Selective oxidation of alcohols in the presence of an Os/O2-system

Article abstract of DOI:10.1016/S0040-4039(01)01747-6

The osmium-catalyzed oxidation of alcohols with molecular oxygen to give aldehydes in good to excellent yields has been developed. Best results are obtained by using a buffered two-phase system with a constant pH of 10.4. Under optimized reaction conditions a remarkable catalyst productivity (TON up to 16600) is observed.

Full text of DOI:10.1016/S0040-4039(01)01747-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8447–8449
Selective oxidation of alcohols in the presence of an
†
Os/O -system
2
a
a
a
b
Christian D o¨ bler, Gerald M. Mehltretter, Uta Sundermeier, Markus Eckert,
b
a,
Hans-Christian Militzer and Matthias Beller *
a
Institut f u¨ r Organische Katalyseforschung (IfOK) an der Universit a¨ t Rostock e.V., Buchbinderstr. 5-6,
D-18055 Rostock, Germany
b
Bayer AG, D-51368 Leverkusen, Germany
Received 3 August 2001; accepted 13 September 2001
Abstract—The osmium-catalyzed oxidation of alcohols with molecular oxygen to give aldehydes in good to excellent yields has
been developed. Best results are obtained by using a buffered two-phase system with a constant pH of 10.4. Under optimized
reaction conditions a remarkable catalyst productivity (TON up to 16600) is observed. © 2001 Published by Elsevier Science Ltd.
The selective oxidation of alcohols to give aldehydes is
an important synthetic tool both for natural product
synthesis as well as for fine chemical production.
Although a number of catalytic procedures are known
tion of 1,2-diols takes place. In this respect it is interest-
ing to note that Osborn and co-workers described very
recently the oxidation of benzylic alcohols to give ben-
zaldehydes in the presence of a bimetallic Os/Cu system
1
7
to achieve this transformation, there is a general inter-
in good to excellent yields. We wondered whether this
est to improve existing procedures or to develop new
methods. When developing new procedures for the
oxidation of alcohols, environmentally benign oxidants,
e.g. air or hydrogen peroxide, should be applied. In
addition, only small amounts of expensive transition
metal catalysts should be used. So far the oxidation of
alcohols to aldehydes with air or molecular oxygen has
been performed in the presence of relatively large
oxidation could be performed simply with an osmium
catalyst under the conditions of our dihydroxylation
procedure. Initially, we studied the oxidation of benzyl
alcohol and 1-phenylethanol in the presence of
K [OsO (OH) ] as model reactions (Table 1).
2
2
4
6
Applying our previously optimized conditions (2 mmol
t
alcohol, 1 bar molecular dioxygen, 35 ml H O/ BuOH
2
2
3
4
5
amounts of Pd, Ru, Cu and Co complexes (Eq. (1)).
(
2.5:1), 0.5 mol% K [OsO (OH) ], 3 mol% DABCO,
2 2 4
5
0°C), we observed the smooth formation of acetophe-
R′
Pd, Ru, Cu, Co
R′
none and benzaldehyde in 95 and 92% yield, respec-
tively (Table 1, entries 2 and 12). Without osmium
catalyst no oxidation is observed under these condi-
tions. Due to the importance of the pH value of the
reaction mixture for the reoxidation of the osmium(VI)
(
1)
R
OH
R
O
O2
R = aryl, alkyl; R′ = H, alkyl
8
to the active Os(VIII) the reaction of 1-phenylethanol
Recently, we reported that the osmium-catalyzed dihy-
droxylation of aliphatic and aromatic olefins proceeds
efficiently in the presence of dioxygen at ambient condi-
tions. While studying this reaction in detail, we noticed
that at reaction temperatures above 60°C further oxida-
was studied at pH 9.5, 11.2 and 12.0 (Table 1, entries
3–5). Excellent yields are obtained in between pH 9.5
and 11.2. At higher pH the conversion is significantly
decreased. The highest reaction rate is observed at pH
10.4. Hence, all further experiments were performed at
6
9
this pH value.
Keywords: oxidation; alcohols; aldehydes; oxygen; osmium.
Obviously, air is the most economical as well as envi-
ronmentally friendly oxidation reagent known. With
regard to the price and safety issues it is significantly
more advantageous to use air than pure dioxygen gas.
*
Corresponding author. Tel.: +49-381/466930; fax: +49-381/4669324;
e-mail: matthias.beller@ifok.uni-rostock.de
Dedicated to Professor Bernhard L u¨ cke on the occasion of his 65th
birthday.
†
0
040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)01747-6

