Controllable Diastereoselective Cyclopropanation. Enantioselective Synthesis of Vinylcyclopropanes via Chiral Telluronium Ylides

Article abstract of DOI:10.1021/ja036254c

Novel chiral telluronium salts 1 are designed for asymmetric synthesis of 1,3-disubstituted 2-vinylcyclopropanes. The allylides, generated in situ from the corresponding telluronium salt in the presence of different base, reacted with α,β-unsaturated este

Full text of DOI:10.1021/ja036254c

Published on Web 10/07/2003
Controllable Diastereoselective Cyclopropanation. Enantioselective Synthesis
of Vinylcyclopropanes via Chiral Telluronium Ylides
Wei-Wei Liao, Kai Li, and Yong Tang*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received May 21, 2003; E-mail: tangy@pub.sioc.ac.cn
Compounds containing vinylcyclopropane fragments have re-
ceived considerable attention because of their frequent occurrence
Table 1. Enantioselective Cyclopropanation via Telluronium
Ylides13
1
in biologically active compounds, as well as their utility as valuable
2
synthetic intermediates. Although many synthetic methods have
3
been developed, asymmetric synthesis of multisubstituted vinyl-
cyclopropanes with high diastereoselectivities and enantioselec-
tivities remains a challenging problem. One of the most common
methods is the transition metal-catalyzed cyclopropanation4 of
5
a
R-diazo carbonyl compounds with electron-rich alkenes. Suzuki
and Taylor5b found that these kinds of compounds could be prepared
from optically pure homoallylic alcohol via several steps. The
+
-
addition of allylic ylides L
is also a convenient and attractive method because ylides are readily
available and L M is easily recovered and reused. However,
n
M CH CHdCHX to Michael acceptors
n
practical methods for the highly enantioselective synthesis of
multisubstituted vinylcyclopropanes via an ylide remain undevel-
oped probably due to the difficulties associated with both enanti-
6
oselectivity and diastereoselectivity. Hanessian et al. described an
efficient protocol for the preparation of these kinds of compounds
with excellent diastereoselectivity using a phosphonic amide as a
7
chiral auxiliary. Recently, Aggarwal et al. reported the reaction
of a chiral silylated allylic sulfur ylide with R-aminoacrylate to
afford the desired vinylcyclopropane with 71% de and 75% ee.
Very recently, our laboratory discovered an efficient method for
the one-step enantioselective synthesis of 1,3-disubstituted-2-
silylvinylcyclopropanes with high diastereoselectivity via a sulfur
8
ylide. However, this method is limited to the cyclopropanation of
â-aryl-R,â-unsaturated esters, amides, ketones, and nitriles. For
â-alkyl-R,â-unsaturated esters such as methyl crotonate, low yields
are obtained due to the rearrangement of the sulfur ylide although
the enantioselectivity is high. In addition, there is still lack of access
to other optical isomers with different relative configurations.
Despite their importance, few reports have appeared from the
literature on catalytic asymmetric synthesis of 1,2,3-trisubstituted
cyclopropanes with high enantioselectivity and diastereoselectivity
via ylide routes. In this communication, we report an enantiose-
lective synthesis of trisubstituted cyclopropanes with controllable
diastereoselectivity and its catalytic version.
a
Determined by GC and/or 1H NMR except noted. b Isolated yield.
c
d
Determined by HPLC using chiral stationary phases and for 3. The
absolute configurations were determined by X-ray diffraction. Determined
e
f
g
by GC using chiral stationary phases. Determined by GC-MS. Conver-
sion. h The ester recovered in 98% yield.
1, Table 1). Encouraged by the high diastereoselectivity and
excellent enantioselectivity, we evaluated a variety of R,â-unsatur-
ated carbonyl compounds as substrates. As shown in Table 1, R,â-
unsaturated esters, amides, ketones were suitable substrates for the
reaction. The reactions afforded high diastereoselectivity and
enantioselectivity for â-aryl- and â-heteroaryl unsaturated esters
in high yields. This ylide also proved to be efficient for methyl
crotonate, which gave 94% ee in moderate yield (entry 8).
Noticeably, R,â-unsaturated ketones gave cyclopropanes in high
regioselectivity (entries 9-13). No epoxides were detected in this
reaction. Additionally, whatever â-aryl- or â-alkyl substituted
ketones were employed, excellent ee (up to 99%) and high
diastereoselectivities were obtained. R,â-Unsaturated amides are
less effective substrates in this reaction. Although both the yield
and enantioselectivity were high, the conversion of cinnamylamide
was low for reasons that remain unclear (entry 14). Unlike the sulfur
2
Metzner found that a C -symmetric sulfur ylide is a good reagent
for the preparation of diarylepoxides with high enantioselectivities.9
Very recently, they reported that the sulfur ylide could react with
aldehydes enantioselectively to afford vinylepoxides and the
a
9b
enantiomeric excess ranged from 37 to 90%. Considering that
allylic telluronium ylides10 are more reactive than the correspond-
ing sulfur ylides, we designed new telluronium salts 1 to start our
study. These salts were readily prepared from (2S,5S)-(+)-2,5-
hexanedioldimethanesulfonate.9 Gratifyingly, it was found that
the salt 1a, after deprotonation by LiTMP/HMPA in situ, could
react with methyl cinnamate to afford vinlcyclopropane 3a with
high diastereoselectivity (96/4, 3/4) and 96% ee in 95% yield (entry
11
a,12
13030
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J. AM. CHEM. SOC. 2003, 125, 13030-13031
10.1021/ja036254c CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
Table 2. Controlled Reversal of Diastereoselectivities13
are improved. The facile synthesis of telluride, controllable dias-
tereoselectivity, and high enantioselectivity give this methodology
high potential for practical use in organic synthesis.
Acknowledgment. We are grateful for financial support by the
National Natural Sciences Foundation of China. This paper is
dedicated to Professor Wei-Shan Zhou on the occasion of his 80th
birthday.
Supporting Information Available: Synthesis and characterization
of key compounds, GC and HPLC data of 3 and 4, mechanistic model
for diastereoselectivity (PDF). X-ray crystallographic files in CIF
format. This material is available free of charge via the Internet at http://
pubs.acs.org.
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with up to 89% ee (Scheme 1).
2
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2
(
(13) For detailed procedures, please see Supporting Information. Compared
-
with the corresponding bromide, the solubility of the salts using [BPh
4
]
To summarize, we have developed an efficient method and the
first example of catalytic ylide reaction for the enantioselective
synthesis of 1,3-disubstituted 2-vinylcyclopropanes with high
diastereoselectivity. Noticeably, two diastereomers could be ob-
tained at will with high enantioselectivity in some cases. Compared
with our previous report, both the yields and enantioselectivities
as the counterion in THF was much improved. Thus, higher yields (with
similar selectivities) were observed when changing the counterion of the
4
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(
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