Efficient use of a surfactant for copper-catalyzed coupling reaction of arylboronic acids with imidazoles in water

Article abstract of DOI:10.1016/j.tet.2012.07.042

Copper-catalyzed oxidative coupling of arylboronic acids with imidazoles in water was realized by using an amphiphilic surfactant. By choosing an appropriate surfactant, reactions of a variety of arylboronic acids proceeded smoothly under mild and base-fr

Full text of DOI:10.1016/j.tet.2012.07.042

Tetrahedron 68 (2012) 7794e7798
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient use of a surfactant for copper-catalyzed coupling reaction of arylboronic
acids with imidazoles in water
*
*
Kiyofumi Inamoto , Kanako Nozawa, Jun Kadokawa, Yoshinori Kondo
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 June 2012
Received in revised form 10 July 2012
Accepted 11 July 2012
Available online 20 July 2012
Copper-catalyzed oxidative coupling of arylboronic acids with imidazoles in water was realized by using
an amphiphilic surfactant. By choosing an appropriate surfactant, reactions of a variety of arylboronic
acids proceeded smoothly under mild and base-free conditions, providing an efficient, practical, and
greener method for the synthesis of N-arylimidazoles.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Arylboronic acids
Copper
Cross-coupling
Surfactant
Water
1. Introduction
undergo side reactions such as oxidative phenol formation (AreB to
AreOH) relatively easily in such an aqueous media.6 Although there
The use of water as a solvent for organic synthesis has recently
attracted considerable attention because it offers a range of ad-
vantages such as inexpensiveness, wide availability, non-toxicity,
and nonflammability, thus providing highly economic and sus-
tainable synthetic routes.1 While its use is sometimes hampered by
the insolubility of the polar organic molecules, the addition of an
amphiphilic surfactant, forming micelles, has been known to have
a positive effect for the reactions conducted in water, including
transition-metal-catalyzed processes, resulting from hydrophobic
and concentration effects in the microheterogeneous two-phase
system.2,3
is only one example of the ChaneLam coupling carried out in water,
the yields are moderate to low and the substrate scope is relatively
narrow.7
During the course of our research program aiming at an effective
use of amphiphilic surfactants in organic synthesis,8 we found that
the ChaneLam coupling can be successfully performed in water in
the presence of a certain surfactant. Interestingly, a fluorous-type
surfactant (F-PEG) has turned out to be efficient for some sub-
strates, representing a rare example of using fluorous surfactants in
organic synthesis.9e11 In this paper, we describe the results of the
studies in detail.
Arylamines are ubiquitous in biologically active molecules,
ranging from natural products to medicinal agents. Among the
methods to access such a motif, the copper-mediated or -catalyzed
oxidative coupling of arylboronic acids with amines, so-called the
ChaneLam coupling, has certain advantages such as mild reaction
conditions (e.g., room temperature, an ambient atmosphere), in-
expensive copper-based catalyst systems, and wide availability of
starting boronic acids.4 Although considerable progress has been
made in expanding the substrate scope of the process in the past
decade,5 the use of water as a reaction medium for this process has
met with almost no success, presumably because arylboronic acids
2. Results and discussion
To probe the viability of the anticipated Cu-catalyzed ChaneLam
coupling in water, we first carried out the reaction of 4-
methoxyphenylboronic acid (1a) with imidazole (2a) in the pres-
ence of 10 mol % of Cu(OAc)2/4,40-dimethyl-2,20-dipyridyl (I) cata-
lyst system under an O2 atmosphere (1 atm). However, the reaction
provided the desired coupling product 3aa only in 33% yield (entry
1). Thus, the effect of adding a surfactant (30 mol %) for the process
was next evaluated (entries 2e9). As a result, it was found that
a certain surfactant did enhance the process: Among the surfac-
tants examined, Brij 30, Triton X-100, and fluorous-type F-PEG
were superior to others for the reaction of 1a, providing 3aa in fairly
good yields (entries 5, 6, and 9). Interestingly, the use of a ligand
* Corresponding authors. Tel.: þ81 22 795 3906; e-mail addresses: inamoto@
m.tohoku.ac.jp (K. Inamoto), ykondo@m.tohoku.ac.jp (Y. Kondo).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.042

K. Inamoto et al. / Tetrahedron 68 (2012) 7794e7798
7795
II,12 possessing fluorous substituents, was crucial for better con-
Table 2
Substrate scope of the process regarding arylboronic acidsa
version when F-PEG was used (entry 9 vs entry 8). Intrigued by the
reaction-improving effect of the surfactant, further examination of
the reaction parameters was conducted using a combination of F-
PEG and ligand II. Among a variety of the copper sources tested
(entries 9e15), Cu(OAc)2 turned out to be the best (entry 9). In
addition, the optimal amount of a surfactant was found to be
50 mol % (entry 17 vs entries 9,16,18, and 19). Whereas the reaction
performed under an air atmosphere gave 3aa in yield similar to that
from the reaction under an O2 atmosphere (entry 20), essentially no
product was obtained from the reaction under an Ar atmosphere
(entry 21). At this juncture, it is worthy to note that F-PEG can be
easily recovered after the coupling reaction and successfully reused
for the same process13 (Table 1).
