Highly efficient copper(0)-catalyzed Suzuki-Miyaura cross-coupling reactions in reusable PEG-400

Article abstract of DOI:10.1016/j.tet.2008.02.068

Readily available copper powder with K₂CO₃ as the base was extremely effective catalyst for Suzuki-Miyaura coupling reaction performed in PEG-400, which afforded almost quantitative coupling products of aryl iodides. Using iodine as additive, coupling products of aryl bromides or chlorides could be obtained with moderate to good yields.

Full text of DOI:10.1016/j.tet.2008.02.068

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3905e3911
www.elsevier.com/locate/tet
Highly efficient copper(0)-catalyzed SuzukieMiyaura
cross-coupling reactions in reusable PEG-400
Jincheng Mao*, Jun Guo, Fubing Fang, Shun-Jun Ji*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical Engineering,
Suzhou (Soochow) University, Suzhou 215123, PR China
Received 22 November 2007; received in revised form 17 February 2008; accepted 22 February 2008
Available online 4 March 2008
Abstract
Readily available copper powder with K CO as the base was extremely effective catalyst for SuzukieMiyaura coupling reaction performed
2
3
in PEG-400, which afforded almost quantitative coupling products of aryl iodides. Using iodine as additive, coupling products of aryl bromides
or chlorides could be obtained with moderate to good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
6
1
. Introduction
environment than any noble metal. Although copper catalysts
have been used in many cross-coupling transformations, sur-
prisingly, there are only few publications on the use of such
The SuzukieMiyaura cross-coupling reaction has been
considered as a very powerful, versatile, and popular tool for
selective construction of carbonecarbon bonds in organic
7
,8
reagents for the SuzukieMiyaura cross-coupling reactions.
Recently, Rothenberg and co-workers firstly reported their
findings about the effective copper-catalyzed coupling reac-
tions of aryl halides with phenylboronic acid using mixed
1
chemistry, especially in the synthesis of biaryl compounds,
which are important structural substructures in numerous poly-
mers, agrochemicals, natural products, and pharmaceutical
7
nanocluster catalysts. However, the nanocopper prepared by
2
mediates. During the past decades, numerous efforts have
been made to develop efficient catalyst systems for Suzukie
strict synthetic procedure could only catalyze the couplings
of aryl iodides and existing additional metals (Pd and Ru)
showed better efficiency. This result prompted us to study
whether the SuzukieMiyaura cross-coupling reaction could
directly be catalyzed by more accessible copper catalyst and
whether the catalytic system could also be reused. To meet
the demands for recyclability and environmental concerns,
a more facile way is to immobilize the catalyst on a liquid
phase by dispersing it into a nonvolatile and low toxicity liq-
uid, such as poly(ethylene)glycols (PEG), which has been
used for biomedical applications, especially in the field of
drug discovery. In this paper, we wish to report our finding
that readily available copper powder, in combination with
K CO as the base, is an extremely effective catalyst for the
3
Miyaura cross-coupling reaction. Among them, a palla-
dium(0) complex together with (phosphorous) ligands is the
most popular catalytic system. However, reuse of this type
of catalysts is difficult since phosphorous ligands are sensitive
4
to air and moisture. Furthermore, the drawbacks of the Pd-
catalyst systems, such as high cost and toxicity, limit their
massive applications for industrial scales. Therefore, the task
of recycling and development of phosphine-free and palla-
dium-free catalytic systems is a current important challenge
in organic chemistry. In this way, the use of a cheaper metal
instead of Pd provides another attractive route. Of these, cop-
per-based alternatives are particularly attractive, due to their
orders of magnitude lower cost and harmfulness to the
9
1
0
5
2
3
Suzuki coupling reaction performed in PEG-400. Furthermore,
we found that PEG-400 worked not only as the recycling sol-
vent but could also accelerate the coupling reactions. In addi-
tion, molecular iodine was firstly employed as co-catalyst for
*
Corresponding authors. Tel.: þ86 512 65880403; fax: þ86 512 65880089.
E-mail address: jcmao@suda.edu.cn (J. Mao).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.068

3906
J. Mao et al. / Tetrahedron 64 (2008) 3905e3911
the coupling reactions of aryl bromide or chloride with aryl-
1
boronic acids.
Table 1
Copper-catalyzed SuzukieMiyaura coupling of iodobenzene and 4-methyl-
1
a
phenylboronic acid
b
Entry Cat.
