Recyclable catalysts for Suzuki-Miyaura cross-coupling reactions at ambient temperature based on a simple merrifield resin supported phenanthroline- palladium(II) complex

Article abstract of DOI:10.1055/s-0030-1258472

A novel Merrifield resin immobilized phenanthroline-palladium(II) complex has been developed and was found to be an efficient catalyst for Suzuki-Miyaura cross-coupling reaction between arylboronic acids and a range of aryl halides under mild reaction conditions. The catalyst exhibited both high catalytic activity and stability for Suzuki-Miyaura reaction. Furthermore, the catalyst could be recycled at least 10 times without a significant loss of catalytic activity. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1258472

PAPER
1295
Recyclable Catalysts for Suzuki–Miyaura Cross-Coupling Reactions at
Ambient Temperature Based on a Simple Merrifield Resin Supported
Phenanthroline–Palladium(II) Complex
a
a
a,b
R
J
ecyclabl
i
e
C
atal
n
f
or Suzuki–Mi
Y
yaura
C
ross-Coup
a
ling
R
eactio
n
ns g, Pinhua Li, Lei Wang*
a
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P. R. of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. of China
b
Fax +86(561)3090518; E-mail: leiwang@chnu.edu.cn
Received 7 January 2011; revised 7 February 2011
reduced. So the application of reusable and recoverable
heterogeneous catalysts has recently attracted much atten-
tion. However, inorganic heterogeneous catalysts show
Abstract: A novel Merrifield resin immobilized phenanthroline–
palladium(II) complex has been developed and was found to be an
efficient catalyst for Suzuki–Miyaura cross-coupling reaction be-
tween arylboronic acids and a range of aryl halides under mild reac-
6
low stability due to leaching of the metal from the sur-
7
tion conditions. The catalyst exhibited both high catalytic activity faces. To overcome these problems, a lot of efforts have
and stability for Suzuki–Miyaura reaction. Furthermore, the catalyst
been made to design and synthesize new efficient and re-
could be recycled at least 10 times without a significant loss of cat-
alytic activity.
cyclable heterogeneous catalysts, such as immobilization
of catalytically active metal complexes in mesoporous
8
Key words: immobilized catalyst, phenanthroline–palladium(II)
silica and covalent grafting of such active complexes
complex, Suzuki–Miyaura reaction, recyclability
9
onto reactive polymer surfaces. The grafting of such sup-
ports with homogeneous catalysts often provides good
catalytic activity together with possible recovery of the
The transition-metal-catalyzed coupling of aryl halides catalyst system by simple conduction. In recent years, the
with arylboronic acids (Suzuki–Miyaura reaction) has be- use of magnetic nano particles as novel supports for catal-
come a very important synthetic tool in organic chemistry ysis has also attracted much of interest due to their conve-
and in particular it is largely employed for the synthesis of nient separation.10
1
symmetric and nonsymmetric biaryls, among which, pal-
Complexes of palladium(II) with nitrogen containing
ladium catalysts are known to possess high activity for the
11
12
ligands, phosphine containing ligands, and N,O-, P,O-,
P,N-, and P,S-heteroligated bidentate ligands13 are well-
known catalysts for Suzuki–Miyaura coupling reactions,
and thus there is a large interest to employ this reaction in
the formation of C–C bonds. However, phosphine con-
taining ligands are expensive, toxic and in large-scale ap-
plications the phosphines may be a more serious
2
coupling reaction. Over the past few decades, a variety of
homogeneous catalysts have been developed in this area.3
Although homogeneous catalysts have many advantages,
common catalysts for the Suzuki–Miyaura reaction are
generally based on homogeneous palladium complexes of
Pd(0) or Pd(II), which cause difficulties in purification of
the final product and recycling of the expensive catalyst.
Moreover, the homogeneous Pd catalysts tend to lose their
catalytic activity due to Pd metal aggregation and precip-
itation; further removal of residual palladium offers con-
siderable complexity to the reaction that may restrict it
14
economical burden than even the metal itself. In recent
years there has been an increasing interest in developing
greener processes. This principle promoted us to develop
new highly efficient and recyclable heterogeneous cata-
lyst – the palladium(II) complexes with simple, low-toxic,
nitrogen containing ligand for Suzuki–Miyaura coupling
reactions. 1,10-Phenanthroline and its derivatives are
well-established ligands for transition-metal coordination
chemistry because their steric and electronic environment
can be conveniently tailored by varying the substituents,15
and are widely used in transition-metal-catalyzed reac-
tions.16 The rigid framework of 1,10-phenanthroline and
its high affinity toward various cations, which can provide
sufficient protecting shield for the transition metal center,
are attractive features for the construction of highly effec-
tive catalyst. However, as typical bidentate nitrogen con-
taining ligand, late transition metal complexes of 1,10-
phenanthrolines, have rarely been reported for catalytic
Suzuki–Miyaura coupling reactions. In continuation of
our efforts in developing greener synthetic pathways for
organic reaction,17 herein we report a new, recoverable,
4
industrially application. Thus, the heterogenation of the
existing homogeneous Pd catalysts could be an attractive
solution to this problem because the heterogeneous cata-
lysts can be easily separated from the reaction mixture.