Substrate scope of the process was next investigated using the
above-obtained optimal reaction conditions (conditions A: 10 mol %
of ligand I and 50 mol % of Brij 30, conditions B: 10 mol % of ligand I
and 50 mol % of Triton X-100, conditions C: 10 mol % of ligand II and
50 mol % of F-PEG). As shown in Table 2, several kinds of arylboronic
acids 1aeh have turned out suitable for the coupling and the cor-
responding N-arylimidazoles were obtained generally in good to
high yields by choosing an appropriate surfactant (entries 1e8).
Good functional group compatibility (e.g., alkoxycarbonyl and cyano
Entry
1
Arylboronic acid
1
Conditionsc
Yieldb (%)
A
B
C
68d
66d
78
1a
A
B
C
58
d
72
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
A
B
C
<46e
<44e
73
A
B
C
74f
24
49
Table 1
A
B
C
74f
61
26
Effect of reaction parametersa
A
B
C
Trace
52g
21
Entry
‘Cu’
Ligand
Surfactant (x mol %)
Yieldb (%)
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OTf)2
CuBr2
CuCl2
CuCl
CuI
Cu2O
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
I
I
I
I
I
I
I
I
II
II
II
II
II
II
II
II
II
II
II
II
II
None
SDS (30)
TPGS (30)
Brij S-100 (30)
Brij 30 (30)
Triton X-100 (30)
PTS (30)
F-PEG (30)
F-PEG (30)
F-PEG (30)
F-PEG (30)
F-PEG (30)
F-PEG (30)
F-PEG (30)
F-PEG (30)
F-PEG (10)
F-PEG (50)
F-PEG (100)
F-PEG (300)
F-PEG (50)
F-PEG (50)
33
21
53
53
68
66
8
26
67
54
36
30
61
62
46
64
78
70
67
77
Trace
A
B
C
22
59
21
1g
1h
1i
A
B
C
64
80
69
9
10
11
12
13
14
15
16
17
18
19
20c
21d
A
B
C
17
23
9
9
a
Reaction conditions: 1 (0.40 mmol), 2a (0.20 mmol), Cu(OAc)2 (0.020 mmol),
ligand (0.020 mmol), surfactant in H2O (6 mL).
b
Isolated yield.
c
Conditions A: 10 mol % of ligand I and 50 mol % of Brij 30, conditions B: 10 mol %
of ligand I and 50 mol % of Triton X-100, and conditions C: 10 mol % of ligand II and
50 mol % of F-PEG.
d
Surfactant of 30 mol % was used.
Including impurities.
Bipyridyl was used instead of ligand I.
Pyridine of 5 equiv was added.
e
f
g
groups, halogen atoms such as bromine and chlorine) was also ob-
served in the process. On the other hand, the reactions of meta-
aminophenylboronic acid 1i only provided low yields (entry 9).
The efficiency of the catalytic system developed was further
evaluated briefly by using several amines instead of imidazole (2a) as
a nucleophile (Table 3). The reactions of benzimidazole (2b) and 2-
phenylimidazole (2c) both afforded the desired coupling products
in high yields especially when a fluorous-type surfactant was used
(entries 1 and 2, conditions C). Use of 4-methylimidazole (2d) affor-
ded the product as a mixture of regioisomers as in the case of the
previous report (entry 3).14 Unfortunately, only low to moderate
yields were obtained from the reactionwith pyrazole (2e) (entry 4).15
a
Reaction conditions: 1a (0.40 mmol), 2a (0.20 mmol), ‘Cu’ (0.020 mmol), ligand
(0.020 mmol), surfactant in H2O (4e6 mL).
b
Isolated yield.
