Bronsted Acid-Catalyzed Regioselective Carboxamidation of 2-Indolylmethanols with Isonitriles

A regioselective direct carboxamidation reaction of 2-indolylmethanolswith readily available isocyanoesters/isocyanides has been reportedin this work. The reaction was catalyzed by Bronsted acid such as p-TsOH to deliver the benzylic regioselective amides in67-86% yield under mild conditions. The developed methodologyprovides alternative access to traditional metal-free carboxamidationvia C-C and C-O bond formation with high atom economy.Furthermore, the developed approach was diversified to synthesizechiral indole-2-carboxamide derivatives with a moderate enantiomericexcess (61-73% ee) using an (R)-chiral phosphoric acid.