TewuJedron

L.enas,Vol. 35.No. 8, pp. 1279-1282.

1994
ElseviuScimx Ltd
Ptb?dillGrutBlit&l
00404039194 36.OOtO.00
oo40-4039(94)Em52-Y

Regio- and Stereoselective Cross-Coupling Reaction of

Optically Active Allylsilanes: Stereocontrol of Palladium-
Mediated SE’ Reactions

Yasuo Hatanaka,* Ken&hi Coda, and Tamejiro Hiyama*t

Sagami C&n&al Research Center

4-4-l Nishiohnuma, Sagamiham, Kanagawa. 229, Japan
tResearch Laboratory of Resources Utilization, Tokyo Institute of Technology
4259 Nagatsuda, Midori-ku. Yokohama, 227, Japan

Aktruct: Optically active allylsilanes undergo the ~regioselective cross-coupling reactions with
aryl tritlates in the presence of a palladium catalyst and a fluoride salt; rhe absolute configuration and
% ee of the coupled products could he conaolled by the choice of the fhtoride salt and the polarity of
the solvent.

Although transition metal catalyzed, asymmetric ally& substitution with nucleophiles is a potentially
versatile method for preparing a wide range of optically active compounds, low enanti~ and ngioselectivity in
this process often sevmly limits the synthetic utility. 1 We have reported previously that the cross-coupling
reaction of allyltrifltxnosilanes with organic halides or uiflates promoted by a palladium catalyst and a fluoride
salt takes place exclusively at the warbon of aUyltrifhmmsihmes, giving a coupled-product in x&chemically
pane form.2 This finding has prompted us to investigate the possibility of stereoselective cross-coupling reaction
of optically active allylsilanes3 with elecuophiles as a route to the selective synthesis of optically active ally1
compounds. We report herein that the stereochemistry of the cross-coupling reaction of optically active
(aJlyl)(difluoro)@henyl)silaues (1) with aryl triflates (2) is decisively influenced by the coordinating ability of
solvent and the nature of a fluoride salt, and under suitable conditions provides accsess to cross-coupled pmducts
in a highly stereoselective manner.

Yriz + Ar-WC&F,
W’phs)r IF

&F,Ph 60% Ar

(R)-la: R = Me 2a = l-C10H7 3a: R = Me, Ar= l-Cl&i7

(R)-lb: R = Et 2b = g-Ct&i7 3b:R=Me,Ar=2+~H7
3c:R=Et. Ar=lC&
9d:R-Et. Ar=2C1&

To evaluate the effect of solvent polarity and fluoride salt on the steswchemisuy of the cmss-coupRng
*action, optically active allylsilanes 1 wereallowedtoreact with 2 in the psence of IWPPh3)4 at 60 OC(TaMe
1). The reaction of (R)-Q-4-(difluoro)(phenyl)silyl-2pentene ((R)-la) (65% ee) with 2-naphthyl uiflate (2b),
promoted by Pd(PPhg)q (5.0 mol %) and (RtzN)#+Me3SiFz- (TASF)4 (4.0 eq) as a fluoride ion source,
1280

smoothly proceeded in teuabydrofuran UT-IF)to give a 4.4 : 1 mixture of Q-Q-4-(2-naphthyl)2-pemene ((0

