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 CuII 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 CuII–alkoxide to a nitroxyl radical is higher
in energy than hydrogen transfer from a CuII–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).