Ruthenium-catalyzed oxidation of alkanes with tert-butyl hydroperoxide and peracetic acid

Article abstract of DOI:10.1021/jo001348f

The ruthenium-catalyzed oxidation of alkanes with tert-butyl hydroperoxide and peracetic acid gives the corresponding ketones and alcohols highly efficiently at room temperature. The former catalytic system, RuCl₂(PPh₃)₃-t-BuOOH, is preferable to the oxidation of alkylated arenes to give aryl ketones. The latter system, Ru/C-CH₃CO₃H, is suitable especially for the synthesis of ketones and alcohols from alkanes. The ruthenium-catalyzed oxidation of cyclohexane with CH₃CO₃H in trifluoroacetic acid/CH₂Cl₂ at room temperature gave cyclohexyl trifluoroacetate and cyclohexanone with 90% conversion and 90% selectivity (85:15). The mechanistic study indicates that these catalytic oxidations of hydrocarbons involve oxo-ruthenium species as key intermediates.

Full text of DOI:10.1021/jo001348f

9186
J . Org. Chem. 2000, 65, 9186-9193
Ru th en iu m -Ca ta lyzed Oxid a tion of Alk a n es w ith ter t-Bu tyl
Hyd r op er oxid e a n d P er a cetic Acid
Shun-Ichi Murahashi,* Naruyoshi Komiya, Yoshiaki Oda,† Toshiyuki Kuwabara, and
Takeshi Naota
Department of Chemistry, Graduate School of Engineering Science, Osaka University,
1-3, Machikaneyama, Toyonaka, Osaka 560-8531, J apan
mura@chem.es.osaka-u.ac.jp.
Received September 11, 2000
The ruthenium-catalyzed oxidation of alkanes with tert-butyl hydroperoxide and peracetic acid gives
the corresponding ketones and alcohols highly efficiently at room temperature. The former catalytic
system, RuCl2(PPh3)3-t-BuOOH, is preferable to the oxidation of alkylated arenes to give aryl
ketones. The latter system, Ru/C-CH3CO3H, is suitable especially for the synthesis of ketones
and alcohols from alkanes. The ruthenium-catalyzed oxidation of cyclohexane with CH3CO3H in
trifluoroacetic acid/CH2Cl2 at room temperature gave cyclohexyl trifluoroacetate and cyclohexanone
with 90% conversion and 90% selectivity (85:15). The mechanistic study indicates that these catalytic
oxidations of hydrocarbons involve oxo-ruthenium species as key intermediates.
In tr od u ction
bond energy. The ruthenium-catalyzed oxidations have
been reported; however, the results reported are low
conversions of alkanes.6 Hydroxylation of alkanes has
been achieved with ruthenium porphyrin catalysts such
as Ru(TMP)(O)2 and Ru(TPFPP)(CO) with 2,6-dichloro-
pyridine N-oxide.7,8 Perfluorinated ruthenium phthalo-
cyanine, which is encapsulated in zeolite, is an effective
catalyst with t-BuOOH.9 Furthermore, a non-porphyrin
cis-dioxo-ruthenium complex bearing the sterically bulky
2,9-dimethyl-1,10-phenanthroline ligand can be used for
the oxidation of alkanes with H2O2.10 Recently, ruthenium-
substituted polyoxometalates were reported to be useful
for oxidation of hydrocarbons, even with molecular
oxygen.11 These reactions are efficient for oxidation of
tertiary C-H bonds of alkanes; however, secondary C-H
bonds of alkanes such as cyclohexane are difficult to
oxidize. Selective catalytic oxidation of cyclohexane with
high conversion at room temperature still awaits to be
explored. Catalytic oxidation of cyclohexane with t-
BuOOH has been investigated extensively; however, the
conversions obtained are still low.12
The catalytic oxidation of unactivated C-H bonds of
alkanes under mild conditions is of importance in view
of synthetic and industrial aspects.1 In biological systems,
harmful organic molecules including hydrocarbons are
metabolized to give water-soluble compounds or biologi-
cally important materials. The existence of enzymatic
systems that can catalyze the oxidation of alkanes has
prompted the creation of their chemical analogues. Much
effort has been devoted to understand the catalytic cycle
of cytochrome P-450s, because of their strong ability for
oxidation.2 In 1979 Groves et al. first reported biomimetic
oxidation of hydrocarbons with PhIO using Fe(TPP)Cl
catalyst.3 Since then, the shunt process has been often
used for the biomimetic oxidations of organic molecules,
because oxo-metal species can be formed readily upon
treatment with various oxygen donors such as iodosyl-
benzenes and hypochlorites.1,4 Among transition metals,
ruthenium as well as iron has become increasingly
important to be utilized for the catalytic oxidations.5
Generally, catalytic oxidation of alkanes under mild
conditions is quite difficult, because of the lack of the
reactivity of alkanes, which stems from their high C-H
To generate oxo-ruthenium species, which may cor-
respond to the oxo-iron(IV) species of cytochrome P-450,
low-valent ruthenium complexes were treated with per-
oxides with the intention of generating middle-valent
oxo-ruthenium species. Then, we found that alkanes can
* To whom correspondence should be addressed.
† On leave from Organic Synthesis Research Laboratory, Sumitomo
Chemical Co., Ltd., Takatsuki, Osaka 569-1093, J apan.
(1) (a) Sheldon, R. A.; Kochi, J . K. Metal-Catalyzed Oxidations of
Organic Compounds; Academic Press: New York, 1981. (b) Shilov, A.
E. Activation of Saturated Hydrocarbons by Transition Metal Com-
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R.; Doller, D. Acc. Chem. Res. 1992, 25, 504-512. (f) Shilov, A. E.;
Shul’pin, G. B. Chem. Rev. 1997, 97, 2879-2932.
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T. Inorg. Chim. Acta 1983, 79, 25-27. (b) Leung, T.; J ames, B. R.;
Dolphin, D. Inorg. Chim. Acta 1983, 79, 180-181. RuCl2(dpp)2/LiClO:
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10.1021/jo001348f CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/28/2000

Ruthenium-Catalyzed Oxidation of Alkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9187
be readily oxidized at room temperature by the two
catalytic systems (i) RuCl2(PPh3)3-t-BuOOH13 and (ii)
Ru/C(Ru on charcoal)-CH3CO3H14 to give the corre-
sponding ketones and alcohols highly efficiently (eq 1).
type oxidations of amines,17 amides,18 nitriles,19 alkenes,20
alcohols,21 and phenols.22
Resu lts a n d Discu ssion
Ru th en iu m -Ca ta lyzed Oxid a tion of Alk a n es. To
generate oxo-metal complexes, which may correspond
to the oxo-iron(IV) species of cytochrome P-450, we
wanted to generate middle-valent RudO species,16 which
may exhibit unique reactivity and be quite different from
high-valent RuO4 species, by the oxidation of low-valent
ruthenium complexes.5 Then, we discovered that low-
valent ruthenium species such as RuCl2(PPh3)313 and Ru/
C14 with peroxides are excellent catalytic systems for the
oxidations of alkanes.
