Efficient ruthenium-catalyzed aerobic oxidation of alcohols using a biomimetic coupled catalytic system

Article abstract of DOI:10.1021/jo0163750

Efficient aerobic oxidation of alcohols was developed via a biomimetic catalytic system. The principle for this aerobic oxidation is reminiscent of biological oxidation of alcohols via the respiratory chain and involves selective electron/proton transfer. A substrate-selective catalyst (ruthenium complex 1) dehydrogenates the alcohol, and the hydrogens abstracted are transferred to an electron-rich quinone (4b). The hydroquinone thus formed is continuously reoxidized by air with the aid of an oxygen-activating Co-salen type complex (6). Most alcohols are oxidized to ketones in high yield and selectivity within 1-2 h, and the catalytic system tolerates a wide range of O² concentrations without being deactivated. Compared to other ruthenium-catalyzed aerobic oxidations this new catalytic system has high turnover frequency (TOF).

Full text of DOI:10.1021/jo0163750

J . Org. Chem. 2002, 67, 1657-1662
1657
Efficien t Ru th en iu m -Ca ta lyzed Aer obic Oxid a tion of Alcoh ols
Usin g a Biom im etic Cou p led Ca ta lytic System
Ga´bor Csjernyik,† Alida H. EÄ ll,† Luca Fadini,‡ Benoit Pugin,‡ and J an-E. Ba¨ckvall*,†
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-106 91 Stockholm Sweden, and Catalysis Research, Solvias AG, CH-4002 Basel, Switzerland
jeb@organ.su.se
Received December 14, 2001
Efficient aerobic oxidation of alcohols was developed via a biomimetic catalytic system. The principle
for this aerobic oxidation is reminiscent of biological oxidation of alcohols via the respiratory chain
and involves selective electron/proton transfer. A substrate-selective catalyst (ruthenium complex
1) dehydrogenates the alcohol, and the hydrogens abstracted are transferred to an electron-rich
quinone (4b). The hydroquinone thus formed is continuously reoxidized by air with the aid of an
oxygen-activating Co-salen type complex (6). Most alcohols are oxidized to ketones in high yield
and selectivity within 1-2 h, and the catalytic system tolerates a wide range of O2 concentrations
without being deactivated. Compared to other ruthenium-catalyzed aerobic oxidations this new
catalytic system has high turnover frequency (TOF).
In tr od u ction
catalytic electron-transfer systems for 1,4-oxidations of
conjugated dienes,5 allylic oxidations,5a oxidations of
alcohols,6 and dihydroxylations of olefins7 where either
O2 or H2O2 are used as oxidant.
Oxidation of secondary alcohols is an important process
in living organisms, in particular in animals and aerobic
bacteria.1,2 These oxidations occur under very mild reac-
tion conditions and involve selective electron transfer
processes. The dehydrogenation of the alcohol is usually
carried out by NAD+ to give the ketone and NADH +
H+. The NADH is subsequently reoxidized by molecular
oxygen via the respiratory chain.3 The latter process
involves electron transfer from NADH to ubiquinone (Q)
to give ubiquinol (QH2), and the QH2 formed carries the
electrons to cytochrome c, which as its reduced form
transfers them to O2.
Because of the increased demand of environmentally
benign oxidation processes in organic chemistry, espe-
cially on large-scale synthesis, there is a growing interest
to mimic biological transformations. In the biomimetic
approach one would employ a substrate-selective redox
catalyst for the oxidation (cf. NAD+ in biological alcohol
oxidation) and then transfer the electrons of the reduced
form of the redox catalyst to O2 or H2O2. The latter
process requires electron-transfer mediators (ETMs)
between the substrate-selective redox catalyst and O2 or
H2O2 to proceed under mild conditions. A limited number
of oxidation reactions with such coupled electron-transfer
systems are known in nonbiological systems.4-10 Our own
group has recently designed and developed coupled
A number of methods for metal-catalyzed aerobic
oxidations of alcohols have been developed.6a,b,9-16 There
is a demand to make these reactions more efficient, and
particular emphasis has been put on facilitating electron
transfer from the alcohol to molecular oxygen. We now
describe an efficient aerobic biomimetic catalytic system
for dehydrogenation of alcohols to ketones involving a
(6) (a) Ba¨ckvall, J .-E.; Chowdhury, R. L.; Karlsson, U. J . Chem. Soc.
