Silica supported palladium-phosphine complex: Recyclable catalyst for Suzuki-Miyaura cross-coupling reactions at ambient temperature

Article abstract of DOI:10.1016/j.tet.2010.11.042

A new silica immobilized palladium-phosphine complex has been developed. It was found to be an efficient catalyst for Suzuki-Miyaura cross-coupling reactions under mild conditions. It is important to note that the supported catalyst could be reused at least 10 times without a significant loss of catalytic activity. Copyright

Full text of DOI:10.1016/j.tet.2010.11.042

Tetrahedron 67 (2011) 318e325
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Silica supported palladium-phosphine complex: recyclable catalyst for
SuzukieMiyaura cross-coupling reactions at ambient temperature
Wei Chen , Pinhua Li ,*, Lei Wang a
a
a
,b,
*
a
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, PR China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 July 2010
Received in revised form 1 November 2010
Accepted 9 November 2010
Available online 12 November 2010
A new silica immobilized palladium-phosphine complex has been developed. It was found to be an
efficient catalyst for SuzukieMiyaura cross-coupling reactions under mild conditions. It is important to
note that the supported catalyst could be reused at least 10 times without a significant loss of catalytic
activity.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Immobilized catalyst
Palladium-phosphine complex
SuzukieMiyaura reactions
Recyclability
1
. Introduction
activity together with possible recovery of the catalyst system by
simple conduction. More recently, new smart supports, such as
1
The SuzukieMiyaura reaction, palladium-catalyzed cross-cou-
pling of aryl halides with arylboronic acids, is one of the most
valuable synthetic methods for the preparing symmetric and
nonsymmetric biaryls, which are important skeletons in the
structures of biologically active compounds, agrochemicals,
pharmaceuticals, ligands, and functional materials. Over the past
magnetic nanoparticles (MNPs) have emerged and have great
11
potential for catalyst recovery.
Thiel et al. have reported supported palladium-phosphine
complex catalyzed SuzukieMiyaura cross-coupling reaction, but
2
12
the results were not representing the best of advance in this area.
3
4
5
In continuing our efforts to develop greener synthetic methodology
13
few decades, significant progresses in this area have been achieved
with a variety of homogeneous catalysts. Although homogeneous
for the organic transformations, we here report the synthesis of
a new, recoverable, and highly active silica anchored palladium-
phosphine catalyst and its application for the SuzukieMiyaura
cross-coupling reactions in aqueous medium under aerobic con-
dition (Scheme 1). The catalyst shows a high catalytic activity in the
coupling reactions of various aryl halides and organoboronic acids.
Easy catalyst recovery and excellent recycling efficiency of the
catalyst make it as an ideal catalytic system for the coupling re-
actions in aqueous phase. It is important to note that the grafted
catalyst could be recovered and reused at least 10 times without
significant loss of its reactivity.
6
catalysts have many advantages, and homogeneous catalysts were
difficult to be recovered and reused, and the residual Pd metal
along with the products could induce serious problems in the
synthesis of bioactive and functional substrates, and it could not be
used in large-scale syntheses particular on environmental and
economic concerns. To overcome these problems, the application of
reusable and recoverable heterogeneous catalysts has recently
attracted much attention due to the increasing worldwide mo-
mentum for the development of environmentally friendly reactions
7
in terms of green chemistry. In this context, a lot of efforts have
been made to design and synthesize recoverable catalysts. Various
inorganic and organic supports have been explored, such as mes-
oporous silica, ionic liquids, and polymers. The grafting of such
supports with homogeneous catalysts often provides good catalytic
2
. Results and discussion
8
9
10
The silica gel immobilized palladium catalyst was prepared
according to the four-step procedure summarized in Scheme 1. The
aminopropyl functionalized silica gel (1) was prepared through the
reaction of a commercially available silica gel with 3-amino-
propyltriethyoxylsilane (APTS) in refluxing toluene for 20 h, then it
was isolated and washed subsequently with toluene, methanol, and
*
Corresponding authors. Tel.: þ86 561 3802 069; fax: þ86 561 3090 518; e-mail
address: leiwang@chnu.edu.cn (L. Wang).
0
040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.042

W. Chen et al. / Tetrahedron 67 (2011) 318e325
319
(
EtO) Si(CH ) NH
3 2 3 2
OH
OH
OH
O
(
APTS)
O
O
O
SiO
2
SiO
2
O Si
O
NH2
P
o
Toluene, 120 C
CH Cl
2
2
(
1)
NH2
O
H
N
Ph
2
OH
(3)
SiO
2
O Si
O
O
O
HOBt, DIC/CH Cl
2 2
(
2)
O
H
N
H
SiO
2
O Si
O
N
Pd(OAc)2
PPh2
THF-CH OH
3
O
O
(4)
O
H
N
H
N
SiO
2
O Si
O
O
PPh2
PPh2
Supported
Palladium
Catalyst (5)
O
O
O
O
Pd
2
H
N
H
N
SiO
2
O Si
O
Scheme 1.
