New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

F.C.E. Sarabèr, A. Baranovsky, B.J.M. Jansen, M.A. Posthumus, Æ. de Groot

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19 Citations (Scopus)

Abstract

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9, 11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr2 front a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton.
Original languageEnglish
Pages (from-to)1726-1742
JournalTetrahedron
Volume62
Issue number8
DOIs
Publication statusPublished - 2006

Keywords

  • (+)-9(11)-dehydroestrone methyl-ether
  • vitamin-d-3 northern portion
  • optically-active steroids
  • ring closure reactions
  • claisen-ene strategy
  • conjugate addition
  • one-pot
  • alpha,beta-unsaturated ketones
  • enantioselective synthesis
  • 2+2+2 construction

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