A novel water-soluble NHC-Pd polymer: An efficient and recyclable catalyst for the Suzuki coupling of aryl chlorides in water at room temperature

Article abstract of DOI:10.1039/c1cc00017a

A novel water-soluble NHC-Pd polymer with triethylene glycol legs was developed as a water soluble and highly recyclable catalyst that shows high catalytic activity in the Suzuki-Miyaura coupling of aryl chlorides in high yields in water at room temperature.

Full text of DOI:10.1039/c1cc00017a

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COMMUNICATION
A novel water-soluble NHC-Pd polymer: an efficient and recyclable
catalyst for the Suzuki coupling of aryl chlorides in water at room
temperaturew
Babak Karimi* and Pari Fadavi Akhavan
Received 2nd January 2011, Accepted 11th May 2011
DOI: 10.1039/c1cc00017a
1
extent by the use of auxiliaries such as co-solvents, and/or
0
A novel water-soluble NHC-Pd polymer with triethylene glycol
legs was developed as a water soluble and highly recyclable
catalyst that shows high catalytic activity in the Suzuki–
Miyaura coupling of aryl chlorides in high yields in water at
room temperature.
phase-transfer catalysts, only very few catalytic systems are
known capable of combining the advantages of using pure
water as reaction medium for the Suzuki coupling of highly
challenging chloroarenes, and at the same time demonstrating
1
1
the possibility to recover and recycle the catalyst. To the best
of our knowledge, there has been yet no example of using
recyclable catalyst for the Suzuki coupling reaction of aryl
The palladium-catalyzed cross coupling reactions of aryl
halides with arylboronic acids, universally called ‘‘Suzuki–
Miyaura reaction’’, are among the most versatile reactions
for the selective construction of biaryls, which are often
12
chlorides in water at room temperature. Therefore, the quest
for green, efficient and recyclable catalyst systems for the
coupling reaction of aryl chlorides in water at room temperature
without the need of any co-solvent remains a great challenge.
1
2
important units in natural products, pharmaceuticals, and
3
functional materials. Although, wide varieties of homogeneous
4
catalytic systems such as phosphines, N-heterocyclic carbenes
13
Recently, we reported that NHC-Pd-MCOP bearing the
5
6
NHCs) and palladacycle complexes have been established
(
N-benzyl group (1a) were effective, insoluble and recyclable
for this transformation, catalyst separation and recycling, high
catalyst loading, and product contamination with traces of
heavy metals are often problematic in the homogeneous
systems. This inherent limitation of homogeneous catalyst
systems, in addition to increasing environmental standards,
has recently resulted in the development of new strategies to
design highly efficient transition-metal-based systems with
catalyst for the Suzuki coupling of aryl chlorides to the
1
4
corresponding biaryls in water at 80–90 1C. However, despite
the high catalytic performance of 1a in coupling of chloroarenes
in water, it requires high reaction temperatures and its catalytic
activity significantly decreased after 5 reaction cycles when
1
4
a classical filtration technique was used for its separation.
Our preliminary investigations demonstrated that the gradual
decrease in catalytic activity of 1a arises from loss of the
recovered 1a which is actually the major reason for the slow
decline in catalytic activity over the recycling experiments. To
address this issue, we hypothesized that if we could design and
prepare a water soluble version of 1, it could be possible to
easily separate the water-insoluble reaction products of the
coupling reactions using solvent extraction, whilst maintaining
the catalyst in the reaction mixture for the subsequent reaction
runs without the need for filtration. Furthermore, owing to the
polymeric nature of the main body of these materials, it would
be also possible to use a suitable membrane with proper pore
size to separate the catalyst residue from the aqueous reaction
mixture. If this strategy could be realized in practice, then it
would be possible to combine in the same material the
advantages of homogeneous and heterogeneous catalysis such
as high activity and practical recyclability, respectively.
7
improved recovery and recycling properties. The major aim of
these efforts is to reduce the energy and time used in achieving
chemical transformations and separations. In particular, interest
in catalytic processes by recyclable metal-based catalysts in
aqueous media is dramatically increasing from a sustainable
8
chemistry point of view. Water is safe, abundant, non-toxic,
and inexpensive. Water has also an additional advantage that
the organic products for example those obtained from the
Suzuki coupling reactions are often poorly soluble in it and
thus can easily be separated from the reaction mixture. However,
in reactions in which water participates as reaction medium,
there are often several difficulties such as low solubility of
substrates and deactivation of metal catalysts owing to the
9
occupation of coordination sites by water molecules.
Although, the solubility problem can be overcome to some
By analogy with the architecture of a living centipede, we
decided to prepare a nano-centipede-like NHC polymer by
changing the N-benzyl groups in 1a with triethylene glycol
moieties (TEGs) in order to investigate the validity of the
above mentioned hypothesis. Our strategy and procedure
for the preparation of water-soluble NHC-Pd-MCOP 1b
Department of Chemistry, Institute for Advanced Studies in Basic
Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran.
E-mail: karimi@iasbs.ac.ir; Fax: +98-241-4214949;