ꢀ
dichloromethane, and dried at 80 C for 10 h under reduced pres-
sure. The above aminopropyl functionalized silica gel (1) was sub-
sequently reacted with glutaric anhydride in dichloromethane at
room temperature with shaking for 24 h.
as MeOH, EtOH, and i-PrOH, resulted in excellent yields of the
products (Table 1, entries 1e3). When the reactions were conducted
in water, good yield of the product was obtained (Table 1, entry 4).
While the reactions were carried out in aprotic polar solvents, such
After the organics were filtered, the silica was washed with
toluene, water, and methanol and dried in vacuum, carboxylic acid-
functionalized silica gel (2) was obtained, and then the silica gel (2)
reacted with phosphine (3) to generate the phosphine-functional-
ized silica gel (4). The obtained 4 then reacted with palladium(II)
3
as THF, DMF, DMSO, CH CN, and 1,4-dioxane, moderate yields of the
products were isolated (Table 1, entries 6e10).
Unfortunately, in nonpolar solvents, such as toluene and hexane,
poor results were obtained (Table 1, entries 11 and 12). It was worth
noting that the best result was observed when the reaction was
acetate in THF/CH
3
OH at room temperature for 5 h to generate the
2
performed in MeOH/H O (1:1, v/v) (Table 1, entry 5). Hence, the
silica supported palladium-phosphine complex, so called sup-
ported palladium catalyst (5).
aqueous MeOH was finally selected as the solvent for the reaction
because it is highly efficient, less expensive, and readily available.
Our next studies focused on the effect of base. With regard to other
Our initial investigation was directed toward exploring the re-
action conditions for the model cross-coupling of phenylboronic
acid with 4-bromoanisole in the presence of catalyst 5. At first, the
solvent effect was examined, and a significant solvent effect was
observed (Table 1). The use of non-aqueous alcoholic solvents, such
reaction conditions, K
2
CO
3
was found to act as an excellent base
Table 2
a
Effect of the base on SuzukieMiyaura reaction
5
(1.0 % mol)
B(OH)
2
+
H
3
CO
Br
OCH
3
Table 1
MeOH/H O
2
a
Effect of the solvent on SuzukieMiyaura reaction
Entry
Bases
Yieldb [%]
5
(1.0 % mol)
H CO
Br +
B(OH)2
OCH
3
3
K CO , solvent
1
2
3
4
5
6
7
8
9
K2CO3
94
89
88
93
86
81
43
69
0
2
3
Na
2
CO
CO
PO
3
Cs
2
3
Entry
Solvent
Yieldb [%]
K
3
4
1
2
3
4
5
6
7
8
9
MeOH
EtOH
i-PrOH
92
89
87
80
94
71
68
70
41
47
31
19
KOAc
KF
TBAA
H
2
O
3
Et N
MeOH/H
DMF
DMSO
2
O (1:1)
DBU
c
10
11
12
K
2
K
2
K
2
CO
CO
CO
3
95
94
72
d
3
3
e
CH
3
CN
Dioxane
THF
Toluene
Hexane
a
Reaction conditions: 4-bromoanisole (94 mg, 0.5 mmol), phenylboronic acid
(42.4 mg, containing Pd
O (1:1, v/v, 2.0 mL) at room temperature
1
1
1
0
1
2
(
0
72 mg, 0.6 mmol), supported palladium catalyst
.005 mmol), base (1.0 mmol) in MeOH/H
for 4 h.
5
2
a
b
Reaction conditions: 4-bromoanisole (94 mg, 0.5 mmol), phenylboronic acid
(42.4 mg, containing Pd
(138 mg, 1.0 mmol) in solvent (2.0 mL) at room temperature for
Isolated yields.
c
(
72 mg, 0.6 mmol), supported palladium catalyst
5
Supported palladium catalyst 5 (84.8 mg, containing Pd 0.01 mmol) was used.
Supported palladium catalyst 5 (21.2 mg, containing Pd 0.0025 mmol) was used.
Supported palladium catalyst 5 (10.6 mg, containing Pd 0.0005 mmol) was used,
d
e
0
4
2 3
.005 mmol), K CO
h.
b
Isolated yields.