Carried out under air.
Carried out under Ar.
c
d

7796
K. Inamoto et al. / Tetrahedron 68 (2012) 7794e7798
using the method similar to the Mecozzi’s synthesis.9a,b Fluorous-
Table 3
Substrate scope of the process regarding aminesa
type ligand II was prepared according to the previously reported
method.12
4.2. Synthesis of fluorous surfactant (F-PEG)
Under an Ar atmosphere, Et3N (10.5 mL, 75.0 mmol) was added
to a mixture of [poly(ethylene glycol)methyl ether (Mn¼2000)]
(9.9 g, 5.0 mmol) and p-toluenesulfonyl chloride (4.8 g, 25.0 mmol)
in CH2Cl2 (30 mL) at 0 ꢀC and the reaction mixture was stirred for
3 h at the same temperature, and then stirred at room temperature
overnight. The solvent was evaporated and the residue was rep-
recipitated in Et2O/iPrOH (4:1). The resulting precipitates were
filtrated and washed with Et2O to give the tosylated product (11.4 g,
>99%) as a colorless powder. 1H NMR (400 MHz, CDCl3/TMS)
Entry
1
HeNR2
2
Conditionsc
Yieldb (%)
A
B
C
23
51
78
2b
A
B
C
15
10
68
2
3
2c
2d
2e
d
(ppm): 2.45 (s, 3H), 3.38 (s, 3H), 3.53e3.81 (m, PEGeH), 7.34 (d,
2H, J¼8.1 Hz), 7.79 (d, 2H, J¼8.1 Hz); IR (neat): 2863, 2855, 2365,
2163, 1471, 1343, 1112, 1060, 841, 699 cmꢁ1
A
B
C
38 (3:1)d
44 (2:1)d
48 (3:2)d
.
NaH (0.53 g, 13.0 mmol, 60% dispersion in oil) was added to
a solution of C8F17CH2OH (2.7 g, 6.4 mmol) in THF (100 mL) and
stirred at room temperature for 1 h. The above tosylated product
(2.3 g, 2.0 mmol) was added and the reaction mixture was refluxed
for 24 h. The solvent was evaporated and the residue was diluted
with H2O, and then extracted with CHCl3 (30 mLꢂ3). The organic
layer was dried over MgSO4 and the solvent was evaporated. The
residue was reprecipitated in Et2O and the resulting precipitates
were filtrated and dissolved in CH2Cl2, and then reprecipitated in
hexane. The resulting precipitates were filtrated and washed with
hexane to give F-PEG (2.3 g, 81%) as a colorless powder. 1H NMR
A
B
C
44
45
24
4
a
Reaction conditions: 1 (0.40 mmol), 2a (0.20 mmol), Cu(OAc)2 (0.020 mmol),
ligand (0.020 mmol), surfactant in H2O (6 mL).
b
Isolated yield.
c
Conditions A: 10 mol % of ligand I and 50 mol % of Brij 30, conditions B: 10 mol %
of ligand I and 50 mol % of Triton X-100, conditions C: 10 mol % of ligand II and
50 mol % of F-PEG.
d
Ratio of regioisomers.
(400 MHz, CDCl3/TMS) d (ppm): 3.38 (s, 3H), 3.45e3.83 (m, PEG-H),
4.04 (t, 2H, J¼14.1 Hz); 13C{1H} NMR (100 MHz, CDCl3/TMS)
d
(ppm): 59.0, 70.46, 70.51, 70.6, 70.7, 71.9, 72.3; IR (neat): 3800,
3. Conclusions
3674, 3587, 3438, 2194, 2157, 1962, 1651, 1107, 843 cmꢁ1
.
We have described the copper-catalyzed coupling reaction of
arylboronic acids with imidazoles in water containing an amphi-
philic surfactant. By choosing an appropriate surfactant, the re-
actions of a variety of arylboronic acids proceed smoothly under
mild, base-free conditions in aqueous media, providing a facile,
efficient access to a biologically important N-arylimidazole nucleus.