Base
Solvent
Temp Time Yield
ꢀ
(
C)
(h)
(%)
2
. Results and discussion
1
2
3
4
CuI
CuCl
K
K
K
K
2
2
2
2
CO
CO
CO
CO
3
3
3
3
DMF
DMF
DMF
DMF
110
110
110
110
8
8
8
8
2
2
In order to explore copper catalysts for the Suzukie
2
Cu O
Trace
7
Miyaura coupling reactions, the coupling of 4-methylphenyl-
boronic acid with iodobenzene was chosen as the model
reaction to study the efficiency of different ligands (AeE),
Cu(OAc)
2
$
2
H O
5
6
7
8
9
1
CuSO4
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
K CO
2
3
3
3
3
3
3
3
3
DMF
DMF
110
110
110
110
80
8
8
Trace
72
15
1
2
which have proved effective in other coupling reactions.
As shown in Figure 1, it can be seen that different ligands
AeE) provided poor yields of the coupling product while
K
K
K
K
K
2
2
2
2
2
CO
CO
CO
CO
CO
DMSO
Toluene
IPOH
8
8
15
(
8
Trace
18
14
no ligand gave the best result (42% yield). Encouraged by
this finding, we screened other copper salts for the coupling
reaction (Table 1, entries 1e6). The results showed that copper
powder could catalyze the coupling reaction with best yield of
72% (entry 6). Subsequently, several common solvents and ba-
ses were screened and the results showed that DMF was the
0
Dioxane
H O
100
80
8
11
12
K CO
2
2
8
K
Cs
2
CO
CH
DMF
3
CN
80
8
9
1
1
1
1
3
4
5
6
2
CO
3
110
110
110
110
110
110
110
110
rt
8
1
K
t
BuOK
KOH
KF
3
PO
4
$H
2
O
DMF
DMF
8
8
8
Trace
20
DMF
DMF
8
best solvent (entries 7e12) and K CO was the most effective
2
17
18
8
4
84
3
base (entries 13e17). Then various phase transfer catalysts
including TBAB (tetrabutyl ammonium bromide), 16-3-Br
cetyl trimethyl ammonium bromide) and 18-18-2-Br (diocta-
decyl dimethyl ammonium bromide) were employed as addi-
tives. However, they had no positive effect on the catalytic
reactions. Changes of the loading of copper powder could
not lead to better results. In order to reuse the catalytic system,
PEG-400 was chosen as the reaction medium. To our surprise,
K
K
K
K
K
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
PEG-400
PEG-400
PEG-400
PEG-400
PEG-200
Ethanediol
8
1
2
2
2
9
0
1
2
12
12
18
12
12
12
99
32
c
(
d
Trace
99
110
110
23
24
a
K CO
2
5
77
K
2
CO
Propanediol 110
Reaction conditions: iodobenzene (1.0 equiv), 4-methylphenylboronic acid
(1.3 equiv), copper source (0.1 equiv), solvent (2.0 ml); base (2.0 equiv); tem-
ꢀ
perature: 110 C.
b
Isolated yield based on aryl halide.
The catalytic reaction was performed in air.
The catalytic reaction was performed at room temperature.
c
CuBr,Ligand
I +
B(OH)
d
DMF,K CO
2
3
1
10 °C,8h
the yield of the coupling product was enhanced to 84% (entry
18). When the reaction was run for 12 h, almost quantitative
coupling product was obtained (entry 19). The control exper-
iments showed that the catalytic reactions performed in air af-
forded the product with 32% yield (entry 20) and at room
temperature no product was obtained (entry 21). PEG-200
with lower molecular weight was also tested as solvent, pro-
viding the product with 99% yield (entry 22). In order to tes-
tify whether structure of polymeric alcohol was necessary, the
smaller alcohols with different structures were employed in
the coupling reactions, affording worse results (entries 23
and 24). The results showed that PEGs acted not only as recy-
cling solvent but could also accelerate the coupling reactions.
Under the optimized condition, high yields were obtained
in the coupling reactions of various aryl iodides and arylbor-
onic acids. The results are summarized in Table 2. It can be
seen that almost all of the coupling reactions could get com-
plete conversions. In addition, we found that a catalytic
5
0
0
0
0
0
0
4
3
2
1
A
B
C
D
E
No ligand
N
O
N
N
OH
OH
N
N
N
N
N
H
OH
ꢀ
OH
amount (10%) of copper powder with 12 h at 110 C could
catalyze the coupling reactions of iodobenzene and sterically
hindered arylboronic acids to give the corresponding products
with moderate yields (Table 2, entries 5 and 8).
