Desulfitative Suzuki cross-couplings of arylsulfonyl chlorides and boronic acids catalyzed by a recyclable polymer-supported N-heterocyclic carbene-palladium complex catalyst

Article abstract of DOI:10.1055/s-2006-948163

An effective and easy-to-handle process for the desulfitative Suzuki cross-couplings of arylsulfonyl chlorides and boronic acids in the presence of a recyclable polymer-supported NHC-Pd complex was developed. The supported catalyst could be reused several times with little loss of catalytic activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-948163

LETTER
1891
Desulfitative Suzuki Cross-Couplings of Arylsulfonyl Chlorides and Boronic
Acids Catalyzed by a Recyclable Polymer-Supported N-Heterocyclic
Carbene–Palladium Complex Catalyst
Desulfitative
S
u
uzuki Cross
ju
a
lfonyl Chlo
n
rides
a
nd Boronic
ZAcids hang, Xiaoming Zeng, Zhijun Wei, Dongbing Zhao, Tairan Kang, Weifeng Zhang, Mei Yan, Meiming Luo*
Key Laboratory of Green Chemistry & Technology of Ministry of Education at Sichuan University, College of Chemistry, Sichuan
University, Chengdu 610064, P. R. of China
Fax +86(28)85462021; E-mail: luomm@scu.edu.cn
Received 15 March 2006
metal–carbon bonds in NHC–metal complexes make
Abstract: An effective and easy-to-handle process for the desulfit-
NHCs good ligands for heterogeneous systems. With
ative Suzuki cross-couplings of arylsulfonyl chlorides and boronic
these concerns, several immobilized NHC–metal com-
acids in the presence of a recyclable polymer-supported NHC–Pd
plexes have been developed. For examples, supported
NHC–Ru complexes have been used in ring-closing meta-
thesis.6a Silica- and polymer-supported NHC–Rh com-
plexes for the addition of arylboronic acids to aldehydes
have also been reported.7 The immobilization of a
NHC–Rh complex to a water-soluble, amphiphilic block
copolymer for hydroformylation of alkenes has been de-
scribed.8 Polymer-supported NHC–Pd complex has been
applied in the Heck reaction.9 For the Suzuki cross-cou-
pling, only a few examples using supported NHC–Pd
complexes as catalysts appeared.10 In addition, the reus-
ability of those catalysts was not satisfactory in most
cases.10a–c We recently reported an active and recyclable
polystyrene-supported NHC–Pd catalyst for the Suzuki
cross-coupling reaction of aryl bromides and arylboronic
acids at room temperature that gave biaryls in good to ex-
cellent yields.10e As part of our ongoing investigations
aimed at the development of transition metal catalysis, we
wish to report here that the Suzuki cross-couplings of
arylsulfonyl chlorides and boronic acids can be readily ef-
fected with our polystyrene-supported NHC–Pd catalyst.
complex was developed. The supported catalyst could be reused
several times with little loss of catalytic activity.
Key words: Suzuki reaction, N-heterocyclic carbene–palladium
complex, polymer-supported catalysts, recyclable catalysts, aryl-
sulfonyl chlorides
Synthesis of unsymmetrical biaryls plays an important
role in organic synthesis because of their numerous appli-
cations in pharmaceuticals, polymers, advanced materials
and liquid crystals.1 The palladium-catalyzed Suzuki
cross-coupling reactions provide a general and efficient
synthetic route to biaryl compounds and have found wide-
spread use in organic synthesis.2 The Suzuki cross-cou-
pling reactions are usually realized with aryl iodides,
bromides and chlorides.3
Arylsulfonyl chlorides are inexpensive and readily avail-
able compounds.4 In 2004, Dubbaka and Vogel found that
arylsulfonyl chlorides could be used in place of aryl-
halides in the Suzuki reaction, and could be coupled with
arylboronic acids to yield biaryls.5
The polystyrene-supported NHC–Pd catalyst 1 was
prepared using our reported procedure (Scheme 1).10e The
Pd loading was determined to be 0.1 mmol/g by induc-
tively coupled plasma-atomic emission spectrometry
(ICP-AES).
