National Technical University of Ukraine 1

‘Igor Sikorsky Kiev Polytechnic Institute’

Organometallic Chemistry
(Structure, Reactivity, and Mechanisms)

Hydrogenation

Andrey O. Kushko, Ph.D.,

Senior Lecturer

Kiev-KPI-2023
 2
Hydrogenation: Main Trends

• Homogeneous
• Asymmetric
• Heterogeneous
 3
Hydrogenation: Catalysts and Approaches

Catalysts Approaches
• Ionic Hydrogenations

• Rhodium • Homogeneous Hydrogenation by

Defined Metal Clusters
• Iridium
• Homogeneous Hydrogenation:
• Ruthenium and Osmium
• Colloids – Hydrogenation with Noble
• Palladium and Platinum
Metal Nanoparticles
• Nickel
• Hydrogenation with Early Transition Metal, Lanthanide
and Actinide Complexes

The Handbook of Homogeneous Hydrogenation. Edited by J.

G. de Vries and C. J. Elsevier Copyright © 2007 WILEY-VCH
Verlag GmbH & Co. KGaA, Weinheim
 4
Hydrogenation: Application
• Homogeneous Hydrogenation of Alkenes, Alkynes and Dienes
• Homogeneous Hydrogenation of Aldehydes, Ketones, Imines
and Carboxylic Acid Derivatives
• Hydrogenation of Arenes and Heteroaromatics
• Homogeneous Hydrogenation of Carbon Dioxide
• Dehalogenation Reactions
• Homogeneous Catalytic Hydrogenation of Polymers
• Transfer Hydrogenation Including the Meerwein-Ponndorf-
Verley Reduction
• Diastereoselective Hydrogenation
• Hydrogen-Mediated Carbon-Carbon Bond Formation
The Handbook of Homogeneous
Catalyzed by Rhodium Hydrogenation. Edited by J. G. de
• Asymmetric Homogeneous Hydrogenation Vries and C. J. Elsevier
Copyright © 2007 WILEY-VCH Verlag
GmbH & Co. KGaA, Weinheim
 5

Hazards associated with Laboratory Scale Hydrogenations

T. Chandra, J. P. Zebrowski, Journal of Chemical Health & Safety, July/August, 2016, 16-25.
 6
Various Laboratory Hydrogenation Techniques

T. Chandra, J. P. Zebrowski, Journal of Chemical Health & Safety, July/August, 2016, 16-25.
 7
Various Laboratory Hydrogenation Techniques

T. Chandra, J. P. Zebrowski, Journal of Chemical Health & Safety, July/August 2016, 16-25.
 8
Ambient Pressure Hydrogenation

T. Chandra, J. P. Zebrowski, Journal of Chemical Health & Safety, July/August 2016, 16-25.
 Laboratory Large-Scale Hydrogenations 9

T. Chandra, J. P. Zebrowski, Journal of Chemical Health & Safety, July/August 2016, 16-25.
 10

Main Groups of Homogeneous Hydrogenation Catalysts

• Monohydride catalysts;
• Wilkinson’s catalysts;
• Schrock-Osborn/Crabtree: Cationic catalysts;
• Titanocene catalysts

The Handbook of Homogeneous Hydrogenation. Edited by J. G. de Vries and C. J. Elsevier

Copyright © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
 11

Monohydride catalysts
 Monohydride Catalysts: RuClH(PPh3)3 12

Wilkinson's original report:

"In contrast to the rhodium system, ethanol plays an intimate part in the hydrogenation
mechanism; in the absence of such a co-solvent, hydrogenation is exceedingly slow."

Wilkinson, Nature, 1965, 208, 1203.

The active species was identified
as the monohydride, thought to
form via heterolytic cleavage of H2,
with ethanol acting as a base. The
monohydride can also be prepared
in 100% benzene if an equivalent of
NEt3 is added. One mole of H2 is
absorbed with respect to Ru and
amine hydrochloride is Wilkinson, J. Chem. Soc. (A), 1968, 3143.
quantitatively formed.
 13
Effect of Base on Conversion

Tsuneda, Bull. Chem. Soc. Jpn. 1973, 46, 279.

 14
Mechanism of H2 Activation
Base promoted heterolytic cleavage:

-donation>>
-back bonding

Heterolytic Cleavage

Note: there is no oxidation

state change at the metal
-Complex

Generally observed for electrophilic metals that are in their

highest stable oxidation state within the context of their ligand
framework.

Crabtree, Chem. Commun. 1999, 297.

