Diastereoselective approaches to trans-hydrindane derivatives - Total synthesis of 8-(phenylsulfonyl)de-A,B-cholestane precursors to 25-hydroxyvitamin D3

Article abstract of DOI:10.1002/1099-0690(200208)2002:16<2727::AID-EJOC2727>3.0.CO;2-1

The total diastere os elective synthesis of the C,D rings/side chain building block for the synthesis of 1α,25 -dihydroxyvitain D₃ 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-hydindane 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] dioxoIane as Michael acceptors was also examined. c Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.