7576
J . Org. Chem. 1998, 63, 7576-7577
Efficien t a n d P r a ctica l Ca ta lytic Oxid a tion of
Alcoh ols Usin g Molecu la r Oxygen †
Istva´n E. Marko´,*,‡ Arnaud Gautier,‡
Isabelle Chelle´-Regnaut,‡ Paul R. Giles,‡
Masao Tsukazaki,‡ Christopher J . Urch,§ and
Stephen M. Brown
F igu r e 1.
Universite´ catholique de Louvain, De´partement de Chimie,
Laboratoire de Chimie Organique, Baˆtiment Lavoisier,
Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium,
Zeneca Agrochemicals, J ealott’s Hill Research Station,
Bracknell, Berkshire RG42 6ET, U.K., and Zeneca Process
Technology Department, Huddersfield Works, P.O. Box A38,
Leeds Road, Huddersfield HD2 1FF, U.K.
Received April 28, 1998
The oxidation of alcohols into aldehydes and ketones is a
ubiquitous functional group transformation in organic chem-
istry.1 However, despite its obvious commercial importance
and the detrimental ecological impact of the usual oxidants,
few efficient and mild catalytic oxidation procedures have
been reported that utilize dioxygen (or air) as the stoichio-
metric oxidant.2 Recently, we have disclosed two catalytic
aerobic oxidation protocols3 that allow the transformation
of alcohols 1 into carbonyl derivatives 2 in high yield and
which release water as the only byproduct (Figure 1).
Both of these systems are compatible with a variety of
sensitive functionalities and protecting groups. However,
the ruthenium-based aerobic oxidation procedure requires
5 mol % of the rather expensive tetrapropylammonium
perruthenate (TPAP) and is thus unsuitable for large-scale
operations. Moreover, the much cheaper copper chloride/
phenanthroline protocol necessitates the use of 2 equiv of
K2CO3. The stringent requirement for such a large amount
of K2CO3 was puzzling, and we initiated some studies in
order to understand the role(s) of this heterogeneous base.
In particular, we wished to find suitable reaction conditions
F igu r e 2.
in which smaller amounts of base could be employed in order
to transform our original system into a more ecologically
friendly protocol.
Therefore, a variety of other bases (Na2CO3, Li2CO3, Na2-
HPO4, NaH2PO4, Al2O3, NaOAc, KOAc, KOH, and CuCO3)
were initially tested in this aerobic oxidation system.
Surprisingly, none proved to be as efficient as K2CO3.4
Examination of the postulated mechanism of this transfor-
mation (Figure 2) suggested a number of possible roles for
K2CO3.5 First, K2CO3 should act as a base and react with
the HCl formed during the initial replacement of the chloride
ligand by the alcohol. However, if this was the sole purpose
of K2CO3, then only 5 mol % should actually be necessary
in the reaction to fulfill the requirement of catalyst forma-
tion.
Second, examination of the oxidation in toluene revealed
its heterogeneous nature. Filtration of the dark-brown
suspension gave a filtrate devoid of oxidizing activity and a
solid material that, once resuspended in toluene, smoothly
oxidized alcohols to the corresponding ketones and alde-
hydes. It thus appears that K2CO3 may also serve as a solid
support on which the copper catalyst can be anchored.
Finally, since water is released during the oxidation process,
K2CO3 might also be acting as a water scavenger.
* To whom correspondence should be addressed. Fax: 32-10-47 27 88.
E-mail: marko@chor.ucl.ac.be.
† Dedicated with deep respect to Professor S.-I. Murahashi.
‡ Universite´ catholique de Louvain.
§ Zeneca Agrochemicals.
Zeneca Process Technology Department.
(1) (a) Sheldon, R. A.; Kochi, J . K. In Metal-Catalyzed Oxidations of
Organic Compounds; Academic Press: New York, 1981. (b) Ley, S. V.;
Norman, J .; Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639. (c)
Murahashi, S.-I.; Naota, T.; Oda, Y.; Hirai, N. Synlett 1995, 733. (d) Krohn,
K.; Vinke, I.; Adam, H. J . Org. Chem. 1996, 61, 1467 and references therein.
For general reviews on oxidation reactions, see: (a) Larock, R. C. In
Comprehensive Organic Transformations; VCH Publishers Inc.: New York,
1989; p 604. (b) Procter, G. In Comprehensive Organic Synthesis; Ley, S.
V., Ed.; Pergamon: Oxford, 1991; Vol. 7, p 305. (c) Ley, S. V.; Madin, A. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Perga-
mon: Oxford, 1991; Vol. 7, p 251. (d) Lee, T. V. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7,
p 291.
(2) (a) Sheldon, R. A. In Dioxygen Activation and Homogeneous Catalytic
Oxidation; Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 573. (b) J ames,
B. R. In Dioxygen Activation and Homogeneous Catalytic Oxidation;
Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 195. (c) Ba¨ckvall, J .-E.;
Chowdhury, R. L.; Karlsson, U. J . Chem. Soc., Chem. Commun. 1991, 473.
(d) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron Lett.
1995, 36, 6923. (e) Mandal, A. K.; Iqbal, J . Tetrahedron 1997, 53, 7641 and
references therein.
(3) (a) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch C. J .
Science 1996, 274, 2044. (b) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle´-
Regnaut, I.; Urch C. J .; Brown, S. M. J . Am. Chem. Soc. 1997, 119, 12661.
For an independent report of the same discovery, see: Lenz, R.; Ley, S. V.
J . Chem. Soc., Perkin Trans. 1 1997, 3291. For previous work on the use of
CuCl‚Phen as a catalyst for the aerobic oxidation of alcohols, see: (a)
J allabert, C.; Riviere, H. Tetrahedron Lett. 1977, 1215. (b) J allabert, C.;
Riviere, H. Tetrahedron 1980, 36, 1191. (c) J allabert, C.; Lapinte, C.; Riviere,
H. J . Mol. Catal. 1982, 14, 75. For the use of CuCl2/TEMPO/O2 as a mild
oxidant, see: Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chon, C. S.
J . Am. Chem. Soc. 1984, 106, 3374.
The importance of the dehydrating properties of K2CO3
was clearly revealed by performing the oxidation reaction
using only 10 mol % of K2CO3 in the presence of an excess
of 4 Å MS. Although 4 Å MS proved to be less efficient than
K2CO3 in trapping the released water (larger loading and
(4) One rare exception appears to be KOBut. For example, the aerobic
oxidation of 2-undecanol (5 mol % CuCl‚Phen, 5 mol % KOBut, toluene,
80-90 °C) afforded 2-undecanone in almost quantitative yields. However,
this system appears, so far, to be limited to secondary alcohol oxidations.
(5) For a discussion of the possible mechanism of this reaction, see:
Marko´, I. E.; Tsukazaki, M.; Giles, P. R.; Brown, S. M.; Urch C. J . Angew.
Chem., Int. Ed. Engl. 1997, 36, 2208.
10.1021/jo980770h CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/06/1998