Efficient, Aerobic, Ruthenium-Catalyzed Oxidation of Alcohols into Aldehydes and Ketones

Full text of DOI:10.1021/ja973227b

J. Am. Chem. Soc. 1997, 119, 12661-12662
12661
Efficient, Aerobic, Ruthenium-Catalyzed Oxidation
of Alcohols into Aldehydes and Ketones
Istva´n E. Marko´,*,† Paul R. Giles,† Masao Tsukazaki,†
Isabelle Chelle´-Regnaut,† Christopher J. Urch,‡ and
Stephen M. Brown§
Figure 1.
De´partement de Chimie, Laboratoire de Chimie Organique
UniVersite´ Catholique de LouVain, Baˆtiment LaVoisier
Place Louis Pasteur 1, B-1348 LouVain-la-NeuVe, Belgium
Zeneca Agrochemicals, Jealott’s Hill Research Station
Bracknell, Berkshire RG42 6ET, U.K.
many cases, the stoichiometric oxidant used in these processes
is either an amine N-oxide, an iodosobenzene derivative, a per-
oxide, or a combination of oxygen and an aldehyde. In this
latter case, 1 equiv of a carboxylic acid is also produced.11 Few
ruthenium-catalyzed oxidations of alcohols into carbonyl deriva-
tives are known that employ molecular oxygen as the ultimate
oxidant.
Zeneca Process Technology Department
Huddersfield Works, P.O. Box A38, Leeds Road
Huddersfield HD2 1FF, U.K.
ReceiVed September 15, 1997
In 1978, Tang and co-workers reported that hydrated RuCl3
catalyzed the aerobic oxidation of secondary alcohols into
ketones, albeit in modest yields.12 Subsequently, Matsumoto
has revealed that RuO2‚H2O is an effective catalyst for the
transformation of allylic alcohols into enals and enones.13 More
efficient catalysis can be achieved by the use of trinuclear
ruthenium complexes. These organometallics have been shown
by Drago to oxidize a variety of simple alcohols into aldehydes
and ketones under a 40 psi of O2.14 Finally, the elegant work
of Ba¨ckvall, which uses a combination of cobalt and ruthenium
catalysts for the oxidation of some allylic and benzylic alcohols,
is also a notable contribution to this area of research.15
The eagerness of Cu(I) salts to react with O2 and generate
bis-copper peroxides16 coupled with the ability of Ru(VII)
complexes to smoothly oxidize a range of alcohols prompted
us to investigate this bimetallic combination. For our initial
experiments, we selected p-chlorobenzyl alcohol 3 as the test
substrate and reacted it in toluene, under a stream of oxygen,
with catalytic quantities of ruthenium salts, in the presence of
copper(I) ions and base. The results of these studies are
collected in Table 1.
When commercially available tetrapropylammonium perru-
thenate (TPAP; 5 mol %) was added to a suspension of CuCl‚
Phen (5 mol %), K2CO3 (200 mol %), and 1,2-bis(ethoxycar-
bonyl)hydrazine (DEADH2; 25 mol %) in toluene, and the
oxidation was performed as described previously,5 an 80%
conversion of 3 into 4 was realized within 2.5 h (entry 1). This
success prompted us to investigate the need for all of the com-
ponents of this mixture for the oxidation process. Omission of
DEADH2 led to an improvement in catalyst activity and com-
plete conversion of the alcohol took place within the same reac-
The oxidation of alcohols into aldehydes and ketones is of
paramount importance in synthetic organic chemistry.1 The
plethora of reagents that have been developed to accomplish
this reaction is testimony to its importance.2 Unfortunately, one
or more equivalents of these, often hazardous or toxic, oxidizing
agents are usually required. From an economical and environ-
mental viewpoint, catalytic oxidation processes are thus ex-
tremely valuable and those employing molecular oxygen or air
are particularly attractive.3 However, few efficient, catalytic,
aerobic oxidations are known that proceed under mild conditions
and are amenable to the preparation of fine chemicals.4
We have recently reported a copper-catalyzed oxidation
system which employs molecular oxygen or air as the ultimate,
stoichiometric oxidant.5 Using this method, alcohols are
smoothly converted into carbonyl compounds in good yields
and water is released as the only byproduct. During optimiza-
tion of this procedure, we decided to investigate the ability of
other metallic species to catalyze the aerobic oxidation of
alcohols into ketones and aldehydes. Our preliminary studies
focused on the use of various ruthenium salts (Figure 1).
The propensity of ruthenium complexes to transform alcohols
into carbonyl derivatives has been well documented.6-10 In
† 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 cited
therein.
(2) For general reviews on oxidation reactions, see: (a) Larock, R. C.
In ComprehensiVe Organic Transformations; VCH Publishers Inc.: New
York, 1989, 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.;
Pergamon: 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.
