Catalytic asymmetric C-Si bond formation to acyclic α,β- unsaturated acceptors by RhI-catalyzed conjugate silyl transfer using a Si-B linkage

Article abstract of DOI:10.1002/anie.200800361

(Chemical Equation Presented) A perfect match: The Rh^I-catalyzed conjugate silylation of acyclic Z-configured α,β-unsaturated carboxyl compounds including imides with silylboronic ester yields almost enantiopure α-chiral quaternary silanes (see scheme; R=aryl and (branched) alkyl, cod=cycloocta-1,5-diene, pin=pinacolato).

Full text of DOI:10.1002/anie.200800361

Communications
DOI: 10.1002/anie.200800361
Asymmetric Catalysis
ꢀ
Catalytic Asymmetric C Si Bond Formation to Acyclic
a,b-Unsaturated Acceptors by RhI-Catalyzed Conjugate Silyl
ꢀ
Transfer Using a Si B Linkage**
Christian Walter and Martin Oestreich*
Dedicated to Professor Larry E. Overman on the occasion of his 65th birthday
Transition-metal-catalyzed activation of interelement link-
ages[1] for the subsequent functionalization of unsaturated
carbon skeletons is now part of the standard repertoire of
synthetic organic chemistry;[2] currently its elusive enantiose-
lective variants are garnering considerable attention.[3] In this
ꢀ
context, the catalytic asymmetric addition of both a Si Si
[6]
(Cl2PhSi-SiMe3)[4,5] and a Si B (Me2PhSi-Bpin) (pin =
ꢀ
pinacolato) bond across a,b-unsaturated acceptors[7] is par-
ticularly attractive as it provides direct access[8,9] to syntheti-
cally versatile, chiral b-silyl carbonyl compounds.[10] Indeed,
an exciting report disclosed a Pd0-catalyzed disilylation of an
acyclic enone with promising enantiomeric excess (92% ee)
almost two decades ago.[4] It remained, however, the sole
example until we recently devised a RhI-catalyzed silabora-
tion of cyclic enones and a lactone with useful enantioselec-
tivity (92–98% ee).[6]
Scheme 1. Unexpected reaction pathways of acyclic acceptors. Reaction
We soon learned that application of this procedure to
acyclic a,b-unsaturated acceptors is certainly not a simple
task (Scheme 1).Strikingly, conjugate reduction was found to
occur with a,b-unsaturated ketones (R’ = aryl or alkyl)
exclusively (A!C), a reaction pathway that is not seen in
related cyclic systems.[6] Moreover, a Z double bond rapidly
isomerized [(Z)-A!(E)-A] prior to any product formation
(kiso > kE and kZ).To our delight, a,b-unsaturated esters (R’ =
conditions: [Rh(cod)2]OTf (5.0 mol%), (R)-binap (10 mol%[11]),
Me2PhSi-Bpin (1)[12] (2.5 equiv), Et3N (1.0 equiv), 1,4-dioxane/H2O
(10:1, 0.20m), 508C. Si=SiMe2Ph, R=aryl or alkyl, OTf=trifluorome-
thanesulfonate, (R)-binap=(R)-2,2’-bis(diphenylphosphanyl)-1,1’-
binaphthyl, cod=cycloocta-1,5-diene.
ꢀ
Oalkyl) underwent the desired C Si bond formation (A!B)
The unexpected isomerization and 1,4-reduction are still
not understood at all.A few control experiments were
inconclusive; we were able to rule out RhI-catalyzed hydro-
silylation after hydrolysis of 1.We currently believe that the
boron reagent Me2PhSi-Bpin (1)[12] in aqueous media might
provide an entry into radical chemistry.[13,14] With the focus on
methodology development, we then continued to assess a,b-
unsaturated esters with Z geometry in this RhI catalysis.In
this communication, we present an unprecedented conjugate
silyl transfer onto Z-configured carboxyl compounds with
exceptional levels of enantioselection.
With ethyl (Z)-cinnamate (R = Ph and R’ = OEt) as a
model, we tested selected chiral ligand motifs using [Rh-
(cod)2]OTf as a precatalyst [(Z)-2a!(S)-3a, Table 1].In the
presence of (R)-binap the catalysis afforded (S)-3a along with
some reduced material with impressive enantioselecitivity of
> 99% ee (Table 1, entry 1).In contrast, the surrogate ligands
(S)-Cl-MeO-biphep and (R)-solphos failed to produce appre-
ciable quantities of the product (Table 1, entries 2 and 3).