In order to extend the range of substrates, we intended to
apply our methodology to a wide range of difficult halides,
A
B
C
D
E
Figure 1. Suzuki reactions promoted by different ligands (the catalytic condi-
tions: iodobenzene (1.0 equiv), 4-methylphenylboronic acid (1.3 equiv), CuBr
ꢀ
(
0.1 equiv), DMF (2.0 ml), K
2
CO
3
(2.0 equiv); temperature: 110 C; 8 h).

J. Mao et al. / Tetrahedron 64 (2008) 3905e3911
3907
Table 2
Copper-catalyzed SuzukieMiyaura couplings of aryl iodides and arylboronic acids
a
Copper powder
I
+
B(OH)2
R
R'
PEG-400
K2CO3
R
R'
b
Yield (%)
Entry
1
ArX
Arylboronic acid
Product
I
I
I
I
B(OH)2
99
2
3
4
F
B(OH)2
B(OH)2
F
99
99
90
Cl
Cl
MeO
OMe
B(OH)2
OMe
B(OH)2
MeO
5
I
85
OHC
OHC
CHO
6
7
8
I
I
I
99
94
77
B(OH)2
B(OH)2
CHO
CH3
B(OH)2
H3C
9
I
99
97
99
99
B(OH)2
1
1
0
1
2
MeO
MeO
I
I
OHC
B(OH)2
MeO
CHO
B(OH)2
MeO
1
1
Cl
I
B(OH)2
B(OH)2
Cl
3
2
O N
I
O N
99
2
a
Reaction conditions: aryl iodide (1.0 equiv); arylboronic acid (1.3 equiv); copper powder (0.1 equiv); solvent as PEG-400 (2.0 ml); base: K
ꢀ
2
CO
3
(2.0 equiv);
temperature: 110 C; 12 h.
b
Isolated yield based on aryl halide.
such as aryl bromides or chlorides. To our surprise, we could
not get the coupling products, even at elevated temperature
other iodides such as potassium iodide or copper iodide
were used which showed poor reactivity. Since our novel cat-
alytic system contains copper and iodine at the same time,
copper iodide alone was used instead of copper powder in
the coupling reaction. Under these conditions, no coupling
product was afforded.
ꢀ
(
lecular iodine is regarded as an effective catalyst or additive in
140 C) and extended time (36 h). As is well known that mo-
1
3
many organic syntheses, iodine (20 mol %) was added into
this catalyst system in hope of good efficiency. Luckily, the
coupling products of aryl bromides or chlorides were obtained.
After heating for extended periods of time, the corresponding
coupling products were obtained with good yields. In order to
verify the unique catalytic properties of molecular iodine,
Varying the loading of iodine, we found that 0.2 equiv of
iodine was enough to avoid getting large amount of the homo-
coupling product. Therefore, with the improvement of our pro-
tocol using Cu/I /K CO /PEG-400, the results listed in Table 3
2
2
3

3908
J. Mao et al. / Tetrahedron 64 (2008) 3905e3911
Table 3
Copper-catalyzed SuzukieMiyaura couplings of aryl bromides or chlorides and arylboronic acids mediated with iodine as the additive
a
Copper powder, I2
PEG-400, K2CO3
X +
B(OH)2
R
R'
R
R'
X = Br, Cl
b
Yield (%)
Entry
1
ArX
Arylboronic acid
Product
MeO
Br
B(OH)2
MeO
81
91
78
86
84
71
75
51
43
2
3
4
5
6
7
8
9
Br
Br
B(OH)2
Cl
B(OH)2
Cl
Cl
Cl
Cl
Cl
Cl
Br
B(OH)2
Br
Br
Br
F
Cl
B(OH)2
B(OH)2
B(OH)2
F
Cl
Cl
Cl
OHC
Cl
CHO
2
O N
Cl
B(OH)2
2
O N
2
O N
Cl
F
B(OH)2
B(OH)2
2
O N
F
1
1
0
2
O N
Cl
Cl
Cl
O N
Cl
23
38
2
1
F3C
B(OH)2
F3C
a
Reaction condition: aryl bromide or chloride (1.0 equiv) arylboronic acid (1.3 equiv), copper powder (0.1 equiv), solvent as PEG-400 (2.0 ml); base: K
ꢀ
2
CO
3
(
2.0 equiv); I
b
2
(0.2 equiv); temperature: 140 C; 36 h.