Further studies to broaden the substrate scope of the process as
well as to improve the catalytic efficiency are vigorously underway
in our laboratory.
4.3. Synthesis of fluorous-type ligand (II)
Under an Ar atmosphere, BuLi (7.3 mL, 19.0 mmol, 2.6 M in
hexanes) was added to a THF solution (50 mL) of Pr2NH (0.81 mL,
i
11.3 mmol) at ꢁ78 ꢀC and stirred for 20 min at the same tempera-
ture. The reaction mixture was stirred for 30 min at 0 ꢀC and then
cooled to ꢁ78 ꢀC. A THF solution (30 mL) of 4,40-dimethyl-2,20-
bipyridine (0.92 g, 5.0 mmol) was added and stirred for 3 h at the
same temperature, and then 3-(perfluorohexyl)ethyl iodide (4.8 g,
10.2 mmol) was added. The reaction mixture was stirred at ꢁ78 ꢀC
for 1 h and stirred at room temperature overnight. The mixture was
diluted with brine and extracted with Et2O (30 mLꢂ3). The organic
layer was dried over Na2SO4 and the solvent was removed under
the reduced pressure. The residue was purified by recrystallization
from MeOH to give ligand II (0.53 g, 12%) as brown scales. Mp
4. Experimental section
4.1. General
Melting points were measured with a Yazawa micro melting
point apparatus and uncorrected. IR spectra were recorded on
a SHIMADZU IRAffinity. 1H NMR spectra were recorded on a JEOL
JNM-AL400 (400 MHz) or JNM-ECA600 (600 MHz) spectrometer.
112e115 ꢀC; 1H NMR (400 MHz, CDCl3/TMS)
d (ppm): 2.02e2.19 (m,
8H), 2.82 (t, 4H, J¼7.8 Hz), 7.17 (dd, 2H, J¼5.3, 1.7 Hz), 8.28 (s, 2H),
8.61 (d, 2H, J¼5.3 Hz); 13C{1H} NMR (100 MHz, CDCl3/TMS)
Chemical shifts (
d
) are given from TMS (0 ppm) in CDCl3 and cou-
d
(ppm): 21.0, 30.4 (t, J¼22.2 Hz), 34.6, 121.1, 123.8, 149.3, 150.6,
pling constants are expressed in hertz (Hz). The following abbre-
viations are used: s¼singlet, d¼doublet, t¼triplet, q¼quartet,
dd,¼double doublet, dt¼double triplet, m¼multiplet, and br
s¼broad singlet. 13C NMR spectra were recorded on a JEOL JNM-
AL400 (100 MHz) or JNM-ECA600 (150 MHz) spectrometer.
156.3; LRMS (EI) m/z: 876 (Mþ); HRMS: calcd for C28H18F26N2:
876.1055, found: 876.1044; IR (neat): 3800, 3674, 3587, 3438, 2194,
2157, 1962, 1651, 1107, 843 cmꢁ1
.
4.4. Representative procedure for N-arylation of imidazoles
Chemical shifts (d
) are given from 13CDCl3 (77.0 ppm). Mass spectra
and high-resolution mass spectra were measured on a JEOL JMS-DX
303 and JMS-700/JMS-T 100 GC instruments, respectively. Ele-
mental analyses were performed by Yanaco CHN CORDER MT-6.
Boronic acids and other commercially available materials in-
cluding copper salts and surfactants were purchased from Tokyo
Kasei Co., Aldrich Inc., and other commercial suppliers and were
used as received. Fluorous-type surfactant ‘F-PEG’ was prepared
4.4.1. Coupling reaction using Brij 30 as a surfactant (Table 2, entry 1,
conditions A). Under an O2 atmosphere,
a mixture of 4-
methoxyphenylboroic acid (1a, 60.8 mg, 0.40 mmol), imidazole
(2a, 13.6 mg, 0.20 mmol), Cu(OAc)2 (3.6 mg, 0.020 mmol), ligand I
(3.7 mg, 0.020 mmol), and Brij 30 (21.8 mg, 0.060 mmol) in H2O
(4 mL) was stirred at room temperature for 24 h. The mixture was
diluted with brine and extracted with AcOEt (30 mLꢂ3). The

K. Inamoto et al. / Tetrahedron 68 (2012) 7794e7798
7797
organic layer was washed with H2O (10 mLꢂ3) and dried over
MgSO4. The solvent was removed under the reduced pressure and
the residue was purified by SiO2 column chromatography using
AcOEt to give N-(4-methoxyphenyl)imidazole (3aa) (23.7 mg, 68%).