Other privileged ligands such as (R,Sp)-josiphos and Carrei-
raꢀs diene[15] were totally inefficient in this reaction (Table 1,
entries 4 and 5).
but 1,4-reduction was again competing (A!C).As for the
conjugate silyl transfer, Z acceptors were markedly more
reactive than the corresponding E precursors (kZ > kE) and
were, in this case, not prone to isomerization (kiso = 0).
[*] C. Walter, Prof. Dr. M. Oestreich
Organisch-Chemisches Institut
Westfälische Wilhelms-Universität Münster
Corrensstrasse 40, 48149 Münster (Germany)
Fax: (+49)251-83-36501
E-mail: martin.oestreich@uni-muenster.de
Homepage: http://www.uni-muenster.de/Chemie.oc/research/oes-
treich/oe_welcome.html
[**] We thank the Deutsche Forschungsgemeinschaft (Oe 249/3-1) for
financial support as well as Solvias AG (Basel, Switzerland) and
Saltigo GmbH (Leverkusen, Germany) for the donation of several
ligands. Barbara Hildmann, Kristine Müther, and Patrick Seelheim
provided skillful technical assistance. M.O. is indebted to the
Aventis Foundation for a Karl-Winnacker-Stipendium (2006–2008).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
3818
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 3818 –3820

Angewandte
Chemie
Table 1: Ligand screening in the enantioselective conjugate silyl transfer Table 2: Enantioselective conjugate silyl transfer onto Z-configured
onto ethyl (Z)-cinnamate [(Z)-2a!(S)-3a].[a,b]
acceptors.[a]
Entry Ligand
t [h] Substrate Reduced Conjugate silyl
acceptor transfer
yield [%] yield [%] yield [%] ee [%][c]
Entry Acceptor
Product
Yield ee
[%][b] [%][c]
1
2
3
4
a: X=H
b: X=Me
66[d] >99
58[d] >99
c: X=OMe 50
>99
d: X=Cl
58[d] >99
1
2
3
0
10
30
56
>99
5
6
e: R=nBu 55
>99
>99
f: R=iBu
44
2
3
40
5
–
[e]
7
–
–
2
15
75
10
–
8
9
a: R=Ph
65
>99
b: R=nBu 72[d] 98
4
5
2
15
0
50
75
10
0
–
–
10
11
a: R=Ph
60
>99
b: R=nBu 58[d] >99
0.5
[a] All reactions were conducted using [Rh(cod)2]OTf (5.0 mol%), the
indicated ligand (10 mol%[11]), 1[12] (2.5 equiv), and Et3N (1.0 equiv) in
1,4-dioxane/H2O (10:1; 0.20m) at 508C. [b] Absolute configuration
assigned by comparison with reported optical rotation values.[8a]
[c] Determined by HPLC analysis using a Daicel Chiralcel IA column
(baseline separation of enantiomers).
[e]
12
–
–
[a] Unless otherwise noted, all reactions were conducted using [Rh-
(cod)2]OTf (5.0 mol%), (R)-binap (10 mol%[11]), 1[12] (2.5 equiv), and
Et3N (1.0 equiv) in 1,4-dioxane/H2O (10:1; 0.20m) at 508C. [b] Yield of
analytically pure product after flash chromatography; in some cases,
trace amounts of the reduced acceptor were removed under high
vacuum. [c] Determined by HPLC analysis using Daicel Chiralcel
columns (baseline separation of enantiomers). [d] Yield obtained when
the reaction temperature was carefully maintained at 458C. [e] No
reaction.
Subsequent variation of the substitution pattern of the Z-
configured a,b-unsaturated ethyl ester (Z)-2 underscored the
generality of the enantioselective conjugate silyl transfer
(Table 2, entries 1–6).Both aryl and alkyl groups, including a
branched alkyl chain, are tolerated.( S)-3a–d and (R)-3e,f
were invariably formed with > 99% ee in reasonable yields.In
order to improve the yields, we employed the activated
acceptors (Z)-4a and (Z)-6a,b (Table 2, entries 7–9).The
methyl thioester (Z)-4a was inert, but the trifluoroethyl esters
(Z)-6 were more reactive than the parent compounds,
furnishing (S)-7a and (R)-7b in slightly improved yields at
the cost of enantioselectivity in the case of (R)-7b (98% ee).
Diastereoselective conjugate silylation using cuprates[9] had
also been developed using Evansꢀ auxiliary.[9e] Application of
our catalyst-controlled enantioselective 1,4-silylation of achi-
ral imides is also possible (Table 2, entries 10 and 11); (Z)-8a
and (Z)-8b cleanly reacted to yield (S)-9a and (R)-9b in
> 99% ee. a,b-Unsaturated nitrile (Z)-10a showed, however,
no reaction (Table 2, entry 12).