Isolated yield based on aryl halide.
were obtained. It is found that the coupling products of aryl
bromides were obtained with good yields (Table 3, entries
1e7) and the coupling reactions of aryl chlorides were
conducted with moderate results due to their poor reactivity
biphenylamines (Scheme 1). Notably, the way to recover the
catalytic system was very simple, only by adding diethyl ether
to the reaction and decanting the upper layer. It was found that
at the same temperature and similar reaction time our catalytic
system with low cost could be conveniently reused (up to five
cycles) with good catalytic activity for the process, which is
potentially useful for large-scale processes (Table 4).
(
CeCl bond.
entries 8e11), which is attributed to the strength of the
1
4
In order to show the versatility of our methodology, several
commercially available sources of copper powder have been
tested in our catalytic system, affording similar results. In ad-
dition, the feasibility of recycling the catalytic system was also
tested. In the view that the various biphenylamines are used as
intermediates in the synthesis of numerous organic compounds
including the azo dyes and as antioxidants in consumer goods
Based on our understanding about copper-catalyzed cross-
6
e8
coupling reactions,
the possible mechanism of copper
R1
R4
R1
R3
R4
R5
R2
B(OH)2
+
X
NO2
R2
NH2
1
5
R3
R5
X = I, Br, Cl
including most rubber products, the model coupling reaction
between phenylboronic acid and 4-nitro-iodobenzene was cho-
sen and studied, since its products are the precursors for
Scheme 1. A useful route to obtain biphenylamines.

J. Mao et al. / Tetrahedron 64 (2008) 3905e3911
3909
Table 4
Recycling data for copper powder-catalyzed SuzukieMiyaura coupling of
4. Experimental
a
4-nitro-iodobenzene and phenylboronic acid performed in PEG-400
4.1. General experimental
b
Yield (%)
Run
Time (h)
0
1
12
12
12
16
18
18
99
95
88
79
69
66
All reactions were carried out under an argon atmosphere con-
dition. Solvents were dried and degassed by standard methods,
and all arylboronic acids and aryl halides were purchased from
Aldrich and Alfa. Flash column chromatography was performed
using silica gel (300e400 mesh). Analytical thin-layer chroma-
tography was performed using glass plates pre-coated with
200e400 mesh silica gel impregnated with a fluorescent indica-
c
2
3
4
5
a
Reaction conditions: 4-nitro-iodobenzene (1.0 equiv), phenylboronic acid
(
1.3 equiv), copper powder (0.1 equiv), solvent as PEG-400 (2.0 ml); base:
ꢀ
K
2
b
CO
3
(4.0 equiv); temperature: 110 C.
Isolated yield based on aryl halide.
tor (254 nm). NMR spectra were measured in CDCl on a Varian
3
Inova-400 NMR spectrometer (400 MHz or 300 MHz) with
TMS as an internal reference. Products were characterized by
1 13
comparison of H and C NMR data with that in the literatures.
c
2 3
Additional 2.0 ml of PEG-400 and 1.5 equiv K CO were added into the
system.
powder-catalyzed ligand-free SuzukieMiyaura coupling reac-
tion performed in PEG-400 was proposed in Figure 2. It is pre-
sumed that PEG-400 works not only as the recycled medium
but also as a ligand. In addition, iodine in the system could
possibly make aryl bromides or chlorides transform into aryl
iodides in the presence of K CO as the base, which makes
the coupling of difficult substrates facile to be performed.
The related experiments were under way in our laboratory to
prove the mechanism.
4.2. General procedure for SuzukieMiyaura coupling
reactions of arylboronic acid and aryl iodides
A schlenk tube (evacuated and back-filled with argon) was
charged with copper powder (0.1 equiv), potassium carbonate
(2.0 equiv),arylboronicacid(1.0 equiv),andanyremainingsolids
(aryl iodide) in the solvent of PEG-400 (2 ml) and then aryl iodide
(1.3 equiv) was added under argon. The tube was sealed under ar-
2
3
ꢀ
gon, andthemixturewasheatedto 110 C andstirredfor 12 h. Af-
ter cooling to room temperature, the mixture was diluted with
water, and the combined aqueous phases were extracted three
times with ethyl acetate. The organic layers were combined, dried
over Na SO , and concentrated to yield the crude product, which
was further purified by silica gel chromatography, using petro-
leum ether as eluent to provide the desired product.
