Studies of Enamidic Δ5-4-Azasteroidal Selenoxides: Preparation, Pummerer Reactions, Configurational Stability, and Conversion to Carbinol Amides

Article abstract of DOI:10.1021/jo00138a017

Enamidic 4-azasteroids 5a,b were oxidized by benzeneseleninic anhydride (1) to afford carbinol amides 6a,b, 7α- and 7β-hydroxy-6-phenylseleno derivatives 7a,b and 8a,b, and selenides 9a,b.Selenoxide intermediates 12a,b are initially formed in this process and generate the observed products through Pummerer reactions.Selenoxide 12a was prepared independently in excellent yield by the sequential treatment of enamide 5a with benzeneselenenylchloride and 1 equiv of m-chloroperbenzoic acid.A 2:1 mixture of selenoxide diastereomers was obtained, from which the majorisomer could be separated by equilibration and percipitation from aqueous pottasium carbonate solution.The selenoxide is thermally stable but racemizes via an achiral selnoxide hydrate.The further oxidation of 12a,b with m-chloroperbenzoic acid produced carbinol amides 6a,b in yields of 72percent and 62percent, respectively.Compound 6a underwent facile hydroxyl exchange in acidic methanol.The oxidation of enamide 5a with the peracid in the presence of methanol produced the 6-hydroxy carbinol amide methyl ether 18, which readily eliminated methanol to give 6-keto lactam 19.