68. (a) Bednarski M, Maring C, Danishefsky S (1983) Tetrahedron Lett 24:3451. See also
(b) Quimpere M, Jankowski K (1987) J Chem Soc, Chem Commun 676. Quite recently,
Shibasaki et al. reported catalytic asymmetric nitro aldol reactions using a chiral lan-
thanum complex as a base: (c) Sasai H, Suzuki T, Itoh N, Tanaka K, Date T, Okumura
K, Shibasaki M (1993) J Am Chem Soc 115:10,372 and references cited therein
69. Cotton FA, Wilkinson G (1988) Advanced inorganic chemistry, 5th edn. Wiley, New
York, p 973
70. While Yb(OTf)3 or (R)-(+)-binaphthol dissolved only sluggishly in dichloromethane,
the mixture of Yb(OTf)3, (R)-(+)-binaphthol, and an amine became an almost clear
solution
71. Narasaka et al. first reported an excellent chiral titanium catalyst for this reaction: Nar-
asaka K, Iwasawa N, Inoue M, Yamada T, Nakashima M, Sugimori J (1989) J Am Chem
Soc 111:5340
72. Kobayashi S, Hachiya I, Ishitani H, Araki M (1993) Tetrahedron Lett 34:4535
73. Kobayashi S, Ishitani H (1994) J Am Chem Soc 116:4083
74. Stinson SC (1993) Chem Eng News Sept 27:38
75. 3-Acyl-1,3-oxazolidin-2-ones are weakly coordinating ligands, whereas PAA is strong-
er coordinating. From the experiments, site A seems to be more easily available for co-
ordination than site B
76. Kobayashi S, Araki M, Hachiya I (1994) J Org Chem 59:3758
77. Narasaka K, Tanaka H, Kanai F (1991) Bull Chem Soc Jpn 64:387
78. Review: Hart, FA (1987) In: Wilkinson G (ed) Comprehensive coordination chemistry,
vol 3. Pergamon, New York, p 1059
79. Fritsch J, Zundel G (1981) J Phys Chem 85:556
80. (a) Maruoka K, Yamamoto H (1989) J Am Chem Soc 111:789; (b) Bao J, Wulff WD,
Rheingold AL (1993) J Am Chem Soc 115:3814
81. Hattori K, Yamamoto H (1992) J Org Chem 57:3264
82. (a) Reetz MT, Kyung S-H, Bolm C, Zierke T (1986) Chem Ind 824; (b) Mikami K, Terada
M, Nakai T (1990) J Am Chem Soc 112:3949
83. Since the amine part can be freely chosen, the design of the catalyst was easier than
other catalysts based on (R)-(+)-binaphthol. Although some “modified” binaphthols
were reported to be effective as chiral sources, their preparations often require long
steps: Bao J, Wulff WD, Rheingold AL (1993) J Am Chem Soc 115:3814. See also [68a]
84. (a) Oguni N, Matsuda Y, Kaneko T (1988) J Am Chem Soc 110:7877; (b) Kitamura M,
Okada S, Suga S, Noyori R (1989) J Am Chem Soc 111:4028; (c) Puchot C, Samuel O,
Dunach E, Zhao S, Agami C, Kagan H (1986) J Am Chem Soc 108:2353
85. Lower enantiomeric excesses of the product were observed when (R)-(+)-binaphthol
in less than 60% ee was used. This may be ascribed to turnover of the catalyst
86. (a) Maruoka K, Yamamoto H (1993) In: Ojima I (ed) Catalytic asymmetric synthesis.
VCH, Weinheim, p 413; (b) Narasaka K (1991) Synthesis 1
87. (a) Kametani T, Kasai H (1989) Studies in Natural Product Chem 3:385; (b) Grigos VI,
Povarov LS, Mikhailov BM (1965) Izv Akad Nauk SSSR, Ser Khim 2163; CA (1966)
64:9680
88. (a) Waldmann H (1994) Synthesis 535; (b) Borrione E, Prato M, Scorrano G, Stiranello
M (1989) J Chem Soc, Perkin Trans 1 2245; (c) Ishihara K, Miyata M, Hattori K, Tada
T, Yamamoto H (1994) J Am Chem Soc 116:10,520
89. Kobayashi S, Ishitani H, Hachiya I, Araki M (1994) Tetrahedron 50:11,623
90. Some interesting biological activities have been reported in 8-hydroxyquinoline deriv-
atives. For example: (a) Rauckman BS, Tidwell MY, Johnson JV, Roth B (1989) J Med
Chem 32:1927; (b) Johnson JV, Rauckman BS, Baccanari DP, Roth B (1989) J Med Chem
32:1942; (c) Ife RJ, Brown TH, Keeling DJ, Leach CA, Meeson ML, Parsons ME, Reavill
DR, Theobald CJ, Wiggall KJ (1992) J Med Chem 35:3413; (d) Sarges R, Gallagher A,
Chambers TJ, Yeh L-A (1993) J Med Chem 36:2828; (e) Mongin F, Fourquez J-M, Rault
