An Enantioselective Synthesis of an 11-β-HSD-1 Inhibitor via an Asymmetric Methallylation Catalyzed by (S)-3,3'-F2-BINOL

J Org Chem. 2016 Mar 18;81(6):2665-9. doi: 10.1021/acs.joc.6b00189. Epub 2016 Mar 2.

Abstract

An efficient asymmetric synthesis of 11-β-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenases / chemistry
  • Catalysis
  • Ketones / chemistry
  • Naphthols / chemical synthesis*
  • Naphthols / chemistry
  • Propane / analogs & derivatives*
  • Propane / chemical synthesis
  • Propane / chemistry
  • Stereoisomerism

Substances

  • 3,3'-F2-BINOL
  • 3-chloro-1-phenylpropan-1-one
  • Ketones
  • Naphthols
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Propane