Pd(OAc)2-Catalyzed Oxidative Coupling Reaction of Benzenes with Olefins in the Presence of Molybdovanadophosphoric Acid under Atmospheric Dioxygen and Air

Article abstract of DOI:10.1021/jo035568f

The direct oxidative coupling reaction of benzenes with alkenes bearing an electron-withdrawing group was successfully achieved by the use of Pd(OAc) ₂/molybdovanadophosphoric acid (HPMoV) as the key catalyst under O₂ or air atmosphere. Thus, the reaction of benzene with ethyl acrylate under air (1 atm) assisted by Pd(OAc)₂/HPMoV afforded ethyl cinnamate as a major product in satisfactory yield (74%). This catalytic system could be extended to the coupling reactions between various substituted benzenes and alkenes through the direct aromatic C-H bond activation. In the reaction of benzene with ethyl acrylate under O₂ (1 atm), the best turn-over number (TON) of Pd(OAc)₂ reached was 121. This reaction provides a green route to cinnamate derivatives, which are important precursors of a variety of pharmaceuticals.

Full text of DOI:10.1021/jo035568f

P d (OAc)2-Ca ta lyzed Oxid a tive Cou p lin g Rea ction of Ben zen es w ith
Olefin s in th e P r esen ce of Molybd ova n a d op h osp h or ic Acid u n d er
Atm osp h er ic Dioxygen a n d Air
Masayuki Tani, Satoshi Sakaguchi, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering, Kansai University,
Suita, Osaka 564-8680, J apan
ishii@ipcku.kansai-u.ac.jp
Received October 23, 2003
The direct oxidative coupling reaction of benzenes with alkenes bearing an electron-withdrawing
group was successfully achieved by the use of Pd(OAc)2/molybdovanadophosphoric acid (HPMoV)
as the key catalyst under O2 or air atmosphere. Thus, the reaction of benzene with ethyl acrylate
under air (1 atm) assisted by Pd(OAc)2/HPMoV afforded ethyl cinnamate as a major product in
satisfactory yield (74%). This catalytic system could be extended to the coupling reactions between
various substituted benzenes and alkenes through the direct aromatic C-H bond activation. In
the reaction of benzene with ethyl acrylate under O2 (1 atm), the best turn-over number (TON) of
Pd(OAc)2 reached was 121. This reaction provides a green route to cinnamate derivatives, which
are important precursors of a variety of pharmaceuticals.
In tr od u ction
catalytic C-H bond activation of arenes. Since the
success of the activation of aryl C-H bonds through
ortho-chelation by Ru complexes by Murai et al.,3 similar
catalytic reactions that can activate the ortho C-H bond
of substituted arenes have been reported.4 However, it
is still very difficult to carry out the direct activation of
the C-H bond of nonsubstituted aromatic compounds
such as benzene through a catalytic process.5 Fujiwara
and co-worker have reported the stoichiometric and
catalytic oxidative coupling of arenes with alkenes through
the cleavage of the aromatic C-H bond assisted by Pd
compounds.6 In 1978, Matveev et al. reported the Pd(II)-
catalyzed arylation of ethylene in the presence of molyb-
dovanadophosphoric acid.7 The Pd-catalyzed oxidative
The arylation of olefins (Heck-Mizoroki reaction) is
frequently used as an important reaction in the synthesis
of arene derivatives. Although the reaction is applicable
to the coupling between various aryl halides and alkenes,
there have been several drawbacks in this methodology.
For example, the formation of undesired waste salts
which come from aryl halides used as starting materials
is unavoidable, and a stoichiometric amount or more of
a base must be added to complete the reaction. As a
result, the reaction is difficult to carry out in large scale
in industry except for the synthesis of expensive phar-
maceutical materials. Development of a novel catalytic
method for the synthesis of arene derivatives through the
direct aromatic C-H bond activation is a challenging
subject in synthetic organic chemistry, since there has
been a growing demand for the construction of a waste-
free synthetic method.1
(3) (a) Murai, S.; Kakiuchi, F.; Sekine, Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature 1993, 366, 529-531. (b) Kakiuchi, F.;
Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N.; Murai,
S. Bull. Chem. Soc. J pn. 1995, 68, 62-83. (c) Kakiuchi, F.; Yamakazu,
M.; Chatani, N.; Murai, S. Chem. Lett. 1996, 111-112. (d) Kakiuchi,
F.; Sato, T.; Yamakazu, M.; Chatani, N.; Murai, S. Chem. Lett. 1999,
19-20. (e) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826-
834.