12 h.

320
W. Chen et al. / Tetrahedron 67 (2011) 318e325
(
Table 2, entry 1). Na
2
CO
3
, Cs
2
CO
3
, K
3
PO
4
, KOAc, and KF were also
reactions smoothly and generate the cross-coupling products in
good yields (Table 3, entries 18 and 19). Unfortunately, the coupling
reactions of aryl chlorides, such as 4-nitrocholorobenzene,
4-chloroacetophenone, and 4-choloroanisole with phenylboronic
acid gave the poor results (Table 3, entries 21e23). On the other
hand, arylboronic acids bearing electron-withdrawing and elec-
tron-donating groups also coupled efficiently with 4-bromoanisole
within 4 h and good to excellent yields of the products were iso-
lated (Table 3, entries 24e29). However, when thiophene-2-bo-
ronic acid was used as coupling partner, no desired product was
obtained (Table 3, entry 32), because of poisoning of palladium
catalyst on the sulfur atom. The supported palladium-catalyzed
cross-coupling could tolerate ortho-substituted aryl halides, as well
as arylboronic acid (Table 3, entries 5, 6e7, 10, 25, 29e31). When
the reactions of 2,4-dimethoxybenzeneboronic acid with iodo-
benzene, 2,4-dichlorobenzeneboronic acid with iodobenzene,
2-bromoanisole with phenylboronic acid, 2-methoxybenzenebor-
onic acid with 4-bromoanisole, and 2,4-dimethoxybenzeneboronic
acid with bromobenzene were carried out under the present re-
action conditions, the products were obtained in high yields (Table
effective (Table 2, entries 2e6). Other bases, such as triethylamine
and TBAA (tetra-n-butylammonium acetate) were substantially less
effective (Table 2, entries 7 and 8). To our surprise, the reaction did
not work when DBU (1,8-diazabicyclo [5.4.0] undec-7-ene) was
used as base (Table 2, entry 9). We also have screened the amount
of supported palladium catalyst, and 0.5 mol % loading of palladium
was found to be optimal (Table 2, entries 10ꢁ12).
Having established a standard set of reaction conditions
(
0.5 mol % of supported palladium catalyst 5, K
2 3 2
CO , MeOH/H O
(
1:1, v/v), room temperature), several representative coupling re-
14
actions involving a variety of arylboronic acids and aryl halides
were investigated, the results were illustrated in Table 3. A wide
array of electronically diverse aryl iodides, bromides, and chlorides
with phenylboronic acid were examined. As can be seen from Table
3
, aryl iodides and bromides bearing electron-withdrawing and
electron-donating groups coupled efficiently with phenylboronic
acid, and generated the corresponding products in good to excel-
lent yields within 4 h (Table 3, entries 1e5 and 9e17). 2-Bromo-
pyridine and 3-bromopyridine were able to undergo the coupling
Table 3
a
SuzukieMiyaura coupling reaction of aryl halide with arylboronic acid
5
( 0.5 % mol )
B(OH)
2
+
X
R1
R2
MeOH/H
2
O, r. t.
R1
R2
Entry
1
Arylboronic acid
Aryl halide
Product
Yieldb [%]
92
3a
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
H CO
I
3
2
3
4
5
6
7
8
9
3b
3c
3d
3e
3f
91
89
93
83
94
80
77
94
86
H C
I
I
3
O N
2
I
I
OH
H CO
B(OH)2
OCH3
B(OH)2
3
I
I
Cl
3g
3h
3a
3i
Cl
B(OH)2
I
I
B(OH)2
B(OH)2
H CO
Br
3
Br
10
OCH3

W. Chen et al. / Tetrahedron 67 (2011) 318e325
321
Table 3 (continued )
Entry
Arylboronic acid
Aryl halide
Product
3j
Yieldb [%]
Br
1
1
1
1
1
1
1
1
1
2
2
2
2
1
88
89
84
90
87
89
86
93
89
80
42
37
Trace
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
H CO
3
2
3b
H C
Br
Br
Br
3
3
3c
O N
2
4
3k
NC
O
5
Br
3l
H C
3
6
3m
3n
OHC
Br
7
C
H
O
C
Br
2
5
2
8
Br
Br
3o
N
9
3p
N
0
3q
t-C
H
Br
4
9
1c
2c
3c
3c
O N
Cl
Cl
Cl
2
3m
3a
OHC
H CO
3
2
2
4
5
3r
3s
87
82
H CO
B(OH)2
H CO
Br
Br
3
3
B(OH)2
OCH3
H CO
3
B(OH)2
26
3t
84
H CO
Br
3
(
continued on next page)
H CO
3

322
W. Chen et al. / Tetrahedron 67 (2011) 318e325
Table 3 (continued )
Entry
Arylboronic acid
Aryl halide
Product
Yieldb [%]
85
2
7
8
3u
H C
B(OH)2
H CO
Br
Br
3
3
2
3v
91
F
B(OH)2
H CO
3
B(OH)
2
2
3
9
0
3w
3x
82
79
H CO
Br
3
Cl
B(OH)2
Br
OCH3
OCH3
H CO
B(OH)2
OCH3
3
3
3
3
1
2
3
3f
80
0
Br
3y
3a
H CO
Br
Br
3
B(OH)2
S
4
Ph BNa
86
H CO
3
34
3r
89
H CO
BF3K
H CO
Br
3
3
a
Reaction conditions: aryl halide (0.5 mmol), organoboron compound (0.6 mmol), supported palladium catalyst 5 (25 mg, containing Pd 0.0025 mmol), K
O (1:1, v/v, 2.0 mL) at room temperature for 4 h.
