Catalytic Oxidative Coupling of Primary Amines under Air: A Flexible Route to Benzimidazole Derivatives

Benzimidazoles are of fundamental importance in chemistry and biology, and the development of efficient, environmentally benign methods for their preparation remains a key challenge for organic chemists. In a biomimetic approach inspired by copper amine oxidases, we disclose herein the scope and factors influencing the success of the cooperative action of CuBr2 as electron‐transfer mediator and a topaquinone‐like substrate‐selective catalyst in the oxidative cyclocondensation of primary amines with o‐aminoanilines. This one‐pot atom‐economic multistep process, which works under green conditions with ambient air as the terminal oxidant, low loadings of catalyst, and equimolar amounts of commercially available amine substrates, is particularly suitable for the preparation of 1,2‐disubstituted benzimidazoles. Furthermore, it allows the functionalization of nonactivated primary aliphatic amines, which are known to be challenging substrates for non‐enzymatic catalytic aerobic systems. Atom‐economical! Factors influencing the success of the biomimetic cooperative action of CuBr2 as electron‐transfer mediator and a topaquinone‐like substrate‐selective catalyst in the oxidative cyclocondensation of primary aliphatic amines with o‐aminoanilines are disclosed in order to provide a flexible route to benzimidazole derivatives under green conditions.