Chem. Commun. 1991, 473. (b) Wang, G.-Z.; Andreasson, U.; Ba¨ckvall,
J .-E. J . Chem. Soc. Chem. Commun. 1994, 1037. (c) Andreasson, U.;
Wang, G.-Z.; Ba¨ckvall, J .-E. J . Org. Chem. 1994, 59, 1196. (d) Almeida,
M. L. S.; Beller, M.; Wang, G.-Z.; Ba¨ckvall, J .-E. Chem. Eur. J . 1996,
2, 1533.
(7) (a) Bergstad, K.; J onsson, S. Y.; Ba¨ckvall, J .-E. J . Am. Chem.
Soc. 1999, 121, 10424. (b) J onsson, S. Y.; Fa¨rnegårdh, K.; Ba¨ckvall,
J .-E. J . Am. Chem. Soc. 2001, 123, 1365.
(8) (a) Bystro¨m, S. E.; Larsson, E. M.; A° kermark, B. J . Org. Chem.
1990, 55, 5674. (b) Yokota, T.; Sakurai, Y.; Sakaguchi, S.; Ishii, Y.
Tetrahedron Lett. 1997, 38, 3923. (c) Hanyu, A.; Takezawa, E.;
Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 1998, 39, 5557.
(9) For aerobic oxidation of alcohols involving formal coupled
electron-transfer, see: (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.; Gautier, A.; Brown, S.
M.; Urch, C. J . J . Org. Chem. 1999, 64, 2433.
(10) Dijksman, A.; Marino-Gonzales, A.; Mairata i Payeras, A.;
Arends, I. W. C. E.; Sheldon, R. A. J . Am. Chem. Soc. 2001, 6826.
(11) (a) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle´-Regnaut,
I.; Urch, C. J .; Brown, S. M. J . Am. Chem. Soc. 1997, 119, 12661. (b)
Lenz, R.; Ley, S. V. J . Chem. Soc., Perkin Trans. 1 1997, 3291.
(12) (a) Naota, T.; Takaya, H.; Murahashi, S.-I. Chem. Rev. 1998,
98, 2599. (b) Murahashi, S.-I.; Naota, T.; Hirai, N. J . Org. Chem. 1993,
58, 7318. (b) Arterburn, J . B. Tetrahedron 2001, 57, 9765.
(13) (a) Blackburn, T. F.; Schwartz, J . J . J . Chem. Soc. Chem.
Commun. 1977, 158. (b) Kaneda, K.; Fujie, Y.; Ebitani, K. Tetrahedron
Lett. 1997, 38, 9023. (c) Peterson, K. P.; Larock, R. C. J . Org. Chem.
1998, 63, 3185. (d) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S.
Tetrahedron Lett. 1998, 39, 6011.
† Stockhom University.
‡ Solvias AG.
(1) Pyridine Nucleotide Coenzymes: Chemical Biochemical, and
Medical Aspects; Dolphin, D., Avramovic, O., Poulson, R., Eds.; J ohn
Wiley & Sons: New York, 1987.
(2) Lehninger’s Principles of Biochemistry, 3rd ed.; Nelson, D. L.,
Lox, M. M., Eds.; Worth Publishers: New York, 2000.
(3) (a) Duester, G. Biochemistry 1996, 35, 12221. (b) Gille, L.; Nohl,
H. Arch. Biochem. Biophys. 2000, 375, 347. (c) Electron Transfer in
Chemistry; Balzani, V., Ed.; Wiley VCH: Weinheim, 2001.
(4) Tsuji, J . Palladium Reagents and Catalysts. Innovations in
Organic Synthesis; Wiley: Chichester, UK, 1995.
(14) Iwahama, T.; Yoshino, Y.; Keitoku, T.; Sakaguchi, S.; Ishii, Y.
