Microwave-promoted heck reaction using Pd(OAc)2 as catalyst under ligand-free and solvent-free conditions

Article abstract of DOI:10.1080/00397910601031801

A rapid and efficient microwave-promoted Heck reaction of aryl iodides and bromides with terminal olefins using a Pd(OAc)2 (0.05 mol%)/K3PO4 catalytic system under ligand-free and solvent-free conditions is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601031801

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Microwave‐Promoted Heck Reaction Using
Pd(OAc)2 as Catalyst under Ligand‐Free and
Solvent‐Free Conditions
Li‐Hua Du a & Yan‐Guang Wang a
a Department of Chemistry, Zhejiang University, Hangzhou, China
Version of record first published: 25 Jul 2007.
To cite this article: Li‐Hua Du & Yan‐Guang Wang (2007): Microwave‐Promoted Heck Reaction Using Pd(OAc)2
as Catalyst under Ligand‐Free and Solvent‐Free Conditions, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 37:2, 217-222
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Synthetic Communicationsw, 37: 217–222, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601031801
Microwave-Promoted Heck Reaction Using
Pd(OAc)2 as Catalyst under Ligand-Free
and Solvent-Free Conditions
Li-Hua Du and Yan-Guang Wang
Department of Chemistry, Zhejiang University, Hangzhou, China
Abstract: A rapid and efficient microwave-promoted Heck reaction of aryl iodides and
bromides with terminal olefins using a Pd(OAc)2 (0.05 mol%)/K3PO4 catalytic system
under ligand-free and solvent-free conditions is described.
Keywords: aryl halides, Heck reaction, microwave, palladium
Palladium-catalyzed Heck coupling reaction is one of the most powerful tools
for carbon–carbon formation in organic synthesis.[1] The traditional Heck
reaction is typically performed with 1–5 mol% of a palladium catalyst
along with phosphine ligands in the presence of a suitable base under an
inert atmosphere.[2] However, the palladium complex is always expensive,
and the phosphine ligands, especially the electron-rich phosphine ligands,
are often toxic and sensitive to water and air. Consequently, several
phosphine-free palladium catalytic systems have been developed, which
include the heterogeneous palladium catalysts,[3] nanopalladium catalysts,[4]
sulfur-based palladacyles,[5] palladium complexes of nitrogen ligands,[6] and
carbene complexes of palladium.[7] Recently, there has been increasing
interest in the use of ligand-free catalyst systems of the Heck reaction.[8]
Yao and coworkers[9] have shown that Pd(OAc)2, in combination with
K3PO4 as the base and DMA as the solvent, was an active catalyst for the
ligand-free Heck reaction of aryl bromides, but long reaction times (17–
25 h) were required for full conversion. Attempts to reduce the reaction
time through enhancing the reaction temperature are seldom effective
Received in Japan April 26, 2006
Address correspondence to Yan-Guang Wang, Department of Chemistry, Zhejiang
University, Hangzhou, China. E-mail: orgwyg@zju.edu.cn
217

