Steroid nitrogen compounds. III. A general method for introduction of O, N, S and other functionality into position-5 of cholestanes. conjugate addition of nucleofhiles to 6-nitrosocholesteryl acetate generated in situ from the 5α-chloro-6-oxime

Abstract

The conjugate addition of organic and inorganic nucleophiles to 6-nitrosocholesteryl acetate (II) generated in situ from 3β-acetoxy-5-chloro-6-hydroxyimino-5α-cholestane (I) has been shown to give high yields of 5α-substituted 6-oximes (IIIa-h) under mild reaction conditions. Nucleophiles include ethanethiol, ethanol, methylamine, ammonia, nitrite, cyanide, thiocyanate and azide. Validity of the proposal that the replacement of chlorine atom of α-chlorooximes by nucleophiles proceeds via an elimination-addition mechanism through nitrosoolefins has been confirmed by the isolation and conversion of II into methoxy oxime (III, X = OMe) by the treatment with methanol. Due to the steric hindrance exerted by α-hydrogen atoms at λ-positions, bulky nucleophiles, which have been reported to react with α-chlorooximes, failed to react with the chlorooxime (I). Effects of 5α-substituents upon the signal position of the 3α-proton are described.