Palladium(II)/Cationic 2,2'-Bipyridyl system as a highly efficient and reusable catalyst for the Mizoroki-Heck reaction in water

Article abstract of DOI:10.3390/molecules15010315

A water-soluble and air-stable Pd(NH₃)₂Cl ₂/cationic 2,2'-bipyridyl system was found to be a highly-efficient and reusable catalyst for the coupling of aryl iodides and alkenes in neat water using Bu3N as a base. The reaction was conducted at 140 °C in a sealed tube in air with a catalyst loading as low as 0.0001 mol % for the coupling of activated aryl iodides with butyl and ethyl acrylates, providing the corresponding products in good to excellent yields with very high turnover numbers. In the case of styrene, Mizoroki-Heck coupling products were obtained in good to high yields by using a greater catalyst loading (1 mol %) and TBAB as a phase-transfer agent. After extraction, the residual aqueous solution could be reused several times with only a slight decrease in its activity, making the Mizoroki-Heck reaction "greener".

Full text of DOI:10.3390/molecules15010315

Molecules 2010, 15, 315-330; doi:10.3390/molecules15010315
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Palladium(II)/Cationic 2,2’-Bipyridyl System as a Highly
Efficient and Reusable Catalyst for the Mizoroki-Heck Reaction
in Water
Shao-Hsien Huang, Jun-Rong Chen and Fu-Yu Tsai *
Institute of Organic and Polymeric Materials, National Taipei University of Technology, 1, Section 3,
Chung-Hsiao E. Rd., Taipei 106, Taiwan
* Author to whom correspondence should be addressed; E-Mail: fuyutsai@ntut.edu.tw.
Received: 18 December 2009; in revised form: 8 January 2009 / Accepted: 12 January 2010 /
Published: 12 January 2010
Abstract: A water-soluble and air-stable Pd(NH3)2Cl2/cationic 2,2’-bipyridyl system was
found to be a highly-efficient and reusable catalyst for the coupling of aryl iodides and
alkenes in neat water using Bu3N as a base. The reaction was conducted at 140 °C in a
sealed tube in air with a catalyst loading as low as 0.0001 mol % for the coupling of
activated aryl iodides with butyl and ethyl acrylates, providing the corresponding products
in good to excellent yields with very high turnover numbers. In the case of styrene,
Mizoroki-Heck coupling products were obtained in good to high yields by using a greater
catalyst loading (1 mol %) and TBAB as a phase-transfer agent. After extraction, the
residual aqueous solution could be reused several times with only a slight decrease in its
activity, making the Mizoroki-Heck reaction “greener”.
Keywords: Mizoroki-Heck reaction; water-soluble catalyst; reusable; cross-coupling
1. Introduction
Palladium-catalyzed coupling of aryl halides and alkenes, known as the Mizoroki-Heck reaction, is
one of the most powerful processes available in organic synthesis for carbon–carbon bond formation
[1,2]. This reaction is greatly facilitated in polar aprotic solvents such as DMA, DMF, DMSO, MeCN,
and NMP under homogeneous catalysis (for recent reviews, see refs. [3–6]). However, the catalyst and
organic products are often of similar solubility in organic solvents, and hence it is difficult to separate

Molecules 2010, 15
316
the catalyst from the reaction mixture and recycle it at the end of the reaction, leading to wastage of
precious metals. Because water is an organic immiscible solvent, the introduction of a water-soluble
ligand to combine with transition-metal catalysts and use of water as the reaction medium is one of the
best methods of overcoming this problem (for recent reviews, see refs. [7–14]), although the reaction
rates of organic reactions in water may be slower than in organic solvents due to the low effective
concentration of the organic substrate in the aqueous phase. The water-soluble catalytic system may be
easily separated from the water-insoluble organic products by simple filtration or extraction, leading to
the possibility of reuse of the catalyst. Therefore, the development of a water-compatible and reusable
catalytic system is highly attractive and valuable from the green chemistry and economics viewpoints.
There are some reports of the Mizoroki-Heck reaction being performed in neat water, which include
reactions in the presence of phase-transfer agents [15–19] and the use of hydrophilic ligands such as
phosphines [20,21], oxime derivatives [22], oligoether-substituted benzimidazolim salts [23] and
anionic N-donor ligands [24]. Other methods involving the use of supported materials [25–31] and Pd-
nanoparticles [32–34] as heterogeneous catalysts also allow the reaction to be conducted in the
aqueous phase. We have recently prepared water-soluble cationic 2,2’-bipyridyl ligand 1 and utilized it
to bring a palladium complex into the aqueous phase for carbon–carbon bond-forming reactions
[35–37], a rhodium complex for phenylacetylene polymerization [38], and an iron salt for S-arylation
[39] under aerobic conditions. As part of our continuing efforts in the development of green and
reusable catalytic systems for carbon–carbon bond-forming reactions, we report herein the
combination of Pd(NH3)2Cl2 and 1 to create a highly-efficient and reusable catalyst for the coupling of
aryl iodides and alkenes in water under air, making the Mizoroki-Heck reaction green and
economically viable (Scheme 1).
Scheme 1. The Mizoroki-Heck reaction in water.
Br
Br
NMe3
Me3N
N
N
1
R'
Pd(NH3)2Cl2/1 (1-0.0001 mol%)
R'
I
+
Bu3N, H2O, 140oC
R
R
R' = CO2Bu,CO2Et,Ph
2. Results and Discussion
The catalytic system was prepared by mixing equimolar amounts of Pd(NH3)2Cl2 and 1 in water.
The catalyst is stable in water and can be stored under air; hence, stock solutions of this catalytic
system could be prepared at different concentrations. In preliminary studies, our goal was to find the
best base for use in the Mizoroki-Heck reaction in water (Table 1). We found that inorganic bases
were ineffective for the coupling of iodobenzene 2a and butyl acrylate 3a, even at a reaction
temperature of 140 °C (Entries 1–6). Replacing inorganic bases by organic amines such as Et3N led to
the formation of trans-cinnamic acid n-butyl ester 4a in a 32% yield (Entry 7). Among the amines
used, the use of 2 equiv. of Bu3N provided the best results, and a near quantitative yield was obtained
(Entry 10). The blank reaction was also examined under identical conditions, and no desired product