(E)-3b) (41% ee) and (R)-(2)-4-(2-naphthyl)-2-pentene ((It)-Q-3b) (58% ee) (entry 1). The magnitude of the
enantiomeric excess and the E/Z ratio of the coupled products increased dramatically when the reaction was
carried out in N,N-dimethylformatuide @Ml=). Thus, @)-la (67% ee) reacted with 2b in DMF under the same
conditions with 99% of stereoselectivity to give (S)-(IT)-3b (66% cc) (encry 2).5 A similar solvent dependence
was also observed in the reactions of (R)-Q-4-(difluoro)@henyl)silyl-2-hexene ((@-lb) (69% ee) with ti
or 2b. affording (.S)-(E)-3cor (S)-Q-3d with high stereoselectivity especially in DMF (entries 4-7).
To our surprise, the absolute configuration of the coupled products was reversed when metal fluorides
such as CsF or KF were employed in place of TASF in THF. Thus, the reaction of @)-lb (69% ee) with 2b
conducted in THF using CsF afforded (I?)-(E)-3d (51% ee) (entry 8). Also (R)-(E)-3d (10% ee) was isolated
from the reaction of the same substrates using KF in THF (entry lo).6 However, in DMF which can effectively
solvate metal cation, the stereochemistry of the cross-coupling reaction was the same as that observed using
TASF in this solvent. The reaction of @)-lb (69% ce) with 2b using CsF in DMF rtsulted in the selective
formation of (S)-(I?)-3d (62% ee) (entry 9). Upon addition of 18-crown-6 to CsF in THF, (s)-(E)-3d (13% ee)
also predominated (entry 11). These observations suggest that metal coordination plays an important role in
determining the absolute configuration of the product in THF.

Table 1. Cross-couplin~ Rections of Optiiliy A&w Altyl(difluoro)pt?enylsila~ wtth Aryl Trtfktes Pmmotsd
byW’W4=JF-

product
ailylsitane
entry (%W ArOlV’ F- solvent (% ee, confign) % stersoselectivttb %yield(ElZ)

lq la (65)q 2bq TAS@ THP (If)-3b (41,S)q 63q 64 (4.4)q

(Z)-3b W,R) 89
2 la (87) 2b TASF DMF (E)-3b (86,s) 99 70 (8.8)
3 la (87) 2a TASF DMF (wa (59,s) 88 39 (3.1)
4 lb (89) 2 b TASF THF m-m (5X5) 77 50 (9.3)
5 lb (89) 2b TASF DMF (E)-a (6315) 91
64 (24)
6 lb (69) 2a TASF TIIF (0-X (4OsI 58
88 (4.5)
7 lb (89) 2a TASF DMF (E)-= (67,5) 97
55 (4.3)
8 lb (89) 2b CsF THF (E)+J (51 *m 74
50 (42)
9 lb (69) 2b CsF DMF (E)-3d (62*5) 90
10 lb (69) 2b KF THF (E)-3d (mm 14 50 (15)
11 lb (69) 2b CsF THF (w3d (13,s) 19 50 (100/O)
/18crown-6 38 (16)

‘OTf=OS@CF, b%eeof3/%eeof1

The palladium catalyzed cross-coupling reaction of (allyl)(difluoro)(phenyl)silanes with aryl triflates is

assumed to involve the electrophilic substitution (SE’ reaction) of an allylsilicate7 by an arylpalladium complex
and the reductive elimination of the resulting (qt-allyl)(aryl)palladium complex (Scheme 1)_8 Since the
reductive elimination of a diorgauopalladium complex proceeds with retention of the configuration of the alkyl
ligand,g the observed stereochemistry should reflect that of the SE’ reaction of the allylsilicate with the
aryipalladium complex. To explain the above observations, we propose two plausible transition state models for
 1281

