Ni‐Catalyzed Divergent Synthesis of 2‐Benzazepine Derivatives via Tunable Cyclization and 1,4‐Acyl Transfer Triggered by Amide N‐C Bond Cleavage

Abstract Ligand‐directed divergent synthesis can transform common starting materials into distinct molecular scaffolds by simple tuning different ligands. This strategy enables the rapid construction of structurally rich collection of small molecules for biological evaluation and reveals novel modes of catalytic transformation, representing one of the most sought‐after challenges in synthetic chemistry. We herein report a Ni‐catalyzed ligand‐controlled tunable cyclization/cross‐couplings for the divergent synthesis of pharmacologically important 2‐benzazepine frameworks. The bidentate ligand facilitates the nucleophilic addition of the aryl halides to the amide carbonyl, followed by 1,4‐acyl transfer and cross‐coupling to obtain 2‐benzazepin‐5‐ones and benzo[c]pyrano[2,3‐e]azepines. The tridentate ligand promotes the selective 7‐ endo cyclization/cross‐coupling to access to 2‐benzazepin‐3‐ones. The protocol operates under mild reaction conditions with divergent cyclization patterns that can be easily modulated through the ligand backbone.