Cascade Vinyl Radical Ipso-Cyclization Reactions and the Formation of α,β-Unsaturated-β-aryl-γ-lactams from N-Propargyl Benzamides

J Org Chem. 2021 Nov 5;86(21):15033-15044. doi: 10.1021/acs.joc.1c01717. Epub 2021 Sep 30.

Abstract

Various N-(2-bromo-allyl) benzamides were used as the starting materials to study vinyl radical cyclization reactions. The vinyl radicals underwent ipso-cyclization, fragmentation, and cyclization reactions to produce β-aryl-γ-lactams with the carbonyl group remaining intact. To further study this cascade radical reaction, vinyl radicals were generated by the addition of a tributyltin radical to alkyne moieties, followed by radical ipso-cyclization, fragmentation, cyclization, and β-scission reactions with the production of a series of α,β-unsaturated-β-aryl-γ-lactam derivatives. This new type of radical reaction was examined from the substituent effects on both the amino groups and the aryl groups. A bulky tert-butyl substituent on the amino group enhanced the formation of a Z-conformation of the benzamides and facilitated vinyl radical ipso-cyclization reactions. A synthetic method for preparing α,β-unsaturated-β-aryl-γ-lactams from N-propargyl benzamides was developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides*
  • Cyclization
  • Molecular Structure
  • Morphinans
  • beta-Lactams*

Substances

  • Benzamides
  • Morphinans
  • N-propargyl
  • beta-Lactams