PdEDTA held in an ionic liquid brush as a highly efficient and reusable catalyst for Suzuki reactions in water

Article abstract of DOI:10.1021/jo900481y

(Chemical Equation Presented) An efficient and reusable catalyst with PdEDTA immobilized in an ionic liquid brush and a green procedure have been developed for coupling aryl iodides and bromides with phenylboronic acid. These reactions were conducted in water under aerobic conditions with water-insoluble or even solid aryl halides. The protocol has the advantages of excellent yields, environmental friendliness, and catalyst recyclability. There was no apparent loss of catalyst efficiency until the 10th cycle.

Full text of DOI:10.1021/jo900481y

pubs.acs.org/joc
reactions,1 were carried out with the aid of organic solvents.
PdEDTA Held in an Ionic Liquid Brush as a Highly
Efficient and Reusable Catalyst for Suzuki Reactions
in Water
While the Suzuki-Miyaura reaction has become a powerful
and convenient synthetic tool for the construction of C-C
bonds in biaryl compounds4,5 and is also nowadays of great
industrial significance,6,7 it suffers from at least one of the
following shortcomings: the need for complicated and/or
toxic ligands (i.e., phosphine) and organic solvent or cosol-
vent, and the lack of reusability. In the past decades, many
efforts have been made to solve these problems through the
development of active, reusable catalysts and more facile and
benign procedures,8-10 but satisfactory solutions are still a
challenge. Consequently, the development of reusable
and highly efficient alternatives and environment-friendly
procedures with water as the reaction medium is highly
desirable.
Jun-Fa Wei,* Jiao Jiao, Jin-Juan Feng, Jing Lv,
Xi-Ru Zhang, Xian-Ying Shi, and Zhan-Guo Chen
School of Chemistry and Materials Science, Shaanxi Normal
University, Shaanxi Xi’an, 710062, People’s Republic of
China
weijf@snnu.edu.cn
Received March 9, 2009
We recently reported a series of SiO2-supported multi-
imidazolium ionic liquid brushes as a new type of catalyst
that proved to be efficient for either hydrogenation of nitro
aromatics or dihydroxylation of alkenes with H2O2.11 The
coral-like brush provides an ionic liquid microenvironment
for catalytically active species, and has the advantage of
being used in neat water. Moreover, the brush is easy to
separate from reaction mixtures by simple filtration. From
An efficient and reusable catalyst with PdEDTA immo-
bilized in an ionic liquid brush and a green procedure have
been developed for coupling aryl iodides and bromides
with phenylboronic acid. These reactions were conducted
in water under aerobic conditions with water-insoluble or
even solid aryl halides. The protocol has the advantages
of excellent yields, environmental friendliness, and cata-
lyst recyclability. There was no apparent loss of catalyst
efficiency until the 10th cycle.
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DOI: 10.1021/jo900481y
r
Published on Web 07/08/2009
J. Org. Chem. 2009, 74, 6283–6286 6283
2009 American Chemical Society

Wei et al.
JOCNote
SCHEME 1. Preparation of Silica-Immobilized Ionic Liquid
Brush Catalysts
TABLE 1. The Catalytic Activity of SiO2-BisILsR [PdEDTA] in the
Coupling Reaction of 4-Bromoanisole and Phenylboronic Acid a
entry R in cat. (mol %)b (wt %)c time (h) temp (°C) yield (%)d
1
2
3
4
5
6
7
8
9
n-Bu (2.0) (2.0)
n-Oct (1.0) (2.0)
n-Oct (2.0) (2.0)
n-Oct (1.0) (2.0)
n-Oct (0.5) (2.0)
n-Oct (1.0) (1.0)
n-Oct (1.0) (0.5)
n-dodecyl (2.0) (2.0)
CH2Ph (2.0) (2.0)
10
10
6
100
60
77(5)
75
99
99
98
96
89
87
90(2)
FIGURE 1. Silica-immobilized PdEDTA2- ionic liquids.
100
100
100
100
100
100
100
the viewpoints of environmental security and economic
viability, the recoverability and recyclability of such ionic
liquid brushes assume great importance. The significant
advantages of the brushes and a recent report by Bumagin12
in which [PdEDTA2-] was proved to be an efficient catalyst
for the Suzuki-Miyaura reaction motivated us to develop
more efficient and environmentally friendly catalysts and
procedures for this reaction. As part of our investigations of
organic transformations in water, the present communica-
tion reports, for the first time, the use of a palladium-in-
brush catalyst for the Suzuki-Miyaura reaction in water
with excellent yields.
