Oxidative coupling of benzenes with α,β-unsaturated aldehydes by the Pd(OAc)2/molybdovanadophosphoric acid/O2 system

Article abstract of DOI:10.1021/jo050534o

The oxidative coupling reaction of benzene with an α,β- unsaturated aldehyde was examined by the combined catalytic system of Pd(OAc)₂ with molybdovanadophosphoric acid (HPMoV) under atmospheric dioxygen. Thus, the reaction of benzene with acrolein under dioxygen (1 atm) by the use of catalytic amounts of Pd(OAc)₂ and H₄PMo ₁₁VO₄₀·26H₂O in the presence of dibenzoylmethane as a ligand in propionic acid at 90 °C for 1.5 h afforded cinnamaldehyde in 59% yield and β-phenylcinnamaldehyde in 5% yield. This catalytic system was extended to the direct oxidative coupling through the C-H bond activation of various arenes with acrolein and methacrolein.

Full text of DOI:10.1021/jo050534o

Oxidative Coupling of Benzenes with r,â-Unsaturated Aldehydes
by the Pd(OAc)2/Molybdovanadophosphoric Acid/O2 System
Tomoyuki Yamada, Satoshi Sakaguchi, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita,
Osaka 564-8680, Japan
ishii@ipcku.kansai-u.ac.jp
Received March 16, 2005
The oxidative coupling reaction of benzene with an R,â-unsaturated aldehyde was examined by
the combined catalytic system of Pd(OAc)2 with molybdovanadophosphoric acid (HPMoV) under
atmospheric dioxygen. Thus, the reaction of benzene with acrolein under dioxygen (1 atm) by the
use of catalytic amounts of Pd(OAc)2 and H4PMo11VO40‚26H2O in the presence of dibenzoylmethane
as a ligand in propionic acid at 90 °C for 1.5 h afforded cinnamaldehyde in 59% yield and
â-phenylcinnamaldehyde in 5% yield. This catalytic system was extended to the direct oxidative
coupling through the C-H bond activation of various arenes with acrolein and methacrolein.
Result and Discussion
Pd(OAc)2 to form cinnamaldehyde.5 To our best knowl-
edge, however, there is no report so far on the Pd-
catalyzed direct coupling of benzene with acrolein. There-
fore, it is very interesting to examine the oxidative
coupling of benzene with acrolein. Recently, we have
successfully carried out the Heck-Mizoroki reaction
through the direct C-H bond activation of benzenes with
acrylates by the use of Pd(OAc)2 combined with molyb-
dovanadophosphoric acid (HPMoV) under air.6 In this
paper, we report the first direct oxidative coupling
reaction of benzene (1) with acrolein (2), leading to
cinnamaldehyde (3) and â-phenylcinnamaldehyde (4) by
the Pd(OAc)2/HPMoV/O2 system (eq 1), although the
coupling is not fully successful owing to the difficulty in
suppressing the polymerization of 2.
The arylation of olefins represented by the Heck-
Mizoroki reaction is an important synthetic tool for
constructing C-C bonds, and the reaction is carried out
between various aryl halides and substituted alkenes,
especially electron-deficient alkenes having -COOR and
-CN groups. However, there have been only a few
reports on the coupling reaction of aryl halides with R,â-
unsaturated aldehydes such as acrolein. The first trial
of arylation with acrolein was made by using diaryl-
mercury compounds and LiPdCl3 as the arylating com-
bination.1 Jeffery reported the Pd-catalyzed coupling
reaction of phenyl, m-tolyl, and p-chlorophenyl iodides
with acrolein in the presence of Bu4NCl.2 To avoid the
polymerization problem of aldehydes, acrolein dimethyl
acetal, a synthetic equivalent of acrolein, is used instead
of acrolein, and the reaction with bromobenzene by
Pd(OAc)2 in the presence of a tri-o-tolylphosphine ligand
and triethylamine as a base is reported to give a mixture
of cinnamaldehyde dimethyl acetal (56%) and methyl
3-phenylpropionate (39%).3 Quite recently, Cacchi et al.
showed the Pd-catalyzed coupling of aryl iodides and
bromides with acrolein diethyl acetal, leading to the
corresponding cinnamaldehydes in good yields.4 It is
reported that dimethyl(phenyl)silanol reacts with ac-
rolein in the presence of a stoichiometric amount of
The representative results for the coupling reaction
between 1 and 2 using the Pd(OAc)2/HPMoV/O2 system
(5) Hirabayashi, K.; And, J.; Kawashima, J.; Nishihara, Y.; Mori,
A.; Hiyama, T. Bull. Chem. Soc. Jpn. 2000, 73, 1409.