Tel: +98-241-4153225
w Electronic supplementary information (ESI) available: The experi-
mental details for the preparation of catalyst 1b, H- and C-NMR
for all intermediates, coupling products. See DOI: 10.1039/c1cc00017a
1
13
7
686 Chem. Commun., 2011, 47, 7686–7688
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Table 1 The Suzuki coupling of various aryl halides with arylboronic
acid in the presence of 1b in water
a
1
R
2
R
b
Entry
X
n
T/1C Time/h Yield [%]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
4-CHO
H
Br 0.005 rt
4-CHO 4-Me Br 0.005 rt
11
10
15
14
16
18
16
24
24
24
30
30
24
24
30
30
16
18
24
30
30
30
12
12
90
91
89
91
90
88
90
90
85
88
78
74
93
90
82
78
80
79
81
69
70
29
92
86
3-Ac
H
H
H
H
Br 0.005 rt
Br 0.005 rt
4-CN
4-Et
4-MeO
Br 0.05
Br 0.05
rt
rt
4-MeO 4-Me Br 0.05
rt
4-CHO
3-CHO
4-CN
4-Me
4-MeO
4-CHO 4-Me Cl 0.05
4-CN
4-Me
4-MeO 4-Me Cl 0.1
2-CHO Br 0.05
4-MeO 2-Me Br 0.05
2-CHO 2-Me Br 0.05
2-Et
2-CHO 2-Me Cl 0.1
2-CHO 2-Me Cl 0.3
3-Ac
3-Ac
H
H
H
H
H
Cl 0.05
Cl 0.05
Cl 0.05
Cl 0.05
Cl 0.1
rt
rt
rt
rt
0
1
2
3
4
rt
rt
rt
rt
rt
60
60
80
80
80
80
4-Me Cl 0.05
4-Me Cl 0.05
Scheme 1 The strategy for preparation of water-soluble (nano-
centipede-like) main chain NHC-Pd polymer 1b.
15
1
1
1
1
2
6
7
8
9
0
H
is demonstrated in Scheme 1. The average molecular weight
of 1b was determined by means of gel-permeation chromato-
2-Me Br 0.05
1
5
graphy (GPC) to be around 107 000 Da. Notably, 1b exhibits
good solubility in dipolar aprotic solvents such as DMF and
DMSO and showed excellent solubility in water, whereas it has
21
c
2
2
2
2
3
4
H
H
Br 0.005 60
Br 0.005 60
d
2 2 3
poor solubility in solvents such as CH Cl , CHCl , and toluene.
a
Reaction conditions for the Suzuki reaction: aryl halide (1.0 mmol),
CO (3.0 mmol), water (3.0 mL).
The initial assessment of the catalytic activity of 1b was
conducted at catalyst loading as low as 0.005 mol% in the
coupling of 4-bromobenzaldehyde with phenylboronic acid at
room temperature in water. The reaction proceeded efficiently
to give 4-phenylbenzaldehyde in 90% yield within 11 h
arylboronic acid (1.2 mmol), K
b
2
3
c
Isolated yield after flash chromatography. 0.3 mol% of catalyst 1a
d
was used. The reaction was performed in the presence of Hg.
system but they also result in consistent higher catalytic activity
within shorter reaction times when 1b is used instead of 1a.
Since the initial goal of this research was to develop a highly
and easily recyclable catalyst system, we further investigated
the possibility to recycle the catalyst in the model reaction
between 4-chlorobenzaldehyde and phenylboronic acid. In this
regard, we found that catalyst 1b demonstrated excellent
durability and reusability without any need to classical separation
techniques such as filtration and centrifugation.
(
Table 1, entry 1). With this promising result in hand, we then
investigated the general usefulness of our new catalyst system
b with respect to different coupling partners (Table 1). Under
1
the optimized reaction conditions, a range of electron-rich and
electron-poor bromoarenes could successfully be converted to
their coupled products (Table 1, entries 1–7).
We decided then to expand the catalytic scope of 1b in the
coupling of highly challenging chloroarene substrates at room
temperature. Gratifyingly, we found that the coupling reaction
of both activated and deactivated aryl chlorides with arylboronic
acid proceeded smoothly using 1b (0.05 mol%) to furnish the
corresponding Suzuki products with excellent yields at room
temperature (Table 1, entries 8–16). Worthy of note is that
sterically hindered coupling partners led to the corresponding
biaryl products in good yields while higher catalyst loading
To prove this, after the first use of catalyst 1b in the above-
mentioned coupling reaction to give 4-phenylbenzaldehyde in
1
5,16
90%, the products were extracted with n-hexane,
upon
which the catalyst 1b remained in the aqueous phase. In the
next stage, the recovered aqueous phase containing 1b was
1
7
loaded with fresh coupling partner and base. The results
obtained using this simple technique show that the recovered
aqueous phase can be used at least in 17 subsequent reaction
runs and exhibited remarkably consistent activity (ESIw, Fig. S2).
In order to separate 1b from other water-soluble species in the
reaction mixture such as the excess of K CO , and boronic
(
(
0.05 mol%) and high temperature (60–80 1C) were required
Table 1, entries 17–21). Even more challenging hindered aryl
chlorides such as 2-chlorobenzaldehyde coupled well over
0.1 mol% of 1b with hindered 2-methylphenylboronic acid and
2
3
0
afforded the corresponding 2,2 -disubstituted biaryl product in
good yields (Table 1, entry 21). These results are very remark-
able because the same reaction using our previously reported
NHC-Pd-MCOP with the N-benzyl group was unsatisfactory
acid salts, a dialysis technique was performed. To do this, the
aqueous reaction mixture was transferred into a dialysis bag
(molecular weight cut-off = 10 kDa) in 400 ml deionized
water (diasylate) and allowed to equilibrate for 48 h. To ensure
a perfect separation, the used diasylate was changed every 8 h.
Interestingly, a typical retention of the catalyst 1b on the order
of about 99% inside the tubular dialysis bag was achieved. It is
also noteworthy that the leaching of Pd species into the used
1
4
under the same reaction conditions (Table 1, entry 22). These
results also clearly indicate that N-TEG moieties attached to
the main chain NHC-Pd polymer framework of 1b are not
only indispensable in high water solubility of our catalyst
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 7686–7688 7687

