An active and recyclable polystyrene-supported N-heterocyclic carbene-palladium catalyst for the Suzuki reaction of arylbromides with arylboronic acids under mild conditions

Article abstract of DOI:10.1055/s-2005-872669

A novel polymer-supported imidazolium salt has been prepared from a bisimidazolium salt and cross-linked chloromethyl polystyrene. The polymer-supported N-heterocyclic carbene-palladium complex, generated from the supported bisimidazolium salt and Pd(OAc)₂, efficiently catalyzed the Suzuki coupling reaction of aryl bromides and arylboronic acids under air in aqueous DMF solution at room temperature, giving biaryls in good to excellent yields. The catalyst could be reused several times still retaining high activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872669

LETTER
2305
An Active and Recyclable Polystyrene-Supported N-Heterocyclic Carbene–
Palladium Catalyst for the Suzuki Reaction of Arylbromides with Arylboronic
Acids under Mild Conditions
P
olystyrene-Sup
a
ported
N
-H
i
eteroc
r
yclic Ca
a
rbene–Palla
n
diumCatalyst Kang,a,b Qiang Feng,a Meiming Luo*a
a
Key Laboratory of Green Chemistry & Technology of Ministry of Education at Sichuan University, College of Chemistry,
Sichuan University, Chengdu 610064, P. R. China
b
College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002, P. R. China
Fax +86(28)85462021; E-mail: luomm@email.scu.edu.cn
Received 2 May 2005
examples of heterogeneous catalysts by anchoring NHC–
Pd complexes for Suzuki reaction have been reported.7
Zhang’s group7a has recently reported a SiO2-supported
NHC–Pd catalyst that could only be used for 2–3 times
Abstract: A novel polymer-supported imidazolium salt has been
prepared from a bisimidazolium salt and cross-linked chloromethyl
polystyrene. The polymer-supported N-heterocyclic carbene–palla-
dium complex, generated from the supported bisimidazolium salt
and Pd(OAc)2, efficiently catalyzed the Suzuki coupling reaction of since the NHC–Pd complex was physically absorbed on
aryl bromides and arylboronic acids under air in aqueous DMF
solid surface. The polymer-supported NHC–Pd catalysts
solution at room temperature, giving biaryls in good to excellent
developed by Lee’s group required heating condition and
yields. The catalyst could be reused several times still retaining high
more active aryliodide as substrate in most cases, and the
activity.
reuse of those catalysts was not satisfactory. Herein, we
report an active polystyrene-supported NHC–Pd catalyst
that enables the Suzuki couplings of aryl bromides and
Key words: Suzuki reaction, N-heterocyclic carbene–palladium
complex, polymer-supported catalyst, recyclable catalyst
arylboronic acids at room temperature without the need of
inert gas protection. The catalyst showed outstanding
Suzuki cross-coupling reaction is one of the most effi-
stability in air, water and organic solvents, and was reused
cient, popular, and convenient methods for synthesizing
five times still retaining high activity.
unsymmetrical biaryls.1 As the biaryl motif is found in a
range of pharmaceuticals, herbicides, and natural prod-
ucts as well as in conducting polymers and liquid crystal-
OH
N
N
NCH3
NCH3
Cl
Cl
2Cl–
+
N
HO
line materials, development of new efficient ligands and
improved conditions for Suzuki reaction has received
much attention.2 Due to their versatile processing capabil-
ities, ease of separation and recycling, polymer-supported
catalysts offer many advantages for industrial applica-
tions. Many immobilized Pd catalysts based on polymer-
supported phosphine or amine ligands have been devel-
oped for Suzuki reaction.3 However, the activity of those
catalysts decreased in recycling experiments because of
Pd leaching from their supports. Generally, mild condi-
tions and strong interactions between Pd and ligands are
in favor of avoiding Pd leaching.
