Homogeneous, Heterogeneous and Nanocatalysis - Transition Metal Catalysis in Aerobic Alcohol Oxidation - page 3

atmosphere. 5 Extensive descriptions of the history and development of this
subject can be found in Chapters 2 and 6. In any case, copper/TEMPO and
related systems deserve a brief introduction in order to understand their
important role in sustainable developments in homogeneous catalysis.
Recent advances reported by Stahl and co-workers 16 demonstrated that the
(bpy)Cu( I )/TEMPO catalyst system with NMI (bpy ¼ 2,2 0 -bipyridine, NMI ¼
N-methylimidazole) overcomes nearly all of the limitations associated with
Pd( II ) catalysts. This catalyst system permits the chemoselective oxidation of
benzylic, allylic and aliphatic primary alcohols to the corresponding alde-
hydes, with rates at least one order of magnitude higher than those observed
with Pd( II ) catalysts. Moreover, this method is compatible with substrates
bearing diverse functional groups and uses ambient air as the source of the
O 2 oxidant. A significant rate enhancement has been found with the
replacement of Cu( II ) with a Cu( I ) source and the catalyst system in
Scheme 1.1 is notable for its eciency in the oxidation of aliphatic alcohols.
Mechanistic investigations 16f support a two-stage catalytic mechanism
consisting of (1) 'catalyst oxidation' in which Cu( I ) and TEMPO-H are oxi-
dized by O 2 via a binuclear Cu 2 O 2 intermediate and (2) 'substrate oxidation'
mediated by Cu( II ) and the nitroxyl radical of TEMPO via a Cu( II )-alkoxide
intermediate (Scheme 1.2). Catalytic rate laws, kinetic isotope effects and
spectroscopic data show that reactions of benzylic and aliphatic alcohols
have different turnover-limiting steps. Catalyst oxidation by O 2 is turnover
limiting with benzylic alcohols, whereas numerous steps contribute to the
turnover rate in the oxidation of aliphatic alcohols.
Another excellent study by Stahl et al. explored in depth the substrate
scope and the applicability of different nitroxyl co-catalysts, particularly
evidencing the complementary role of TEMPO versus ABNO (9-azabicyclo-
[3.3.1]nonane N-oxyl). 18 A catalyst system consisting of (MeObpy)Cu I (OTf)
and ABNO (MeObpy ¼ 4,4 0 -dimethoxy-2,2 0 -bipyridine) mediates the aerobic
oxidation of all classes of alcohols, including primary and secondary allylic,
benzylic and aliphatic alcohols, with nearly equal eciency. The catalyst
exhibits broad functional group compatibility and most reactions are
complete within 1 h at room temperature, using ambient air as the source
of oxidants. Whereas Cu( I )/TEMPO shows high chemoselectivity for
primary alcohols, allowing excellent steric discrimination between un-
protected primary and secondary alcohols and also primary alcohols in
different steric environments, Cu( I )/ABNO is equally effective with all classes

d n 4 r 4 n g | 1

.

O

(bpy)Cu(I) 5 mol%, TEMPO 5 mol%
NMI 10 mol%

N

N N

R OH

R

O

air or O 2 , MeCN, rt

TEMPO

NMI

Scheme 1.1 (bpy)Cu( I )/TEMPO/NMI alcohol oxidation system.