Efficient and selective aerobic oxidation of alcohols into aldehydes and ketones using ruthenium/TEMPO as the catalytic system

Article abstract of DOI:10.1021/ja0103804

The combination of RuCl₂(PPh₃)₃ and TEMPO affords an efficient catalytic system for the aerobic oxidation of a variety of primary and secondary alcohols, giving the corresponding aldehydes and ketones, in >99% selectivity in all cases. The Ru/TEMPO system displayed a preference for primary vs secondary alcohols. Results from Hammett correlation studies (ρ = -0.58) and the primary kinetic isotope effect (k_H/k_D = 5.1) for the catalytic aerobic benzyl alcohol oxidations are inconsistent with either an oxoruthenium (O=Ru) or an oxoammonium based mechanism. We postulate a hydridometal mechanism, involving a "RuH₂(PPh₃)₃" species as the active catalyst. TEMPO acts as a hydrogen transfer mediator and is either regenerated by oxygen, under catalytic aerobic conditions, or converted to TEMPH under stoichiometric anaerobic conditions.

Full text of DOI:10.1021/ja0103804

6826
J. Am. Chem. Soc. 2001, 123, 6826-6833
Efficient and Selective Aerobic Oxidation of Alcohols into Aldehydes
and Ketones Using Ruthenium/TEMPO as the Catalytic System
Arne´ Dijksman, Arturo Marino-Gonza´lez, Antoni Mairata i Payeras,
Isabel W. C. E. Arends, and Roger A. Sheldon*,†
Contribution from the Laboratory for Organic Chemistry and Catalysis, Department of Biotechnology,
Delft UniVersity of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands
ReceiVed February 12, 2001
Abstract: The combination of RuCl2(PPh3)3 and TEMPO affords an efficient catalytic system for the aerobic
oxidation of a variety of primary and secondary alcohols, giving the corresponding aldehydes and ketones, in
>99% selectivity in all cases. The Ru/TEMPO system displayed a preference for primary vs secondary alcohols.
Results from Hammett correlation studies (F ) -0.58) and the primary kinetic isotope effect (kH/kD ) 5.1) for
the catalytic aerobic benzyl alcohol oxidations are inconsistent with either an oxoruthenium (OdRu) or an
oxoammonium based mechanism. We postulate a hydridometal mechanism, involving a “RuH2(PPh3)3” species
as the active catalyst. TEMPO acts as a hydrogen transfer mediator and is either regenerated by oxygen, under
catalytic aerobic conditions, or converted to TEMPH under stoichiometric anaerobic conditions.
Introduction
tions using a variety of stoichiometric oxidants such as
iodosobenzene,12 methylmorpholine N-oxide,2,13 bromate,14 hy-
pochlorite,15 peroxides,16 or a combination of oxygen and an
aldehyde. In the latter case, 1 equiv of carboxylic acid is also
formed.17
The number of ruthenium-catalyzed alcohol oxidations,
employing oxygen (or air) as the sole oxidant, is limited.18 For
example, RuCl2(PPh3)3,19 hydrated RuO2,20 and Ru-hydrotal-
cite21 have been shown to catalyze the oxidation of alcohols
using oxygen as the primary oxidant, but in these cases the scope
was generally limited to activated alcohols, i.e., allylic and
benzylic alcohols. On the other hand, tetrapropylammoniumper-
ruthenate (TPAP), either as such22 or supported on an ion-
exchange resin23 or MCM-41,24 catalyzes the aerobic oxidation
of nonactivated aliphatic alcohols (reaction 1). Other examples
The oxidation of alcohols into their corresponding aldehydes
and ketones is of significant importance in synthetic organic
chemistry.1-3 Many reagents for alcohol oxidations are known,3
e.g., hypochlorite,4 chromium(VI) oxide,5 dichromate,6 man-
ganese(IV) oxide,7 permanganate,8 and ruthenium(VIII) oxide.9
Unfortunately, one or more equivalents of thesesoften hazard-
ous or toxicsoxidizing agents are required. From both an
economic and environmental point of view, the quest for
effective catalytic oxidation processes that use clean, inexpensive
primary oxidants, such as molecular oxygen or hydrogen
peroxide, i.e., a “green method” for converting alcohols to
carbonyl compounds on an industrial scale, remains an important
challenge.10
Most examples of alcohol oxidations, both homogeneous and
heterogeneous, involve the use of group 8 metal complexes as
catalysts. Especially ruthenium compounds, which are widely
used as catalysts in organic synthesis,11 have been thoroughly
investigated. RuCl2(PPh3)3, RuCl3, and some high-valent oxo-
ruthenium complexes are known to mediate in alcohol oxida-
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Chem Soc., Chem. Commun. 1987, 1625-1627. (b) Vijayasri, K.; Rajaram,
J.; Kuriacose, J. C. J. Mol. Catal. 1987, 39, 203-217.
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(b) Bailey, A. J.; Griffith, W. P.; Mostafa, S. I.; Sherwood, P. A. Inorg.
Chem. 1993, 32, 268-271.
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289,053 [86,289,053], 1986; Chem. Absrt. 1987, 106, 175781g.
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Nozaki, H. Tetrahedron Lett. 1983, 24, 2185-2188. (c) Tanaka, M.;
Kobayashi, T.-A.; Sakakura, T. Angew. Chem. 1984, 96, 519-520.
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7319.
† E-mail: secretariat-ock@tnw.tudelft.nl.
(1) Sheldon, R. A.; Kochi, J. K. Metal-Catalysed Oxidations of Organic
Compounds; Academic Press: New York, 1981.
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1994, 639-666.
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Society: Washington, DC, 1990 and references therein.
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45, 2030-2032.
(5) Holum, J. R. J. Org. Chem. 1961, 26, 4814-4816.
(6) Lee, D. G.; Spitzer, U. A. J. Org. Chem. 1970, 35, 3589-3590.
(7) Highet, R. J.; Wildman, W. C. J. Am. Chem. Soc. 1955, 77, 4399-
4401.
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10.1021/ja0103804 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/21/2001

Aerobic Oxidation Using Ruthenium/TEMPO
J. Am. Chem. Soc., Vol. 123, No. 28, 2001 6827
Table 1. Aerobic Ruthenium/TEMPO-Catalyzed Oxidation of
Octan-2-ola
entry
S/C ratio
time (h)
convn (%)b
sel. (%)b
TONc
of catalytically active ruthenium systems are trinuclear ruthe-
nium complexes,25 ruthenium complexes in combination with
hydroquinone as cocatalyst,26 Ru/CeO2,27 and the improved Ru/
Co-hydrotalcite.28 Besides ruthenium, a few other metals, e.g.,
palladium,29 cobalt,30 and copper,10,31 have also been shown to
catalyze reaction 1. However, most reported systems require
relatively large quantities of catalyst (5-10 mol %) and/or
additives, i.e., cocatalyst (10-20 mol %) and drying agents (2
equiv), to achieve their activity.