(3) (a) Meunier, B. Bull. Soc. Chim. Fr. 1986, 578. (b) Groves, J. T.;
Quinn, R. J. Am. Chem. Soc. 1985, 107, 5790. (c) Leising, R. A.; Takeuchi,
K. Inorg. Chem. 1987, 26, 4391. (d) Okamoto, T.; Sasaki, K.; Oka, S. J.
Am. Chem. Soc. 1988, 110, 1187. (e) Davis, S.; Drago, R. S. J. Chem.
Soc., Chem. Commun. 1990, 250.
(4) (a) Sheldon, R. A. In Dioxygen ActiVation and Homogeneous
Catalytic Oxidation; Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p
573. (b) James, B. R. In Dioxygen ActiVation and Homogeneous Catalytic
Oxidation; Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 195.
(5) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C. J.
Science 1996, 274, 2044.
(6) Sharpless, K. B.; Akashi, K.; Oshima, K. Tetrahedron Lett. 1976,
29, 2503.
(7) (a) Murahashi, S.-I. Pure Appl. Chem. 1992, 64, 403. (b) Murahashi,
S.-I.; Naota, T. In AdVances in Metal-Organic Chemistry; JAI Press:
Greenwich, CT, 1994; Vol. 3, p 225. (c) Murahashi, S.-I.; Naota, T. Synthesis
1993, 433.
(8) (a) Griffith, W. P.; Ley, S. V. Aldrichimica Acta 1990, 23, 13. (b)
Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994,
639.
(9) Griffith, W. P. Chem. Soc. ReV. 1992, 21, 179.
(10) For example, see: (a) Bressan, M.; Mengarda, M.; Morvillo, A. In
Dioxygen ActiVation and Homogeneous Catalytic Oxidation; Simandi, L.
L., Ed.; Elsevier: Amsterdam, 1991; p 155. (b) Agarwal, D. D.; Jain, R.;
Sangha, P.; Rastogi, R. Ind. J. Chem. 1993, 32B, 381. (c) Morris, P. E.;
Kiely, D. E. J. Org. Chem. 1987, 52, 1149. (d) Barak, G.; Dakka, J.; Sasson,
Y. J. Org. Chem. 1988, 53, 3553. (e) Boelrijk, A. E. M.; van Velzen, M.
M.; Neenan, T. X.; Reedijk, J.; Kooijman, H.; Spek, A. L. J. Chem. Soc.,
Chem. Commun. 1995, 2465. (f) Tomioka, H.; Takai, K.; Oshima, K.;
Nozaki, H. Tetrahedron Lett. 1981, 22, 1605. (g) Genet, J. P.; Pons, D.;
Juge´, S. Synth. Commun. 1989, 19, 1721. (h) Inokuchi, T.; Nakagawa, K.;
Torii, S. Tetrahedron Lett. 1995, 36, 3223.
(11) (a) Murahashi, S.-I.; Oda, Y.; Naota, T. J. Am. Chem. Soc. 1992,
114, 7913. (b) Murahashi, S.-I.; Naota, T.; Hirai, N. J. Org. Chem. 1993,
58, 7318.
(12) Tang, R.; Diamond, S. E.; Neary, N.; Mares, F. J. Chem. Soc., Chem.
Commun. 1978, 562.
(13) Matsumoto, M.; Watanabe, N. J. Org. Chem. 1984, 49, 3435.
(14) Bilgrien, C.; Davis, S.; Drago, R. S. J. Am. Chem. Soc. 1987, 109,
3786.
(15) (a) Ba¨ckvall, J.-E.; Chowdhury, R. L.; Karlsson, U. J. Chem. Soc.,
Chem. Commun. 1991, 473. (b) Ba¨ckvall, J.-E.; Awasthi, A. K.; Renko, Z.
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S0002-7863(97)03227-7 CCC: $14.00 © 1997 American Chemical Society

12662 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Communications to the Editor
Table 1. Aerobic, Ruthenium-Catalyzed Oxidation of
p-Chlorobenzyl Alcohol
Table 2. Ruthenium-Catalyzed Aerobic Oxidation of Alcohols
a The conversion was measured by 1H NMR spectroscopy and by
capillary GC analysis.
tion time (entry 2). Removing the CuCl‚Phen complex sig-
nificantly enhanced the rate of oxidation of 3 into 4 without
affecting the conversion to aldehyde 4 (entry 3). Thus, in con-
trast to our earlier assumption (Vide supra), the presence of the
copper complex has a retarding effect on the oxidation process.
Finally, we achieVed a quantitatiVe transformation of 3 into 4,
in less than half an hour, using TPAP in the presence of O2
and 4 Å MS (entry 4).17 This remarkably simple procedure was
then applied to a range of representative alcohols (Table 2).
