Evidence for a fully Cu(II)-catalyzed CuAAC reaction: A combined experimental and computational study

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is one of the most broadly applied catalytic processes, with significant applications throughout synthetic chemistry, drug discovery, chemical biology, and materials science. This entire field of research is built upon the mechanistic premise that the reaction proceeds via Cu(I) catalysis. Here, we report details of a CuAAC reaction that is catalyzed exclusively by Cu(II) through a self-assembled dinuclear Cu(II) complex that incorporates the triazole product. Computational analysis supports the experimental findings and the autocatalytic role of the triazole. This work provides a mechanistic basis for a new catalytic model for the CuAAC reaction.