Redox-Neutral Copper-Catalyzed Syntheses of Allylic and Benzo-Fused Secondary Lactams

Abstract Building upon our previously developed Cu/N-methoxyamide combination for amidyl radical generation, we report the cyclization of amidyl radicals to tethered olefins and aromatic rings to synthesize allylic and benzo-fused lactams. Cyclization of the electrophilic amidyl radical affords secondary lactams with adjacent alkyl or aryl radicals, which, after a Cu(II)-mediated hydride elimination or oxidation, gives unprotected allylic or benzo-fused lactams. Cu(I)/Cu(II)/Cu(III) oscillation in the catalytic cycle renders the reaction redox-neutral, and it provides direct access to secondary lactams, unlike previously described methods that produced mostly tertiary lactams.