Immobilization of homogeneous catalysts on various in-
soluble supports with high surface areas is usually the
method of choice since the immobilized catalysts can be
facilely recovered via a simple filtration process after the
5
reaction. At the same time, the catalyst recovery also de-
creases the contamination of the desired products with
hazardous or unhealthy compounds, and also environ-
mental pollution caused by residual toxic metals can be
SYNTHESIS 2011, No. 8, pp 1295–1301
x
x
.
x
x
.2
0
1
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Advanced online publication: 10.03.2011
DOI: 10.1055/s-0030-1258472; Art ID: H10010SS
Georg Thieme Verlag Stuttgart · New York
©

1
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J. Yang et al.
PAPER
highly active Merrifield resin supported phenanthroline– 1,4-dioxane, which are commonly used for the homoge-
Pd(II) catalyst and illustrate its application for the Suzuki– neous palladium-catalyzed Suzuki–Miyaura coupling re-
Miyaura coupling reactions under aerobic condition actions, afforded moderate yields of the products
(
Scheme 1). The catalyst shows a high catalytic activity in (Table 1, entries 4–8). It is worth noting that a high yield
the coupling reactions of various aryl halides and orga- was also achieved when the reaction was performed in
noboronic compounds. Furthermore, the catalyst could be H O (Table 1, entry 9). However, the nonpolar solvents,
2
easily quantitatively recovered from the reaction mixture such as toluene and hexane, gave low yields (Table 1, en-
by a simple filtration and reused at least 10 times without tries 10 and 11). Hence, considering the yield of the prod-
significant loss of its catalytic activity. High activity, con- uct and the convenience of separating the catalyst, ethanol
venient catalyst recovery and excellent recycling efficien- was finally selected as the solvent for the reaction for it is
cy make the catalyst to be an ideal coupling reactions less expensive and readily available.
system.
Table 1 Effect of the Solvents on Suzuki Reaction of 4-Bromo-
anisole and Phenylboronic Acida
CHO
NaH
DMF
4 (1 mol%)
MeO
Br
+
B(OH)2
OMe
P
P
K2CO3
solvent, r. t.
Cl
O
CHO
OH
P
1
Yield (%)b
H2N
N
Entry
Solvent
MeOH
EtOH
1
2
3
4
5
6
7
8
9
92
93
90
87
85
80
78
70
84
30
17
2
N
N
N
O
N
i-PrOH
MeCN
DMF
3
Pd(OAc)2
N
N
OAc
P
Pd
O
OAc
1,4-dioxane
THF
N
4
Scheme 1 Preparation of Merrifield resin supported palladium cata-
DMSO
lyst
H O
2
The Merrifield resin supported phenanthroline palladium
catalyst 4 was prepared according to the three-step proce-
dure summarized in Scheme 1. Firstly, the commercially
available Merrifield resin was reacted with 4-hydroxy-
1
0
1
toluene
hexane
1
a
Reaction conditions: 4-bromoanisole (0.5 mmol), phenylboronic
benzaldehyde in the presence of sodium hydroxide in an- acid (0.6 mmol), supported Pd catalyst 4 (23 mg, containing Pd 0.005
hydrous DMF at 90 °C for six hours to generate the mmol), K
CO (1.0 mmol) in solvent (2.0 mL) at r.t. for 4 h.
Isolated yields.
2
3
b
functionalized resin 1. The above functionalized resin 1
was subsequently treated with 5-amino-1,10-phenanthro-
line (2) in ethanol under reflux condition for 24 hours. Af-
ter filtering the organics, the resin was washed with
ethanol and diethyl ether, and dried under vacuum. The
phenanthroline-functionalized resin 3 obtained was react-
Our next studies focused on the effect of bases. Among
the bases examined, it turned out that K CO acts as an ex-
cellent base (Table 2, entry 1), while other inorganic
bases, such as Na CO , Cs CO , K PO , Na PO , KOAc,
and KF were also effective (Table 2, entries 2–5). Howev-
er, the organic bases, such as triethylamine and TBAA
2
3
2
3
2
3
3
4
3
4
ed with Pd(OAc) in MeCN at room temperature for four
2
hours to generate the polystyrene-immobilized phenan-
throline palladium catalyst 4 as a brown powder. ICP-
AES measurements showed a catalyst loading of 0.22
mmol palladium per gram of resin.