In addition to metal complexes, stable nitroxyl radicals, such
as 2,2′,6,6′-tetramethylpiperidine N-oxyl (TEMPO), have been
used as catalysts for the mild and selective oxidation of alcohols
to aldehydes, ketones, and carboxylic acids.32 Typically, these
transformations employ 1 mol % of the nitroxyl radical and a
stoichiometric amount of a terminal oxidant, e.g., sodium
hypochlorite,33,34 trichloroisocyanuric acid,35 m-chloroperbenzoic
acid,36 sodium bromite,37 sodium chlorite,38 and oxone.39 In
these systems, an oxoammonium cation is generated and acts
as the active oxidant (reaction 2). The hydroxylamine (2), which
1
no Ru
100
100
100
1225
24
24
7
7
1
5
22
0
18
98 (90)
89
8.5
17
2d
3
>99
>99
>99
>99
>99
>99
18
98
89
104
208
466
4e
5f
38
a Reaction conditions: 15 mmol of substrate, Ru:TEMPO ) 1:3,
30 mL of chlorobenzene, 10 mL/min O2/N2 (8/92; v/v), p (total pressure)
) 10 bar, T ) 100 °C (see Experimental Section). b Conversions and
selectivities based on GC results using n-hexadecane as internal
standard; numbers in parentheses are isolated yields (see Experimental
Section). c TON ) turnover number in mmol of product per mmol of
Ru catalyst. d No TEMPO. e Toluene as solvent. f Neat octan-2-ol as
solvent.
easily oxidized benzylic and allylic alcohols, with simple
primary and secondary alcohols being largely unreactive.
Ruthenium/TEMPO as Catalytic System. On the basis of
the catalytic systems described above, we reasoned that the
combination of ruthenium and TEMPO would likely lead to an
efficient catalytic system for the aerobic oxidation of alcohols.
For our initial experiments, we selected octan-2-ol as a test
substrate and allowed it to react in chlorobenzene with catalytic
quantities of RuCl2(PPh3)3 in the presence of TEMPO43 and
42
oxygen.
As shown in Table 1, RuCl2(PPh3)3 alone is a poor catalyst
for the aerobic oxidation of octan-2-ol to octan-2-one (entry
2). On the other hand, addition of TEMPO, which itself is not
active as catalyst (entry 1), to RuCl2(PPh3)3 leads to a substantial
increase in activity (entry 3). The use of chlorobenzene as a
solvent is not essential and was chosen merely to simplify the
GC analysis. Toluene can also be employed (entry 4), and even
better results were obtained in neat octan-2-ol (entry 5). In this
case, a turnover number (TON) of approximately 100 was
achieved within 1 h compared to the 7 h needed for the same
TON in chlorobenzene (entry 3).
Besides RuCl2(PPh3)3, other ruthenium compounds were also
tested. RuCl3 gave lower rates and 18e complexes of ruthenium,
e.g., RuCl2(bipy)2 and RuCl2(DMSO)4, were completely unre-
active. Also, other metal chlorides, e.g., Fe(II and III), Ni(II),
Pd(II), Cu(I and II), Mn(II), and Co(II and III), show no activity
in combination with TEMPO. Similarly, the combination of
RuCl2(PPh3)3 and other hydrogen/electron-transfer systems, such
as ABTS and 2-ethylanthraquinone, is not able to catalyze the
aerobic oxidation of octan-2-ol. In conclusion, the best results
were obtained when using 1.0 mol % of RuCl2(PPh3)3 and 3.0
mol % of TEMPO. In this case, the turnover frequency (TOF)
was 14 h-1, which is superior to the most active aerobic
ruthenium system described in the literature, i.e., TPAP,22 which
in our hands gave a TOF of 5.5 h-1 for octan-2-ol.44
is formed, is reoxidized by the terminal oxidant to regenerate
1.40 Alternatively, the use of TEMPO in combination with
copper salts and oxygen as the primary oxidant was reported
by Semmelhack.41 However, this system was effective only with
(25) Bilgrien, C.; Davis, S.; Drago, R. S. J. Am. Chem. Soc. 1987, 109,
3786-3787.
(26) (a) Hanyu, A.; Takezawa, E.; Sakaguchi, S.; Ishii, Y. Tetrahedron
Lett. 1998, 39, 5557-5560. (b) Wang, G.-Z.; Andreasson, U.; Ba¨ckvall,
J.-E. J. Chem. Soc., Chem. Commun. 1994, 1037-1038.
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Commun. 1998, 28, 2577-2582.
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266.
(29) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetrahedron Lett.
1998, 39, 6011-6014.
(30) Iwahama, T.; Sukaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron
Lett. 1998, 36, 6923-6926.
(31) Marko, I. E.; Gautier, A.; Chelle´-Regnaut, I.; Giles, P. R.; Tsukazaki,
M.; Urch, C. J.; Brown, S. M. J. Org. Chem. 1998, 63, 7576-7577.
(32) (a) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis
1999, 1153-1174 and references therein. (b) Bobbitt, J. M.; Flores, M. C.
L. Heterocycles 1988, 27, 509-533.
(33) Anelli, P. L.; Biffi, C.; Montari, F.; Quici, S. J. Org. Chem. 1987,
52, 2559-2562.
(34) Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Chem. Commun.
2000, 271-272.
(35) Jenny, C.-J.; Lohri, B.; Schlageter, M. Eur. Pat. 0775684A1, 1997.
(36) (a) Cella, J. A.; Kelley, J. A.; Kenehan, E. F. J. Org. Chem. 1975,
40, 1860-1862. (b) Rychovsky, S. D.; Vaidyanathan, R. J. Org. Chem.
1999, 64, 310-312.
(37) Inokuchi, T.; Matsumoto, S.; Nishiyama, T.; Torii, S. J. Org. Chem.
1990, 55, 462-466.
(38) Zhao, M.; Li, J.; Mano, E.; Song, Z.; Tschaen, D. M.; Grabowski,
E. J. J.; Reider, P. J. J. Org. Chem. 1999, 64, 2564-2566.
(39) Bolm, C.; Magnus, A. S.; Hildebrand, J. P. Org. Lett. 2000, 2, 1173-
1175.
(40) (a) Miyazawa, T.; Endo, T. J. Org. Chem. 1985, 50, 3930-3931.
(b) Rozantsev, E. G.; Sholle, V. D. Synthesis 1971, 190-202.
