Green synthesis of fluorinated biaryl derivatives via thermoregulated ligand/palladium-catalyzed Suzuki reaction

Article abstract of DOI:10.1016/j.jorganchem.2011.04.007

Fluorinated compounds have attracted considerable attention in pharmaceuticals, agrochemicals and material science due to their unique physical properties. This paper reports an efficient and environmentally benign protocol for the Suzuki reaction of aryl halides with fluorinated arylboronic acids over a thermoregulated ligand/palladium catalyst using water as sole medium, affording a variety of fluorinated biaryls, including fluorinated liquid crystals, in excellent yields. The catalyst could be recycled four times with high activity. The active catalyst was proved to be a palladium/ligand complex via a mercury-poisoning test.

Full text of DOI:10.1016/j.jorganchem.2011.04.007

Journal of Organometallic Chemistry 696 (2011) 2641e2647
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Green synthesis of fluorinated biaryl derivatives via thermoregulated
ligand/palladium-catalyzed Suzuki reaction
*
Ning Liu, Chun Liu , Zilin Jin
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Linggong Road 2, Dalian 116024, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Fluorinated compounds have attracted considerable attention in pharmaceuticals, agrochemicals and
material science due to their unique physical properties. This paper reports an efficient and environ-
mentally benign protocol for the Suzuki reaction of aryl halides with fluorinated arylboronic acids over
a thermoregulated ligand/palladium catalyst using water as sole medium, affording a variety of fluori-
nated biaryls, including fluorinated liquid crystals, in excellent yields. The catalyst could be recycled four
times with high activity. The active catalyst was proved to be a palladium/ligand complex via a mercury-
poisoning test.
Received 26 February 2011
Received in revised form
4 April 2011
Accepted 8 April 2011
Keywords:
Thermoregulated ligand
Suzuki reaction
Palladium
Ó 2011 Elsevier B.V. All rights reserved.
Fluorinated biaryl
Water
1. Introduction
is one of the exceedingly important methodologies for the
construction of carbonecarbon bond in the synthesis of biaryls
Fluorinated compounds find diverse applications in pharma-
ceuticals, agrochemicals and material science [1e3]. In recent years,
fluorinated compounds have attracted attention from many
researchers due to the anomalous physical properties and physio-
logical activity. For example, the fluorinated graphene films
exhibited significant changes on the optical, structural and transport
properties [4]. Li et al. reported an efficient protocol for the synthesis
of 2-fluoromethylated quinolines, which are of significant pharma-
cological interest for their use as potent antimalarial agents [5].
A series of fluorinated benzyloxyphenyl piperidine-4-carboxamides
were synthesized and proved to be potent antithrombotic drugs [6].
Generally, synthetic methods for fluorinated biaryls are classified
into two types: carbon-fluorine bond-forming reactions and car-
bonecarbon bond-forming reactions [1,2]. In the synthesis of fluo-
rinated biaryls via the carbonecarbon bond-forming reactions, the
cross-couplings involving organochlorosilanes [7,8], potassium
aryltrifluoroborates [9e11], Grignard reagents [12,13] or organo-
lithium reagents [14], have been developed, respectively. However,
these methods require the use of highly specialized reagents.
The palladium-catalyzed cross-coupling reaction of arylboronic
acid with aryl halide, known as the Suzuki cross-coupling reaction,
[15e22], in particular for the preparation of the fluorinated biaryls.
Recently, the synthesis of fluorinated liquid crystals via the
palladium-catalyzed Suzuki reaction of fluorinated arylboronic
acids with aryl bromides containing cyclohexyl moiety in ethanol
has been reported [23,24].
Recovery and recycling of catalysts poses a serious problem for
industrial applications of homogeneous catalysis. So far, intensive
work has been focused on developing efficient catalytic systems to
solve this problem. Thermomorphic systems offer an alternative
approach to facilitate the catalyst separation and preserve the
benefits of homogeneous catalysis [25e31]. We have a long-
standing interest in developing efficient aqueous/organic biphasic
catalytic system for solving such a problem and a concept of the
thermoregulated phase-transfer catalysis (TRPTC) has been repor-
ted [32e35]. In the traditional TRPTC system, a suitable organic
solvent is necessary as a co-solvent for the efficient aqueous/
organic biphasic catalysis.