At first, the efficiency of these catalytic systems was
examined for the oxidation of cyclohexane. To a stirred
mixture of cyclohexane and ruthenium catalyst in ben-
zene or ethyl acetate was added either a t-BuOOH
solution in benzene or a CH3CO3H solution in ethyl
acetate dropwise over a period of 30 min. Because the
reaction is very rapid, it is completed immediately after
the addition of the peroxide. The conversions of cyclo-
hexane and the yields of cyclohexanone and cyclohexanol
were determined by GC analysis using an internal
standard after the addition of the peroxide. The RuCl2-
(PPh3)3-catalyzed oxidation of cyclohexane with 1 equiv
of t-BuOOH proceeds to give cyclohexanone and cyclo-
hexanol (68:32) with 9.3% conversion and 82% selectivity.
On the other hand, peracetic acid is more reactive. The
Ru/C-catalyzed oxidation of cyclohexane with 0.7 equiv
of CH3CO3H proceeds with 9.1% conversion and 93%
selectivity, where the ratio of cyclohexanone and cyclo-
hexanol is 94:6. In view of the reactivity and selectivity,
the Ru/C-CH3CO3H system is more suitable for the
oxidation of alkanes.
The former catalytic system using RuCl2(PPh3)3 and
t-BuOOH is particularly effective for the oxidation of
alkylated arenes to the corresponding aryl ketones, while
the latter Ru/C-catalyzed oxidation with peracetic acid
is useful for the conversion of alkanes to the correspond-
ing ketones. Catalytic oxidations using t-BuOOH and
CH3CO3H are convenient because (i) t-BuOOH and
CH3CO3H are readily obtained from aerobic oxidation of
isobutane and acetaldehyde, respectively, and (ii) tert-
butyl alcohol formed can be used for tert-butyl methyl
ether as high octane fuel, and the acetic acid formed can
be also used.
To raise the reactivity, a ruthenium-catalyzed oxida-
tion was carried out in the presence of trifluoroacetic acid.
Thus, the oxidation of cyclohexane with CH3CO3H in the
presence of RuCl3‚nH2O catalyst in trifluoroacetic acid-
CH2Cl2 gave cyclohexyl trifluoroacetate and cyclohex-
anone with 90% conversion and 90% selectivity.
Full details of these novel oxidations of alkanes are
described with respect to scope and reaction mecha-
nism.15 These results are consistent with our previous
results16 for the ruthenium-catalyzed cytochrome P-450
(12) [Cu(bpy)2](ClO4): (a) Sobkowiak, A.; Qui, A.; Liu, X.; Llobet,
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1991, 939-940. Fe(PA)2: (d) Tung, H.-C.; Kang, C.; Sawyer, D. T. J .
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Leising, R. A.; Kim, J .; Pe´rez, M. A.; Que, L., J r. J . Am. Chem. Soc.
1993, 115, 9524-9530. Fe(NO3)3-PA: (f) Barton, D. H. R.; Chavasiri,
W. Tetrahedron 1994, 50, 19-30. Fe2(Mebpy)4O(OAc): (g) Vincent, J .
M.; Me´nage, S.; Lambeaux, C.; Fontecave, M. Tetrahedron Lett. 1994,
35, 6287-6290. Mn4O2(O2CPh)7(bpy)2: (h) Fish, R. H.; Fong, R. H.;
Vincent, J . B.; Christou, G. J . Chem. Soc., Chem. Commun. 1988,
1504-1506. [Mn2O2(bpy)4](ClO4)3: (i) Me´nage, S.; Collomb-Dunand-
Sauthier, M.-N.; Lambeaux, C.; Fontecave, M. J . Chem. Soc., Chem.
Commun. 1994, 1885-1886. [MnL(OAc)]n: (j) Ganeshpure, P. A.;
Tembe, G. L.; Satish, S. Tetrahedron Lett. 1995, 36, 8861-8864. Mn-
(C8F17(CH2)2CO2)2(C8F17(CH2)3)3TACN: (k) Vincent, J .-M.; Rabion, A.;
Yachandra, V. K.; Fish, R. H. Angew. Chem., Int. Ed. Engl. 1997, 36,
2346-2349. [Mn3O4(dipy)4(OH2)2](ClO4)4: (l) Sarneski, J . E.; Michos,
D.; Thorp, H. H.; Didiuk, M.; Poon, T.; Blewitt, J .; Brudvig, G. W.;
The rate of the addition of peracetic acid to the mixture
of alkane and Ru/C catalyst in ethyl acetate must be
controlled, because the reaction of ruthenium with per-
acetic acid is very fast and exothermic. The addition of
peracetic acid solution dropwise over a period of 30 min
(15) (a) Murahashi, S.-I.; Oda, Y.; Naota, T. J . Am. Chem. Soc. 1992,
114, 7913-7914. (b) Murahashi, S.-I.; Naota, T.; Komiya, N. Tetrahe-
dron Lett. 1995, 36, 8059-8062.
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2443-2465. (b) Murahashi, S.-I. Pure. Appl. Chem. 1992, 64, 403-
412. (c) Murahashi, S.-I.; Komiya, N. Catal. Today 1998, 41, 339-
349. (d) Murahashi, S.-I.; Naota, T. Comprehensive Organic Chemistry
II, Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford,
U.K., 1995; Vol. 12, pp 1177-1192. (e) Murahashi, S.-I.; Komiya, N.
Biomimetic Oxidations Catalyzed by Transition Metal Complexes;
Meunier, B., Ed.; Imperial College Press: London, 2000; pp 563-611.
(17) (a) Murahashi, S.-I.; Naota, T.; Taki, H. J . Chem. Soc., Chem.
Commun. 1985, 613-614. (b) Murahashi, S.-I.; Naota, T.; Yonemura,
K. J . Am. Chem. Soc. 1988, 110, 8256-8258. (c) Murahashi, S.-I.;
Naota, T.; Miyaguchi, N.; Nakato, T. Tetrahedron Lett. 1992, 33, 6991-
6994.
Crabtree, R. H. Tetrahedron Lett. 1991, 32, 1153-1156. Mn2+
-
exchanged clay: (m) Tateiwa, J .; Horiuchi, H.; Uemura, S. J . Chem.
Soc., Chem. Commun. 1994, 2567-2568. V-MCM-41 zeolite: (n)
Neumann, R.; Khenkin, A. M. Chem. Commun. 1996, 2643-2644.
Metal-substituted polyoxometalate: (o) Faraj, M.; Hill, C. L. J . Chem.
Soc., Chem. Commun. 1987, 1487-1489. cis-[Ru(6,6-Cl2bpy)2(OH2)2](CF3-
SO3)2: (p) Lau, T.-C.; Che, C.-M.; Lee, W.-O.; Poon, C.-K. J . Chem.
Soc., Chem. Commun. 1988, 1406-1407. [Ru(Me3tacn)O2(CF3CO2)]-
(ClO4): (q) Cheng, W.-C.; Yu, W.-Y.; Cheung, K.-K.; Che, C.-M. J .
Chem. Soc., Chem. Commun. 1994, 1063-1064. RuCl3‚nH2O: (r)
Launay, F.; Roucoux, A.; Patin, H. Tetrahedron Lett. 1998, 39, 1353-
1356.