(41) Semmelhack, M. F.; Schmid, C. R.; Corte´s, D. A.; Chou, C. S. J.
Am. Chem. Soc. 1984, 106, 3374-3376.
The dependence of the initial rate of the catalytic oxidation
on the temperature can be employed to determine the activation
energy of the reaction (Arrhenius plot). The data for the Ru/
(42) RuCl2(PPh3)3 was prepared according to: Hallman, P. S.; Stephen-
son, T. A.; Wilkinson, G. Inorg. Synth. 1970, 12, 237-240.
(43) TEMPO free radical was purchased from the Aldrich Chemical Co.
and used without further purification.
(44) Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Chem. Commun.
1999, 1591-1592.

6828 J. Am. Chem. Soc., Vol. 123, No. 28, 2001
Dijksman et al.
Table 2. Ruthenium/TEMPO-Catalyzed Aerobic Oxidation of Several Alcoholsa
entry
substrate
product
octan-2-one
octanal
benzaldehyde
p-nitrobenzaldehyde
acetophenone
cyclooctanone
adamantan-2-one
geranial
3-methyl-2-butenal
octan-2-one/octanal
benzaldehyde/acetophenone
S/C ratio
time (h)
convn (%)b
1
2c
3
4
5
6
7
octan-2-ol
octan-1-ol
100
50
7
7
2.5
6
4
7
6
7
7
98 (90)
85
>99 (90)
97
>99 (93)
92
98
91
96
benzyl alcohol
p-nitrobenzyl alcohol
1-phenylethanol
cyclooctanol
adamantan-2-ol
200
200
100
100
100
67
67
50
200
8c
9c
10c
11
geraniol
3-methyl-2-buten-1-ol
octan-2-ol/octan-1-ol
benzyl alcohol/1-phenylethanol
7
3
10/80
90/5
a Reaction conditions: 15 mmol of substrate, RuCl2(PPh3)3/TEMPO ratio of 1:3, 30 mL of chlorobenzene, 10 mL min-1 O2/N2 (8/92; v/v), p )
10 bar, T ) 100 °C. b Conversions based on GC results (selectivity >99% in all cases) using n-hexadecane as internal standard; numbers in
parentheses are isolated yields. c O2 atmosphere (see Experimental Section).
Figure 2. Unreactive alcohols.
Figure 1. The correlation of the initial rate and the temperature (40-
120 °C) for the Ru/TEMPO-catalyzed aerobic oxidation of octan-2-ol.
oxidations are generally believed to involve the intermediate
formation of an alkoxy-ruthenium complex,46 we interpret this
TEMPO-catalyzed aerobic oxidation of octan-2-ol plotted in
result as an indication that the ruthenium preferentially com-
plexes with primary alcohols, leading to selective oxidation of
the latter. In addition to the (intermolecular) competition
experiments, the same behavior was observed in the intramo-
lecular competition of two primary/secondary diols, i.e., 1,5-
hexanediol and 4-(1′-hydroxyethyl)benzyl alcohol (see Experi-
mental Section). As shown in reactions 3 and 4, the Ru/TEMPO
Figure 1 can be readily fitted to the familiar expression k ) A
exp(-Ea/RT), to give an activation energy (Ea) of 47.8 kJ/mol.
Scope of the Ru/TEMPO-Catalyzed Aerobic Oxidation.
The use of RuCl2(PPh3)3/TEMPO as catalyst for the aerobic
oxidation of alcohols was applied to a range of representative
primary and secondary alcohols. As shown in Table 2, octan-
1-ol is oxidized selectively into octanal (entry 2). TEMPO not
system again displayed a preference for the primary versus the
only accelerates the oxidation of octan-1-ol but also completely
secondary hydroxyl group of either an aliphatic or a benzylic
suppresses the overoxidation of octanal to octanoic acid.
diol.
Attempted oxidation of octanal under the same reaction condi-
tions, in the presence of TEMPO, gave no reaction in 1 week.
On the other hand, without TEMPO octanal was converted
completely to octanoic acid within 1 h. The ability to suppress
overoxidation is due to the well-known antioxidant activity of
TEMPO. This stable nitroxyl radical efficiently scavenges free
radical intermediates during autoxidation and thereby terminates
free radical chains.
Allylic alcohols were selectively converted into the corre-
sponding unsaturated aldehydes in high yields without intramo-
lecular hydrogen transfer (entries 8 and 9). Some ruthenium(II)
phosphine complexes are known to catalyze the rearrangement
of allylic alcohols to saturated ketones via intramolecular
hydrogen transfer,45 which obviously is not occurring in the
present system. Besides aliphatic and allylic alcohols, cyclic
and benzylic alcohols were also smoothly oxidized into the
corresponding ketones and aldehydes (entries 3-7). In these
cases lower catalyst loadings (S/C g 100) were sufficient to
obtain the same results.
The Ru/TEMPO system displayed a preference for primary
versus secondary alcohols, as was observed in competition
experiments (entries 10 and 11). Since ruthenium-catalyzed
In summary, the combination of RuCl2(PPh3)3 and TEMPO
affords an efficient catalytic system for the aerobic oxidation
of a variety of primary and secondary alcohols, e.g., aliphatic,
allylic, benzylic, and cyclic ones. Unfortunately, a number of
alcohols remain that are unreactive toward this system. Gener-
ally, these unreactive alcohols (Figure 2) contain heteroatoms
(O, N, S), which probably coordinate to ruthenium and thereby
inactivate the catalyst.
(46) (a) Sharpless, K. B.; Akashi, K.; Oshima, K. Tetrahedron Lett. 1976,
29, 2503-2506. (b) Sasson, Y.; Blum, J. Tetrahedron Lett. 1971, 24, 2167-
2170. (c) Murahashi, S.-I.; Noata, T.; Ito, K.; Maeda, Y.; Taki, H. J. Org.
Chem. 1987, 52, 4319-4327.
(45) (a) Ba¨ckvall, J.-E.; Andreasson, U. Tetrahedron Lett. 1993, 34,
5459-5462. (b) Trost, B. M.; Kulawiec, R. J. Tetrahedron Lett. 1991, 32,
3039-3042.

Aerobic Oxidation Using Ruthenium/TEMPO
J. Am. Chem. Soc., Vol. 123, No. 28, 2001 6829
Figure 3. Yield after 1 h in RuCl2(PPh3)3 (1 mol %)/TEMPO catalyzed
aerobic oxidation of octan-2-ol in chlorobenzene at 100 °C at different
concentrations of TEMPO.
Figure 6. Hammett plots for the aerobic oxidation of substituted benzyl
alcohols using different Ru/TEMPO ratios: (2) /2; (9) /6.
