Stereoselectivity in the epoxidation and cis-hydroxylation of 16-methylene-estra-1,3,5(10)-trienes

Epoxidation of 3-methoxy-16-methylene-estra-1,3,5(10)-trien-17-one in the presence of alkaline hydrogen peroxide gives rise to (16R)- and (16S)-spiro[3- methoxy-17-oxoestra-1,3,5(10)-triene-16,2'-oxirane] in similar proportions. Epoxidation of the corresponding 16-methylene 17 beta-alcohol and 16-methylene-17 beta-acetate with m-chloroperbenzoic acid does not display any significant directing effects associated with allylic functionality, whereas Sharpless epoxidation of the 16-methylene 17 beta-alcohol is highly stereoselective, leading exclusively to the (16R) isomer. cis-Hydroxylation of the 16-methylene 17-ketone with osmium tetroxide/4-methylmorpholine-4-oxide proceeds stereoselectively to give mainly 16 alpha-hydroxy-16 beta-hydroxymethyl-3-methoxyestra-1,3,5(10)-trien-17-one. The isomeric addition products derived from these reactions are correlated by appropriate interconversions, and the assignments are corroborated by comparative reactivity of derived products.