Molecules 2010, 15
317
was found in the absence of the catalyst, which indicates that the reaction is indeed catalyzed by the Pd
system at a very low catalytic concentration. In the absence of 1, a yield of only 34% was obtained,
suggesting the importance of the use of a water-soluble ligand for reaction in water. Thus, the optimal
reaction conditions were obtained and are shown in entry 10 of Table 1.
Table 1. Base screening for the Mizoroki-Heck reaction of iodobenzene 2a and butyl
acrylate 3a in water.a
Entry
1
2
3
4
5
6
Base (equiv.)
NaOH (2)
NaHCO3 (2)
KOH (2)
KOAc (2)
K2CO3 (2)
Yield (%)b
NR
2
NR
NR
NR
4
KF (2)
7
8
9
10
11
12c
13d
Et3N (2)
32
17
6
99
49
NR
34
Diisopropylamine (2)
N,N-Diisopropylethylamine (2)
Bu3N (2)
Bu3N (1)
Bu3N (2)
Bu3N (2)
a
Reaction conditions: iodobenzene (1 mmol), butyl acrylate (1.5 mmol), base,
Pd(NH3)2Cl/1 (0.01 mol %), and H2O (3 mL) in 140 °C for 12 h; b Isolated yields; c
In the absence of catalyst; d In the absence of 1.
Using the optimal conditions, we next investigated the scope of the reaction of aryl iodides with
butyl acrylate (Table 2). Iodobenzene and its derivatives with electron-withdrawing groups at the
para-position afforded very high activities, offering the corresponding products, 4b–4f, in excellent
yields (Entries 2, 4, 6, 8, and 10, respectively). Further reduction of the catalyst loading to
0.0001 mol % gave the products at yields between 48% and 92% (Entry 1, 3, 5, 7, 9, and 11), and the
turnover number (TON) was up to 920,000 (Entry 3). A longer reaction time was required for aryl
iodides bearing an electron-donating group at the para-position. Hence, good to high yields could be
isolated in 48 h with a catalyst loading of 0.01 mol % (Entries 12–15). Similarly, in the cases of entries
12–15, both meta- and ortho-substituted aryl iodides gave excellent isolated yields under identical
conditions (Entries 16–18).
Although the boiling point of ethyl acrylate 3b is lower than the reaction temperature, the Mizoroki-
Heck coupling of aryl iodides with 3b still proceeded smoothly in a sealed tube. As shown in Table 3,
the corresponding products were isolated in yields slightly lower than that of the coupling with butyl
acrylate under similar conditions (Entries 1–17). The catalyst loading for the reaction of activated aryl
iodides with 3b could also be further reduced to 0.0001 mol %, which led to the formation of the
desired products in good to high yields with a very high TON (Entries 2, 4, 6, 8, 10, and 12).

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318
Table 2. Mizoroki-Heck reaction of aryl iodides 2a-l and butyl acrylate 3a in water.a
Pd/1
%)
(mol
Entry Aryl iodide
Time (h) Product (%)b
TON
CO Bu
2
1c
2a
0.0001
48
4a (48) 480,000
I
CO2Bu
O
2
2b
2b
2c
2c
2d
2d
2e
2e
2f
0.01
12
48
12
48
12
48
12
48
12
48
12
48
4b (99) 9,900
4b (92) 920,000
4c (99) 9,900
4c (80) 800,000
4d (99) 9,900
4d (86) 860,000
4e (91) 9,100
4e (68) 680,000
I
I
I
I
I
COMe
NO2
CN
3c
0.0001
0.01
CO Bu
2
4
O N
2
5c
6
0.0001
0.01
CO2Bu
NC
7c
0.0001
0.01
CO Bu
2
O
8
CO2Et
Cl
9c
10
11c
12
13
0.0001
0.01
EtO
CO2Bu
4f (92)
4f (91)
9,200
Cl
2f
0.0001
0.01
910,000
CO Bu
2
2g
2g
4g (67) 6,700
4g (94) 9,400
I
I
OMe
MeO
0.01
CO2Bu
CO2Bu
CO2Bu
Me
14
15
2h
2i
0.01
0.01
48
48
4h (92) 9,200
I
I
OH
HO
4i (56)
4j (96)
5,600
9,600
16
17
18
2j
2k
2l
0.01
0.01
0.01
48
48
48
Me
I
CO2Bu
CO2Bu
4k (95) 9,500
4l (96) 9,600
Me
I
OMe
OMe
a
Reaction conditions: aryl iodide (1 mmol), butyl acrylate (1.5 mmol), Bu3N (2 mmol),
Pd(NH3)2Cl/1 (0.01 or 0.0001 mol %), and H2O (3 mL) at 140 °C; Isolated yields. c Ten mmol of
b
aryl iodide was used.
Table 3. Mizoroki-Heck reaction of aryl iodides 2a-k and ethyl acrylate 3b in water.a
Entry Aryl iodide
Pd/1 (mol %) Time (h) Product (%)b
TON
CO2Et
1
2a
2a
2b
2b
2c
2c
2d
2d
2e
2e
0.01
12
48
12
48
12
48
12
48
12
48
5a (63)
5a (58)
6,300
I
2c
0.0001
0.01
580,000
O
CO2Et
3
5b (82) 8,200
I
I
I
I
COMe
4c
5
0.0001
0.01
5b (81) 810,000
CO Et
2
5c (74)
5c (51)
7,400
NO2
CN
O N
2
6c
0.0001
0.01
510,000
CO2Et
7
5d (80) 8,000
NC
8c
9
0.0001
0.01
5d (76) 760,000
CO2Et
O
5e (81)
5e (45)
8,100
CO2Et
10c
0.0001
450,000
EtO

