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

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.