(18) (a) Murahashi, S.-I.; Naota, T.; Kuwabara, T.; Saito, T.;
Kumobayashi, H.; Akutagawa, S. J . Am. Chem. Soc. 1990, 112, 7820-
7822. (b) Murahashi, S.-I.; Saito, T.; Naota, T.; Kumobayashi, H.;
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Chem. Soc. 1996, 118, 2509-2510.
(13) For preliminary communications (RuCl2(PPh3)3-t-BuOOH),
see: (a) Murahashi, S.-I.; Naota, T.; Kuwabara, T. 56th Annu. Meet.
J pn. Chem. Soc. (Tokyo), 1988, Abstr. II, 2A 19. (b) Murahashi, S.-I.;
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35, 7953-7956.

9188 J . Org. Chem., Vol. 65, No. 26, 2000
Murahashi et al.
Ta ble 1. Ru /C-Ca ta lyzed Oxid a tion of Cycloh exa n e w ith
P er a cetic Acid : Rela tion betw een Con ver sion of
Cycloh exa n e a n d Selectivity of Cycloh exa n on e a n d
Cycloh exa n ola
Ta ble 2. Ru /C-Ca ta lyzed Oxid a tion of Alk a n es a n d
Alk yla ted Ar en es w ith CH3CO3Ha
convb
(%)
seld
(%)
entry
1
substrate
productc
amt of
total of
selectivitye
(%)
yieldb (selectivityd) (%)
cyclohexane
7.6 cyclohexanone
cyclohexanol
9.1 cyclohexanone
cyclohexanol
93
4
87
5
87
4
CH3CO3H convb,c
(equiv)
(%)
cyclohexanone cyclohexanol
2e
3
cyclohexane
cyclooctane
methylcyclohexane
adamantane
adamantane
adamantane
n-heptane
0
0
9.1
20
29
38
45
51
0
0
0.7
1.2
1.7
2.2
2.7
3.0
7.9 (87)
16 (82)
22 (76)
28 (73)
32 (71)
35 (68)
0.5 (5)
0.9 (5)
1.1 (4)
1.1 (3)
0.9 (2)
0.9 (2)
92
87
80
76
73
70f
11
cyclooctanone
cyclooctanol
4
7.7 methylcyclohexanonesh 59
methylcyclohexanolsi
adamantanolsj
35
87
13
85
12
84
12
86
3
5
18
37
58
2-adamantanone
6f
7g
8
adamantanolsk
a
To a stirred mixture of cyclohexane (2.00 mmol) and 5% Ru/C
(0.020 mmol) in dry ethyl acetate (2.0 mL) was added dropwise a
30% solution of CH3CO3H in dry ethyl acetate at 20 °C under
2-adamantanone
adamantanolsl
2-adamantanone
b
argon. Determined by GLC analysis based on the starting
8.4 heptanonesm
substrate using an internal standard. c Conversion was controlled
heptanolsn
d
by the amount of peracetic acid. Determined by GLC analysis
9
n-decane
7.2 decanoneso
decanolsp
86
6
based on the converted cyclohexane using an internal standard.
e Cyclohexanone + cyclohexanol. f The overoxidation products,
adipic acid, glutaric acid, and succinic acid (46:44:10), were formed
in 25% yield.
a
To a stirred mixture of substrate (2.00 mmol) and 5% Ru/C
(0.020 mmol) in dry ethyl acetate (2.0 mL) was added dropwise a
30% solution of CH3CO3H (1.00 mmol) in dry ethyl acetate at 20
b
for each 1 equiv of peracetic acid with respect to alkane
is recommended.
°C over a period of 15 min under argon. Determined by GLC
analysis based on the starting substrate using an internal
d
standard. c Identified by GC-MS. Determined by GLC analysis
To determine the optimized reaction conditions, the
oxidation of cyclohexane was carried out with Ru/C
catalyst by changing the amount of peracetic acid. The
ketone/alcohol ratios of the present system are dependent
on the conversions. The relation between the conversion
of cyclohexane and the selectivity of products (cyclohex-
anol and cyclohexanone) was examined (Table 1). Al-
though the conversion was increasing in proportion to
the amount of peracetic acid, the selectivity for the sum
of cyclohexanone and cyclohexanol was decreasing. Typi-
cally, the oxidation of cyclohexane with 0.7 equiv of
CH3CO3H proceeds to give cyclohexanone and cyclohex-
anol (87:5) with 9.1% conversion and 92% selectivity,
whereas the reaction with 3 equiv of CH3CO3H afforded
cyclohexanone and cyclohexanol (68:2) with 51% conver-
sion and 70% selectivity along with dicarboxylic acids
(adipic acid:glutaric acid:succinic acid ) 46:44:10) with
25% selectivity and trace amounts of diketones such as
1,4-cyclohexanedione. Control experiments showed that
these dicarboxylic acids were formed by the oxidation of
diketones such as 1,2- and 1,3-cyclohexanedione under
the reaction conditions. Thus, the high selectivity (>90%)
can be obtained using 0.7-1.0 equiv of peracetic acid with
10% conversion.
The representative results of the oxidation of various
alkanes at 20 °C are shown in Table 2. It is noteworthy
that all reactions proceed with high selectivity (>90%),
when the conversion is controlled to around 10%. Cyclic
alkanes such as cyclohexane and cyclooctane can be
readily converted to the corresponding ketones and
alcohols with 91-93% selectivities (entries 1-3). The
product distribution of the oxidation of methylcyclohex-
ane shows that the relative reactivity of the C-H bonds
is in the order tertiary > secondary . primary (entry 4).
The tertiary/secondary selectivity on a per-bond basis for
the oxidation of adamantane was calculated to be 20
(entry 5). Poorly reactive n-alkanes such as n-heptane
and n-decane are also oxidized (entries 8 and 9). Because
the reaction is heterogeneous, Ru/C catalyst can be
recovered by the filtration and is reusable. Actually, the
oxidation of cyclohexane with CH3CO3H can be repeated
by using recovered Ru/C catalyst three times without loss
based on the converted substrate using an internal standard.
e CH3CO3H (1.40 mmol) was used. f CH3CO3H (2.00 mmol) was
h
used. g CH3CO3H (4.00 mmol) was used. 2-one:3-one:4-one ) 36:
i
j
k
46:18. 1-ol:2-ol:3-ol:4-ol ) 94:2:3:1. 1-ol:1,3-diol ) 95:5. 1-ol:2-
l
m
ol:1,3-diol ) 88:1:12. 1-ol:2-ol:1,3-diol ) 82:1:17. 2-one:3-one:
4-one ) 36:42:22. 2-ol:3-ol:4-ol ) 40:40:20. o 2-one:3-one:(4 + 5)-
n
p
ones ) 18:24:58. 2-ol:3-ol:(4 + 5)-ols ) 25:25:50.