Water is a desirable medium for chemical reactions for reasons
of low cost, safety, and environmental concerns [36e43]. Recently,
we reported an environmentally benign thermoregulated system
using water as sole solvent for the Suzuki reaction [44]. In the
present paper, this thermoregulated system is applied for the
construction of fluorinated biaryls, providing a green and efficient
protocol for the Suzuki cross-coupling of aryl bromides with fluo-
rinated aryl boronic acids. To the best of our knowledge, the
* Corresponding author. Tel.: þ86 411 84986182.
E-mail address: chunliu70@yahoo.com (C. Liu).
0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.04.007

2642
N. Liu et al. / Journal of Organometallic Chemistry 696 (2011) 2641e2647
shown in Fig. 2. It is clear that the reaction temperature is crucial to
the catalytic efficiency. The cross-coupling reaction was difficult to
proceed at 60 ꢀC. When increasing the reaction temperature from
60 ꢀC to 66 ꢀC, the isolated yield of the desired product was slowly
increased from 6% to 13%. In contrast, the coupling reaction was
sharply accelerated at 67 ꢀC, affording 38% yield. Furthermore, 45%
of the product yield was obtained when the reaction temperature
increasing to 70 ꢀC. These results indicate that the palladium
catalyst stays in the aqueous phase at a lower temperature (<67 ꢀC)
and transfers into the substrate phase at a higher temperature
(>67 ꢀC).
The palladium source and base employed in the Suzuki reaction
are also important to the catalytic efficiency. As shown in Table 1,
the palladium sources have dramatic effects on the reaction
activity. It is clear that palladium(II) salts such as Pd(OAc)2 or PdCl2
exhibited high catalytic activity (Table 1, entries 3 and 4), respec-
tively. Using 0.1 mol% PdCl2 as catalyst, 79% yield of the product
could be obtained in 30 min (Table 1, entry 4). However, the cata-
lytic activity of zero-valent palladium sources such as Pd2(dba)3 or
Pd/C, was relatively low (Table 1, entries 1 and 2). The results
showed that the use of PdCl2 gave the best results.
Subsequently, the impact of various bases on the reaction was
evaluated. As described in Table 1, the reaction rate is greatly
affected by the base used. For instance, the coupling reactions using
K3PO4,7H2O or CH3ONa (Table 1, entries 5 and 6) as base were less
effective than those using K2CO3, NaOH or Na2CO3 (Table 1, entries
7, 8 and 9). It is noteworthy that the weak base Na2CO3 achieved the
best yield among the inorganic bases, which is consistent with
what Leadbeater reported [45]. Furthermore, the effect of an
organic base Et3N in the Suzuki reaction is evaluated. Interestingly,
the yield was greatly improved when Et3N was used (Table 1, entry
4). In addition, decreasing the palladium loading to 0.05 mol% for
the cross-coupling of 4-bromoanisole with 4-fluorophenylboronic
acid resulted in only 39% product yield (Table 1, entry 10).
To establish the best molar ratio of ligand-to-palladium, the
Suzuki reaction of 4-bromoanisole and 4-fluorophenylboronic acid
was carried out under various L/Pd molar ratio. The best result was
obtained with L/Pd molar ratio of 2:1 (Table 2, entry 3). The yield
was noticeably low when the L/Pd molar ratio increased to 8:1
(Table 2, entry 5). The reason for this might be that excess ligands
led to an over-coordinated palladium complex, which could
diminish the catalytic activity [46,47]. However, the blank experi-
ment without ligand did not show competitive result under the
same reaction conditions, only an 8% isolated yield was obtained
(Table 2, entry 1).
Fig. 1. Thermoregulated ligand/palladium-catalyzed Suzuki reaction in water.
synthesis of fluorinated biaryls in a thermoregulated system using
water as sole medium has not been described in the literature. The
key to the efficient protocol is the use of a polyethylene glycol
modified phosphine ligand, which possesses a phase-transfer
property due to the cloud point (Cp) like a non-ionic surfactant.
