One-Pot Synthesis of 1-Aminoisoquinolines via Copper-Catalyzed Coupling and Cyclization of Bromoaryl-Substituted Tetrazoles with Terminal Alkynes, Followed by Reductive Denitrogenation

1-Aminoisoquinolines are important scaffolds in medicinal chemistry, exhibiting diverse biological activities. Efficient methods for their synthesis are valuable for drug discovery. Recent advances focus on one-pot strategies that streamline synthesis, enhance atom economy, and improve scalability under mild or catalytic conditions. A one-pot synthetic method for 1-aminoisoquinolines is developed through the initial treatment of 5-(2-bromoaryl)tetrazoles with terminal alkynes in the presence of CuI and a base under microwave irradiation. This is followed by adding NaBH4 and further microwave irradiation. The reaction seems to proceed via an initial formation of tetrazole-fused isoquinolines through copper-catalyzed Sonogashira coupling of both substrates, followed by endo-dig cyclization. Subsequently, a thermal rearrangement of the tetrazole-fused isoquinolines occurs, leading to 1-azido isoquinolines, which undergo reductive denitrogenation with NaBH4.