of reactivity and selectivity. It is noteworthy that the Ru/
C-CH3CO3H system shows extremely high reactivity
toward the oxidation of alkanes even at room tempera-
ture. The oxidation of cyclohexane can be carried out with
>50% conversion, although such a high conversion can-
not be achieved at room temperature in the other
systems.6-11
Next we aimed at both high conversion and high
selectivity for the oxidation of alkanes. One can expect
that active oxo-metal species bearing electron-withdraw-
ing ligands would be more reactive species.23 We found
that trifluoroacetic acid is a suitable acid for such a
purpose. Actually, we found that the RuCl3‚nH2O-
catalyzed oxidation of cyclohexane with CH3CO3H in a
mixture of trifluoroacetic acid and dichloromethane (5:
1) at 20 °C for 4 h gave cyclohexyl trifluoroacetate (1)
and cyclohexanone in 90% selectivity (85:15) with 90%
conversion (eq 2).14 It is particularly important that the
overoxidation is suppressed despite extremely high con-
version. The oxidation is also successful for the oxidation
of t-C-H bonds of alkanes. Thus, adamantane was
converted to 1-adamantyl trifluoroacetate (89%), which
was readily hydrolyzed to give 1-adamantanol during the
workup, along with 2-adamantyl trifluoroacetate (9%)
with 70% conversion (eq 3). Although trifluoroacetoxy-
(23) Lau, T.-C.; Mak, C.-K. J . Chem. Soc., Chem. Commun. 1995,
943-944.

Ruthenium-Catalyzed Oxidation of Alkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9189
Ta ble 3. Ru Cl2(P P h 3)3-Ca ta lyzed Oxid a tion of Alk yla ted
Ar en es w ith t-Bu OOHa
lation of hydrocarbons has been reported to occur upon
treatment with hydrogen peroxide in trifluoroacetic acid
without metal catalyst,24 the oxidation of alkanes does
not take place under our reaction conditions. Thus, the
reaction of cyclohexane with peracetic acid in a mixture
of trifluoroacetic acid and CH2Cl2 (5:1) in the absence of
RuCl3‚nH2O for 24 h gave 1 only in 3% yield, indicating
that the present oxidation is based on the ruthenium-
catalyzed reactions. Furthermore, the second-order rate
constants for the ruthenium-catalyzed oxidation of cy-
clohexane with CH3CO3H in trifluoroacetic acid and
CH2Cl2 was determined to be k ) 5.4 M-1 s-1, where the
rate law for the reaction is expressed by eq 4. The value
[cyclohexane]
-
) k[RuCl3‚nH2O][CH3CO3H] (4)
dt
is much larger than that (k < 10-5 s-1) for the oxidation
without the catalyst. The present reaction is a general
and efficient method for conversion of aliphatic C-H
bonds of alkanes to the corresponding trifluoroacetates.
R u t h en iu m -Ca t a lyzed Oxid a t ion of Alk yla t ed
Ar en es. In contrast to the Ru/C-catalyzed oxidation of
alkanes with peracetic acid, the RuCl2(PPh3)3-t-BuOOH
system is highly useful for the oxidation of alkylated
arenes. Thus, the RuCl2(PPh3)3-catalyzed oxidation of
ethylbenzene with 4 equiv of t-BuOOH proceeds with 98%
selectivity to give acetophenone and R-phenethyl alcohol
(93:7).
Various alkylated arenes can be oxidized to the corre-
sponding aryl ketones, as listed in Table 3. Ethylbenzene
and its derivatives are oxidized at the benzylic C-H
bonds to give acetophenone and its derivatives selectively
(entries 1-5). Diphenylmethane and fluorene can be
readily converted into the corresponding ketones in high
yields (entries 6 and 7). The reaction is convenient,
because the product ketones can be readily isolated in
high yields by short column (silica gel). Recently, benzylic
oxidation with iodosylbenzene (3 equiv) in the presence
of manganese salen catalyst (8-15 mol %) has been
reported to give similar yields of ketones.25
a
To a stirred mixture of alkylated arene (2.00 mmol) and
RuCl2(PPh3)3 (0.020 mmol) in dry benzene (2.0 mL) was added
dropwise a 3.59 M solution of t-BuOOH in dry benzene (2.23 mL,
8.00 mmol) at 20 °C over a period of 2 h under argon. b Determined
by GLC analysis based on the starting alkylated arene using an
internal standard. c Determined by GLC analysis based on the
d
converted alkylated arene. R-Phenethyl alcohol is also produced
in 7% yield. e Values in parentheses correspond to isolated yields.
Rea ction Mech a n ism for th e Ru Cl2(P P h 3)3-Ca ta -
lyzed Oxid a tion of Alk a n es w ith t-Bu OOH. Oxo-
ruthenium complexes bearing bulky ligands such as
porphyrins and bipyridines have been isolated and
characterized.7,8,26 However, an oxo-ruthenium complex
bearing simple ligands is unstable and has never been
isolated. A reactive oxo-ruthenium complex may be
formed in the RuCl2(PPh3)3/t-BuOOH system, and this
is the reason the present system is highly efficient for
the oxidation of secondary C-H bonds of alkanes at room
temperature.
It is noteworthy that the oxidation of 9-methylfluorene
gave 9-(tert-butyldioxy)-9-methylfluorene in 98% yield (eq
5). Furthermore, the ruthenium-catalyzed oxidation of
To clarify the mechanism, the relative reactivity of
substituted toluenes (X-C6H4CH3, X ) p-CH3, H, p-Cl,
m-Cl) with t-BuOOH in the presence of RuCl2(PPh3)3 was
determined. In the competitive reaction, a large excess
of substrate was used to ensure that the rate is zero order
in substrate. The relative rates can be determined by the
conversions of toluenes when conversions are low (<5%).
indane with t-BuOOH in methanol gave 1-methoxyin-
dane (20%) along with 1-indanone (12%) at 36% conver-
sion of indane (eq 6). These results may indicate the
intermediacy of carbocation species.
(24) (a) Deno, N. C.; Messer, L. A. J . Chem. Soc., Chem. Commun.
1976, 1051. (b) Deno, N. C.; J edziniak, E. J .; Messer, L. A.; Meyer, M.
D.; Stroud, S. G.; Tomezsko, E. S. Tetrahedron 1977, 33, 2503-2508.
(25) Lee, N. H.; Lee, C.-S.; J ung, D.-S. Tetrahedron Lett. 1998, 39,
1385-1388.
(26) For reviews, see: (a) Holm, R. H. Chem. Rev. 1987, 87, 1401-
1449. (b) Griffith, W. P. Chem. Soc. Rev. 1992, 21, 179-185. (c) Che,
C.-M.; Yam, V. W.-W. Adv. Inorg. Chem. 1992, 39, 233-325. (d) Che,
C.-M.; Yam, V. W.-W. Adv. Transition Met. Coord. Chem. 1996, 1, 209-
237.

9190 J . Org. Chem., Vol. 65, No. 26, 2000
Murahashi et al.