As shown in Fig. 1, the thermoregulated catalyst is able to transfer
into the substrate phase (organic phase) to catalyze reaction at the
temperature higher than its Cp, thus allowing the reaction to take
place in the substrate phase, and the recovery of the catalyst in the
water phase upon cooling to room temperature (<Cp).
2. Results and discussion
2.1. Optimization of reaction conditions
As known, an efficient palladium-catalyzed cross-coupling
reaction is regulated by a number of factors, such as reaction
temperature, palladium source, base and molar ratio of ligand-to-
metal. Initially, the cross-coupling of 0.5 mmol 4-bromoanisole
with 0.75 mmol 4-fluorophenylboronic acid using palladium/L as
catalyst in 1 mL H2O is chosen as a model reaction for screening the
reaction temperature. The reaction conditions and the results are
2.2. Mercury poisoning test
To determine whether the active catalytic species was a palla-
dium/L complex or palladium particles, a mercury-poisoning test
was performed accordingly. The coupling of 4-bromoanisole and
4-fluorophenylboronic acid under the conditions listed in Table 1 in
the presence or absence of mercury was investigated. The reaction
was allowed to proceed for 30 min (79% yield) before the mercury
was added in a molar ratio of 300 equivalents to the palladium.
Then the reaction was continued to proceed for another 30 min,
a 98% product yield was obtained. The result verifies that the
palladium/L complex is the true catalyst in the reaction.
50
40
30
20
10
0
2.3. Scope and limitations of substrates
60
62
64
66
68
70
Temperatureo(C)
The scope of the reaction system was explored with a range of
aryl bromides and fluorinated arylboronic acids under the opti-
mized conditions. As shown in Table 3, all reactions of fluorinated
arylboronic acids provided the biaryl derivatives in good to
Fig. 2. The effect of temperature on the Suzuki reaction. Reaction conditions: 0.5 mmol
of 4-bromoanisole, 0.75 mmol of 4-fluorophenylboronic acid, 1 mmol of Et3N, 0.1 mol %
PdCl2, L/Pd ¼ 2: 1 (molar ratio), 1 h, 1 mL H2O.

N. Liu et al. / Journal of Organometallic Chemistry 696 (2011) 2641e2647
2643
Table 1
the presence of 0.1 mol% palladium, probably because the trans-
metalation of the highly electron-deficient 3,4,5-trifluorophenyl
group to the Pd centre proceeds difficultly. The moderate to good
yields could be obtained when palladium loading up to 0.5 mol%
and prolonging the reaction time to 4 h (Table 3, entries 13 and 14).
As aryl-substituted pyridines are the most common N-heteroaryl
units in pharmaceutically active compounds [50], we further
investigated the Suzuki reaction of N-heteroaryl bromides with
4-fluorophenylboronic acid. In the presence of 0.5 mol % PdCl2, the
Suzuki reaction of 3-bromopyridine with 4-fluorophenylboronic
acid afforded excellent yields (Table 3, entries 15 and 16). For
example, a 95% isolated yield was reached between 2-methoxy-5-
bromopyridine and 4-fluoro-phenylboronic acid in 2 h (Table 3,
entry 16). In addition, the reaction of 3-bromoquinoline with
4-fluorophenylboronic acid provided 92% yield after 2 h (Table 3,
entry 17).
The optimization of reaction conditions for the Suzuki reaction.