S, Levacher V, Godard A, Trecourt F, Queguiner G (1995) Tetrahedron Lett 36:8415
91. Kobayashi S, Ishitani H, Araki M, Hachiya I (1994) Tetrahedron Lett 35:6325
92. Ishitani H, Kobayashi S (1996) Tetrahedron Lett 37:7357
93. Inverse electron-demand asymmetric Diels-Alder reactions of 2-pyrone derivatives
were reported: (a) Posner GH, Carry J-C, Lee JK, Bull DS, Dai H (1994) Tetrahedron
Lett 35:1321; (b) Markó IE, Evans GR (1994) Tetrahedron Lett 35:2771
94. (a) Tufariello JJ (1984) In: Padwa A (ed) 1,3-Dipolar cycloaddition chemistry, vol 2.
Wiley, Chichester, p 83; (b) Torssell KBG (1988) Nitrile oxides, nitrones and nitronates
in organic synthesis. VCH, Weinheim
95. Review: Frederickson M (1997) Tetrahedron 53:403
96. Pioneering works in this field: (a) Seerden J-PG, Scholte OP, Reimer AWA, Scheeren
HW (1994) Tetrahedron Lett 35:4419; (b) Gothelf KV, Jørgensen KA (1994) J Org
Chem 59:5687; (c) Seerden J-PG, Kuypers MMM, Scheeren HW (1995) Tetrahedron
Asym 6:1441; (d) Gothelf KV, Thomsen I, Jørgensen KA (1996) J Am Chem Soc 118:59;
(e) Seebach D, Marti RE, Hintermann T (1996) Helv Chim Acta 79:1710; (f) Hori K,
Kodama H, Ohta T, Furukawa I (1996) Tetrahedron Lett 37:5947; (g) Jensen KB,
Gothelf KV, Hazell RG, Jørgensen KA (1997) J Org Chem 62:2471 and references cited
therein
97. It was recently found that lanthanide triflates are excellent catalysts in achiral 1,3-di-
polar cycloadditions between nitrones and alkenes and also in three-component cou-
pling reactions of aldehydes, hydroxylamines, and alkenes: Kobayashi S, Akiyama R,
118 Shu Kobayashi Lanthanide Triflate-Catalyzed Carbon-Carbon Bond-Forming Reactions
Kawamura M, Ishitani H (1997) Chem Lett 1039. Cf. Minakata S, Ezoe T, Ilhyong R, Ko-
matsu M, Ohshiro Y (1997) The 72nd Annual Meeting of the Chemical Society of Japan,
Tokyo, 2F3 37. See also [98]
98. Quite recently, Jøgensen et al. reported similar asymmetric 1,3-dipolar cycloadditions
using Yb(OTf)3-PyBOX; however, enantiomeric excesses obtained were up to 73%:
Sanchez-Blanco AI, Gothelf KV, Jøgensen KA (1997) Tetrahedron Lett 38:7923
99. (R)-MNEA was prepared from (R)-1-(1-naphthyl)ethylamine
100. It is believed that bidentate coordination (ex. Yb(III)-3-(2-alkenoyl)-1,3-oxazolidin-2-
one) is necessary to obtain high selectivities in many chiral lanthanide-catalyzed reac-
tions [101]. These results are very interesting and promising because it has been
shown that even monodentate coordination can achieve good selectivities by using the
hetero-chiral Yb(III) catalyst
101. [72, 73, 76, 89, 91]. See also (a) Marko IE, Evans GR (1994) Tetrahedron Lett 35:2771;
(b) Burgess K, Lim H-J, Porte AM, Sulikowski GA (1996) Angew Chem, Int Ed Engl
35:220
102. A bond pair (953 and 987 cm–1), which indicated hydrogen bonds (the OH•••N and O–
•••H+N equilibrium), was observed in the area from 930 to 1000 cm–1 in the IR spectra
of the hetero-chiral Yb(III) catalyst [103]. Direct coordination of the amine to Yb(III)
is doubtful in light of the fact that the 1,3-dipolar cycloaddition proceeded very slowly
when Yb(OTf)3 and (R)-MNEA were first combined and then (S)-BINOL was added
103. Evans DA, Morrissey MM, Dorow RL (1985) J Am Chem Soc 107:4346
104. Kametani T, Huang SP, Nakayama A, Honda T (1982) J Org Chem 47:2328
105. Sekiya M, Ikeda K, Terao Y (1981) Chem Pharm Bull 29:1747
106. As for carbapenems and penems: (a) Palomo C (1990) In: Lukacs G, Ohno M (eds) Re
cent progress in the chemical synthesis of antibiotics. Springer, Berlin Heidelberg New
York, p 565; (b) Perrone E, Franceschi G (1990) In: Lukacs G, Ohno M (eds) Recent
progress in the chemical synthesis of antibiotics. Springer, Berlin Heidelberg New
York, p 613
107. Kobayashi S (1998) Chem Soc Rev (in press)

