Synthesis of 3-substituted 4-aroylisoquinolines via Pd-catalyzed carbonylative cyclization of 2-(1-alkynyl)benzaldimines

A number of 3-substituted 4-aroylisoquinolines have been prepared in good yields by treating N-tert-butyl-2-(1-alkynyl)benzaldimines with aryl halides in the presence of CO and a palladium catalyst. Synthetically the methodology provides a simple and convenient route to isoquinolines containing an aryl, alkyl, or vinylic group at C-3 and an aroyl group at C-4 of the isoquinoline ring. The reaction is believed to proceed via cyclization of the alkyne containing a proximate nucleophilic center promoted by an acylpalladium complex.