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Table 3. Cont.
(mol
Pd/1
%)
Entry Aryl iodide
Time (h) Product (%)b
TON
CO Et
2
11
12c
2f
2f
0.01
12
48
5f (82) 8,200
Cl
I
Cl
0.0001
5f (81) 810,000
CO2Et
OMe
Me
I
I
MeO
13
2g
2h
2i
0.01
48
48
48
48
5g (82) 8,200
CO Et
2
14
15
16
0.01
0.01
0.01
5h (74) 7,400
5i (44) 4,400
5j (59) 5,900
CO2Et
I
I
OH
HO
Me
CO2Et
2j
Me
I
Me
CO Et
2
17
2k
0.01
48
5k (65) 6,500
Me
a
Reaction conditions: aryl iodide (1 mmol), ethyl acrylate (1.5 mmol), Bu3N (2 mmol),
Pd(NH3)2Cl/1 (0.01 or 0.0001 mol %), and H2O (3 mL) at 140 °C; b Isolated yields; c Ten mmol of
aryl iodide was used.
The reaction rate of iodobenzene with styrene under this catalytic system was much slower than that
of butyl and ethyl acrylate, providing only 36% of 6a when 1 mol % of catalyst was employed (Table
4, Entry 1). The addition of a phase-transfer agent, TBAB, to the mixture improved the reaction
efficiently to give 6a in an 89% yield (Entry 2). Thus, TBAB was added when styrene was used as the
reactant. Under such conditions, aryl iodides with not only electron-withdrawing but also electron-
donating groups at the para-position could couple with styrene efficiently to afford the corresponding
trans-stilbene derivatives, 6b–6i, in high yields (Entries 3–9). In addition, 3-iodotoluene could also
react with styrene to furnish 6j in a 68% yield (Entry 10), and even sterically-hindered aryl iodides,
2k–2m, were able to be coupled efficiently under this system, the corresponding products being
obtained at yields between 73% and 93% at 140 °C within 24 h (Entries 11–13).
Table 4. Mizoroki-Heck reaction of aryl iodides 2a-m and styrene 3c in water.a
Entry Aryl iodide
Pd/1 (mol %) TBAB (equiv) Product (%)b
1
2a
2a
1
1
0
1
6a (36)
6a (89)
I
2
O
I
I
I
I
COMe
3
4
5
6
7
2b
2c
2d
2e
2f
1
1
1
1
1
1
1
1
1
1
6b (93)
6c (82)
6d (83)
6e (76)
6f (87)
NO2
CN
O N
2
NC
O
CO2Et
EtO
Cl
I
Cl

Molecules 2010, 15
320
Table 4. Cont.
Entry
Aryl iodide
Pd/1 (mol
TBAB (equiv)
Product (%)b
%)
OMe
Me
I
I
8
2g
2h
2i
1
1
1
1
6g (82)
MeO
HO
9
1
1
6h (71)
6i (69)
OH
I
I
10
11
12
2j
1
1
1
1
6j (68)
6k (73)
Me
I
I
2k
Me
OMe
OH
13
14
2l
1
1
1
1
6l (93)
OMe
I
2m
6m (84)
OH
a Reaction conditions: aryl iodide (1 mmol), styrene (1.5 mmol), Bu3N (2 mmol), Pd(NH3)2Cl/1
(1 mol %), TBAB (1 mmol), and H2O (3 mL) at 140 °C for 24h; b Isolated yields.
As for the coupling of cheaper aryl bromides, we found that only activated aryl bromides could
couple with butyl acrylate to afford the corresponding Mizoroki-Heck coupling products in good
yields with 1 mol % catalyst in the presence of 0.5 equiv TBAB. The use of bromobenzene and a
deactivated aryl bromide such as 4-bromoanisole did not furnish any desired product (Scheme 2).
Scheme 2. The Mizoroki-Heck reaction of aryl bromides with butyl acrylate in water.
Pd(NH3)2Cl2/1 (1 mol%)
CO2Bu
CO2Bu
1.5 eq
R
Br
+
R
Bu3N (2 eq), TBAB (0.5 eq), H2O,
140oC, 24h
1 eq
R = MeC(O)-: 4b 75%
NO2-: 4c
NC-: 4d
H-: 4a
71%
74%
0%
MeO-: 4g
0%
We then examined the reusability of the residual aqueous solution, which is important from the
viewpoints of practical utilization and economics. We employed butyl and ethyl acrylates and styrene
individually to react with 4-iodoacetophone, 2b, to test the reusability of this catalytic system
(Table 5). The Mizoroki-Heck coupling of butyl acrylate and 2b with a 0.01 mol % catalyst loading
led to the formation of 4b in a 99% yield in 12 h. After completion of the first cycle, hexane was used
to extract the organic product and the residual aqueous solution was recharged with Bu3N, butyl
acrylate, and 4-iodoacetophone for the second cycle. It was found that the residual aqueous solution
could be reused at least four times with only a slight decrease in activity (Entry 1). The employment of
ethyl acrylate led to a similar reusability with slightly lower yields as compared with butyl acrylate
(Entry 2). In the case of styrene, a higher catalyst loading (1 mol %) and TBAB were employed in the

