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

Article abstract of DOI:10.1016/0039-128X(94)90018-3

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 17β-alcohol and 16-methylene-17β-acetate with m-chloroperbenzoic acid does not display any significant directing effects associated with allylic functionality, whereas Sharpless epoxidation of the 16-methylene 17β-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 16α-hydroxy-16β-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. - Keywords: estra-1,3,5(10)-trienes; 16-methylene-estra-1,3,5(10)-trienes; epoxidation; Sharpless epoxidation; hydroxylation