1
1
Indeed, results obtained in the aerobic oxidation of various
substituted benzyl alcohols using different TEMPO/Ru ratios
are consistent with this notion. Using either a TEMPO/Ru ratio
of 6:1 or 2:1, the logarithm of the initial rate plotted against
the σ value of the para- or meta-substituent resulted in a linear
relationship (Figure 6). However, the slopes of the lines were
different, i.e., at a low TEMPO/Ru ratio a F value of -0.44
was obtained, whereas at a high ratio a F value of -0.58 was
found. The increase of the F value is consistent with dehydro-
genation playing a more significant role at higher TEMPO/Ru
ratios.
Besides Hammett plots, kinetic isotope effects (kH/kD) also
give information regarding the rate-determining step. As shown
in Table 3, for both inter- (entries 2 and 3) and intramolecular
(entries 1 and 4) H/D competition in aliphatic and benzylic
alcohols (see Experimental Section), the values for the kinetic
isotope effect increase with increasing amounts of TEMPO.
These results provide further support for the notion that
dehydrogenation plays a more important role at higher TEMPO/
Ru ratios.
Figure 4. Yield after 15 min in the RuCl2(PPh3)3 (0.5 mol %)/TEMPO
catalyzed aerobic oxidation of benzyl alcohol in chlorobenzene at 100
°C at different TEMPO/Ru ratios.
Using TEMPO and ruthenium in a ratio of 5:1 at 100 °C, the
intramolecular kinetic isotope effect for the aerobic oxidation
of p-methyl-R-deuteriobenzyl alcohol is 3.9 (entry 1). This value
indicates that dehydrogenation plays a substantial role. To
provide more insight into the mechanism and to compare the
system with other ruthenium-catalyzed oxidations of alcohols,
the catalytic aerobic oxidation of p-methyl-R-deuteriobenzyl
alcohol was also performed at different temperatures (Table 4).
The hydride ion transfer may take place either by a concerted
cyclic process or by an acyclic one. Kwart et al. showed that a
dependence of the kinetic isotope effect (kH/kD) on the temper-
ature could provide a basis for distinguishing between the two
processes.48 The data for the Ru/TEMPO-catalyzed aerobic
oxidation of p-methyl-R-deuteriobenzyl alcohol listed in Table
4 and plotted in Figure 7 can be readily fitted to the familiar
expression kH/kD ) AH/AD exp(-∆Ea/RT). They correspond with
the properties of a symmetrical transition state in which the
activation energy difference (∆Ea) for kH/kD is equal to the zero-
point energy difference for the respective C-H and C-D bonds
(≈ 4.3 kJ/mol) and the frequency factors (AH/AD ) 0.92) and
thus entropies of activation of the respective reactions are nearly
equal.
Figure 5. Schematic mechanism of Ru/TEMPO catalyzed aerobic
oxidation of alcohols.
Mechanistic Studies. The effect of the TEMPO concentration
on the rate of the oxidation was investigated. An almost linear
increase was observed with respect to the TEMPO concentration
in the range of 0-4 mol % in the oxidation of octan-2-ol (Figure
3). Above 4 mol % the increase starts to level out, and further
addition of TEMPO led to only a minor increase in the yield
obtained after 1 h. In addition, the oxidation of benzyl alcohol
to benzaldehyde using only 0.5 mol % of Ru and different
concentrations of TEMPO showed the same trend (Figure 4).
In this case, no significant increase in rate was observed above
a TEMPO/Ru ratio of about 3.
The same “mediator” dependency was observed with a
ruthenium/benzoquinone/MnO2 system, reported by Ba¨ckvall
et al.,47 in which a ruthenium-centered dehydrogenation takes
place with ruthenium hydrides as the intermediates. For the Ru/
TEMPO-catalyzed aerobic oxidation of alcohols, we propose a
similar mechanism (Figure 5). The result can be explained in
terms of a change in the rate-limiting step. At low concentrations
of TEMPO, reoxidation of the “ruthenium hydride” species may
be the slowest step, whereas at high concentrations of TEMPO
dehydrogenation is probably rate limiting.
The primary kinetic isotope effect (kH/kD) for the Ru/TEMPO-
catalyzed aerobic oxidation of p-methyl-R-deuteriobenzyl al-
cohol at 25 °C was 5.1 (Table 4, entry 1). Although this value
indicates substantial C-H bond cleavage on progressing to the
transition state, it is still far smaller than those reported for the
stoichiometric benzyl alcohol oxidations by ruthenium-oxo
(47) Karlson, U.; Wang, G.-Z.; Ba¨ckvall, J.-E. J. Org. Chem. 1994, 59,
1196-1198.
(48) Kwart, H.; Nickle, J. H. J. Am. Chem. Soc. 1973, 95, 3394-3396.

6830 J. Am. Chem. Soc., Vol. 123, No. 28, 2001
Dijksman et al.
Table 3. Ruthenium/TEMPO-Catalyzed Aerobic Oxidation of Several Alcoholsa
kinetic isotope effect (kH/kD)b
entry
substrate
convn (%)
TEMPO/Ru ) 2
TEMPO/Ru ) 5
1
2
3
4
p-methyl-R-deuteriobenzyl alcohol
1-deuterio-1-phenylethanol/1-phenylethanol (1/1)
2-deuteriooctan-2-ol/octan-2-ol (1/1)
1-deuterioheptan-1-ol
100
35
25
3.2
2.3
2.2
2.1
3.9
3.0
2.4
2.8
70
a Reaction conditions: 5 mmol of substrate, 0.05 mmol (1 mol %) of RuCl2(PPh3)3, 0.10-0.25 mmol (2-5 mol %) of TEMPO, 10 mL of
1
chlorobenzene, O2 atmosphere, T ) 100 °C. b H/D ratio determined by H NMR.
Table 4. Kinetic Isotope Effect for the Ru/TEMPO-Catalyzed
Aerobic Oxidation of p-Methyl-R-deuteriobenzyl Alcohol at
Different Temperaturesa
According to the mechanism presented in Figure 5, no
regeneration of TEMPOH should take place under an inert
atmosphere. In this case, RuCl2(PPh3)3 catalyzes the oxidation
of octan-2-ol when a stoichiometric amount of TEMPO is used.
