Mechanistic insights into cobalt(ii/iii)-catalyzed C-H oxidation: a combined theoretical and experimental study

Cobalt-mediated C-H functionalization has been the subject of extensive interest in synthetic chemistry, but the mechanisms of many of these reactions (such as the cobalt-catalyzed C-H oxidation) are poorly understood. In this paper, possible mechanisms including single electron transfer (SET) and the concerted metalation-deprotonation (CMD) pathways of the Co^II/Co^III-catalyzed alkoxylation of C(sp²)-H bonds have been investigated for the first time using the DFT method. Co^II(OAc)₂ has been employed as an efficient catalyst in our previous experimental study, but the calculated results unexpectedly indicated that the intermolecular SET pathway with Co^III as the actual catalyst might be the most favorable pathway. To support this theoretical prediction, we have explored a series of Cp*Co^III(CO)I₂ catalyzed C(sp²)-H bond alkoxylations, extending the application of cobalt-catalyzed functionalization of C-H bonds. Furthermore, kinetic isotope effect (KIE) data, electron paramagnetic resonance (EPR) data, and TEMPO inhibition experiments also support the SET mechanism in both the Co-catalyzed alkoxylation reactions. Thus, this work should support an understanding of the possible mechanisms of the Co^II/Co^III-catalyzed C(sp²)-H functionalization, and also provide an example of the rational design of novel catalytic reactions guided by theoretical calculations.