J . Org. Chem. 2000, 65, 6502.
(15) (a) Bilgrien, C.; Davis, S.; Drago, R. S. J . Am. Chem. Soc. 1987,
109, 3786. (b) Tang, R.; Diamond, S. E.; Neary, N.; Mares, F. J . Chem.
Soc. Chem. Commun. 1978, 562.
(16) Brink, G.-J .; Arends, I. W. C. E.; Sheldon, R. A. Science 2000,
287, 1636.
(5) (a) Ba¨ckvall, J .-E.; Hopkins, R. B.; Grennberg, H.; Mader, M.;
Awasthi, A. K. J . Am. Chem. Soc. 1990, 112, 5160. (b) Wo¨ltinger, J .;
Ba¨ckvall, J .-E.; Zsigmond, A. Chem. Eur. J . 1999, 5, 1460.
10.1021/jo0163750 CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/05/2002

1658 J . Org. Chem., Vol. 67, No. 5, 2002
Csjernyik et al.
Ta ble 1. Oxid a tion of 1-P h en yleth a n ol (2a ) w ith
Stoich iom etic Am ou n ts of Qu in on esa
Sch em e 1
yield (%)b
30
min min 1 h
10
entry
benzoquinone
1
2
3
4
tetrafluoro-1,4-benzoquinone (4a )
2,6-dimethoxy-1,4-benzoquinone (4b)
2-chloro-1,4-benzoquinone (4c)
2,3-dimethoxy-5-methyl-
1,4-benzoquinone (4d )
1,4-benzoquinone (4e)
70
61
58
59
89 >99
84 >99
82 >99
80 >99
biomimetic coupled catalytic system. The design of the
system was inspired by the biological oxidation of second-
ary alcohols. Instead of NAD+ we are employing a
ruthenium complex as the substrate-selective catalyst,
the ubiquinone (Q) was replaced by another electron-rich
quinone, and in place of cytochrome c, a metal macrocycle
(MLm) such as iron phthalocyanine or a cobalt salen
complex was used for the O2 activation.
5
6
7
55
34
75
43
41
91
78
71
2,5-di-tert-butyl-1,4-benzoquinone (4f)
2,6-di-tert-butyl-1,4-benzoquinone (4g) 36
a
The reactions were carried out on a 0.5 mmol scale with 0.1
mol % of catalyst 1 and 1.2 equiv of the benzoquinone in 3 mL of
toluene at 100 °C under argon. Derminined by GC.
b
involving electron/proton transfer to and from the quino-
ne, and therefore a number of quinones were screened.
In a stoichiometric test reaction various quinones (4a )
were employed as hydrogen acceptors for the ruthenium-
catalyzed dehydrogenation of 1-phenylethanol (2a ) to
acetophenone (3a ) using ruthenium catalyst 1 (eq 1).
Resu lts a n d Discu ssion
Ruthenium complexes have been extensively studied
as catalysts for aerobic oxidation of alcohols.12 In most
cases a high-valent ruthenium complex acts as the active
catalyst in the reaction, and examples on the use of low-
valent ruthenium complexes are rare.6a,b,8,10 The combi-
nation of a low-valent ruthenium complex with a stabi-
lized free radical ligand (TEMPO) was reported recently
to affect aerobic oxidation of aliphatic alcohols.10 Also,
low-valent ruthenium and hydroquinone was recently
used for the oxidation of primary alcohols.8c In our
preliminary work on selective alcohol oxidation we
employed a triple catalytic system with a low-valent
ruthenium complex as the dehydrogenating catalyst.6b In
our search for an efficient coupled catalytic system for
biomimetic oxidation of alcohols via selective elctron
transfer (cf. Scheme 1) it was of importance to choose an
active substrate-selective catalyst and to find a quinone
together with an appropriate oxygen-activating metal
complex that both give low barriers in the electron-
transfer reactions according to Scheme 1.
