Synthesis of Polysubstituted Isoquinolines and Related Fused Pyridines from Alkenyl Boronic Esters via a Copper-Catalyzed Azidation/Aza-Wittig Condensation Sequence

An efficient and straightforward synthesis of isoquinolines is reported from internal alkenyl boronic esters, easily prepared from the corresponding 1,2-bis(boronates), via a sequential copper-catalyzed azidation/aza-Wittig condensation. This synthetic method has been used to synthesize quinisocaine, a topical anesthetic used for the treatment of pain and pruritus, and further extended to thieno[2,3-c]pyridines by using 2-thiophenecarboxaldehyde as coupling partner in the first step.