Ta ble 5. Kin etics a n d In tr a - a n d In ter m olecu la r
Deu ter iu m Isotop e Effects for th e
Ru Cl2(P P h 3)3-Ca ta lyzed Oxid a tion of Hyd r oca r bon s w ith
t-Bu OOH
Ta ble 4. Rela tive Ra te Con sta n ts for th e
Ru th en iu m -Ca ta lyzed Oxid a tion of Su bstitu ted Tolu en es
w ith t-Bu OOHa
X in XC6H4CH3
σ+
kX/kH
log(kX/kH)
b
c
syst
Fa
kH/kD
kH/kD
p-CH3
H
-0.311
0
2.77
1
0.443
0
-0.142
-0.543
RuCl2(PPh3)3-t-BuOOH
cytochrome P-450
t-BuO•
-1.39
-1.6d
-0.4e
-0.6f
9.0
11g
9.2
p-Cl
m-Cl
0.114
0.399
0.722
0.286
4.2h
t-BuOO•
a
Reaction conditions: toluene (1 mmol), substituted toluene (1
mmol), RuCl2(PPh3)3 (0.01 mmol), t-BuOOH (0.2 mmol), benzene
(2 mL), 20 °C.
a
Values from Hammett plots of log krel vs σ+ for the competitive
b
oxidation of substituted toluenes. Intramolecular isotope effect
for the oxidation of 1,1-dideuterio-1,3-diphenylpropane. c Inter-
molecular isotope effect for the oxidation of cyclohexane/cyclohex-
d
ane-d12
.
Reference 29. e Reference 30. f Reference 31. g Reference
h
32. Reference 33.
F igu r e 1. Plot of log krel vs σ+ values for the ruthenium-
catalyzed oxidation of substituted toluenes with t-BuOOH.
Because the rate for oxidation of toluene to benzyl alcohol
(k1 ) 0.24 M-1 s-1) is slower than those for benzyl alcohol
to benzaldehyde (k2 ) 4.8 M-1 s-1) or benzaldehyde to
benzoic acid (k3 ) 1900 M-1 s-1),27 the relative rates of
oxidation of toluenes can be calculated by the sum of the
yields of benzyl alcohols (X-C6H4CH2OH), benzaldehydes
(X-C6H4CHO), and benzoic acids (X-C6H4CO2H) at low
conversion (<5%) (Table 4). The rate data correlate well
(γ ) 0.999) with the Hammett linear free energy rela-
tionship with use of σ+ values (Figure 1). Better correla-
tion was obtained with a σ+ value rather than σ,
suggesting the existence of electrophilic high-valent metal
species.28 The F value is -1.39, which is similar to those
obtained for the oxidation with cytochrome P-450 (-1.6)29
and Fe(TPP)Cl-PhIO (-1.69).28 The result indicates that
substantial charge transfer from the substrate to the
electrophilic oxo-metal complex is involved.27 The ob-
served F value (-1.39) is quite different from those
obtained from the t-BuO• radical (-0.4)30 and the t-BuOO•
radical (-0.6)31 (Table 5). These kinetic data indicate the
existence of a metal-dependent species such as oxo-
ruthenium, which is similar to FedO of cytochrome
P-450, rather than t-BuO• and t-BuOO• intermediates.
The intramolecular deuterium isotope effect (kH/kD)
was examined for the oxidation of 1,1-dideuterio-1,3-
diphenylpropane (2).32 The products were 3,3-dideuterio-
1,3-diphenylpropan-1-one (3) and 1,3-diphenylpropan-1-
one (4) (eq 7). The kH/kD value was determined to be 9.0
F igu r e 2. Relative rate of oxidation of cyclohexane (upper)
and cyclohexane-d12 (lower) by RuCl2(PPh3)3 and t-BuOOH.
Reaction conditions: cyclohexane (1.00 mmol), cyclohexane-
d12 (1.00 mmol), RuCl2(PPh3)3 (0.01 mmol), t-BuOOH (0.03-
0.18 mmol), benzene (2 mL), 20 °C.
obtained for the oxidation with cytochrome P-450 (11),32
indicating that the C-H bond breaking is the rate-
determining step. Furthermore, the intermolecular iso-
tope effect of the oxidation of cyclohexanes was deter-
mined to be 9.2 at low conversion (<2%) by GLC analysis
of the competitive reactions of cyclohexane and cyclohex-
ane-d12 (Figure 2). This is in contrast to the smaller
isotope effect (4.2) which was obtained from the reaction
with t-BuO• (Table 5).33
The oxidation can be rationalized by assuming the
mechanism shown in Scheme 1. The ruthenium(II)
complex 5 reacts with t-BuOOH to give the alkylperoxo-
ruthenium(II) complex 6,34 which subsequently under-
goes heterolytic cleavage of the O-O bond to give oxo-
ruthenium(IV) species (7).35 The reaction with t-BuO• or
t-BuOO• is unlikely, because the oxidation of alkanes
proceeds efficiently even in the presence of radical
scavengers such as 2,6-di-tert-butyl-4-methylphenol. Ab-
straction of a hydrogen atom from an alkane by the
intermediate 7 would form the caged complex 8, bearing
an alkyl radical and a hydroxo-ruthenium(III) interme-
(30) (a) Sakurai, H.; Hosomi, A. J . Am. Chem. Soc. 1967, 89, 458-
460. (b) Walling, C.; McGuinness, J . A. J . Am. Chem. Soc. 1969, 91,
2053-2058.
(31) Russell, G. A. Free Radicals; Kochi, J . K., Ed.; Wiley: New York,
1973; Vol. 1, pp 275-331.
(32) Hjelmeland, L. M.; Aronow, L.; Trudell, J . R. Biochem. Biophys.
Res. Commun. 1977, 76, 541-549.
by means of GC-MS analyses of a mixture of the product
ketones 3 and 4. This large kH/kD value is similar to that
(33) Kim, J .; Harrison, R. G.; Kim, C.; Que, L., J r. J . Am. Chem.
Soc. 1996, 118, 4373-4379.
(34) Ru-OO-t-Bu: (a) Fung, W.-H.; Yu, W.-Y.; Che, C.-M. J . Org.
Chem. 1998, 63, 2873-2877. Fe-OO-t-Bu: (b) Arasasingham, R. D.;
Cornman, C. R.; Balch, A. L. J . Am. Chem. Soc. 1989, 111, 7800-
7805.
(27) Reference 1a, p 350.
(28) Khanna, R. K.; Pauling, T. M.; Vajpayee, D. Tetrahedron Lett.
1991, 32, 3759-3762.
(29) Blake, R. C., II; Coon, M. J . J . Biol. Chem. 1981, 256, 12127-
12133.
(35) Che, C.-M. Pure Appl. Chem. 1995, 67, 225-232.

Ruthenium-Catalyzed Oxidation of Alkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9191
Sch em e 1
formation of 12 is remarkable. The product ratio of the
alcohol 12 to the other products derived from benzyl
radical is 53:28. The alcohol 12 would be formed by the
heterolytic O-O bond cleavage of the PhCH2C(CH3)2-
OORuLn complex (eq 8).37 The corresponding ratio ob-
tained from the Gif system (FeCl3-picolinic acid-t-
BuOOH in pyridine and AcOH) has been determined to
be 16:59, where t-BuO• was determined to be a major
reaction species.36b,38 The results for the Gif system is
quite different from those for the present system. It seems
reasonable to conclude that the reaction of MPPH with
the ruthenium species would give an oxo-ruthenium
species (RudO) as a major intermediate.