120e122 ꢀC). 1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 7.23 (br s,
1H), 7.26 (br s, 1H), 7.28 (dt, 2H, J¼9.3, 2.5 Hz), 7.61 (dt, 2H, J¼9.3,
2.5 Hz), 7.84 (br s, 1H); 13C{1H} NMR (150 MHz, CDCl3/TMS)
d
(ppm): 118.2,121.0, 123.0, 130.8, 133.0,135.5,136.4; LRMS (EI) m/z:
222 (Mþ); HRMS: calcd for C9H7BrN2: 221.9793, found: 221.9774; IR
(neat): 3853, 3753, 3587, 3503, 1696, 1653, 1559, 1507, 748,
4.4.2. Coupling reaction using Triton X-100 as a surfactant (Table 2,
entry 1, conditions B). Under an O2 atmosphere, a mixture of 4-
methoxyphenylboroic acid (1a, 60.8 mg, 0.40 mmol), imidazole
(2a, 13.6 mg, 0.20 mmol), Cu(OAc)2 (3.6 mg, 0.020 mmol), ligand I
(3.7 mg, 0.020 mmol), and Triton X-100 (38.8 mg, 0.060 mmol) in
H2O (4 mL) was stirred at room temperature for 24 h. The mixture
was diluted with brine and extracted with AcOEt (30 mLꢂ3). The
organic layer was washed with H2O (10 mLꢂ3) and dried over
MgSO4. The solvent was removed under the reduced pressure and
the residue was purified by SiO2 column chromatography using
AcOEt to give N-(4-methoxyphenyl)imidazole (3aa) (23.0 mg, 66%).
658 cmꢁ1
.
4.4.9. N-(4-Cyanophenyl)imidazole (3fa).19 Recrystallized from
Et2O/hexane, yellow prisms, mp 143e145 ꢀC (lit.19 mp
152e154 ꢀC). 1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 7.28 (br s,
1H), 7.35 (br s, 1H), 7.54 (d, 2H, J¼8.8 Hz), 7.81 (d, 2H, J¼8.8 Hz),
7.96 (br s, 1H); 13C{1H} NMR (150 MHz, CDCl3/TMS)
(ppm):
d
111.2, 117.7, 117.8, 121.4, 131.5, 134.2, 135.3, 140.5; LRMS (EI) m/z:
169 (Mþ); HRMS: calcd for C10H7N3: 169.0640, found: 169.0647;
IR (neat): 3903, 3753, 2960, 2854, 2372, 2359, 1733, 1559, 1271,
831 cmꢁ1
.
4.4.3. Coupling reaction using F-PEG as a surfactant (Table 2, entry 1,
conditions C). A mixture of Cu(OAc)2 (3.6 mg, 0.020 mmol), ligand
II (21.6 mg, 0.020 mmol), and F-PEG (0.25 g, 0.10 mmol) in MeOH
(1 mL) was heated to dissolve all the reagents added completely
and MeOH was removed under the reduced pressure. H2O (6 mL)
was added to the residue and then 4-methoxyphenylboroic acid
(1a, 60.8 mg, 0.40 mmol) and imidazole (2a, 13.6 mg, 0.20 mmol)
were added. The whole reaction mixture was stirred under an O2
atmosphere at room temperature for 24 h. The mixture was diluted
with brine and extracted with AcOEt (30 mLꢂ3). The organic layer
was washed with H2O (10 mLꢂ3) and dried over MgSO4. The sol-
vent was removed under the reduced pressure and the residue was
purified by SiO2 column chromatography using AcOEt to give N-(4-
methoxyphenyl)imidazole (3aa) (26.4 mg, 78%).
