Thermodynamically controlled enol acetylation of Δ4-3-oxo-steroids

Abstract

Treatment of steroid ketones with acetic anhydride–hydrobromic acid reagent yields, under thermodynamic control, mixtures of enol acetates. 17β-Hydroxy-2α-phenylandrost-4-en-3-one affords a mixture of 2α-phenylandrosta-3,5-diene-3,17β-diol diacetate and 2-phenylandrosta-2,4-diene-3,17β-diol diacetate in the ratio 3:2. The influence of a 6-methyl group on this reaction is to favour formation of the 3,5-dienol acetate rather than the 2,4-dienol acetate by a free-enrgy difference of 1·44 kcal./mole.