We performed this experiment (see Experimental Section) and
found octan-2-one and TEMPH as products in a 3:2 ratio
(reaction 5). We assume that TEMPH is formed by dispropor-
time (h) for
100% convn
kinetic isotope
entry
temp (°C)
effect (kH/kD)b
1
2
3
4
5
6
25
43
63
83
100
118
67
40
6
3
2
5.1
5.0
4.1
4.0
3.9
3.4
1.5
a Reaction conditions: 5 mmol of p-methyl-R-deuteriobenzyl alcohol,
0.05 mmol of RuCl2(PPh3)3, 0.25 mmol of TEMPO, 10 mL of
1
chlorobenzene, O2 atmosphere. b H/D ratio determined by H NMR.
tionation of the extremely unstable TEMPOH (reaction 6).
Attempts to prepare TEMPOH53 under an inert atmosphere
always resulted in the formation of TEMPH. On the other hand,
in the presence of oxygen TEMPOH is rapidly oxidized to
TEMPO. These results support the mechanism depicted in
Figure 5 and indicate that TEMPO acts as a hydrogen transfer
mediator.
Figure 7. The correlation of the kinetic isotope effect and the
temperature (25-118 °C) for the Ru/TEMPO catalyzed aerobic
oxidation of p-methyl-R-deuteriobenzyl alcohol.
complexes, e.g., trans-[RuVI(tpy)(O)2(CH3CN)]2+ (kH/kD
)
12.1),49 cis-[(N4)RuVIO2]2+ (kH/kD ) 21),50 [(bpy)2(py)RuIV-
(O)]2+ (kH/kD ) 50),51 and [RuIV(tpy)(CH3CN)2(O)]2+ (kH/kD
) 61.5).49 On the other hand, the value is substantially larger
than that found for the stoichiometric oxidation of benzyl
alcohols by the oxoammonium cation (1) (reaction 2) at 25 °C
(kH/kD ) 1.7-2.3).52 We suggest that these results indicate that
neither a ruthenium-oxo complex (RuIVO, RuVIO2) nor the
oxoammonium cation is the active oxidant, consistent with the
proposed schematic mechanism in Figure 5.
The absence of a ruthenium-oxo complex (RuIVO, RuVIO2)
or the oxoammonium cation as the active oxidant can also be
derived from the slope of the Hammett plots (F value). The F
value for the Ru/TEMPO-catalyzed oxidation of benzyl alcohols
(-0.58) is significantly higher than that of the stoichiometric
oxidation by the oxoammonium cation (F ≈ -0.3).52 On the
other hand, the value is much lower than those obtained in the
stoichiometric oxidations by ruthenium-oxo compounds, e.g.,
cis-[(N4)RuVIO2]2+ (F ) -1.2 to -1.9).50
Similarly, the RuCl2(PPh3)3-catalyzed stoichiometric reaction
of TEMPO and benzyl alcohol at either 25 or 100 °C afforded
TEMPH and benzaldehyde in a 3:2 ratio. By using p-methyl-
R-deuteriobenzyl alcohol as substrate, the kinetic isotope effect
of the RuCl2(PPh3)3-catalyzed anaerobic oxidation could also
be studied. The results were similar to those obtained in the
catalytic aerobic oxidations presented in Table 4 (entries 1 and
5). At 25 °C a kinetic isotope effect (kH/kD) of 5.1 was obtained,
whereas at 100 °C a value of 3.4 was found. These results are
consistent with the aerobic and anaerobic oxidation following
the same pathway and, therefore, support the mechanism
depicted in Figure 5, whereby TEMPO acts as a hydrogen
transfer mediator.
A likely candidate for the active ruthenium hydride species
is RuH2(PPh3)3, as observed in RuCl2(PPh3)3-catalyzed hydrogen-
transfer reactions.54 In the ruthenium/TEMPO-catalyzed aerobic
oxidation of octan-2-ol, RuH2(PPh3)4 was as active as RuCl2-
(49) Lebeau, E. L.; Meyer, T. J. Inorg. Chem. 1999, 38, 2174-2181.
(50) Cheng, W.-C.; Yu, W.-Y.; Li, C.-K.; Che, C.-M. J. Org. Chem.
1995, 60, 6840-6846.
(51) Roecker, L.; Meyer, T. J. J. Am. Chem. Soc. 1987, 109, 746-754.
(52) Semmelhack, M. F.; Schmid, C. R.; Corte´s, D. A. Tetrahedron Lett.
1986, 27, 1119-1122.
(53) Paleos, C. M.; Dais, P. J. Chem. Soc., Chem. Commun. 1977, 345-
346.
(54) Aranyos, A.; Csjernyik, G.; Szabo´, K. J.; Ba¨ckvall, J.-E. Chem.
Commun. 1999, 351-352.

Aerobic Oxidation Using Ruthenium/TEMPO
J. Am. Chem. Soc., Vol. 123, No. 28, 2001 6831
Figure 8. Stoichiometric reaction of “RuH2(PPh3)3” with TEMPO in
chlorobenzene under an inert atmosphere at 25 °C, followed by in situ
IR.
Figure 10. RuCl2(PPh3)3 catalyzed oxidation of benzyl alcohol with
TEMPO (up to 0.1 equiv) in chlorobenzene under an inert atmosphere
at 25 °C, followed by in situ IR.
is present and therefore a formal reductive elimination to give
a Ru0 species would predominate.
The above-described intermediate (a) is postulated by analogy
with other ruthenium-based hydrogen transfer systems, in which
no reduction of Ru2+ to Ru0 takes place during catalysis.54,56
To provide support for the formation of (mono)hydride species
in the catalytic cycle, the RuCl2(PPh3)3 (5 mol %) catalyzed
anaerobic oxidation of benzyl alcohol with only 5 mol % of
TEMPO was performed in chlorobenzene at 25 °C. During this
reaction, both TEMPH and a (mono)hydride ruthenium species
(νRuH 2038 cm-1) were formed. Further addition of TEMPO (5
mol %) resulted again in the disappearance of the ruthenium
hydride complex (Figure 10).
Figure 9. Proposed mechanism for the Ru/TEMPO catalyzed aerobic
oxidation of alcohols.
In summary, we propose that the Ru/TEMPO-catalyzed
aerobic oxidation of alcohols proceeds via a hydridometal
mechanism, involving a “RuH2(PPh3)3” species as the active
catalyst (Figure 9). This ruthenium dihydride complex reacts
with two molecules of TEMPO to form complex a and one
molecule of TEMPOH. Proton transfer from the incoming
alcohol to the piperidinyloxy ligand in complex a affords
complex b and another molecule of TEMPOH. In the aerobic
oxidation, the two molecules of TEMPOH are oxidized by
oxygen to regenerate two molecules of TEMPO. Under anaero-
bic conditions, in the Ru-catalyzed stoichiometric reaction of
an alcohol with TEMPO, TEMPH is formed by disproportion-
ation of TEMPOH. In both cases, complex b undergoes normal
â-hydrogen elimination to produce the ketone/aldehyde and the
active ruthenium dihydride species.