4.4.10. N-(4-Ethoxycarbonylphenyl)imidazole
lized from Et2O, colorless needles, mp 103e104 ꢀC (lit.18 mp
101e103 ꢀC); 1H NMR (400 MHz, CDCl3/TMS)
(ppm): 1.42 (t, 3H,
(3ga).18 Recrystal-
d
J¼7.1 Hz), 4.42 (q, 2H, J¼7.1 Hz), 7.25 (br s, 1H), 7.36 (br s, 1H),
7.47 (d, 2H, J¼8.3 Hz), 7.95 (br s, 1H), 8.17 (d, 2H, J¼8.3 Hz); 13C
{1H} NMR (125 MHz, CDCl3/TMS)
d (ppm): 14.4, 61.4, 117.9, 120.7,
129.5, 131.2, 131.6, 135.5, 140.7, 165.6; LRMS (EI) m/z: 216 (Mþ);
HRMS: calcd for C12H12N2O2: 216.0899, found: 216.0900; IR
(neat): 3852, 3674, 2926, 2853, 2374, 1733, 1652, 1508, 1369,
1122 cmꢁ1
.
4.4.11. N-(2-Methylphenyl)imidazole (3ha).20 Obtained as yellow
oil. 1H NMR (400 MHz, CDCl3/TMS)
(ppm): 2.19 (s, 3H), 7.06 (s,
1H), 7.21e7.36 (m, 5H), 7.59 (br s, 1H); 13C{1H} NMR (150 MHz,
d
4.4.4. N-(4-Methoxyphenyl)imidazole (3aa) .16 Obtained as a color-
CDCl3/TMS) d (ppm): 17.5, 120.5, 126.5, 126.8, 128.7, 129.3, 131.2,
less solid. 1H NMR (400 MHz, CDCl3/TMS)
d
(ppm): 3.85 (s, 3H), 6.98
133.8, 136.6, 137.4; LRMS (EI) m/z: 158 (Mþ); HRMS: calcd for
(d, 2H, J¼8.8 Hz), 7.18e7.26 (m, 2H), 7.30 (d, 2H, J¼8.8 Hz), 7.78 (br
C10H10N2: 158.0844, found: 158.0827; IR (neat): 3110, 2861, 1502,
s, 1H); 13C{1H} NMR (100 MHz, CDCl3/TMS)
d
(ppm): 55.4, 114.7,
1309, 1240, 1057, 963, 817, 761, 662 cmꢁ1
.
118.5, 123.0, 129.9, 130.5, 135.6, 158.4; LRMS (EI) m/z: 174 (Mþ);
HRMS: calcd for C10H10N2O: 174.0793, found: 174.0770; IR (neat):
4.4.12. N-(3-Aminophenyl)imidazole (3ia).18 Obtained as a yellow
solid. 1H NMR (400 MHz, CDCl3/TMS)
(ppm): 3.87 (br s, 2H),
3113, 2836, 1609, 1590, 1515, 1465, 1242, 1055, 828, 730 cmꢁ1
.
d
6.64e6.68 (m, 2H), 6.75e6.77 (m, 1H), 7.18e7.25 (m, 3H), 7.83 (br s,
1H); LRMS (EI) m/z: 159 (Mþ); HRMS: calcd for C9H9N3: 159.0796,
found: 159.0784; IR (neat): 3419, 3327, 3207, 1607, 1588, 1507,
4.4.5. N-(4-Methylphenyl)imidazole (3ba).16 Obtained as yellow oil.
1H NMR (400 MHz, CDCl3/TMS)
(ppm): 2.41 (s, 3H), 7.20 (br s, 1H),
7.25e7.28 (m, 5H), 7.83 (br s, 1H); 13C{1H} NMR (100 MHz, CDCl3/
d
1236 cmꢁ1
.
TMS)
d (ppm): 20.9, 118.3, 121.4, 130.2, 130.3, 135.0, 135.6, 137.4;
LRMS (EI) m/z: 158 (Mþ); HRMS: calcd for C10H10N2: 158.0844,
4.4.13. N-(4-Methoxyphenyl)benzimidazole (3ab).19 Obtained as
a colorless solid. 1H NMR (400 MHz, CDCl3/TMS)
(ppm): 3.89 (s,
found: 158.0827; IR (neat): 3113, 2861, 1520, 1487, 1303, 1112, 1056,
d
963, 810, 730 cmꢁ1
.
