Bromoacetic Acid-Promoted Nonheme Manganese-CatalyzedAlkane Hydroxylation Inspired by?-Ketoglutarate-DependentOxygenases

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(sp(3))-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 O-18 was incorporated from (H2O)-O-18 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(sp(3))-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 alpha-ketoglutarate (alpha KG)-dependent nonheme iron oxygenases

Automated summary

Biomimetic iron and manganese complexes have been used as catalysts for selective oxidation reactions. In this study, a remote hydroxylation of undirected C(sp(3))-H bonds using a manganese catalyst and hydrogen peroxide as an oxidant was described. The catalytic system showed excellent activity, low catalyst loading, short reaction time, wide substrate scope, and easy scale-up. Mechanistic studies revealed the role of an additive in facilitating the generation of an electrophilic oxidant.