Macroporous polystyrene-supported palladium catalyst containing a bulky N-heterocyclic carbene ligand for Suzuki reaction of aryl chlorides

Article abstract of DOI:10.1021/ol8003047

Macroporous polystyrene (MPS)-supported 1-mesitylimidazolium chloride resin was prepared by reacting macroporous chloromethyl polystyrene with 1-mesitylimidazole as a supported N-heterocyclic carbene (NHC) precursor for the immobilization of a palladium c

Full text of DOI:10.1021/ol8003047

ORGANIC
LETTERS
2008
Vol. 10, No. 8
1609-1612
Macroporous Polystyrene-Supported
Palladium Catalyst Containing a Bulky
N-Heterocyclic Carbene Ligand for
Suzuki Reaction of Aryl Chlorides
Dong-Ho Lee,† Jong-Ho Kim,†,§ Bong-Hyun Jun,† Homan Kang,‡
Juyoung Park,† and Yoon-Sik Lee*,†,‡
School of chemical and Biological Engineering, Seoul National UniVersity,
Interdisciplinary Program in Nano-science and Technology, Seoul National UniVersity,
Seoul 151-744, South Korea
yslee@snu.ac.kr
Received February 11, 2008
ABSTRACT
Macroporous polystyrene (MPS)-supported 1-mesitylimidazolium chloride resin was prepared by reacting macroporous chloromethyl polystyrene
with 1-mesitylimidazole as a supported N-heterocyclic carbene (NHC) precursor for the immobilization of a palladium catalyst. This MPS-
supported NHC precursor readily formed a stable complex with Pd(OAc)2, which effectively catalyzed the Suzuki reaction of aryl iodide and
bromides at room temperature and even aryl chlorides at elevated temperatures (100
reaction of aryl bromide.
°C). This catalyst showed reusability in the Suzuki
The Suzuki reaction catalyzed by palladium is one of the
most powerful routes for the formation of C(sp2)-C(sp2)
bonds. This reaction has been used to make biaryl derivatives
that are important intermediates in polymers, liquid crystals,
pharmaceuticals, and herbicides.1,2 From an industrial point
of view, one of significant issue in the Suzuki reaction has
focused on aryl chlorides because they are cheaper than aryl
iodides and bromides and are readily available.3
Over the past few years, the Suzuki reaction of aryl
chlorides were carried out successfully using homogeneous
catalysts.4 However, homogeneous catalysts have several
problems, such as the need to separate and recycle the
catalysts and the contamination from ligand residues in
products. Therefore, a heterogeneous catalyst for the Suzuki
reaction of aryl chlorides is still needed for industrial
applications. Recently, several types of heterogeneous cata-
lysts in the Suzuki reaction of aryl chlorides were reported
using mesoporous silica-supported palladium catalysts,5 Pd/C
† School of Chemical and Biological Engineering.
‡ Interdisciplinary Program in Nano-science and Technology.
§ Current address: Department of Chemical Engineering, Massachusetts
Institute of Technology, Cambridge, MA 02139.
(1) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11,
513. (b) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (c) Suzuki,
A. J. Organomet. Chem. 1999, 576, 147.
(2) For recent reviews, see: (a) Bellina, F.; Carpita, A.; Rossi, R.
Synthesis 2004, 2419. (b) Pershichini, P. J. Curr. Org. Chem. 2003, 7, 1725.
(c) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem.
ReV. 2002, 102, 1359. (d) Kotha, S.; Lashiri, S.; Kashinath, D. Tetrahedron
2002, 58, 9633.
(4) (a) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed. 2000,
39, 4153. (b) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37,
3387. (c) Stu¨rmer, R. Angew. Chem., Int. Ed. 1999, 38, 3307. (d) Old, D.
W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722. (e)
Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64,
3804. (f) Bohn, V. P. W.; Gstottmayer, C. W. K.; Weskamp, T.; Herrmann,
W. A. J. Organomet. Chem. 2000, 595, 186.
(5) (a) Yang, Q.; Ma, S.; Li, J.; Xiao, F.; Xiong, H. Chem. Commun.
2006, 2495. (b) Trilla, M.; Pleixats, R.; Man, M. W. C.; Bied, C.; Moreau,
J. J. E. Tetrahedron Lett. 2006, 47, 2399. (c) Sayah, R.; Glegola, K.;
Framery, E.; Dufaud, V. AdV. Synth. Catal. 2007, 349, 373.
(3) Review: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002,
41, 4176. (b) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem.
ReV. 2004, 248, 2283.
