Nitroxide-Catalyzed Alcohol Oxidations in Organic Synthesis - Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds - page 449

NHBoc NHBoc

TEMPO (cat.), CuBr 2 (cat.),
2,2

OH

-bipyridine (cat.), O 2 ,
t- BuOK (cat.), MeCN, H 2 O

′

OH OH OHC

(94 %)

OMe

OMe

Scheme 12.35

A special case of the air oxidations are those involving laccases as cocatalysts. These lignin-degrading
enzymes expressed by white rot fungi can oxidize nitroxides to oxoammonium ions, and they can be
rejuvenated by air. 163 TEMPO/laccase has been used for the oxidation of benzylic alcohols (Scheme 12.5)
and sugar derivatives, 164 and mechanistic studies of this reaction have become available. 70,165

12.9.5 Peroxides
The use of cost effective and environmentally benign hydrogen peroxide as secondary oxidant would also
be desirable. Aside from an example in an hydrogen bromide/ionic liquid system 166 or in the presence

of methyltrioxorhenium as cocatalysts, 167 it is, however, not a generally applicable secondary oxidant in

TEMPO-catalyzed reactions.
Nitroxide-catalyzed reactions using m -chloroperoxybenzoic acid ( m -CPBA) as a secondary oxidant were
the first nitroxide-catalyzed reactions to be discovered. 127,168 The reactions are somewhat simplified in
that the reactions can be carried out using 2,2,6,6-tetramethylpiperidine hydrochloride ( 1 H + )

because
m -CPBA also oxidizes this piperidine to TEMPO (Scheme 12.1). 168 Bromide appears to be obligatory as
a cocatalyst. 169 The reaction works best only for the oxidation of secondary alcohols to ketones, since
some over-oxidation of primary alcohols to carboxylic acids may be observed. 168 Also, known peracid
oxidations such as the Baeyer - Villiger oxidation of ketones to esters or lactones and the epoxidation of
alkenes may occur, requiring a careful selection of the alcoholic substrates to be oxidized, though this
reaction can also be taken advantage of (see Section 12.10 on Tandem Reactions).
Oxone

·

is a cost effective solid peroxymonosulfate-based oxidant,
which is reduced to sulfate during the reaction. It can be used in purely organic solvents when used in
conjunction with a cocatalyst and phase transfer agent (Scheme 12.36). 68 Other peracid ions, such as
peracetate, perborate, percarbonate, and peroxydisulfate, have been explored primarily for the oxidation of
carbohydrates. 170

(DuPont; 2 KHSO 5 · KHSO 4 · K 2 SO 4 )

OH O

TEMPO (cat.), Bu 4 NBr (cat.),
Oxone TM , CH 2 Cl 2 , or toluene, rt

(96 %)

Scheme 12.36