In this substrate screening (Table 2), we had identified
reactive trifluoroethyl esters to be ideal in terms of reactivity
and susceptibility to reduction.We therefore returned to the
problematic acceptors having E configuration [Eq.(1)].
When we treated (E)-6a with 1 under standard reaction
conditions (MeOH instead of H2O), we were indeed able to
isolate moderate amounts of (S)-7a with poor enantiomeric
Angew. Chem. Int. Ed. 2008, 47, 3818 –3820
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3819

Communications
[7] We note that the obvious alternative of an enantioselective CuI-
catalyzed conjugate silylation has not been successful so far: G.
Auer, B.Weiner, M.Oestreich, Synthesis 2006, 2113 – 2116.
ꢀ
[8] Aside from asymmetric C Si bond formation, a number of
alternative approaches relying on established catalytic asym-
I
ꢀ
ꢀ
metric C C and C H bond formation were developed.Rh
catalyzed conjugate addition: a) T.Hayashi, R.Shintani, K.
Okamoto, Org. Lett. 2005, 7, 4757 – 4759; b) R.Shintani, Y.
-
Ichikawa, T.Hayashi, J.Chen, Y.Nakao, T.Hiyama,
2007, 9, 4643 – 4645; CuI-H-catalyzed conjugate reduction:
c) B.H. Lipshutz, N. Tanaka, B.R. Taft, C.-T. Lee, Org. Lett.
Org. Lett.
2006, 8, 1963 – 1966; Lewis acid catalyzed 1,4-addition: d) E.P.
Balskus, E.N. Jacobsen, J. Am. Chem. Soc. 2006, 128, 6810 –
6812; CuI-catalyzed 1,4-addition: e) M.A. Kacprzynski, S.A.
Kazane, T.L. May, A.H. Hoveyda, Org. Lett. 2007, 9, 3187 –
3190.
excess.Unexpectedly, the absolute configuration is the same
as that of the product obtained from the Z precursor.As
depicted in Scheme 1, we had anticipated the opposite
enantiomer.This outcome indicates to us that Z und E
isomers pass through totally different enantioselectivity-
determining transition states.
[9] Diastereoselective conjugate addition of silicon-based cuprates:
a) W.Oppolzer, R.J.Mills, W.Pachinger, T.Stevenson,
Helv.
Chim. Acta 1986, 69, 1542 – 1545; b) I.Fleming, N.D.Kindon, J.
Chem. Soc. Chem. Commun. 1987, 1177 – 1179; c) C.Palomo,
In summary, this catalytic asymmetric silaboration[16] of
acyclic a,b-unsaturated carboxyl compounds complements
existing methods for the formation of stereodefined a-chiral
organosilanes.The present work also revealed a surprising
1,4-reduction, which will require serious efforts towards its
mechanistic elucidation.
J.M.Aizpurua, M.Iturburu, R.Urchegui,
J. Org. Chem. 1994,
59, 240 – 244; d) M.R.Hale, A.H.Hoveyda, J. Org. Chem. 1994,
59, 4370 – 4374; e) I.Fleming, N.Kindon, J. Chem. Soc. Perkin
Trans. 1 1995, 303 – 315; f) J.Dambacher, M.Bergdahl, J. Org.
Chem. 2005, 70, 580 – 589.
[10] I.Fleming in Science of Synthesis, Vol. 4 (Ed.: I. Fleming),
Thieme, Stuttgart, 2002, pp.927 – 946.
Received: January 23, 2008
Published online: April 3, 2008
[11] The unusual RhI/(R)-binap ratio (1:2 instead of 1:1) resulted in
better overall performance (chemical yields and enantiomeric
excesses) of the system.For a related observation, see Table 5
(entry 6, footnote [d]) in R.Itooka, Y.Iguchi, N.Miyaura, J. Org.
Chem. 2003, 68, 6000 – 6004.
Keywords: asymmetric catalysis · boron ·
.
homogeneous catalysis · rhodium · silicon
[12] a) M.Suginome, T.Matsuda, Y.Ito, Organometallics 2000, 19,
4647 – 4649; b) T.Ohmura, K.Masuda, H.Furukawa, M.
Suginome, Organometallics 2007, 26, 1291 – 1294.
[1] K.Tamao, S.Yamaguchi, J. Organomet. Chem. 2000, 611, 3 – 4.
