Cu-promoted intramolecular hydroxylation of CH bonds using directing groups with varying denticity

In this research article, we describe the Cu-promoted intramolecular hydroxylation of sp² and sp³ CH bonds using directing groups with varying denticity (bi-, tri- and tetradentate) and natural oxidants (O₂ and H₂O₂). We found that bidentate directing groups, in combination with Cu and H₂O₂, led to high hydroxylation yields. On the other hand, tetradentate directing groups did not form the hydroxylation products. Our mechanistic investigations suggest that bidentate directing groups allow for generating reactive mononuclear copper(II) hydroperoxide intermediates while tetradentate systems form dinuclear Cu₂O₂ species that do not oxidize CH bonds. Our findings might shed light on the reaction mechanism(s) by which Cu-dependent metalloenzymes such as particulate methane monooxygenase or lytic polysaccharide monooxygenase oxidize strong CH bonds.