Diastereoselective Approaches to trans-Hydrindane Derivatives − Total Synthesis of 8-(Phenylsulfonyl)de-A,B-cholestane Precursors to 25-Hydroxyvitamin D3

Abstract

The total diastereoselective synthesis of the C,D rings/side chain building block for the synthesis of 1α,25-dihydroxyvitamin D 3 is described. Two tandem Mukaiyama−Michael additions involving silylated ketene acetals derived from tert-butyl 6-methylhept-5-enethioate or tert-butyl 6-methylhept-6-enethioate, 2-methylcyclopent-2-en-1-one, and 1-(phenylthio)but-3-en-2-one afforded the corresponding intermediates with the complete carbon framework of the target compound. The further transformation of these key interme-

A Concise Account of Various Approaches for Stereoselective Construction of the C-20(H) Stereogenic Center in Steroid Side Chain

“…Ketene acetal 298 , upon treatment with enone 294 in the presence of a catalytic amount of TrSbCl 6 and then addition of the reaction mixture to 1-thiophenylbut-3-en-2-one 303 as the second Michael acceptor, gave diketone 304 in 72% yield (Scheme ).…”

Enantioselective Total Synthesis of a trans‐Hydrindane Rings/Side‐Chain Building‐Block of Vitamin D − Asymmetric Induction in an Acid‐Catalyzed Conjugate‐Addition Reaction

“…the ''northern'' portion) presents an ongoing challenge to organic chemists. [10Ϫ15] Recently, we reported [16] a concise diastereoselective synthesis of the northern building-block of 25-hydroxyvitamin D 3 8 (Scheme 2), in which we utilized two tandem MukaiyamaϪMichael reactions. Herein, we present the results from our efforts to combine diastereoselectivity and efficiency in carbonϪcarbon bond-forming reactions with the demands of enantioselectivity in the generation of four contiguous stereogenic centers, at C-13, C-14, C-17 and C-20 (steroid numbering), in 8.…”