(6) (a) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J. Am. Chem.
Soc. 2003, 125, 1476. (b) Tani, M.; Sakaguchi, S.; Ishii, Y. J. Org. Chem.
2004, 69, 1221.
(1) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518.
(2) Jeffery, T. J. Chem. Soc., Chem. Commun. 1984, 1287.
(3) Zebovitz, T. C.; Heck, R. F. J. Org. Chem. 1977, 42, 3907.
(4) Battistuzzi, G.; Cacchi, S.; Fabrizi, G. Org. Lett. 2003, 5, 777.
10.1021/jo050534o CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/09/2005
J. Org. Chem. 2005, 70, 5471-5474
5471

Yamada et al.
TABLE 1. Oxidative Coupling of 1 with 2 by the
Pd(OAc)2/H4PMo11VO40‚26H2O/O2 System under Various
Conditionsa
yield/%
run
ligand
time/h
conv/%
3
4
1
2
DBM
DBM
DBM
DBM
DBM
1.5
2
94
96
97
61
95
76
92
85
96
74
82
72
93
59
45
17
26
53
33
52
48
54
3
5
18
40
0
3
3
4
1
5b
6
1.5
1.5
1.5
1.5
2
6
0
7
BA
AA
AA
AA
AA
6
8
1
9
8
10c
11d
12e
13f
2
0
FIGURE 1. Time-dependence curves of the coupling reaction
of 1 with 2.
2
44
5
52
2
2
5
DBM
1.5
5
TABLE 2. Oxidative Coupling of 1 with 2 by Pd(OAc)2
Combined with Several HPAsa
a Benzene (1) (30 mmol) was reacted with acrolein (2) (1.5 mmol)
by Pd(OAc)2 (0.1 mmol), H4PMo11VO40‚26H2O (45.2 mg. ca. 0.02
mmol), Na2CO3 (0.05 mmol), and ligand (0.1 mmol) under O2 (1
atm) in EtCOOH (5 mL) at 90 °C. b 1 (20 mmol) was used. c In
the absence of Na2CO3. d NaOAc (0.08 mmol) was used instead of
Na2CO3. e Pd(acac)2 was used instead of Pd(OAc)2. f In the presence
of BHT (0.05 mmol).
yield/%
run
HPA
conv/%
3
4
1
2
3
4
5
6
H4PMo11VO40‚26H2O
H5PMo10V2O40‚28H2O
H6PMo9V3O40‚30H2O
H7PMo8V4O40‚28H2O
H5PW10V2O40‚27H2O
H3PMo12O40‚30H2O
94
92
93
80
28
66
59
54
47
35
0
5
6
6
1
0
0
are shown in Table 1. To suppress the polymerization of
2, the reaction was carried out using excess benzene (1)
with respect to 2. From the practical synthetic viewpoint,
it is important for 1 of low boiling point to be easily
recovered from the reaction mixture. Thus, the reaction
of 1 (30 mmol) with 2 (1.5 mmol) in the presence of
Pd(OAc)2 (0.1 mmol), H4PMo11VO40‚26H2O (45.2 mg, ca.
