Asymmetric hydrogenation of protected allylic amines

Org Lett. 2010 Sep 17;12(18):4201-3. doi: 10.1021/ol101804e.

Abstract

A general method for the enantioselective hydrogenation of protected allylic amine derivatives is described. This procedure relies on the generation of a cationic ruthenium complex with the axially chiral ligand (-)-TMBTP. The utility is highlighted by the highly enantioselective hydrogenation of a diene substrate that can then be elaborated to prepare Telcagepant, a compound currently in Phase III clinical trials. The scope of the hydrogenation reaction was studied, and a variety of substituted allylic amine derivatives could be hydrogenated with enantiomeric ratios of 92:8 or higher.

MeSH terms

  • Allyl Compounds / chemistry*
  • Amines / chemistry*
  • Azepines / chemical synthesis
  • Caprolactam / chemical synthesis
  • Catalysis
  • Hydrogenation
  • Imidazoles / chemical synthesis
  • Molecular Structure
  • Stereoisomerism

Substances

  • Allyl Compounds
  • Amines
  • Azepines
  • Imidazoles
  • Caprolactam
  • telcagepant