Copper-Catalyzed Oxidative [3 + 2] Cycloaddition of Enamines and Pyridotriazoles toward Indolizines

An efficient copper catalytic system has been established for the synthesis of highly functional indolizines through oxidative [3 + 2] cycloaddition of enamines and pyridotriazoles. This modular platform is compatible with a broad range of functional groups, including natural and complex skeletons, allowing for late-stage modifications. It features a step-economical, highly regioselective, and easy-handling procedure and has been applied in constructing small molecules of potent activity toward inhibiting the VEGF-NRP1 interaction through a one-pot reaction of pyridotriazoles, amines, and aldehydes.