0.02 mmol), Na2CO3 (0.05 mmol), and dibenzoylmethane
(DBM) (0.1 mmol) under O2 (1 atm) in propionic acid (5
mL) at 90 °C for 1.5 h afforded 3 in 59% yield along with
4 (5%) formed by the further coupling of the resulting 3
with 1 (run 1). In the present reaction, the yield of
cinnamic acid, a further oxidation product of 3, was found
to be less than 2%. Because of the easy polymerization
of 2, the desired coupling product 3 was difficult to obtain
in high yield. But it is important to note that the direct
oxidative coupling of 1 with 2, leading to 3, was first
performed by the Pd(OAc)2/HPMoV/O2 system. When the
reaction was prolonged to 3 h, dicoupling product 4
became a major product rather than 3 (run 3). The yield
of 3 was found to become maximum in the reaction for
1.5 h (run 4). The amount of 1 was reduced to 20 mmol,
but the result was almost the same as that of the reaction
using 30 mmol of 1 (run 5). The reaction lacking a DBM
ligand resulted in a slight decrease of the yield of 3 (run
6). Thus, the effect of several ligands on the present
coupling reaction was examined. The use of benzoyl-
acetone (BA) led to a result similar to that of DBM (run
7). The use of acetylacetone (AA) instead of DBM needed
a longer reaction time (runs 8 and 9). The reaction in
the absence of Na2CO3 resulted in a considerable decrease
of the selectivity in the coupling product 3, and several
unidentified products (probably oligomers of 2) were
formed (run 10). A similar effect was observed when
NaOAc was added to the catalytic solution (run 11). It
was found that the base inhibited the polymerization of
2. When Pd(acac)2 was employed in place of Pd(OAc)2, 3
was formed in poor selectivity (run 12). To suppress the
polymerization of 2, the reaction was examined in the
presence of a radical inhibitor such as 2,6-di-tert-butyl-
24
a Benzene (1) was reacted with acrolein (2) under the same
conditions as run 1 in Table 1 except for HPA.
4-methylphenol (BHT), but the result was almost the
same as that in the absence of BHT (run 13). This fact
shows that 2 is not polymerized through a radical process.
Figure 1 shows the time-dependence curves for the
coupling products 3 and 4 in the reaction of 1 with 2.
Although 2 was immediately consumed when the reaction
started, a short induction period was observed till the
formation of coupling product 3. The coupling product 3
was attained maximum after 1.5 h, and gradually
decreased because of further coupling with 1, leading to
dicoupling product 4. An independent reaction of 3 with
1 under these conditions produced 4 in fair yield (61%)
(eq 2).
Table 2 shows the coupling reaction of 1 with 2 by the
combination of Pd(OAc)2 with several heteropoly acids
(HPAs). The reaction by the combined catalyst of Pd(OAc)2
with H5PMo10V2O40‚28H2O gave 3 and 4 in 54% and 6%
yield, respectively (run 2). The employment of H6-
PMo9V3O40‚30H2O and H7PMo8V4O40‚28H2O as HPMoV
brought about a slight decrease of coupling products 3
and 4 (runs 3 and 4). However, vanadotungstphosphoric
acid (H5PW10V2O40‚27H2O) did not catalyze the coupling
reaction at all (run 5). H3PMo12O40‚30H2O not containing
a vanadium atom was found to be less efficient than
HPMoV (run 6).
5472 J. Org. Chem., Vol. 70, No. 14, 2005

Coupling of Benzenes with R,â-Unsaturated Aldehydes
TABLE 3. Oxidative Coupling of Substituted Benzenes
(Ar-H) with 2 by the Pd(OAc)2/H4PMo11VO40‚26H2O/O2
Systema
Table 4 shows the results of the oxidative coupling of
substituted benzenes with 15. In these reactions, mono-
coupling products were obtained as a mixture of struc-
tural isomers such as 16a-16c along with small amounts
of the corresponding dicoupling product 17 depicted in
eq 3. The reaction of 15 with tert-butylbenzene (7) pro-
duced mainly four monocoupling products corresponding
to 16 in 66% yield. Due to difficulty of the isolation of
these products, the hydrogenation with H2 (1 atm)
catalyzed by Pd/C was performed. After the hydrogena-
tion, meta and para products 18 were found to be formed
(meta:para ) 56:44) without formation of the ortho
isomer (run 1). Similarly, the coupling reaction of 15 with
cumene (19) followed by hydrogenation produced a regio-
isomeric mixture (o-20:m-20:p-20 ) 9:51:40) (run 2).
p-Xylene (21) coupled with 15 to form a single coupling
product which, after hydrogenation, produced 22 (run 3).