H3CN
CH3CN, 80 °C
1
Cl
N
N
NCH3
KI, Bu3N, DMF
25 °C
O
2X–
NCH3
X = Cl or I
2
Pd(OAc)2, Na2CO3
DMF/H2O (1:1), 50 °C, 4 h
supported NHC–Pd catalyst
3
Scheme 1 Preparation of the polystyrene-supported NHC–Pd
catalyst 3
In recent years, the stable N-heterocyclic carbene (NHC)
complexes of PdII or Pd0 have been used as catalysts for
Suzuki reactions.4 In contrast to the widely used phos-
phine complexes,5 they have shown remarkable stability
towards heat, oxygen and moisture, and represent a re-
markable improvement with respect to the catalytic activ-
ity. The NHC ligands bind to both Pd0 and PdII centers
substantially stronger than phosphine ligands, and are
highly suitable for attachment to solid supports owing to
anticipated low level of metal leaching.6 So far, only a few
Our work focused on the use of an ether linkage to attach
the bisimidazolium salt 1 to the Merrifield resin (2%
cross-linked with divinylbenzene, 100–200 mesh size, 2.7
mmol Cl/g; Scheme 1). The bisimidazolium salt 1 was
prepared in 60% yield by heating one equivalent of 1,3-
dichloro-2-propanol and two equivalents of 1-methylimi-
dazole in MeCN at 80 °C for four days.8 The polystyrene-
supported bisimidazolium salt 2 was readily prepared by
reacting 1 with chloromethyl polystyrene in the presence
of KI.9 The loading of the imidazolium groups was de-
termined by means of the nitrogen content obtained from
elementary analysis (N, 1.4%, 0.5 mmol imidazolium/g).
SYNLETT 2005, No. 15, pp 2305–2308
1
9
.0
9
.2
0
0
5
Advanced online publication: 07.09.2005
DOI: 10.1055/s-2005-872669; Art ID: U12905ST
© Georg Thieme Verlag Stuttgart · New York

2306
T. Kang et al.
LETTER
Table 2 Coupling of 4-Bromoanisole and Phenylboronic Acid
The polystyrene-supported NHC–Pd catalyst 3 was pro-
duced by mixing Pd(OAc)2 and 2 in DMF–H2O (1:1, v/v)
with Na2CO3 as the base at 50 °C for 4 hours.10 The Pd
loading was 0.1 mmol/g as measured by inductively cou-
pled plasma-atomic emission spectrometry (ICP-AES)
suggesting only partial imidazolium groups in the support
participated in the formation of NHC–Pd complex. It is
not clear whether both of the imidazolium groups in each
bisimidazolium salt took part in the formation of NHC–Pd
complex.
Catalyzed by 3a
Entry Solvent (v:v)
Base
Time (h) Yield (%)b
1
2
DMF
Na2CO3
K2CO3
NaOH
12
12
12
12
12
12
12
12
12
12
12
16
20
24
23
21
0
DMF
3
DMF
4
DMF
Na3PO4
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
Na3PO4
Na2CO3
Na2CO3
Na2CO3
20
13
24
79
75
88
87
75
93
96
99
5
Dioxane
The swelling properties of the polystyrene-supported
bisimidazolium salt 2 and the catalyst 3 in various sol-
vents were measured (Table 1).11 The swelling studies are
important for identifying the suitable reaction medium to
perform reaction on polymer supports. As can be seen
from Table 1, the polymeric supports have high swelling
volumes in water, MeOH and DMF. In these solvents, the
catalyst 3 would be able to capture reagents easily, and
higher efficiency of the catalytic cycle would be reached.
6
H2O
7
DMF–H2O (2:1)
DMF–H2O (1:2)
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
8
9
10
11
12
13
14
Table 1 Swelling Properties of the Polymer-Supported Bisimidazo-
lium Salt 2 and the Catalyst 3
Polymeric Swelling volume in solvent (mL/g polymeric support)
support
Dry
H2O
MeOH DMF CH2Cl2 THF Diox-
ane
a Reaction conditions: 4-bromoanisole (0.5 mmol), phenylboronic
acid (0.6 mmol), base (2.5 mmol), solvent (4 mL), catalyst 3 (20 mg,
2 mmol Pd), r.t.
2
3
1.8
1.8
4.0
4.0
4.4
4.4
5.0
5.0
3.5
3.5
2.3
2.3
2.9
2.9
b Isolated yields were based on bromide.
The catalytic activity of the polymer-supported NHC–Pd
catalyst 3 was investigated by coupling 4-bromoanisole
and phenylboronic acid.12 As illustrated in Table 2, the
presence of water appears to be essential in order to per-
form the reactions (entries 7–14). The conversion of 4-
bromoanisole was very low when DMF, dioxane or water
each was used as solvent (entries 1–6). Among the sol-
vents tested, the DMF–water (v/v 1:1) gave the best result,
which is likely attributed to the better solubility of both
the reactants and the base in the co-solvent.