(4) (a) Miura, M.; Tsuda, T.; Satoh, T.; Nomura, M. Chem. Lett. 1997,
1103-1104. (b) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S. J . Org.
Chem. 1998, 63, 5211-5215. (c) Lenges, P. C.; Brookhart, M. J . Am.
Chem. Soc. 1999, 121, 6616-6623. (d) Ritleng, V.; Sutter, J .; Pfeffer,
M.; Sirlin, C. Chem. Comm. 2000, 129-130. (e) Trost, B. M.; Toste, F.
D.; Greenman, K. J . Am. Chem. Soc. 2003, 125, 4518-4526.
(5) (a) Chen, H. Y.; Schlecht, S.; Semple, T. C.; Hartwig, J . F. Science
2000, 287, 1995-1997. (b) Matsumoto, T.; Taube, D. J .; Periana, R.
A.; Taube, H.; Yoshida, H. J . Am. Chem. Soc. 2000, 122, 7414-7415.
(c) Ishiyama, T.; Takagi, J .; Ishida, K.; Miyaura, N.; Anastasi, N. R.;
Hartwig, J . F. J . Am. Chem. Soc. 2002, 124, 390-391. (d) Cho, J . Y.;
Tse, M. K.; Holmes, D.; Maleczka, R. E.; Smith, M. R. Science 2002,
295, 305-308. (e) Tsukada, N.; Mitsuboshi, T.; Setoguchi, H.; Inoue,
Y. J . Am. Chem. Soc. 2003, 125, 12102-12103.
Although several transition metal compounds are
known to activate stoichiometrically the aryl C-H bond,2
a limited number of methods have appeared for the
(1) (a) Activation of unreactive bonds and organic synthesis; Murai,
S., Ed.; Springer: New York, 1999. (b) Dyker, G. Angew. Chem. 1999,
111, 1808-1822; Angew. Chem., Int. Ed. 1999, 38, 1698-1712. (c) J ia,
C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633-639. (d)
J ia, C.; Piao, D.; Oyamada, J .; Kitamura, T.; Fujiwara, Y. Science 2000,
287, 1992-1995. (e) Labinger, J . A.; Bercaw, J . E. Nature (London)
2002, 417, 507-514. (f) Ritleng, V.; Sinlin, C.; Pfeffer, M. Chem. Rev.
2002, 102, 1731-1770.
(2) (a) Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 1119-1122.
(b) J ones, W. D.; Feher, F. J . Acc. Chem. Res. 1989, 22, 91-100. (c)
Ryabov, A. D. Chem. Rev. 1990, 90, 403-424. (d) Chin, R. M.; Dong,
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(6) (a) Fujiwara, Y.; Takaki, K.; Taniguchi, Y. Synlett 1996, 591-
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2097-2100 and references therein.
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10.1021/jo035568f CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/21/2004
J . Org. Chem. 2004, 69, 1221-1226
1221

Tani et al.
TABLE 1. Oxid a tive Cou p lin g of Ben zen e (1a ) w ith
Eth yl Acr yla te (2a ) u n d er Sever a l Con d ition sa
coupling of arenes with alkenes using peroxides and
benzoquinones as oxidants has been studied by several
authors.8 The oxidative coupling reaction with molecular
oxygen as a terminal oxidant is very useful from envi-
ronmental and economical points of view, but attempts
with dioxygen or air as a terminal oxidant are not fully
successful and the turnover numbers of catalysts are still
less than 10.9 Recently, a few oxidative arylations of
alkenes with dioxygen as a terminal oxidant have been
reported. For instance, Matsumoto et al. have obtained
styrene from benzene and ethylene catalyzed by a Rh
complex in acetic acid with high dioxygen pressure (5.4
atm).10 The Ru-catalyzed reaction of benzene with acry-
lates under the influence of O2 (2 atm) and CO (6.1 atm)
at 180 °C is reported by Milstein et al.11 Quite recently,
J acobs et al. reported the Pd(OAc)2-catalyzed coupling
reaction of benzene with olefins under 0.4-1.6 MPa (4-
16 atm) of O2 without solvent at 90 °C.12 However, these
reactions must be carried out at high reaction tempera-
ture or high pressure of dioxygen. Therefore, it has been
desired for a long time to develop an efficient catalytic
method for the coupling through the direct aromatic C-H
bond activation under mild conditions.