(
tetra-n-butylammonium acetate) were substantially less
effective (Table 2, entries 6, 7). The amount of supported
palladium catalyst was also screened, and the experimen-
In our initial screening experiments, the reaction between tal data indicated that the reaction was complete within
phenylboronic acid and 4-bromoanisole was investigated four hours at room temperature when 0.5 mol% loading of
to optimize the reaction conditions, and the results are palladium was used (Table 2, entries 8–10).
summarized in Table 1. At first, the solvent effect was ex-
To examine the scope of this coupling reaction, we ex-
amined, and a significant solvent effect was observed. It
tended our studies to different combinations of arylboron-
is evident that high yields were obtained when the reac-
ic acids and aryl halides under the optimized reaction
tion was performed in alcoholic solvents, such as MeOH,
conditions (supported Pd catalyst 4, 0.5 mol%, K CO ,
2
3
EtOH, and i-PrOH (Table 1, entries 1–3), whereas aprotic
polar solvents, such as THF, DMF, DMSO, MeCN, and
EtOH, r.t.). The results are listed in Table 3. At the begin-
ning of the determination of the aryl halide substrate
Synthesis 2011, No. 8, 1295–1301 © Thieme Stuttgart · New York

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Recyclable Catalysts for Suzuki–Miyaura Cross-Coupling Reactions
1297
Table 2 Effect of the Bases on Suzuki Reaction of 4-Bromoanisole
and Phenylboronic Acid
substituted aryl halides, as well as arylboronic acid
a
(Table 3, entries 3, 19–22). When the reaction of 2-bro-
moanisole with phenylboronic acid or 2-methoxyben-
zeneboronic acid, and bromobenzene with 2,4-
dimethoxybenzeneboronic acid was carried out under the
present reaction conditions, the products were obtained in
high yields. Furthermore, it was noteworthy that the
present protocol is applicable even to sodium tetraphe-
nylborate and potassium aryltrifluoroborate; they could
also couple efficiently with 4-bromoanisole and generate
the cross-coupling products in good yields (Table 3, en-
tries 23 and 24). In addition, when 2,4-diiodobenzene was
reacted with phenylboronic acid (2 equiv), the corre-
sponding product terphenyl was isolated in 71% yield
4
(1 mol%)
EtOH
+
B(OH)2
OMe
MeO
Br
base, r. t.
Yield (%)b
Entry
Bases
1
K CO
93
87
91
93
88
62
37
94
93
74
2
3
2
Na CO
2
3
3
Cs CO
2
3
4
K PO
3
4
5
Na PO
3
4
(
Table 3, entry 25).
6
Et N
3
Table 3 Suzuki Coupling Reaction of Aryl Halide with Arylboronic
7
TBAA
K CO
Acida
8c
9d
2
3
3
3
4
(0.5 mol%)
EtOH
X
+
B(OH)2
K CO
R1
R2
2
R1
R2
K2CO3, r. t.
5
1
0e
K CO
2
Entry Arylboronic acid
Aryl halide
Product Yield
a
b
Reaction conditions: 4-bromoanisole (0.5 mmol), phenylboronic
(%)
acid (0.6 mmol), supported Pd catalyst 4 (23 mg, containing Pd 0.005
mmol), base (1.0 mmol) in EtOH (2.0 mL) at r.t. for 4 h.
1
5a
5a
93
93
B(OH)2
MeO
MeO
I
b
Isolated yields.
c
Supported Pd catalyst 4, (35 mg, containing Pd 0.0075 mmol) was
2
used.
B(OH)2
Br
d
Supported Pd catalyst 4 (12 mg, containing Pd 0.0025 mmol) was
used.
Br
e
3
5b
5c
88
90
Supported Pd catalyst 4 (6 mg, containing Pd 0.0013 mmol) was
used.
B(OH)2
OMe
scope, phenylboronic acid was used as a model substrate,
and several substituted aryl bromides containing both
electron-withdrawing and electron-donating groups on
different position were examined, in order to test the tol-
erance of functional groups (Table 2, entries 1–12), good
to excellent yields of biphenyls were achieved in most
cases. It was shown that this coupling reaction was appli-
cable to aryl bromides substituted with various functional
groups on different positions at room temperature. In ad-
dition, the highly active catalytic protocols have also been
developed for the cross-coupling between heteroaryl ha-
lides and phenylboronic acid, for instance, 2-bromopyri-
dine and 3-bromopyridine were able to undergo the
coupling reactions smoothly with phenylboronic acid and
generate the cross-coupling products in good yields
Br
Br
4
B(OH)2
MeO
5
5d
5e
5f
88
87
91
B(OH)2
6
Br
B(OH)2
7
B(OH)2
2
O N
Br
Br
8
5g
88
B(OH)2
O2N
NC
9
5h
5i
91
90
89
83
90
B(OH)2
Br
(
Table 3, entries 13 and 14).
