NHC-Pd(II)-Im (NHC = N-heterocyclic carbene; Im = 1-methylimidazole) complexes as efficient catalysts for Suzuki-Miyaura coupling reactions of aryl chlorides

Article abstract of DOI:10.1016/j.jorganchem.2011.08.042

A new type of well-defined N-heterocyclic carbene (NHC)-palladium chloride-imidazole complexes derived from IPr HCl or IMes HCl, PdCl₂ and 1-methylimidazole exhibits high catalytic activity in the room-temperature Suzuki-Miyaura coupling reactions of aryl or heteroaryl chlorides. Moreover, the large-scale (20.0 mmol) couplings in the presence of 0.01 mol% catalyst loading can also give the corresponding coupling products in high yields.

Full text of DOI:10.1016/j.jorganchem.2011.08.042

Journal of Organometallic Chemistry 696 (2011) 3741e3744
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
NHCePd(II)eIm (NHC ¼ N-heterocyclic carbene; Im ¼ 1-methylimidazole)
complexes as efficient catalysts for Suzuki-Miyaura coupling reactions
of aryl chlorides
*
Yi-Qiang Tang, Jian-Mei Lu, Li-Xiong Shao
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Zhejiang Province 325035, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new type of well-defined N-heterocyclic carbene (NHC)-palladium chloride-imidazole complexes
derived from IPrꢀHCl or IMesꢀHCl, PdCl2 and 1-methylimidazole exhibits high catalytic activity in the
room-temperature Suzuki-Miyaura coupling reactions of aryl or heteroaryl chlorides. Moreover, the
large-scale (20.0 mmol) couplings in the presence of 0.01 mol% catalyst loading can also give the cor-
responding coupling products in high yields.
Received 12 July 2011
Received in revised form
18 August 2011
Accepted 23 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
N-heterocyclic carbene
Palladium complex
Imidazole
Suzuki-Miyaura coupling reaction
Synthetic method
1. Introduction
and Organ [16,18], et al. [34e37]. Recently, we reported the
synthesis of a novel type of NHC-palladium chloride-imidazole
Transition metal-catalyzed cross-coupling reactions are versa-
tile methods for the formation of CeC bonds [1,2]. Among them, the
Suzuki-Miyaura reactions play important roles in modern synthetic
chemistry [3e11]. A great number of catalytic systems have been
developed for the coupling of aryl bromides and iodides with
arylboronic acids as well as aryl chlorides, which are attractive
substrates because of their low cost and wide availability, though
they are relatively unreactive compared to bromides and iodides
[12,13]. Introduction of sterically bulky, electron-rich ligands in the
transition metal center will enhance the catalyst performance in
both of the oxidative addition and reductive elimination steps
[11,14e19]. It is reported that N-heterocyclic carbenes (NHCs) are
[NHCePd(II)eIm] complexes 1 derived from PdCl2, IPrꢀHCl or
IMesꢀHCl and 1-methylimidazole. In addition, we found that these
complexes showed efficient catalytic activity toward amination
reactions between secondary amines and aryl chlorides (Scheme 1)
[38]. These results prompted us to further investigate other appli-
cations of these complexes in organic synthesis. In continuing
investigations, we found that the NHCePd(II)eIm complexes 1
showed high activity in the Suzuki-Miyaura coupling of aryl chlo-
rides at room temperature [39e49]. Herein, we wish to report these
results in detail.
2. Experimental
a very important class of ligands because of their strong
s-donor
and poor -acceptor abilities [20e27]. By far, several air-stable and
p
2.1. General remarks
well-defined monocoordinated NHCePd(II) complexes derived
from IPr, and IMes, etc., have been developed and been established
to be highly efficient catalysts in various cross-coupling reactions,
mainly contributed from Beller [28e30], Nolan [21], Cloke [31e33]
1H and 13C NMR spectra were recorded on Bruker AV-II 300 MHz
and Bruker AV-III 500 MHz spectrometer for solution in CDCl3 with
tetramethylsilane (TMS) as an internal standard; J-values are in Hz.
THF, DME and toluene were distilled from sodium (Na) under
nitrogen (N2) atmosphere. Commercially obtained reagents were
used without further purification. Flash column chromatography
was carried out using Huanghai 300e400 mesh silica gel at
increased pressure.
* Corresponding author. Tel./fax: þ86 577 86689300.
E-mail addresses: Shaolix@wzu.edu.cn, shaolix@163.com (L.-X. Shao).
0022-328X/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jorganchem.2011.08.042

