Dinuclear Copper Intermediates in Copper(I)-Catalyzed Azide-Alkyne Cycloaddition Directly Observed by Electrospray Ionization Mass Spectrometry

The mechanism of the CuAAC reaction has been investigated by electrospray ionization mass spectrometry (ESI‐MS) using a combination of the neutral reactant approach and the ion‐tagging strategy. Under these conditions, for the first time, putative dinuclear copper intermediates were fished out and characterized by ESI(+)‐MS/MS. New insight into the CuAAC reaction mechanisms is provided and a catalytic cycle is proposed. Mechanistic aspects of the CuAAC reaction have been clarified by electrospray ionization mass spectrometry (ESI‐MS). Dinuclear copper intermediates have been detected for the first time and characterized. Neutral and ion‐tagged reactants provided complementary evidence for the reaction catalytic cycle.