In situ generation of palladium nanoparticles: Reusable, ligand-free heck reaction in PEG-400 assisted by focused microwave irradiation

Article abstract of DOI:10.1055/s-0030-1259310

A rapid and efficient Heck coupling reaction of aryl iodides with terminal olefins was conducted in PEG-400 at 120 °C in the presence of potassium carbonate and palladium nanoparticles formed in situ from palladium chloride under focused microwave irradiation. High to excellent product yields were achieved. The reaction medium and catalyst could be easily recycled at least five times without significant loss in reactivity. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1259310

LETTER
369
In Situ Generation of Palladium Nanoparticles: Reusable, Ligand-Free Heck
Reaction in PEG-400 Assisted by Focused Microwave Irradiation
Efficient
H
ec
k
C
h
oupling of
e
ryl Iodide
n
s
with
T
ermi
g
nal
O
lefins yin Du,*a Wanwei Zhou,a Lin Bai,*b Fen Wang,a Jin-Xian Wanga
a
Key Laboratory of Eco-Environment Related Polymer Materials of Ministry of Education, Key Laboratory of Polymer Materials of
Gansu Province & College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, P. R. of China
Fax +86(931)7971989; E-mail: zhengyin_du@nwnu.edu.cn
b
School of Chemistry and Environmental Sciences, Lanzhou City University, Lanzhou 730070, P. R. of China
Received 13 October 2010
sis due to its interesting characteristics, including high
polarity, high boiling points, wide range for the regulation
of molecular weight, low toxicity, and good environmen-
tal compatibility.10 In recent years, Heck reaction per-
Abstract: A rapid and efficient Heck coupling reaction of aryl io-
dides with terminal olefins was conducted in PEG-400 at 120 °C in
the presence of potassium carbonate and palladium nanoparticles
formed in situ from palladium chloride under focused microwave ir-
radiation. High to excellent product yields were achieved. The reac- formed in PEG has begun to catch the attention of
tion medium and catalyst could be easily recycled at least five times
without significant loss in reactivity.
chemists. The Heck reaction of aryl bromide was success-
fully conducted in PEG-2000 catalyzed by 5 mol% of pal-
ladium acetate.11 In 2006, Lamaty and co-workers12 also
Key words: Heck reaction, ligand-free palladium catalysis, palla-
dium nanoparticles, focused microwave irradiation, PEG-400,
green chemistry
reported a ligand-free copper-catalyzed Heck reaction in
PEG-3400 in the presence of potassium carbonate under
microwave irradiation. The use of PEGs is not limited
only to the reaction media in the chemical transforma-
Palladium-catalyzed coupling of olefins with aryl and vi-
nyl halides, known as the Heck reaction, is one of the most
powerful synthetic methods for the formation of carbon–
carbon bonds.1,2 The traditional Heck reaction is typically
performed with various palladium-phosphine complexes
as catalysts in the presence of a suitable base.3–5 However,
most of these palladium complexes suffer from some
drawbacks, such as the tedious multistep syntheses, the
high sensitivity of ligands toward air and moisture, the
high cost of the catalysts, and the use of various additives.