Due to their versatile processing capabilities, ease of
product/catalyst separation, immobilized catalysts offer
many advantages for industrial applications. Although N-
heterocyclic carbenes (NHCs) as ligands for transition-
metal complexes have found many successes in homo-
geneous catalysis,6 including the above-mentioned cross-
couplings of arylsulfonyl chlorides with arylboronic
acids, heterogenizing NHC–metal complexes still remain
practically useful. The high dissociation energies of
The desulfitative Suzuki cross-couplings of arylsulfonyl
chlorides and boronic acids catalyzed by the polymer-
supported NHC–Pd catalyst 1 were investigated in detail
using the coupling reaction between 3-nitrophenyl-
N
N
NCH3
NCH3
Pd(OAc)2, Na2CO3
supported NHC-Pd
O
catalyst
DMF–H2O (1:1), 50 °C, 4 h
2X
X = Cl or I
1
Scheme 1
SYNLETT 2006, No. 12, pp 1891–1894
0
1
.0
8
.2
0
0
6
Advanced online publication: 24.07.2006
DOI: 10.1055/s-2006-948163; Art ID: W05506ST
© Georg Thieme Verlag Stuttgart · New York

1892
S. Zhang et al.
LETTER
O2N
O2N
supported catalyst
base, solvent
B(OH)2
SO2Cl
+
Scheme 2
sulfonyl chloride and phenylboronic acid as a model used as a base. Other bases such as NaOAc, K3PO4 and
reaction (Scheme 2). To optimize the reaction conditions, t-BuOK afforded moderate to low yields of the coupling
several reaction parameters such as the amount of cata- products. When the organic base triethylamine was em-
lyst, solvent and base were surveyed.
ployed, the lowest yield was obtained. Hence, Na2CO3
was finally selected as the base for the reaction because it
was less expensive and readily available.
The effect of the amount of the polymer-supported NHC–
Pd complex on the reaction is shown in Table 1. No prod-
uct was observed in the absence of the polymer-supported The recyclability of the polymer-supported NHC–Pd cat-
NHC–Pd complex (Table 1, entry 1). When the catalyst alyst for the desulfitative Suzuki cross-couplings of aryl-
loading was less than 2.0 mol% Pd, lower yield of the cor- sulfonyl chlorides and boronic acids was also explored
responding biaryl product was obtained (Table 1, entries using 3-nitrophenylsulfonyl chloride and phenylboronic
2–4). The yield (87%) was markedly improved when 2.5 acid as substrates (Table 3). The catalyst could be reused
mol% Pd was applied. Catalyst of more than 2.5 mol% Pd after filtration, washing and drying in vacuum under the
did not apparently improve the yield further (Table 1, en- same reaction conditions with no noticeable loss of reac-
try 7). The results unfolded a strong influence of the tivity. The polymer-supported NHC–Pd catalyst could be
amount of the catalyst on product yield.
reused five times with only slightly decreasing in catalytic
activity. Analysis of the reaction mixture following sepa-
ration and washing of the resin by ICP-MS indicated that
after the initial run, Pd-leaching was amount to 0.21%
from the resin, but were reduced to 89 ppm for the second
run and 53 ppm for the fifth run. In order to confirm that
the reactive catalyst was the solid-supported catalyst
rather than a boomerang system, we undertook experi-
ments in which the boiling reaction mixture was immedi-
ately filtered to remove the solid support catalyst after five
hours (at about 50% conversion), and yet no further reac-
tion was observed despite heating the remaining aliquot
for further 40 hours.
Table 1 Effect of the Amount of Catalyst on the Cross-Coupling
Reactiona
Entry
Pd (mol%)
Yield (%)b
1
2
3
4
5
6
7
0
0
19
30
45
83
87
87
0.75
1.2
1.5
2.0
2.5
3.0
Table 2 Cross-Coupling of 3-Nitrophenylsulfonyl Chloride and
Phenylboronic Acid Catalyzed by the Polymer-Supported Catalyst 1a
a Reaction conditions: 3-nitrophenylsulfonyl chloride (0.5 mmol),
phenylboronic acid (2.0 mmol), Na2CO3 (1.5 mmol), THF (5 mL),
reflux, 20 h.
