Evidence for a Cu(II)‐Catalysed CuAAC Reaction: A Combined Experimental and Computational Study

The Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction is one of the most broadly applied catalytic processes, with applications throughout synthetic chemistry, drug discovery, chemical biology, and materials science. This field of research is built upon the mechanistic premise that the metal-centred events proceed via Cu(I) catalysis. Here, we report details of a CuAAC reaction that can also be catalysed 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. Assessment across additional alkyne substrates reveals a more nuanced role in other cases. This work provides an additional mechanistic pathway possible for CuAAC reactions, establishing a mechanistic continuum that extends through Cu(I), mixed Cu(I)/Cu(II), and Cu(II) catalytic frameworks.