Ch oice of Su bstr a te-Selective Ca ta lyst. A number
of ruthenium catalysts are known to be active in hydro-
gen transfer reactions. They have been used in asym-
metric transfer hydrogenation17 and also for racemization
of alcohols in the presence of a lipase to obtain a dynamic
kinetic resolution of the alcohol.18 For the present purpose
it is desirable to employ a catalyst that can readily
dehydrogenate an alcohol. Preliminary DFT calculations
show that electron-withdrawing ligands on the metal
increases the rate of dehydrogenation, whereas electron-
donating ligands depresses the rate of dehydrogenation.
A few catalysts were tested and among those the Shvo
catalyst 1 was found to be by far the best for promoting
dehydrogenation of alcohols.
The results given in Table 1 show that tetrafluoro-1,4-
benzoquinone (4a ) and 2,6-dimethoxy-1,4-benzoquinone
(4b) are the two best quinones in this stoichiometric test
reaction, and they gave a turnover frequency (TOF) of
3600-4200 h-1 during the first 10 min. Interestingly, the
2,6-di-tert-butyl-1,4-benzoquinone (4g) employed in our
preliminary study6b turned out to be the slowest quinone
of those tested.
We have previously demonstrated that the hydro-
quinone can be in-situ reoxidized to the corresponding
quinone by a metal macrocyclic complex/O2, and in this
way the quinone can be used in catalytic amounts. In
this dynamic electron-transfer process (cf. Scheme 1) it
is also important that the oxidation of the hydroquinone
to quinone be fast. Now, of the two hydroquinones
produced from entry 1 and 2 in Table 1, the tetrafluoro-
hydroquinone is more difficult to reoxidize to quinone
than the corresponding 2,6-dimethoxyhydroquinone. This
is because of the considerably higher oxidation potential
for quinone 4a compared to the electron-rich quinone 4b.
As anticipated, the latter quinone was superior to the
former in the aerobic triple catalytic system (cf. Scheme
1). Therefore, 4b was chosen as quinone in the aerobic
process.
Ch oice of Oxygen -Activa tin g Ca ta lyst. A number
of metal macrocyclic complexes and related complexes are
known to activate molecular oxygen. In living organisms
various metal porhyrins are used for this purpose. We
have previously used three different types of complexes
Scr een in g of Qu in on es. To increase the efficiency
of the reaction it was necessary to optimize the steps
(17) (a) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40,
40. (b) Gladiali, S.; Mestroni, G. Transition Metals for Organic
Synthesis; Beller, M., Bolm C., Eds.; Wiley VCH: Weinheim, 1998, pp
97-119.
(18) Persson, B. A.; Larsson, A. L. E.; LeRay, M.; Ba¨ckvall, J .-E. J .
Am. Chem. Soc. 1999, 121, 1645.

Ruthenium-Catalyzed Aerobic Oxidation of Alcohols
J . Org. Chem., Vol. 67, No. 5, 2002 1659
An important advantage with the present system is
that the catalytic reaction tolerates a wider range of O2
concentrations. In the preliminary study6b it was neces-
sary to run the reaction at very low O2 concentrations,
in the range 1-5% O2 in N2. The present system tolerates
much higher O2 concentrations without being deactivated
and is preferentially run under air.
When we applied our system to the oxidation of
benzylic alcohols the isolated yields of ketones are good
to high (Table 3, entries 1-3). These oxidation reactions
were performed also at lower oxygen concentration using
air:nitrogen of 1:10 (∼2% O2 in N2, Table 2) and with
different oxygen activators (such as iron(II) phthalo-
cyanine). The conversion (monitored by GC) to the
corresponding ketone was still high (>85%), but under
these reaction conditions the reaction was slower.
More resistant substrates, such as cyclic aliphatic
alcohols and linear aliphatic alcohols, can be oxidized
with the current system in good to excellent yields
(entries 4-12) and with good turnover frequencies (TOFs).
Since the reaction takes 1-2 h with a substrate to
catalyst (S/C) ratio of 200, the turnover frequency (TOF)
is 100-200 h-1 (50-100 h-1 based on ruthenium). For
example 2-octanol gave a TOF of 194 h-1 (97 h-1 based
on ruthenium), which is the highest ever reported for a
ruthenium-catalyzed aerobic oxidation of this substrate.
