An Efficient Procedure for Preparing 1α,3β-Dihydroxy-Δ5-sterois by Reduction of 1α,2α-Epoxy-4,6-dien-3-ones with Lithium in Ammonia

Article abstract of DOI:10.1002/hlca.19810640621

A number of 1α,3β-dihydroxy-Δ⁵-steroids of the cholestane, (20S)-20-methylpregnane (23,24-dinorcholane), pregnane and androstane series were synthesized from common steroidal precursors.A process originally reported by Barton et aI., based on 1,4,6-trien-3-ones as intermediates, was used for the introduction of the lα-hydroxyl function.The last step of this process, consisting of lithium/ammonia reduction of 1α,2α-epoxy-4,6-dien-3-ones, was found to be crucial and therefore subjected to particular study.A reproducible procedure permitting high-yield conversion was developed. lt consists of first reducing the epoxydienone with an approximately stoichiometric amount of lithium in ammonia to give, after protonation with ammonium chloride, a 1α-hydroxy-5-en-3-one.This intermediate is then further reduced by repeated alternating treatment with ammonium chloride and an equivalent amount of lithium.