Isolated yields.
2
CO
3
(1.0 mmol) in
MeOH/H
2
b
3
2
, entries 6e7, 10, 25, and 31). Fortunately, the coupling reaction of
-bromoanisole with 2-methoxyphenylboronic acid also provided
reaction conditions. It was noteworthy that the present protocol is
applicable even to sodium tetraphenylborate and potassium aryl-
trifluoroborate, they could also couple efficiently with 4-
the product in 79% yield (Table 3, entry 30). When 2,4-diiodo-
benzene reacted with phenylboronic acid (2 equiv), the corre-
sponding product terphenyl was isolated in 77% yield (Table 3,
entry 8). However, on further increasing the steric hindrance of the
substrate, the catalytic activity decreased. 2,2 ,6-Biphenyl de-
rivatives and 2,2 ,6,6 -biphenyl derivatives could not be obtained
from the corresponding substrates under the present coupling
0
0
0
Table 4
a
Successive trials by using recoverable catalyst 5
Reused 5
H CO
Br +
B(OH)
2
OCH3
3
Entry
Yieldb [%]
Entry
Yieldb [%]
1
2
3
4
5
94
92
93
90
90
6
7
8
9
10
92
90
89
88
86
a
Reaction conditions: 4-bromoanisole (94 mg, 0.5 mmol), phenylboronic acid
0
10
20
30
40
50
60
70
80
90
(
72 mg, 0.6 mmol), reused supported palladium catalyst 5 (42.4 mg, containing Pd
2
Theta
2 3 2
0.005 mmol), K CO (138 mg, 1.0 mmol) in MeOH/H O (1:1, v/v, 2.0 mL) at room
temperature for 4 h.
Fig. 1. Black line, XRD pattern of phosphine-functionalized silica gel 4; red line, XRD
pattern of silica supported Pd catalyst 5.
b
Isolated yields.

W. Chen et al. / Tetrahedron 67 (2011) 318e325
323
bromoanisole and generate the cross-coupling products in good to
excellent yields (Table 3, entries 33 and 34). When phenyl tosylate
was used as one of the substrate, there was no desired product was
observed.
for 30 min, and then 1.0 g of the above phosphine-functionalized
silica gel 4 was added. The mixture was stirred at room temperature
for 5 h, then the organics were filtered, the solid was washed
ꢀ
thoroughly with THF, and dried under vacuum at 60 C for 3 h. A
The recyclability of supported palladium catalyst 5 was also
surveyed. After carrying out the reaction, the reaction solution was
vacuum-filtered using a sintered-glass funnel and washed with
silica supported Pd catalyst 5 powder (1.11 g) was obtained with
a loading of 0.118 mmol of palladium per gram determined via in-
ductively coupled plasma atomic emission spectrometry (ICP-AES).
ꢁ
1
ꢁ1
ꢁ1
Et
2
O (5.0 mL), water (5.0 mL), C
2
H
5
OH (5.0 mL), and Et
2
O (5.0 mL).
IR (KBr):
n
SieO 1083 cm
,
n
C]O 1673 cm
,
n
CeH 2938 cm , n
ꢁ1
After being dried, the supported catalyst could be reused directly
without further purification, and it could be recovered, recycled
and used for 10 consecutive trials without loss of its catalytic ac-
tivity (Table 4). Moreover, palladium leaching in catalyst 5 was also
determined and ICP analysis of the clear filtrates indicated that Pd
content is <0.30 ppm.
