Ni–Al Bimetal-Catalyzed Dual C–H Annulation of Formamides with Alkynes for Synthesis of Seven-Membered Lactams

Seven-membered rings, prevalent in natural products, are valuable yet challenging synthetic targets. Existing strategies mainly rely on prefunctionalized substrates via dual C-FG or single C-H activation. A dual C-H annulation using non-prefunctionalized materials would offer superior atom and step economies but is daunting, as it requires sequential activation of two inert, distal C-H bonds. Herein, we report a distal 1,5-dual C-H annulation of formamides with alkynes enabled by a synergistic Ni-Al bimetallic catalyst and a tailored N-protecting group, delivering efficient access to seven-membered lactams in up to 84% yield.