yield (%)b
entry
catalyst
base
conv (%)b
3a a
4a a
5
1
2c
3
Pd(OAc)2
Pd(OAc)2
NaOAc
NaOAc
NaOAc
100
100
3
74
6
0
13
81
0
4
0
0
4
8
1
16
0
7
1
4
Pd(OAc)2
Pd(OAc)2
Pd(acac)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
21
63
100
93
26
83
21
19
18
90
16
6
0
2
16
5
0
5
0
0
0
5d
6d
7e
8f
NaOAc
NaOAc
NaOAc
NaOAc
LiOAc
CsOAc
KOAc
NH4OAc
NaOAc
NaOAc
53
75
51
20
66
13
11
12
74
10
9
10
11
12
13g
14h
0
0
6
3
8
0
a
1a (30 mmol) was allowed to react with 2a (1.5 mmol) in the
presence of Pd-species (0.1 mmol), HPMo11V1 (47 mg, ca. 0.02
mmol), base (0.08 mmol), and acetylacetone (0.1 mmol) in EtCOOH
b
(5 mL) at 90 °C for 2.5 h. Conversion and yield were based on
d
2a . c The reaction was carried out for 5 h. In the absence of
acetylacetone. e 1a (6 mmol) was used. f AcOH was used instead
g
h
of EtCOOH. Under air (1 atm) for 5 h. Under Ar (1 atm)
In the course of our study on the activation of benzenes
with the Pd(II)/molybdovanadophosphoric acid (HPMoV)
catalytic system,13 we have recently disclosed a highly
efficient catalytic system for oxidative coupling of benzene
with acrylates under atmosphere dioxygen in a com-
munication.14 In this paper, we wish to report in detail
our works on the coupling reaction of arenes with alkenes
(eq 1).
H4PMo11V1O40‚nH2O (HPMo11V1, n ) 30) proceeded
smoothly in the presence of small amounts of acetylac-
etone and NaOAc under atmospheric O2 in propionic acid
at 90 °C for 2.5 h to give coupling products, ethyl
cinnamate (3a a ) (74%) and ethyl â-phenylcinnamate
(4a a ) (13%), together with ethyl 3-propionyloxyacrylate
(5) (4%) derived from 2a and propionic acid (entry 1).
When the reaction was prolonged to 5 h under these
conditions, double coupling product 4a a was formed in
good yield (81%) (entry 2). Needless to say, the reaction
did not take place at all without Pd(OAc)2 (entry 3). It
was found that a small amount of a base like NaOAc is
necessary to carry out the coupling in higher conversion
(entry 4). Removing acetylacetone from the present
catalytic system resulted in the decrease of the coupling
products, 3a a and 4a a (entry 5). It is interesting to note
that the acetylacetone ligand is not necessary when Pd-
(acac)2 was employed in place of Pd(OAc)2 (entry 6). This
fact indicates the importance of acetylacetone ligand in
the present reaction. It has been reported that the
oxidative arylation of benzene with ethylene to styrene
by Rh and Pd complexes is accelerated by adding a small
amount of acetylacetone and the formation of a byproduct
like vinyl acetate is depressed.10 When the amount of 1a
was reduced from 30 mmol to 6 mmol, the amount of 5
that is formed by the reaction of 2a with propionic acid
increased from 4% to 16% and the yield of 3a a decreased
to 51% (entry 7). The use of acetic acid as the solvent
resulted in considerable decrease of 3a a and 4a a (entry
8). Although the effect of several alkali metal acetates
in the present coupling was examined, the addition of
lithium acetate furnished 3a a in 66% yield, and potas-
sium, cesium, and ammonium acetates led to 3a a in very
low yields (entries 9-12). There results show that the
NaOAc is the best base in the present catalytic system.
From the practical synthetic viewpoint, it is important
to carry out the reaction under air in place of pure O2.
Interestingly, it was found that the reaction smoothly
took place even under air (1 atm), and 3a a was obtained
Resu lts a n d Discu ssion
To confirm the optimum reaction conditions, the reac-
tion of benzene (1a ) with ethyl acrylate (2a ) was chosen
as a model reaction and carried out under various
reaction conditions. Table 1 shows the representative
results for the reaction of 1a with 2a catalyzed by
Pd(OAc)2 combined with heteropoly acids. The coupl-
ing reaction catalyzed by Pd(OAc)2 combined with
(8) (a) Tsuji, J .; Nagashima, H. Tetrahedron 1984, 40, 2699-2702.