NeH 3329 cm . XRD measurements of supported palladium cat-
alyst (5) exhibit diffraction peaks corresponding to the typical
structure of palladium particles formed and seem consistent with
that of metallic palladium (Fig. 1).
4
.4. General procedure for catalytic SuzukieMiyaura
3
. Conclusions
reactions
In summary, we have successfully developed a silica sup-
Under air atmosphere, a round-bottomed flask was charged
with the silica supported Pd catalyst 5 (21.2 mg, contain palladium
.0025 mmol), K CO (138 mg, 1.0 mmol), aryl halide (0.5 mmol),
organoboron compound (0.6 mmol), and MeOH/H O (1:1, v/v,
.0 mL). The reaction mixture was stirred at room temperature for
h, then the reaction solution was vacuum-filtered using a sin-
O (5.0 mL), the combined
, filtered, concentrated, and
ported Pdephosphine complex 5, which was used as an efficient
heterogeneous catalyst for SuzukieMiyaura cross-coupling re-
action in aqueous medium at ambient temperature. The catalyst
shows not only high catalytic activity, but also offers many
practical advantages, such as oxygen insensitivity, thermal sta-
bility, and recyclability. The catalyst could be reused for 10 con-
secutive cycles without a significant loss of its catalytic activity.
These advantages make the process highly valuable from the
synthetic and environmental points of view. Further in-
vestigation on the application of this kind of catalyst is in prog-
ress in our laboratory.
0
2
3
2
2
4
tered-glass funnel and washed with Et
organic layers were dried over Na SO
2
2
4
the residue was purified by flash chromatography on silica gel to
obtain the desired cross-coupling product.
4
4
. Experimental
4.5. Analytical data for the SuzukieMiyaura coupling
products
.1. General methods
17
1
4
.5.1. 4-Methoxybiphenyl (3a) . A white solid. H NMR (400 MHz,
Unless otherwise stated, all the reactions were carried out under
an air atmosphere, and commercially obtained materials were used
CDCl ): 7.56e7.52 (4H, m), 7.43e7.39 (2H, m), 7.32e7.28 (1H, m),
7.00e6.96 (2H, m), 3.85 (3H, s); C NMR (100 MHz, CDCl ): d 159.1,
3
3
d
13
without further purification. Products were purified by flash
140.8, 133.7, 128.7, 128.1, 126.7, 114.2, 55.3.
1
13
chromatography on 230e400 mesh silica gel, SiO
NMR spectra were measured on a Bruker Avance NMR spectrom-
eter (400 MHz or 100 MHz, respectively) with CDCl as solvent and
2
. All H NMR,
C
4.5.2. 4-Methylbiphenyl (3b)18. A white solid. 1H NMR (400 MHz,
CDCl ):
7.57 (2H, d, J¼7.3 Hz), 7.49 (2H, d, J¼8.0 Hz), 7.42 (2H, t,
3
3
d
1
3
recorded in parts per million relative to tetramethylsilane as in-
ternal standard. The CHN analysis was performed on a Vario El III
elementar. The Pd content was determined by a Jarrell-Ash 1100 ICP
analysis. The preparation of aminopropyl functionalized silica gel 1,
and carboxylic acid-functionalized silica gel 2 has been previously
J¼7.8 Hz), 7.36e7.30 (1H, m), 7.25e7.21 (2H, m), 2.39 (3H, s);
C
3
NMR (100 MHz, CDCl ): d 141.1, 138.3, 137.0, 129.5, 128.7, 127.0,
126.9, 21.1.
4.5.3. 4-Nitrobiphenyl (3c)18. A pale yellow solid. 1H NMR
(400 MHz, CDCl ): 8.26e8.24 (2H, m), 7.70e7.67 (2H, m),
7.59e7.57 (2H, m), 7.47e7.38 (3H, m); C NMR (100 MHz, CDCl
15
described, and phosphine 3 was prepared according to the
3
d
literature.16
13
):
3
d
147.6, 147.0, 138.7, 129.1, 128.9, 127.8, 127.4, 124.1.
4
.2. Preparation of phosphine-functionalized silica gel 4
.5.4. 1,1 -Biphenyl (3d)18. A white solid. 1H NMR (400 MHz,
0
4
To a suspension of the carboxylic acid-functionalized silica gel 2
2.0 g, the loading was 0.72 mmol/g) in dichloromethane (20 mL)
CDCl
3
):
d
7.65e7.62 (4H, m), 7.48 (4H, t, J¼7.6 Hz), 7.38 (2H, t,
13
(
J¼7.6 Hz); C NMR (100 MHz, CDCl
3
):
d
141.5, 128.9, 127.5, 127.4.
were added N,N-diisopropylcarbodiimide (4.5 mmol), 1-hydrox-
ybenzotriazole (4.5 mmol), triethylamine (4.5 mmol), and phos-
phine 3 (2.0 mmol). The mixture was shaken for 18 h at room
temperature and filtered. The residue was washed with dichloro-
methane, THF, methanol and dried to constant weight in vacuum.
