Chemoselective Ru-Catalyzed Oxidative Lactamization vs Hydroamination of Alkynylamines: Insights from Experimental and Density Functional Theory Studies

J Org Chem. 2023 Jan 20;88(2):1185-1193. doi: 10.1021/acs.joc.2c02770. Epub 2022 Dec 29.

Abstract

The Ru-catalyzed intramolecular oxidative amidation (lactamization) of aromatic alkynylamines with 4-picoline N-oxide as an external oxidant has been developed. This chemoselective process is very efficient to achieve medium-sized ε- and ζ-lactams (seven- and eight-membered rings) but not for the formation of common δ-lactams (six-membered rings). DFT studies unveiled the capital role of the chain length between the amine and the alkyne functionalities: the longer the connector, the more favored the lactamization process vs hydroamination.

MeSH terms

  • Amines*
  • Catalysis
  • Density Functional Theory
  • Lactams*
  • Oxidative Stress

Substances

  • Lactams
  • Amines