In the reaction of anisole (9) with 15, the corresponding
monocoupling products consisting of o-23:m-23:p-23 ) 18:
7:75 after the hydrogenation were obtained (run 4). 1,2-
Methylenedioxybenzene (13) produced the corresponding
monocoupling products which formed a 40:60 mixture of
R-methyl-1,3-benzodioxole-4-propanal (24a) and R-meth-
yl-1,3-benzodioxole-5-propanal (24b) by hydrogenation
(run 5).
a Method A: The reaction was carried out by the same method
as run 1 in Table 1. Method B: The reaction was carried out by
the same method as run 9 in Table 1. Method C: The method is
the same as method B, except using Ar-H (10 mmol) for 1 h.
b Ratio of ortho to meta to para isomers. c 2,3-Dimethoxycinnam-
aldehyde was in 2% yield. d Ratio of 2,3-methylenedioxycinnam-
aldehyde (14a) to 3,4-methylenedioxycinnamaldehyde (14b).
On the basis of these results, several substituted
benzenes were reacted with 2 under varying conditions
(Table 3). The reaction of toluene (5) with 2 afforded a
mixture of structural isomers 6 (ortho:meta:para ) 13:
44:43) in 59% yield along with small amounts of dicou-
pling products (run 1). An almost similar result was
obtained when the reaction was carried out using AA in
place of DBM (run 2). In the reaction with tert-butylben-
zene (7), the ortho product was not detected because of
its steric hindrance (runs 3 and 4). Anisole (9) coupled
with 2 to give a mixture of the corresponding coupling
products 10 (ortho:meta:para ) 17:10:73) in 45% yield
(run 5). The reaction of 1,2-dimethoxybenzene (11) with
2 proceeded in high regioselectivity to produce 3,4-di-
methoxycinnamaldehyde (12) (47%), and the yield of
2,3-dimethoxycinnamaldehyde was found to be less than
2% (run 6). In contrast, the reaction of 1,2-methylene-
dioxybenzene (13) with 2 led to a 45:55 mixture of 2,3-
and 3,4-methylenedioxycinnamaldehydes (14a and 14b)
in 45% yield (run 7).
SCHEME 1
In conclusion, we have shown the first direct oxidative
coupling of arenes with R,â-unsaturated aldehydes. Thus,
the direct oxidative coupling of aromatic hydrocarbons
with acrolein (2) could be performed by Pd(OAc)2 com-
bined with H4PMo11VO40‚26H2O using dioxygen as the
terminal oxidant to produce the corresponding coupling
products in moderate yields. This synthetic method would
The oxidative coupling of methacrolein (15) with 1 was
examined (eq 3).
In this reaction, three isomeric coupling products
consisting of 16a, 16b, and 16c were obtained in 54%
yield (16a:16b:16c ) 65:6:29) and dicoupling product 17
was obtained in 7% yield. The formation of 16a, 16b, and
16c can be rationally explained by reaction paths a and
b, through phenylpalladium intermediate II formed by
the insertion of phenylpalladium σ-complex I into 15
(Scheme 1).7
(7) Jia, C.; Lu, W.; Kitamura, T.; Fujiwara, Y. Org. Lett. 1999, 1,
2097.
J. Org. Chem, Vol. 70, No. 14, 2005 5473

Yamada et al.
TABLE 4. Oxidative Coupling of Substituted Benzenes
(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 h. After the reaction, the
reaction mixture was diluted with ethyl acetate and extracted
with the saturated sodium hydrogen carbonate solution. The
organic layer was dried over MgSO4 and concentrated by using
a rotary vacuum evaporator. The crude products was reacted
under H2 (1 atm) in the presence of 5 wt % Pd/C (50 mg) in
ethyl acetate (10 mL) at 40 °C for 8 h. The products were
isolated by flash chromatography on silica gel (n-hexane/ethyl
acetate, 95:5).
with 15 by the Pd(OAc)2/H4PMo11VO40‚26H2O/O2 Systema
The products 18 and 20 were converted into the correspond-
ing carboxylic acids 18′ and 20′ during the isolation process.