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Preface

While the lanthanides (strictly deﬁned as the 14 elements following lanthanum

Tokyo, December 1998 Shu Kobayashi

Anorganisch-chemisches Institut, Technische Universität München, Lichten-

Keywords: Lanthanides, Intrinsic properties, Reactivity, Synthesis, Ligands

2 Intrinsic Properties of the Lanthanide Elements . . . . . . . . . . 4

2.1 Electronic Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

3 Synthesis of Organolanthanide Compounds . . . . . . . . . . . . . 8

3.1 Thermodynamic and Kinetic Guidelines . . . . . . . . . . . . . . . 9

4.1 Steric Bulk and Donor Functionalization . . . . . . . . . . . . . . . 24

5 Reactivity Pattern of Organolanthanide Complexes . . . . . . . . . 32

5.1 Donor-Acceptor Interactions . . . . . . . . . . . . . . . . . . . . . . . 32

Ln[N(SiMe3)2]3 pseudo - pseudo- Ln(OTf)3

Fig. 1. Rare earth metal reagents in organic synthesis (NTf2=bis[triﬂuoromethyl)sulfonyl]amide,

Ln4+ [E0 (M4+/M3+), V] 1.74 3.2 3.1

Ln2+ [E0 (M2+/M3+), V] -1.55 -0.36 -2.1 -1.15

Cation Size (Å) [11] 0.745 1.032 1.01 0.938 0.861

Electronic Configuration [Ar] [Kr] [Xe] [Xe]4f1 [Xe]4f14

Scheme 1. Trends within intrinsic properties of the lanthanide elements

oligomeric, A (sym., P21/c) monomeric, B (P212121)

oligomeric, A (asym., P21, Pna21) oligomeric, C (Pbc21)

Marks and co-workers provided a most valuable examination of absolute bond

D(Ln—TTB) [D(Cp*2Sm-R), (kcalmol-1)]

pKa (HL / H2O)

Ln–OR Ln–Cp Ln–

Scheme 2. Synthetic strategies towards organolanthanide compounds [A: amine elimina-

≈150 °C/10-2 torr, -H2O

> 350 °C/10-2 torr, -H2O

Scheme 3. Laboratory procedures for the preparation of lanthanide chloride precursors

+ 1.5 HgI2, THF

+1.5 I2, HOiPr

Scheme 4. Small-scale synthesis of solvated Ln(III) iodides

Scheme 4 shows small-scale syntheses of solvated iodides [64–66]. Strongly

HBraq. methyl orthoformate

The complex (pyH)2(CeCl6) has been discussed as an alternative Ce(IV) pre-

Other Inorganic Salts

Cerium ammonium nitrate [(NH4)2Ce(NO3)6, CAN], a key oxidizing agent, is the

The co-condensation of electron-beam vaporized lanthanide metals with

According to Scheme 2, inorganics and pseudo-inorganics are suitable precur-

The Silylamide Route

Scheme 5. The silylamide route

compounds of relevance in precursor chemistry of ceramic and electronic ma-

The bis(dimethylsilylamide) ligand [N(SiHMe2)2] not only favors the attack

+ 3 LiCH2SiMe3, + H2L, NMe2

Scheme 6. In situ generation of a reactive alkyl precursor

Scheme 7. Heterobimetallic Sm(II) complexes according to the silylamide route

Organometallic derivatives of europium and ytterbium are also readily

2 HR + 2 e–(NH3)n 2 R– + H2 + n NH3 (21b)

Ln2+(NH3)6 + 2 R– LnR2 + 6 NH3 (21c)

Generation of Lanthanide Alkyl Bonds

CpR OtBu CpR

Scheme 9. Reaction of AlMe3 with a mixed alkoxide halide cluster

conditions [115]. However, peralkylated products are obtained from

Generation of Lanthanide Hydride Bonds

Although solid state structures of these complexes exclusively display bridg-

Scheme 12. Generation of lanthanide hydride bonds via thermal degradation

Generation of Cationic Organolanthanide Species

100 200 300 sublimation temperature

Fig. 8. Modes of homoleptic Ln(III) coordination (Do donor functionality)

"Cp2LnH" + CH2=CHR Cp2LnCH2CH2R (2)