OCH3
Br
B(OH)2
PdCl2/L (n = 22)
+
PPh2
H3C
O
L
OCH3
F
n
F
Entry
Pd source
Base
Yield [%]a
1
2
3
4
5
6
7
8
9
Pd2(dba)3
Pd/C
Pd(OAc)2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Et3N
Et3N
Et3N
Et3N
K3PO4,7H2O
CH3ONa
K2CO3
NaOH
Na2CO3
Et3N
16
27
76
79
51
38
65
63
68
39b
2.4. Application in synthesis of fluorinated liquid crystals
Fluorinated biphenyl derivatives are fundamental building blocks
for synthesis of fluorinated liquid crystals, such as thin-film transistor
liquid crystal displays (TFT-LCDs) [51]. The Suzuki reaction is one of
the most powerfulmethods for the construction offluorinated biaryls
through two alternative cross-coupling paths (Scheme 1). The
synthetic path I employing cyclohexylphenylboronic acids and aryl
bromides has been reported for the construction of liquid crystals
materialunits [52,53]. However, thismethodislimitedinapplications
due to harsh reaction conditions and low product yield. Recently, the
synthesis of TFT-LCDs in organic solvent via path II was emerged
[23,24]. However, to the best of our knowledge, there is no previous
report of the efficient synthesis of fluorinated liquid crystals using the
commercially available arylboronic acids in water.
Therefore, the scope of substrates for the Suzuki reaction over
the thermoregulated L/palladium catalyst for the synthesis of TFT-
LCDs was investigated. The reaction was carried out with 0.5 mmol
of aryl bromides, 0.75 mmol of fluorinated arylboronic acids with
0.1 mol % PdCl2. As shown in Table 4, monofluoro, difluoro, trifluoro,
or trifluoromethyl substituted arylboronic acids could be coupled in
excellent yields in this thermoregulated system. For instance, the
coupling reaction of inactive 3,4,5-trifluorophenylboronic acid also
achieved good results by prolonging the reaction time (Table 4,
entries 4 and 10).
10
PdCl2
Reaction conditions: 0.5 mmol of 4-bromoanisole, 0.75 mmol of 4-fluo-
rophenylboronic acid, 1 mmol of base, 0.1 mol % Pd catalyst, L/Pd ¼ 2: 1 (molar ratio),
80 ꢀC, 30 min, 1 mL H2O.
a
Isolated yield.
0.05 mol % PdCl2.
b
excellent yields. Various para-substituted aryl bromides bearing
either electron-donating groups or electron-withdrawing groups
such as methyl, methoxy, cyano and acetyl, afforded the corre-
sponding products in excellent yields in 1 h (Table 3, entries 1, 2, 3
and 4). To our delight, sterically hindered aryl bromides were also
highly reactive in this reaction system, giving the desired cross-
coupling products in high yields (Table 3, entries 5 and 6). The
present protocol obtains similar results with that catalyzed by the
polyethylene-supported FibreCat Pd catalysts [48]. Recently,
Scheuermann and co-workers developed a palladium nanoparticle
catalyst on graphite oxide, which showed excellent catalytic
activity in the Suzuki reaction of 4-bromo-1,2-difluorobenzene
with arylboronic acids [49]. However, the coupling reaction of 3,4-
difluorophenylboronic acid with aryl bromide is rarely reported
[23,24]. Therefore, the Suzuki reaction of 3,4-difluorophenylbor-
onic acid was also investigated in this thermoregulated system. As
shown in Table 3, electron-deficient, electron-rich or sterically
hindered aryl bromide substrates could be coupled with
3,4-difluorophenylboronic acids in excellent yields (Table 3, entries
7e10). The effect of the fluorine-substituents in different positions
of the arylboronic acid on the Suzuki coupling reaction was studied
further. As shown in Table 3, the reactivity of 2,3-difluor-
ophenylboronic acid (Table 3, entries 11 and 12) was less active
than that of 3,4-difluorophenylboronic acid (Table 3, entries 7, 8
and 9). 3,4,5-Trifluorophenylboronic acid is an inactive substrate in
2.5. Recycling of the catalyst
To test the reusability of the thermoregulated catalyst, we chose
the Suzuki reaction of 4-(4-propyl-cyclohexyl)-bromobenzene with
4-fluorophenylboronic acid as a model reaction (Table 5). The
reaction was performed under organic solvent-free conditions, in
which water was the sole medium. When the reaction was
completed, the reaction mixture was cooled down to room
temperature. The catalyst could be recovered in water phase, and
the organic phase gave 4-fluoro-40-(4-propyl-cyclohexyl)-biphenyl
as white solid product. The catalyst could be recycled at least four
consecutive cycles. To further ascertain whether the recovered
catalyst is a palladium/L complex or palladium particles, a mercury-
poisoning test was designed for the reuse of the catalyst in the
second run of the coupling of 4-(4-propyl-cyclohexyl)-bromo-
benzene with 4-fluorophenylboronic acid under the reaction
conditions in Table 5. The reaction was allowed to proceed for
10 min before the mercury was added in a molar ratio of 300
equivalents to the palladium. The coupling reaction was quantita-
tively completed after another 50 min. The result indicates that the
recovered catalyst is a palladium/L complex.
