Stereochemical studies of Ag-catalyzed hosomi-sakurai reaction using

Article abstract of DOI:10.1002/ejoc.200900670

Stereochemical aspect of asymmetric Ag-catalyzed HosomiSakurai reaction with ketones has been investigated. Several allyltrimethoxysilanes have been synthesized and used for the asymmetric reaction. Remarkably, among several possible diastereomers only tw

Full text of DOI:10.1002/ejoc.200900670

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900670
Stereochemical Studies of Ag-Catalyzed Hosomi–Sakurai Reaction Using
Chiral Silanes
Manabu Wadamoto,[a] Marina Naodovic,[a] and Hisashi Yamamoto*[a]
Dedicated to Professor Alain Krief
Keywords: Ketones / Silver / Asymmetric synthesis / Allylation / Chiral allylsilanes
Stereochemical aspect of asymmetric Ag-catalyzed Hosomi–
Sakurai reaction with ketones has been investigated. Several
allyltrimethoxysilanes have been synthesized and used for
the asymmetric reaction. Remarkably, among several pos-
sible diastereomers only two are generated with high levels
of diastereo- and enantioselectivities. Based on the observa-
tions for different allyltrimethoxysilanes, we hypothesize for-
mation of a single allylsilver species which undergoes ad-
dition to the ketone.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Our group has recently developed a method for highly
diastereo- and enantioselective AgF-Difluorophos allyl-
and crotylation reaction of ketones.[4,5] Main features of the
reaction are (i) high level of enantioselectivity, (ii) excellent
syn-selectivity regardless of the configuration of the starting
crotylsilane and (iii) exclusive γ-regioselectivity (with re-
spect to the starting crotylsilane). We discuss here the regio-
and stereochemical aspects of the reaction and report the
development of the robust asymmetric Hosomi–Sakurai re-
action using chiral silver catalyst.
Introduction
Hosomi–Sakurai reaction of enantio-enriched allyl-
silanes[1] and carbonyls under Lewis acidic conditions gen-
erally proceeds through a SEЈ mechanism.[2] One of the
main characteristics of those reactions is stereospecific chi-
rality transfer from the α-position of allylsilanes to the re-
sulting homoallylalcohols [Scheme 1, equation (1)]. In con-
trast to those methodologies, protocols based on the trans-
metallation of allylsilane to a metal would generate a com-
plex mixture of regio- and diastereomers due to the forma-
tion of highly reactive allylanion species [Scheme 1, equa-
tion (2)]. Distribution of these products can be controlled
by the fine optimization of the catalyst. In that case, the
process will be asymmetric transformation controlled by the
chiral catalyst even when racemic allylsilanes are used.[3]
Results and Discussion
When the reaction was carried out using (but-3-en-2-yl)-
trimethoxysilane, γ adduct was formed with remarkable
syn-selectivity. The same product, with the same level of
diastereoselectivity, was obtained when 2-butenyltrimeth-
oxysilane was subjected to the standard reaction conditions
(Scheme 2). We speculate that the reaction proceeds via a
single allylsilver intermediate, generated through transme-
tallation process, and that the regio- and stereoselectivity of
the reaction are determined by the stability and/or reactiv-
ity of that intermediate. Our hypothesis of a single reactive
species is supported by the observation that the same re-
gioisomer was formed from structurally isomeric allyl-
silanes (Scheme 2).
Considering the geometry of allylsilane, there are two
possible stereo faces of the allylsilane that can approach
the ketone, the face in which the silicon group resides (syn-
addition) and the face opposite the silicon group (anti-ad-
dition). To clarify which of the two faces approaches the
ketone, allylsilane 1 bearing phenyl group in 5-position was
subjected to the standard reaction conditions (Table 1). Sur-
Scheme 1. Generation of four possible isomers from chiral allyl-
silane.
[a] Department of Chemistry, The University of Chicago,
5735 South Ellis Avenue, Chicago, Illinois 60637, USA
Fax: +1-773-702-5059
E-mail: yamamoto@uchicago.edu
5132
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5132–5134