3H), 7.07 (d, 2H, J¼8.8 Hz), 7.29e7.35 (m, 2H), 7.41(d, 2H,
J¼8.8 Hz), 7.44e7.47 (m, 1H), 7.86e7.88 (m, 1H), 8.05 (s, 1H); 13C
4.4.6. N-Phenylimidazole (3ca).16 Obtained as colorless oil. 1H NMR
(400 MHz, CDCl3/TMS) (ppm): 7.22 (br s, 1H), 7.30 (br s, 1H),
7.35e7.41 (m, 3H), 7.46e7.51 (m, 2H), 7.87 (br s, 1H); 13C{1H} NMR
{1H} NMR (100 MHz, CDCl3/TMS)
d (ppm): 55.6, 110.3, 115.1,
d
120.5, 122.5, 123.5, 125.7, 129.1, 134.2, 142.5, 143.8, 159.3; LRMS
(EI) m/z: 224 (Mþ); HRMS: calcd for C14H12N2O: 224.0950, found:
224.0964.
(100 MHz, CDCl3/TMS)
d (ppm): 118.2, 121.4, 127.4, 129.8, 130.4,
135.6, 137.3; LRMS (EI) m/z: 144 (Mþ); HRMS: calcd for C9H8N2:
144.0687, found: 144.0677; IR (neat): 3407, 3116, 1718, 1600, 1507,
4.4.14. N-(4-Methoxyphenyl)-2-phenylimidazole (3ac). Obtained as
1303, 1056, 963, 757, 685 cmꢁ1
.
a colorless solid. 1H NMR (400 MHz, CDCl3/TMS)
d (ppm): 3.82 (s,
3H), 6.90(d, 2H, J¼8.8 Hz), 7.10 (s, 1H), 7.13 (d, 2H, J¼8.8 Hz),
4.4.7. N-(4-Chlorophenyl)imidazole (3da).17 Obtained as a colorless
solid. 1H NMR (400 MHz, CDCl3/TMS)
(ppm): 7.23 (br s, 1H), 7.26
(br s, 1H), 7.34 (d, 2H, J¼8.8 Hz), 7.46 (d, 2H, J¼8.8 Hz), 7.83 (br s,
7.22e7.26 (m, 4H), 7.39e7.42 (m, 2H); 13C{1H} NMR (100 MHz,
d
CDCl3/TMS) d (ppm): 55.4, 114.5, 123.1, 127.0, 128.1, 128.05, 128.08,
128.7, 130.3, 131.5, 146.7, 159.2; LRMS (EI) m/z: 250 (Mþ); HRMS:
1H); 13C{1H} NMR (100 MHz, CDCl3/TMS)
d
(ppm): 118.2, 122.7,
calcd for C16H14N2O: 250.1106, found: 250.1102.
130.1, 130.8, 133.2, 135.6, 135.9; LRMS (EI) m/z: 178 (Mþ); HRMS:
calcd for C9H375ClN2: 178.0298, found: 178.0292; IR (neat): 3407,
4.4.15. N-(4-Methoxyphenyl)-4-methylimidazole (3ad-1).14 and N-
(4-methoxyphenyl)-5-methylimidazole (3ad-2) Obtained as a color-
3116, 1718, 1600, 1507, 1303, 1056, 963, 757, 685 cmꢁ1
.
less solid. 1H NMR (400 MHz, CDCl3/TMS)
d (ppm): 2.13 (s, 1.2H),
4.4.8. N-(4-Bromophenyl)imidazole (3ea).18 Recrystallized from
AcOEt/hexane, colorless needles, mp 120e122 ꢀC (lit.18 mp
2.29 (s, 1.8H), 3.84 (s, 1.8H), 3.86 (s, 1.2H), 6.88 (s, 0.4H), 6.92 (s,
0.6H), 6.97 (d, 1.2H J¼9.0 Hz), 6.99 (d, 0.8H, J¼9.2 Hz), 7.20 (d, 0.8H,

7798
K. Inamoto et al. / Tetrahedron 68 (2012) 7794e7798
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J¼9.2 Hz), 7.27 (d, 1.2H, J¼9.0 Hz), 7.52 (s, 0.4H), 7.65 (d, J¼1.4 Hz,
0.6H); LRMS (EI) m/z: 188 (Mþ).