218
L.-H. Du and Y.-G. Wang
because of collapse of the catalytic system. On the other hand, microwave-
promoted synthesis is an area of increasing research interest as evidenced
by a number of papers and reviews appearing in the literature,[10] and
microwave irradiation has also been employed for the Heck reaction.[11] As
a part of our research on microwave chemistry[12] and the Heck reaction,[13]
we investigated the microwave-promoted Heck reaction of aryl halides
using a Pd(OAc)2/K3PO4 catalytic system under solvent-free and ligand-
free conditions. We herein report the full results of this effort.
Initially, we examined the coupling between bromobenzene and styrene
using a Pd(OAc)2/K3PO4 system under solvent-free conditions. When
0.1 mol% of Pd(OAc)2 and 1.4 equiv of/K3PO4 were employed, irradiation
at 300 W of microwave power for 15 min gave trans-stilbene in 67% yield
(Table 1, entry 1). We then optimized the reaction conditions. As shown in
Table 1, the best yield was obtained when 0.05 mol% of Pd(OAc)2 and
1.4 equiv of K3PO4 were used under 300 W for 20–25 min.
With the optimal reaction conditions, we examined a variety of aryl
halides and terminal olefins, and the results are summarized in Table 2.
Both aryl bromides (Table 2, entries 1–7 and 15–18) and aryl iodides
(Table 2, entries 8–11) gave good to excellent yields, whereas aryl
chlorides gave poor yields (21–55%) even in the presence of 0.1 mol% of
catalyst (Table 2, entries 12–14). The electron-deficient aryl halides
(Table 2, entries 1, 4, 15, and 18) are more active than the electron-rich aryl
halides (Table 2, entries 3, 11, and 17). Furthermore, 4-methylphenyl
halides (Table 2, entries 2 and 9) are more active than their 2-methyl
Table 1. Optimal conditions for Pd(OAc)2-catalyzed Heck reaction of
bromobenzene and styrene
Microwave
power (W)
Pd(OAc)2
(mol%)
Time
(min)
Yielda
(%)
Entry
1
2
200
150
100
250
300
300
300
300
300
300
300
0.1
0.1
15
15
15
15
15
20
15
20
25
25
50
67
55
35
78
93
93
70
85
93
87
80
3
0.1
0.1
4
5
0.1
0.1
6
7
0.05
0.05
0.05
0.01
0.005
8
9
10
11
aIsolated yield.

Microwave-Promoted Heck Reaction
219
Table 2. Ligand-free Pd(OAc)2-catalyzed Heck reactions under microwave and
solvent-free conditions
Pd(OAc)2
(mol%)
Time
(min)
Yield
(%)a
Entry
R1
X
R2
1
2
4-COCH3
4-CH3
4-OMe
2-Me
4-Cl
Br
Br
Br
Br
Br
Br
Br
I
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.1
20
25
25
25
25
20
25
20
20
20
20
25
25
25
20
20
20
20
98
90
82
75
95
98
93
96
94
85
88
38
21
55
95
90
86
94
3
4
5
6
4-CN
H
7
8
H
9
4-CH3
2-Me
4-OMe
H
I
10
11
12
13
14
15
16
17
18
I
I
Cl
Cl
Cl
Br
Br
Br
Br
4-CH3
4-COCH3
4-CN
H
0.1
0.1
CO2Et
CO2Et
CO2Et
CO2Et
0.05
0.05
0.05
0.05
4-CH3
4-COCH3
aIsolated yield.
counterparts (Table 2, entries 4 and 10) because of the stereo hindering. The
products were isolated as trans-isomers in all cases. Compared with Yao’s
method,[9] our reaction is rapid and solventfree.
In summary, we have demonstrated that microwave irradiation could effi-
ciently promote the Heck reaction using a Pd(OAc)2/K3PO4 catalytic system.
A few notable advantages of this procedure are (1) that Pd(OAc)2 was used as
catalyst without utilizing expensive ligands and/or requiring the presence of
various additives, (2) reasonably good yields, (3) fast reaction times (20–
25 min), and (4) avoidance of toxic solvents.
EXPERIMENTAL
General Procedure for the Heck Reaction
Aryl halides (1 mmol), olefin (1.2 mmol), K3PO4 (1.4 mmol, 0.298 g), and
Pd(OAc)2 (1.67 ꢀ 1024 mmol/g, 3 g, 0.0005 mmol) absorbed on neutral

