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 ( L¹ ) or non-activated ( L² ) 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.