Homogeneous oxidation of C–H bonds with m-CPBA catalysed by a Co/Fe system: mechanistic insights from the point of view of the oxidant

Abstract

Oxidations of C–H bonds with m-chloroperoxybenzoic acid (m-CPBA) catalyzed by transition metal complexes are known to proceed through a number of routes, from the non-selective free radical to selective concerted and metal-mediated ones. However, there is a lack of understanding of the m-CPBA oxidative behavior, reaction mechanisms and factors that trigger its activity. An experimental and theoretical investigation of sp³ C–H bond oxidation with m-CPBA in the presence of the heterometallic pre-catalyst [Co^III₄Fe^III₂O(Sae)₈]·4DMF·H₂O (1) (H₂Sae = salicylidene-2-ethanolamine) and HNO₃ promoter has been performed herein. The catalytic system 1/HNO₃/m-CPBA allows mild hydroxylation of tertiary C–H bonds with 99% retention of stereoconfiguration of model alkane substrates, supported by high TOFs up to 2 s⁻¹ (for cis-1,2-dimethylcyclohexane) and TONs up to 1.4 × 10⁴ (at 50 °C). The catalytic effect of 1 is seen at the ppm level, while 1000 ppm (0.1 mol%) loading allows 1000-fold increase of the initial reaction rate up to 9 × 10⁻⁵ M s⁻¹. The reaction mechanism was investigated by means of combined kinetic studies (including isotope effects), isotopic labeling (¹⁸O₂, H₂¹⁸O, D₂O), ESI-MS spectroscopy and DFT theoretical studies. The results suggest that the main oxidation pathway proceeds through a concerted mechanism involving a cobalt-peroxo C–H attacking species or via a cobalt–oxyl species (rebound process), rather than a free-radical pathway. Remarkably, the Co(III) catalyst does not change its oxidation state during the most energetically favored pathway, consistent with a metal–ligand cooperativity. The chlorobenzene radical is responsible for H abstraction in the non-selective side route, which is efficiently suppressed by the acidic promoter. Finally, signs for slow direct oxygen exchange between m-CPBA and water in the presence of a proton or a metal complex are found, suggesting that the results of ¹⁸O-tests should be treated cautiously when m-CPBA is used as the oxidant.