CuAAC mechanistically

20 April 2010 - organometallic chemistry

CuAAC is an organic reaction that stands for copper-catalysed alkyne-azide-cycloaddition (review:DOI). It is an extension of the Azide alkyne Huisgen cycloaddition with copper independently introduced by Meldal (DOI) and Sharpless (DOI) both in 2002. A regular thermal reaction results in a mixture of triazole isomers but copper forces the formation of just one. Earlier in 2010 Buckley et al. published the preparation of a dicopper compound they say plays a part in the reaction mechanism for this reaction (DOI) and in even more recent publication (DOI) they expand on it.

This polymeric ladderane ((PhCCCu)2)n can be prepared from copper acetate through copper(II) hydroxyacetate and phenylacetylene with Cu(II) reduced to Cu(I) at the expense of solvent methanol. The same ladderane can also be obtained from copper sulfate with reducing agent sodium ascorbate. ((PhCCCu)2)n is then the catalyst in the actual cycloaddition between phenylacetylene and benylazide to the triazole. You may wonder why in this reaction sodium ascorbate is again listed as an ingredient. It should not be there. In a control experiment with another substrate the authors themselves make it clear the reducing agent no longer plays a part but for some reason the ingredient stayed.
CuAAC mechanism Buckley 2010