The catalyst 3 was used 5 times and still remained highly
active.
Table 4 summarizes the coupling of different arylboronic
acids with various arylbromides catalyzed by catalyst 3.
The results reveal the wide scope of this method that is
compatible with nitro, methoxy, trifluoromethyl, and car-
bonyl in bromides. It was observed that bromides with
electron-rich groups to electron-poor groups reacted effi-
ciently affording the corresponding products in high
yields. Arylboronic acids with ortho substituents led to
lower, but still good yields (entries 15–17).
Several bases were examined to indicate the base effect on
the reaction. It seems that carbonate bases are more effec-
tive in activating the palladium catalyst. No detectable
coupling products were observed when NaOH was used
as a base (entry 3). When the reaction was carried out in
DMF–water (v/v 1:1), both Na2CO3 and K2CO3 gave ex-
cellent yields (entries 9, 10, 12–14). Higher yields were
observed by prolonging the reaction time (entries 12–14).
The product formation was almost quantitative after 24
hours (entry 14).
It is noteworthy that all crossing-coupling reactions listed
in Table 2, Table 3 and Table 4 were carried out under air
and no visible palladium black formation was observed
during the course of the reaction.
Table 3 Recycling of the Catalyst 3a
Run
1
2
3
4
5
Yield (%)b
99
96
95
95
94
The recycling of the catalyst 3 was also investigated for
the reaction of 4-bromoanisole with phenylboronic acid
(Table 3). The catalyst 3 was stable to air and moisture,
and the reactions could be carried out under air by using
technical grade solvents. After separation and washing,
the catalyst was reused under the same reaction conditions
as for the initial run without any need for regeneration.
a Reaction conditions: 4-bromoanisole (0.5 mmol), phenylboronic
acid (0.6 mmol), catalyst 3 (20 mg, 2 mmol Pd), Na2CO3 (2.5 mmol),
DMF (2 mL), H2O (2 mL), r.t., 24 h.
b Isolated yields were based on bromide.
Synlett 2005, No. 15, 2305–2308 © Thieme Stuttgart · New York

LETTER
Polystyrene-Supported N-Heterocyclic Carbene–Palladium Catalyst
2307
In conclusion, we have developed an active, reusable carried out under extremely mild conditions: room tem-
polymer-supported NHC–Pd catalyst prepared from perature, aqueous DMF solution, Na2CO3 as the base, and
Pd(OAc)2 and the polystyrene-supported bisimidazolium without the need of inert gas protection. Using very low
salt 2. The catalyst was highly active in catalyzing the catalyst loading, the catalyst 3 could be reused several
Suzuki reaction of aryl bromides with arylboronic acids times still retaining its activity.
affording biaryls in high yields. The Suzuki reaction was
Table 4 Coupling Reactions of Various Arylbromides with Different Arylboronic Acids Catalyzed by Polystyrene-Supported NHC–Pd
Catalyst 3a
Entry
1
Arylbromide
Arylboronic acid
Product
Yield (%)b
98
Br
CH3
B(OH)2
CH3
2
3
4
99
97
95
OCH3
Br
Br
OCH3
C(CH3)3
C(CH3)3
OCH3
OCH3
OCH3
OCH3
CF3
Br
Br
5
6
94
73
CF3
CF3
NO2
CF3
NO2
Br
Br
7
8
89
87
Br
Br
9
97
73
CH3
H3C
Br
10
COCH3
H3COC
Br
11
12
13
14
15
98
92
99
97
85
COOH
Br
Br
Br
COOH
NO2
NO2
OCH3
H3C
B(OH)2
H3C
OCH3
(H3C)3C
B(OH)2
H3CO
C(CH3)3
OCH3
OCH3
B(OH)2
OCH3
16
17
85
77
CH3
OCH3
CH3
Br
H3C
Br
OCH3
H3C
a Reaction conditions: aryl bromide (0.5 mmol), arylboronic acid (0.6 mmol), catalyst 3 (20 mg, 2 mmol Pd), Na2CO3 (2.5 mmol), DMF (2 mL),
H2O (2 mL), r.t., 24 h.
b Isolated yields were based on bromide.
