Computational Strategies to Probe CH Activation in Dioxo-Dicopper Complexes

Our work addresses the long-standing question of the preferred mechanism of CH activation in dioxodicopper complexes, with implications for [Cu2O2]2+ -containing enzymes as well as homogeneous and heterogeneous catalysts, which are capable of performing selective oxidation. Using density functional theory (DFT), we show that the two proposed mechanisms, one-step oxo-insertion and two-step radical recombination, have very distinct and measurable responses to changes in the electrophilicity of N-donors in the catalyst. Using energy decomposition analysis, we calculate the electronic interactions that contribute to transition state stabilization, and the effect of N-donors on these interactions. The analysis shows that oxo-insertion, by virtue of possessing a late and charged transition state, is highly sensitive to N-donor electrophilicity and barriers decrease with more electron-withdrawing N-donors. On the other hand, the radical pathway possesses an early transition state and is therefore relatively insensitive to N-donor variations. One possible strategy, going forward, is the design and execution of complementary experiments to deduce the mechanism based on the presence or absence of N-donor dependence. We adopt an alternative approach where DFT results are contrasted with prior experiments via Hammett relationships. The remarkable agreement between experimental and calculated trends for oxo-insertion with imidazole N-donor catalysts presents compelling evidence in favor of the one-step pathway for CH activation.