Mechanistic Insights into Copper(I)-Catalyzed Azide-Alkyne Cycloadditions using Continuous Flow Conditions

The copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was studied employing copper-in-charcoal (Cu/C) and a variety of copper metal sources as heterogeneous catalysts. The type and pretreatment conditions of the different copper sources oil the CuAAC were investigated. In addition, the effect of copper leaching from the catalyst over time and in dependence on the reaction mixture composition was studied by ICP-MS analysis in the continuous flow mode. These investigations confirm a homogeneous mechanism and suggest Surface layer copper(I) oxide as the catalytically active species in CUAAC chemistry involving zerovalent copper metal.