Molecules 2010, 15
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initial cycle in order to lead to a higher product yield. Addition of the phase-transfer agent in
subsequent runs was not required (Entry 3).
Table 5. Reuse studies of the Mizoroki-Heck reaction of 4-iodoacetophone 2b and alkenes 3.a
Cycle (%)b
Pd/1
%)
(mol
Entry
Alkene
Time (h)
1st
99
90
93
2nd
98
3rd
95
4th
93
83
92
5th
90
81
90
CO Bu
2
1
2
3a
3b
3c
12
12
24
0.01
CO2Et
0.01
1
90
86
Ph
3c
94
93
a
Reaction conditions: 4-iodoacetophone (1 mmol), alkene (1.5 mmol), Bu3N (2 mmol),
c
Pd(NH3)2Cl/1 (1 or 0.01 mol %), and H2O (3 mL) at 140 °C; b Isolated yields; One mmol of
TBAB was added.
3. Experimental
3.1. General
Chemicals were purchased from commercial suppliers and were used without further purification.
The cationic 2,2’-bipyridyl ligand was prepared according to the published procedures [24,25]. GC
analysis was performed on a Shimadzu GC-14B equipped with a fused silica capillary column, and all
1H- and 13C-NMR spectra were recorded in CDCl3 at 25 °C on a Varian 200 NMR spectrometer.
Elemental analyses were performed and high resolution mass spectra recorded at the Instrument Center
Service, National Science Council of Taiwan.
3.2. Typical procedure for the Mizoroki-Heck reaction
A sealable tube equipped with a magnetic stirrer bar was charged with aryl iodide (1 mmol), alkene
(1.5 mmol), Bu3N (2 mmol), and H2O (2 mL). In the case of styrene, the addition of TBAB (1 mmol)
was required. After the addition of Pd(NH3)2Cl2/1 aqueous solution (in 1 mL H2O, at different
concentrations for various substrate/catalyst ratios), the tube was sealed under air by a Teflon-coated
screw cap. The reaction vessel was then placed in an oil bath at 140 °C for the indicated reaction time
period (see Tables 2–4). After cooling of the reaction mixture to room temperature, the aqueous
solution was extracted with hexane, the organic phase was dried over MgSO4, and the solvent was then
removed under vacuum. Column chromatography on silica gel afforded the desired product.
1
(E)-3-Phenylacrylic acid n-butyl ester (4a) [40]. Yellow oil. H-NMR: δ 0.97 (t, J = 7.0 Hz, 3H),
1.35–1.53 (m, 2H), 1.63–1.77 (m, 2H), 4.21 (t, J = 6.6 Hz, 2H), 6.44 (d, J = 16.0 Hz, 1H), 7.35–7.41
(m, 3H), 7.49–7.56 (m, 2H), 7.67 (d, J = 16.0 Hz, 1H); 13C NMR: δ 13.6, 19.1, 30.7, 64.2, 118.2,
127.8, 128.7, 129.9, 134.4, 144.3, 166.8.
1
(E)-3-(4-Acetylphenyl)acrylic acid n-butyl ester (4b) [41]. Yellow oil. H-NMR: δ 0.94 (t, J = 7.6 Hz,
3H), 1.34–1.51 (m, 2H), 1.61–1.75 (m, 2H), 2.60 (s, 3H), 4.21 (t, J = 6.4 Hz, 2H), 6.51 (d, J = 16.0 Hz,