(b) Mikami, K.; Hatano, M.; Terada, M. Chem. Lett. 1999, 55-56. (c)
Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries, A. H. M.; Kamer, P.
C. J .; de Vries, J . G.; van Leeuwen, P. W. N. M. J . Am. Chem. Soc.
2002, 124, 1586-1587.
(9) (a) Fujiwara, Y.; Moritani, I.; Danno, S.; Teranishi, S. J . Am.
Chem. Soc. 1969, 91, 7166-7169. (b) Fujiwara, Y.; Asano, R.; Moritani,
I.; Teranishi, S. J . Org. Chem. 1976, 41, 1681-1683.
(10) (a) Matsumoto, T.; Yoshida, H. Chem. Lett. 2000, 1064-1065.
(b) Matsumoto, T.; Periana, R. A.; Taube, D. J .; Yoshida, H. J . Catal.
2002, 206, 272-280.
(11) Weissman, H.; Song, X.; Milstein, D. J . Am. Chem. Soc. 2001,
123, 337-338 and references therein.
(12) Dams, M.; De Vos, D. E.; Celen, S.; J acobs, P. A. Angew. Chem.,
Int. Ed. 2003, 42, 3512-3515.
(13) Yokota, T.; Sakaguchi, S.; Ishii, Y. Adv. Synth. Catal. 2002,
344, 849-854.
(14) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J . Am. Chem. Soc.
2003, 125, 1476-1477.
1222 J . Org. Chem., Vol. 69, No. 4, 2004

Oxidative Coupling Reaction of Benzenes with Olefins
TABLE 2. Effect of HP A on Oxid a tive Cou p lin g of
Ben zen e (1a ) w ith Eth yl Acr yla te (2a )a
TABLE 3. Oxid a tive Cou p lin g of Ben zen e (1a ) w ith
Va r iou s Alk en es by th e P d (OAc)2/HP Mo11V1 Ca ta lytic
System u n d er O2 (1 a tm )a
yield (%)b
entry
HPA
conv (%)b 3a a 4a a
5
1
2
3
4
5
6
7
8
9
H4PMo11V1O40‚nH2O (HPMo11V1)
none
100
14
100
96
76
52
44
21
14
74
9
13
0
14
13
4
1
1
0
0
5
1
4
5
5
4
4
0
1
H5PMo10V2O40‚nH2O (HPMo10V2)
H6PMo9V3O40‚nH2O (HPMo9V3)
H7PMo8V4O40‚nH2O (HPMo8V4)
73
70
62
43
37
14
9
H3PMo12O40‚nH2O (HPMo12
)
HPMo11W1O40‚nH2O (HPMo11W1)
HPW10V2O40‚nH2O (HPW10V2)
HPW12O40‚nH2O (HPW12
)
a
A mixture of 1a (30 mmol), 2a (1.5 mmol), Pd(OAc)2 (0.1
mmol), HPA (ca. 0.02 mmol, calculated as n ) 30), NaOAc (0.08
mmol), and acetylacetone (0.1 mmol) in EtCOOH (5 mL) was
placed in a round-bottom flask (30 mL) equipped with a balloon
filled with O2 and allowed to react under stirring at 90 °C for 2.5
b
h. Conversion and yield were based on 2a .
F IGURE 1. Time dependence curves for the oxidative cou-
pling of 1a with 2a under air (1 atm).
in 74% yield after 5 h (entry 13). However, the reaction
under Ar (1 atm) was difficult (entry 14).15a
a
Benzene (30 mmol) was allowed to react with alkene (1.5
mmol) in the presence of Pd(OAc)2 (0.1 mmol), HPMo11V1 (47 mg,
ca. 0.02 mmol), acetylacetone (0.1 mmol), and NaOAc (0.08 mmol)
The yield of coupling products, 3a a and 4a a , was
markedly influenced by the combination of Pd(OAc)2 with
heteropoly acids (HPA) which serve as reoxidation cata-
lysts of the reduced Pd(0) to Pd(II) during the reaction
course (Table 2). When H4PMo11V1O40‚nH2O (HPMo11V1)
was employed as the reoxidation catalyst, 3a a , 4a a , and
5 were obtained in 74%, 13%, and 5% yields, respectively
(entry 1). The reaction was difficult to in the absence of
HPA (entry 2). The catalytic potential of various HPMoV
compounds was affected by the vanadium content in the
HPMoV catalysts (entries 3 to 5). The reaction by the
use of 12-molybdophosphoric acid (HPMo12) not involving
V ion brought about 3a a in somewhat lower conversion
(52%)(entry6).Molybdotungstphosphoricacid (HPMo11W1)
and tungustvanadophosphoric acid (HPW10V2) were found
to be less efficient than HPMoV (entries 7 and 8).
