Bromoacetic Acid-Promoted Nonheme Manganese-Catalyzed Alkane Hydroxylation Inspired by α-Ketoglutarate-Dependent Oxygenases

Biomimetic iron and manganese complexes have emerged as important catalysts in chemo-, regio-, and stereoselective oxidation reactions. In this study, we describe a remote hydroxylation of undirected C(sp³)-H bonds utilizing a simple manganese complex as a catalyst and hydrogen peroxide (H₂O₂) as a terminal oxidant in the presence of bromoacetic acid (BrCH₂CO₂H) as an additive. Crucial features of this catalytic system are the excellent catalytic activity of an easily preparable manganese catalyst, [Mn(R,R-BPMCN)]²⁺ (1), a low catalyst loading, a short reaction time, a broad substrate scope, and an easy scale-up. Mechanistic studies were also performed to elucidate the role of BrCH₂CO₂H and the nature of the hydroxylating intermediate, revealing that the BrCH₂CO₂H additive facilitates the generation of a highly electrophilic Mn(V)-oxo bromoacetate intermediate as a responsible oxidant via a heterolytic O-O bond cleavage of a postulated Mn(III)-OOH precursor. One notable observation in the mechanistic studies was that a significant amount of ¹⁸O was incorporated from H₂¹⁸O into the alcohol product in these catalytic oxidation reactions. On the basis of the above experimental observations and from the support of density functional theory (DFT) calculations, we conclude that a highly electrophilic Mn(V)-oxo bromoacetate complex was generated as a responsible oxidant that effects the undirected C(sp³)-H hydroxylation via an oxygen-rebound mechanism, thus mimicking both the structure and the function of the active intermediate of iron(IV)-oxo succinate for α-ketoglutarate (αKG)-dependent nonheme iron oxygenases.