this pmcess as ibaaed in S&me 1.10 In reactions co&uXed in THF using TASF. the arylpalhtdium complex
attacks the double bond ofthe allylsibcate with unti selectivity with mapect to the silyl leaving graup. giving (s)-
Q-3. In contrast, in the presence of CsF or KF in THF, metal coo&mtion to the flunride ion might form a
silicon-fluorine-met bridge10 and favors a cyclic transition state, wherein the electtophilic attack of the
ary1palladium complex on the double bond of the allylsilicate takes place with syn selectivity so as to yiekl (I!)-
(0-3. The presence of a crown ether in the THF/CsF system or the use of DMF may well cleave this bridge by
CoMdination to the alkali metal_ favaing anti attack of the arylpalladium complex to give (S)-(E)-1
The stetwchemisuy of the SE’ reaction of allylsilanes has been of synthetic and mechanistic interest for a
long time, and it is well-established that, in the absence of other conauaints. the maction takes place with anri
se1e~tivity.t~ In contrast, SE*reactions with syn selectivity wete exceptionally observed for highly bii
hit&red allylsiis such as 2-(trimethylsilyl)bicyclo[3,2,0]-3-hepten-7-one,t2 trans-3,6-bis(uimethylsilyl)-l-
cyclohexenc,t f and 1-fluoro(dimethyl)silyl- 1-trimcthylsilyl-2-alkenes,t4 wherein stereochemistry of the
electrophilic attack was determined by steric reasons. Present work, however, demonstrates that the syn
selectivity can be realized for the SE’ reaction of unbiased,strain-freeallylsilancssuch as 1 when electropbihc
attack is controlled by coordination between the silicon and the electrophile. mediated by fluoride ion and alkali
metal.

Scheme 1

In conclusion, our results clearly show that the stereochemistry of the SE’ maction of allylfluorosilanes can
be controlled by choice of solvent and fluoride salt. The present reaction is particularly important as a method for
accomplishing the stereoselective coupling of an allylic unit in a manner that allows the selective synthesis of both
enantiomcrs ikom a common precursor.

REFERENCES AND NOTES

1. Consiglio, G.; Waymouth, R. M. Chem. Rev. 1989.89.257 and the references therein.
2. (a) Hatanalm, Y.; Ebina, Y.; Hiyama. T. J. Am. Chem, Sot, L991.223,7075. (b) Hatanaka. Y.;
Hiyama, T. SYNLEZT 1991.845.
3. The optically active, allyl(difluoro)phenylsilanes used in this work were conveniently prepared by the
asymmeuic hydrosilylation of 1,3dienes with PhFzSiH in the presence of PdCl2[(R)-(S)-PPFA], Hatanaka,
Y.; Yaxnashita, F.; Gcda, K.; Hiyama, T. to be published.
4. Middleton, W. J. U. S. Pat. 3940402, 1976; Chem. Absn. 1976,85, P6388j. Cf.: Middleton, W. J. Org.
Synch. 1985,64, 221. The (EtzN)$?Me3SiF2- used in this work is much more effective than
commercialy available (Me$)3S+Me3SiF2- (Aldrich) due to its greater solubility in organic solvents.
5. The following procedure is representative (Table 1. entry 2): To a DMF solution of 2b (66 mg, 0.24
mmol) and Pd(PPhgk (12 mg, 0.010 mmol. 4.3 mol%) were added @)-la (42 mg, 0.20 mmol. 67% ee)
and then a DMF solution of TASF (0.97 M, 0.82 mL, 0.80 mmol). The nsulting mixture was heated at 60
1282

