Thermodynamic and Kinetic Studies on Copper-Catalyzed Cross-Dehydrogenative Couplings of N-Aryl Glycine Esters with Phenols

Copper-catalyzed cross-dehydrogenative coupling (CDC) reactions have been esteemed as a straightforward and efficient tool for C–C bonds formation. The single electron transfer (SET) process plays a vital role during the overall catalytic cycle. In the present density functional theory (DFT) study on the oxidation potential (Eox), which could reflect the SET occurring tendency from a thermodynamic respect as well as the substituent effects and structure-activity relationships for four classes of N-based compound substrates including THIQs, N,N-dimethylanilines, 3-benzylindoles, and N-phenylglycine esters derivatives have been fulfilled. Many quantitative structure-activity relationships between Eox and structural parameters, including HOMO energies, the Hammett substituent constant σ+ and so on were found. Furthermore, in the kinetics research section, we have performed four possible pathways of CDC reaction of N-aryl glycine esters with phenols in a CuBr/TBHP catalytic oxidation system. The results support the pathway wherein the formation of an iminium cation-type intermediate is involved would be more favorable. In addition, the solvent and substituent effects of two key steps including H-abstraction and C–C bond formation rate-determining step were explored, which could afford a total understanding of the mechanism regarding the Cu-catalyzed CDC reaction as well as the substrates and solvents screening.