Stereospecific Grignard reactions of cholesteryl 1-alkenesulfinate esters: Application of the Andersen Protocol to the preparation of non-racemic α,β-unsaturated sulfoxides

Abstract

Enantiomerically enriched α,β-unsaturated sulfinate esters of (–)-cholesterol undergo stereospecific substitutions at sulfur when treated in benzene at 6°C with Grignard reagents. Sulfoxides with ees of 85–99.5% are obtained when enantiopure sulfinates are used. The substitution reactions proceed with inversion of sulfur configuration. Enantiomerically pure cholesteryl (E)-2-carbomethoxyethenesulfinate is not a suitable reactant under the Grignard reaction conditions. It is suggested that the ester group induces unwanted reactions significantly lowering both the yield and sulfur stereogenicity.Key words: sulfinate, sulfoxide, Grignard reagents, stereospecific, unsaturated.