Cu(0)
OH
2
OH
2
4
ArI + base
ArX + I2 + K2CO3
Ar-Ar'
OH (0) HO
(
X= Br, Cl)
Cu
OH
HO
OH
=
PEG-400
4.3. General procedure for SuzukieMiyaura coupling
reactions of arylboronic acid and aryl bromides or chlorides
OH
(
IV)
O
O
Ar
Ar'
O
O
(IV)
Cu
Ar
Cu
I
A schlenk tube (evacuated and back-filled with argon) was
charged with copper powder (0.1 equiv), potassium carbonate
K2CO3-X + K2CO3-B(OH)2 Ar'B(OH)2 + 2K2CO3
(2.0 equiv), iodine (0.2 equiv), arylboronic acid (1.0 equiv),
Figure 2. The proposed mechanism of copper powder-promoted ligand-free
SuzukieMiyaura coupling reaction in PEG-400.
andany remainingsolids(arylbromideorchloride)inthesolvent
of PEG-400 (2 ml) and then aryl bromide or chloride (1.3 equiv)
was added under argon. The tubewas sealed under argon, and the
ꢀ
mixture was heated to 140 C and stirred for 36 h. After cooling
3
. Conclusion
to room temperature, the mixture was diluted with water and the
combined aqueous phases were extracted three times with ethyl
acetate. The organic layers were combined, dried over Na SO ,
and concentrated to yield the crude product, which was further
purified by silica gel chromatography, using petroleum ether as
eluent to provide the desired product.
In summary, we have developed an effective catalytic sys-
tem for copper-catalyzed SuzukieMiyaura coupling reaction:
Cu/K CO /PEG-400. It could afford almost quantitative
2
2
4
3
coupling products of aryl iodides. Using molecular iodine
as additive, we could get moderate to good yields of coupling
products of aryl bromides or chlorides. With simple workup,
we could reuse our catalytic system several times. All these
characteristics of our protocol make the reaction quite suit-
able for scale-up and commercialization. Further work is in
progress in this laboratory with the aim of expanding this cat-
alytic system to other processes and studying on the mecha-
nism of this copper-catalyzed SuzukieMiyaura coupling
reaction.
4.4. General procedure for recycled SuzukieMiyaura
coupling reactions of phenylboronic acid and
4-nitro-iodobenzene
A schlenk tube (evacuated and back-filled with argon)
was charged with copper powder (0.1 equiv), potassium car-
bonate (4.0 equiv), phenylboronic acid (1.0 equiv), and
4-nitro-iodobenzene (1.3 equiv) in the solvent of PEG-400

3910
J. Mao et al. / Tetrahedron 64 (2008) 3905e3911
2
3
(
2 ml). The tube was sealed under argon, and the mixture was
4.4.8. 3-Methoxylbiphenyl
ꢀ
1
heated to 110 C and stirred for 12 h. After cooling to room tem-
perature, the mixture was directly extracted three times with di-
ethyl ether. The upper layers were decanted, combined, and
concentrated to yield the crude product, which was further puri-
fied by silica gel chromatography, using petroleum ether and
ethyl acetate (10:1) as eluent to provide the desired product.
The mixture of copper powder, potassium carbonate, and
PEG-400 was solidified (cooled) and subjected to a second run
of the SuzukieMiyaura coupling reaction by charging with the
same substrates (phenylboronic acid and 4-iodo-nitrobenzene).
Then the system was evacuated and back-filled with argon for
three times. The following procedure is the same as above.
H NMR (CDCl , 300 Hz) (d, ppm) 3.76 (s, 3H, CH O),
3 3
6.80 (d, J¼7.8 Hz, 1H, ArH), 7.08 (t, J¼9.3 Hz, 6H, ArH),
1
3
7.23e7.36 (m, 2H, ArH), 7.50 (d, J¼7.5 Hz, 2H, ArH);
C
NMR (100 MHz, CDCl ) (d, ppm) 160.37, 143.20, 141.53,
3
130.20, 129.18, 127.86, 127.64, 120.11, 113.33, 113.10, 55.71.
