Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

Transition metal-catalyzed radical-radical cross-coupling reactions provide innovative methods for C-C and C-heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C-N radical-radical cross-coupling reaction. The concerted coupling pathway, in which a C-N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)-N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)-N species before C-N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)-N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)-N intermediate. The higher activation free energy for N-N radical-radical homo-coupling is attributed to the mismatch of Cu(II)-N species with the nitrogen radical because the electrophilicity for both is strong.