Entry
Solvent
THF
Base
Yield (%)b
1
2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
NaOAc
K3PO4
t-BuOK
Et3N
87
b Isolated by silica-gel column chromatography and based on 3-nitro-
phenylsulfonyl chloride.
DME
DMF
76
3
Trace
75
As shown in Table 2, employing THF as the solvent re-
sulted in the highest yield (Table 2, entry 1) as compared
to other solvents, such as DME, DMF, MeCN and 1,4-
dioxane (Table 2, entries 2–5). DME or 1,4-dioxane pro-
vided a moderate yield of the desired biaryl products
while DMF was found to be less efficient giving only
trace amounts of the product. This result revealed that
ethereal solvents were better solvents for the cross-
coupling of 3-nitrophenylsulfonyl chloride and phenyl-
boronic acid in the presence of polystyrene-supported
NHC–Pd catalyst 1.
4
1,4-Dioxane
MeCN
THF
5
53
6
81
7
THF
57
8
THF
61
9
THF
60
10
THF
52
a Reaction conditions: 3-nitrophenylsulfonyl chloride (0.5 mmol),
phenylboronic acid (2.0 mmol), Na2CO3 (1.5 mmol), catalyst (125
mg, 12.5 mmol Pd), 68 °C, 20 h.
After the optimal solvent (THF) for the cross-coupling re-
action was chosen, we embarked on the study of the effect
of base on the reaction. As can be seen from Table 2, sev-
eral bases were examined. The investigation revealed that
better yields were obtained when Na2CO3 or K2CO3 was
b Isolated by silica-gel column chromatography and based on 3-nitro-
phenylsulfonyl chloride.
Synlett 2006, No. 12, 1891–1894 © Thieme Stuttgart · New York

LETTER
Desulfitative Suzuki Cross-Coupling of Arylsulfonyl Chlorides and Boronic Acids
1893
Table 3 Recycling of the Polymer-Supported NHC–Pd Catalyst 1a
rides containing both electron-donating and electron-
withdrawing substitutents tolerated well under the reac-
tion conditions, providing the corresponding cross-cou-
pling products in good yields in most cases. It was
observed that the sulfonyl chloride group in halogenated
benzenesulfonyl chlorides possessed similar reactivity as
the aryl bromide functionality (Table 4, entry 5), but was
more reactive than aryl chlorides (Table 4, entries 6 and 7)
in the Suzuki cross-coupling reaction catalyzed by the
supported NHC–Pd catalyst.
Run
1
2
3
4
5
Yield (%)b 87
88
85
86
81
a Reaction conditions: 3-nitrophenylsulfonyl chloride (0.5 mmol),
phenylboronic acid (2.0 mmol), Na2CO3 (1.5 mmol), catalyst (125
mg, 12.5 mmol Pd), THF (5 mL), reflux, 20 h.
b Isolated by silica-gel column chromatography and based on 3-nitro-
phenylsulfonyl chloride.
