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

Abstract

A regioselective direct carboxamidation reaction of 2-indolylmethanols with readily available isocyanoesters/isocyanides has been reported in this work. The reaction was catalyzed by Bronsted acid such as p-TsOH to deliver the benzylic regioselective amides in 67–86% yield under mild conditions. The developed methodology provides alternative access to traditional metal-free carboxamidation via C–C and C–O bond formation with high atom economy. Furthermore, the developed approach was diversified to synthesize chiral indole-2-carboxamide derivatives with a moderate enantiomeric excess (61–73% ee) using an (R)-chiral phosphoric acid.

Palladium-catalyzed ligand-regulated divergent synthesis of pyrrole[2,3-b]indoles and ureas from 2-ethynylanilines and isocyanides

“…Among them, ligand-controlled chemoselectivity is a key issue in achieving diverse synthesis for discovering new bioactive molecules. 4 In recent years, transition metal-catalyzed tandem reactions have been in accordance with the concept of diversity-oriented synthesis for the construction of complex molecules in a step-economic approach. 5 In this context, the subtle regulation of the electronic properties and coordination configuration of metal centres through ligands has become an important method for achieving excellent chemoselectivity.…”