10.1021/ol8003047 CCC: $40.75
© 2008 American Chemical Society
Published on Web 03/20/2008

catalyst,6 polymer-incarcerated palladium catalysts,7 poly-
urea-encapsulated palladium catalysts,8 and dendrimer-sup-
ported palladium catalyst.9 However, these systems catalyzed
the Suzuki reaction of activated aryl chlorides but failed to
work for deactivated aryl chlorides.
As shown in Scheme 1, 1-(mesityl)imidazole was first
synthesized to prepare the MPS-supported bulky N-hetero-
Scheme 1. Synthesis of Macroporous Polystyrene-Supported
Bulky NHC-Pd Complex 4
In order to carry out the Suzuki reaction of activated and
deactivated aryl chloride, macroporous polystylene (MPS)
resin and bulky N-heterocyclic carbenes (NHC)s were used
as a support and a ligand, respectively. MPS resin is an
efficient support with a large surface area and high porosity.
Therefore, MPS might solve the diffusion problem of
reagents and solvents.10 NHCs behave like typical σ- donor
ligands in metal coordination chemistry. Moreover, NHCs
have excellent air and moisture stability and have higher
dissociation energies. Therefore, NHCs11-13 can enhance the
reactivity and stability of palladium catalysts compared with
phosphines.14,15 In particular, when bulky NHCs are used in
the palladium catalyzed Suzuki reaction of aryl chlorides,
its catalytic activity is enhanced by their steric and electronic
effect.16
This paper reports that MPS-supported bulky NHC-
palladium is an effective catalyst for the Suzuki reaction of
both activated and deactivated aryl chlorides. This catalyst
also showed outstanding reusability in the Suzuki reaction
of aryl bromide.
cyclic carbene palladium complex. In order to accomplish
this, an ammonium chloride solution was added to a
vigorously stirred solution of H2O and 1,4-dioxane at 100
°C containing paraformaldehyde, mesitylammonium salt, and
glyoxal. This mixture was maintained at 100 °C for 2 h.17
After the reaction was complete, the resulting 1-(mesityl)-
imidazole (1) was obtained in 15% yield. This ligand
precursor has a bulky group that can enhance the catalytic
activity in the Suzuki reaction. Next, a mixture of chlorom-
ethyl MPS resin (2) (0.7 mmol Cl/g) and compound 1 (3
equiv) in DMF/THF (4:1) were stirred at 70 °C for 2 days.
After being cooled to room temperature, the reaction mixture
was filtered, and the resin was washed thoroughly and dried
to afford the MPS-supported 1-mesitylimidazolium chloride
resin (3) with a 1-(mesityl)imidazolium loading of 0.32
mmol/g, as determined by the nitrogen content from elemen-
tary analysis. Based on the Cl contents, the reaction
proceeded to 52% conversion.
(6) (a) LeBlond, C. R.; Andrews, A. T.; Sun, Y.; Sowa, J. R. Org. Lett.
2001, 3, 1555. (b) Arvela, R. K.; Leadbeater, N. E. Org. Lett. 2005, 7,
2101.
(7) (a) Nishio, R.; Sugiura, M.; Kobayashi, S. Chem. Asian J. 2007, 2,
983. (b) Hagio, H.; Sugiura, M.; Kobayashi, S. Org. Lett. 2006, 8, 375. (c)
Nishio, R.; Sungiura, M.; Kobayashi, S. Org. Lett. 2005, 7, 4831. (d)
Okamoto, K.; Akiyama, R.; Kobayashi, S. Org. Lett. 2004, 6, 1987.
(8) (a) Lee, C. K. Y.; Holmes, A. B.; Ley, S. V.; McConvey, I. F.; Al-
Duri, B.;Leeke, G. A.; Santos, R. C. D.; Seville, J. P. K. Chem. Commun.
2005, 2175. (b) Ley, S.V.; Ramarao, C.; Gordon, R. S.; Holmes, A. B.;
Morrison, A. J.; McConvey, I. F.; Shirley, I. M.; Smith, S. C.; Smith, M.
D. Chem. Commun. 2002, 1134.
(9) Garcia-Bernabe, A.; Tzchucke, C. C.; Bannwarth, W.; Haag, R. AdV.
Synth. Catal. 2005, 347, 1389.
(10) (a) Hori, M.; Gravert, D. J.; Wentworth, P., Jr.; Janda, K. D. Bioorg.
Med. Chem. Lett. 1998, 8, 2363. (b) Jang, H. S.; Chung, W. J.; Lee, Y. S.
Tetrahedron Lett. 2007, 48, 3731.
(11) (a) O¨ fele, K. J. Organomet. Chem. 1968, 12, 11.(b) Wanzlick, H.