2
4
4.4.9. 4-Methoxylbiphenyl
1
H NMR (CDCl , 300 Hz) (d, ppm) 3.86 (s, 3H, CH O),
3
3
6
2
1
.96e7.00 (m, 2H, ArH), 7.26 (s, 1H, ArH), 7.40e7.44 (m,
1
H, ArH), 7.52e7.57 (m, 4H, ArH); C NMR (CDCl3,
00 Hz) (d, ppm) 129.19, 128.63, 127.21, 127.13, 114.66, 55.8.
3
0
.4.10. 4-Chloro-4 -nitrobiphenyl
3h
4
1
6
4
.4.1. 4-Methylbiphenyl
ꢀ
1
Mp 112e113 C; H NMR (CDCl , 400 Hz) (d, ppm), 7.47
3
ꢀ
1
Mp 46e47 C, H NMR (CDCl , 300 Hz) (d, ppm) 2.37 (s,
3
(
d, J¼8.4 Hz, 2H, ArH), 7.56 (d, J¼8.4 Hz, 2H, ArH), 7.71 (d,
3
H, CH ), 7.22 (d, J¼7.5 Hz, 2H, ArH), 7.30 (t, J¼7.2 Hz, 1H,
13
3
J¼8.8 Hz, 2H, ArH), 8.30 (d, J¼8.8 Hz, 2H, ArH); C NMR
ArH), 7.40 (t, J¼7.5 Hz, 2H, ArH), 7.48 (d, J¼7.8 Hz, 2H,
(
1
CDCl , 100 Hz) (d, ppm) 147.67, 146.76, 137.62, 135.70,
3
29.83, 129.08, 128.13, 124.67.
1
3
ArH), 7.56 (d, J¼7.5 Hz, 2H, ArH); C NMR (75 MHz,
CDCl ) (d, ppm) 141.59, 138.79, 137.44, 129.93, 129.16,
3
1
27.44, 127.42, 21.56.
0
25
4
.4.11. 4-Fluoro-4 -nitrobiphenyl
1
H NMR (CDCl , 400 Hz) (d, ppm) 7.17e7.21 (m, 2H,
3
1
7
4
.4.2. Biphenyl
1
ArH), 7.59e7.62 (m, 2H, ArH), 7.69e7.71 (m, 2H, ArH),
13
.29e8.31 (m, 2H, ArH); C NMR (CDCl , 100 Hz) (d,
H NMR (400 MHz, CDCl ) (d, ppm) 7.36 (d, J¼7.2 Hz,
3
8
ppm) 165.06, 147.03, 138.20, 135.39, 129.66, 129.58,
3
2
4
1
H, ArH), 7.45 (t, J¼7.2 Hz, 4H, ArH), 7.60 (t, J¼7.2 Hz,
1
H, ArH); C NMR (100 MHz, CDCl ) (d, ppm) 141.67,
3
3
1
28.18, 128.12, 124.66, 116.78, 116.56.
29.22, 127.72, 127.64.
0
1
8
4.4.12. 4-Chloro-4 -fluorobiphenyl
4
.4.3. 4-Fluorobiphenyl
1
1
H NMR (CDCl
ArH), 7.38e7.51 (m, 6H, ArH); C NMR (CDCl , 100 Hz)
(d, ppm) 164.27, 161.82, 139.13, 136.57, 136.54, 133.85,
129.42, 128.70, 116.34, 116.13.
, 400 Hz) (d, ppm) 7.12 (t, J¼8.8 Hz, 2H,
3
H NMR (CDCl , 300 Hz) (d, ppm) 7.12 (t, J¼8.7 Hz, 2H,
3
13
3
ArH), 7.34 (t, J¼7.1 Hz, 1H, ArH), 7.43 (t, J¼7.2 Hz, 2H,
1
3
ArH), 7.51e7.56 (m, 4H, ArH);
CDCl ) (d, ppm) 164.15, 161.70, 140.71, 137.80, 137.77,
C NMR (100 MHz,
3
1
29.29, 129.19, 129.11, 127.72, 127.48, 116.18, 115.97.
0
26
4
.4.13. 4-Chloro-biphenyl-4 -carbaldehyde
1
0
19
H NMR (CDCl , 400 Hz) (d, ppm) 7.44 (d, J¼8.4 Hz, 2H,
3
4
.4.4. 4-Methoxylbiphenyl-4 -carbaldehyde
1
ArH), 7.55 (d, J¼8.4 Hz, 2H, ArH), 7.70 (d, J¼8.0 Hz, 2H,
ArH), 7.94 (d, J¼8.0 Hz, 2H, ArH), 10.05 (s, 1H, CHO).
H NMR (CDCl , 300 Hz) (d, ppm) 3.87 (s, 3H, CH O),
3
3
7
7
1
1
.01 (d, J¼6.3 Hz, 2H, ArH), 7.60 (d, J¼6.6 Hz, 2H, ArH),
.71 (d, J¼6.0 Hz, 2H, ArH), 7.93 (d, J¼6.0 Hz, 2H, ArH),
2
7
1
0.04 (s, 1H, CHO); C NMR (CDCl , 75 Hz) (d, ppm)
3
4
.4.14. Biphenyl-4-carbaldehyde
3
1
H NMR (CDCl , 400 Hz) (d, ppm) 7.42e7.51 (m, 2H,
3
92.39, 130.80, 128.98, 127.63, 119.38, 114.94, 55.88.
