An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction

Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5776-81. doi: 10.1073/pnas.0307415101. Epub 2004 Apr 12.

Abstract

An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.

MeSH terms

  • Boranes / chemistry*
  • Estrogen Receptor Modulators / chemical synthesis*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Oxidation-Reduction
  • Safrole / analogs & derivatives*
  • Safrole / chemistry*
  • Stereoisomerism

Substances

  • Boranes
  • Estrogen Receptor Modulators
  • Safrole
  • sulfoxide