Computational studies of the CuAAC reaction mechanism with diimine and phosphorus ligands for the synthesis of 1,4-disubstituted 1,2,3-triazoles

Abstract

The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with diimine and phosphorus ligands have been studied using DFT calculations at the MN12-L/Def2-SVP (Def2-TZVP for Cu) level of theory in order to understand the effect of the nature of the ligands on the catalytic cycle for the formation of the 1,4-regioisomer. The mono- and bi-nuclear mechanisms with these ligands were also studied. The computational result indicates that the CuAAC reactions take place via a stepwise mechanism. In the mononuclear pathway, the activation energies in the toluene solvent are about 15.1, 12.9, 11.9, 10.1, and 13.0 kcal mol⁻¹ with diimine (L1, L2, L3) and phosphorus (L4, L5) ligands, respectively, while these energies in the case of the binuclear pathway with the corresponding ligands are about 7.6, 8.8, 9.9, 16.8, and 9.3 kcal mol⁻¹, respectively. These results indicate that the binuclear pathway is dominant compared to the mononuclear pathway with all studied ligands (except for the L4 ligand leading to the opposite result), and this is consistent with previous computational and experimental studies with other ligands.