Efficient Synthesis of 1-Benzo[4,5]imidazo[1,2-][1,3]oxazin-1-one Derivatives Using AgCO/TFA-Catalyzed 6- Cyclization: Reaction Scope and Mechanistic Study.

A small library of 1-benzo[4,5]imidazo[1,2-][1,3]oxazin-1-one derivatives was prepared in good to excellent yields, involving a AgCO/TFA-catalyzed intramolecular oxacyclization of -2-alkynylbenzimidazole substrates. In all experiments, the 6-- cyclization was exclusively achieved since the possible heterocycle was not observed, indicating the high regioselectivity of this process. The scope and limitations of the silver catalyzed cyclization of --2-alkynylbenzimidazoles as substrates, bearing various substituents, were investigated. While ZnCl has shown limits for alkynes with an aromatic substituent, AgCO/TFA demonstrated its effectiveness and compatibility regardless of the nature of the starting alkyne (aliphatic, aromatic or heteroaromatic), providing a practical regioselective access to structurally diverse 1-benzo[4,5]imidazo[1,2-][1,3]oxazin-1-ones in good yields. Moreover, the rationalization of oxacyclization selectivity in favor of over was explained by a complementary computational study.