J.; Scho¨nherr, H. J. Angew. Chem. 1968, 80, 154. For a recent review, see:
(c) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(12) (a) Weskamp, T.; Kohl, F. J.; Hieringer, W.; Gleich, D.; Herrmann,
W. A. Angew. Chem., Int. Ed. 1999, 38, 2416. (b) Schwarz, J.; Bo¨hm, V.
P. W.; Gardiner, M. G.; Grosche, M.; Herrmann, W. A.; Hieringer, W.;
Raud-aschl-Sieber, G. Chem. Eur. J. 2000, 6, 1773.
(13) (a) Byun, J. W.; Lee. Y. S. Tetrahedron Lett. 2004, 45, 1837. (b)
Kim, J, H.; Jun, B. H.; Byun, J. W.; Lee, Y. S. Tetrahedron Lett. 2004, 45,
5827. (c) Kim, J. H.; Kim, J. W.; Shokouhimehr, M.; Lee, Y. S. J. Org.
Chem. 2005, 70, 6714. (d) Kim, J. W.; Kim, J. H.; Lee, D. H.; Lee, Y. S.
Tetrahedron Lett. 2006, 47, 4745.
In order to immobilize Pd on resin 3, a mixture of resin 3
and Pd(OAc)2 was stirred in DMSO at 50 °C for 4 h. The
temperature was then increased to 100 °C, and the reaction
was then allowed to proceed for a further 30 min at 100 °C,
which led to the formation of a MPS-supported bulky NHC-
Pd catalyst (4).18
After immobilizing the palladium, catalyst 4 was analyzed
by inductively coupled plasma-atomic emission spectrom-
etry (ICP-AES) and energy dispersive X-ray (EDX) to
determine the amount of palladium bound to the ligand. The
EDX spectra showed that palladium was only present in
catalyst 4 with none detected in resin 3. According to the
loading levels of 1-(mesityl)imidazole on resin 3 (0.32 mmol
IM/g) and Pd on catalyst 4 (0.33 mmol Pd/g), we indirectly
(14) (a) Cai, M.; Sha, J.; Xu, Q. J. Mol. Catal. A Chem. 2007. 268. 82.
(b) Yu, H. W.; Tong, Q. S.; Peng, Y. R.; Jia, L.; Shi, J. C.; Jin, Z. L. Chin.
Chem. Lett. 2007. 18. 37. (c) Leyva, A.; Garcia, H.; Corma, A. Tetrahedron
2007. 63. 7097
(15) (a) Uozumi, Y.; Kimura, M. Tetrahedron: Asymmetry 2006, 17,
161.(b) Uozumi, Y.; Kikuchi, M. Synlett 2005, 1775. (c) Hocke, H.; Uozumi,
Y. Tetrahedron. 2004, 60, 9297. (d) Uozumi, Y.; Tanaka, H.; Shibatomi,
K. Org. Lett. 2004, 6, 281. (e) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4,
2997. (f) Danjo, H.; Tanaka, D.; Hayashi, T.; Uozumi, Y. Tetrahedron.
1999, 55, 14341. (g) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem
1999, 64, 3384. (h) Uozumi, Y.; Watanabe, T. J. Org. Chem 1999, 64,
6921. (i) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron Lett. 1997, 38,
3557.
(17) Gardiner, M. G.; Herrmann, W. A.; Reisinger, C.; Schwarz, J.;
Spiegler, M. J. Organomet. Chem. 1999, 572, 239.
(18) Herrmann, W. A.; Schwarz, J.; Gardiner, M. G. Organometallics
1999, 18, 4082.
(16) (a) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2004, 43, 1871.(b) Kantchev, E. A. B.; Brien, C.
J.; Organ, M. G. Aldrichim. Acta 2006. 4. 97
1610
Org. Lett., Vol. 10, No. 8, 2008

concluded that MPS-supported bulky NHC-palladium cata-
lyst 4 was mostly a monodentic complex, as shown in
Scheme 1. X-ray photoelectron spectroscopy (XPS) of
catalyst 4 showed 336.5 eV (Pd 3d5) as the major peak and
337.7 eV as a minor peak, which corresponds to Pd(II) and
PdCl2 respectively.19 Therefore, MPS-supported bulky NHC-
Pd catalyst contained only Pd(II) with no Pd(0). It was
concluded that the palladium was immobilized specifically
to the imidazolium ligand in the forms of Pd(NHC)OAcCl
(4, major) and Pd(NHC)Cl2 (minor).
