A novel chiral sulfonium yilde: Highly enantioselective synthesis of vinylcyclopropanes

Article abstract of DOI:10.1021/ja0172969

A newly designed chiral sulfonium allylide, generated in situ from the corresponding sulfonium salt in the presence of KOBu^t, reacted with α,β-unsaturated esters, ketones, amides, and nitriles to afford trans-2-silylvinyl-trans-3-substituted cy

Full text of DOI:10.1021/ja0172969

Published on Web 02/22/2002
A Novel Chiral Sulfonium Yilde: Highly Enantioselective Synthesis of
Vinylcyclopropanes
Song Ye, Zheng-Zheng Huang, Chun-An Xia, Yong Tang,* and Li-Xin Dai
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received October 13, 2001
Chart 1
The occurrence of the vinylcyclopropane subunit in many natural
and synthetic biologically active compounds,1 as well as its utility
as a synthetic intermediate,2 has promoted many strategies for its
construction.3-6 No successful direct asymmetric synthesis of
vinylcyclopropanes has been reported except for a few examples
of those related to disubstituted or 1,1,2-trisubstituted compounds.4
For the preparation of 1,2,3-trisubstituted cyclopropanes, Hanessian
et al. reported a cycloaddition reaction of chiral chloroallylphos-
phonic amide to afford this type of compound with excellent
diastereoselectivity.5a Very recently, Taylor found that these kind
of compound also could be prepared from chiral homoallylic alcohol
via several steps.5b In view of the difficulty associated with the
regioselectivity and diastereoselectivity (cis/trans) and enantio-
selectivity, the highly selective synthesis of optically active 1,2,3-
trisubstituted cyclopropanes in one step remains a challenging
problem. In this paper, we wish to report our preliminary results
on this subject.
Chart 2
The high yield and excellent enantioselectivity encouraged us
to study the generality of this reaction by investigating a variety of
R,â-unsaturated carbonyl compounds. As shown in Table 1, â-aryl-
R,â-unsaturated esters, amides, ketones, and nitriles all worked well
to give the desired products in good yields with excellent enanti-
oselectivities (Table 1). For the esters, amides (entries 1-5),
diastereoselectivities of this reaction were outstanding and only one
diastereoisomer was obtained. When R,â-unsaturated ketones
(entries 6 and 7) were applied, the chemoselectivities were excellent
and no epoxides were detected. Both diastereoselectivities and
enantioselectivities of their cyclopropanation reactions were excel-
lent. Unlike simple sulfonium allylide that is hard to react with
R,â-unsaturated nitrile,9 to our surprise, ylide 3a worked well.
Moreover, their diasteroselectivities were outstanding and enantio-
selectivities were also excellent (entries 8 and 9). From the X-ray
structure analysis of salt 2a, the distance between the atom of sulfur
and oxygen is only 2.78 Å10 and the distortion angle of O-C1-
C2-S is 0°. These results showed that there may exist a bonding
interaction between the sulfur and the oxygen, which probably
stabilizes the ylide and partially inhibits the [2,3]-σ rearrangement
of ylide 3a.
In our previous publications, we found lithium ion played a
crucial role on the stereoselective tuning of the cyclopropanation
reaction of telluronium allylides with R,â-unsaturated esters or
amides.6 The mechanistic reason for this tuning in the presence of
lithium ion has also been rationalized by the formation of a chelating
six-membered-ring transition state, which is formed by coordination
of lithium ion with carbonyl oxygen and ylidic carbanion simul-
taneously (A in Chart 1). On the basis of this mechanistic insight,
we envisaged that it is possible to enhance the diastereoselectivity
and enantionselectivity by formation of a rigid six-membered ring
if a coordination group such as a hydroxyl, amino group is
introduced into a chiral ylide molecule in the presence of metal
ion (B in Chart 1). Thus, chiral sulfonium ylide 3a was designed
and its precursor 2a7 was found to be readily available from the
corresponding sulfide 1a that was easily prepared from D-camphor
8
in two steps by a known procedure (eq 1).
The diastereoselectivity of reaction with methyl acrylate was very
high and a 95% ee was obtained (entry 10). The reaction with
methyl crotonate afforded cyclopropanes 5k/5k′ with 84/16 dia-
stereoselectivity and 92% ee in 20% yield (entry 11). The reaction
with methyl cis-cinnamate only gave a trace of the desired product,
probably due to its low activity (entry 12). In these two cases
(entries 11 and 12) the ylide rearrangement products 6a and 6b
(Chart 2) were obtained.
It is worth noting that the endo-isomer 2b (Chart 2) could also
react with methyl cinnamate to afford the corresponding cyclopro-
panation product with moderate, but opposite enantioselectivity
(entry 13). Thus, either of the two enantiomers could be obtained
at will just by the choice of exo- or endo-sulfonium salts, both of
which were derived from cheap D-camphor.
We are pleased to find that ylide 3a, generated from the
corresponding salt 2a and KOBut (3.0 equiv) in situ, could react
with methyl cinnamate in one pot to afford vinylcyclopropane 5a
with 97% ee in 85% yield (eq 2).
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10.1021/ja0172969 CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Asymmetric Ylide Cyclopropanation of Sulfonium Salts
2a or 2b with Michael Acceptors
Scheme 1. Chemical Transformations of the Cyclopropane 5a
a Conditions: (a) acetyl chloride, AlCl3, DCM, room temperature, 72%,
ref 6d; (b) NaIO4, OsO4 (cat.), Py, t-BuOH/H2O, room temperature, 84%,
97% ee; (c) m-CPBA, CH2Cl2, room temperature, 89%; (d) HClO4, THF/
H2O, room tmeperature, 100%.
was treated with HClO4 to form aldehyde 9 in quantitative yield
(Scheme 1).
In conclusion, we have developed an efficient method for one-
step enantioselective synthesis of 1,3-disubstituted-2-silylvinylcy-
clopropanes. As a result, both diastereoselectivity (cis/trans) and
enantioselectivity are excellent in most cases studied. Since the ylide
is readily available from cheap D-camphor and the enantioselectivity
is partially tunable, the current method has a high potential for
practical use in organic synthesis. Asymmetrical ylide epoxidation
is in progress in our laboratory.
Acknowledgment. We are grateful for financial support by the
National Natural Sciences Foundation of China (No. 20172066).
This paper is dedicated to professor Yao-Zeng Huang on the
occasion of his 90th birthday.
Supporting Information Available: Synthesis and characterization
of a key compound, chiral HPLC data of 5a-j, ent-5a, and 7, and
determination of the absolute configurations of 5a,e,i,j (PDF), and the
X-ray structure of 2a and 5i (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
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Figure 1. Proposed transition states.
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The transition state model shown in Figure 1 supports all the
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The silylvinylcyclopropane derivatives prepared by the current
method should be synthetically useful. For example, compound 5a
was easily oxidized into aldehyde 7 without loss of ee, which is a
key intermediate for the synthesis of biologically active compound
PCCGs.11 It could also be oxidized to afford the epoxide 8 that
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