Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and alpha-Methylidene-beta-Lactams

Abstract

Ru-catalyzed cross-metathesis (CM) reaction between beta-arylated alpha-methylidene-beta-lactams and terminal olefins was developed. The CM reaction is effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording corresponding alpha-alkylidene-beta-aryl-beta-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.

Keywords

• one-pot synthesis
• cholesterol absorption
• olefin metathesis
• natural-products
• formal synthesis
• inhibitors
• reduction
• chemistry
• acid
• discovery