1
0
B(OH)2
B(OH)2
B(OH)2
B(OH)2
OHC
O
Br
Unfortunately, the coupling reaction of aryl chloride, such
as 4-choloroanisole, with phenylboronic acid gave poor 11
result (Table 3, entry 15). On the other hand, the scope of
the arylboronic acids was further investigated. The results
indicated that the functional groups had little influence on
the phenyl ring for the coupling reactions. Arylboronic
acids bearing electron-withdrawing and electron-donating
groups also coupled efficiently with 4-bromoanisole with-
in four hours and good to excellent yields of the products
were isolated (Table 3, entries 16–20). The supported
palladium-catalyzed cross-coupling could tolerate ortho-
5j
5k
5l
Br
1
1
1
2
3
4
EtO2C
Br
Br
Br
N
5m
85
B(OH)2
N
Synthesis 2011, No. 8, 1295–1301 © Thieme Stuttgart · New York

1
298
J. Yang et al.
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Table 3 Suzuki Coupling Reaction of Aryl Halide with Arylboronic
Acid (continued)
was also determined. ICP analysis of the clear filtrates in-
dicated that the palladium content was less than 0.2 ppm.
Furthermore, in order to investigate the heterogeneity of
the catalyst systems, hot filtration test was performed.
However, no additional amount of the desired product
was obtained for the model reaction by adding substrates
to a filtrate obtained from the filtration of the immobilized
palladium catalyst 4 after the reaction. It is confirmed the
heterogeneous character of the catalytically active species
in this reaction.
a
4
(0.5 mol%)
EtOH
X
+
B(OH)2
R1
R2
R1
R2
K2CO3, r. t.
5
Entry Arylboronic acid
Aryl halide
Product Yield
b
(
%)
1
1
5
6
5a
5n
trace
85
B(OH)2
MeO
MeO
Cl
Br
B(OH)2
Table 4 Recycling Polystyrene-Immobilized Supported Palladium
Catalyst 4 for the Suzuki Reaction of 4-Bromoanisole and Phenyl-
boronic Acida
MeO
MeO
1
1
7
8
5o
5p
93
84
B(OH)2
MeO
MeO
Br
Br
4
(0.5 mol%)
MeO
Br +
B(OH)2
OMe
EtOH
K2CO3, r. t.
F3C
B(OH)2
Entry
Yield (%)b
Entry
Yield (%)b
B(OH)2
OMe
1
2
2
2
9
0
1
2
5q
5r
5s
5t
83
78
80
81
MeO
MeO
Br
Br
1
2
3
4
93
93
91
90
90
6
89
88
87
85
83
7
B(OH)2
8
Cl
9
B(OH)2
Br
5
10
OMe
OMe
a
Reaction conditions: 4-bromoanisole (0.5 mmol), phenylboronic
MeO
B(OH)2
OMe
acid (0.5 mmol), reused supported Pd catalyst 4 (12 mg, containing Pd
Br
0
.0025 mmol), K CO (138 mg, 1.0 mmol) in EtOH (2.0 mL) at r.t.
2 3
for 4 h.
b
Isolated yields.
2
2
3
4
5
5a
5o
5u
82
87
71
Ph4BNa
MeO
MeO
MeO
I
Br
Br
In summary, a simple Merrifield resin supported phenan-
throline–Pd(II) complex has been developed and success-
fully used as an efficient heterogeneous catalyst for
Suzuki cross-coupling reaction at room temperature under
aerobic condition. The catalyst exhibits high catalytic ac-
tivity and many practical advantages such as thermal sta-
bility and oxygen insensitivity. Furthermore, the catalyst
could be reused for ten consecutive cycles without a sig-
nificant loss of catalytic activity. These advantages make
the process highly valuable for industrial applications.
BF3K
2
B(OH)2
I
a
Reaction conditions: aryl halide (0.5 mmol), organoboron com-
pound (0.5 mmol), supported Pd catalyst 4 (12 mg, containing Pd
.0025 mmol), K CO (1.0 mmol) in EtOH (2.0 mL) at r.t. for 4 h.
0
2
3
b
Isolated yields.
An important point concerning the use of heterogeneous
catalysts is its lifetime, particularly for the industrial and
pharmaceutical applications of cross-coupling reactions.