Therefore, operationally and economically more advanta-
geous ligand-free Heck reaction catalyst systems have be-
come an important aspect of studying this reaction. A few
examples were reported by using Pd(OAc)2 as ligand-free
palladium precursor in the presence of rhodium or copper
co-catalyst and tetrabutylammonium bromide or iodine as
additives in organic solvents.6,7 A variant Heck reaction of
alkenyl nonaflates and terminal alkenes was also conduct-
ed in good yields with Pd(OAc)2 as catalyst in DMF at
room temperature,8 but long reaction time (11–37 h) was
required for complete conversion. Although a simple cat-
alyst system of Pd(OAc)2 in combination with K3PO4 as
the base and DMA as the solvent was used as a highly re-
active catalyst for the Heck reaction of aryl bromide in the
absence of any stabilizing ligands or special additives, it
still suffered from long reaction times of more than 20
hours.9
tions. PEG polymers with high molecular weight are also
regarded as reducing agents for the preparation of palladi-
um nanoparticles from Pd(II). Wang et al. reported that
PEG-2000, as a green, recoverable medium and stabilizer,
was used in Pd(OAc)2-catalyzed Heck reaction, wherein
PEG could reduce Pd(II) to Pd(0), which made it possible
to prepare palladium nanoparticles easily in PEG in the
absence of normally adopted reducing agents such as hy-
drazine, hydrogen, sodium borohydride, etc.13
As we know, palladium chloride is a convenient and inex-
pensive source of palladium. However, palladium chlo-
ride as a ligand-free catalyst for Heck reaction remains
extremely rare. It was described that Heck coupling of io-
dobenzene and olefins using a simple PdCl2 and Et3N cat-
alytic system was explored in the ionic liquid of
[bmim][PF6].14 Palladium nanoparticles formed from the
reduction of palladium chloride with methanol in per-
fluorinated solvents were proved to be an efficient recov-
erable catalysts for Heck reactions.15 Moreover, Pd(0)
nanoparticles could be generated from palladium chloride
in water under ultrasonic irradiation and acted as good
catalyst for Heck reaction under these conditions.16 How-
ever, to the best of our knowledge, there has been no re-
port about palladium nanoparticles generated from
ligand-free PdCl2-catalyzed Heck reaction in liquid PEG
of lower molecular weight under microwave irradiation.
We report herein our preliminary results regarding the
Heck reaction performed with palladium chloride as cata-
lyst in PEG-400 under microwave irradiation, wherein
PEG-400 was found to act as both a reducing agent and a
stabilizer, which can reduce Pd(II) to Pd(0) to form and
stabilize palladium nanoparticles. The reaction was per-
formed in a focused microwave synthesis system so that it
was possible to control the temperature, pressure, micro-
Recently, polyethylene glycol (PEG) has been found to be
a highly prospective solvent system to replace volatile or-
ganic solvents in separation, catalysis and organic synthe-
SYNLETT 2011, No. 3, pp 0369–0372
x
x.
x
x.
2
0
1
1
Advanced online publication: 13.01.2011
DOI: 10.1055/s-0030-1259310; Art ID: W16310ST
© Georg Thieme Verlag Stuttgart · New York

370
Z. Du et al.
LETTER
wave power, and reaction time very easily and with a high results previously reported, wherein a higher excess of the
degree of reproducibility. What is more important is that base was used.8,15,16 The amount of PdCl2 was also evalu-
the reaction is insensitive to air and moisture, and the Pd- ated. It was seen that all the reactions examined led to
PEG catalyst system can be readily recovered and reused some degree of conversions but only the use of 1 mol% of
five times without obvious deactivation.
palladium chloride gave the best result (Table 1, entries 6,
14 and 15). In addition, the reaction was sensitive to mi-
crowave irradiation time. A reaction time of 12 minutes
was the optimal time to give the coupling product in high
yield (Table 1, entry 6), while shorter and longer reaction
time decreased the yield (Table 1, entries 11 and 12).
Temperature as an important factor for this reaction was
examined in the range of 110–130 °C (Table 1, entries 6–
10). The results indicated that the highest yield of cinnam-
ic acid was obtained at 120 °C with an irradiation time of
12 minutes.
As a starting point for the development of our microwave-
mediated methodology and reaction in PEG-400, we ini-
tially studied the microwave-promoted coupling of iodo-
benzene with acrylic acid for optimizing reaction
conditions. The effects of base, temperature, reaction time
and the amount of catalyst on the yield of the coupling
reaction are summarized in Table 1.
Table 1 Optimized Conditions via the Coupling of Iodobenzene
with Acrylic Acida
PdCl2
According to the above optimized conditions, other sub-
strates were examined for the Heck reaction. Unfortunate-
ly, low yields were obtained by using stoichiometric
amount of K2CO3. Therefore the effect of the amount of
the base was further investigated through a representative
reaction of the coupling of 4-iodoanisole with acryloni-
trile (Table 2). The results showed that too little or large
excess of potassium carbonate gave low yields of the
product. It was evident that two equivalents of K2CO3
made the coupling reaction more efficient.
