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 N -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] 2 Cl 2 complex. The transmetalation step with an energy span of 26.2 kcal mol -1 is rate-determining, while the subsequent disproportionation and reductive elimination are relatively facile (δ E = 16.4 kcal mol -1 ) in comparison to the CL amination of secondary amines. The final oxidative catalyst regeneration results in the presence of O 2 , accompanying an energy span of 12.8 kcal mol -1 , where hydrogen transfer from the coordinated water allows the reduction of superoxo linkage. Couplings performed in the presence of a combination of bidentate sp 3 - N ligands with single and double -(CH 2 )- spacer units afford a kinetically facile transformation (24.5 kcal mol -1 ). Furthermore, our results agree with the experimental outcomes of regioselective couplings of substituted imidazoles.