 Mechanism of H2 Activation 15

1 2

Complexation of dihydrogen to the electrophilic, cationic Ir(III) center is predominantly σ-donating in nature.
Donation of electron density from the H-H σ-bond to an empty Ir orbital leaves the H-H with a partial positive
charge. The pendent NH2 group is thought to act as an internal base affecting heterolytic cleavage of the
acidified dihydrogen σ-complex via deprotonation. When L = PPh3, the equilibrium lies far to the right and
only the dihydride 2 is observed. When more basic alkyl phosphines are used (L= PBu3) the equilibrium lies
to the left with the H2 complex 1 being observed exclusively by NMR. It was hypothesized that moving to a
more basic phosphine increases the electron density at the metal center. This makes the metal a less
effective σ-acceptor and attenuates its ability to effectively acidify the dihydrogen complex.

Crabtree. Chem. Commun. 1999, 297.

 16
Mechanism of H2 Activation
σ-Bond Metathesis: The base is effectively one of the ligands on the metal

σ-Bond Metathesis

External amine base may still drive

the reaction forward by forming
insoluble amine hydrochloride salts

Crabtree, The Organometallic Chemistry of the Transition Metals: 3rd Edition; Wiley: New York; 2001.
 17
BINAP-Ru Complexes: Noyori
increases the substrate scope Ryoji Noyori
2001 Nobel Prize in
for asymmetric hydrogenations Chemistry

The first report: asymmetric hydrogenation of

(Z)-enamides
Interestingly, E-enamides are completely unreactive
air-sensitive towards these hydrogenation conditions. No rationale
for this has been presented.

R. Noyori, JACS 1986 (108) 7117.; R. Noyori, ACIEE 2002 (41) 2008.
 18
Asymmetric Hydrogenation of Allylic and Homoallylic Alcohols
Regioselectivity: allylic and homoallylic
alcohols are hydrogenated whereas bis
homoallylic and higher analogues are left
untouched.

Geraniol (R)-citronellol
97 to >99% yields 96% ee

(S)-citronellol
Nerol
98% ee
Allylic olefin geometry may dictate the stereochemical outcome of the hydrogenation. Practical
consequence: to obtain high ee's must start with stereochemically pure olefins.
R. Noyori, J.Am. Chem. Soc., 1987, 109, 1596.
 Hydrogenation of ,-Unsaturated Acids 19

BINAP-Ru Complexes: Noyori increases the substrate scope for asymmetric hydrogenations
The first demonstration of high asymmetric induction in the hydrogenation of substrates lacking an
acylamino group: asymmetric hydrogenation of α,β-unsaturated carboxylic acids

The degree of asymmetric

induction is significantly
affected by the H2 pressure in a
substrate-specific manner. The
implication of this is that a
range of H2 pressures must be
screened to achieve optimal
asymmetric induction on a
substrate-by-substrate basis.
No trend was observed and no
rationale for the empirical
observation was given.

R. Noyori, J. Org. Chem. 1987, 52, 3174.

 Mechanism of BINAP-Ru Hydrogenation of 20

,-Unsaturated Acids

Note: The Mechanism is valid for both enantiomers of BINAP.

No rationalization for the enantiofacial selectivity is given.

Heterolytic cleavage of H2
RDS

Protonolysis Note: No oxidation state change to the metal

cis-Migratory
Insertion
Halpern, J. Am. Chem. Soc., 1991, 113, 589.
 21
Question of the Week
Ru(CH3CO2)2-[(S)-BINAP] catalyzes the hydrogenation of α-(acylamino)acrylic esters to give
the (S) saturated product in >90% ee’s. Propose a mechanism that accounts for the
observed mixture of hydrogenation products when the reaction is run in MeOD. Note: your
mechanism need not rationalize the absolute stereochemistry obtained.
 22

Wilkinson’s catalysts
 23
Wilkinson Hydrogenation: Original Report

Investigations into the reactivity of (PPh3)RhCl uncovered its

high activity as a homogeneous hydrogenation catalyst. This
was the first homogeneous catalyst that compared in rates
with heterogeneous counterparts.

Geoffrey Wilkinson J. Wilkinson, J. Chem. Soc. (A), 1966, 1711.

(1921-1996)

Quantitative!!!
 24
Wilkinson Hydrogenation: Functionality tolerated
and minimal H/D Scrambling

Minimal H/D scrambling in the product

Compatibility with carbonyl is indicative of the formation of a dihydro
groups indicates that the metal metal intermediate that transfers both of
hydride intermediate is primarily its hydrido ligands to the unsaturated
covalent in character (lacks substrate.
hydridic properties characteristic
of strongly ionic M-H).

