New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions
- 作者：Florence C.E. Sarabè ; r ; Alexander Baranovsky ; Ben J.M. Jansen ; Maarten A. Posthumus and Aede de Groot
- 关键词：Mukaiyama– ; Michael addition ; Silyl enol ethers ; Torgov reagent ; (D-homo) steroid synthesis ; Carvone
- 刊名：Tetrahedron
- 出版年：2006
- 期刊代码：107_00404020
- 类别：ch
- 出版时间：20 February 2006
- 卷：62
- 期：8
- 页码：1726-1742
- 文件大小：475 K
摘要
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 from 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.