Neighbouring group effects. Part 1. Effect of α-hydroxy- and α-acetoxy-groups on the ring opening of steroidal 4,5-epoxides

Abstract

Ring-opening of steroidal 4β,5β-epoxides (1)–(5) and 4α,5α-epoxides (6)–(10) having a hydroxy- or acetoxy group at C-6 with perchloric acid in tetrahydrofuran occurs at C-4 regioselectively. The reactivity of these epoxides is noticeably affected by the presence of a neighbouring group at the 6-position. A 6β-axial acetoxy-group completely blocks cleavage of the epoxide ring and 6α-equatorial acetoxy- and 6β-hydroxy-groups retard the reaction, while a 6α-equatorial hydroxy-group has no significant effect. Differences in the regioselectivity and reactivity of ring opening of the 4α,5α-epoxide system in (22)–(24) arise from differences in the degree of participation of the 3β- or 6β-acetoxy-group.