Field emission scanning electron microscopy (FE-SEM)
showed that there were no morphological changes in MPS
(2), MPS-NHC (3), and MPS-NHC-Pd (4), which con-
firms that the shape of the MPS resins had remained intact.
Therefore, MPS-NHC-Pd is a rigid and stable complex.
In addition, the surface area and porosity of compounds 2,
3 and 4 were analyzed by BET. Although a series of reactions
were performed on the MPS resins, the surface area (130-
190 m2/g) and porosity (9.4-11.0 nm) of each resin were
maintained.
Table 2. Effect of the Solvents on the Suzuki Reaction of
4-Chloroanisole and Phenylboronic Acida
entry
solvent
time (h)
T (°C)
yieldb (%)
1
2
3
4
5
DMF/water
DMA/water
dioxane/water
toluene/water
water
24
24
24
24
24
100
100
100
100
100
76
40
41
none
1
a 4-Chloroanisole (0.5mmol), phenylboronic acid (0.6 mmol), MPS-
NHC-Pd (2 mo l%), K2CO3 (2.5 mmol), and solvent (2:1, v/v). b Isolated
yield by column chlomatography.
reaction of 4-chloroanisole with phenylboronic acid for 24
h at 100 °C. A reaction also occurred using only water.
However, there was poor yield due to the poor solubility of
4-chloroanisole in water and the decrease in the water
compatibility of the MPS-supported bulky NHC-Pd catalyst
(4).
The catalytic activity of catalyst 4 was examined for its
ability to catalyze the Suzuki reaction of aryl chlorides with
phenylboronic acid. In order to optimize the reaction
conditions, the coupling of 4-chloroanisole (0.5 mmol) and
phenylboroic acid (0.6 mmol) as a model reaction was carried
out using catalyst 4 (2 mol %). Different bases were used to
confirm the effect of the base in the Suzuki reaction of
deactivated aryl chloride. As shown in Table 1, K2CO3 as a
Table 3. Suzuki Reaction of Aryl Halide, Including Aryl
Chloride, with Phenylboronic Acida
Table 1. Effect of Bases on the Suzuki Reaction of
4-Chloroanisole and Phenylboronic Acida
entry
R
X
time (h)
T (°C)
yieldb (%)
1
2
3
4
5
6c
7c
8d
9c
10c
11c
12e
p-COCH3
p-OCH3
p-COCH3
p-OCH3
o-OCH3
p-COCH3
p-CN
p-NO2
p-OCH3
p-CH3
I
I
0.5
0.5 (6)
1
1 (12)
1
24
24
24
24
50
50 (25)
50
50 (25)
50
100
100
100
100
100
100
100
95
99 (99)
94
97 (88)
85
83
71
82
76
70
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
entry
base
time (h)
T (°C)
yieldb (%)
1
2
3
4
5
6
Cs2CO3
K3PO4
K2CO3
NaOH
t-BuOK
Na2CO3
24
24
24
24
24
24
100
100
100
100
100
100
50
46
76
30
41
51
24
24
24
o-OCH3
p-OCH3
58
31
a 4-Chloroanisole (0.5 mmol), phenylboronic acid (0.6 mmol), MPS-
NHC-Pd (2 mol %), base (2.5 mmol), and DMF/water (2:1, v/v). b Isolated
yield by column chromatography.
a Aryl halide (0.5 mmol), phenylboronic acid (0.6 mmol), MPS-NHC-
Pd (1 mol %), K2CO3 (2.5 mmol), and DMF/water (2:1, v/v). b Isolated
yield by column chromatography. c Phenylboronic acid (0.8 mmol), MPS-
NHC-Pd (2 mol %). d Phenylboronic acid (0.8 mmol), MPS-NHC-Pd
(2 mol %), DMF/water (14:1, v/v). e 1-Methylimidazole was used as a ligand
instead of 1-mesitylimidazole.
base gave the highest yield (76%) in the reaction of
4-chloroanisole with phenylboronic acid. The use of other
bases resulted in lower yields due to their low activity.
The effect of various solvents was next investigated.
According to the results shown in Table 2, a solution of
DMF/water (2:1) gave an excellent yield (76%) in the
As shown in Table 3, the Suzuki reaction of various aryl
halides, even aryl chloride, was examined under optimal
reaction conditions to show the high catalytic activity of
MPS-supported bulky NHC-Pd catalyst (4). The Suzuki
reactions of deactivated aryl chloride including 4-chloroani-
sole and 4-chlorotoluene proceeded with high yields of 76%
and 70%, respectively, at 100 °C (Table 3, entries 9 and
(19) (a) Kumar, G.; Blackburn, J. R.; Albridge, R. G.; Moddeman, W.