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dialysate was negligible as determined by atomic absorption
spectroscopy (AAS) (less than a detection limit of 1 ppm).
Moreover, using the diasylate in each stage as the reaction
solvent showed no detectable activity in catalyzing the Suzuki
coupling reaction of 4-bromobenzaldehyde with phenylboronic
acid under over optimized reaction conditions. This successful
dialytic separation of 1a from the aqueous reaction phase is
highly significant, because it will open a new pathway for the
design and set up of membrane type reactors which are
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particles which could act as active catalyst species, a poisoning
9
1
mercury test was performed. To do this, we managed to
establish a new experiment by addition of an excess of mercury
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(
Hg : Pd; 400 : 1) to the coupling reaction of 3-bromoaceto-
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excess of Hg (Table 1, entries 23 and 24), it is unlikely that Pd
nanoparticles acted as the active catalyst in our protocol at
room temperature.
2
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1
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a novel designed nano-centipede-like
1
2 It has been shown that amphiphilic resin-supported Pd catalyst is
an efficient system for the Suzuki coupling of aryl iodides and
bromides (not aryl chlorides) with arylboronic acids at room
temperature in water; Y. Uozumi, H. Danjo and T. Hayashi,
J. Org. Chem., 1999, 64, 3384.
main-chain NHC-Pd polymer with triethylene glycol legs
was developed, a new water-soluble and yet highly recyclable
composite. This water-soluble organometallic polymer was
found to present high activity in catalyzing the Suzuki–
Miyaura coupling of a variety of aryl halides including activated,
deactivated and hindered substrates to afford the desired
product in high yields under aqueous and homogeneous
reaction conditions. Furthermore, the catalyst shows high
catalytic activity and excellent reusabilities over at least 17
reaction cycles. More importantly, the catalyst can be easily
separated in pure form using a simple dialysis technique
without the need for inefficient filtration methods.
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The authors acknowledge the IASBS Research Council and
Iran National Science Foundation (INSF) for support of this
work. We also acknowledge Dr Saeed Emadi from IASBS for
his help and reading the manuscript.
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15 See ESIw for experimental details.
16 n-Hexane was chosen in order to minimize the product contamination
to Pd below the limit 1 ppm as determined by atomic absorption
spectroscopy (AAS). The reaction was performed on a 20 mmol scale.
17 The amount of base needed in each run was estimated by pH
analysis of the recovered aqueous reaction phase.
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688 Chem. Commun., 2011, 47, 7686–7688
This journal is c The Royal Society of Chemistry 2011