In summary, we have disclosed for the first time that the
Suzuki cross-couplings of arylsulfonyl chlorides and aryl-
boronic acids could be catalyzed by a recyclable polysty-
rene-supported NHC–Pd complex in boiling THF to
As illustrated in Table 4, the desulfitative cross-couplings
of various arylsulfonyl chlorides and different arylboronic
acids could be efficiently catalyzed by the polymer-sup-
ported NHC–Pd catalyst.11 A variety of arylsulfonyl chlo-
Table 4 Cross-Couplings of Various Arylsulfonyl Chlorides and Arylboronic Acids Catalyzed by the Polystyrene-Supported NHC–Pd Cat-
alysta
Entry
1
Arylsulfonyl chloride
Arylboronic acid
Time (h)
20
Product
Yield (%)b Mp (°C)
87
59–6012,19
O2N
NO2
B(OH)2
SO2Cl
2
3
4
13
15
16
90
86
80
113–11412
89–9013
O2N
MeO
MeO
SO2Cl
SO2Cl
SO2Cl
B(OH)2
B(OH)2
B(OH)2
NO2
OMe
OMe
60–6114,15
OMe
MeO
5
6
7
24
24
20
50
62
81
209–21116
76.5–7817
Oil
Br
Cl
SO2Cl
SO2Cl
B(OH)2
B(OH)2
B(OH)2
Cl
Cl
Cl
SO2Cl
Cl
Cl
8
20
88
75.5–76.512
NO2
O2N
Me
B(OH)2
SO2Cl
H3C
Me
9
10
11
13
15
20
91
87
89
140–14118
110–11113
79–8019
O2N
SO2Cl
NO2
Me
B(OH)2
B(OH)2
B(OH)2
MeO
O2N
SO2Cl
Me
OMe
NO2
Me
MeO
SO2Cl
MeO
Me
12
15
21
18
85
70
72
110–11113
242–24320
75.5–76.512
Me
Me
Me
SO2Cl
SO2Cl
SO2Cl
MeO
B(OH)2
OMe
13c
14
HOOC
O2N
B(OH)2
Me
CO2H
NO2
Me
B(OH)2
a Reaction conditions: arylsulfonyl chloride (0.5 mmol), arylboronic acid (2.0 mmol), Na2CO3 (1.5 mmol), catalyst (125 mg, 12.5 mmol Pd),
THF (5 mL), reflux.
b Isolated by silica-gel column chromatography and based on arylsulfonyl chloride.
c Na2CO3 (3.5 mmol) was added.
Synlett 2006, No. 12, 1891–1894 © Thieme Stuttgart · New York

1894
S. Zhang et al.
LETTER
(10) (a) Zhao, Y.; Zhou, Y.; Ma, D.; Liu, J.; Zhang, T. Y.; Zhang,
H. Org. Biomol. Chem. 2003, 1, 1643. (b) Byun, J. W.; Lee,
Y. S. Tetrahedron Lett. 2004, 45, 1837. (c) Kim, J. H.; Jun,
B. H.; Byun, J. W.; Lee, Y. S. Tetrahedron Lett. 2004, 45,
5827. (d) Steel, P. G.; Teasdale, C. W. T. Tetrahedron Lett.
2004, 45, 8977. (e) Kang, T.; Feng, Q.; Luo, M. Synlett
2005, 2305.
afford the corresponding biaryls in good isolated yields.
This method could accommodate a variety of functional
groups substituted on both the arylsulfonyl chlorides and
arylboronic acids. The process was easy to handle and the
catalyst could be recovered simply by filtration and reused
several times.
(11) General Procedure for the Suzuki Cross-Couplings of
Arylsulfonyl Chlorides and Arylboronic Acids Catalyzed
by the Polymer-Supported NHC–Pd Catalyst.
A 25 mL, round-bottom flask equipped with a magnetic
stirring bar and a reflux condenser was charged with
arylboronic acid (2 mmol), arylsulfonyl chloride (0.5 mmol),
Na2CO3 (1.5 mmol) and the polymer-supported NHC–Pd
catalyst 1 (125 mg, 12.5 mmol Pd). The flask was connected
to a vacuum line and then filled with argon (three times)
before 5 mL THF was added. The resulting mixture was
stirred and heated to reflux. After cooling to ambient
temperature, the catalyst was filtered and washed with THF
(3 × 4 mL), and then dried in vacuum for use in next run. The
combined organic phase was dried over anhydrous MgSO4,
filtered and evaporated under reduced pressure. The product
was purified by column chromatography.
Acknowledgment
The authors are grateful to National Natural Science Foundation of
China (No. 20372049) for the financial support.
References and Notes
(1) (a) Stanforth, S. P. Tetrahedron 1998, 54, 263.
(b) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 977.