(PPh3)3, i.e., octan-2-ol was quantitatively converted to octan-
2-one within 9 h using 1.5 mol % of either catalyst and 4.5
mol % of TEMPO under an oxygen atmosphere at 100 °C.
Additional support for a dihydride as the active catalyst was
obtained from stoichiometric reaction of “RuH2(PPh3)3” (gener-
ated from RuH2(PPh3)455 in situ) with TEMPO in chlorobenzene,
under an inert atmosphere at 25 °C, monitored by in situ IR
(see Experimental Section). Following the intensity of the Ru-H
vibration of “RuH2(PPh3)3” (2150 cm-1) in time, it was found
that the ruthenium dihydride slowly decreased in the presence
of 3 equiv of TEMPO but rapidly disappeared upon addition
of another 5 equiv (Figure 8) without formation of any other
ruthenium hydride complex.
On the other hand, TEMPO was again converted to TEMPH
in a 2:3 ratio with respect to the molar amount of RuH2(PPh3)4
added (reaction 7). These results can be explained on the basis
Heterogenization of the Catalyst. A problem in the present
aerobic Ru/TEMPO-catalyzed oxidation of alcohols is the slow
deactivation of both ruthenium and TEMPO during catalysis.
Unfortunately, the combination of PIPO34 (polymer-immobilized
TEMPO) and RuCl2(PPh3)3 in chlorobenzene is not able to
catalyze the aerobic oxidation of octan-2-ol,57 probably owing
to coordination of ruthenium to the polyamine leading to an
18e complex. Similarly, attempts to use silica and MCM-41
supported TEMPO systems58 lead to an inactive system.57 Most
probably, adsorption of ruthenium on the silica and MCM-41
surface took place, leading to an inactive catalyst. Indeed, our
attempts to perform the (homogeneous) Ru/TEMPO-catalyzed
of the catalytic cycle for the RuCl2(PPh3)3/TEMPO-catalyzed
aerobic oxidation of alcohols shown in Figure 9. In the catalytic
system, where there is a large excess of alcohol, it is likely that
proton transfer from the alcohol to the piperidinyloxy ligand in
complex a takes place, leading to an exchange of “alkoxy”
groups to give complex b. In contrast, in reaction 7 no alcohol
(56) (a) Haack, K.-J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R.
Angew. Chem., Int. Ed. Engl. 1997, 36, 285-288. (b) Koh, J. H.; Jeong,
H. M.; Park, J. Tetrahedron Lett. 1998, 39, 5545-5548.
(57) Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Synlett 2001,
102-104.
(58) (a) Verhoef, M. J.; Peters, J. A.; van Bekkum, H. Stud. Surf. Sci.
Catal. 1999, 125, 465-472. (b) Bolm, C.; Fey, T. Chem. Commun. 1999,
1795-1796. (c) Brunel, D.; Lentz, P.; Sutra, P.; Deroide, B.; Fajula, F.;
Nagy, J. B. Stud. Surf. Sci. Catal. 1999, 125, 237-244.
(55) RuH2(PPh3)4 was prepared according to: Levinson, J. J.; Robinson,
S. D. J. Chem. Soc. A 1970, 2947-2954.

6832 J. Am. Chem. Soc., Vol. 123, No. 28, 2001
Dijksman et al.
aerobic oxidation of octan-2-ol in the presence of silica59 resulted
in much lower activities. In addition, a discoloration of the
reaction mixture from dark brown to light orange took place,
due to adsorption of ruthenium on the silica surface. Because
of these disappointing results and the fact that ruthenium is much
more expensive than TEMPO, we are currently focusing our
attention on the heterogenization of ruthenium and will report
our results in due course.
Synthesis of 4-Acetylbenzoic Acid. A mixture of p-acetylbenzoni-
trile (34.5 mmol, 5 g) in sulfuric acid (20 mL, 96%) and water (20
mL) was refluxed for 45 min. After the reaction, the solution was cooled
to room temperature and water (200 mL) was added to precipitate an
off-white solid. This solid was filtered off and dried via azeotropic
distillation with toluene (50 mL) to give a fine pale-yellow powder.
1H NMR (300 MHz, DMSO, TMS): δ 13 (s, 1H, COOH), 8.05 (s,
4H, 2Hortho and 2Hmeta), 2.63 (s, 3H, CH3). 13C NMR (75 MHz, DMSO,
TMS): δ 198.2 (CO), 167.1 (COOH), 140.3 (Cpara), 135.0 (Cipso), 130.0
(2Cmeta), 128.8 (2Cortho), 27.5 (CH3).
Conclusion
Synthesis of 4-(1′-Hydroxyethyl)benzyl Alcohol. A mixture of
4-acetylbenzoic acid and LiAlH4 (132 mmol, 4 g) in anhydrous THF
(50 mL) was refluxed overnight under dry nitrogen. The usual workup
gave 2.2 g (14.5 mmol, 42%) of a viscous orange-yellow oil which
The combination of RuCl2(PPh3)3 and TEMPO affords an
efficient catalytic system for the aerobic oxidation of a variety
of primary and secondary alcohols, giving the corresponding
aldehydes and ketones in >99% selectivity in all cases. To our
knowledge this is one of the most reactive catalysts reported to
date for the aerobic oxidation of (aliphatic) alcohols. Unfortu-
nately, alcohols containing a heteroatom (O, N, S), such as
butylproxitol and 4-(methylthio)butan-2-ol, are unreactive. In
both inter- and intramolecular competition experiments, the Ru/
TEMPO system displayed a preference for primary versus
secondary alcohols.
Results from Hammett correlation studies (F ) - 0.58) and
the primary kinetic isotope effect (kH/kD ) 5.1) for the catalytic
aerobic oxidation of benzyl alcohol are inconsistent with either
an oxoruthenium (OdRu) or an oxoammonium based mecha-
nism. On the basis of this and the results from stoichiometric
and in situ IR experiments, we postulate a hydridometal
mechanism, involving a “RuH2(PPh3)3”-species as the active
catalyst. TEMPO acts as a hydrogen transfer mediator and is
regenerated by oxygen. Under anaerobic conditions, TEMPO
acts as a stoichiometric oxidant.
was used without further purification: m/z 152 (M+, 19), 137 (M+
-
Me, 96), 134 (M+ - H2O, 19), 121 (22), 107 (31), 105 (28), 91 (60),
79 (100), 77 (58), 63 (16), 51 (35). 1H NMR (300 MHz, CDCl3,
TMS): δ 7.28 (d, 2H, 3JHH ) 8.4 Hz, 2Hmeta), 7.24 (d, 2H, 3JHH ) 8.4
3
Hz, 2Hortho), 4.81 (q, 1H, JHH ) 6.6 Hz, CHCH3), 4.60 (s, 2H, CH2-
OH), 2.72 (s, 2H, CH2OH and CH(CH3)OH), 1.43 (d, 3H, 3JHH ) 6.6
Hz, CH3). 13C NMR (75 MHz, CDCl3, TMS): δ 145.1 (Cipso), 140.0
(Cpara), 127.1 (2Cmeta), 125.6 (2Cortho), 70.0 (CHOH), 64.7 (CH2OH),
25.1 (CH3).
