Stereoselective synthesis of (±)-ancistrofuran and its stereoisomers

Abstract

The four possible stereoisomers of ancistrofuran have been prepared from γ-cyclohomocitral. Addition of 3-furyl-lithium yielded two epimeric alcohols. Each alcohol was epoxidised with m-chloroperbenzoic acid and reduction with lithium aluminium hydride gave mixtures of two diols in each case. Treatment of each mixture with toluene-p-sulphonyl chloride gave the four stereoisomers of ancistrofuran. A stereoselective synthesis was also developed to the trans-fused ancistrofuran which was identical with the natural isomer. Lactol (22) was conveniently prepared by di-isobutyl aluminium hydride reduction of lactone (23). Reaction of the lactol with 2 mol equiv. of 3-furyl-lithium gave a mixture of two diols in 3:1 ratio. Oxidation with manganese dioxide gave ketone (24) which underwent reduction with lithium triethylborohydride in a highly stereoselective manner to yield diol (13). Ketone (24) was also prepared in one step by reaction of lactone (23) with 1 mol equiv. of 3-furyl-lithium. Subsequent treatment of diol (13) with toluene-p-sulphonyl chloride gave ancistrofuran, identical with the natural product. The stereoselective reduction of the γ-hydroxy ketone has been discussed and is suggested to involve ‘chelation control’.