ORGANIC
LETTERS
1999
Vol. 1, No. 2
285-287
Stereochemically Controlled
Cyclopropanation of (S)-Glyceraldehyde
Acetonide-Derived Olefins. Synthesis of
(2S,1′R,2′R,3′R)-2-(2′,3′-Dicarboxycyclopropyl)glycine
,†
Dawei Ma,* Yeyu Cao,† Yi Yang,‡ and Dongliang Cheng‡
State Key Laboratory of Bioorganic and Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China, and Department of Chemistry,
Lanzhou UniVersity, Lanzhou 730000, China
Received April 16, 1999
ABSTRACT
The reactions of ethyl (dimethylsulfuranylidene)acetate or other related sulfonium ylides with olefins 1 derived from (S)-glyceraldehyde acetonide
provide cyclopropanation products in good to excellent diastereoselectivity. On the basis of this reaction, a new synthetic protocol for
(2S,1′R,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (L-DCG-IV), an isotype-selective agonist of metabotropic glutamate receptors, is developed.
The 1,2,3-trisubstituted cyclopropane subunit can be found
in many natural and synthetic compounds with important
biological activities.1 Although the enantioselective construc-
tion of cyclopropanes has attracted significant attention in
the past two decades,2 few examples have been reported for
synthesizing enantiopure 1,2,3-trisubstituted cyclopropanes.1,2
In connection with our efforts on the development of
selective modulators for metabotropic glutamate receptors
(mGluRs),3 we recently reported that the olefin 1a reacted
with dimethylsulfoxonium methylide at -30 °C to provide
the cyclopropanation product 2 in 93% diastereoselectivity3a
(Scheme 1). This result stimulated us to try the reaction of
the olefins 1a-g with the sulfoxonium ylide possessing a
suitable electron-withdrawing group to provide 1,2,3-trisub-
stituted cyclopropanes diastereoselectively. The studies thus
undertaken are reported herein.
† Shanghai Institute of Organic Chemistry.
‡ Lanzhou University.
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Initially, we tried the reaction of 1b with ethyl (dimethyl-
sulfuranylidene)acetate (EDSA) generated in situ by treat-
ment of ethyl dimethylsulfonium acetate bromide with DBU.4
(2) For reviews, see: (a) Doyle, M. P.; Protopova, M. N. Tetrahedron
1998, 54, 7919. (b) Burgess, K.; Ho, K. K.; Moye-Sherman, D. Synlett
1994, 574.
(3) (a) Ma, D.; Ma, Z. Tetrahedron Lett. 1997, 38, 7599. (b) Ma, D.;
Tian, H.; Zou, G. J. Org. Chem. 1999, 64, 120.
10.1021/ol990598j CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/15/1999