Mechanistic Insight into Silver-catalyzed Cycloaddition Synthesis of 1,4-Disubstituted-1,2,3-triazoles: the Key Role of Silver
Abstract: The silver-catalyzed cycloaddition synthesis of 1,4-disubstituted-1,2,3-triazoles was investigated by using density functional theory (DFT) calculations. In the article, we studied computationally the main reaction mechanism, two proposed side reaction mechanisms and the role of silver(I) to elucidate the principal features of the transformation. The mechanism exploration indicates that the [3+2]-cycloaddition is more likely to be the rate-determining step for the main reaction, whereas both competitive side reaction pathways have relatively large barriers and are all kinetically unfavorable. Frontier Molecular Orbital (FMO) analysis implies that coordination of silver(I) with isocyanides changes the characteristics of isocyanides FMO and FMO overlapping manner of the cycloaddition. Natural Population Analysis (NPA) charge analysis suggests the electron-withdrawing property of silver(I) leads to the decrease of charge density of the –NC group, which improves the reactivity and substituent tolerance of isocyanides. Furthermore, the effect of substituents on aryl rings on –NC groups is almost negligible compared with the strong electron-withdrawing effect of silver(I) on isocyanides. Hence, silver(I) as the catalyst should be responsible for the excellent aryl-substituted tolerance as well as high regioselectivity for the protocol.