Oxidation of 4-(1′-Hydroxyethyl)benzyl Alcohol. The oxidation
of 1-(4′-hydroxymethylphenyl)ethanol was carried under the standard
conditions. The reaction mixture was analyzed by GC and the products
were identified by GCMS and were identical to literature values.
4-(Hydroxymethyl)acetophenone: m/z 150 (M+, 31), 135 (100),
107 (23), 89 (37), 77 (29).
4-(1′-Hydroxyethyl)benzaldehyde: m/z 150 (M+, 5), 149 (5), 107
(100), 79 (74), 77 (50), 51 (21).
4-Acetylbenzaldehyde: m/z 148 (M+, 41), 134 (17), 133 (100), 105
(49), 77 (33), 51 (24), 50 (15).
Synthesis of R-Deuterio-p-methylbenzyl Alcohol. R-Deuterio-p-
methylbenzyl alcohol was synthesized according to a literature proce-
dure.60 1H NMR (400 MHz, CDCl3, TMS): δ 7.25 (d, 2H, 3JHH ) 8.0
Hz, 2Hortho), 7.16 (d, 2H, 3JHH ) 7.8 Hz, 2Hmeta), 4.60 (s, 1H, CHDOH),
Experimental Section
3
2.35 (s, 3H, CH3), 1.69 (d, 1H, JHH ) 5.1 Hz, OH). 13C NMR (100
Aerobic Oxidation of Octan-2-ol at High Pressure. Octan-2-ol
(15.0 mmol, 1.96 g), n-hexadecane (internal standard; 3.0 mmol, 0.69
g), RuCl2(PPh3)3 (0.225 mmol, 216 mg), and TEMPO (0.675 mmol,
106 mg) were dissolved in 30 mL of chlorobenzene, heated in a high-
pressure reactor (10 bar) to 100 °C under a continuous stream (10 mL
min-1) of an oxygen-nitrogen mixture (8:92; v/v), and stirred (1000
rpm) for 7 h. Octan-2-ol conversion and octan-2-one selectivity were
determined using GC analysis (50 m × 0.53 mm CP-WAX 52 CB
column).
Aerobic Oxidation of Octan-1-ol at Atmospheric Pressure. Octan-
1-ol (15.0 mmol, 1.96 g), n-hexadecane (internal standard; 3.0 mmol,
0.69 g), RuCl2(PPh3)3 (0.30 mmol, 286 mg), and TEMPO (0.90 mmol,
141 mg) were dissolved in 30 mL of chlorobenzene, heated to 100 °C
under an oxygen atmosphere, and stirred (1000 rpm) for 7 h. Octan-
1-ol conversion and octanal selectivity were determined using GC
analysis (50 m × 0.53 mm CP-WAX 52 CB column).
Product Isolation. The reaction mixture was diluted with n-hexane
(to precipitate ruthenium compounds) and dried over MgSO4. The
resulting mixture was filtered and the solvent was removed in vacuo.
The product was separated from chlorobenzene using Kugelrohr
distillation.
Oxidation of 1,5-Hexanediol. The oxidation of 1,5-hexanediol was
carried out under the standard conditions. The reaction mixture was
analyzed by GC and the products were identified by GCMS and were
identical to literature values.
1,5-Hexanediol: m/z 100 (M+ - H2O, 1), 85 (17), 75 (25), 67 (21),
57 (32), 56 (75), 45 (100).
5-Hydroxyhexanal: m/z 116 (M+, 2), 98 (M+ - H2O, 11), 88 (21),
83 (13), 70 (25), 69 (17), 57 (56), 55 (38), 45 (100), 44 (76).
5-Oxohexanal: m/z 114 (M+, 14), 99 (13), 85 (4), 71(27), 70 (100),
55 (67).
MHz, CDCl3, TMS): δ 137.8 (Cipso), 137.4 (Cpara), 129.2 (2Cmeta), 127.2
(2Cortho), 64.9 (t, 1JCD ) 21.8 Hz, CHDOH), 21.2 (CH3). m/z: 124 (17),
123 (M+, 92), 122 (25), 108 (100), 106 (33), 94 (50), 93 (31), 92 (32),
91 (48), 80 (71), 78 (52), 77 (36), 65 (28).
Synthesis of 2-Deuteriooctan-2-ol. 2-Deuteriooctan-2-ol was syn-
thesized according to a literature procedure.60 1H NMR (400 MHz,
CDCl3, TMS): δ 1.42 (m, 2H, C3H2), 1.29 (m, 8H, C4-7H2), 1.18 (s,
3
3H, C1H3), 0.89 (t, 3H, JHH ) 6.4 Hz, C8H3). 13C NMR (100 MHz,
1
CDCl3, TMS): δ 67.5 (t, JCD ) 21.4 Hz, C2HDOH), 39.3 (C3H2),
31.9 (C6H2), 29.3 (C5H2), 25.7 (C4H2), 23.7 (C7H2), 22.6 (C1H3), 14.1-
(C8H3). m/z: 116 (M+ - CH3, 30), 113 (M+ - H2O, 30), 98 (53), 84
(41), 70 (27), 56 (35), 46 (100).
Synthesis of 1-Deuterio-1-phenylethanol. 1-Deuterio-1-phenyle-
thanol was synthesized according to a literature procedure.61 1H NMR
(400 MHz, CDCl3, TMS): δ 7.33 (m, 4H, 2Hmeta and 2Hortho), 7.25
(m, 1H, Hpara), 2.13 (s, 1H, OH), 1.46 (s, 3H, CH3). 13C NMR (100
MHz, CDCl3, TMS) δ 145.7 (Cipso), 128.4 (2Cmeta), 127.4 (Cpara), 125.4
(2Cortho), 70.0 (t, 1JCD ) 22.1 Hz, CDOH), 25.0 (CH3). m/z: 123 (M+,
27), 108 (100), 105 (M+ - H2O, 40), 80 (91), 79 (25), 78 (49), 77
(36), 51 (35).