Figure 1 shows the time-dependence curves for the
oxidative coupling of 1a with 2a , using the Pd(OAc)2/
HPMo11V1 system under air atmosphere. The yield of 3a a
increased with time to reach 74% after 5 h, and then the
3a a gradually decreased in contrast to an increase of 4a a .
After 15 h, the yields of 3a a and 4a a were 1% and 81%,
respectively. The time dependence of the reaction clearly
shows that 4a a is formed by the further oxidative
coupling of the resulting 3a a with 1a .
b
in propionic acid (5 mL) at 90 °C for 2.5 h. The number in
parentheses shows the yield of â-phenylcinnamates. c The reaction
was carried out for 12 h.
To extend the present reaction, 1a was allowed to react
with various alkenes under the same conditions as entry
1 in Table 1. These results are shown in Table 3. 1a
reacted smoothly with several acrylates to give the
corresponding cinnamates (68-88%) along with â-phe-
nylcinnamate (11-16%) (entries 1 to 5). The arylation
of 4-phenyl-2-butenone (2e) under these reaction condi-
tions gave 1,1-diphenyl-3-butenone (3a e) in 93% yield
(entry 6). Styrene (2f) and acrylonitrile (2g) reacted with
difficulty to generate the corresponding product, 3a f and
3a g, in 31% and 9% yields, respectively (entry 7 and 9).
3a f, however, reacted smoothly with 1a to give the
triphenylethylene (4a f) in 76% yield (entry 8).
Table 4 summarizes the oxidative coupling of various
arenes with 2a under several conditions. The reaction of
toluene (1b) with 2a afforded an isomeric mixture of
coupling products 3ba (70%) consisting of o-3ba :m-3ba :
p-3ba ) 15:41:44 (entry 1). Anisole (1c) coupled with 2a
even at 60 °C to give a mixture of coupling products 3ca
(o-3ca :m-3ca :p-3ca ) 17:7:76) in 73% yield (entry 2). It
is interesting that the reaction of chlorobenzene (1d ) and
bromobenzene (1e) with 2a gave the corresponding
coupling products, 3d a and 3ea , in 74% and 49% yields,
(15) (a) Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171-198. (b)
Nomiya, K.; Yagishita, K.; Nemoto, Y.; Kamataki, T. J . Mol. Catal. A:
Chemical 1997, 126, 43-53.
J . Org. Chem, Vol. 69, No. 4, 2004 1223

Tani et al.
TABLE 4. Oxid a tive Cou p lin g of Va r iou s Ar en es w ith
Eth yl Acr yla te (2a ) by th e P d (OAc)2/HP Mo11V1 Ca ta lytic
System u n d er O2 (1 a tm )a
F IGURE 2. TON of Pd(OAc)2 combined with various HPMoV
compounds for the reaction of 1a with 2a . Reaction condi-
tions: 1a (45 mmol) was allowed to react with 2a (3 mmol) in
the presence of Pd(OAc)2 (0.03 mmol), HPMoV (0.02 mmol),
NaOAc (0.08 mmol), and acetylacetone (0.03 mmol) in Et-
COOH (5 mL) under O2 (1 atm) at 90 °C for 12 h.
coupling of 1a with 2a . It was found that TON of Pd-
(OAc)2 was markedly affected by the vanadium content
in the HPMoV catalysts. Increasing V content in HPMoV
resulted in the decrease of TON of the Pd(OAc)2. The
highest total TON (76) was obtained when HPMo11V1 was
employed.