Molecules 2010, 15
322
13
1H), 7.59 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 16.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 2H); C-NMR: δ 13.6,
19.1, 26.5, 30.7, 64.5, 120.7, 128.0, 128.7, 137.9, 138.7, 142.8, 166.3, 197.0.
1
(E)-3-(4-Nitrophenyl)acrylic acid n-butyl ester (4c). Yellow solid. Mp. 67–68 (lit.[41] 67–69 °C). H-
NMR: δ 0.95 (t, J = 7.4 Hz, 3H), 1.33–1.51 (m, 2H), 1.61–1.76 (m, 2H), 4.22 (t, J = 6.6 Hz, 2H), 6.54
(d, J = 16.0 Hz, 1H), 7.62–7.73 (m, 3H), 8.23 (d, J = 9.0 Hz, 2H); 13C-NMR: δ 13.6, 19.1, 30.7, 64.8,
122.6, 124.0, 128.5, 140.5, 141.4, 148.4, 165.9.
(E)-3-(4-Cyanophenyl)acrylic acid n-butyl ester (4d). Yellow solid. Mp. 43.1–43.5 (lit.[42] 43.5–46.9
1
°C). H-NMR: δ 0.95 (t, J = 7.2 Hz, 3H), 1.32–1.51 (m, 2H), 1.61–1.75 (m, 2H), 4.21 (t, J = 6.6 Hz,
13
2H), 6.50 (d, J = 16.2 Hz, 1H), 7.56–7.68 (m, 5H); C-NMR: δ 13.5, 19.0, 30.5, 64.5, 113.1, 118.1,
121.7, 128.2, 132.4, 138.5, 141.8, 165.9.
(E)-4-(2-Butoxycarbonylvinyl)benzoic acid ethyl ester (4e). Yellow oil. 1H-NMR: δ 0.97 (t, J = 7.2 Hz,
3H), 1.36–1.57 (m, 5H), 1.63–1.77 (m, 2H), 4.22 (t, J = 6.6 Hz, 2H), 4.39 (q, J = 7.2 Hz, 2H), 6.52 (d,
13
J = 16.0 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 16.0 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H); C-
NMR: δ 13.5, 14.1, 18.9, 30.5, 60.9, 64.3, 120.4, 127.5, 129.7, 131.4, 138.3, 142.8, 165.5, 166.1;
HRMS calcd. for C16H20O4, 276.1362; found, 276.1353.
1
(E)-3-(4-Chlorophenyl)acrylic acid n-butyl ester (4f) [43]. Colorless oil. H-NMR: δ 0.96 (t,
J = 7.4 Hz, 3H), 1.34–1.53 (m, 2H), 1.62–1.76 (m, 2H), 4.21 (t, J = 6.6 Hz, 2H), 6.41 (d, J = 16.0 Hz,
13
1H), 7.35 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H), 7.62 (d, J = 16.0 Hz, 1H); C-NMR: δ 13.5,
19.9, 30.6, 64.2, 188.7, 128.8, 128.9, 132.8, 135.8, 142.7, 166.3.
1
(E)-3-(4-Methoxyphenyl)acrylic acid n-butyl ester (4g) [40]. Yellow oil. H-NMR: δ 0.96 (t,
J = 7.2 Hz, 3H), 1.26–1.53 (m, 2H), 1.62–1.76 (m, 2H), 3.84 (s, 3H), 4.20 (t, J = 6.4 Hz, 2H), 6.31 (d,
13
J = 16.0 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.64 (d, J = 16.0 Hz, 1H); C-
NMR: δ 13.7, 19.1, 30.8, 55.2, 64.1, 114.2, 115.7, 127.1, 129.5, 144.1, 161.2, 167.2.
1
(E)-3-(4-Tolyl)acrylic acid n-butyl ester (4h) [41]. Yellow oil. H-NMR: δ 0.96 (t, J = 7.2 Hz, 3H),
1.38–1.53 (m, 2H), 1.62–1.76 (m, 2H), 2.37 (s, 3H), 4.20 (t, J = 6.6 Hz, 2H), 6.39 (d, J = 16.0 Hz, 1H),
7.19 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 16.0 Hz, 1H); 13C-NMR: δ 13.5, 19.0,
21.2, 30.7, 64.0, 117.1, 127.8, 129.3, 131.6, 140.3, 144.2, 166.9.
(E)-3-(4-Hydroxyphenyl)acrylic acid n-butyl ester (4i). Yellow solid. Mp. 74–76 (lit.[44] 72–74 °C).
1H-NMR: δ 0.94 (t, J = 7.2 Hz, 3H), 1.32–1.50 (m, 2H), 1.63–1.74 (m, 2H), 4.18 (t, J = 6.4 Hz, 2H),
5.29 (s, 1H), 6.28 (d, J = 16.0 Hz, 1H), 6.82 (d, J = 8.6 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 7.61 (d,
J = 16.0 Hz, 1H); 13C-NMR: δ 13.6, 19.1, 30.6, 64.6, 114.5, 116.0, 126.2, 129.9, 145.2, 158.9, 168.5.
1
(E)-3-(3-Tolyl)acrylic acid n-butyl ester (4j) [41]. Colorless oil. H-NMR: δ 0.97 (t, J = 7.6 Hz, 3H),
1.38–1.54 (m, 2H), 1.62–1.73 (m, 2H), 2.37 (s, 3H), 4.21 (t, J = 6.8 Hz, 2H), 6.42 (d, J = 16.0 Hz, 1H),

