Nickel-Catalyzed 8-Endo Cyclization/Carbonylation for the Synthesis of Eight-Membered Lactams

Medium-sized lactams are prevalent motifs in many bioactive molecules and natural products. However, their construction remains challenging due to unfavorable enthalpic and entropic barriers during the transition state. Herein, a novel nickel-catalyzed 8-endo cyclization/carbonylation has been achieved for the synthesis of eight-membered lactams bearing a gem-difluoro group. This approach features high regioselectivity, good functional group tolerance, and CO gas-free operation, which provides a good supplement for the preparation of eight-membered lactams via a nickel-catalyzed carbonylation process.