We next examined Minisci’s test to distinguish the
reactivities of t-BuO• and t-BuOO•. Minisci et al. deter-
mined the relative rates for Gif and Kharasch reactions,
where t-BuO• and t-BuOO• radicals are key intermedi-
ates, respectively.38b In these systems the solvent effect
is remarkable; t-BuO• radical would be formed in polar
solvents such as pyridine and acetic acid, whereas the
t-BuOO• radical is formed in nonpolar solvents.38a The
relative reactivity of cyclohexane, toluene, cumene, cy-
clohexene, styrene, and THF in benzene toward the
present RuCl2(PPh3)3-t-BuOOH system was determined
to be 1:0.26:1.5:13:3.2:2.0 at low conversions (0.5-5%),
as shown in Table 6. The ratio is quite similar to that
(1:0.27:1.2:7.2:3.5:3.3) obtained from the Fe(TPFPP)Cl-
t-BuOOH system, where oxo-iron species are actually
generated.39 The relative reactivity obtained from the
present system are different from those obtained from
t-BuOO• reactions (1:65:>100:>100:>100:>100)38a (Table
6). The difference between the present system and the
t-BuO• system is rather small to distinguish; however, a
remarkable difference in reactivity was observed for the
oxidation of cumene. The ratio of reactivity between
cyclohexane and cumene is 1.5 for RuCl2(PPh3)3/t-
BuOOH, while the ratio for the t-BuO• system is 0.5.
Furthermore, the relative reactivity of the oxidation of
tertiary and secondary hydrogen in adamantane is 9.2
for the RuCl2(PPh3)3-t-BuOOH system, while that for the
t-BuO• system is 2.7.38b These results also show that the
active species of the RuCl2(PPh3)3-t-BuOOH system is
neither t-BuO• nor t-BuOO• radical.
All data such as F values, kH/kD ratios, and relative
oxidation rates in the various substrates described above
revealed that the active species of the RuCl2(PPh3)3-t-
BuOOH system is the oxo-ruthenium species.
Rea ction Mech a n ism for th e Ru th en iu m -Ca ta -
lyzed Oxid a tion of Alk a n es w ith P er a cetic Acid . An
intermolecular deuterium isotope effect (kH/kD) was ex-
amined for the Ru/C-catalyzed oxidation of cyclohexane
and cyclohexane-d12 with peracetic acid. The kH/kD value
was determined to be 6.8 by GC analysis at 0.05-2.1%
conversion. The isotope effect (kH/kD ) 6.8) is smaller
than those (9.2) obtained for the RuCl2(PPh3)3-catalyzed
oxidation with t-BuOOH, indicating that a more reactive
diate. Transfer of the hydroxy ligand to the caged alkyl
radical (path A) would afford an alcohol and the Ru(II)
species 10 to complete the catalytic cycle. The involve-
ment of a Ru(III)-Ru(V) cycle to form an oxo-rutheni-
um(V) species cannot be excluded.8 Further oxidation of
secondary alcohol thus formed gives the corresponding
ketones under the reaction conditions. When the alkyl
radical 8 has low oxidation potential, fast single-electron
transfer would take place to give cation 9 (path B), which
undergoes reaction with the second molecule of t-BuOOH
to give the corresponding tert-butyldioxy product and
water. The ratios of the tert-butyldioxy products to the
total sums of ketones and alcohols for the RuCl2(PPh3)3-
catalyzed oxidation of hydrocarbon with t-BuOOH are in
the order 9-methylfluorene (10:0) > cyclohexene (3:7) >
cyclohexane (1:9). This tendency is in accordance with
the stability of the corresponding cationic intermediate.
Furthermore, the formation of 1-methoxyindane from the
ruthenium-catalyzed oxidation of indane in methanol (eq
6) indicates the formation of the cationic intermediate
9, which is trapped with the methanol under the reaction
conditions.
To obtain further information about the reactive
intermediate, Ingold’s mechanistic probe of 2-methyl-1-
phenyl-2-propyl hydroperoxide (MPPH; 11)36 was applied
to the present oxidation. The peroxide 11 has been used
to determine the mode of scission of the peroxidic O-O
bond.36 When MPPH is allowed to react with a metal
catalyst, an oxo-metal or alkoxyl radical will be formed.
In the case of formation of PhCH2C(CH3)2O• radical, fast
â-scission occurs to give benzyl radical, from which
typical radical reaction products are formed. The product
distributions derived from MPPH may enable the dis-
crimination of the mechanism between RudO and t-BuO•.
The reaction of RuCl2(PPh3)3 with MPPH (11) was
carried out in benzene at room temperature (eq 8).
Dimethylbenzylcarbinol (12) was obtained as a major
product (53%) along with the products derived from ben-
zyl radical such as benzaldehyde (19%), benzoic acid (1%),
benzyl benzoate (1%), phenyl benzoate (1%), diphenyl-
methane (2%), 1,2-diphenylethane (2%), and 2-methyl-
1-phenyl-2-propyl benzyl ether (2%). The predominant
(37) Nam, W.; Choi, H. J .; Han, H. J .; Cho, S. H.; Lee, H. J .; Han,
S.-Y. Chem. Commun. 1999, 387-388.
(38) (a) Minisci, F.; Fontana, F.; Araneo, S.; Recupero, F.; Zhao, L.
Synlett 1996, 119-125. (b) Minisci, F.; Fontana, F.; Araneo, S.;
Recupero, F.; Banfi, S.; Quici, S. J . Am. Chem. Soc. 1995, 117, 226-
232.
(36) (a) Arends, I. W. C. E.; Ingold, K. U.; Wayner, D. D. M. J . Am.
Chem. Soc. 1995, 117, 4710-4711. (b) Snelgrove, D. W.; MacFaul, P.
A.; Ingold, K. U.; Wayner, D. D. M. Tetrahedron Lett. 1996, 37, 823-
826. (c) McFaul, P. A.; Ingold, K. U.; Wayner, D. D. M.; Que, L., J r. J .
Am. Chem. Soc. 1997, 119, 10594-10598.
(39) (a) Traylor, T. G.; Kim, C.; Fann, W.-P.; Perrin, C. L. Tetrahe-
dron 1998, 54, 7977-7986. (b) Traylor, T. G.; Kim, C.; Richards, J . L.;
Xu, F.; Perrin, C. L. J . Am. Chem. Soc. 1995, 117, 3468-3474. (c)
Traylor, T. G.; Tsuchiya, S.; Byun, Y. S.; Kim, C. J . Am. Chem. Soc.
1993, 115, 2775-2781.

9192 J . Org. Chem., Vol. 65, No. 26, 2000
Murahashi et al.