3742
Y.-Q. Tang et al. / Journal of Organometallic Chemistry 696 (2011) 3741e3744
temperature for 24 h. Preliminary results showed that the solvents
R1
R2
Cl
used dramatically affect the reaction. For example, with
K3PO4∙3H2O (2.0 equiv) as the base, almost no reaction occurred
whenH2Oor THFalonewas usedas the solvent, respectively(Table 1,
entries 1 and 2). To our pleasure, when the combination of H2O and
THF (2.0/1.0 mL) was used, high yield of the corresponding coupling
product4awas obtained(Table 1, entry3). Further screeningofbases
showed that K3PO4∙3H2O was the best one (Table 1, entries 4e7).
With other solvents screened, all did not give the yields as good as
that of H2O/THF (Table 1, entries 8e11). Complex 1b gave inferior
result for the same reaction (Table 1, entry 12).
N
H
N
NHC-Pd(II)-Im 1
+
R1
R2
N
R
R
Cl
1a: NHC = IPr
1b: NHC = IMes
Pd NHC
Cl
NHC-Pd(II)-Im 1:
N
N
N
N
N
..
..
The scope of this reaction was then investigated under the
optimal conditions (Table 1, entry 3) and the results are summa-
rized in Table 2. We were delighted to find out that a range of
chlorides 2 and boronic acids 3 can be coupled to give the products
4 in good to high yields at room temperature. The functional groups
in both of the substrates of aryl chlorides and arylboronic acids
almost have no effect on the generality of this reaction. For
example, functional groups as formyl group, acetyl group and nitro
group can be tolerant in these reactions (Table 2, entries 11e13).
IMes
IPr
Scheme 1. NHCePd(II)eIm complexes catalyzed aminations of aryl chlorides.
2.2. General procedure for the complex 1a-catalyzed Suzuki-
Miyaura coupling reaction
(If aryl chloride is liquid) under N2 atmosphere, arylboronic acid
3 (0.6 mmol), 1a (1.0 mol%), K3PO4$3H2O (2.0 equiv), H2O (2.0 mL),
and THF (1.0 mL) were added into a Schlenk reaction tube, then aryl
chloride 2 (0.5 mmol) was added. The mixture was stirred at room
temperature for 24 h. Then the mixture was extracted with EtOAc,
dried over anhydrous Na2SO4, filtered and purified by flash column
chromatography to give the pure products.
Table 2
Complex 1a catalyzed coupling reactions of aryl chlorides 2 with boronic acids 3
under the optimized conditions.
Cl
B(OH)2
R1
1a (1.0 mol%)
.
K3PO4 H2O (2.0 equiv)
(If aryl chloride is solid) under N2 atmosphere, aryl chloride 2
+
H2O, THF, rt, 24 h
(0.5 mmol), arylboronic acid
3 (0.6 mmol), 1a (1.0 mol%),
R2
R2
K3PO4∙3H2O (2.0 equiv), H2O (2.0 mL), and THF (1.0 mL) were
added into a Schlenk reaction tube. The mixture was stirred at room
temperature for 24 h. Then the mixture was extracted with EtOAc,
dried over anhydrous Na2SO4, filtered and purified by flash column
chromatography to give the pure products.
R1
3
2
4
Entrya
2 (R1)
3 (R2)
Yield (%)b
1
2
3
4
5
6
7
8
2b (4-OMe)
2b
2b
2b
2b
3b (H)
3c (4-Me)0
3d (2-Me)
3e (3-Me)
3f (3,5-Me2)
3g (4-F)
3a (4-MeO)
3a
3a
3b
3b
3b
4a, 90
4b, 86
4c, 99
4d, 87
4e, 80
4f, 99
4b, 92
4d, 99
4c, 99
4g, 96
4h, 99
4i, 99
4j, 99
4k, 99
3. Results and discussion
2b
Initial examinations were carried out using chlorobenzene 2a
(0.5 mmol) and 4-methoxyphenylboronic acid 3a (1.2 equiv) as the
substrates in the presence of complex 1a (1.0 mol%) at room
2c (4-Me)
2d (3-Me)
2e (2-Me)
2f (3-OMe)
2g (4eCHO)
2h (4-Ac)
2i (4-NO2)
2j (2,6-Me2)
9
10
11
12
13
14
3b
3d
Table 1
Optimization for the reaction of 2a with 3a catalyzed by complexes 1.
Cl
B(OH)2
cat. 1 (1.0 mol%)
3h
base (2.0 equiv)
15
2j
4l, 96
OMe
+
solvent, rt, 24 h
B(OH)2
4a
2a
OMe
3a
Entrya
Cat.
Base
Solvent (mL)
Yield (%)b
3i
16
2b
4m, 85
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
K3PO4∙3H2O
K3PO4∙3H2O
K3PO4∙3H2O
KOtBu
K2CO3
KOH
H2O (2)
THF (2)
e
B(OH)2
<5
95
16
54
81
33
31
e
17
18
2b
2e
3h
3h
4n, 99
4o, 95
H2O/THF (2/1)
H2O/THF (2/1)
H2O/THF (2/1)
H2O/THF (2/1)
H2O/THF (2/1)
H2O/DME (2/1)
H2O/Toluene (2/1)
H2O/EtOH (2/1)
H2O/iPrOH (2/1)
H2O/THF (2/1)
3j
B(OH)2
19
2b
4p, 97
4q, 99
KHCO3
O
K3PO4∙3H2O
K3PO4∙3H2O
K3PO4∙3H2O
K3PO4∙3H2O
K3PO4∙3H2O
9
10
11
12
36
74
74
20
2k
3a
Cl
N
a
a
All reactions were carried out using 2a (0.5 mmol), 3a (1.2 equiv), base
(2.0 equiv), 1 (1.0 mol%) in the listed solvent at room temperature for 24 h.
All reactions were carried out using 2 (0.5 mmol), 3 (1.2 equiv), 1a (1.0 mol%),
K3PO4∙3H2O (2.0 equiv), H2O (2.0 mL), THF (1.0 mL) at room temperature for 24 h.
b
b
Isolated yields.
Isolated yields.