Then 2.32 g of 4 was obtained. The loading of 4 was quantified via
CHN microanalysis and was found to be 0.52 mmol/g based on the
nitrogen content determination.
4.5.5. 2-Hydroxybiphenyl (3e)19. A white solid. H NMR (400MHz,
1
3
CDCl ): d 7.47e7.43 (4H, m), 7.38e7.33 (1H, m), 7.25e7.21 (2H, m),
6.99e6.94 (2H, m), 5.28 (1H, s); C NMR (100 MHz, CDCl ): d 152.3,
3
137.0, 130.2, 129.1, 129.0, 128.1, 127.8, 120.8, 115.8.
13
4.5.6. 2,4-Dimethoxybiphenyl (3f)20. A colorless oil. 1H NMR
(400 MHz, CDCl ):
7.48 (2H, d, J¼7.6 Hz), 7.35 (2H, t, J¼7.6 Hz),
.27e7.20 (2H, m), 6.53e6.51 (2H, m), 3.78 (3H, s), 3.73 (3H, s);
NMR (100 MHz, CDCl ): 160.2, 157.3, 138.3, 131.1, 129.3, 127.9,
26.4, 123.5, 104.5, 98.9, 55.3, 55.2.
3
d
13
7
C
4
.3. Preparation of supported palladium catalyst (5)
3
d
1
To
a
round-bottomed flask, palladium acetate (33.6 mg,
OH (v/v, 4/1, 10 mL) were added. The so-
4.5.7. 2,4-Dichlorobiphenyl (3g) . A colorless oil. 1H NMR
21
0
.15 mmol) and THF/CH
3
lution was stirred at room temperature under an inert atmosphere
(400 MHz, CDCl ): 7.47e7.45 (1H, m), 7.40e7.35 (5H, m),
3
d

324
W. Chen et al. / Tetrahedron 67 (2011) 318e325
7
1
.24e7.22 (2H, m); 13C NMR (100 MHz, CDCl
33.2, 132.0, 129.6, 129.3, 128.1, 127.8, 127.1.
3
):
d
139.0, 138.2, 133.6,
7.03e6.93 (4H, m), 3.84 (3H, s), 3.81 (3H, s); 13C NMR (100 MHz,
CDCl ): 158.6, 156.4, 130.8, 130.6, 130.2, 128.1, 120.8, 113.4, 111.1,
5.5, 55.2.
3
d
5
.5.8. Terphenyl (3h)22. A white solid. H NMR (400 MHz, CDCl
1
4
3
):
d
7.67(4H, s), 7.65e7.63(4H, m), 7.47e7.44(4H, m), 7.38e7.34(2H, m);
0
0
19
1
4
(
7
6
(
1
.5.20. 3,4 -Dimethoxy-1,1 -biphenyl (3t) . A white solid. H NMR
13
C NMR (100 MHz, CDCl
3
):
d
140.7, 140.1, 128.8, 127.5, 127.3, 127.0.
400 MHz, CDCl
3
):
d
7.52 (2H, d, J¼6.8 Hz), 7.33 (1H, t, J¼8.0 Hz),
.14 (1H, d, J¼7.6 Hz), 7.09 (1H, t, J¼2.0 Hz), 6.97 (2H, d, J¼5.2 Hz),
.5.9. 2-Methoxybiphenyl (3i)23. A colorless oil. H NMR (400 MHz,
1
4
CDCl
7
1
13
.85 (1H, dd, J¼1.6, 5.6 Hz), 3.86 (3H, s), 3.84 (3H, s); C NMR
3
): d 7.54e7.52 (2H, m), 7.41e7.39 (2H, m), 7.34e7.30 (3H, m),
3
100 MHz, CDCl ): d 159.9, 159.2, 142.3, 133.6, 129.7, 128.2, 119.2,
13
.05e6.97 (2H, m), 3.80 (3H, s); C NMR (100 MHz, CDCl ): d 156.4,
3
14.1, 112.5, 112.0, 55.3, 55.2.
38.5, 130.9, 130.6, 129.5, 128.6, 127.9, 126.9, 120.8, 111.1, 55.5.
