Highly efficient Lewis acid catalyzed, one step conversions of 16α,17α-epoxy-3β-hydroxypregn-5-en-20-one to d-homosteroid and Δ 13-steroids

Abstract

Conversion of 16α,17α-epoxy-3β-hydroxypregn-5-en-20-one ( 1a) to 16β-chloro-3β,17α-dihydroxy-17β-methyl-17a-homoandrost-5-en-17a-one ( 3) in very high yields (95%), in one step by treatment with 3 equiv. of anhyd. AlCl 3, has been achieved; use of two equiv. of AlCl 3 affords mixture of d-homosteroid 3 (70%) and chlorohydrin 4 (27%). On the other hand, treatment of 1a with excess of acetic anhydride and anhydrous ZnCl 2 at room temperature leads to reversal of the direction of epoxide ring opening with concomitant methyl migration, leading to 3β,16α-diacetoxy-17-methyl-17α-pregna-5,13-diene-20-one ( 6) in high yield (92 %). The conversions are a remarkable improvement over related routes in terms of both yield and selectivity.