4,8 6,4 p-8,9 10,4 12,10 14,11 16,12 17,13 m-18,14 20,15 22,16 23,17
and 24a17 are known compounds and have been reported
previously. 3, m- and p-10, p-18, p-18′, p-20, p-20′, and 24b
are commercially available.
Data for r-methyl-1,3-benzodioxole-4-propanal (24a):
1
light yellow liquid; H NMR (270 MHz, CDCl3) δ 1.10 (d, J )
6.71 Hz, 3 H), 2.57-2.79 (m, 2H), 2.98-3.05 (m, 1 H), 5.91 (s,
2 H), 6.62-6.62 (m, 3 H), 9.70 (s, 1 H); 13C NMR (67.5 MHz,
CDCl3) δ 13.3, 30.5, 46.5, 100.5, 106.9, 120.2, 121.4, 123.0,
145.5, 146.9, 204.0; IR (GC-IR) 726, 836, 942, 1061, 1171,
1250, 1351, 1460, 1743, 2706, 2880, 2939, 2979; MS m/z 77,
135, 164, 192; HRMS (EI) m/z calcd for C11H12O3 [M]+
192.0786, found 192.0797.
a Method D: The reaction was carried out under the same
conditions as eq 3. Method E: Ar-H (20 mmol), EtCOOH (4 mL),
3 h. Method F: Ar-H (10 mmol), EtCOOH (4 mL), 70 °C, 4 h.
Method G: The method is the same as method F, except for 3 h.
b The structure of the coupling products was identified after
hydrogenation of the resulting mixture by H2 (1 atm) on Pd/C.
c The yields are given for regioisomeric mixtures of the monocou-
pling products corresponding to 16. d Ratio of ortho to meta to para
isomers. e Ratio of R-methyl-1,3-benzodioxole-4-propanal (24a) to
R-methyl-1,3-benzodioxole-5-propanal (24b).
Acknowledgment. This work was partially sup-
ported by a Grant-Aid for Scientific Research (KAK-
ENHI) (S) (No. 13853008) from the Japan Society for
the Promotion of Science (JSPS). All heteropolyacids
were contributed by Nippon Inorganic Chemical Co.,
Ltd.
Supporting Information Available: 1H and 13C NMR,
IR, MS, and HRMS spectral data of 4, 6, 8, 12, 14, 16, 17, 18,
18′, 20, 20′, 22, 23, and 24. This material is available free of
charge via the Internet at http://pubs.acs.org.
provide an alternative route to a variety of cinnamalde-
hyde derivatives.
Experimental Section
JO050534O
Procedure for Oxidative Coupling of 1 with 2. A
solution of Pd(OAc)2 (0.1 mmol), H4PMo11V1O40‚26H2O (45.2
mg, ca. 0.02 mmol), Na2CO3 (0.05 mmol), dibenzoylmethane
(0.1 mmol), 1 (30 mmol), and 2 (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 1.5 h. After the reaction, the
reaction mixture was diluted with ethyl acetate and extracted
with the saturated sodium hydrogen carbonate solution. The
organic layer was dried over MgSO4 and concentrated by using
a rotary vacuum evaporator. The residue was purified by flash
chromatography on silica gel (n-hexane/ethyl acetate, 95:5) to
give the oxidative coupling products. Yields were determined
by GLC analysis using dodecane as internal standard. The
products were characterized by 1H and 13C NMR, GC-MS, and
GC-IR. The yield of cinnamic acid was determined by LC
analysis.
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A Typical Procedure for Oxidative Coupling of 7 with
15. A solution of Pd(OAc)2 (0.1 mmol), H4PMo11V1O40‚26H2O
(45.2 mg, ca. 0.02 mmol), NaOAc (0.08 mmol), acetylacetone
(0.1 mmol), 7 (30 mmol), and 15 (1.5 mmol) in propionic acid
5474 J. Org. Chem., Vol. 70, No. 14, 2005