0
25
1
.5.10. 3-Methoxybiphenyl (3j)23. A colorless oil. 1H NMR
4.5.21. 4-Methoxy-4 -methylbiphenyl (3u)
400 MHz, CDCl ):
7.51 (2H, d, J¼8.8 Hz), 7. 45 (2H, d, J¼8.0 Hz),
.22 (2H, d, J¼8.0 Hz), 6.95 (2H, d, J¼8.8 Hz), 3.81 (3H, s), 2.36 (3H,
. A white solid. H NMR
4
(
(
7
3
d
400 MHz, CDCl
3
):
d
7.59 (2H, d, J¼8.0 Hz), 7.43 (2H, t, J¼7.6 Hz),
7.37e7.33 (2H, m), 7.18 (1H, d, J¼7.7 Hz), 7.13 (1H, s), 6.91e6.88 (1H,
13
13
s); C NMR (100 MHz, CDCl
27.8, 126.4, 114.1, 55.3, 21.0.
3
): d 158.9, 137.8, 136.4, 133.7, 129.5,
m), 3.86 (3H, s); C NMR (100 MHz, CDCl ): 159.9, 142.7, 141.1,
3
d
1
1
29.7, 128.7, 127.4, 127.2, 119.7, 112.9, 112.6, 55.3.
.5.11. 1,1 -Biphenyl-4-carbonitrile (3k)23. A white solid. 1H NMR
400 MHz, CDCl ):
7.65 (4H, dd, J¼8.4, 8.8 Hz), 7.55e7.53 (2H, m),
0
18
1
0
4.5.22. 4-Fluoro-4 -methoxybiphenyl (3v) . A white solid. H NMR
400 MHz, CDCl ): 7.51e7.45 (4H, m), 7.12e7.06 (2H, m),
6.98e6.95 (2H, m), 3.84 (3H, s); C NMR (100 MHz, CDCl
d, J¼244 Hz), 160.8, 159.1, 136.9 (d, J¼3.2 Hz), 132.8, 128.1 (d,
J¼22.4 Hz), 115.5 (d, J¼21.2 Hz), 114.2, 55.3.
4
(
3
d
(
3
d
13
1
3
3
): d 162.1
3
7.46e7.36 (3H, m); C NMR (100 MHz, CDCl ): d 145.6, 139.1, 132.5,
(
129.0, 128.6, 127.6, 127.1, 118.9, 110.8.
17
4
.5.12. 1-(4-Biphenylyl)ethanone (3l) . A white solid. 1H NMR
): 8.05e8.02 (2H, m), 7.70e7.67 (2H, m),
.64e7.62 (2H, m), 7.49e7.45 (2H, m), 7.42e7.38 (1H, m), 2.64 (3H,
0
26
1
4
.5.23. 2-Chloro-4 -methoxybiphenyl (3w) . A white solid. H NMR
400 MHz, CDCl ):
7.72 (1H, dd, J¼1.6, 7.6 Hz), 7.44 (2H, d,
J¼8.8 Hz), 7.39e7.28 (3H, m), 7.02 (2H, d, J¼8.8 Hz), 3.89 (3H, s);
NMR (100 MHz, CDCl ): 159.3, 140.1, 132.7, 131.9, 131.3, 130.8,
(
400 MHz, CDCl
7
s); C NMR (100 MHz, CDCl
3
d
(
3
d
13
13
C
3
): d 197.8, 145.7, 139.8, 135.8, 128.9,
3
d
128.2, 127.2, 26.7.
1
30.0, 128.1, 126.7, 113.6, 55.3.
.5.13. 1,1 -Biphenyl-4-carboxaldehyde (3m)18. A white solid. 1
NMR (400 MHz, CDCl ):
10.05 (1H, s), 7.95 (2H, d, J¼8.4 Hz), 7.75
2H, d, J¼8.4 Hz), 7.65e7.63 (2H, m); 7.50e7.46 (2H, m), 7.44e7.42
0
H
4
.5.24. 2,2 -Bis(methoxy)-1,1 -biphenyl (3x)27. A colorless oil. 1
):
7.38 (2H, dt, J¼1.2, 7.8 Hz), 7.29 (2H, dd,
J¼1.6, 7.6 Hz), 7.06 (2H, dt, J¼1.2, 7.6 Hz), 7.03 (2H, d, J¼8.0 Hz), 3.81
0
0
H
4
3
d
NMR (400 MHz, CDCl
3
d
(
(
1
1H, m); 1 C NMR (100 MHz, CDCl
30.2, 129.0, 128.4, 127.6, 127.3.
3
3
): d 191.9, 147.1, 139.7, 135.1,
13
(
1
s, 6H); C NMR (100 MHz, CDCl
11.3, 55.6.