Y.-Q. Tang et al. / Journal of Organometallic Chemistry 696 (2011) 3741e3744
3743
Table 3
Acknowledgements
Varied loading of NHCePd(II)eIm 1a for the Suzuki-Miyaura reactions.
OMe
Financial support from the National Natural Science Foundation
of China (No. 21002072), and the start-up fund of Wenzhou
University is greatly acknowledged. Yi-Qiang Tang thanks the
Science and Technology Department of Zhejiang Province for
financial support (No. 2010R424050).
Cl
B(OH)2
1a (X mol%)
.
K3PO4 H2O (2.0 equiv)
+
H2O, THF, 50 oC
R1
2
Appendix. Supplementary material
OMe
3a
R1
4
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.jorganchem.2011.08.
042. These data include MOL files and InChiKeys of the most
important compounds described in this article.
Entry
2 (R1)
[X]
Time (h)
Yield (%)c
1a
2b
3a
4b
2a (H)
2a
0.1
0.01
0.1
12
24
12
24
4a, 99
4a, 96
4b, 88
4b, 84
2c (Me)
2c
0.01
References
a
Reaction conditions: 2 (5.0 mmol), 3a (1.2 equiv), 1a (0.1 mol%), K3PO4∙3H2O
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Reaction conditions: 2 (20.0 mmol), 3a (1.2 equiv), 1a (0.01 mol%), K3PO4∙3H2O
(2.0 equiv), N2, 50 ꢁC, 24 h.
c
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Suzuki-Miyaura coupling reactions of aryl chlorides at room
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