Synthesis of Diverse γ-Lactams via Rh-Catalyzed C(sp2)-H Addition to Aliphatic Nitriles

Org Lett. 2022 Jul 22;24(28):5090-5094. doi: 10.1021/acs.orglett.2c01867. Epub 2022 Jul 13.

Abstract

We herein report an unprecedented pathway to access γ-lactams using acetonitrile analogues as coupling partners without oxidants, ligands, and Lewis acids. The reaction undergoes Rh-catalyzed C(sp2)-H addition to carbon-bound nitriles with the aid of an amide traceless auxiliary followed by an annulation sequence, featuring a broad substrate scope, good functional group tolerance, and excellent chemo/stereoselectivity. Scale-up reactions and late-stage derivatizations highlight the potential synthetic utility of this methodology. A plausible mechanism is proposed based on mechanistic investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Lactams*
  • Molecular Structure
  • Nitriles
  • Rhodium*

Substances

  • Lactams
  • Nitriles
  • Rhodium