The preparation of enantiomerically pure /3,~epoxyesters was achieved by chemoselective opening of &hydroxybutanoli&s with trimethylsilyliodide followed by cyclisation of the resulting iodohydrins with silver oxide. The reaction of these epoxyesters with lithio or magnesiocuprates ajorded stereochemically pure a-substituted /3-hydroxyesters.
Alternatively, (-)-GABOB was synthesized in optically pure form from the iodohydrin 2'0.
Optically active epoxydes are very valuable synthetic intennediis due to their great facility to give both electrophilic and nucleophilic opening and to allow the access to chiral building-blocks possessing several chiral centers. They may be obtained by asymmetric epoxydation, by moditication of natural products from the "chiral pool" t or by microbial reactions.2
All these methods were applied with success to the preparation of a-functionalixed epoxydes but frequently failed when applied to f%-functionalixed substrates. For example, the asymmetric epoxydation of homoallylic alcohols gives low enantiomeric excesses3, and the resolution of racemic ~,-y-epoxyesters by lipases or esterases is not general enough.4
We want to report here an efftcient chemical method to prepare p,y-epoxyesters based on the chemoselective opening of P-hydmxylactones followed by a basic cychsation of the intermediate iodohydrines.5 P-hydroxybutanolides la are easily obtained in R or S form from malic, aspartic and ascorbic acid.6 or by microbial reduction of P-ketoesters.7 They may be stereoseIectively alkylated into the trans lactones lb or l'b.8 Moreover, the cis isomer lc is available from the microbial reduction of a-methyl p-ketoester.9 H Me&l -' """, EtOH 1