8
448
C. D o¨ bler et al. / Tetrahedron Letters 42 (2001) 8447–8449
a
Table 1. Osmium catalyzed oxidation of benzyl alcohol and 1-phenylethanol
R′
K [OsO (OH) ]
2
2
4
R′
t
R
OH
O , H O / BuOH
R
O
2
2
Alcohol
Osmium (mol%)
Oxidant
pHb
T (°C)
DABCO (L:Os)
t (h)
Conversion
Yieldc
1
2
3
4
5
6
0.5
0.5
0.5
0.5
0.5
0.02
1 bar O2
1 bar O2
1 bar O2
1 bar O2
1 bar O2
20 bar air
10.4
10.4
9.5
11.2
12.0
10.4
50
50
50
50
50
80
–
3:1
3:1
3:1
3:1
3:1
12
12
24
14
24
24
100
100
100
100
79
95
95
93
95
74
94
d
CH3
100
Ph
OH
d
d
d
7
8
9
1
0.01
0.005
0.005
–
20 bar air
40 bar air
40 bar air
40 bar air
10.4
10.4
10.4
10.4
80
80
100
100
3:1
3:1
3:1
–
24
24
24
24
91
70
82
6
85
66
76
5
0d
1
1
1
1
1
–
1 bar O2
1 bar O2
20 bar air
20 bar air
10.4
10.4
10.4
10.4
80
50
50
80
–
3:1
3:1
3:1
24
16
24
24
–
100
88
–
92
82
92
2
0.5
0.02
0.02
d
3
d
4
100
Ph
OH
d
1
1
1
5
0.005
0.005
–
40 bar air
40 bar air
20 bar air
10.4
10.4
10.4
80
100
80
3:1
3:1
–
24
24
24
80
90
5
74
83
4
d
6
d
7
a
b
c
t
General conditions: 2 mmol alcohol, K [OsO (OH) ], 35 ml H O/ BuOH (2.5:1).
The given value is the pH value of the water phase.
GC yield of benzaldehyde or acetophenone.
2
2
4
2
d
4
mmol alcohol.
a
Hence, we investigated the influence of air on the
oxidation of alcohols (Table 1, entries 6–10 and 13–17).
Increasing the pressure and the temperature leads to a
much faster reaction. Thus, it is possible to decrease the
amount of the expensive osmium catalyst up to 0.005
mol%. Despite this low amount of catalyst acetophenone
and benzaldehyde are produced in 83 and 76% yields,
respectively. In the case of acetophenone this corre-
sponds to a catalyst turnover number (TON) of 16600
Table 2. Osmium-catalyzed oxidation of different alcohols
−
1
and catalyst activity (TOF) of ca. 700 h .
Next we applied the method to other alcohols. As shown
in Table 2 the oxidation of different benzylic (aromatic
and heteroaromatic) alcohols proceeds under mild condi-
tions in excellent yields, even at 1 bar of molecular
oxygen. However, secondary aliphatic alcohols need a
larger amount of catalyst and/or higher reaction temper-
atures in order to obtain sufficient conversion. It should
be noted that these reactions have not been optimized.
Higher product yields can be expected most likely at
higher pressure of air.
In conclusion, we have shown that the oxidation of
benzylic and secondary aliphatic alcohols is possible with
molecular oxygen or air in the presence of a commercially
available osmium catalyst. Upon optimization a remark-
able catalyst productivity and activity is observed.
Acknowledgements
We gratefully acknowledge support of this research by
the Ministry of Education, Science and Cultural Affairs

