Computational Insights of Selective Intramolecular O‐atom Transfer Mediated by Bioinspired Copper Complexes

The stereoselective copper‐mediated hydroxylation of intramolecular C−H bonds from tridentate ligands is reinvestigated using DFT calculations. The computational study aims at deciphering the mechanism of C−H hydroxylation obtained after reaction of Cu(I) precursors with dioxygen, using ligands bearing either activated (L(1) ) or non‐activated (L(2) ) C−H bonds. Configurational analysis allows rationalization of the experimentally observed regio‐ and stereoselectivity. The computed mechanism involves the formation of a side‐on peroxide species (P) in equilibrium with the key intermediate bis‐(μ‐oxo) isomer (O) responsible for the C−H activation step. The P/O equilibrium yields the same activation barrier for the two complexes. However, the main difference between the two model complexes is observed during the C−H activation step, where the complex bearing the non‐activated C−H bonds yields a higher energy barrier, accounting for the experimental lack of reactivity of this complex under those conditions.