Synthesis of 1-Deuterioheptan-1-ol. 1-Deuterioheptan-1-ol was
synthesized according to a literature procedure.62 1H NMR (400 MHz,
3
CDCl3, TMS): δ 3.61 (t, 1H, JHH ) 6.6 Hz, CHDOH), 1.56 (m, 3H,
C2H2 and OH), 1.30 (m, 8H, C3-6H2), 0.96 (t, 3H, 3JHH ) 7.0 Hz, C7H3).
1
13C NMR (100 MHz, CDCl3, TMS): δ 62.7 (t, JCD ) 21.4 Hz,
CHDOH), 32.7 (C5H2), 31.8 (C2H2), 29.1 (C4H2), 25.7 (C3H2), 22.6
(C6H2), 14.1 (C7H3). m/z: 99 (M+ - CH3, 7), 84 (10), 71 (40), 70
(100), 69 (50), 58 (18), 57 (68), 56 (88), 55 (58), 44 (18).
(60) Holland, H. L.; Brown, F. M.; Conn, M. J. Chem. Soc., Perkin Trans.
2 1990, 1651-1655.
(61) Streiweiser, A., Jr. J. Am. Chem. Soc. 1953, 75, 5014-5018.
(62) Cogen, J. M.; Maier, W. F. J. Am. Chem. Soc. 1986, 108, 7752-
7762.
(59) Purchased from ACROS, for column chromatography, 0.060-0.200
mm, pore diameter 6 nm.

Aerobic Oxidation Using Ruthenium/TEMPO
J. Am. Chem. Soc., Vol. 123, No. 28, 2001 6833
1
Determination of Intramolecular Kinetic Isotope Effect. The
oxidation of the deuterated primary alcohols, R-deuterio-p-methylbenzyl
alcohol and 1-deuterioheptan-1-ol, was carried under the standard
conditions. The reaction mixture was analyzed by GC, and the products,
(R-deuterio)-p-methylbenzaldehyde and (1-deuterio)heptanal, respec-
tively, were isolated using Kugelrohr distillation. The intramolecular
1-Phenylethanol: H NMR (400 MHz, CDCl3, TMS) δ 7.33 (m,
4H, 2Hmeta and 2Hortho), 7.25 (m, 1H, Hpara), 4.90 (m, 1H, CHOH), 2.10
3
(s, 1H, OH), 1.46 (d, JHH ) 6.4 Hz, 3H, CH3).
1
1-Deuterio-1-phenylethanol: H NMR (400 MHz, CDCl3, TMS)
δ 7.33 (m, 4H, 2Hmeta and 2Hortho), 7.25 (m, 1H, Hpara), 2.10 (s, 1H,
OH), 1.46 (s, 3H, CH3).
1
kinetic isotope effect was determined by H NMR.
Stoichiometric Reaction of Octan-2-ol with TEMPO. Octan-2-ol
(2.5 mmol, 0.33 g), RuCl2(PPh3)3 (0.025 mmol, 23.8 mg), and TEMPO
(5 mmol, 0.78 g) were dissolved in 5 mL of chlorobenzene, heated to
100 °C under an inert atmosphere (N2), and stirred for 24 h. Substrate
(octan-2-ol/TEMPO) conversion and product (octan-2-one and TEMPH)
selectivity were determined using GC analysis (50 m × 0.53 mm CP-
WAX 52 CB column).
p-Methylbenzaldehyde: 1H NMR (300 MHz, CDCl3, TMS) δ 9.95
3
3
(s, 1H, CHO), 7.75 (d, 2H, JHH ) 7.8 Hz, 2Hortho), 7.31 (d, 2H, JHH
) 7.8 Hz, 2Hmeta), 2.42 (s, 3H, CH3).
1
R-Deuterio-p-methylbenzaldehyde: H NMR (300 MHz, CDCl3,
TMS) δ 7.75 (d, 2H, JHH ) 7.8 Hz, 2Hortho), 7.31 (d, 2H, JHH ) 7.8
3
3
Hz, 2Hmeta), 2.42 (s, 3H, CH3).
Heptanal: 1H NMR (300 MHz, CDCl3, TMS) δ 9.78 (s, 1H, CHO),
Stoichiometric Reaction of RuH2(PPh3)4 with TEMPO. TEMPO
(1.35 mmol, 211 mg) and RuH2(PPh3)4 (0.45 mmol, 517 mg) were
dissolved in 15 mL of chlorobenzene and stirred at 25 °C under an
inert atmosphere (N2) for 6 h. After 2 h, an extra portion of TEMPO
(2.25 mmol, 351 mg) was added. Conversion of TEMPO and RuH2-
(PPh3)4 was determined using respectively GC analysis (50m × 0.53
mm CP-WAX 52 CB column) and an in situ IR technique (ASI Applied
Systems ReactIR 1000; νRuH 2150 cm-1).
2.42 (t, 2H, JHH ) 6.7 Hz, C2H2), 1.30 (m, 8H, C3-6H2), 0.96 (t, 3H,
3
3JHH ) 7.0 Hz, C7H3).
1-Deuterioheptanal: 1H NMR (300 MHz, CDCl3, TMS) δ 2.42 (t,
2H, JHH ) 6.7 Hz, C2H2), 1.30 (m, 8H, C3-6H2), 0.96 (t, 3H, JHH
)
3
3
7.0 Hz, C7H3).
Determination of Intermolecular Kinetic Isotope Effect. Oxidation
of the deuterated secondary alcohol mixtures, (2-deuterio)octan-2-ol
and (1-deuterio)-1-phenylethanol, was carried out by using the standard
conditions. The reaction mixture was followed by GC and the reaction
was stopped at 25-35% conversion. The unreacted substrate was
isolated using Kugelrohr distillation, and the intermolecular kinetic
Acknowledgment. We gratefully acknowledge IOP Cataly-
sis (Innovation-Oriented Research Program on Catalysis) for
financial support, Avantium Technologies for the use of their
in situ IR system, and Johnson Matthey, Inc. for their donation
of RuCl3 hydrate.
1
isotope effect was determined by H NMR.
Octan-2-ol: 1H NMR (400 MHz, CDCl3, TMS) δ 3.81 (m, 1H,
C2HOH), 1.42 (m, 2H, C3H2), 1.29 (m, 8H, C4-7H2), 1.18 (d, 3H, 3JHH
3
) 5.9 Hz, C1H3), 0.89 (t, 3H, JHH ) 6.4 Hz, C8H3).
1
2-Deuteriooctan-2-ol: H NMR (400 MHz, CDCl3, TMS) δ 1.42
(m, 2H, C3H2), 1.29 (m, 8H, C4-7H2), 1.18 (s, 3H, C1H3), 0.89 (t, 3H,
3JHH ) 6.4 Hz, C8H3).
JA0103804