General CuAAC Reaction Conditions

While the aqueous Cu(II)/ascorbate method is ubiquitous, the reducing conditions are not always compatible with sensitive substrates. For this reason, alternative approaches to 1,4-disubstituted-l,2,3-triazole ligands have been 

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The success achieved in CuAAC click reactions prompted researchers to look for better and more stable catalysts to carry out the azide-alkyne cycloaddition to triazoles. However, despite several efforts, Cu is found to be the best catalyst. The unique activity of Cu over other metal ions is due to its ability to involve the terminal alkynes in both a and it interactions and the possibility of immediate replacement of the ligands in its coordination sphere (generally in aqueous medium). However, Cu is thermodynamically unstable and oxidizes to Cu" " or disproportionates to a mixture of Cu and Cu under aerobic conditions. Cu" is catalytically inactive, and its generation halts the reaction. 

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