Copper-catalyzed aerobic oxidation of alcohols under fluorous biphasic conditions

Article abstract of DOI:10.1016/S0040-4039(00)00620-1

A catalytic amount of perfluoroalkyl substituted bipyridine 1 (2 mol%), CuBr·Me₂S (2 mol%) and TEMPO (3.5 mol%) allow the oxidation of various alcohols to aldehydes and ketones in a fluorous biphasic system of chlorobenzene and perfluorooctane directly with oxygen. The catalyst can be used for several reaction runs without a loss of reactivity. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00620-1

Tetrahedron Letters 41 (2000) 4343±4346
Copper-catalyzed aerobic oxidation of alcohols under
¯uorous biphasic conditions
Bodo Betzemeier,a Marco Cavazzini,b Silvio Quicib and Paul Knochela,*
aInstitut fur Organische Chemie der Ludwig-Maximilians-Universitat, Butenandtstraûe 5-13,
È
È
D-81377 Munchen, Germany
È
bCentro CNR Sintesi e Stereochimica di Specali Sistemi Organici e Dipartimento di Chimica Organica e Industriale,
via Golgi 19, I-20133 Milano, Italy
Received 6 April 2000; accepted 10 April 2000
Abstract
.
A catalytic amount of per¯uoroalkyl substituted bipyridine 1 (2 mol%), CuBr Me2S (2 mol%) and
TEMPO (3.5 mol%) allow the oxidation of various alcohols to aldehydes and ketones in a ¯uorous
biphasic system of chlorobenzene and per¯uorooctane directly with oxygen. The catalyst can be used for
several reaction runs without a loss of reactivity. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: bipyridine; copper; ¯uorous phase; oxidation; TEMPO.
The oxidation of primary and secondary alcohols to aldehydes and ketones is one of the most
important transformations in organic chemistry both at a laboratory and industrial scale.1
Therefore, it is surprising that only a few examples of catalytic oxidations using cheap oxidation
agents such as oxygen or hydrogen peroxide have been reported.2 Most reactions require stoichio-
metric amounts of often toxic oxidation reagents. The removal of traces of those reagents from
the reaction mixture is often costly and dicult. Recently, we have described the utility of ¯uorous
biphase catalysis3,4 for oxidation reactions.5 In such a system, per¯uoroalkylated catalysts have
been used to achieve a selective solubility in per¯uorinated solvents whereas the reagents and
starting materials are soluble in the organic phase. This method allows a facile separation of the
catalyst from the product by decantation of the ¯uorous phase. Furthermore, the catalyst can be
potentially reused for further reaction runs.4d
The use of per¯uoroalkylated bipyridines of type 1 as ligand for the ruthenium-catalyzed
epoxidation of trans-stilbene have been reported by one of us recently.6 Semmelhack et al.7 have
also described the aerobic oxidation of primary and secondary alcohols to the corresponding
* Corresponding author. Fax: +49-89-21807679; e-mail: paul.knochel@cup.uni-muenchen.de, quici@mailserver.
unimi.it
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00620-1

4344
aldehydes and ketones catalyzed by copper(I) chloride and 2,2,6,6-tetramethylpiperidine N-oxyl
(TEMPO).8 This work led us to design a similar reaction in a ¯uorous phase by modifying the
.
copper catalyst with the ¯uorinated ligand 1. The catalyst prepared in situ from CuBr Me2S and
the per¯uoroalkylated bipyridine 1 is selectively soluble in per¯uorooctane as indicated by its
green colour. With 2 mol% of this catalyst and TEMPO (3.5 mol%) the oxidation of 4-nitro-
benzylalcohol (2a) to 4-nitrobenzaldehyde (3a) has been carried out in a biphasic system of
per¯uorooctane and chlorobenzene at 90ꢀC under a gentle stream of oxygen. After 4 h the
conversion was completed and the aldehyde 3a was isolated in 93% yield (Scheme 1).
Scheme 1.
To demonstrate the recyclability of the catalyst, the ¯uorous phase containing the catalyst
was reused several times for further reaction runs without a signi®cant decrease in yield and in
rate. Even after eight cycles, 86% of analytical pure 4-nitrobenzaldehyde (3a) was isolated
(Table 1).
Table 1
Reuse of the catalyst solution for the oxidation of 4-nitrobenzylalcohol
With this method, various primary and secondary alcohols have been oxidized with high
selectivity to their corresponding aldehydes and ketones. Under these reaction conditions, not
only benzylic and allylic alcohols (entries 1±6 of Table 2) but also aliphatic alcohols (entries 7±12
of Table 2) were smoothly oxidized. However, benzylic alcohols react faster (2±7 h) compared to
aliphatic alcohols (7±13 h).
For secondary aliphatic alcohols, the success of the reaction is strongly dependent on the steric
environment of the carbinol moiety. With 4-tridecanol (2n) a conversion of only 31% was
observed after 17 h, while the reaction of the less hindered alcohols 2l and 2m was completed
within 8 and 12 h, respectively (entries 10±12 of Table 2).

4345
Table 2
Aldehydes and ketones prepared under ¯uorous biphasic conditions
We have shown that the per¯uoralkylated bipyridine 1 is an ecient ligand for the perform-
ance of the copper-catalyzed oxidation of various primary and secondary alcohols to their
corresponding aldehydes and ketones under ¯uorous biphasic conditions. The facile recovering
of the catalyst is a great advantage of this method since it allows its reuse without observing a
signi®cant decrease in reactivity.9

4346
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft (Schwerpunktprogramm `Peroxidchemie'
and Leibniz program), the European Union (COST-program `Fluorous medium: a tool for
environmentally compatible oxidation processes') and the Fonds der Chemischen Industrie for
generous ®nancial support. The companies BASF AG (Ludwigshafen), Bayer AG (Leverkusen),
ELF Atochem SA (Pierre-Benite, France) and Chemetall GmbH (Frankfurt) are acknowledged
for the generous gift of chemicals.
References
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9. Typical procedure: For preparation of 4-nitrobenzaldehyde (3a) a 25 mL (Schlenk) ¯ask was charged with the
.
bipyridine 1 (44 mg, 40 mmol, 2 mol%) dissolved in per¯uorooctane (2 mL) and CuBr Me2S (9.2 mg, 40 mmol, 2
mol%) dissolved in a small amount of dimethyl sul®de leading to a deep green solution. After stirring for 0.5 h, a
solution of 4-nitrobenzylalcohol (2a: 306 mg, 2.0 mmol) and TEMPO (10.0 mg, 67 mmol, 3.4 mol%) in
chlorobenzene (2 mL) was added. The biphasic reaction mixture was stirred at 90ꢀC for 3 h while a gentle
stream of oxygen was passing. At the end of the reaction, the mixture was cooled to 0ꢀC, the organic layer was
decanted and the ¯uorous phase was washed with chlorobenzene (3Â2 mL). The combined organic phases were
diluted with ether (30 mL) and washed with brine. After drying (MgSO4), ®ltration and evaporation of the solvent
in vacuo the crude product was puri®ed by ¯ash chromatography (pentane:ether, 4:1) yielding pure 4-nitro-
benzaldehyde (3a, 281 mg, 93%) as a pale yellow solid. The ¯uorous phase was separated and was used directly for
further reaction runs.