On the regioselectivity of the mononuclear copper-catalyzed cycloaddition of azide and alkynes (CuAAC). A quantum chemical topological study.

New density functional theory (DFT) calculations show that the nature of the mechanism for the classical copper-catalyzed cycloaddition of azide to terminal alkynes--widely known as the CuAAC reaction--also depends on the ligands attached to Cu(I). Further, the topological evolution of the charge density, ρ (r), the laplacian of ρ (r), ∇²ρ(r), and its gradient field along the reaction coordinate shed light on the regioselectivity of the process. The performance of most suitable functionals for DFT calculations in this kind of system was tested.