ArH), 7.64 (d, J¼7.6 Hz, 2H, ArH), 7.76 (d, J¼8.0 Hz, 2H,
ArH), 7.96 (d, J¼8.0 Hz, 2H, ArH), 10.06 (s, 1H, CHO);
2
0
4
.4.5. 2-Methoxylbiphenyl
1
1
3
C NMR (CDCl , 100 Hz) (d, ppm) 192.41, 147.64, 140.15,
3
H NMR (CDCl , 300 Hz) (d, ppm) 3.70 (s, 3H, CH O),
3
3
1
35.62, 130.73, 129.47, 128.93, 128.13, 127.81.
6
.987e6.96 (m, 2H, ArH), 7.21 (t, J¼6.3 Hz, 3H, ArH),
.31 (t, J¼7.2 Hz, 2H, ArH), 7.44 (d, J¼7.5 Hz, 2H, ArH);
7
1
3
28
C NMR (100 MHz, CDCl ) (d, ppm) 156.84, 138.93,
3
4.4.15. Biphenyl-3-carbaldehyde
1
1
31.30, 129.95, 129.02, 128.39, 127.32, 121.22, 111.60, 55.94.
H NMR (CDCl , 400 Hz) (d, ppm) 7.40 (s, 1H, ArH), 7.41e
3
7
.49 (m, 3H, ArH), 7.62 (t, J¼6.8 Hz, 3H, ArH), 7.86 (d,
2
1
4
.4.6. 1-Phenylnaphthalene
1
J¼7.2 Hz, 2H, ArH), 8.10 (s, 1H, ArH), 10.09 (s, 1H, CHO);
13
H NMR (CDCl , 300 Hz) (d, ppm) 7.45e7.49 (m, 6H,
3
C NMR (CDCl , 100 Hz) (d, ppm) 192.85, 142.66, 140.18,
3
1
3
ArH), 7.82e7.84 (m, 6H, ArH); C NMR (CDCl , 75 Hz)
3
137.39, 133.56, 129.99, 129.49, 129.12, 128.69, 128.50, 127.64.
(
d, ppm) 133.82, 130.46, 129.86, 128.64, 128.26, 126.20.
0
29
4
.4.16. 4,4 -Dichlorobiphenyl
2
2
1
4
.4.7. 2-Methylbiphenyl
1
H NMR (300 MHz, CDCl ) (d, ppm) 7.40 (d, J¼8.1 Hz,
3
13
H NMR (CDCl , 300 Hz) (d, ppm) 2.19 (s, 3H, CH ),
3
4H, ArH), 7.33 (d, J¼8.4 Hz, 4H, ArH);
C NMR
(75 MHz, CDCl ) (d, ppm) 138.88, 134.02, 129.52, 128.70.
3
3
7
.15e7.32 (m, 9H, ArH).

J. Mao et al. / Tetrahedron 64 (2008) 3905e3911
3911
3
0
4
.4.17. 4-Nitrobiphenyl
S. L. Angew. Chem., Int. Ed. 2005, 44, 6173e6177; (k) Liu, D.; Gao, W.;
Dai, Q.; Zhang, X. Org. Lett. 2005, 7, 4907e4910; (l) Lebel, H.; Janes,
M. K.; Charette, A. B.; Nolan, S. P. J. Am. Chem. Soc. 2004, 126,
1
H NMR (400 MHz, CDCl ) (d, ppm) 7.49e7.56 (m, 3H,
3
ArH), 7.67 (d, J¼7.6 Hz, 2H, ArH), 7.78 (d, J¼8.4 Hz, 2H,
5
046e5047; (m) Schweizer, S.; Becht, J.-M.; DrianLe, C. Adv. Synth.
1
3
ArH), 8.34 (d, J¼8.4 Hz, 2H, ArH); C NMR (100 MHz,
Catal. 2007, 349, 1150e1158 and references cited therein.
4. Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and
Applications of Organotransition Metal Chemistry; University Science:
Mill Vallley, CA, 1987.
CDCl ) (d, ppm) 147.85, 138.98, 129.38, 129.14, 128.02,
3
1
27.61, 125.11, 124.38.