J. Wilkinson, J. Chem. Soc. (A), 1966, 1711.

 Wilkinson Hydrogenation 25

Ethylene is not hydrogenated under these conditions but...stoichiometric

hydrogen transfer from a preformed dihydride complex occurs

Data indicates that formation of an ethylene/

Rh(Cl)(PPh3)3 complex inhibits hydrogen
activation by the complex. This implies that
dihydride formation precedes olefin complexation
in the catalytic cycle.

J. Wilkinson, J. Chem. Soc. (A), 1966, 1711.

 26
Wilkinson Hydrogenation: Stereochemistry

The stereochemical outcome of this

experiment indicates that the
mechanism involves stereospecific
cis hydrometallation of the
unsaturated substrate followed by
stereospecific reductive elimination
meso-Compound from the resulting alkenyl (or alkyl)
major product observed
hydrido species.

cis- Hexene: trans-hexene

(>20:1)

J. Wilkinson, J. Chem. Soc. (A), 1966, 1711.

 Wilkinson Hydrogenation: Substrate Selectivity 27
Unsaturated substrate Competition figure

+ unsaturated + saturated
substrate substrate

Competition figure = Rate of hydrogenation of unsaturated

substrate/Rate of hydrogenation of 1-octene

Candlin, Faraday Discuss. Chem. Soc. 1968, 46, 60.

 28
Wilkinson Hydrogenation: Classic Dihydride Mechanism
oxidative
addition
Solution structure
determined by NMR.
strong -acids (e.g. ethylene) bind
tightly to the electron rich Rh
center and inhibit hydrogenation

Catalytic Cycle oxidative

addition

coordinatively unsaturated
complex reacts w/ H2 104 x
faster than Rh(Cl)PPh3

migratory
reductive insertion
elimination RDS

Intermediates observed by NMR or as isolated

solids in the reaction system. Formation of Halpern, Chem. Comm. 1973, 629.; Halpern, J. Mol. Catal. 1976, 2, 65.; Halpern, Inorg.
these "side-products" results in a reduction in
the rate of hydrogenation.
Chim. Acta. 1981, 50, 11.
 29
Wilkinson Hydrogenation: Site Selectivity
Site-selective Hydrogenation: Sterics
ketone activated
cis-disubstituted

highly active heterogeneous

catalysts often cannot achieve
high levels of selectivity

tetrasubstituted

Pedro, J. Org. Chem. 1996, 61, 3815.

 30
Wilkinson Hydrogenation: Site Selectivity
Site-selective Hydrogenation: Sterics and Electronics

trisubstituted

cis-disubstituted only site of

conjugated hydrogenation
diene
trisubstituted

Fisher J. Med. Chem. 1980, 23, 1134. Ivermectin

 31
Wilkinson Hydrogenation: Site Selectivity

Cis- and trans-disubstituted olefins:

cis-disubstituted

trans-disubstituted
PGE2 PGE1

Schneider, J. Org. Chem. 1973, 38, 951.

 Wilkinson Hydrogenation: Diastereoselectivity 32

R = H : 73% endo
R = Me : 92% endo

Endo- Exo-
Rationale for observed diastereoselectivity:
Olefin binds the catalyst from the least
sterically hindered exo face. Subsequent cis
hydrometallation of the exo face followed
by stereospecific reductive elimination of
the alkyl metal hydrido intermediate results
in overall cis addition of H2 to the least
sterically hindered exo face of the olefin.

Rousseau, J. Mol. Cat. 1979, 5, 163.; Jardine, Prog. Inorg. Chem. 1981, 28, 63.
Wilkinson Hydrogenation: Directing Group Effects 33

Note: When Pd/C was used

no reaction a mixture of cis and trans
isomers resulted

trisubstituted
cis isomer (exclusive)

The slow reaction without the alkoxide is

attributed to the steric hindrance of the
tri-substituted double bond, which renders it
less able to coordinate to the Rh. The
protonated alcohol is not a strong enough
nucleophile to associatively displace the
anionic chloride ligand. Base-assisted
formation of the alkoxide results in
the effective displacement of the chloride
trisubstituted ligand and thus directs olefin complexation
from the same face.

Thompson, J. Am. Chem. Soc. 1974, 96, 6232.; Jardine, Prog. Inorg. Chem. 1981, 28, 63.
 34

Robert Crabtree

Schrock-Osborn/Crabtree:
Cationic catalysts
 Schrock-Osborn/Crabtree: Сationic Сatalysts 35

Diene ligated cationic catalyst mode of activation:

cis-migratory
cis-oxidative insertion
addition
diene ligated
catalyst precursor

repeat

cis-reductive
elimination

solvated active catalyst

Crabtree R., Acc. Chem. Res. 1979, 12, 331.

