Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-β-Lactams

J Org Chem. 2016 Sep 2;81(17):7692-9. doi: 10.1021/acs.joc.6b01406. Epub 2016 Aug 18.

Abstract

Ru-catalyzed cross-metathesis (CM) reaction between β-arylated α-methylidene-β-lactams and terminal olefins was developed. The CM reaction is effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording corresponding α-alkylidene-β-aryl-β-lactams in good isolated yields (41-83%) with exclusive Z-selectivity. The developed protocol was successfully applied for stereoselective preparation of Ezetimibe, the commercial cholesterol absorption inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / chemical synthesis*
  • Anticholesteremic Agents / chemistry
  • Catalysis
  • Cyclization
  • Ezetimibe / chemical synthesis*
  • Ezetimibe / chemistry
  • Propanols / chemistry*
  • Ruthenium / chemistry
  • Spectrum Analysis / methods
  • Stereoisomerism
  • beta-Lactams / chemistry*

Substances

  • Anticholesteremic Agents
  • Propanols
  • beta-Lactams
  • allyl alcohol
  • Ruthenium
  • Ezetimibe