(2) For reviews of metal-catalyzed Suzuki cross-coupling
reactions, see: (a) Suzuki, A. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F.; Stang, P., Eds.; Wiley-
VCH: Weiheim Germany, 1998, Chap. 2. (b) Suzuki, A. J.
Organomet. Chem. 1999, 576, 147; and references cited
therein.
(3) (a) Zhang, C.; Trudell, M. L. Tetrahedron Lett. 2000, 41,
595. (b) Navarro, O.; Kelly, R. A.; Nolan, S. P. J. Am. Chem.
Soc. 2003, 125, 16194. (c) Kwong, F. Y.; Chan, K. S.;
Yeung, C. H.; Chan, A. S. C. Chem. Commun. 2004, 2336.
(d) Kwong, F. Y.; Lam, W. H.; Yeung, C. H.; Chan, K. S.;
Chan, A. S. C. Chem. Commun. 2004, 1922.
(4) Dubbaka, S. R.; Vogel, P. Angew. Chem. Int. Ed. 2005, 44, 2.
(5) Dubbaka, S. R.; Vogel, P. Org. Lett. 2004, 6, 95.
(6) (a) Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1290.
(b) Perry, M. C.; Burgess, K. Tetrahedron: Asymmetry 2003,
14, 951.
2,5-Dichlorobiphenyl: colorless oil. 1H NMR (400 MHz,
CDCl3): d = 7.23–7.28 (m, 1 H), 7.34 (d, J = 2.4 Hz, 1 H),
7.37–7.47 (m, 6 H). 13C NMR (100 MHz, CDCl3): d = 141.9,
138.1, 132.5, 131.1, 131.0, 130.8, 130.6, 129.6, 129.2,
126.4, 126.2, 126.1. MS (EI): m/z (%) = 222 (100) [M+], 186
(7), 152 (49).
Other cross-coupling products were identified by comparing
their NMR spectra and melting points with those reported in
the literature.
(12) Hassan, J.; Hathroubi, C.; Gozzi, C.; Lemaire, M.
Tetrahedron 2001, 57, 7845.
(13) Denmark, S. E.; Ober, M. H. Org. Lett. 2003, 5, 1357.
(14) Cammidge, A. N.; Gopee, H. J. Mater. Chem. 2001, 11,
2773.
(7) (a) Özdemir, I.; Gürbüz, N.; Seçkin, T.; Çetinkaya, B. Appl.
Organomet. Chem. 2005, 19, 633. (b) Yan, C.; Zeng, X.;
Zhang, W.; Luo, M. J. Organomet. Chem. 2006, 691, 3391.
(8) Zarka, M. T.; Bortenschlager, M.; Wurst, K.; Nuyken, O.;
Weberskirch, R. Organometallics 2004, 23, 4817.
(9) Schwarz, J.; Böhm, V. P. W.; Gardiner, M. G.; Grosche, M.;
Herrmann, W. A.; Hieringer, W.; Raudaschl-Sieber, G.
Chem. Eur. J. 2000, 6, 1773.
(15) Blatchly, J. M.; Mcomie, J. F. W.; Watts, M. L. J. Chem.
Soc. 1962, 5085.
(16) (a) Hawkins, E. G. E.; Thompson, R. D. J. Chem. Soc. 1961,
370. (b) Wenzel, T. J.; Betters, T. C.; Sadlowski, J. E.;
Sievers, R. E. J. Am. Chem. Soc. 1980, 102, 5903.
(17) Kabalka, G. W.; Wang, L.; Pagni, R. M.; Hair, C. M.;
Namboodiri, V. Synthesis 2003, 217.
(18) Shudo, K.; Ohta, T.; Okamoto, T. J. Am. Chem. Soc. 1981,
103, 645.
(19) Pourbaix, C.; Carreaux, F.; Carboni, B. Org. Lett. 2001, 3,
803.
(20) Lu, G.; Franzen, R.; Zhang, Q.; Xu, Y. Tetrahedron Lett.
2005, 46, 4255.
Synlett 2006, No. 12, 1891–1894 © Thieme Stuttgart · New York