Synthesis of (2S,1′R,2′R,3′R)-2-(2′,3′-Dicarboxycyclopropyl)-glycine via the Stereochemically Controlled Cyclopropanation of (S)-Glyceraldehyde Acetonide-Derived Enones

The reaction of ethyl dimethylsulfonium acetate bromide with aromatic enones 5a or 5b derived from (S)-glyceraldehyde acetonide under the action of DBU provides cyclopropanation products in excellent yield and good diastereoselectivity (10/1). High geometry-selectivity (>95/1) can be reached when the reaction is carried out at lower temperature in toluene. The cis-enone 5a gives better geometry-selectivity than trans-enone 5b. The ylides with amide groups can also be used for cyclopropanation reaction but neither the yields nor the geometry-selectivity are satisfactory. Based on 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, is developed.