+
I
COOH
PEG-400, base, MW
COOH
Entry
Base
(mmol)
PdCl2
(mmol%) (min)
Time
Temp
(°C)
Yield
(%)b
1
2
none
1
12
12
12
12
12
12
12
12
12
12
8
120
120
120
120
120
120
110
115
125
130
120
120
120
120
120
Trace
75
74
64
92
95
76
92
94
93
88
92
85
60
34
KOH (0.25)
1
3
NaOH (0.25)
Et3N (0.25)
1
4
1
Table 2 Optimizing the Amount of Base via the Coupling of 4-
5
Na2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
K2CO3 (0.25)
1
Iodoanisole with Acrylonitrilea
6
1
PdCl2
MeO
I
MeO
PEG-400, K2CO3, MW
7
1
CN
+
8
1
CN
9
1
Entry
K2CO3 (mmol)
0.50
Yield (%)b
10
11
12
13
14
15
1
1
2
3
4
5
74
78
81
81
80
1
0.75
1
10
14
12
12
1.00
1
1.25
0.5
0.25
1.50
a Reaction conditions: 4-iodioanisole (0.5 mmol), acrylonitrile (0.6
mmol), PdCl2 (1 mmol%), PEG-400 (3 mL), microwave irradiation at
120 °C for 12 min on 10 W.
a Reaction conditions: iodobenzene (0.5 mmol), acrylic acid (0.6
mmol), PEG-400 (3 mL), microwave power: 10 W.
b Isolated yield.
b Isolated yield.
Several bases were first screened for the reaction. The re-
sults showed that the effect of bases on the reaction was
significant (Table 1, entries 1–6). When no base was used
in this reaction, only trace quantities of the desired prod-
uct were detected. A comparative study of various bases,
such as NaOH, KOH, Et3N, Na2CO3, and K2CO3, in the
reaction showed that K2CO3 was more effective for this
coupling. It is noteworthy that the use of stoichiometric
amount of potassium carbonate (i.e., 0.5 equiv relative to
iodobenzene) could lead to high yield of 95% of cinnamic
acid under these conditions, which was different from the
The scope of the reaction was extended to various aryl io-
dides and terminal olefins applying the optimized
conditions17 as shown in Table 2 (entry 3). As shown in
Table 3, it was found that there were obvious electronic
and steric effects of substituents on the yields of this reac-
tion. For terminal alkene with the same functional group,
aryl iodide with electron-donating substituent gave lower
yield of the product than that with electron-withdrawing
group (Table 3, entries 2 vs. 3; 6 and 7 vs. 8; 10 and 11 vs.
12; 14 vs. 15). The carboxyl group as a strong electron-
withdrawing substituent also showed high reactivity. Me-
Synlett 2011, No. 3, 369–372 © Thieme Stuttgart · New York

LETTER
Efficient Heck Coupling of Aryl Iodides with Terminal Olefins
371
Table 3 Heck Reactions of Aryl Iodides with Terminal Olefinsa
thyl 2-iodobenzoate led to a decrease of the product yield
in comparison with 4-iodobenzoic acid (Table 3, entries 4
and 3, respectively), which may be due to the larger steric
hindrance of the benzoate. The reactivity of terminal al-
kenes was also different in accordance with the attached
functional groups. The active order of terminal olefins
with various functional groups was found to be: COOH >
Ph > CN > COOn-Bu > COOEt > COOMe, which could
be seen from the corresponding yields of products (e.g.,
Table 3, entries 3, 12, 8 and 15). It was obvious that the
stronger electron-withdrawing ability of functional group,
the higher the reactivity of the alkene and the yield of the
Heck product. It should be pointed out that all of the ob-
tained products were trans isomers, which were identified
by 1H NMR and melting point.
R2
PdCl2
+
I
R1
PEG-400, K2CO3, MW
R1
R2
Entry
1
R1
R2
Product
1a
Yield (%)b
95
H
COOH
COOH
COOH
COOH
CN
2
4-OMe
1b
1c
87
3
4-COOH
2-COOMe
H
92
4
1d
2a
60
5
71
6
4-OMe
4-NH2
4-COOH
H
CN
2b
2c
81
7
CN
77
In order to further examine the scope and limitation of this
protocol, the reactivity of substituted aryl bromides and
aryl chlorides was studied under the same conditions. It
was unfortunate that poor yields were obtained for aryl
bromides with most of the substrates remaining unreacted
and no reactions were observed for aryl chlorides.
