Mukaiyama and Torgov Chemistry in the Synthesis of (D-homo) Steroid Skeletons

F.C.E. Sarabèr, S.V. Drach, A. Baranovsky, T. Charnikhova, S. Pogrebnoi, B.J.M. Jansen, Æ. de Groot

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Three new, short, and efficient procedures have been developed for syntheses of steroid and D-homo steroid skeletons by application of Mukaiyama and Torgov chemistry. An important element in the first and in the second route is a Mukaiyama-Michael reaction with transfer of the silyl group from the starting silyl enol ether to the carbonyl group of the receiving enone. In this way a new silyl enol ether is obtained which enables either a selective reaction with the silyl enol ether in ring D as in route 1, or a selective reaction with the unprotected carbonyl group in ring B as in route 2. In all three approaches the C12-C13 bond is constructed using a Mukaiyama reaction of a Torgov type carbocation precursor with a silyl enol ether as the key transformation. In route 1, Zieglers triketone, which has been used before in the synthesis of 9,11 -dehydroestrone methyl ether, has been prepared in four easy steps and in 70% overall yield, using the reactions mentioned above. In the second route a selective Grignard reaction of vinyl magnesium bromide with the unprotected carbonyl group of methoxy tetralone leads to a Torgov type intermediate. This can be converted easily into a carbocation, which then reacts intramolecularly with the silyl enol ether in ring D, under formation of the C12-C13 bond to complete the synthesis of cis (D-homo) steroid skeletons. In the third route, C 17 substituted C,D trans coupled (D-homo) steroid skeletons have been prepared via an intermolecular addition of a carbocation, generated with ZnBr2 from a Torgov reagent, to a silyl enol ether containing ring D precursor. The adducts have been cyclized under formation of the C8-C14 bond by treatment with acid and the double bonds in the cyclized products have been reduced to all trans steroid skeletons. A chiral five membered silyl enol ether containing ring D precursor has been synthesized from carvone, and used as starting compound in the synthesis of a chiral C 17 functionalized steroid.
Original languageEnglish
Pages (from-to)535-548
Number of pages13
JournalPolish Journal of Chemistry
Volume80
Issue number4
Publication statusPublished - 2006

Keywords

  • vitamin-d-3 northern portion
  • electrocyclic ring-closure
  • optically-active steroids
  • conjugate addition
  • enantioselective synthesis
  • aromatic steroids
  • allylic alcohols
  • building-block
  • derivatives
  • rearrangement

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