764
Published on the web June 12, 2010
Cross Coupling of Arylboronic Acids with Imidazoles
by Sulfonatocopper(II)(salen) Complex in Water
Lixia Wang,1 Zhaoqiong Jiang,1 Lintao Yu,1 Lili Li,1 Zhengkai Li,*1 and Xiangge Zhou*1,2
1Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University, Chengdu 610064, P. R. China
2State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, P. R. China
(Received April 30, 2010; CL-100421; E-mail: zhengkaili@scu.edu.cn)
A mild and clean protocol for the cross coupling reactions
Table 1. Screening reaction conditions for the N-arylation of imidazole
with arylboronic acid
between imidazoles and arylboronic acids has been developed
in good to excellent yields up to 98% in the presence of
sulfonatocopper(II)(salen) catalyst in water without addition of
other additives and bases.
B(OH)
H
2
N
catalyst, air
H O
N
+
N
2
N
Entry
Time/h
Temp/°C
Catalyst/%
Yielda/%
Carbon-nitrogen bond forming reactions are one of the most
widely used methodologies for the synthesis of biologically active
molecules.1 N-Arylimidazole subunit is a commonly found
structural motif in agrochemical, pharmaceutical, and biological
compounds because of their biomedical applications as thrombox-
ane synthase inhibitors2 and has been exploited as important
precursors of versatile N-heterocyclic carbenes,3 a powerful class
of ligands for transition-metal catalysis4 or room-temperature ionic
liquids.5 Previously, Chan, Lam and co-workers developed an
efficient method for coupling of azoles and arylboronic acids for
the synthesis of N-arylazoles by using stoichiometric Cu(OAc)2
and pyridine as base.6 Later, Collman and co-workers demon-
strated the use of a catalytic amount of [Cu(OH)tmeda]2Cl2 for the
coupling of arylboronic acid with imidazole in dichloromethane
and water at room temperature.7 Thereafter, simple copper salt
catalyzed coupling of imidazoles with arylboronic acids in
methanol was reported.8 A recent notable achievement has been
made by using copper(I) oxide as catalyst in N-arylation of azoles
and amines with arylboronic acids at room temperature in
methanol.9 Despite the synthetic elegance the vast majority of
the existing protocols were generally operated in volatile organic
solvents. To make the catalysis in a “greener” approach, organic
reactions in water have recently attracted much attention on
account of the environmental friendliness.10
Recently, we reported the first example of N-arylation of
imidazoles with iodobenzene catalyzed by sulfonatocopper(II)-
(salen) complex 1 (Figure 1) under mild conditions in water with
satisfactory results.11 To determine the applicability of the complex
catalyzed C-N coupling reaction, N-arylation reactions of imida-
zoles with arylboronic acids in the presence this complex were
carried out in this work.
To identify the best catalytic system for N-arylation reactions
of imidazoles with arylboronic acids, in our initial study, the
reaction between phenylboronic acid (2 equiv) and imidazole (1
equiv) in water (3 mL) was chosen as a model without any
additives and bases, a variety of different catalyst loadings and
reaction temperatures were screened, and the results of optimiza-
tion are listed in Table 1.
1
2
3
4
5
6
7
8
9
24
12
6
4
1
6
6
6
6
100
100
100
100
100
100
100
100
80
10
10
10
10
10
5
97
97
98
90
81
71
49
trace
87
45
2
®
10
10
10
10
11
6
6
60
25
<10
aYields were determined by GC using 1,4-dichlrobenzene as internal
standard.
Comparison of the various reaction times indicated that 6 h
was enough for the catalysis with 98% yield (Table 1, Entry 3).
Meanwhile, the control experiments indicated that the presence of
catalyst was crucial for the reaction, 10% catalyst loading was
proven to be essential in the procedure, and only trace of product
was detected in the absence of catalyst (Table 1, Entries 6-8).
Furthermore, lower temperature than 100 °C decelerated the
reaction and led to lower yields (Table 1, Entries 9-11).
Thus, the optimized reaction conditions for the N-arylation
involved 6 h, 100 °C, and 10% catalyst loading. Then, the scope of
arylboronic acids was investigated under these reaction condi-
tions.12
As shown in Table 2, most of the substituted arylboronic acids
can give moderate to excellent yields. Also, electron-deficient
arylboronic acids resulted in excellent yields ranging from 83 to
93% (Table 2, Entries 6-11), while electron-rich arylboronic acids
depressed the reaction to a certain degree in lower yields (43-
68%). On the other hand, steric hindrance was another important
factor to affect the results (Table 2, Entries 1-5). Heteroarylbor-
onic acid was also tried in a yield of 83%.
Encouraged by these results, a variety of imidazole derivatives
were applied in catalytic coupling reactions with arylboronic acids,
and the results are listed in Table 3.
To our delight, most of the corresponding cross-coupling
products can be afforded in good to excellent yields (77-95%)
under the optimized reaction conditions. Sterically hindered 2-
methylimidazole and 2-ethyl-4-methylimidazole could also under-
go selective N-arylation with heteroarylboronic acid to give good
yields (Table 3, Entries 7-9). The results indicated that arylboronic
acid could be a proper substituent of iodobenzene in the catalytic
coupling reactions.
N
O
N
O
Cu
NaO3S
SO3Na
Figure 1. Structure of sulfonatocopper(II)(salen) complex 1.
Chem. Lett. 2010, 39, 764-765
© 2010 The Chemical Society of Japan
Wang, Lixia
