Construction of Eight-Membered <i>N</i>‑Heterocycles via Palladium-Catalyzed Cyclization of Allenyl Isocyanides

A three-component construction of eight-membered nitrogen-containing heterocycles via palladium-catalyzed imidoylative cyclization of 2-isocyano-<i>N</i>-(propa-1,2-dien-1-yl)benzamides with aryl halides and carbon nucleophiles has been developed. Sequential isocyanide and allene insertion reactions facilitated the formation of medium-sized rings, overcoming the unfavorable transannular interactions and entropic factors, followed by an allylic substitution to yield benzodiazocine derivatives under mild reaction conditions. When the nucleophile was linked with aryl iodide, challenging diazocine-fused macrocycles could be accessed through an intramolecular allylic substitution process.