220
L.-H. Du and Y.-G. Wang
alumina were mixed thoroughly. Subsequently the mixture was placed inside
the cavity of the microwave reactor and irradiated at 300 W power for 25 min.
After the reaction mixture was cooled to room temperature, the solid was
extracted with ethyl acetate, and the solvent was evaporated in a vacuum.
The residue was purified by flash-column chromatography on silica gel
using ethyl acetate/hexane (1:20).
Data
1
(E)-1-(4-Styryl-phenyl)-ethanone (Table 2, entry 1): H NMR (500 MHz,
CDCl3): d 7.96 (d, 2H, J ¼ 8.3 Hz), 7.60 (d, 2H, J ¼ 8.2 Hz), 7.55 (d, 2H,
J ¼ 7.6 Hz), 7.40 (t, 2H, J ¼ 7.5 Hz), 7.30 (m, 1H), 7.23 (d, 1H,
J ¼ 16.3 Hz), 7.13 (d, 1H, J ¼ 16.3 Hz), 2.62 (s, 3H). MS (EI): m/z (%)
222 (66) [Mþ], 207 (100), 178 (66), 152 (15), 89 (20), 76 (16), 43 (43).
(E)-1-Methyl-4-styryl-benzene (Table 2, entry 2): 1H NMR (500 MHz,
CDCl3): d 7.51 (d, 2H, J ¼ 7.6 Hz), 7.42 (d, 2H, J ¼ 8.0 Hz), 7.37 (t, 2H,
J ¼ 7.6 Hz), 7.25 (m, 1H), 7.18 (d, 2H, J ¼ 7.6 Hz), 7.08 (d, 2H,
J ¼ 2.0 Hz), 2.38 (s, 3H). MS (EI): m/z (%) 180 (100) [Mþ], 179 (68), 178
(38), 165 (34), 102 (8), 76 (11), 51 (17).
(E)-Methoxy-4-styryl-benzene (Table 2, entry 3): 1H NMR (500 MHz,
CDCl3): d 7.50 (q, 4H, J ¼ 8.2 Hz), 7.36 (t, 2H, J ¼ 7.6 Hz), 7.26 (d, 1H,
J ¼ 7.3 Hz), 7.07 (d, 1H, J ¼ 16.3 Hz), 6.98 (d, 1H, J ¼ 16.3 Hz), 6.90
(d, 2H, J ¼ 8.7 Hz), 3.83 (s, 3H). MS (EI): m/z (%) 210 (100) [Mþ], 195
(22), 179 (14), 167 (33), 165 (37), 152 (27), 89 (15), 63 (15), 51 (12).
(E)-1-Methyl-2-styryl-benzene (Table 2, entry 4): 1H NMR (500 MHz,
CDCl3): d 7.60 (d, 1H, J ¼ 7.3 Hz), 7.53 (d, 2H, J ¼ 7.6 Hz), 7.37–7.43
(m, 3H), 7.23–7.33 (m, 4H), 7.05 (d, 1H, J ¼ 16.2 Hz), 2.48 (s, 3H). MS
(EI): m/z (%) 194 (100) [Mþ], 195 (22), 179 (14), 167 (33), 165 (37), 152
(27), 89 (15), 63 (15), 51 (12).
(E)-1-Chloro-4-styryl-benzene (Table 2, entry 5): 1H NMR (500 MHz,
CDCl3): d 7.50 (d, 2H, J ¼ 7.5 Hz), 7.44 (d, 2H, J ¼ 8.5 Hz), 7.37 (t, 2H,
J ¼ 7.5 Hz), 7.32 (d, 2H, J ¼ 8.5 Hz), 7.28 (m, 1H), 7.06 (d, 2H,
J ¼ 4.3 Hz). MS (EI): m/z (%) 214 (70) [Mþ], 216 (23) [M þ 2þ], 179
(90), 178 (100), 152 (20), 89 (25), 76 (10).
(E)-1-Cyano-4-styryl-benzene (Table 2, entry 6): 1H NMR (500 MHz,
CDCl3): d 7.63 (d, 2H, J ¼ 8.3 Hz), 7.59 (d, 2H, J ¼ 8.4 Hz), 7.53 (d, 2H,
J ¼ 7.5 Hz), 7.39 (t, 2H, J ¼ 7.5 Hz), 7.33 (d, 1H, J ¼ 7.3 Hz), 7.22 (d, 1H,
J ¼ 16.3 Hz), 7.09 (d, 1H, J ¼ 16.3 Hz). MS (EI): m/z (%) 205 (100)
[Mþ], 190 (28), 177 (7), 165 (6).

Microwave-Promoted Heck Reaction
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