Efficient Synthesis of 1<i>H</i>-Benzo[4,5]imidazo[1,2-<i>c</i>][1,3]oxazin-1-one Derivatives Using Ag₂CO₃/TFA-Catalyzed 6-<i>endo-dig</i> Cyclization: Reaction Scope and Mechanistic Study

Abstract

A small library of 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-one derivatives was prepared in good to excellent yields, involving a Ag2CO3/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 ZnCl2 has shown limits for alkynes with an aromatic substituent, Ag2CO3/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 1H-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.

Keywords

• 6-<i>endo-dig</i> cyclization
• silver
• oxacyclization
• catalytic process
• 1H-benzo[4,5]imidazo[1,2-<i>c</i>][1,3]oxazin-1-ones
• computational study