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

A small library of 1 H -benzo[4,5]imidazo[1,2- c ][1,3]oxazin-1-one derivatives was prepared in good to excellent yields, involving a Ag 2 CO 3 /TFA-catalyzed intramolecular oxacyclization of N-Boc -2-alkynylbenzimidazole substrates. In all experiments, the 6- endo - dig cyclization was exclusively achieved since the possible 5-exo-dig heterocycle was not observed, indicating the high regioselectivity of this process. The scope and limitations of the silver catalyzed 6-endo-dig cyclization of N - Boc -2-alkynylbenzimidazoles as substrates, bearing various substituents, were investigated. While ZnCl 2 has shown limits for alkynes with an aromatic substituent, Ag 2 CO 3 /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 H -benzo[4,5]imidazo[1,2- c ][1,3]oxazin-1-ones in good yields. Moreover, the rationalization of oxacyclization selectivity in favor of 6-endo-dig over 5-exo-dig was explained by a complementary computational study.