C. D o¨ bler et al. / Tetrahedron Letters 42 (2001) 8447–8449
8449
of Mecklenburg-Western Pomerania and the Bayer
AG.
Chelle-Regnaut, I.; Gautier, A.; Brown, S. M.; Urch, C. J.
J. Org. Chem. 1999, 64, 2433.
. Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y.
5
Tetrahedron Lett. 1995, 36, 6923.
References
6. (a) D o¨ bler, C.; Mehltretter, G.; Beller, M. Angew. Chem.,
Int. Ed. 1999, 38, 3026; (b) D o¨ bler, C.; Mehltretter, G. M.;
Sundermeier, U.; Beller, M. J. Am. Chem. Soc. 2000, 122,
1
. For reviews see: (a) Sheldon, R. A.; Arends, I. W. C. E.;
Dijksman, A. Catal. Today 2000, 57, 157; (b) Friedrich, H.
B. Platin. Metal. Rev. 1999, 43, 94.
. (a) Blackburn, T. F.; Schwartz, J. J. Chem. Soc., Chem.
Commun. 1977, 157; (b) Ait-Mohand, S.; Henin, F.;
Muzart, J. Tetrahedron Lett. 1995, 36, 2473; (c) Ait-
Mohand, S.; Muzart, J. J. Mol. Catal. A 1998, 129, 135;
d) Peterson, K. P.; Larock, R. C. J. Org. Chem. 1998, 63,
185–3189; (e) Nishimura, T.; Onoue, T.; Ohe, K.;
Uemura, S. Tetrahedron Lett. 1998, 39, 6011; (f) Hallman,
K.; Moberg, C. Adv. Synth. Catal. 2001, 343, 260.
10289; (c) D o¨ bler, C.; Mehltretter, G. M.; Sundermeier,
U.; Beller, M. J. Organomet. Chem. 2001, 621, 70; (d) See
also: Krief, A.; Colaux-Castillo, C. Tetrahedron Lett. 1999,
2
40, 4189.
7
8
9
. Coleman, K. S.; Coppe, M.; Thomas, C.; Osborn, J. A.
Tetrahedron Lett. 1999, 40, 3723.
. Mehltretter, G. M.; D o¨ bler, C.; Sundermeier, U.; Beller,
M. Tetrahedron Lett. 2000, 41, 8083.
(
3
. General procedure: (a) Oxidation of alcohols under atmo-
spheric dioxygen pressure: In a 100 ml Schlenk tube,
K [OsO (OH) ] and DABCO were dissolved in 25 ml
2
2
4
3
. (a) Matsumoto, M.; Ito, S. J. Chem. Soc., Chem. Commun.
aqueous buffer solution and 10 ml tert-BuOH. The
Schlenk tube was purged with oxygen and the biphasic
mixture was heated to the reaction temperature. Then the
alcohol was added in one portion by a syringe and the
tube connected to a graduated gas burette filled with
oxygen. The reaction mixture was stirred vigorously with a
magnetic stirring bar. After 12–24 h a little amount of
Na SO was added and the mixture was cooled to room
1
981, 907; (b) Bilgrien, C.; Davis, S.; Drago, R. S. J. Am.
Chem. Soc. 1987, 109, 3786; (c) Coleman, K. S.; Lorber, C.
Y.; Osborn, J. A. Eur. J. Inorg. Chem. 1998, 1673; (d)
B a¨ ckvall, J.-E.; Chowdhury, R. L.; Karlsson, U. J. Chem.
Soc., Chem. Commun. 1991, 473; (e) Wang, G.-Z.;
Andreasson, U.; B a¨ ckvall, J.-E. J. Chem. Soc., Chem.
Commun. 1994, 1037; (f) Hanyu, A.; Takezawa, E.; Sak-
aguchi, S.; Ishii, Y. Terahedron Lett. 1998, 39, 5557; (g)
Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Chem.
Commun. 1999, 1591.
. (a) Capdevielle, P.; Sparfel, D.; Baranne-Lafont, J.;
Cuong, N. K.; Maumy, M. J. Chem. Res. 1993, 10; (b)
Coleman, K. S.; Lorber, C. Y.; Osborn, J. A. Eur. J.
Inorg. Chem. 1998, 1673; (c) Skibida, I. P.; Sakharow, A.
M. Catal. Today 1996, 27, 187; (d) Sakharow, A. M.;
Skibida, I. P. J. Mol. Cat. 1988, 49, 157; (e) Semmelhack,
M. F.; Schmid, C. R.; Cortes, D. A.; Chou, C. S. J. Am.
Chem. Soc. 1984, 106, 3374; (f) Marko, I. E.; Giles, P. R.;
Tsukazaki, M.; Brown, S. M.; Urch, C. J. Science 1996,
2
3
temperature under stirring. The mixture was then
extracted twice with 20 ml portions of ethyl acetate. The
combined organic layers were dried over MgSO4 and
submitted for GC analysis after addition of 100 ml of
diethyleneglycol di-n-butyl ether as an internal GC stan-
dard. (b) Oxidation under elevated pressure: In a 100 ml
steel autoclave (Parr Instruments), equipped with a mag-
netic stirrer and a glass inline, K [OsO (OH) ] and
4
2
2
4
DABCO were dissolved in 25 ml aqueous buffer solution
and 10 ml tert-BuOH. After addition of alcohol the auto-
clave was closed, pressurized with air and heated to the
reaction temperature. After 12–24 h, the reaction mixture
was worked up as described.
2
74, 2044; (g) Marko, I. E.; Giles, P. R.; Tsukazaki, M.;