8
12
15
18
12
10
aConditions: 4-bromoanisole (2 mmol), phenylboronic acid
(2.1 mmol), Na2CO3 (4 mmol), Pd catalyst, H2O (10 mL), 100 °C. bThe
charge of catalyst based on Pd relative to the aryl halide (number in the
first set of parentheses). cThe Pd loading on the brush catalysts (number
in the second set parentheses). dYield after chromatographic separation
(based on aryl halide, biphenyl yields in parentheses); average of two
runs.
The PdEDTA held in SiO2-diimidazolium ionic liquid
brushes, termed SiO2-BisILsR [PdEDTA] (Figure 1), were
prepared via the ion-exchange reaction of SiO2-immobilized
diimidazolium ionic liquid brushes, SiO2-BisILsR [Cl], with
aqueous PdEDTA solution, as shown in Scheme 1.
The coupling of 4-bromoanisole and phenylboronic acid
was used as a prototypical reaction for discovery of suitable
reaction conditions, and examination of the activity of
various catalysts. All of the reactions were carried out by
stirring under reflux a mixture of the catalyst, 4-bromoani-
sole, phenylboronic acid, and Na2CO3 in ordinary (not
degassed) water under aerobic conditions. No organic co-
solvent, phosphine ligand, or phase transfer catalyst was
required. 4-Bromoanisole was chosen as the substrate for its
modest reactivity to Suzuki coupling.
The analogue catalysts with n-butyl, benzyl, or n-dodecyl
as the terminal alkyl group were less reactive and gave the
coupling products in lower yields. Moreover, small amounts
of undesired self-coupling products were formed as bypro-
ducts with the n-butyl and benzyl catalysts. These results
indicate that catalysts bearing more or less than eight
carbons in the alkyl chain are less effective. The explanation
may be that the octyl group is more efficient in balancing
critical hydrophobic and hydrophilic parameters. Thus, it
provides a suitable hydrophobic and hydrophilic environ-
ment for the aryl halides and phenylboronic acid to move
into the brushes where the active catalyst attached and for
the coupled product and byproduct (boronate) to move out
of the brushes.
The optimal reaction temperature is 100 °C, at which the
reactions were completed within 8 h with excellent yields,
and no self-coupling products were observed. The reaction
also worked with the n-octyl-terminated catalyst at lower
temperature, but with lower yield (entry 2). The palladium
loading is also important in the brush. The catalyst with a
2 wt % loading worked more efficiently. The catalyst with
a palladium loading less than 0.5 wt % gave inferior
results.
The results listed in Table 1 show that the catalyst with n-
octyl as the terminal alkyl group was the most effective for
the Suzuki-Miyaura coupling reaction. For smooth reac-
tion, 1 mol % of the catalyst was sufficient, giving the desired
coupled product in nearly quantitative yield without detect-
able unwanted self-coupling product (entry 4). Even with an
amount as small as 0.5 mol % the catalyst exhibits good
performance in the reaction, affording the desired product in
a yield comparable with the literature yields (entry 5).
The counteranions of the catalysts had negligible influence
on the reaction. Replacement of chloride with PF6-, which
is generally considered as the best counteranion in ionic
(12) Korolev, D. N.; Bumagin, N. A. Tetrahedron Lett. 2005, 46, 5751–
5754.
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Wei et al.
JOCNote
TABLE 2. The Recycling of SiO2-BisILsOct[PdEDTA] (Runs 1-10)
in the Coupling Reaction of p-Bromoanisole and Phenylboronic Acida
TABLE 4. The PdEDTA-Ionic Liquid Brush-Catalyzed Suzuki Reac-
tion with Substituted Arylboronic Acids
1
2
3
4
5
6
7
8
9
10
yieldb
99
99
99
99
99
100
96
97
98
99
aConditions: 4-bromoanisole:phenylboronic acid:Na2CO3:Pd cata-
lyst=1:1.05:2:0.01 (mol), H2O=5 mL per mmol substrate, 100 °C, 8 h.
bYields after chromatographic separation.
