Copper‐Catalyzed Tandem Cyclization of 2‐(Alkynylaryl)Acetonitriles and Amines: Access to 3‐Hydroxyisoindolinones

Abstract Herein, we describe an approach to the synthesis of 3‐hydroxyisoindolinone derivatives via copper‐catalyzed tandem cyclization of 2‐(alkynylaryl)acetonitriles and amines. This reaction is compatible with 2‐(alkynylaryl)acetonitriles and primary alkyl amines containing various functional groups, providing the corresponding 3‐hydroxyindolinone derivatives with yields ranging from 44%–82%. Preliminary mechanistic studies suggest that the reaction involves oxidation of the benzylic carbon, amide formation, hydration of the alkyne and intramolecular cyclization to produce various 3‐hydroxyisoindolinones. The practicality of the strategy was further demonstrated by gram‐scale synthesis, late‐stage functionalizations, and the post modification of natural products.