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13
7.18–7.35 (m, 4H), 7.65 (d, J = 16.0 Hz, 1H); C-NMR: δ 13.5, 19.0, 21.0, 30.7, 64.0, 117.9, 124.9,
128.4, 128.4, 130.7, 134.2, 138.1, 144.4, 166.7.
1
(E)-3-(2-Tolyl)acrylic acid n-butyl ester (4k) [45]. Pale yellow oil. H-NMR: δ 0.97 (t, J = 7.2 Hz,
3H), 1.38–1.54 (m, 2H), 1.63–1.74 (m, 2H), 2.44 (s, 3H), 4.22 (t, J = 6.8 Hz, 2H), 6.36 (d, J = 16.0 Hz,
13
1H), 7.21 (m, 3H), 7.55 (d, J = 7.0 Hz, 1H), 7.98 (d, J = 16.0 Hz, 1H); C-NMR: δ 13.7, 19.2, 19.7,
30.8, 64.4, 119.3, 126.2, 126.4, 129.8, 130.7, 133.4, 137.5, 142.2, 167.0.
(E)-3-(2-Methoxyphenyl)acrylic acid n-butyl ester (4l) [46]. Yellow oil. 1H-NMR: δ 0.94 (t, J = 7.4 Hz,
3H), 1.36–1.51 (m, 2H), 1.61–1.74 (m, 2H), 3.87 (s, 3H), 4.19 (t, J = 6.6 Hz, 2H), 6.51 (d, J = 16.0 Hz,
13
1H), 6.88–6.98 (m, 2H), 7.28–7.36 (m, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 16.2 Hz, 1H); C-
NMR: δ 13.5, 19.0, 30.7, 55.1, 63.9, 110.9, 118.5, 120.4, 123.2, 128.5, 131.1, 139.6, 158.0, 167.2.
1
(E)-3-Phenylacrylic acid ethyl ester (5a) [47]. Oil. H-NMR: δ 1.32 (t, J = 7.2 Hz, 3H), 4.25 (q,
J = 7.2 Hz, 2H), 6.42 (d, J = 16.0 Hz, 1H), 7.35–7.38 (m, 3H), 7.49–7.53 (m, 2H), 7.67 (d,
J = 16.0 Hz, 1H); 13C-NMR: δ 14.2, 60.3, 118.2, 127.9, 128.7, 130.0, 134.4, 144.4, 166.8.
(E)-3-(4-Acetylphenyl)acrylic acid ethyl ester (5b). Yellow solid. Mp. 43–45 °C (lit.[48] 40–42 °C).
1H-NMR: δ 1.35 (t, J = 7.2 Hz, 3H), 2.62 (s, 3H), 4.28 (q, J = 7.2 Hz, 2H), 6.53 (d, J = 16.0 Hz, 1H),
13
7.61 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 16.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 2H); C-NMR: δ 14.0, 26.3,
60.4, 120.5, 127.7, 128.5, 137.6, 138.4, 142.6, 165.9, 196.7.
(E)-3-(4-Nitrophenyl)acrylic acid ethyl ester (5c). Yellow solid. Mp. 134–136 °C (lit.[49] 132–134
°C). 1H-NMR: δ 1.36 (t, J = 7.2 Hz, 3H), 4.29 (q, J = 7.2 Hz, 2H), 6.56 (d, J = 16.0 Hz, 1H), 7.67 (d,
13
J = 8.8 Hz, 2H), 7.71 (d, J = 16.0 Hz, 1H), 8.25 (d, J = 8.8 Hz, 2H); C-NMR: δ 14.2, 60.9, 122.5,
124.0, 128.5, 140.5, 141.4, 148.4, 165.8.
(E)-3-(4-Cyanophenyl)acrylic acid ethyl ester (5d). White solid. Mp. 68–70 °C (lit.[50] 69–69.3 °C).
1H-NMR: δ1.32 (t, J = 7.2 Hz, 3H), 4.26 (q, J = 7.2 Hz, 2H), 6.49 (d, J = 16.0 Hz, 1H), 7.56–7.68 (m,
5H); 13C-NMR: δ 14.2, 60.9, 113.3, 118.2, 121.9, 128.2, 132.5, 138.7, 142.0, 165.9.
1
(E)-4-(2-Ethoxycarbonylvinyl)benzoic acid ethyl ester (5e). Yellow solid. Mp. 51–53 °C. H-NMR: δ
1.35 (t, J = 7.2 Hz, 3H), 1.40 (t, J = 7.0 Hz, 3H), 4.28 (q, J = 7.2 Hz, 2H), 4.39 (q, J = 7.0 Hz, 2H),
6.52 (d, J = 16.0 Hz, 1H), 7.58 (d, J = 8.6 Hz, 2H), 7.70 (d, J = 16.0 Hz, 1H), 8.05 (d, J = 8.6 Hz, 2H);
13C-NMR: δ 14.2, 60.6, 61.0, 120.5, 127.7, 129.9, 131.6, 138.4, 143.0, 165.7, 166.3; Anal. calcd. for
C14H16O4: C, 67.73; H, 6.50, found C, 67.91; H, 6.64.
(E)-3-(4-Chlorophenyl)acrylic acid ethyl ester (5f) [51]. Oil. 1H-NMR: δ 1.34 (t, J = 7.2 Hz, 3H), 4.27
(q, J = 7.2 Hz, 2H), 6.41 (d, J = 16.0 Hz, 1H), 7.35 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H), 7.63
(d, J = 16.0 Hz, 1H); 13C-NMR: δ 14.3, 60.5, 118.8, 128.6, 129.1, 132.9, 136.0, 142.9, 166.6.