All H and 13C NMR spectra were recorded with a Bruker Avance
1
The polystyrene-immobilized supported palladium cata- NMR spectrometer (400 MHz or 100 MHz, respectively). The C, H,
lyst 4 was therefore tested for recoverability and reusabil- and N analyses were performed with a Vario El III elementar. The
Pd content was determined by a Jarrell-Ash 1100 ICP analysis.
ity. After carrying out the reaction, the reaction solution
Products were purified by flash column chromatography on 200–
was vacuum-filtered and the original supported-palladium
catalyst was filtered off and washed with EtOH (3.0 mL)
4
00 mesh silica gel. All the reactions were carried out under an air
atmosphere, and commercially obtained materials were used with-
and Et O (3.0 mL). After drying, the supported catalyst
2
out further purification, 5-amino-1,10-phenanthroline (2) was pre-
could be reused directly without further purification. Re-
sults in Table 4 show that the palladium resin catalyst can
18
pared according to the literature.
be recovered and reused in further reactions without a sig- Benzaldehyde-Functionalized Resin 1
Into a 100 mL round-bottomed flask were introduced anhyd DMF
40.0 mL), 4-hydroxybenzaldehyde (1.17 g), and NaOH (0.44 g).
nificant degradation in activity. Although the catalytic ac-
tivity gradually diminished, a conversion of over 83% was
still achieved in the tenth run. Moreover, low contamina-
tion of residual metal in the isolated products is an impor-
tant characteristic for supported metal catalyst. Therefore
(
After stirring the solution at r.t. for 2 h, the Merrifield resin (4.0 g)
was added and the solution was heated at 90 °C for 6 h. The solution
was then filtered, and the solid was washed subsequently with DMF
(
4.0 mL), CH Cl (4.0 mL), Et O (4.0 mL), and dried under reduced
2 2 2
possible palladium leaching in palladium(II) catalyst 4 pressure to yield 4.4 g of product.
Synthesis 2011, No. 8, 1295–1301 © Thieme Stuttgart · New York

PAPER
Recyclable Catalysts for Suzuki–Miyaura Cross-Coupling Reactions
1299
1
3
IR (KBr): 3436, 3057, 3024, 2919, 2849, 1671 (C=O), 1599, 1508,
C NMR (100 MHz, CDCl ): d = 141.7, 138.6, 137.3, 129.7, 128.8,
3
–
1
1
492, 1419, 1384, 1250, 1157, 1066, 1017, 829, 758, 697 cm .
127.2, 126.9, 21.3.
Phenanthroline-Functionalized Resin 3
-Amino-1,10-phenanthroline (2; 0.41 g, 5.0 mmol) and benzalde-
3-Methylbiphenyl (5e)20
Colorless oil.
5
hyde functionalized resin 1 (2.0 g) were mixed in EtOH (25.0 mL)
in a round-bottomed flask. The reaction was carried out at 80 °C for
1
H NMR (400 MHz, CDCl ): d = 7.69–7.67 (2 H, m), 7.54–7.48 (4
3
H, m), 7.45–7.26 (2 H, m), 7.25 (1 H, d, J = 7.6 Hz), 2.51 (3 H, s).
1
2
4 h. Then the solution was filtered, and the solid was washed with
3
C NMR (100 MHz, CDCl ): d = 141.3, 141.2, 138.3, 128.7, 128.7,
EtOH (3.0 mL) and Et O (3.0 mL), and dried under vacuum to yield
3
2
1
28.6, 128.0, 127.9, 127.2, 127.1, 127.1, 124.2, 21.5.
2
.27 g of a yellow powder. The loading of the phenanthroline func-
tionalized resin was quantified by CHN microanalysis and found to
be 0.76 mmol⋅g based on the N content.
4-Nitrobiphenyl (5f)20
Pale yellow solid; mp 111–113 °C (Lit. mp 112–114 °C).
–
1
2
0
IR (KBr): 3081, 3057, 3023, 2919, 2849, 1675 (C=N), 1601, 1508,
1
–
1
H NMR (400 MHz, CDCl ): d = 8.30 (2 H, dd, J = 6.8, 2.0 Hz),
1
492, 1419, 1392, 1302, 1244, 1165, 1017, 758, 698 cm .
3
7
.74 (2 H, d, J = 8.8 Hz), 7.63 (2 H, dd, J = 8.4, 1.6 Hz), 7.53–7.45
(
13
3 H, m).
Merrifield Resin-Supported Phenanthroline–Pd(II) Catalyst 4
In an oven-dried round-bottomed flask were added Pd(OAc) (67.4
2
C NMR (100 MHz, CDCl ): d = 147.6, 147.0, 138.7, 129.1, 128.9,
3
27.8, 127.4, 124.1.
mg, 0.3 mmol), phenanthroline-functionalized resin 3 (1.0 g), and
MeCN (5.0 mL). The resulting suspension was stirred at r.t. for 2 h.
