Mechanism of Alcohol Oxidation Mediated by Copper(II) and Nitroxyl Radicals

2,2′-Bipyridine-ligated copper complexes, in combination with TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl), are highly effective catalysts for aerobic alcohol oxidation. Considerable uncertainty and debate exist over the mechanism of alcohol oxidation mediated by Cu^II and TEMPO. Here, we report experimental and density functional theory (DFT) computational studies that distinguish among numerous previously proposed mechanistic pathways. Oxidation of various classes of radical-probe substrates shows that long-lived radicals are not formed in the reaction. DFT computational studies support this conclusion. A bimolecular pathway involving hydrogen-atom-transfer from a Cu^II–alkoxide to a nitroxyl radical is higher in energy than hydrogen transfer from a Cu^II–alkoxide to a coordinated nitroxyl species. The data presented here reconcile a collection of diverse and seemingly contradictory experimental and computational data reported previously in the literature. The resulting Oppenauer-like reaction pathway further explains experimental trends in the relative reactivity of different classes of alcohols (benzylic versus aliphatic and primary versus secondary), as well as the different reactivity observed between TEMPO and bicyclic nitroxyls, such as ABNO (ABNO = 9-azabicyclo[3.3.1]­nonane N-oxyl).