entry
X
R1
R2
time (h)
yield b (%)
1
2
3
4
5
6
7
8
9
Br
Br
Br
I
Br
Br
Br
I
H
4-MeO
4-MeO
4-MeO
4-MeO
4-CF3
4-CF3
4-CF3
4-CF3
7
6
5
6
6
7
8
6
6
6
7
94
94
99
99
98
99
93
4-MeO
3-NO2
4-NO2
H
TABLE 3. Scope of the Suzuki Reaction with PdEDTA-Ionic Liquid
Brush
4-Ac
4-MeO
4-MeO
H
4-Ac
4-MeO
99
Br
Br
Br
4-CO2H
4-CO2H
4-CO2H
88 c
90c
91c
10
11
aConditions: aryl halide (2 mmol), arylboronic acid (2.1 mmol),
Na2CO3 (4 mmol), Pd catalyst (1.0 mol %), H2O (10 mL), 100 °C.
bYield after chromatographic separation (based on aryl halides, biphe-
c
nyl yields in parentheses). Yield after recrystallization from ethanol-
water.
catalyst charge, in sharp contrast to the reported 14%
leaching of Pd/C catalyst.5c No trace of coupled product
was found by addition of the substrate, phenylboronic acid,
and Na2CO3 to the filtrate after the brush was removed.
Tables 3 and 4 present examples demonstrating the scope
of the reactions catalyzed by SiO2-BisILsOct [PdEDTA]. All
of the reactions proceeded under the conditions shown in
Table 2, and were manipulated in air without any special
precautions.
The results show that all of the reactions of aryl halides
including aryl bromides and iodides with the arylboronic
acids were carried out successfully in neat water. Aryl iodides
were clearly more reactive; they gave the coupled products in
yields ranging from 90% to almost 100% for the examples
screened. Aryl bromides readily coupled with arylboronic
acids under the reaction conditions employed and also gave
high yields of coupled products, but the reaction time
required was longer. Even chlorobenzene yielded the
coupled product with PhB(OH)2 in 66% yield when the
reaction time was extended to 30 h. This yield is comparable
to that reported previously wherein chlorobenzene gave a
65% yield under microwave irradiation conditions with
1 mol % of Pd/C.9n The catalyst also worked efficiently with
heteroaryl halides such as 2-iodothiophene, 3-bromopyri-
dine, and 3-iodopyridine (entries 14, 28, and 29, Table 3) as
the coupling partners with high yields.
A broad range of functional groups can be tolerated in the
reaction. Electron-withdrawing and electron-donating sub-
stituents on either the aryl halide or phenylboronic acid did
not have a detrimental effect on the ability of the catalysts to
promote this reaction to completion. The couplings pro-
ceeded successfully to give the desired products in high yields
even in the presence of sensitive groups such as MeCO,
CO2H, NH2, CN, and OH, without any protection. Similar
to the Suzuki-Miyaura reactions reported previously, the
aryl halides with electron-withdrawing groups gave higher
yields than those with electron-donating substituents. No-
tably, 1-bromo-4-iodobenzene gave 4-bromodiphenyl in ex-
cellent yield when 1 equiv of phenylboronic acid was used,
indicating that the reaction was highly selective.
aConditions: aryl halide (2 mmol), phenylboronic acid (2.1 mmol),
Na2CO3 (4 mmol), Pd catalyst (1.0 mol %), H2O (10 mL), 100 °C. bYield
after chromatographic separation (based on aryl halides, biphenyl yields
in parentheses). c2.1 equiv of phenylboronic acid was used. dYield after
recrystallization from ethanol-water.
liquids of the imidazolium type, did not improve the re-
action yields.
It is noteworthy that the palladium-in-brush catalyst can
be recovered by simple filtration after extraction of the
product by ethyl acetate, and recycled. Ten consecutive
preparations of 4-methoxybiphenyl showed no significant
reduction in yield (Table 2). In each case, the catalyst was
recovered by filtration and washed with ethyl acetate and
water, then the experiment repeated. ICP-MS analysis
showed that after filtration of the brush the reaction stream
contained only 0.96 mg L-1 of Pd, i.e., 0.45% of the initial
J. Org. Chem. Vol. 74, No. 16, 2009 6285

Wei et al.
JOCNote
It is particularly noteworthy that because of the solvent
power of the immobilized ionic liquid, water-insoluble aryl
halides were efficiently transformed to the desired products
in excellent yield without the aid of organic cosolvent. The
brush works well with solid aryl halides that do not melt at
the reaction temperature. By contrast, most of the previously
reported heterogeneous and homogeneous catalysts func-
tioned efficiently only with water-soluble aryl halides,10 such
as halobenzoic acids and halophenols; or they had to be used
in organic solvent or water-organic mixed solvent if water-
insoluble haloarylenes were used as the starting material.10f
Furthermore, all of the present reactions were carried out in
neat water without the need for phase transfer catalyst and
protection from air, showing that the methodology has
distinct advantages.