As can be seen from Table 2, benzylic, allylic, and secondary
alcohols undergo smooth oxidation into the corresponding alde-
hydes and ketones (entries 1-3, 5-6, and 10). Whereas gera-
niol affords geranial without isomerization of the conjugated
C-C double bond, nerol gives neral with minor erosion of the
geometric integrity of the alkene (entries 5 and 6). It is note-
worthy that these reactions proceed faster and with improved
yields in 1,2-dichloroethane as compared to those in toluene.18
Remarkably, the catalyst is compatible with a range of hetero-
atoms, including sulfur heterocycles (entry 9).19 The oxidation
of R-ketols produces 1,2-diketones with no overoxidation in the
case of benzoin (entry 7). Some cleavage could be observed
for the dibutyl derivative (entry 8). Primary aliphatic alcohols
are smoothly converted into the corresponding aldehydes in good
yields (entry 4). However, the reaction has to be performed in
the absence of the 4 Å MS. The reason for this behavior is not
clear at present.
a All yields are for pure, isolated products. b The conversion is
quantitative. c The reaction was performed without molecular sieves,
in refluxing toluene, and proceeded with a 94% conversion. d The
reaction was performed in 1,2-dichloroethane, at reflux, without
molecular sieves. The conversion was quantitative, and no double bond
isomerization occurred. e The reaction was carried out in 1,2-dichlo-
roethane, at reflux, and proceeded in 88% conversion. Some geranial
was also detected (∼5%). f Pentanoic acid could also be isolated in
low yield (<10%). g A 73% conversion was realized under the standard
conditions. The recovered starting material amounted to 20%.
aldehydes and ketones.21 To the best of our knowledge, this
novel procedure superseeds any previously reported aerobic,
catalytic oxidations of alcohols by virtue of its simplicity,
efficiency, and versatility. Although much work still remains,
mild and ecologically benign aerobic oxidations of alcohols now
appear to be within reach.
Acknowledgment. This paper is dedicated with deep respect to
Professors S. V. Ley and W. P. Griffith. Financial support of this work
was provided by Zeneca Limited, through the Zeneca Strategic Research
Fund. IEM is grateful to Zeneca for receiving the Zeneca Fellowship
(1994-1997).
It is noteworthy that smaller amounts of TPAP could be used
in this process, though the reaction becomes more sluggish. For
example, whereas the oxidation of 3 to aldehyde 4 is complete
within 30 min under standard conditions (5 mol % TPAP), about
18 h are required to afford the same yield of 4 if only 1 mol %
TPAP is employed.20 Quite remarkably, the catalyst remains
active even after this extended period of time.
JA973227B
(20) While this process proved rather insensitive to changes in concentra-
tion, a small increase in temperature resulted in a dramatic improvement in
the reaction rate and the conversions (3 into 4, 20 °C, 55% conversion, 2.5
h; 50 °C, >98% conversion, 2.5 h).
In summary, we have discovered that TPAP can be used as
an effective catalyst for the aerobic oxidation of alcohols to
(17) Other ruthenium salts, e.g., RuCl3, RuCl2(PPh3)2, KRuO4, and
Bu4N+RuO4-, were also tested and proved to be less efficient than TPAP.
(18) The nature of the solvent appears to be critical to the success of
these aerobic oxidations. While CH2Cl2 or CH3CN are commonly used for
the TPAP/NMO protocol, rapid catalyst deactivation occurs under our
aerobic procedure if CH2Cl2 or CH3CN is employed as the solvent. Toluene
and fluorobenzene proved to be the solvents of choice, though 1,2-
dichloroethane could be superior at times.
(19) In addition to entry 9, pyridine-3-methanol is smoothly converted
into pyridine-3-carboxaldehyde. Attempted ruthenium-catalyzed oxidations
of triphenylphosphine, N-methylmorpholine, and thioanisole to the corre-
sponding oxides resulted in quantitative recovery of the starting materials.
This observation suggests that the aerobic oxidation proceeds probably by
a dehydrogenation mechanism rather than an oxygen transfer process. The
reaction also tolerates a range of protecting groups, such as benzyl and
silyl ethers.
(21) Typical experimental procedure, preparation of p-chlorobenz-
aldehyde: A suspension of TPAP (48 mg, 6.125 mmol, 0.05 equiv) and
powdered, activated 4 Å MS (200 mg) in toluene (12 mL) was stirred for
2-3 min. p-Chlorobenzyl alcohol (0.27 g, 2.5 mmol) was added, and a
gentle current of oxygen was passed through the dark suspension Via a
glass-inlet tube. The reaction mixture was heated at 60-70 °C. After 30
min, TLC (SiO2; EtOAc/petrol ) 1:4; Rf(3) ) 0.48, Rf(4) ) 0.80) indicated
the complete disappearance of the starting material and the mixture was
cooled to room temperature. The suspension was filtered through a pad of
Celite, and the pad was further washed with CH2Cl2/hexane (1:1). The
combined filtrates were carefully evaporated under reduced pressure, and
the product was further purified by column chromatography on silica gel,
using CH2Cl2/hexane (1:1) as eluent, to give the title compound (0.23 g,
1
81% yield). H NMR (CDCl3, 300 MHz): δH 9.98 (1H, s), 7.82 (2H, d, J
) 8.4 Hz), 7.50 (2H, d, J ) 8.4 Hz). 13C NMR (CDCl3, 75.5 MHz): δC
191.3, 141.5, 135.4, 131.5, 130.0.