Table 2
The effect of L/Pd on the Suzuki reaction.
Entry
L/Pd
Yield [%]a
1
2
3
4
5
0:1
1:1
2:1
4:1
8:1
8
52
79
65
27
Reaction conditions: 0.5 mmol of 4-bromoanisole, 0.75 mmol of 4-fluo-
rophenylboronic acid, 1 mmol of Et3N, 0.1 mol % PdCl2, 80 ꢀC, 30 min, 1 mL H2O.
a
Isolated yield.

Table 3
The synthesis of fluorinated biphenyl derivatives.
R
R
Fn
L
PdCl2/
Br
+
B(OH)2
H2O, Et3N
Fn
Entry
1
Aryl bromides
Product
Time [h]
1
Yield [%]a
98
H3C
F
H3C
Br
Br
2
3
1
1
98
98
H3CO
NC
F
H3CO
F
NC
Br
4
5
1
2
97
93
H3COC
CN
F
H3COC
CN
Br
F
F
Br
OCH3
Br
OCH3
6
7
2
1
91
96
F
NC
Br
NC
F
F
8
9
2
2
98
93
H3CO
H3C
Br
H3CO
H3C
F
F
Br
F
F
CN
Br
CN
10
11
12
2
4
4
95
76
68
F
F
F
H3COC
H3C
Br
H3COC
H3C
F
F
Br
F
13
14
NC
F
4
4
65b
NC
Br
F
F
H3C
F
68b
H3C
Br
F
94b
95b
F
Br
15
16
2
2
N
N
H3CO
F
H3CO
Br
N
N
F
Br
17
2
92b
N
N
Reaction conditions: 0.5 mmol of aryl bromides, 0.75 mmol of arylboronic acids, 1 mmol of Et3N, 0.1 mol % PdCl2, L/Pd ¼ 2: 1 (molar ratio), 80 ꢀC, 1 mL H2O.
a
Isolated yield.
0.5 mol % PdCl2.
b

N. Liu et al. / Journal of Organometallic Chemistry 696 (2011) 2641e2647
2645
3. Conclusion
In summary, we have developed an environmentally benign
thermoregulated system using water as sole medium for the Suzuki
reaction of aryl bromides with a range of fluorinated arylboronic
acids in excellent yields, which offers an alternative approach to
facilitate the separation and recycling of the catalyst. The mercury
poisoning tests demonstrate that the Suzuki reaction is catalyzed
by a palladium/L complex. Efforts including the application of the
thermoregulated ligand/palladium system to other transformations
and the development of more efficient thermoregulated ligands
Scheme 1. Alternative synthetic paths for fluorinated liquid crystals.
Table 4
The synthesis of fluorinated liquid crystals.
Fn
L
PdCl2/
R
R
Br +
B(OH)2
H2O, Et3N
Fn
Entry
1
Aryl bromides
Product
Time [h]
1
Yield [%]a
95
C3H7
Br
Br
C3H7
F
F
F
2
3
4
1
2
4
98
93
91
C3H7
C3H7
C3H7
C3H7
F
F
Br
C3H7
C3H7
F
F
Br
Br
F
5
6
7
8
3
1
1
1
89
98
96
97
C3H7
C3H7
CF3
C5H11
C5H11
C5H11
Br
C5H11
F
F
Br
Br
C5H11
F
C5H11
F
F
9
2
90
C5H11
Br
C5H11
F
F
10
11
F
4
3
88
92
C5H11
C5H11
Br
Br
C5H11
C5H11
CF3
Reaction conditions: 0.5 mmol of aryl bromides, 0.75 mmol of arylboronic acids, 1 mmol of Et3N, 0.1 mol % PdCl2, L/Pd ¼ 2: 1 (molar ratio), 80 ꢀC, 1 mL H2O.
a
Isolated yield.

