Palladium-Catalyzed Domino Synthesis of 2,3-Difunctionalized Indoles via Migratory Insertion of Isocyanides in Batch and Continuous Flow

We report, herein, a palladium-catalyzed cascade comprising carbopalladation, migratory insertion of isocyanide and triple bond activation followed by a nucleophilic attack (OR-) to construct difunctionalized acyl indoles. The process involves multiple bond formations via key palladium-chemistry steps, to construct these bis-heterocycles containing two privileged scaffolds (indole and oxindole) in a single operational step, along with attempts to generate enantioselectivity at a quaternary carbon center. The methodology also demonstrates a continuous-flow process to synthesize aryl isocyanides within minutes and using them in a telescopic manner.