Studies of Ag-Catalyzed Hosomi–Sakurai Reactions
ity would therefore depend on the stability or reactivity of
that intermediate.
An electron-withdrawing group in the 4-position of the
acetophenone (Entry 1, Table 2) does not affect the dia-
stereoselectivity of the reaction. However, introduction of
the isopropyl group in the 5-position of the allylsilane (4,
Table 2) provides an increased level of the diastereoselec-
tivtity. Remarkably, asymmetric induction was observed at
the C-5 atom despite the fact that the starting allylsilane
was racemic.
Scheme 2. Catalyst controlled crotylation of ketones.
prisingly, only two isomers (2A and 2B, Table 1) with high
ee values were obtained. It was determined that those iso-
mers were epimeric at 5-position. It is important to note
that diastereo- and enantioselectivity do not depend on the
syn/anti ratio of the starting silane 1 (Table 1). These results
suggest that a single allylsilver intermediate, which un-
dergoes addition to the ketone, is formed. Diastereoselectiv-
Conclusions
In summary, a detailed stereochemical study of asymmet-
ric AgI-catalyzed Hosomi–Sakurai reaction of ketones has
been described. Plausible mechanistic scenario involves for-
mation of a single reactive allylsilver species that reacts with
ketones to furnish homoallyl alcohols in a highly regio-,
diastereo- and enantioselective fashion. Our hypothesis is
supported by the observation that stereochemical infor-
mation in the allylsilane does not translate to the product.
From this point of view, the main advantage of the method
is that it does not necessitate tedious procedures for the
preparation of enantio-pure allylsilanes.
Table 1. Enantioselective allylation of acetophenone with (5-
phenyl-1-cyclohexenyl)trimethoxysilane.[a]
Experimental Section
General Experimental Procedure for Allylation of Ketones: A flame-
dried test tube was charged with AgF (1.6 mg, 0.012 mmol) and
(R)-Difluorophos (8.4 mg, 0.012 mmol). To this mixture were
added dry THF (2.5 mL) and MeOH (0.24 mmol) and the resulting
mixture was stirred for 15 min. After 15 min, THF and MeOH
were removed in vacuo. After all the volatiles were removed, the
solid residue was dissolved in THF (2.5 mL) and cooled to –78 °C.
After the reaction mixture was cooled, ketone (0.24 mmol) and al-
lyltrimethoxysilane (0.24 mmol) were added. Upon reaction com-
pletion, as determined by TLC analysis, the reaction mixture was
filtered through a short silica plug and concetrated in vacuo. The
crude reaction mixture was purified by column chromatography
(hexanes/Et2O).
[a] The reactions were carried out at –78 to –40 °C for 24 h. [b]
Yields of the isolated products. [c] Diastereomeric ratio was deter-
1
mined by H NMR spectroscopy. [d] Enantiomeric excess was de-
termined by HPLC analysis (OD-H, Chiracel column).
Acknowledgments
Table 2. Enantioselective allylation of ketones with 5-substituted
cyclohexenyltrimethoxysilanes.[a]
We thank the National Institutes of Health (NIH) and the National
Science Foundation (NSF) for the financial support.
[1] a) S. E. Denmark, N. G. Almstead, in: Modern Carbonyl Chem-
istry (Ed.: J. Otera), Wiley-VCH, Weinheim, 2000, chapter 10;
b) S. R. Chemler, W. R. Roush, in: Modern Carbonyl Chemistry
(Ed.: J. Otera), Wiley-VCH, Weinheim, 2000, chapter 11.
[2] T. Hayashi, M. Konishi, H. Ito, M. Kumada, J. Am. Chem.
Soc. 1982, 104, 4963.
[3] For reviews of dynamic asymmetric transformation, see: a)
B. M. Trost, Chem. Pharm. Bull. 2002, 50; b) B. M. Trost,
M. L. Crawley, Chem. Rev. 2003, 103, 2921.
[4] M. Wadamoto, H. Yamamoto, J. Am. Chem. Soc. 2005, 127,
14556.
[5] H. Yamamoto, M. Wadamoto, Chem. Asian J. 2007, 2, 692,
[a] The reactions were carried out at –78 to –40 °C for 24 h. [b]
Yields of the isolated products. [c] Diastereomeric ratio was deter-
and references cited therein.
1
mined by H NMR spectroscopy. [d] Enantiomeric excess was de-
Received: June 17, 2009
termined by HPLC analysis (OD-H, Chiracel column).
Published Online: September 11, 2009
Eur. J. Org. Chem. 2009, 5132–5134
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www.eurjoc.org
5133

M. Wadamoto, M. Naodovic, H. Yamamoto
SHORT COMMUNICATION
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5132–5134