Silica-Supported TEMPO Catalysts
J . Org. Chem., Vol. 66, No. 24, 2001 8155
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Sch em e 2
nium(VII),17 various peroxides in the presence of a silver
cocatalyst,18 or oxygen in combination with a high-valent
metal salt.19 Furthermore, electrochemical methods20 for
catalyst regeneration are known.
One of the most important protocols in this area was
introduced by Anelli and co-workers as early as 1987. It
involves the use of nontoxic reagents and is a metal-free
catalytic route to carbonyl compounds. According to the
original protocol,9a a TEMPO-type nitroxyl radical is used
as catalyst in combination with potassium bromide as
cocatalyst and a solution of buffered bleach as the
terminal oxidant.
Besides its high catalytic efficiency, Anelli’s oxidation
protocol is known for its mild reaction conditions and
pronounced selectivities. Thus, primary hydroxyl groups
are oxidized with high preference over secondary ones
and over-oxidations of the resulting aldehydes can usu-
ally be avoided by simply adjusting the amount of
oxidant.21 As a consequence of the mild reaction condi-
tions, even substrates which possess labile protecting
groups or stereogenic centers in the R-position to the
hydroxyl group can efficiently be oxidized.9c For example,
the Anelli oxidation has been applied in the synthesis of
R-alkoxy aldehydes,22 R-amino aldehydes,22,23 and various
amino acid derivatives.24 Even on larger scale the method
proved reliable as illustrated by examples from the patent
literature. At BASF Ku¨kenho¨hner and Goetz25 and at
Degussa Drauz and co-workers26 used Anelli’s protocol
in oxidations of 2,3-disubstituted benzyl alcohols and
hydroxyproline derivatives, respectively.
The broad applicability of the Anelli oxidation attracted
the interest of various research groups with the aim of
finding further improvements for the original method.
In particular the use of polymer-supported catalysts
seemed desirable, since they enable both catalyst recy-
cling and simplified workup of the reaction mixture.27
After the oxidation the carbonyl compounds could easily
be obtained from the organic phase by a simple phase
separation step as they are usually formed in high yields
without significant amounts of byproducts.28 Scheme 2
illustrates this approach schematically.
Previous to our work,29 various polymer-supported
nitroxyl radicals had already been synthesized based on
organic30 as well as inorganic supports.31 Some of them
were applied as catalysts in oxidation reactions,30a-d,31b,c
(25) Drauz, K.; Kottenhahn, M.; Stingl, K. U. S. Patent 5 631 385,
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Chem. 1996, 61, 7452-7454.
(26) Ku¨kenho¨hner, T.; Goetz, N. German Patent 4 007 923, 1990.
(27) The topic of polymer-supported reagents and catalysts has been
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Ellis Horwood ltd.: Chichester, West Sussex, 1992. (b) Chiral Catalyst
Immobilization and Recycling; De Vos, D. E., Vankelecom, I. F. J .,
J acobs, P. A., Eds.; Wiley-VCH: Weinheim, 2000. (c) Akelah, A.;
Sherrington, D. C. Chem. Rev. 1981, 81, 557-587. (d) Shuttleworth,
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