Then, the solution was filtered, and the solid was washed with
1
-Nitrobiphenyl (5g)20
3
MeCN (5.0 mL), Et O (5.0 mL), and dried under vacuum. The
20
2
Pale yellow solid; mp 60–61 °C (Lit. mp 60–61 °C).
Merrifield resin supported phenanthroline–Pd(II) catalyst was ob-
tained as a yellow powder. The Pd content of the catalyst was found
1
H NMR (400 MHz, CDCl ): d = 8.44 (1 H, s), 8.22 (1 H, d, J = 7.6
3
–
1
Hz), 7.91 (1 H, d, J = 8.0 Hz), 7.66–7.58 (3 H, m), 7.53–7.26 (3 H,
to be 0.22 mmol⋅g based on ICP analysis.
m).
IR (KBr): 3399, 3057, 3023, 2918, 1601 (C=N), 1573, 1507, 1492,
13C NMR (100 MHz, CDCl
1
): d = 148.6, 142.7, 138.7, 133.1, 129.8,
29.1, 128.6, 127.1, 122.2, 121.8.
–
1
3
1
451, 1419, 1374, 1300, 1221, 1109, 1002, 826, 740, 697 cm .
Catalytic Suzuki–Miyaura Reaction; General Procedure
A mixture of aryl halide (0.5 mmol), organoboron compound (0.5
mmol), K CO (1.0 mmol), immobilized Pd catalyst 4 (12 mg, con-
taining 0.0025 mmol of Pd), and EtOH (2.0 mL) was stirred at r.t.
for 4 h. Then, the reaction solution was vacuum-filtered and washed
2
0
1
,1¢-Biphenyl-4-carbonitrile (5h)
20
White solid; mp 84–86 °C (Lit. mp 85–86 °C).
2
3
1H NMR (400 MHz, CDCl
J = 7.6 Hz), 7.48–7.41 (3 H, m).
): d = 7.74–7.67 (4 H, m), 7.59 (2 H, d,
3
with EtOH (3.0 mL) and Et O (3.0 mL), concentrated, and the resi-
due was purified by flash chromatography on silica gel using PE–
EtOAc as eluent to obtain the desired product 5 (Table 3).
13
2
C NMR (100 MHz, CDCl ): d = 145.6, 139.1, 132.6, 129.1, 128.6,
3
1
27.7, 127.2, 118.9, 110.9.
2
0
1
,1¢-Biphenyl-4-carboxaldehyde (5i)
4
-Methoxybiphenyl (5a)19
20
White solid; mp 56–58 °C (Lit. mp 57–59 °C).
1
9
White solid; mp 85–87 °C (Lit. mp 85–86 °C).
1
H NMR (400 MHz, CDCl ): d = 10.05 (1 H, s), 7.94 (2 H, d, J = 8.0
3
1
H NMR (400 MHz, CDCl ): d = 7.59–7.55 (4 H, m), 7.44 (2 H, t,
3
Hz), 7.74 (2 H, d, J = 8.0 Hz), 7.63 (2 H, d, J = 7.6 Hz), 7.49 (2 H,
J = 7.6 Hz), 7.33 (1 H, m), 7.00–6.99 (2 H, m), 3.87 (3 H, s).
dd, J = 8.0, 2.0 Hz), 7.46–7.41 (1 H, m).
1
3
C NMR (100 MHz, CDCl ): d = 159.1, 140.8, 133.7, 128.7, 128.1,
13
3
C NMR (100 MHz, CDCl ): d = 191.9, 147.1, 139.6, 135.1, 130.2,
3
1
26.7, 126.6, 114.2, 55.3.
1
29.0, 128.4, 127.6, 127.3.
2
-Methoxybiphenyl (5b)19
-(4-Biphenylyl)ethanone (5j)20
White solid; mp 119–121 °C (Lit. mp 120–121 °C).
1
Colorless oil.
20
1
H NMR (400 MHz, CDCl ): d = 7.58–7.56 (2 H, m), 7.43–7.39 (2
1
3
H NMR (400 MHz, CDCl ): d = 8.03 (2 H, d, J = 8.4 Hz), 7.68 (2
3
H, m), 7.35–7.31 (2 H, m), 7.17–7.12 (2 H, m), 6.87 (1 H, dd,
H, d, J = 8.4 Hz), 7.62 (2 H, d, J = 7.6 Hz), 7.48–7.41 (2 H, m), 7.40
J = 8.0, 2.4 Hz), 3.82 (3 H, s).
(
1 H, m), 2.63 (3 H, s).
1
3
C NMR (100 MHz, CDCl ): d = 159.9, 142.7, 141.0, 129.7, 128.7,
13
3
C NMR (100 MHz, CDCl ): d = 197.7, 145.7, 139.8, 135.8, 128.9,
3
1
27.3, 127.1, 119.6, 112.8, 112.6, 55.2.