In the oxidative coupling reaction of benzene to biphe-
nyl under O2, we reported that a 1:1 mixture of HPMo11V1
and HPMo12 as the reoxidation catalyst was the most
efficient system for the Pd-catalyzed oxidative coupling
of benzene to biphenyl under O2 (1 atm).13 In the present
reaction, the similar synergy effect of HPMo11V1 and
HPMo12 was observed. Thus, the reaction by Pd(OAc)2
combined with a 1:1 mixture of HPMo11V1 and HPMo12
gave the best TON (121) of Pd (eq 2). Recently J ocob
a
Arene (30 mmol) was allowed to react with ethyl acrylate (1.5
mmol) in the presence of Pd(OAc)2 (0.1 mmol), HPMo11V1 (47 mg,
ca. 0.02 mmol), acetylacetone (0.1 mmol), and NaOAc (0.08 mmol)
in propionic acid (5 mL). Ratio of ortho:meta:para. c Ethyl cin-
b
namate (2a ) was obtained in 5%. Arene (5 mmol) was used. e 2,3-
d
Dimethoxy cinnamate was formed in 3% yield. f Ratio of 2,3-
methylenedioxy cinnamate (3ga ): 3,4-methylenedioxy cinnamate
(3′ga ). g Arene (3 mmol) was used. 5 wt % of Pd(OAc)2/C was used
h
instead of Pd(OAc)2.
respectively, in preference to the Mizoroki-Heck reaction
(entries 3 and 4). In the reaction of 1d with 2a , no
ethylcinnamate 3a a based on the Mizoroki-Heck reac-
tion was observed, but a small amount (5%) of 3a a was
formed when 1e was employed. The reaction of 1,2-
dimetoxybenzene (1f) with 2a afforded ethyl 3,4-dimetoxy
cinnamate (3fa ) (67%) and a small amount of its isomer,
2,3-dimetoxy cinnamate (3%) (entry 5). The reaction of
1,2-methylenedioxybenzene (1g) with 2a led to a 40:60
mixture of 2,3- and 3,4-methylenedioxy cinnamates (3ga
and 3′ga ) in 65% yield (entry 6). The reaction of 2-me-
thylthiopene (1h ) with 2a under these conditions did not
take place at all. It is interesting to note that Pd(OAc)2
supported on active carbon, Pd(OAc)2/C, was efficient for
the coupling of 1h with 2a to give the corresponding
coupling product, 3h a , in satisfactory yield (86%) (entry
7). Owing to the strong coordination of the sulfur atom
of the 1h to the Pd(OAc)2, the coordination of olefin 2a
to the Pd species may be difficult. However, the coordina-
tion of 2a to the Pd on carbon needed for the coupling
with 1h may be possible, since 1h is strongly adsorbed
on activated carbon. Furan (1i) gave the corresponding
coupling product 3ia (47%) along with double coupling
product 4ia (11%).
reported that the TON of Pd(OAc)2 reached 762 in the
reaction of anisole with ethyl trans-cinnamate under 8
atm of O2 at 90 °C.12 To our knowledge, our result is the
best TON for the oxidative coupling of 1a with 2a under
atmospheric dioxygen (1 atm).
To obtain further information on HPMoV used, 31P
NMR spectra of HPMo11V1 (a), HPMo12 (b), and a 1:1
mixture of HPMo12 and HPMo11V1 (c) were measured
(Figure 3). A single peak was observed at δ -2.26 in
HPMo12, while HPMo11V1 indicated principally two main
peaks, δ -2.26 and -1.61, and several small peaks. One
of two main peaks obtained from HPMo11V1 was the same
as that of HPMo12. Another peak (δ -1.61) is attributed
Figure 2 shows the turn-over number (TON) of Pd-
(OAc)2 combined with various HPMoV for the oxidative
1224 J . Org. Chem., Vol. 69, No. 4, 2004

Oxidative Coupling Reaction of Benzenes with Olefins
F IGURE 3. 31P NMR spectra of (a)HPMo12, (b)HPMo11V1, and
(c) a 1:1 mixture of HPMo12 and HPMo11V1 in acetic acid.
F IGURE 5. A possible reaction path for the coupling of arene
with acrylate.
complex [A] reacts with an alkene like acrylate 2 to give
a σ-alkyl-palladium(II) complex [B]. â -Hydride elimina-
tion of B liberates Pd-H to give the coupling product 3.
The Pd-H is readily reduced to Pd(0), and the resulting
Pd(0) is reoxidized by [HPMoV]ox to generate Pd(II). The
[HPMoV]red is oxidized with O2 to [HPMoV]ox.
Con clu sion
F IGURE 4. The time dependence of 3a a and 3a -d a in two
separate reactions of benzene 1a or benzene-d6 (1a -d ) with 2a
under the same conditions as entry 1 in Table 1.