‘X! fcr 30 h under an argon atmosphere. Concentration and purifiion by column chromatography on silica
gel impregnated with silver nitrate using hexandethyl acetate (8: 1) gave Q-3b (27 mg, 70%) and (Z)-34 (3
mg, 8%). To determine the absolute con@uration and the % ee, (E)-3b was converted to methyl 2-(2-
naphthyl)propanoate by oxidative cleavage of the C=C bond with KMnG&aIa& tillowed by estelification
with diazomethane. The % cc of the final product was estimated by HPLC analysis using a chiral colutnn
(Da&l CHlRALcEL AD, hexane). The absolute contiguration was determinai accwding to the litemutte:
Menicagli, R.; Piccolo, 0.; Latdicci, L.; Wis. M. L. Tetrahedron 1979,35, 1301. (S)-Q3b : [a]%
+18.46’ (c 1.33, CHC13), 66% ee; ‘H NMR (CDCl3,400 MHz) 6 1.40 (d, J = 7.0 Hz, 3H). 1.70 (dt, J =
6.4, 1.4 Hz, 3H), 3.85 (m. lH), 5.51 (dqdJ = 15.3, 6.4, 1.2 Hz, II-I),5.69 (ddq, J = 15.3, 6.6, 1.4 Hz,
lH), 7.35 (dd, J = 8.4, 1.7 Hz, 3H), 7.40 (td, J = 7.0, 1.5 Hz, lH), 7.44 (td, J = 7.0, 1.5 Hz, lH), 7.62
(s, lH), 7.75-7.82 (m, 3H); IR (neat) 3048.2960, 1375.959.813.740 cm-l. Anal. Calcd for C~flla: C,
91.78; H., 8.22. Found: C, 91.56; H. 8.28.
6. To examine the possibility of racemization of lb under the reaction conditions, a blank experiment was
carried out. The solution of lb, KF, and Pd(PPh3)4 in THF was heated at 60 OC for 36 h; however, no loss
of the optical purity of lb was observed, demonstrating that the low % ee of the product is due to the low
stereoselectivity of the cross-coupling reaction.
7. The active species of this reaction is considered to be an anionic pentacoordinate species
(allyl)(trifluoro)@l)silicate.~b The transmetalation (SE’ teaction) of the silicate with the arylpalladium
complex gives a (~Ulyl)(aryl)palladium complex.
8. It is still controversial whether the intermediate in the palladium catalyzed cross-coupling reaction of allylic
substrates is a ql-allylpalldium or a q3-allylpalladium complex. However, the high tegiospe&lcity obsexved
here can rule out the participation of q3-allylpalladium intermediate, which should react with nucleophiles at
both allylic termini, leading to loss of regicchemistry. For discussion on this subject, see: (a) Valle. L. D.;
Stille, J. K.; Hegedus, L. S. J. Org. Chem. 1990.55. 3019, and references therein. (b) Shiba. K.;
Kumsawa, H.; Kalciuchi. K.; &da, I. The 39 th Sywsiwn on Organometollic Chemistry, Japan (ToAyo)
Abstract, A208. p. 160 (1992).
9. Milstein, D.: Stille, J. K. 1. Am. Chem. Sot. 1979.101.4981.
10. Previously, we report& that the stereochemistry of the electrophilic attack of an arylpalladium complex on
the Si-C bond of an allcylsilicate is strongly influenced by temperatuxe and the polarity of the solvent, see:
Hatanaka, Y.: Hiyama, T. J. Am. Chem. Sot. 1990,122. 7793.
11. (a) Calvin, E. W. Silicon in Organic Synthesis; Butterworth: London, 1981; ~97. (b) Weber, W. P. Silicon
Reagents for Organic Synthesis; Springer-Verlag: New York, 1983; ~173. (c) Fleming, I; Dunogu& J.;
Smithers, R. Org. React. 1989,37,57. (d) Hayashi, T; Konishi, M.; Kumada, M. J. Chem. Sot., Chum.
Commun. 1983. 736. (e) Buckle, M. J.; Fleming, I.; Gil, S. Tetrahedron L&t. 1992,33, 4479, and
refenmces therein.
12. Au-Yeung. B. W.; Fleming, I. J. Chem. Sot., Chem. Commun. 1977,79.
13. Wickham, G.; Kitching, W. Orgunometallics 1983,2,541.
14. Wetter, H.; Sherer, P.; Schweizer, W. P. ffelv. Chim. Acta 1979,62, 1985.
15. Hay&i and Hosomi reported that allylation of benzaldehyde with allylsilicates proceeds via cyclic transition
state with syn-stereochemistry, see Hay&i, T.; Matsumoto, Y.; Kiyoi, T.; Ito, Y.; Kohra, S.; Tominaga,
Y.; Hosomi, A. Tetrahedron Lett. 198I1,29.5667.

(Received in Japan 16 October 1993; accepted 20 December 1993)