 Schrock-Osborn/Crabtree: Сationic Сatalysts 36

Turnover Frequency (TOF)

Wilkinson’s 650 700 13 ----

Catalyst

Schrock-Osborn 4000 10 ---- ----

Catalyst

Crabtree’s Catalyst 6400 4500 3800 4000

TOF = mol reduced substrate/mol catalyst/h

"Coordinatively" unsaturated cationic hydrogenation catalysts are the most
active homogeneous hydrogenation catalysts developed thus far. Use of weakly
Crabtree R., Acc. Chem. Res. 1979, 12, 331. coordinating solvents provides the olefin substrate with relatively free access to
the metal's reactive site. These cationic catalysts are also remarkably selective. .
 37
Halpern’s Mechanism for Cationic Rh(I) Catalysts
with Bidentate Phosphine Ligands:
Schrock-Osborn Catalyst

stereospecific
reductive diphos
elimination nbd (norbornadiene)
observed by NMR ring strain results
in more facile
hydrogenation

observed by NMR observed by NMR

stereospecific
oxidative addition (OA) Schrock-Osborn type Catalyst most commonly
cis-migratory
insertion RDS used: [Rh(nbd)(diphos-4)]BF4
(rate determining step)

Halpern, Science, 1982, 217, 401.

 38
Asymmetric Hydrogenations of Trisubstituted
“Unfunctionalized” Olefins
Crabtree’s Catalyst

Recall that Crabtree's catalyst can effect the

efficient hydrogenation of both tri-and
tetrasubstituted olefins. Replacement of the
monophosphane and pyridine ligands with the
Pfaltz Hydrogenation Catalyst
bidentate phosphanodihydrooxazole ligand
produces a catalyst that is highly effective in
promoting the asymmetric hydrogenation of
trisubstituted, unfunctionalized olefins.

Pfaltz, Angew. Chem. Int. Eng. Ed. 1998, 37, 2897.

 39
Asymmetric Hydrogenations of Trisubstituted
“Unfunctionalized” Olefins

97 % ee, >99 % conv.

Counterion Catalyst Loading Conversion

hexafluorophosphate 4 mol% 57 %

tetrakis(pentafluorophe
nyl)-borate . 1 mol% 84%

tetrakis[3,5-bis- Pfaltz, Angew. Chem. Int.

(trifluoromethyl)- .05 mol% >99% Eng. Ed. 1998, 37, 2897.
phenyl]borate (BARF)
 40

Titanocene catalysts
 41
Titanocene Catalytic Chemistry
 42
Titanocene Hydrogenation of “Unfunctionalized” Olefins

Original report of catalytic

hydrogenation activity:

heptane/THF, 40oC
quantitative conversion

Stern, Tetrahedron Lett. 1968, 60, 6313.

 43
Titanocene Hydrogenation of “Unfunctionalized” Olefins

The first asymmetric

example resulting in high ee

95% optical purity

Vollhardt, J. Am. Chem. Soc. 1987, 109, 8105.

 44
Titanocene Hydrogenation of “Unfunctionalized” Olefins

Asymmetric hydrogenation of
"unfunctionalized" trisubstituted
olefins:

E olefins are reduced more rapidly

and with higher ee's than Z olefins

79% yield
all substrates reported are
95% ee
alkenes  to an aromatic ring

Buchwald, J. Am. Chem. Soc., 1993, 115, 12569.

 45
Titanocene Hydrogenation of “Unfunctionalized” Olefins

Synthesis of allyldicyclopentadienyltitanium (III) complexes from

dicyclopentadienyltitanium (IV) dichloride:

Martin, and Jellinek, J. Organomet. Chem. 1966, 6, 293; Martin, and Jellinek, J. Organomet. Chem. 1968, 12, 149.
 46
Titanocene Hydrogenation of “Unfunctionalized” Olefins

5 mol% postulated intermediate

based on Martin and
Jellinek papers

-bond metathesis olefin insertion

Buchwald argues that the silane does not serve as an

H source based on the following experiment: when D2
was used in the hydrogenation of (E)-1,2-diphenyl Note:
propene, 1,2-diphenyl propane resulted which was 98% regioselectivity
D2 by GC/MS. Buchwald goes on to note that the only of insertion not
purpose of the phenylsilane is to stabilize the catalyst determined
during manipulations before starting the reaction.

Buchwald, J. Am. Chem. Soc. 1993, 115, 12569.

 47

Catalytic hydrogenation:
what's next?
48