Synthesis of 1-Aminoisoquinolines from 2-Alkynylbenzaldoximines

Significance

Reported is the synthesis of 1-aminoisoquinolines using a two-step, one-pot process. The initial silver-catalyzed cyclization of 2-alkynylbenzaldoximes to form isoquinoline N-oxides has been previously reported (H.-S. Yeom, S. Kim, S. Shin Synlett 2008, 924), and is used extensively by the Wu group. The present article demonstrates the marriage of this cyclization with a recently reported method for the amination of isoquinoline N-oxides using PyBroP (A. T. ­Londregan, S. Jennings, L. Wei Org. Lett. 2010, 12, 5254). The reaction did not proceed in the absence of silver triflate, and treatment of isolated isoquinoline N-oxide with PyBroP gave the final product. A mechanism was proposed (shown above), which basically combined the previously proposed mechanisms for the two individual steps, but failed to explain why two equivalents of PyBroP are required when only 1.3 equivalents were required in the previously reported work.