An efficient catalytic system for the oxidative coupling
of arenes with alkenes through the aromatic C-H bond
activation was developed. Thus, oxidative coupling of
benzene with acrylates using dioxygen as terminal
oxidant could be achieved by Pd(OAc)2 combined with
HPMoV as reoxidation catalyst under O2. The reaction
was smoothly promoted under air (1 atm) to give the
corresponding coupling products in satisfactory yields.
Furthermore, this catalytic system could be extended to
the reaction of various aromatic compounds with alkenes.
By the use of a 1:1 mixture of HPMo11V1 and HPMo12,
the best TON (121) of Pd was obtained in the coupling
reaction of benzene 1a with ethyl acrylate 2a .
to HPMo11V1.13,15 Several small peaks around δ -1 may
be based on HPMo12-XVX (X g 2). These results indicate
that HPMo11V1 available from commercial source is a
mixture of HPMo12, HPMo11V1, and HPMo12-XVX (X g 2).
The 31P NMR spectrum from a 1:1 mixture of HPMo12
and HPMo11V1, which led to the best TON, showed two
main peaks based on HPMo12 and HPMo11V1. Although
the synergistic effect by mixing of two different types of
HPMoV is not clear at this stage, a new signal was not
observed by mixing HPMo12 and HPMo11V1.
To obtain mechanistic information on the present
reaction, the initial rate of the reaction of benzene 1a
Exp er im en ta l Section
with 2a was compared with that of benzene-d6 (1a -d
)
Gen er a l. All solvents and reagents ware purchased from
commercial sources and used without further purification. All
heteropoly acids were obtained from Nippon Inorganic Colour
& Chemical Co., Ltd., except for HPMo12 (from Wako). Ana-
lytical TLC was performed on Merck TLC Plastic sheets F254
silica gel 60, using UV light and I2. GLC analysis was
with 2a under the same conditions (Figure 4). It was
found that the reaction rate of 1a with 2a was about four
times faster than that of benzene-d6 (1a -d ) with 2a , i.e.
kH/kD Z 4. The same results (kH/kD Z 4) were obtained
by the reaction of a 1:1 mixture of 1a and 1a -d with
2a under these conditions. A kinetic isotope effect for
the coupling of 1a with methyl acrylate is reported
to be kH/kD ) 2.10 No scrambling of deuterium was
observed. These facts indicate that the cleavage of the
C-H bond of 1a is the slowest step in a sequence of
reactions.
performed on Shimadzu GC-17A equipped with
a flame
ionization detector, using a 0.22 mm × 25 m capillary column.
Mass spectra were determined at an ionization energy of 70
eV. Visible spectra were recorded on a Shimadzu UV-2500PC
spectrometer. NMR spectra were recorded on a J EOL J EM-
EX-270. 1H and 13C NMR were measured at 270 and 67.5 MHz,
respectively, in CDCl3 with Me4Si as the internal standard.
31P NMR was measured at 109.25 MHz in AcOH with 85%
H3PO4 in a sealed capillary as the external standard. The
chemical shifts were reported on the δ scale with resonances
upfield of H3PO4 (δ 0) as negative.
The coupling reaction is considered to proceed via a
reaction path similar to that proposed by Fujiwara et al.
A plausible reaction path is shown in Figure 5. The
reaction may be initiated by the electrophilic attack of a
Pd(II) to arene 1 leading to a σ-aryl-palladium(II) com-
plex [A]. From the labeled experiment, this step is
considered to be the slowest. The σ-aryl-palladium(II)
Gen er a l P r oced u r e for Oxid a tive Cou p lin g of Ben -
zen e (1a ) w ith Eth yl Acr yla te (2a ). A solution of Pd(OAc)2
(0.1 mmol), H4PMo11V1O40‚nH2O (HPMo11V1, n ) 30) (46.7 mg,
ca. 0.02 mmol), NaOAc (0.08 mmol), acetylacetone (0.1 mmol),
J . Org. Chem, Vol. 69, No. 4, 2004 1225

Tani et al.