1
28.9, 128.2, 127.2, 127.1, 26.7.
3
-Methoxybiphenyl (5c)19
-(Ethoxycarbonyl)-1,1¢-biphenyl (5k)20
4
Colorless oil.
Colorless oil.
1
1
H NMR (400 MHz, CDCl ): d = 7.52 (2 H, dd, J = 8.4, 1.2 Hz),
3
H NMR (400 MHz, CDCl ): d = 8.15 (2 H, d, J = 8.0 Hz), 7.69–
3
7
3
.40 (2 H, t, J = 7.6 Hz), 7.32–7.29 (3 H, m), 7.04–6.96 (2 H, m),
.78 (3 H, s).
7
4
.64 (4 H, m), 7.48 (2 H, t, J = 8.0 Hz), 7.41 (1 H, t, J = 7.6 Hz),
.46–4.38 (2 H, m), 1.45 (3 H, t, J = 7.6 Hz).
1
3
C NMR (100 MHz, CDCl ): d = 156.4, 138.5, 130.8, 130.6, 129.5,
28.6, 127.9, 126.9, 120.8, 111.1, 55.5.
13
3
C NMR (100 MHz, CDCl ): d = 166.8, 145.5, 140.3, 130.0,129.6,
3
1
1
29.2, 128.3, 127.6, 127.3, 61.2, 14.5.
4
-Methylbiphenyl (5d)19
-Phenylpyridine (5l)21
Colorless oil.
2
1
9
White solid; mp 46–47 °C (Lit. mp 46 °C).
1
H NMR (400 MHz, CDCl ): d = 7.63 (2 H, d, J = 7.6 Hz), 7.53 (2
1
3
H NMR (400 MHz, CDCl ): d = 8.72 (1 H, d, J = 7.6 Hz), 8.05–
.00 (2 H, m), 7.78–7.72 (2 H, m), 7.55–7.48 (2 H, m), 7.43–7.41 (1
H, m), 7.27–7.22 (1 H, m).
3
H, d, J = 8.0 Hz), 7.48 (2 H, t, J = 7.6 Hz), 7.41–7.36 (1 H, m),
8
7
.32–7.27 (2 H, m), 2.42 (3 H, s).
Synthesis 2011, No. 8, 1295–1301 © Thieme Stuttgart · New York

1
300
J. Yang et al.
PAPER
1
3
1
C NMR (100 MHz, CDCl ): d = 157.7, 149.8, 139.6, 136.9, 129.1,
H NMR (400 MHz, CDCl ): d = 7.49 (2 H, d, J = 7.6 Hz), 7.37 (2
3
3
1
28.9, 126.8, 122.2, 120.7.
H, t, J = 8.0 Hz), 7.28–7.22 (2 H, m), 6.55–6.52 (2 H, m), 3.78 (3 H,
s), 3.75 (3 H, s).
3
-Phenylpyridine (5m)21
13
C NMR (100 MHz, CDCl ): d = 160.4, 157.4, 138.3, 131.2, 129.2,
3
Colorless oil.
1
28.0, 126.5, 123.6, 104.4, 99.0, 55.4, 55.2.
1
H NMR (400 MHz, CDCl ): d = 8.84 (1 H, s), 8.61 (1 H, d, J = 8.0
3
Hz), 7.86–7.82 (1 H, m), 7.60–7.56 (2 H, m), 7.48–7.44 (2 H, m),
1,4-Diphenylbenzene (5u)19
White solid; mp 212–215 °C (Lit. mp 212–213 °C).
1
9
7
.41–7.32 (2 H, m).
1
3
1
C NMR (100 MHz, CDCl ): d = 148.6, 148.1, 137.6, 134.2, 129.0,
H NMR (400 MHz, CDCl ): d = 7.68 (4 H, s), 7.66–7.63 (4 H, m),
3
3
1
28.0, 127.1, 123.7.
7.47–7.44 (4 H, m), 7.38–7.34 (2 H, m).
1
3
C NMR (100 MHz, CDCl ): d = 140.8, 140.2, 128.8, 127.6, 127.4,
,4¢-Dimethoxybiphenyl (5n)22
3
3
1
27.0.
Colorless oil.
1
H NMR (400 MHz, CDCl ): d = 7.52 (2 H, d, J = 7.6 Hz), 7.33 (1
3
Acknowledgment
H, d, J = 8.0 Hz), 7.14 (1 H, d, J = 7.6 Hz), 7.09 (1 H, d, J = 2.0 Hz),
6
.97 (2 H, d, J = 7.2 Hz), 6.85 (1 H, dd, J = 7.6, 1.6 Hz), 3.86 (3 H,
We gratefully acknowledge the financial support by the National
Natural Science Foundation of China (No. 20972057, 20772043).
s), 3.84 (3 H, s).
