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

We herein report an unprecedented pathway to access gamma-lactams using acetonitrile analogues as coupling partners without oxidants, ligands, and Lewis acids. The reaction undergoes Rh-catalyzed C(sp(2))-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.

Automated summary

We report a novel pathway to synthesize gamma-lactams using acetonitrile analogues as coupling partners. This method does not require oxidants, ligands, and Lewis acids, and exhibits a broad substrate scope, good functional group tolerance, and excellent chemo/stereoselectivity. Scale-up reactions and late-stage derivatizations demonstrate the potential synthetic utility of this methodology.