Ta ble 6. Rela tive Rea ctivities of Hyd r oca r bon s for th e Oxid a tion of Cycloh exa n e, Tolu en e, Cu m en e, Cycloh exen e,
Styr en e, a n d THF by Ru Cl2(P P h 3)3-t-Bu OOH, F e(TP F P P )Cl-t-Bu OOH, Gif, t-Bu O•, Kh a r a sch , a n d t-Bu OO• System s
RuCl2(PPh3)3-
t-BuOOHa
Fe(TPFPP)Cl-
t-BuOOHa
FeIII-t-BuOOH
CuII-t-BuOOH
substrate
AcOH (Gif)b
t-BuO•b
(Kharasch)b
t-BuOO•b
cyclohexane
toluene
cumene
cyclohexene
styrene
THF
1
1
1
1
1
70
>100
>100
>100
>100
1
65
>100
>100
>100
>100
0.26 ( 0.02
1.5 ( 0.1
13 ( 1
3.2 ( 0.3
2.0 ( 0.1
0.27 ( 0.02
1.2 ( 0.1
7.2 ( 0.8
3.5 ( 0.2
3.3 ( 0.3
0.21
0.61
3.66
1.42
2.77
0.14
0.54
3.56
1.63
5.13
a
The competitive reaction was carried out with cyclohexane (1.00 mmol), substrate (1.00 mmol), catalyst (0.010 mmol), and t-BuOOH
b
(0.05-0.20 mmol) in dry benzene (2.0 mL) at 20 °C. The values have been determined at five different conversions (0.5-5%). Reference
38a.
Sch em e 2
and product analyses. Highly efficient and selective
oxidation of hydrocarbons can be also performed by the
ruthenium-catalyzed oxidation of alkanes with peracetic
acid in the presence of trifluoroacetic acid.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Ru th en iu m -Ca ta lyzed Oxi-
d a tion of Alk a n es w ith CH3CO3H. In a 10 mL round-
bottomed flask equipped with a Teflon-coated magnetic stirring
bar and a 10 mL pressure-equalizing dropping funnel to a
three-way stopcock were placed alkane (2.00 mmol), 5% Ru/C
(40 mg, 0.020 mmol for Ru), and dry EtOAc (2.0 mL). A 30%
solution of CH3CO3H in EtOAc (253 mg, 1.00 mmol) was placed
in the dropping funnel and added dropwise to the stirred
mixture at 20 °C over a period of 15 min. The reaction mixture
was then poured into a 10% aqueous Na2SO3 solution (10 mL)
slowly and extracted with ether (5 mL × 2). The combined
organic layer was washed with a saturated aqueous NaHCO3
solution and dried over Na2SO4. The conversion of starting
alkane and the yields of products were determined by GLC
analysis using an internal standard (acetophenone). The
identities of the products were verified by co-injection with
authentic samples and in some cases by GC-MS. These results
are listed in Table 2.
Ru th en iu m -Ca ta lyzed Oxid a tion of Cycloh exa n e w ith
CH3CO3H in th e P r esen ce of Tr iflu or oa cetic Acid . The
reaction was performed using a 50 mL round-bottomed flask,
in which cyclohexane (210 mg, 2.50 mmol), RuCl3‚nH2O (6.5
mg, 0.025 mmol), trifluoroacetic acid (5 mL), and CH2Cl2 (1
mL) were placed. A 30% solution of CH3CO3H in EtOAc (1.27
g, 5.00 mmol) was added dropwise to the stirred mixture at
20 °C over a period of 2 h. After the mixture was stirred for a
further 2 h, the reaction mixture was poured into a 5% aqueous
Na2SO3 solution (5 mL) slowly and extracted with CH2Cl2 (5
mL × 2). The combined organic layer was washed with a
saturated aqueous NaHCO3 solution and water (5 mL) and
dried over Na2SO4. The conversion of cyclohexane (90%) and
the selectivities of products (77% (cyclohexyl trifluoroacetate);
13% (cyclohexanone)) were determined by GLC analysis using
an internal standard (acetophenone). The identities of the
products were verified by co-injection with authentic samples
and by GC-MS.
species is present in the present system. Actually, the
oxidation of secondary C-H bonds of aliphatic hydrocar-
bons with the present system gave higher conversions
than those with RuCl2(PPh3)3-t-BuOOH.
The oxidation can be rationalized by assuming a
reaction pathway similar to that shown in Scheme 2. The
low-valent ruthenium complex LmRun (13) reacts with
peracetic acid to give the acetylperoxo-ruthenium com-
plex 14, which undergoes heterolytic cleavage of the O-O
bond to give the oxo-ruthenium species 1526 and acetic
acid. Bruice et al. showed that the acylperoxo-metal-
loporphyrins undergo heterolytic cleavage more cleanly
than alkylperoxo-metal complexes.40 Abstraction of a
hydrogen atom from an alkane by 15 would form the
caged complex 16, in which transfer of hydroxy ligand
to the caged alkyl radical would afford an alcohol and
the ruthenium species LmRun (13) to complete the cata-
lytic cycle. The presence of freely diffusing alkyl radicals
is unlikely, because Russell-type termination of alkyl-
peroxyl radicals forms equal amounts of alcohols and
ketones,41 but the present reaction gives ketones pre-
dominantly. In the presence of trifluoroacetic acid, the
secondary alcohols thus formed can be trapped with
trifluoroacetic acid to give the corresponding ester faster
than the sequential oxidation to ketones.
Con clu sion s
Oxid a tion of Cycloh exa n e w ith CH3CO3H in Tr iflu o-
r oa cetic Acid in th e Absen ce of Ru Cl3‚n H2O Ca ta lyst
(Con tr ol Exp er im en t). The same reaction as above was
carried out in the absence of RuCl3‚nH2O. After the mixture
was stirred for a further 15 h, the reaction mixture was poured
into a 5% aqueous Na2SO3 solution (5 mL) slowly and extracted
with CH2Cl2 (5 mL × 2). The combined organic layer was
washed with a saturated aqueous NaHCO3 solution and water
(5 mL) and dried over Na2SO4. GLC analysis shows that the
yield of cyclohexyl trifluoroacetate is 3%, and trace amounts
of cyclohexanone and cyclohexanol can be detected.
The two catalytic systems RuCl2(PPh3)3-t-BuOOH and
Ru/C-CH3CO3H have been found to oxidize alkanes at
room temperature. The former is suitable for synthesis
of aryl ketones from alkylated arenes, and the latter is
suitable for catalytic oxidation of alkanes. Both reactions
need only simple ruthenium catalysts and peroxides such
as t-BuOOH and peracetic acid. The intermediacy of oxo-
ruthenium species has been demonstrated in both cata-
lytic systems by means of kinetic study, isotope effects,
Gen er a l P r oced u r e for th e Ru th en iu m -Ca ta lyzed Oxi-
d a tion of Alk yla ted Ar en es w ith t-Bu OOH. To a stirred
solution of alkylated arene (2.00 mmol), RuCl2(PPh3)3 (19 mg,
0.020 mmol), and dry benzene (2.0 mL) was added dropwise a
3.59 M solution of t-BuOOH in dry benzene (2.23 mL, 8.00
(40) (a) Yuan, L.-C.; Bruice, T. C. J . Am. Chem. Soc. 1985, 107, 512-
513. (b) Lee, W. A.; Bruice, T. C. J . Am. Chem. Soc. 1985, 107, 513-
514.
(41) Russell, G. A. J . Am. Chem. Soc. 1957, 79, 3871-3877.

Ruthenium-Catalyzed Oxidation of Alkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9193
mmol) at 20 °C over a period of 2 h. The reaction mixture was
then poured into a 10% aqueous Na2SO3 solution (10 mL)
slowly and extracted with ether (5 mL × 2). The conversion of
alkylated arene and the yields of products were determined
by GLC analysis using an internal standard (acetophenone).
