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Diastereoselective Approaches to trans ‐Hydrindane Derivatives − Total Synthesis of 8‐(Phenylsulfonyl)de‐A,B‐cholestane Precursors to 25‐Hydroxyvitamin D 3
Author(s) -
Prowotorow Igor,
Stepanenko Wiaczesław,
Wicha Jerzy
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200208)2002:16<2727::aid-ejoc2727>3.0.co;2-1
Subject(s) - chemistry , dioxolane , ketene , moiety , total synthesis , sulfone , michael reaction , stereochemistry , ring (chemistry) , yield (engineering) , tandem , cascade reaction , medicinal chemistry , organic chemistry , catalysis , materials science , metallurgy , composite material
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 intermediates involved cyclization, oxidation with m ‐CPBA, and reduction of the vinylic sulfone moiety to afford the trans ‐hydrindane ring system. The synthesis comprises five operations and afforded the product in ca. 30% yield. The application of 2‐[(phenylthio)methyl]‐2‐vinyl[1,3]dioxolane and 2‐(phenylsulfonylmethyl)‐2‐vinyl[1,3]dioxolane as Michael acceptors was also examined. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)