Reduction of 17α-Hydroxy-20-keto Steroids: Convenient Synthesis of (E)-3β-Hydroxy-5,17(20)-pregnadiene 3-Pivaloate and (Z)-3β,16α-Dihydroxy-5,17(20)-pregnadiene 3-Pivaloate

Article abstract of DOI:10.1021/jo00288a021

Reduction of the 20-keto group of both 17α-hydroxy- and 16-α-alkoxy-17α-hydroxy steroids has been examined with various hydride reagents in a number of different solvent systems.For each of these steroids, specific conditions have been established to cleanly reduce to (20R)-17α,20α-diols.These conditions have been applied to the synthesis of (E)-3β-hydroxy-5,17(20)-pregnadiene 3-pivaloate (5) and (Z)-3β,16α-dihydroxy-5,17(20)-pregnadiene 3-pivaloate (6) from commercially available 3β,17α-dihydroxy-5-pregnen-20-one (7a) and 3β-hydroxy-5,16-pregnadien-20-one(11a), respectively.The pivaloate derivative of 7a was reduced with L-Selectride in THF to provide, after mild acid treatment and oxidative workup, (20R)-17α,20-diol 9 as a single stereoisomer in 86percent yield.Subsequent syn-dideoxygenation of its thionocarbonate derivative with triethyl phosphite afforded pure (E)-ethylidene 5 in 56percent overall yield from 7a. <2-(Trimethylsilyl)ethoxy>methyl (SEM) ether derivative of the 16α-hydroxy group of 3β,16α,17α-trihydroxy-5-pregnen-20-one 3-pivaloate (13b), obtained in two steps from 11a, was reduced with (n-Bu)4NBH4 in THF to provide, after mild acid treatment of the quenched solution, (20R)-17α,20-diol 14b as a single stereoisomer in 90percent yield.Similar dideoxygenation of the diol followed by deprotection of the SEM group with CsF gave 16α-hydroxylated (Z)-17-ethylidene 6 in 48percent overall yield from 11a.In addition, results on stereoselective syn-deoxygenation of (20S)-17α,20-epoxides are also discussed.