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(E)-3-(4-Methoxyphenyl)acrylic acid ethyl ester (5g) [51]. Oil. 1H-NMR: δ 1.33 (t, J = 7.2 Hz, 3H),
3.84 (s, 3H), 4.25 (q, J = 7.2 Hz, 2H), 6.31 (d, J = 16.0 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 7.48 (d,
13
J = 8.6 Hz, 2H), 7.64 (d, J = 16.0 Hz, 1H); C-NMR: δ 14.1, 55.0, 60.0, 114.0, 115.5, 126.9, 129.4,
143.9, 161.1, 166.9.
(E)-3-(4-Tolyl)acrylic acid ethyl ester (5h) [51]. Oil. 1H-NMR: δ 1.34 (t, J = 7.2 Hz, 3H), 2.37 (s, 3H),
4.26 (q, J = 7.2 Hz, 2H), 6.39 (d, J = 16.0 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H),
7.66 (d, J = 16.0 Hz, 1H); 13C-NMR: δ 14.2, 21.3, 60.2, 117.1, 127.9, 129.4, 131.6, 140.4, 144.4,
166.9.
1
(E)-3-(4-Hydroxyphenyl)acrylic acid ethyl ester (5i) [52]. Oil. H-NMR: δ 1.33 (t, J = 7.2 Hz, 3H),
4.25 (q, J = 7.2 Hz, 2H), 6.29 (d, J = 15.8 Hz, 1H), 6.84 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H),
7.63 (d, J = 15.8 Hz, 1H); 13C-NMR: δ 14.3, 60.4, 114.7, 116.1, 126.1, 129.9, 144.9, 159.2, 167.8.
(E)-3-(3-Tolyl)acrylic acid ethyl ester (5j) [53]. Oil. 1H-NMR: δ 1.34 (t, J = 7.2 Hz, 3H), 2.37 (s, 3H),
4.26 (q, J = 7.2 Hz, 2H), 6.42 (d, J = 16.0 Hz, 1H), 7.17–7.34 (m, 4H), 7.66 (d, J = 16.0 Hz, 1H); 13C-
NMR: δ 14.2, 21.2, 60.3, 117.9, 125.1, 128.6, 128.6, 130.9, 134.3, 138.3, 144.6, 166.8.
(E)-3-(2-Tolyl)acrylic acid ethyl ester (5k) [51]. Oil. 1H-NMR: δ 1.35 (t, J = 7.2 Hz, 3H), 2.45 (s, 3H),
4.27 (q, J = 7.2 Hz, 2H), 6.36 (d, J = 16.0 Hz, 1H), 7.21–7.26 (m, 3H), 7.55 (d, J = 7.2 Hz, 1H), 7.98
13
(d, J = 16.0 Hz, 1H); C-NMR: δ 14.2, 19.6, 60.3, 119.2, 126, 2, 126.3, 129.8, 130.6, 133.3, 137.4,
142.1, 166.8.
1
(E)-Stilbene (6a). Yellow solid. Mp. 125–126 °C (lit.[54] 125 °C). H-NMR: δ 7.11 (s, 2H), 7.29 (t,
13
J = 6.6 Hz, 2H), 7.40 (t, J = 7.0 Hz, 4H), 7.53 (d, J = 8.2 Hz, 4H); C-NMR: δ 126.5, 127.6, 128.6,
128.7, 137.3.
1
(E)-4-Acetylstilbene (6b). White solid. Mp. 145–147 °C (lit.[55] 148–150 °C). H-NMR: δ 2.61 (s,
3H), 7.12 (d, J = 16.4 Hz, 1H), 7.23 (d, J = 16.4 Hz, 1H), 7.26–7.43 (m, 3H), 7.55 (d, J = 8.0 Hz, 2H),
7.59 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H); 13C-NMR: δ 26.6, 126.4, 126.8, 127.4, 128.3, 128.7,
128.8, 131.4, 135.9, 136.7, 141.9, 197.3.
1
(E)-4-Nitrostilbene (6c). Yellow solid. Mp. 158–160 °C (lit.[56] 158–158.5 °C). H-NMR: δ 7.14 (d,
J = 16.2 Hz, 1H), 7.28 (d, J = 16.2 Hz, 1H), 7.34–7.45 (m, 3H), 7.55 (d, J = 8.0 Hz, 2H), 7.64 (d,
J = 8.0 Hz, 2H); 13C-NMR: δ 124.1, 126.3, 126.8, 126.9, 128.7, 128.8, 133.3, 136.2, 143.8, 146.8.
1
(E)-4-Cyanostilbene (6d). White solid. Mp. 120 °C (lit.[55] 117.4–117.7 °C). H-NMR: δ 7.08 (d,
J = 16.0 Hz, 1H), 7.22 (d, J = 16.0 Hz, 1H), 7.32–7.44 (m, 3H), 7.52–7.67 (m, 6H); 13C-NMR: δ 110.6,
118.9, 126.7, 126.8, 126.9, 128.6, 128.8, 132.3, 132.4, 136.3, 141.8.
1
(E)-4-Ethoxycarbonylstilbene (6e). Colorless solid. Mp 105–107 °C (lit.[57] 106.0–106.5 °C). H-
NMR: δ 1.41(t, J = 7.2 Hz, 3H), 4.39(q, J = 7.2 Hz, 2H), 7.12 (d, J = 16.2 Hz, 1H), 7.23 (d,

