Palladium-Catalyzed Site-Selective [5 + 1] Annulation of Aromatic Amides with Alkenes: Acceleration of β-Hydride Elimination by Maleic Anhydride from Palladacycle

Abstract

The palladium-catalyzed reaction of 2-methylbenzamides with acrylic esters, leading to the production of isoquinolinones, is reported. The reaction occurs exclusively at the ortho methyl C–H bond via a six-membered palladacycle and not at the ortho C–H bond via a five-membered palladacycle. A key to the success of the reaction is the use of maleic anhydride as a ligand. Computational analyses suggest that the coordination of the maleic anhydride ligand highly stabilizes the transition state for β-hydride elimination and accelerates the β-hydride elimination.