The results of the oxidation of alkylated arenes are listed in
Table 3. The product was isolated by column chromatography
on silica gel (eluent hexanes-ethyl acetate).
Com p etitive Rea ction s of Su bstitu ted Tolu en es for
th e Ru th en iu m -Ca ta lyzed Oxid a tion w ith t-Bu OOH. To
a mixture of toluene (92 mg, 1.00 mmol), substituted toluene
(1.00 mmol), and RuCl2(PPh3)3 (10 mg, 0.01 mmol) in dry
benzene (2.0 mL) was added dropwise a 4.32 M solution of
t-BuOOH in dry benzene (0.05 mL, 0.20 mmol) at 20 °C over
a period of 10 min. After complete addition of the peroxide,
the mixture was quenched as described above and analyzed
by GC (TC-WAX column) using an internal standard, and the
ratios of conversions were determined. As products, benzyl
alcohols (X-C6H4CH2OH), benzaldehydes (X-C6H4CHO), and
benzoic acids (X-C6H4CO2H) were formed. Under these condi-
tions, the conversions of toluene and substituted toluene were
<5% with a mass balance of >95%. The ratios obtained are
as follows: X ) p-CH3 (kX/kH ) 2.77), p-Cl (0.722), m-Cl (0.286)
(Table 4). Correlation of the relative rate data using a single-
parameter Hammett equation gave fair linear correlations
against σ+. The F value for the reaction is -1.39 with γ ) 0.999
(Figure 1).
Rela tive Rea ctivities for th e Ru th en iu m -Ca ta lyzed
Oxid a tion of Cycloh exa n e, Tolu en e, Cu m en e, Cycloh ex-
en e, Styr en e, a n d THF w ith ter t-Bu tyl Hyd r op er oxid e.
The reaction was performed by using equal amounts of
cyclohexane (84 mg, 1.00 mmol) and a substrate (1.00 mmol)
in the presence of RuCl2(PPh3)3 (0.0096 g, 0.010 mmol) in
benzene (2 mL), to which a 4.32 M solution of t-BuOOH in
benzene (0.05-0.20 mmol) was added over a period of 10 min.
After complete addition of the peroxide, the mixture was
quenched as described above and analyzed by GC (TC-WAX
column) using an internal standard. The reaction was repeated
five times, and the values of the relative reactivities of six
substrates were determined by the conversion of substrates
at five different conversions (0.5-5%). The results are shown
in Table 6.
Ru th en iu m -Ca ta lyzed Oxid a tion of 1,1-Did eu ter io-1,3-
d ip h en ylp r op a n e (2) w ith t-Bu OOH (In tr a m olecu la r
Deu ter iu m Isotop e Effect). To a mixture of 2 (20 mg, 0.100
mmol) and RuCl2(PPh3)3 (1.0 mg, 0.0010 mmol) in dry benzene
(0.1 mL) was added a 3.59 M solution of t-BuOOH in dry
benzene (0.028 mL, 0.10 mmol) all at once, and the mixture
was stirred at 20 °C for 10 min. Under these conditions, the
conversion of 2 was <5%. The kH/kD value was determined to
be 9.0 by mass chromatography analysis of the mixture of 3,3-
dideuterio-1,3-diphenyl-1-propanone (3) (M+ 212) and 1,3-
diphenyl-1-propanone (4) (M+ 210).
The reaction was performed by using equal amounts of
cyclohexane (84 mg, 1.00 mmol) and cyclohexane-d12 (96 mg,
1.00 mmol) in the presence of RuCl2(PPh3)3 (19 mg, 0.020
mmol) in dry benzene (2.0 mL), to which a 2.94 M solution of
t-BuOOH (0.03-0.18 mmol) in dry benzene was added drop-
wise at 20 °C. After complete addition of the peroxide for 1-10
min, the mixture was quenched as described above and
analyzed by GC (TC-WAX column) using an internal standard
(diethyl carbonate). Under these conditions, the conversions
of cyclohexanes were <2% with a mass balance of >95%. The
conversions were determined from the yields of products such
as cyclohexanol, cyclohexanone, cyclohexanol-d11, and cyclo-
hexanone-d10, and the ratio of the conversion of cyclohexane/
cyclohexane-d12 (kH/kD) was determined to be 9.2 ( 0.1 at six
different conversions between 0.02% and 1.4% (Figure 2).
Com p etitive Rea ction s of Cycloh exa n e a n d Cycloh ex-
a n e-d 12 for th e Ru th en iu m -Ca ta lyzed Oxid a tion w ith
CH3CO3H (In ter m olecu la r Deu ter iu m Isotop e Effect). To
a mixture of cyclohexane (0.0842 g, 1.00 mmol), cyclohexane-
d12 (0.0962 g, 1.00 mmol), and 5% Ru/C (0.040 g, 0.020 mmol
for Ru) in dry EtOAc (2.0 mL) was added a 30% solution of
CH3CO3H (0.04-0.20 mmol) in EtOAc at 20 °C. After complete
addition of the peroxide for 1-10 min, the mixture was
quenched as described above and analyzed by GC (TC-WAX
column) using an internal standard. Under these conditions,
the conversions of cyclohexanes were <2% with a mass balance
of >95%. The conversions were determined from the yields of
products such as cyclohexanol, cyclohexanone, cyclohexanol-
d
11, and cyclohexanone-d10, and the ratio of the conversion of
cyclohexane/cyclohexane-d12 (kH/kD) was determined to be 6.8
( 0.3 at five different conversions between 0.05% and 2.1%.
Rea ction of 2-Meth yl-1-p h en yl-2-p r op yl Hyd r op er ox-
id e (11) w ith Ru Cl2(P P h 3)3. To a stirred solution of RuCl2-
(PPh3)3 (0.9 mg, 0.0009 mmol) in dry benzene (0.5 mL) was
added dropwise a solution of 1136a (30 mg, 0.18 mmol) in
benzene over a period of 15 min at 20 °C. After 2 h, the yields
of dimethylbenzylcarbinol (12; 53%), benzaldehyde (19%),
benzoic acid (1%), benzyl benzoate (1%), phenyl benzoate (1%),
diphenylmethane (2%), 1,2-diphenylethane (2%), and 2-methyl-
1-phenyl-2-propyl benzyl ether (2%) were determined by GLC
analysis (TC-WAX). The product ratio of the alcohol 12 to the
other species, which are derived from benzyl radical, was
determined to be 53:28.
Ack n ow led gm en t. This work was supported by the
Research for the Future program, the J apan Society for
the Promotion of Science, and a Grant-in-Aid for Sci-
entific Research, from the Ministry of Education, Sci-
ence, Sports, and Culture of J apan.
Su p p or tin g In for m a tion Ava ila ble: Text giving detailed
experimental procedures, including analytical and spectro-
scopic data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
Com p etitive Rea ction of Cycloh exa n e a n d Cycloh ex-
a n e-d 12 for th e Ru th en iu m -Ca ta lyzed Oxid a tion w ith
t-Bu OOH (In t er m olecu la r Deu t er iu m Isot op e E ffect ).
J O001348F