Mechanistic Insights into the ortho-Defluorination-Hydroxylation of 2‑Halophenolates Promoted by a Bis(μ-oxo)dicopper(III) Complex

Abstract

C-F bonds are one of the most inert functionalities. Nevertheless, some [Cu_2O_2]^2+ species are able to defluorinate-hydroxylate ortho-fluorophenolates in a chemoselective manner over other ortho-halophenolates. Albeit it is known that such reactivity is promoted by an electrophilic attack of a [Cu_2O_2]^2+ core over the arene ring, the crucial details of the mechanism that explain the chemo- and regioselectivity of the reaction remain unknown, and it has not being determined either if Cu^II_2(η_2:η_2-O_2) or Cu^III_2(μ-O)_2 species are responsible for the initial attack on the arene. Herein, we present a combined theoretical and experimental mechanistic study to unravel the origin of the chemoselectivity of the ortho-defluorination-hydroxylation of 2-halophenolates by the [Cu_2(O)_2(DBED)_2]2+ complex (DBED = N,N′-di-tert-butylethylenediamine). Our results show that the equilibria between (side-on)peroxo (P) and bis(μ-oxo) (O) isomers plays a key role in the mechanism, with the latter being the reactive species. Furthermore, on the basis of quantum-mechanical calculations, we were able to rationalize the chemoselective preference of the [Cu_2(O)_2(DBED)_2]^2+ catalyst for the C-F activation over C-Cl and C-H activations.