As a comparison, previously reported active ruthenium
systems RuCl2(PPh3)3-TEMPO10 and TPAP11 (tetra-
propylammonium perruthenate) gave TOFs of 14 h-1 and
5.5 h-1, respectively, for 2-octanol in aerobic oxida-
tion.10
F igu r e 1. Oxygen-activating catalysts.
Ta ble 2. Aer obic Oxid a tion of 1-P h en yleth a n ola
entry
solvent, temperature
ML complex
conversion (%)b
1
2
3
4
THF, 65 °C
THF, 65 °C
toluene, 100 °C
toluene, 100 °C
7
6
7
6
58
78
100
100c
a
The reactions were carried out on a 1 mmol scale in 5 mL
solvent under a balloon filled with ca. 2% oxygen in nitrogen
employing 0.5 mol % of catalyst 1, 20 mol % of 4b, and 2 mol % of
b
metal-ligand (ML) complex. Reaction time: 48 h. Determined
by GC. c 24 h.
for biomimetic aerobic oxidations: metal complexes of
porphyrins,5a phthalocyanines,5a and salens.5,6 Because
of the tendency for oxidative degradation, porphyrins
were avoided and the three complexes in Figure 1 were
tested.
Attempted aerobic oxidation of 1-phenylethanol using
catalyst 1, quinone 4b, and Co(salophen) (5) in toluene
in the temperature range 20-100 °C was unsuccessful
and gave very low conversions to ketone. We have
previously shown that the addition of a fifth ligand, e.g.,
triphenylphosphine, improves the activity in aerobic
oxidation of primary alcohols with 5 as oxygen-activating
catalyst.6a However, in the oxidation of 1-phenylethanol
poor results were still obtained on addition of triphen-
ylphosphine. The results from the other two complexes
are given in Table 2. Complex 6 seems to be slightly
better than complex 7 but both complexes work well as
oxygen-activating catalysts.
The present catalytic system tolerates the presence of
C-C double bonds, and in the oxidation of unsaturated
alcohol 2g (entry 7) no epoxidation of the alkene bond
could be detected. Sterically hindered alcohols such as
menthol and norborneol (entries 13-15) were also ef-
ficiently oxidized to ketones using this new ruthenium-
based aerobic process.
To demonstrate the utility of this new oxidation, a
scale-up for the aerobic oxidation of cyclohexanol was
carried out. The oxidation was done on a 100 mmol scale
(10 g scale) with a substrate/catalyst (S/C) ratio of 400
which gave a 95% isolated yield of cyclohexanone. Also,
it was demonstrated that for the oxidation of cyclohexanol
a substrate/catalyst (S/C) ratio of 1000 could be used to
give turnover numbers (TONs) of 700 (350 based on
ruthenium)(5M in toluene) and 800 (400 based on ru-
thenium)(neat without solvent).
Mech a n istic Con sid er a tion s. The ruthenium-cata-
lyzed aerobic oxidation of alcohols with 1 as catalyst
involves a highly efficient dehydrogenation step. Catalyst
1 is known to dissociate into 1a and 1b (Scheme 2). The
former can act as a dehydrogenation species, for alcohols,
and the latter can hydrogenate ketones, C-C double
bonds, and other unsaturated compounds. As shown from
the results in Table 1, the dehydrogenation of alcohol 2a
by 1a has a turnover frequency of >4000 h-1 at 100 °C
in toluene.
Biom im etic Oxid a tion of Alcoh ols. The coupled
catalytic system chosen for aerobic oxidation of secondary
alcohols consists of the binuclear ruthenium complex 119
as the substrate-selective catalyst, quinone 4b as electron-
transfer mediator (ETM), and bis(salicylideniminato-3-
propyl)methylamino-cobalt(II) 6 as the oxygen activator.
These new aerobic oxidations are quite efficient and in
most cases complete within 1-2 h. They can be carried
out under air with only 0.5 mol % of catalyst loading and
give high turnover frequency (TOF). GC analysis of the
reactions showed excellent conversion of the alcohols
without any observable byproduct (>99% selectivity), and
the ketone products were isolated in good to high yields
(eq 2).
