Versatile Synthesis of Isoquinolines and Isochromenes by Pd-Catalyzed Oxidative Carbonylation of (2-Alkynyl)benzylideneamine Derivatives

Isoquinoline-4-carboxylic esters 3 and isochromene-4-carboxylic esters 4 have been conveniently prepared by direct PdI2-catalyzed oxidative heterocyclization/alkoxycarbonylation of readily available (2-alkynylbenzylidene)amine derivatives. In particular, (2-alkynylbenzylidene)(tert-butyl)amines 2 selectively afforded isoquinoline derivatives 3 by N-cyclization, whereas N-(2-alkynylbenzylidene)-N'-phenylhydrazines 5 led to the formation of isochromenes 4 through O-cyclization ensuing from water attack on the imino group of the substrate. Reactions were carried out in alcoholic solvents at 80-100 degrees C and under 20-80 atm (at 25 degrees C) of a 4: 1 mixture of CO/air, in the presence of PdI2 (2-10 mol-%) in conjunction with KI (KI/PdI2 molar ratio = 10). In the case of imines 2, the use of a dehydration agent, such as trialkyl orthoformate, was necessary to obtain satisfactory yields of isoquinolines 3.