8
CN
2d
3a
82
9
Ph
74
10
11
12
13
14
15
16
17
18
19
4-OMe
4-NH2
4-COOH
H
Ph
3b
3c
73
Ph
85
To check the reusability of the reaction medium as well as
the catalyst, the coupling of iodobenzene with acrylic acid
in Table 3 (entry 1) was chosen as a model reaction. After
the first experiment, the reaction mixture was acidified
with hydrochloric acid and extracted with diethyl ether.
The residual diethyl ether and water in PEG were re-
moved by evaporation under reduced pressure. After that,
the PEG and Pd catalyst were subjected to the next run of
the Heck reaction by charging with the same substrates.
All recycling experiments were conducted in parallel and
the results in Table 4 are the average yields of two parallel
experiments. As seen from this Table, five subsequent re-
cycle and reuse of the catalyst system showed little de-
crease in the yield of cinnamic acid.
Ph
3d
4a
91
COOn-Bu
COOn-Bu
COOn-Bu
COOEt
COOEt
COOEt
COOMe
71
4-NH2
4-COOH
H
4b
4c
75
78
5a
41
4-OMe
4-NH2
4-OMe
5b
5c
52
53
6a
46
a Reaction conditions: aryl iodide (0.5 mmol), olefin (0.6 mmol),
PdCl2 (1 mmol%), K2CO3 (1.0 mmol; 0.25 mmol for entry 1), PEG-
400 (3 mL), microwave irradiation at 120 °C for 12 min on 10 W.
b Isolated yield.
In order to further investigate the catalyst system, a blank
experiment without any substrate in PEG-400 under the
abovementioned microwave conditions was conducted.
1
Analysis of PEG-400 after the blank experiment by H
Table 4 Recycle of the Catalyst System
NMR revealed that a new peak appeared at d = 9.732 ppm,
which could be attributed to the formation of an aldehyde
group from end hydroxyl of PEG oxidized by Pd(II)
whereas Pd(II) was reduced into Pd(0). This was similar
to the results reported in the previous literature.13 It is
clear that palladium nanoparticles were formed through
the oxidation of the hydroxyl group on PEG under micro-
wave irradiation of PdCl2 in PEG-400 in the absence of
any other reducing agent.
Entry
Recycle number
Yield (%)a
1
0 (fresh)
95
86
92
95
89
83
2
1
2
3
4
5
3
4
5
Transmission electron microscope (TEM) was used for
the analysis of the size and distribution of palladium nano-
particles. Figure 1 presents the TEM images of palladium
nanoparticles in blank experiment (left) and after the reac-
tion (right) under the same microwave conditions. It was
seen that the average dimensions of nano-Pd fabricated in
blank experiment and after the reaction deviated little.
Both samples showed an average size of the particle of 5–
8 nm. This may be a consequence of the good stability and
6
a Isolated yield.
dispersion effect of PEG on the palladium nanoparticles,
which resulted in the excellent storage stability and reus-
ability of the catalyst system. Obviously, the real catalyst
was in situ formed nano-Pd particles, but not the original
Pd(II) species.
Synlett 2011, No. 3, 369–372 © Thieme Stuttgart · New York

372
Z. Du et al.
LETTER
Cole-Hamilton, D. J. Chem. Commun. 2001, 779.
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Dupont, J. Org. Lett. 2003, 5, 983.
The leaching of Pd/PEG-400 system was also studied by
determination of the Pd content in the crude product at the
end of the reaction of Table 3 (entry 1). The result of ICP–
AES analysis showed that only 0.53% of Pd relative to the
original Pd content was leached, which indicated that the
extent of leaching of palladium species was low. It is es-
pecially significant for the obtaining of the products of
high purity and scaleup synthesis by using this protocol.
(4) (a) Kaukoranta, P.; Kallström, K.; Andersson, P. G. Adv.
Synth. Catal. 2007, 349, 2595. (b) Bergbreiter, D. E.;
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Tetrahedron Lett. 1997, 38, 8867. (b) Vries, A. H. M.;
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Synth. Catal. 2007, 349, 1019.
