Nickel-Catalyzed Cyclization of ortho-Iodoketoximes and ortho-Iodoketimines with Alkynes: Synthesis of Highly Substituted Isoquinolines and Isoquinolinium Salts

A convenient method for the synthesis of highly substituted isoquinolines and isoquinolinium salts by the nickel-catalyzed cyclization of ortho-haloketoximes and -ketimines, respectively, with alkynes is described. The reaction of ortho-haloketoximes and various alkynes in the presence of [Ni(PPh3)2Br2] and zinc powder in a mixture of acetonitrile and tetrahydrofuran at 80 degrees C for 15 hours gave 1,3,4-trisubstituted isoquinoline products in moderate to excellent yields and high regioselectivity. The corresponding isoquinoline N-oxide was found to be the intermediate in the cyclization reaction pathway. In contrast, the reaction of ortho-haloketimines and alkynes under similar catalytic conditions in tetrahydrofuran at 70 degrees C for two hours gave 1,2,3,4-tetrasubstituted isoquinolinium salts in good to excellent yields.