Computational Assessment of the Mechanistic Journey in Chan-Lam-Based Arylation of Imidazoles.

Cu(II)-catalyzed C-N bond formation reactions remain one of most widely practiced and powerful protocols for the synthesis of value-added chemicals, bioactive molecules, and materials. Despite numerous experimental contributions, the overall mechanistic understanding of the C-N coupling reaction based on the Chan-Lam (CL) reaction methodology is still limited and underdeveloped, particularly with respect to the use of different substrates and catalytic species. Herein, we report an in-depth DFT-based study on the mechanism of -arylation of imidazoles following Collman's experimental setup. Our findings unfold for the first time the ligand-based CL coupling catalyzed by the [Cu(II)(OH)TMEDA]Cl complex. The transmetalation step with an energy span of 26.2 kcal mol is rate-determining, while the subsequent disproportionation and reductive elimination are relatively facile (δ = 16.4 kcal mol) in comparison to the CL amination of secondary amines. The final oxidative catalyst regeneration results in the presence of O, accompanying an energy span of 12.8 kcal mol, where hydrogen transfer from the coordinated water allows the reduction of superoxo linkage. Couplings performed in the presence of a combination of bidentate sp- ligands with single and double -(CH)- spacer units afford a kinetically facile transformation (24.5 kcal mol). Furthermore, our results agree with the experimental outcomes of regioselective couplings of substituted imidazoles.