5
. (a) Saito, S.; Ohtani, S.; Miyaura, N. J. Org. Chem. 1997, 62, 8024e8030;
b) Zim, D.; Lando, V. R.; Dupont, J.; Monteiro, A. L. Org. Lett. 2001, 3,
3049e3051.
3
1
4
.4.18. 4-Chlorobiphenyl
(
1
H NMR (400 MHz, CDCl ) (d, ppm) 7.33e7.45 (m, 5H,
3
ArH), 7.49e7.55 (m, 4H, ArH); C NMR (75 MHz, CDCl3)
d, ppm) 140.43, 140.11, 133.82, 129.50, 129.43, 129.37,
1
3
6. For special reviews on copper-catalyzed cross-couplings, see: (a) Siemsen,
P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39,
(
1
2
632e2657; (b) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
29.35, 128.85, 128.05, 127.44, 110.20.
M. Chem. Rev. 2002, 102, 1359e1470; (c) Ley, S. V.; Thomas, A. W.
Angew. Chem., Int. Ed. 2003, 42, 5400e5449; (d) Beletskaya, I. P.;
Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337e2364.
3
2
4
.4.19. 4-Trifluoromethylbiphenyl
ꢀ
1
Mp 69e70 C; H NMR (400 MHz, CDCl ) (d, ppm) 7.35
7
. (a) Thathagar, M. B.; Beckers, J.; Rothenberg, G. J. Am. Chem. Soc. 2002,
1
3
24, 11858e11859; (b) Thathagar, M. B.; Beckers, J.; Rothenberg, G.
Adv. Synth. Catal. 2003, 345, 979e985.
(
t, J¼7.6 Hz, 1H, ArH), 7.40e7.49 (m, 3H, ArH), 7.60 (d,
1
3
J¼7.2 Hz, 3H, ArH), 7.69 (s, 2H, ArH);
C NMR
100 MHz, CDCl ) (d, ppm) 129.48, 129.24, 128.67, 127.91,
8
. (a) Li, J.-H.; Wang, D.-P. Eur. J. Org. Chem. 2006, 2063e2066; (b) Li,
J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu,
X.-C. J. Org. Chem. 2007, 72, 2053e2057; (c) Li, J.-H.; Li, J.-L.; Xie,
Y.-X. Synthesis 2007, 7, 984e988.
(
1
3
27.74, 127.65, 126.17.
9
. Using PEG as solvent in coupling reactions, see: (a) Liu, L.; Zhang, Y.;
Wang, Y. J. Org. Chem. 2005, 70, 6122e6125; (b) van der Heiden, M.;
Plenio, H. Chem.dEur. J. 2004, 10, 1789e1797; (c) Glegola, K.;
Framery, E.; Pietrusiewicz, K. M.; Sinou, D. Adv. Synth. Catal. 2006,
348, 1728e1733.
Acknowledgements
The authors would like to thank the Natural Science
Foundation of Education Committee of Jiangsu Province
1
0. Poly(ethylene glycol): Chemistry and Biological Applications; Harris,
J. M., Zalipsky, S., Eds.; American Chemical Society: Washington, 1997.
1. Copper-catalyzed halogen exchange in aryl halides: Klapars, A.;
Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 4844e4845.
(
06KJB150099, 05KJB150116), Natural Science Foundation
of Jiangsu Province (BK2006048), Natural Science Founda-
tion of China (20472062, 20672079), China Postdoctoral
Science Foundation, and Key Laboratory of Organic Synthesis
of Jiangsu Province for financial support.
1
12. (a) Jiang, D.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2007, 72, 672e
674; (b) Wu, G. G.; Wong, Y. S.; Poirier, M. Org. Lett. 1999, 1, 745e
7
47; (c) Fagan, P. J.; Hauptman, E.; Shapiro, R.; Casalnuovo, A. J. Am.
Chem. Soc. 2000, 122, 5043e5051; (d) Cai, J.; Zhou, Z.; Zhao, G.;
Tang, C. Org. Lett. 2004, 4, 4723e4725; (e) Zhu, W.; Ma, D. Chem.
Commun. 2004, 888e889.
Supplementary data
Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2008.02.068.
13. Togo, H.; Iido, S. Synlett 2006, 2159e2175.
1
4. For a review in palladium-catalyzed coupling reactions of aryl chlorides:
Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176e4211.
5. Radomski, J. L. Annu. Rev. Pharmacol. Toxicol. 1979, 19, 129e157.
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1
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