In Situ -Assembled Bidentate Direction for Peri-Selective Three-Component Annulation of Aminocoumarins

Abstract A peri-selective Pd-catalyzed three-component annulation of 4-aminocoumarins, 2-bromobenzoic acids, and iodoarenes has been developed, providing direct access to π-extended N-heterocycles. The reaction proceeds through an in situ-assembled N,O-bidentate directing environment that overrides the intrinsic reactivity of the coumarin scaffold and enables selective peri-C–H activation while preserving the carboxylic acid functionality. DFT studies reveal that regioselectivity arises from preferential formation of a five-membered palladacyclic intermediate over a less-favorable four-membered alternative.