Nitroxide-Catalyzed Alcohol Oxidations in Organic Synthesis - Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds - page 433

12

Nitroxide-Catalyzed Alcohol Oxidations
in Organic Synthesis

Christian Br uckner
Department of Chemistry, University of Connecticut, Connecticut, USA

12.1 Introduction

The oxidation of secondary amines that contain no hydrogen atoms, such as 2,2,6,6-tetramethylpiperidine

( 1 ), leads to the formation of nitroxides, stable free radical compounds such as the prototypical 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO, 2 ) (Scheme 12.1). 1 An one-electron oxidation converts nitroxide 2
into the oxoammonium cation 3 , a strongly oxidizing species. Reactions of a primary or secondary alcohol
with 3 oxidize the alcohol to the corresponding aldehyde or ketone, respectively, and reduce 3 to the corre-
sponding hydroxylammonium salt 4 . If this reaction takes place in the presence of an oxidant that is capable
of the two-electron oxidation needed to convert the hydroxylamine back to the oxoammonium salt, TEMPO
becomes an oxidation catalyst. The latter oxidation by the so-called secondary oxidant ∗ may require a cocat-
alyst, commonly bromide. It is this catalytic cycle that enables nitroxides to be used as oxidation catalysts
in organic synthesis. 2,3 The nitroxide-catalyzed reactions - largely independent from the secondary oxidant
used - tolerate the presence of alkanes, double and triple bonds, protected alcohols, including acetals and
silanes, epoxides, amides, pyridine-type nitrogens, azides, sulfur heterocycles, esters, isonitriles, and other
functional groups. The oxidations are rarely accompanied with C-C bond cleaving side reactions.
Recent and comprehensive reviews of nitroxide-catalyzed and oxoammonium oxidation reactions are
available. 2,3 As such, this review is focused mainly on the application of nitroxide-catalyzed reactions in
organic synthesis, using recent examples from the literature. Emphasis is placed on the scope and limitations
of this reagent in the preparation of complex organic molecules. Excluded here is the use of oxoammo-
nium compounds as stoichiometric oxidants although they are the active species in the catalytic cycle
(Scheme 12.1). As well, the oxidation of non-alcoholic substrates is not reviewed; the reader is referred
to a number of classic or timely reviews on many aspects of the use of nitroxides and/or oxoammonium

α

∗ This oxidant is sometimes also referred to as primary, terminal, or co-oxidant. For a discussion of possible secondary oxidants, see
Section 12.9.