The principle for the biomimetic aerobic oxidation of
alcohols with the coupled catalytic system is shown in
Scheme 3. The dehydrogenation of the alcohol with 1a
(19) (a) Blum, Y.; Czarkie, D.; Rahamin, Y.; Shvo, Y. Organometal-
lics 1985, 4, 1459. (b) Shvo, Y.; Czarkie, D.; Rahamin, Y. J . Am. Chem.
Soc. 1986, 108, 7400. (c) Shvo, Y.; Goldberg, I.; Czerkie, D.; Reshef,
D.; Stein, Z. Organometallics 1997, 16, 133.
The results of the oxidation of secondary alcohols to
the corresponding ketones are summarized in Table 3.

1660 J . Org. Chem., Vol. 67, No. 5, 2002
Ta ble 3. Ru th en iu m -Ca ta lyzed Aer obic Oxid a tion of Secon d a r y Alcoh olsa
Csjernyik et al.
a
Unless otherwise stated, the reactions were carried out under air on a 1 mmol scale in 1 mL of toluene at 100 °C, employing 0.5 mol
% of 1, 20 mol % of 4b, and 2 mol % of 6. Isolated yield. c Employing 1 mol % of 1.
b
produces ketone and 1b. Complex 1b can now deliver the
hydrogen atoms to quinone 4b, which regenerates 1a ,
and 4b is converted to the corresponding hydroquinone.
The reoxidation of the hydroquinone to quinone 4b is
carried out by air/6. This aerobic oxidation of alcohol is
reminiscent of biological dehydrogenations in which
NAD+/NADH-ubiquinone-cytochrome c are employed
for electron transfer.

Ruthenium-Catalyzed Aerobic Oxidation of Alcohols
J . Org. Chem., Vol. 67, No. 5, 2002 1661
Sch em e 2
a hydrogen bond to an acetamido ligand was recently
isolated and characterized by Yi et al.23 Complex 8 is an
18-electron complex, which on ring slipping would give
16-electron complex 9. Simultaneous â-elimination and
proton transfer in 9 would give 10, which would dissoci-
ate ketone and give 1b. This mechanism is consistent
with the combined isotope effect observed for the reverse
reaction, addition of hydrogen to the keto function (10
f 9).24 Alternatively, a direct concerted hydrogen transfer
from the alcohol to 1a , without prior coordination of the
alcohol, could also occur.24
Sch em e 3. Biom im etic Aer obic Oxid a tion of
Alcoh ols
Con clu sion
In conclusion, the present system based on ruthenium-
catalyzed dehydrogenation of secondary alcohols followed
by hydrogen transfer via coupled catalytic cycles is a
highly efficient biomimetic process for aerobic oxidation
of alcohols. The system is robust and does not undergo
deactivation by air. The oxidation of benzylic as well as
aliphatic alcohols can be performed with excellent yield
and selectivity to give the corresponding ketones.
Sch em e 4
Exp er im en ta l Section
1H NMR spectra were recorded in CDCl3 with a Varian XL-
400 spectrometer using the residual peak of CDCl3 (7.26 ppm
for 1H) as internal standard. Analytical gas chromatography
was performed with a Varian 3400 GC with a FID detector,
connected to a Varian computing integrator. A 30-m DB-17
J &M fused silica column was used. Solvents were purified by
standard procedures. Ruthenium catalyst 1 was prepared
according to a literature procedure.25 Bis(salicylideniminato-
3-propyl)methylamino-cobalt(II) (6) was purchased from Al-
drich and used as received. 1-Phenylethanol and 1-cyclopen-
tanol (Aldrich) were distilled prior to use. (Z)-5-Undecen-2-ol
was prepared by literature method.6d All other reagents are
commercially available and were used without further puri-
fication. Column chromatography was performed with Merck
60 silica gel and analytical TLC was performed on Merck
precoated silica 60-F254 plates. Solvents for extraction and
chromatography were technical grade and distilled before use.
