A Molecular Electron Density Theory Study of the Role of the Copper Metalation of Azomethine Ylides in [3 + 2] Cycloaddition Reactions

The copper metalation of azomethine ylides (AYs) in [3 + 2] cycloaddition (32CA) reactions with electron-deficient ethylenes has been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G­(d,p) level, in order to shed light on the electronic effect of the metalation in the course of the reaction. Analysis of the Conceptual Density Functional Theory reactivity indices indicates that the metalation of AYs markedly enhances the nucleophilicity of these species given the anionic character of the AY framework. These 32CA reactions take place through stepwise mechanisms characterized by the formation of a molecular complex. Both nonmetalated and metalated 32CA reactions present similar activation energies. While metalated 32CA reactions are completely regioselective, their stereoselectivity depends on the bulk of the ligand as well as the nature of the ethylene derivative. The metalation of the AY slightly increases the asynchronicity of the C–C single bond formation. Electron Localization Function topological analysis of the C–C bond formation processes makes it possible to characterize the mechanism of these 32CA reactions as a two-stage one-step mechanism. The present MEDT study rules out any catalytic role of the Cu­(I) cation in the kinetics of the 32CA reactions of metalated AYs.