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J = 16.2 Hz, 1H), 7.29–7.33 (m, 1H), 7.34–7.43 (m, 2H), 7.53–7.59 (m, 4H), 8.03 (d, J = 8.4 Hz, 2H);
13C- NMR: δ 14.8, 60.9, 126.2, 126.7, 127.6, 128.2, 128.7, 129.3, 129.9, 131.1, 136.7, 141.7, 166.3.
1
(E)-4-Chlorostilbene (6f). White solid. Mp. 130–132 °C (lit.[58] 129 °C). H-NMR: δ 7.07 (s, 2H),
7.26–7.41 (m, 5H), 7.44 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 7.4 Hz, 2H); 13C-NMR: δ 126.5, 127.3, 127.6,
127.8, 128.7, 128.8, 129.3, 133.1, 135.8, 136.9.
1
(E)-4-Methoxystilbene (6g). Pale white solid. Mp. 135–136 °C (lit.[58] 136 °C). H-NMR: δ 3.82 (s,
3H), 6.89 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 16.4 Hz, 1H), 7.07 (d, J = 16.4 Hz, 1H), 7.20–7.22 (m, 1H),
7.33 (t, J = 7.4 Hz, 2H), 7.41–7.50 (m, 4H); 13C-NMR: δ 55.3, 114.1, 126.2, 126.6, 127.2, 127.7,
128.2, 128.6, 130.2, 137.6, 159.3.
1
(E)-4-Methylstilbene (6h). Light yellow solid. Mp. 120–121 °C (lit.[58] 121 °C). H-NMR: δ 2.36 (s,
3H), 7.07 (s, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.24–7.26 (m, 1H), 7.35 (t, J = 7.4 Hz, 2H), 7.41 (d,
J = 8.0 Hz, 2H), 7.50 (d, J = 7.2 Hz, 2H); 13C-NMR: δ 21.3, 126.3, 126.4, 127.4, 127.7, 128.6, 129.4,
134.5, 137.46, 137.49.
1
(E)-4-Hydroxystilbene (6i). Yellow solid. Mp. 185–187 °C (lit.[59] 186 °C). H-NMR: δ 4.78 (s, 1H),
6.83 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 16.4 Hz, 1H), 7.06 (d, J = 16.4 Hz, 1H), 7.19–7.26 (m, 1H), 7.32
13
(d, J = 7.6 Hz, 2H), 7.41 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 7.2 Hz, 2H); C-NMR: δ 115.6, 126.2,
126.7, 127.2, 127.9, 128.1, 128.6, 130.4, 137.6, 155.2.
1
(E)-3-Methylstilbene (6j). Pale yellow solid. Mp. 48–49 °C (lit.[60] 47–48 °C). H-NMR: δ 2.37 (s,
3H), 7.05–7.08 (m, 3H), 7.22–7.28 (m, 2H), 7.29–7.39 (m, 4H), 7.49–7.53 (m, 2H); 13C-NMR: δ 24.4,
123.7, 126.5, 127.2, 127.5, 128.4, 128.5, 128.5, 128.6, 128.8, 137.3, 137.4, 138.2.
(E)-2-Methylstilbene (6k) [16]. Oil. 1H-NMR: δ 2.42 (s, 3H), 6.99 (d, J = 16.2 Hz, 1H), 7.23–7.33 (m,
13
4H), 7.37–7.43 (m, 3H), 7.52 (d, J = 7.2 Hz, 2H), 7.59 (d, J = 6.8 Hz, 1H); C-NMR: δ 19.9, 125.4,
126.2, 126.5, 127.5, 127.6, 128.6, 129.9, 130.3, 135.7, 136.4, 137.7.
(E)-2-Methoxystilbene (6l). Pink solid. Mp. 58–59 °C (lit.[61] 58.6–59.5 °C). 1H-NMR: δ 3.89 (s, 3H),
6.91 (d, J = 8.4 Hz, 1H), 6.98 (d, J = 7.4 Hz, 1H), 7.11 (d, J = 16.6 Hz, 1H),7.26–7.43 (m, 5H),
13
7.55–7.62 (m, 3H); C NMR: δ 55.5, 110.9, 120.7, 123.5, 126.4, 126.44, 126.5, 127.3, 128.5, 128.6,
129.1, 137.9, 156.9.
(E)-2-Hydroxystilbene (6m). Pale white solid. Mp. 144–145 °C (lit.[62] 143–144 °C). 1H-NMR: δ 5.02
(s, 1H), 6.81 (dd, J = 1.6 Hz, J = 8.0 Hz, 1H), 6.95 (t, J = 7.4 Hz, 1H), 7.12 (d, J = 16.6 Hz, 1H), 7.16
(td, J = 1.6 Hz, J = 8.0 Hz, 1H), 7.21–7.29 (m, 1H), 7.37 (d, J = 16.6 Hz, 1H), 7.32–7.42 (m, 2H),
13
7.51–7.55 (m, 3H); C-NMR: δ 115.9, 121.1, 123.0, 124.7, 126.5, 127.3, 127.6, 128.6, 130.2, 137.6,
152.9.

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3.3. Typical procedure for the reuse of the catalytic aqueous solution
The reaction was conducted following the procedure described in Section 3.2 under the reaction
conditions shown in Table 5. After reaction, the aqueous reaction mixture was washed with hexane
under vigorous stirring three times, and the organic product was isolated from the combined organic
phase according to the previously-described procedure. The residual aqueous solution was then
charged with aryl iodide, alkene, and Bu3N for the next reaction, and in the case of styrene, addition of
TBAB at the first run was required.
4. Conclusions
In conclusion, we have shown here that the above-described Pd(NH3)2Cl2/cationic 2,2’-bipyridyl
system could be a highly-efficient catalyst for the Mizoroki-Heck coupling of aryl iodides and alkenes
using an environmentally benign solvent, water, as the reaction medium. The loading amount of the
catalyst in a single batch reaction can be reduced to as low as 0.0001 mol %, while still affording the
products in high yields. This water-compatible and air-stable catalytic system enables the reaction to
be conducted using a very simple procedure. The catalyst can be easily separated from the organic
products by simple extraction and the residual aqueous solution can be reused for further reactions,
which reduces the wastage of precious metal, making this procedure greener and economically viable.
Acknowledgements
This research was financially supported by the National Science Council of Taiwan (NSC96-2113-
M-027-003-MY2).
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Sample Availability: Samples of the compounds are available from the authors.
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