Computational studies of the metal-free [3+2] cycloaddition reaction of azide with enaminone for the synthesis of 1,2,3-triazoles

In this study, we investigated the mechanism of [3+2] cycloaddition (32CA) reaction between phenyl azide and phenyl enaminone using the M06-2X/6-31+G(d,p) level of theory for the first time. Computational results indicate that the metal-free azide-enaminone 32CA reaction for the selective synthesis of 1,2,3-triazoles in toluene proceeds along the 1,4- and 1,5-pathway, with the corresponding activation free energies (Delta G) of about 30.3 and 39.5 kcal mol-1, respectively, corresponding to the 32CA step. The alternative mechanism for this reaction in the presence of a catalyst and water as the solvent is proposed. The solvents studied displayed similar effects on activation energies (E#) and Delta G. The results of our computational study on the effect of phenyl azide substituents are consistent with the experimental observations in terms of reaction yield. The global and local nucleophilic and electrophilic indices of reagents and non-covalent interactions (NCI) are analyzed to determine the selectivity of the reaction and elucidate the most stable transition state structures.