Iridium-Catalyzed Asymmetric Hydrogenation of Racemic β-Keto Lactams via Dynamic Kinetic Resolution

Org Lett. 2017 Jan 6;19(1):118-121. doi: 10.1021/acs.orglett.6b03397. Epub 2016 Dec 12.

Abstract

A highly efficient Ir-catalyzed asymmetric hydrogenation of racemic β-keto lactams via dynamic kinetic resolution (DKR) for the synthesis of optically active β-hydroxyl lactams has been described. With the Ir-SpiroSAP catalyst, a series of racemic β-keto lactams including β-keto γ-, δ-, and ε-lactams were hydrogenated to chiral β-hydroxy lactams in high yields (87-99%) with excellent enantio- and diastereoselectivity (83-99.9% ee, syn/anti: 97:3->99:1) at low catalyst loading under mild reaction conditions. This efficient method has been successfully applied in the synthesis of the chiral intermediate of fluoroquinolone antibiotic premafloxacine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Catalysis
  • Drug Design
  • Fluoroquinolones / chemical synthesis
  • Hydrogenation
  • Iridium / chemistry*
  • Kinetics
  • Molecular Structure
  • Pyrroles / chemical synthesis
  • Stereoisomerism
  • beta-Lactams / chemistry*

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Pyrroles
  • beta-Lactams
  • Iridium
  • premafloxacin