Iron(II) phthalocyanine (7) was activated as described in ref
5a and Co(salophen) (5) was prepared according to ref 5a.
All 1,4-benzoquinones are available from commercial sources,
4a -4f from Aldrich and 4g from Lancester.
The biomimetic coupled catalytic system shown in
Scheme 3 leads to a mild kinetically controlled electron
transfer/H-transfer from the alcohol to molecular oxygen.
The high kinetic control requires close interaction (con-
tact) between the redox couples involved in the cascade
through coordination or weak bonding. Control experi-
ments showed that no aerobic oxidation took place
according to GC within 24 h if any of the components of
the catalytic system was removed.
Oxid a tion of 1-P h en yleth a n ol w ith Stoich iom etr ic
Am ou n t of Qu in on es. Ruthenium complex 1 (0.54 mg, 0.5
µmol, 0.1 mol %) and quinone 4b (101 mg, 0.6 mmol, 1.2 equiv)
were dissolved under argon atmosphere in 3 mL of toluene in
a round-bottomed flask equipped with a condenser and a
stirring bar. 1-Phenylethanol (0.5 mmol) was added, and the
reaction mixture was heated to 100 °C. The reaction course
was monitored by gas chromatography.
Gen er a l P r oced u r e for Ru th en iu m -Ca ta lyzed Aer obic
Oxid a tion of Secon d a r y Alcoh ols. Ruthenium complex 1
(5.4 mg, 0.005 mmol, 0.5 mol %), quinone 4b (32.8 mg, 0.2
mmol, 20 mol %), and cobalt complex 6 (8.2 mg, 0.02 mmol 2
mol %) were dissolved in 1 mL of toluene under argon
atmosphere in a round-bottomed flask equipped with a con-
denser and a stirring bar. The appropriate alcohol (1 mmol)
was added to this mixture followed by flushing with air for
ca. 1 min. The final reaction mixture was heated to 100 °C
with an oil bath.26 After the appropriate reaction time, the
mixture was cooled to room temperature and purified by flash
The dehydrogenation of the alcohol by ruthenium
species 1a deserves some comments. It is likely that the
alcohol coordinates to the 16-electron complex 1a to give
alcohol complex 8 (Scheme 4). The corresponding amine
complexes are known to form and have been isolated and
characterized.20 Park et al.21 has recently reported on the
alcohol complex 8 from 2-propanol (R1 ) R2 ) CH3).22
A
related ruthenium 2-propanol complex in which there is
(20) Abed, M.; Goldberg, I.; Stein, Z.; Shvo, Y. Organometallics 1988,
7, 2054.
(21) J ung, H.-M.; Shin S.-T.; Kim Y.-H.; Kim M.-J .; Park J . Orga-
nometallics 2001, 20, 3370.
(22) The correctness of the alcohol complex of ref 21 was recently
investigated. It was found that the proposed complex of ref 21 was
not the alcohol complex: Casey, C. P.; Bikzhanova, G. A.; Ba¨ckvall, J .
E.; J ohansson, L.; Park, J .; Kim, Y. H. Organometallics, to be
submitted.
(23) Yi, C. S.; He, Z.; Guzei, I. A. Organometallics 2001, 20, 3641.
(24) Casey, C. P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.;
Kavana, M. J . Am. Chem. Soc. 2001, 123, 1090.
(25) Huerta, F. F.; Laxmi, Y. R. S.; Ba¨ckvall, J .-E. Org. Lett. 2000,
2, 1037.
(26) Air with toluene at 100 °C produces explosive mixtures in the
gas phase.

1662 J . Org. Chem., Vol. 67, No. 5, 2002
Csjernyik et al.
chromatography. The products were characterized by com-
parison with authentic samples. All the product obtained and
shown in Table 1 are known compounds and were character-
ized by comparison with spectral data from the literature.
Swedish Foundation for Strategic Research is gratefully
acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Full experimental
details are available free of charge via the Internet at
http://pubs.acs.org.
Ackn owledgm en t. Financial support from the Swed-
ish Natural Science Research Council, the Swedish
Research Council for Engineering Sciences and the
J O0163750