E.; Jones, M. M. Inorg. Chem. 1972, 11, 296. (b) Kim, K. S.; Gossmann,
A. F.; Winogard, N. Anal. Chem. 1974, 46, 197. (c) Nyholm, R.; Martensson,
N. J. Phys. C 1980, 13, L279.
Org. Lett., Vol. 10, No. 8, 2008
1611

10). However, the Suzuki reaction of 2-chloroanisole, which
may experience some steric effect, gave a somewhat lower
yield of 58% (Table 3, entry 11). To the best of our
knowledge, none of the known heteogenous catalyts pro-
duced such high yields shown in the above Suzuki reaction
of deacivated aryl chlorides. The Suzuki reaction of activated
aryl chlorides with different substituents also gave good
yields. (Table 3, entries 6-8). 4-Aminobiphenyl was ob-
tained as a side product in the Suzuki reaction of 1-chloro-
4-nitrobenzene in DMF/water (2:1) system. As the ratio of
water was reduced to DMF/water (14:1), the side reaction
was suppressed, and 4-nitrobiphenyl was obtained in 82%
yield (Table 3, entry 8). In addition, the Suzuki reaction of
aryl iodides and bromides produced excellent yields, regard-
less of the presence of activated, deactivated and steric
substituents (Table 3, entries 1-5), even at room temperature
(Table 3, entries 2 and 4).
In order to examine the effect of the bulkiness of the
ligand, 1-methylimidazole and 1-mesitylimidazole were
introduced to the catalyst system as ligands, respectively.
When bulky 1-mesitylimidazole was used, a high yield was
obtained compared with 1-methylimidazole. (Table 3, entries
9 and 12). Hence, the bulkiness of the ligand is an important
factor for increasing the catalytic activity in the Suzuki
reaction of aryl chlorides. Therefore, the MPS-supported
bulky NHC-Pd catalyst (4) was confirmed to be an excellent
catalyst showing high activity in the Suzuki reaction of aryl
chlorides including deactivated chlorides.
The reusability of the MPS-supported bulky NHC-Pd
catalyst (4) was examined in the Suzuki reaction of aryl
bromides. As shown in Table 4, the catalytic activities (94%)
and the initial loading levels of catalyst 4 (0.08 mmol/g) on
the resin remained almost the same after being used five
times. However, a small amount of palladium metal was
detected from the filtrates after each runs (3.0%, 1.1%, 1.2%
1.4%, and 1.3%, by ICP-AES analysis). The leached Pd
(homogeneous Pd) may not contribute a major role in their
catalytic activity. Because all of the catalytic activity after
each run looks similar even though the amount of leached
palladium in the first cycle is higher than those of the other
cycles.
Table 4. Reusability of Macroporous Polystyrene-Supported
Bulky NHC-Pd Complex (4) for the Suzuki Reactiona
recycle
yieldb (%)
first
94
second
94
third
94
fourth
89
fifth
94
a 4-Bromoacetophenone (0.5 mmol), phenylboronic acid (0.6 mmol),
MPS-NHC-Pd (1 mol %), K2CO3 (2.5 mmol), DMF/H2O (2:1, v/v), 50
°C, and 1 h. b Isolated yield by column chromatography.
ethyl polystyrene with 1-(mesityl)imidazole as a supported
NHC precursor for the immobilization of a palladium
catalyst. The supported NHC precursor readily formed a
stable complex with Pd(OAc)2 and showed excellent catalytic
activity in the Suzuki reactions of various aryl chlorides,
bromides and iodides. Aryl chlorides with electron-donating
groups were also converted to biaryl products in high yield.
This MPS-supported bulky NHC-Pd catalyst showed reus-
ability up to five times in the Suzuki reaction of aryl bromide.
Acknowledgment. This study was supported by the Nano
Bioelectronics and Systems Research Center of Seoul
National University, which is an ERC supported by the
Korean Science and Engineering Foundation (KOSEF), and
the Brain Korea 21 program supported by the Ministry of
Education & Human Resources Dvelopment.
Supporting Information Available: Experimental pro-
cedure and characterization data (EDX, XPS, FE-SEM, BET)
for MPS-supported N-heterocyclic carbene palladium cata-
lyst, experimental procedure for the Suzuki reaction, and
characterization data (1H NMR, GC-MS) for all of the
products obtained form Suzuki reactions. This material is
available free of charge via the Internet at http://pubs.acs.org.
In summary, MPS-supported 1-mesitylimidazolium chlo-
ride resin was prepared by reacting macroporous chlorom-
OL8003047
1612
Org. Lett., Vol. 10, No. 8, 2008