1
3
C NMR (100 MHz, CDCl ): d = 159.8, 159.2, 142.3, 133.6, 129.7,
3
1
28.2, 119.2, 114.1, 112.5, 112.0, 55.3, 55.2.
References
4
,4¢-Dimethoxybiphenyl (5o)22
(
1) For recent reviews, see: (a) Miyaura, N.; Suzuki, A. Chem.
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2
2
White solid; mp 177–179 °C (Lit. mp 178–179 °C).
1
H NMR (400 MHz, CDCl ): d = 7.49 (4 H, d, J = 8.0 Hz), 6.97 (4
3
H, d, J = 8.4 Hz), 3.86 (6 H, s).
1
3
C NMR (100 MHz, CDCl ): d = 158.7, 133.4, 127.7, 120.8, 114.1,
3
2
007, 40, 275. (f) Martin, R.; Buchwald, S. L. Acc. Chem.
5
5.3.
Res. 2008, 41, 1461. (g) Alonso, F.; Beletskaya, I. P.; Yus,
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2
3
4
-Methoxy-4¢-trifluoromethylbiphenyl (5p)
23
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White solid; mp 122–124 °C (Lit. mp 124–125 °C).
1
H NMR (400 MHz, CDCl ): d = 7.66 (4 H, m), 7.48 (2 H, d, J = 8.0
3
Hz), 7.29 (2 H, d, J = 7.6 Hz), 2.42 (3 H, s).
1
3
C NMR (100 MHz, CDCl ): d = 160.0, 144.2, 132.2, 128.8 (q,
3
2J = 33.6 Hz), 128.3, 126.8, 125.6, 124.5 (q, JC,F = 270.6 Hz),
1
1
C,F
14.6, 55.2.
(
3) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem.
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2
,4¢-Dimethoxybiphenyl (5q)23
2
3
White solid; mp 68–70 °C (Lit. mp 69–70 °C).
1
H NMR (400 MHz, CDCl ): d = 7.49 (2 H, d, J = 8.0 Hz), 7.32–
3
47, 8310. (d) Fujihara, T.; Yoshida, S.; Terao, J.; Tsuji, Y.
7
.28 (2 H, m), 7.05–6.92 (4 H, m), 3.86 (3 H, s), 3.82 (3 H, s).
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1
3
C NMR (100 MHz, CDCl ): d = 158.7, 156.5, 130.7, 130.7, 130.3,
3
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1
28.2, 120.8, 113.5, 111.0, 55.6, 55.2.
2
-Chloro-4¢-methoxybiphenyl (5r)24
12636.
Colorless oil.
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3217. (b) Yin, L.; Liebscher, J. Chem. Rev. 2007, 107, 133.
1
H NMR (400 MHz, CDCl ): d = 7.74 (1 H, dd, J = 7.6, 1.6 Hz),
3
(
6) (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000,
00, 3009. (b) Gent, J. P.; Savignac, M. J. J. Organomet.
7
.46 (2 H, d, J = 8.0 Hz), 7.40–7.29 (3 H, m), 7.04 (2 H, d, J = 8.0
1
Hz), 3.85 (3 H, s).
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1
3
C NMR (100 MHz, CDCl ): d = 159.4, 140.2, 132.8, 131.9, 131.4,
3
(
1
30.8, 130.1, 128.2, 126.8, 113.6, 55.2.
2
004, 226, 101. (b) Yu, K.; Sommer, W.; Richardson, J. M.;
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2
,2¢-Dimethoxybiphenyl (5s)25
(
Colorless oil.
1
H NMR (400 MHz, CDCl ): d = 7.36 (2 H, dt, J = 8.0, 1.6 Hz), 7.28
2 H, dd, J = 7.6, 1.6 Hz), 7.06 (2 H, dt, J = 7.6, 1.2 Hz), 7.05 (2 H,
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(
d, J = 8.0 Hz), 3.80 (s, 6 H).
1
3
(d) Crudden, C. M.; Sateesh, M.; Lewis, R. J. Am. Chem.
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C NMR (100 MHz, CDCl ): d = 157.4, 131.8, 128.9, 127.7, 120.7,
3
1
11.5, 55.5.
,4-Dimethoxybiphenyl (5t)26
2
Colorless oil.
Synthesis 2011, No. 8, 1295–1301 © Thieme Stuttgart · New York

PAPER
Recyclable Catalysts for Suzuki–Miyaura Cross-Coupling Reactions
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(
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(
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(
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Synthesis 2011, No. 8, 1295–1301 © Thieme Stuttgart · New York