4.4.16. N-(4-Methoxyphenyl)pyrazole (3ae).19 Obtained as yellow
oil. 1H NMR (400 MHz, CDCl3/TMS)
d (ppm): 3.84 (s, 3H), 6.43 (t, 1H,
J¼1.9 Hz), 6.97 (d, 2H, J¼9.0 Hz), 7.59 (d, 2H, J¼9.0 Hz), 7.69 (d, 1H,
J¼1.9 Hz), 7.82 (d, 1H, J¼1.9 Hz); 13C{1H} NMR (100 MHz, CDCl3/
TMS)
d (ppm): 55.5, 107.1, 114.5, 120.9, 126.8, 134.0, 140.6, 158.2;
LRMS (EI) m/z: 174 (Mþ); HRMS: calcd for C10H10N2O: 174.0793,
found: 174.0809.
4.4.17. Recovery and reuse of F-PEG. According to the procedure in
Section 4.4.3, the reaction of 1a with 2a in the presence of F-PEG was
carried out. After the reaction was complete, Et2O (5 mL) was added
to the reaction mixture and the organic layer was washed with H2O
(5 mLꢂ5). The combined aqueous layer was evaporated to remove
H2O and the residue was purified by short path SiO2 column chro-
matography usingCHCl3 togiveF-PEG(96% recovery). Therecovered
F-PEG was subjected to the same coupling, which resulted in the
successful formation of the coupling product 3aa in 78% yield.
5. For reviews, see: (a) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42,
5400e5449; (b) Qiao, J. X.; Lam, P. Y. S. Synthesis 2011, 829e856; See also: (c)
Chan, D. M. T.; Lam, P. Y. S. In Boronic Acids; Hall, D. G., Ed.; Wiley-VCH:
Weinheim, 2005, Chapter 5, p 205.
6. (a) Molecular sieves are generally employed as water scavengers for the
ChaneLam coupling. (b) For mechanistic studies of phenol-forming side re-
actions, see: Lam, P. Y. S.; Bonne, C.; Vincent, G.; Clark, C. G.; Combs, A. P. Tet-
rahedron Lett. 2003, 44, 1691e1694; (c) See also Refs. 4b and 5c.
7. Collman, J. P.; Zhong, M.; Zeng, L.; Costanzo, S. J. Org. Chem. 2001, 66,
1528e1531.
8. Inamoto, K.; Nozawa, K.; Yonemoto, M.; Kondo, Y. Chem. Commun. 2011,
11775e11777.
9. (a) Hoang, K. C.; Mecozzi, S. Langmuir 2004, 7347e7350; (b) Slaughter, J. N.;
Schmidt, K. M.; Byram, J. L.; Mecozzi, S. Tetrahedron Lett. 2007, 48, 3879e3882;
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76, 6584e6591.
10. Fluorous-type surfactant ‘F-PEG’ was readily prepared from MeOePEG (poly-
ethylene glycol) using the procedure similar to the Mecozzi’s method (Scheme
1). See Refs. 9a and b.
11. To the best of our knowledge, there has been only two examples of using
a fluorous surfactant for organic synthesis, see: (a) Nishimoto, K.; Kim, S.; Ki-
tano, Y.; Tada, M.; Chiba, K. Org. Lett. 2006, 8, 5545e5547; (b) Yi, W.-B.; Cai, C. J.
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Acknowledgements
This work was partly supported by a Grant-in-Aid for Scientific
Research (B) (No. 23390002), a Grant-in-Aid for Challenging Ex-
ploratory Research (No. 23659001), and a Grant-in-Aid for Young
Scientists (B) (No. 23790002) from Japan Society for the Promotion
of Science, and a Grant-in-Aid for Scientific Research on Innovative
Areas ‘Advanced Molecular Transformations by Organocatalysts’
(No. 23390002) from The Ministry of Education, Culture, Sports,
Science and Technology, Japan.
12. Fluorous-type ligand II was readily prepared according to the previously re-
ported method, see: Bennett, B. L.; Robins, K. A.; Tennant, R.; Elwell, K.; Ferri, F.;
Bashta, I.; Aguinaldo, G. J. Fluorine Chem. 2006, 127, 140e145.
13. For detailed experimental procedures regarding the recovery and reuse of F-
PEG, see ‘Section 4.4.17’ in Experimental section.
14. Zhu, L.; Li, G.; Luo, L.; Guo, P.; Lan, J.; You, J. J. Org. Chem. 2009, 74, 2200e2202.
15. When the reaction results in a low yield, unreacted starting materials are
generally recovered.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.07.042.
References and notes
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