3
): d 157.2, 131.7, 128.7, 127.7, 120.5,
.5.14. 4-(Ethoxycarbonyl)-1,1 -biphenyl (3n)18. A colorless oil. 1
NMR (400 MHz, CDCl ):
8.14 (2H, d, J¼8.4 Hz), 7.68e7.63 (4H, m),
.49 (2H, t, J¼7.6 Hz), 7.40 (1H, t, J¼7.3 Hz), 4.45e4.38 (2H, m), 1.44
0
H
4
Acknowledgements
3
d
7
(
1
13
3H, t, J¼7.2 Hz); C NMR (100 MHz, CDCl
3
):
d
166.7, 145.6, 140.3,
Financial supports from the National Natural Science Founda-
tion of China (No. 20972057, 21002039), the Natural Science
Foundation of Anhui (No. 090416223), the Key Project of Science
and Technology of the Department of Education, Anhui Province
(No. ZD2010-9) are gratefully acknowledged.
30.1,129.5, 129.1, 128.2, 127.5, 127.2, 61.1, 14.5.
4
CDCl
.5.15. 2-Phenylpyridine(3o)23. A colorless oil. H NMR (400 MHz,
):
8.69 (1H, d, J¼4.8 Hz), 8.00e7.98 (2H, m), 7.74e7.72 (2H,
m), 7.50e7.46 (2H, m), 7.43e7.41 (1H, m), 7.24e7.20 (1H, m);
1
3
d
13
C
NMR (100 MHz, CDCl
3
):
d
157.4, 149.6, 139.3, 136.7, 128.9, 128.7,
References and notes
126.8, 122.0, 120.5.
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1
4
CDCl
7
.5.16. 3-Phenylpyridine (3p)23. A colorless oil. H NMR (400 MHz,
1
3
):
d
8.86 (1H, s), 8.59 (1H, d, J¼4.4 Hz), 7.89e7.86 (1H, m),
13
.60e7.57 (2H, m), 7.50e7.47 (2H, m), 7.43e7.35 (2H, m); C NMR
(
100 MHz, CDCl
3
):
d
148.4, 148.3, 137.8, 134.3, 129.0, 128.1, 127.1, 123.5.
17
1
4
.5.17. 1-tert-Butyl-4-phenyl benzene (3q) . A colorless oil. H NMR
d 7.59e7.56 (2H, m), 7.54e7.51 (2H, m),
.47e7.44 (2H, m), 7.43e7.39 (2H, m), 7.32e7.28 (1H, m), 1.35 (9H,
2
(
400 MHz, CDCl
3
):
7
13
s); C NMR (100 MHz, CDCl
3
): d 150.2, 141.0, 138.3, 128.7, 127.0,
3
126.8, 125.7, 34.5, 31.4.
2
000, 56, 9391e9396; (d) Juteau, H.; Gareau, Y.; Labelle, M.; Sturino, C. F.;
0
0
19
1
4
(
3
5
.5.18. 4,4 -Dimethoxy-1,1 -biphenyl (3r) . A white solid. H NMR
Sawyer, N.; Tremblay, N.; Lamontagne, S.; Carriere, M. C.; Denis, D.; Metters, K.
M. Bioorg. Med. Chem. 2001, 9, 1977e1984; (e) Rosowsky, A.; Chen, H.; Fu, H.;
Queener, S. F. Bioorg. Med. Chem. 2003, 11, 59e67; (f) Long, Y. Q.; Jiang, X. H.;
Dayam, R.; Sachez, T.; Shoemaker, R.; Sei, S.; Neamati, N. J. Med. Chem. 2004, 47,
2561e2573; (g) Forsch, R. A.; Queener, S. F.; Rosowsky, A. Bioorg. Med. Chem.
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400 MHz, CDCl
3
):
d
7.47 (4H, d, J¼8.8 Hz), 6.95 (4H, d, J¼8.8 Hz),
.84 (6H, s); 13C NMR (100 MHz, CDCl
5.3.
3
): d 158.6, 133.4, 127.7, 114.1,
4
5
. Tomori, H.; Fox, J. M.; Buchwald, S. L. J. Org. Chem. 2000, 65, 5334e5341.
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0
4
(
.5.19. 2,4 -Dimethoxybiphenyl (3s)24. A white solid. 1H NMR
400 MHz, CDCl
3
):
d
7.47 (2H, d, J¼8.4 Hz), 7.31e7.27 (2H, m),

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1. For recent examples of superparamagnetic nanoparticles (MNPs) supported
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