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7528.
Figure 1 TEM pictures of nano-Pd in PEG-400 under microwave
irradiation at 120 °C for 12 min on 10 W: blank (left) and after reac-
tion, general workup was conducted (right)
(10) Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D.
Green Chem. 2005, 7, 64.
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N. R. Org. Lett. 2002, 4, 4399.
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(13) Luo, C.; Zhang, Y.; Wang, Y. J. Mol. Catal. A: Chem. 2005,
229, 7.
In conclusion, we have disclosed a simple and efficient
palladium-catalyzed protocol for the Heck cross-coupling
reaction of aryl iodides with terminal olefins in PEG-400
under microwave irradiation. Palladium nanoparticles
were formed in situ from PdCl2 and PEG in the absence of
any other reducing reagent. The Pd-PEG system exhibited
a high activity towards the Heck reaction without the use
of any ligand or activation. The medium as well as the cat-
alyst could be easily recycled five times without signifi-
cant loss in reactivity, which was of great importance to
practical applications.
(14) Yoon, B.; Yen, C. H.; Mekki, S.; Wherland, S.; Wai, C. M.
Ind. Eng. Chem. Res. 2006, 45, 4433.
(15) Moreno-Manas, M.; Pleixats, R.; Villarroya, S.
Organometallics 2001, 20, 4524.
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Zhou, M. J. Org. Chem. 2006, 71, 4339.
(17) General Procedure for the Heck Coupling Reactions of
Aryl Iodides with Terminal Olefins: In a 10-mL glass tube
were placed aryl iodide (0.5 mmol), terminal olefin (0.6
mmol), K2CO3 (1.0 mmol), PdCl2 (0.005 mmol), PEG-400
(3 mL), and a magnetic stir bar. The vessel was sealed with
a septum and placed into the microwave cavity. Microwave
irradiation of 10 W was used, and the temperature was
ramped from r.t. to 120 °C. Once the temperature of
120 °C was reached, the reaction mixture was held at this
temperature for 12 min. After cooling the mixture to r.t., the
reaction vessel was opened, the contents were extracted with
Et2O (5 × 5 mL; for substrates with carboxyl group,
acidification using hydrochloric acid was needed before
extraction) and the combined organic layers were dried over
anhyd MgSO4. The solvent was removed by evaporation
under reduced pressure to afford the crude products, which
were further purified by recrystallization or by column
chromatography on silica gel using petroleum ether and
EtOAc as eluent. The catalyst system (Pd-PEG) was
recycled by the evaporation of Et2O and H2O under reduced
pressure and could be reused directly in the next run.
Selected Data for Compound 1a: white crystal; mp 133–
134 °C. 1H NMR (400 MHz, CDCl3): d = 12.13 (s, 1 H), 7.82
(d, J = 16.0 Hz, 1 H), 7.54–7.56 (m, 2 H), 7.39–7.43 (m, 3
H), 6.47 (d, J = 16.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3):
d = 172.75, 147.12, 133.99, 130.75, 128.95, 128.36, 117.30.
MS (EI): m/z = 148 [M+], 105, 77. IR: 1682, 1628, 1419,
767, 705 cm–1. Anal. Calcd for C9H8O2 (148.05): C, 72.96;
H, 5.44. Found: C, 72.64; H, 5.38.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
Financial support by the Natural Science Foundation of China
(20702042) and the Key Laboratory of Polymer Materials of Gansu
Province (zd-06-18) is acknowledged.
References and notes
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R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320.
(2) For selected reviews of Heck reaction, see: (a) Beletskaya,
I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.
(b) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron
2001, 57, 7449. (c) Meyer, F. E. Angew. Chem., Int. Ed.
Engl. 1994, 33, 2379. (d) Crisp, G. T. Chem. Soc. Rev. 1998,
27, 427. (e) Casey, M.; Lawless, J.; Shirran, C. Polyhedron
2000, 19, 517. (f) Dick, H. A.; Heck, R. F. J. Org. Chem.
1975, 40, 1083.
(3) (a) Gibson, S.; Foster, D. F.; Eastam, G. R.; Tooze, R. P.;
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