In summary, we have developed an environmentally be-
nign catalyst and procedure for Suzuki-Miyaura cross-
coupling reactions. The catalyst combines the advantages
of ionic liquid, PTC, and Pd catalyst together, and has
proved to be highly efficient and recyclable for Suzuki
reactions in water. Because of its recyclability and the use
of neat water as the reaction medium it is distinguished by
both green and economic advantages from other palladium-
based catalysts. In addition to those features this catalytic
system has the advantage of avoiding the need for inert gas
and an organic cosolvent for water-insoluble aryl halides. In
view of its simplicity and the mild conditions, the present
protocol has been found to be a versatile and green route to
diaryls in the laboratory, and could find industrial applica-
tions. Applications of this type of catalyst to other palla-
dium-catalyzed reactions are in progress and will be reported
in due course.
under vacuum. The catalyst is insensitive to air and moisture,
and stable at room temperature.
2. General Procedure for the Suzuki Reaction. In air, aryl
halide (2 mmol), phenylboronic acid (2.1 mmol, 0.256 g),
Na2CO3 (4 mmol, 0.424 g), 10 mL of distilled water, and
PdEDTA-brush catalyst were combined in a 50 mL round-
bottomed flask. The reaction mixture was magnetically stirred
and the temperature was maintained at 100 °C with an oil bath.
Reaction progress was monitored by TLC. After reaction was
completed, the reaction mixture was cooled to room tempera-
ture and ethyl acetate (20 mL) was added. The catalyst was
separated by filtration, washed with EtOAc (3 Â 5 mL) and
water, and dried in vacuum. The combined organic layer was
washed with saturated NaCl solution then dried with anhydrous
MgSO4, and the solvent was removed under reduced pressure to
give crude product that was purified by silica gel column
chromatography with petroleum ether-EtOAc as eluent.
3. Preparation of 4-Methoxybiphenyl. In air, a mixture of 4-
bromoanisole (0.374 g, 2.0 mmol), phenylboronic acid (0.256 g,
2.1 mmol), Na2CO3 (0.424 g, 4 mmol), and the brush (0.104 g,
1.0 mol % of Pd) in 10 mL of H2O was magnetically stirred and
refluxed at 100 °C. The reaction was monitored by TLC. After
the reaction was completed, the reaction mixture was cooled to
room temperature and ethyl acetate (20 mL) was added. The
catalysts were separated by filtration, washed with EtOAc (3 Â
5 mL) and water, and dried in vacuum. The combined organic
layer was washed with saturated NaCl solution, dried with
anhydrous MgSO4, and concentrated under reduced pressure
to give crude product that was purified by silica gel column
chromatography with petroleum ether as eluent to produce
0.3662 g (99.5%) of 4-methoxybiphenyl. Mp 89-90 °C (recrys-
tallized from EtOH); 1H NMR (300 MHz, CDCl3) δ 3.84
(s, 3H), 7.49 (m, 3H), 7.64-7.72 (m, 4H), 8.18-8.20 (d, J =
7.50 Hz, 2H).
Acknowledgment. The authors are grateful to the Na-
tional Foundation of Natural Science in China (Grant
No.20572066), the Natural Science Foundation of Shaanxi
Province (2006B20), and the Innovation Foundation of
Postgraduate Cultivation of Shaanxi Normal University.
Experimental Section
1. Preparation of Catalyst (2 wt % Pd). A mixture of PdCl2
(0.19 mmol, 0.034 g), Na2EDTA (0.19 mmol, 0.071 g), and
Na2CO3 (0.38 mmol, 0.040 g) in water (5 mL) was magnetically
stirred at room temperature and pH 8-9 for 3 h. One gram of
SiO2-BisILsC8H15Cl and 5 mL of EtOH were added and the
mixture was stirred for 12 h. The resulting yellowish powder was
filtered, washed thoroughly with H2O and EtOH, and dried
Supporting Information Available: Experimental proce-
dures and spectral data for products. This material is available
free of charge via the Internet at http://pubs.acs.org.
6286 J. Org. Chem. Vol. 74, No. 16, 2009