Synlett 2005, No. 15, 2305–2308 © Thieme Stuttgart · New York

2308
T. Kang et al.
LETTER
white solid, which was filtered and dried under vacuum
Acknowledgment
affording the salt 1 in 60% yield. 1H NMR (600 MHz,
DMSO-d6): d = 3.88 (s, 6 H, NCH3), 4.20 (m, 1 H, CHOH),
4.22–4.51 (br, 4 H, NCH2), 7.79 (s, 2 H, NCH), 7.87 (s, 2 H,
NCH), 9.36 (s, 2 H, NCHN). 13C NMR (150 MHz, DMSO-
d6): d = 36.23 (NCH3), 52.17 (CHOH), 68.21 (NCH2),
123.44 (NCH), 123.77 (NCH), 137.74 (NCHN). HRMS
(ESI): m/z calcd for C11H18Cl2N4O [M – 2Cl]2+: 111.0741;
found: 111.0729.
The authors are grateful to National Natural Science Foundation of
China (No. 20372049) for financial support.
References
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A mixture of Merrifield polymer (200 mg 2.7 mmol Cl/g),
KI (30 mg, 0.18 mmol), tributylamine (0.3 g, 1.62 mmol)
and the bisimidazolium salt 1 (158 mg, 0.54 mmol)
dissolved in DMF (10 mL) was stirred for 4 d at r.t. The
polymer was filtered off and washed with DMF (6 × 10 mL),
MeOH (6 × 10 mL), H2O (6 × 10 mL), and then dried under
vacuum. The loading of the imidazolium groups was
determined by means of the nitrogen content obtained from
elemental analysis (N, 1.4%, 0.5 mmol imidazolium/g).
(10) Procedure for the Preparation of Polystyrene-Supported
NHC–Pd Complex 3.
In a dry nitrogen atmosphere, a mixture of the imidazolium
loaded polymeric support 2 (200 mg, 0.5 mmol
imidazolium/g) and Pd(OAc)2 (22.5 mg, 0.1 mmol) was
suspended in DMF (2 mL). To this suspension was added an
aqueous solution (2 mL) of Na2CO3 (106 mg, 1.0 mmol).
The mixture was stirred at r.t. for 30 min, and then agitated
for 4 h at 50 °C in an oil bath. After filtration, the polymeric
support was washed vigorously with distilled H2O (10 × 10
mL), MeOH (10 × 10 mL), and dried under reduced pressure
to give 3. ICP-AES: 100 mmol Pd/g.
(11) Procedure for Measuring the Swelling Properties of the
Polystyrene-Supported Bisimidazolium Salt 2 and the
Catalyst 3.
The swelling volumes of polymeric supports in various
solvents were measured in a fritted column (ID 0.8 cm,
length 20 cm). The polymeric support (1.0 g) was swollen in
a solvent at r.t. for 2 h, and then washed with a 10-fold
volume of each solvent. After filtration, the volume of the
polymeric support was measured.
(12) Representative Procedure for Suzuki Reaction (Table 2,
Entry 14).
The catalyst 3 (20 mg, 2 mmol Pd) was suspended with DMF
(2 mL). After a mixture of 4-bromoanisole (63 mL, 0.5
mmol), phenylboronic acid (75 mg, 0.6 mmol), and Na2CO3
(265 mg, 2.5 mmol) in distilled H2O (2 mL) was added, the
reaction mixture was stirred at r.t. for 24 h without the
protection of inert gas. The catalyst was filtered and washed
with distilled H2O (5 × 4 mL) and Et2O (5 × 4 mL), and dried
in vacuo for use in the next run. The organic portion was
dried over MgSO4 and evaporated under reduced pressure.
The biphenyl product (91 mg, yield 99%) was isolated by
column chromatography (eluent: n-hexane).
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5827.
(8) Procedure for the Preparation of the Bisimidazolium
Salt 1.
In a dry nitrogen atmosphere, a mixture of 1,3-dichloro-2-
propanol (1.29 g, 10 mmol) and 1-methylimidazole (1.72 g,
21 mmol) was stirred in MeCN (20 mL) at 80 °C for 4 d in
an oil bath. The solvent was removed completely under
vacuum. Then, CH2Cl2 was added to the residue to give a
Synlett 2005, No. 15, 2305–2308 © Thieme Stuttgart · New York