Pd-Catalyzed Aminocarbonylation of the Blaise Reaction Intermediate: One-Pot Synthesis of (Z)-3-Methyleneisoindolin-1-ones from Nitriles

A highly efficient method for the one-pot synthesis of stereocontrolled (Z)-3-methyleneisoindolin-1-ones was developed starting from 2-bromoarylnitriles via tandem sequential reaction with a Reformatsky reagent (Blaise reaction), followed by Pd-catalyzed intramolecular aminocarbonylation with carbon monoxide at 1 atm pressure. It has been found that the conformational flexibility of the bisphophine ligand is of great importance to the success of this tandem aminocarbonylation reaction.