benzene (1a ) (30 mmol), and ethyl acrylate (2a ) (1.5 mmol) in
propionic acid (5 mL) was placed in a round-bottom flask (30
mL) equipped with a balloon filled with O2, and the mixture
was allowed to react under stirring at 90 °C for 2.5 h. The
reaction gave ethyl cinnamate (3a a ), â-phenylcinnamate (4a a ),
and 3-propionylacrylate (5) in 74%, 14%, and 5% yields,
respectively. All yields were detected by GLC analysis with
nonane as internal standard. The products were characterized
MHz, CDCl3) δ 1.32 (t, J ) 7.2 Hz, 3H), 4.24 (q, J ) 7.2 Hz,
2H), 6.31 (d, J ) 15.7 Hz, 1H), 7.42 (d, J ) 15.7 Hz, 1H), 6.45-
7.47 (m, 3H); 13C NMR (67.5 MHz, CDCl3) δ 14.4, 60.4, 112.1,
114.5, 115.9, 130.8, 144.5, 150.8, 166.8. 3i′a : 1H NMR (270
MHz, CDCl3) δ 1.33 (t, J ) 7.2 Hz, 6H), 4.26 (q, J ) 7.2 Hz,
4H), 6.42 (d, J ) 15.7 Hz, 2H), 6.64 (s, 2H), 7.38 (d, J ) 15.7
Hz, 2H); 13C NMR (67.5 MHz, CDCl3) δ 14.4, 60.6, 116.5, 118.0,
129.9, 152.3, 166.4.
Da ta for n ew com p ou n d s: eth yl cin n a m a te-d 5 (3a -d a ):
1H NMR (270 MHz, CDCl3) δ 1.27 (t, J ) 7.1 Hz, 3H), 4.19 (q,
J ) 7.1 Hz, 2H), 6.36 (d, J ) 16.0 Hz, 1H), 7.62 (d, J ) 16.0
Hz, 1H); HRMS (EI) calcd for C11H7D5O2 [M]+ 181.1151, found
181.1142. 3-P r op ion yloxya cr yla te (5): 1H NMR (270 MHz,
CDCl3) δ 1.21 (t, J ) 7.8 Hz, 3H), 1.29 (t, J ) 7.0 Hz, 3H),
2.50 (q, J ) 7.8 Hz, 2H), 4.20 (q, J ) 7.0 Hz, 2H), 5.70 (d, J )
12.6 Hz, 1H), 8.30 (d, J ) 12.6 Hz, 1H); 13C NMR (67.5 MHz,
CDCl3) δ 8.60, 14.3, 27.2, 60.4, 105.6, 149.3, 166.0, 170.2;
HRMS (EI) calcd for C8H12O4 [M]+ 172.0736, found 172.0747.
1
by H and 13C NMR and GC-MS, respectively.
3a c, 3a d , 3ba , 3ca , 3d a , 3ea , 3fa , and 3ga were obtained
by the independent esterification of the corresponding cin-
namic acids available from commercial source and identified
through the comparison of the isolated products with authentic
samples. 3a a , 3a b 3a f, 4a f, and 3a g were commercially
available and 3a e11 3h a ,16 3ia ,11 4a a ,11 and 4i′a 11 were
reported previously.
3a e: 1H NMR (270 MHz, CDCl3) δ 1.88 (s, 3H), 0.98 (s, 1H),
7.19-7.42 (m, 10H); 13C NMR (67.5 MHz, CDCl3) δ 30.3, 127.3,
127.8, 128.3, 128.6, 129.3, 138.8, 140.6, 153.8, 200.0. 3h a : 1H
NMR (270 MHz, CDCl3) δ 1.31 (t, J ) 7.0 Hz, 3H), 2.47 (s,
3H), 4.20 (q, J ) 7.0 Hz, 2H), 6.08 (d, J ) 15.7 Hz, 1H), 6.68
(d, J ) 3.4 Hz, 1H), 7.02 (d, J ) 3.4 Hz, 1H), 7.67 (d, J ) 15.7
Hz, 1H); 13C NMR (67.5 MHz, CDCl3) δ 14.4, 15.8, 60.3, 115.4,
126.3, 131.4, 137.2, 137.4, 143.7, 166.8. 3ia : 1H NMR (270
Ack n ow led gm en t. This work was partially sup-
ported by a Grant-Aid for Scientific Research (KAK-
ENHI) (S) (No. 15036265) from the J apan Society for
the Promotion of Science (J SPS). All heteropoly acids
except HPMo12 were contributed by Nippon Inorganic
Colour & Chemical Co., Ltd.
(16) Schmodt, R. R.; Hirsenkorn, R. Tetrahedron 1983, 39, 2043-
2054.
J O035568F
1226 J . Org. Chem., Vol. 69, No. 4, 2004