[2] a) M.Suginome, T.Matsuda, T.Ohmura, A.Seki, M.Murakami
in Comprehensive Organometallic Chemistry III, Vol. 10 (Eds.:
D.M.P. Mingos, R.H. Crabtree, I. Ojima), Elsevier, Oxford,
2007, pp.725 – 787; b) I. Beletskaya, C. Moberg, Chem. Rev.
2006, 106, 2320 – 2354; c) M.Suginome, Y.Ito, Chem. Rev. 2000,
100, 3221 – 3256; d) L.-B. Han, M. Tanaka, Chem. Commun.
1999, 395 – 402.
ꢀ
[13] For photochemically induced homolytic cleavage of the Si B
bond, see: A.Matsumoto, Y.Ito, J. Org. Chem. 2000, 65, 5707 –
5711.
[14] a) D.Pozzi, P.Renaud,
Chimia 2007, 61, 151 – 154; b) D.A.
Spiegel, K.B. Wiberg, L.N. Schacherer, M.R. Medeiros, J.L.
Wood, J. Am. Chem. Soc. 2005, 127, 12513 – 12515; c) D.Pozzi,
E.M.Scanlan, P.Renaud, J. Am. Chem. Soc. 2005, 127, 14204 –
14205.
[3] H.E. Burks, J.P. Morken, Chem. Commun. 2007, 4717 – 4725.
[4] a) T.Hayashi, Y.Matsumoto, Y.Ito, J. Am. Chem. Soc. 1988, 110,
[15] a) C.Fischer, C.Defieber, T.Suzuki, E.M.Carreira,
J. Am.
5579 – 5581; b) Y.Matsumoto, T.Hayashi, Y.Ito,
1994, 50, 335 – 346.
Tetrahedron
Chem. Soc. 2004, 126, 1628 – 1629; b) T.Hayashi, K.Ueyama, N.
Tokunaga, K.Yoshida, J. Am. Chem. Soc. 2003, 125, 11508 –
11509.
I
ꢀ
[5] For Si Si bond activation in the racemic series, see: Cu : a) H.
ꢀ
Ito, T.Ishizuka, J-.i.Tateiwa, M.Sonoda, A.Hosomi,
J. Am.
[16] For seminal Si B chemistry, see: a) reagent- and catalyst-
Chem. Soc. 1998, 120, 11196 – 11197; b) C.T.Clark, J.F.Lake,
K.A. Scheidt, J. Am. Chem. Soc. 2004, 126, 84 – 85; Pd0: c) T.
Hayashi, Y.Matsumoto, Y.Ito, Tetrahedron Lett. 1988, 29, 4147 –
4150; Pd0/Me3SiOTf: d) S.Ogoshi, S.Tomiyasu, M.Morita, H.
Kurosawa, J. Am. Chem. Soc. 2002, 124, 11598 – 11599; RhI: e) Y.
Nakao, J.Chen, H.Imanaka, T.Hiyama, Y.Ichikawa, W-.L.
Duan, R.Shintani, T.Hayashi, J. Am. Chem. Soc. 2007, 129,
9137 – 9143; f) PtII: K.Okamoto, T.Hayashi, Chem. Lett. 2008,
37, 108 – 109.
controlled Pd-catalyzed addition to allenes: M.Suginome, T.
Ohmura, Y.Miyake, S.Mitani, Y.Ito, M.Murakami,
J. Am.
Chem. Soc. 2003, 125, 11174 – 11175; b) catalyst-controlled Pt-
catalyzed addition to cyclic 1,3-dienes: M.Gerdin, C.Moberg,
Adv. Synth. Catal. 2005, 347, 749 – 753; c) catalyst-controlled Pd-
catalyzed addition to allenes: T.Ohmura, H.Taniguchi, M.
Suginome, J. Am. Chem. Soc. 2006, 128, 13682 – 13683; d) cata-
lyst-controlled Pd-catalyzed desymmetrization of methylenecy-
clopropanes: T.Ohmura, H.Taniguchi, Y.Kondo, M.Suginome,
J. Am. Chem. Soc. 2007, 129, 3518 – 3519.
[6] a) C.Walter, G.Auer, M.Oestreich, Angew. Chem. 2006, 118,
5803 – 5805; Angew. Chem. Int. Ed. 2006, 45, 5675 – 5677; b) for
ꢀ
the related Si P activation including a tentative mechanism, see:
V.T.Trepohl, M.Oestreich, Chem. Commun. 2007, 3300 – 3302.
3820 www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 3818 –3820