2646
N. Liu et al. / Journal of Organometallic Chemistry 696 (2011) 2641e2647
Table 5
4.5. Characterization of the coupling products
4.5.1. 5-(4-Fluorophenyl)-2-methoxylpyridine
Reusability of the catalyst in the synthesis of fluorinated liquid crystals.
L
PdCl2/
1H NMR (400 MHz, CDCl3, TMS):
d
8.33 (d, J ¼ 2.4 Hz, 1H), 7.74
C3H7
Br
C3H7
F
4-F-Ph-B(OH)2
(dd, J ¼ 8.4, 2.4 Hz, 1H), 7.49e7.45 (m, 2H), 7.15e7.11 (m, 2H), 6.81
(d, J ¼ 8.4, 1H), 3.98 (s, 3H), ppm; 13C NMR
d 163.6, 162.5, 144.8,
137.4, 134.1, 129.2, 128.3, 115.9, 110.9, 53.57, ppm; MS (EI) m/z 203
(Mþ, 100%): 203, 175, 172, 146, 133, 132, 107, 83, 63. Melting Point:
75 ꢀC.
Run
1st
2nd
3rd
4th
5th
Time [h]
1
95
1
92
1
94
1
87
2
74
Yield [%]a
Reaction conditions: 0.5 mmol of 4-(4-propylcyclohexyl)-bromobenzene,
0.75 mmol of 4-fluorophenylboronic acid, 1 mmol of Et3N, 0.1 mol % PdCl2, L/Pd ¼ 2:
1 (molar ratio), 80 ꢀC, 1 mL H2O.
4.5.2. 30,40-difluoro-[1,10-biphenyl]-4-carbonitrile
1H NMR (400 MHz, CDCl3, TMS):
d
7.74 (d, J ¼ 8.4 Hz, 2H), 7.62 (d,
J ¼ 8.4 Hz, 2H), 7.37e7.43 (m, 1H), 7.28e7.33 (m, 2H), ppm; 13C NMR
a
Isolated yield.
d
151.9, 149.5, 143.5, 136.2, 132.8, 127.6, 123.4, 118.6, 118.1, 117.9,
116.4, 116.2, 111.6, ppm; MS (EI) m/z 215 (Mþ, 100%): 215, 195, 164,
151, 123, 94, 87, 75, 51. Melting Point: 109e110 ꢀC.
capable of activating aryl chlorides are currently under investiga-
tions in our laboratory.
4.5.3. 30,40-difluoro-[1,10-biphenyl]-2-carbonitrile
1H NMR (400 MHz, CDCl3, TMS):
d
7.77e7.79 (m, 1H), 7.64e7.68
4. Experimental
(m, 1H), 7.47e7.50 (m, 2H), 7.35e7.39 (m, 1H), 7.28e7.31 (m, 2H),
ppm; 13C NMR
d 152.0, 151.5, 149.5, 149.0, 143.3, 135.0, 133.4, 129.9,
4.1. General remarks
128.2, 125.2, 118.1, 118.0, 111.3, ppm; MS (EI) m/z 215 (Mþ, 100%):
215, 195, 188, 168, 138, 121, 94, 88, 75, 39. Melting Point:
102e103 ꢀC.
All the reactions were carried out in nitrogen. All aryl halides
and arylboronic acids were purchased from Alfa Aesar, or Avocado.
Other chemicals were purchased from commercial sources and
used without further purification. 1H NMR spectra were recorded
on a Brucker Advance II 400 spectrometer. 13C NMR spectra were
recorded at 100 MHz using TMS as internal standard. Mass spec-
troscopy data of the products were collected on an MS-EI instru-
ment. All products were isolated by short chromatography on
a silica gel (200e300 mesh) column using petroleum ether
(60e90 ꢀC), unless otherwise noted. Compounds described in the
literature were characterized by 1H NMR spectra to reported data.
4.5.4. 30,40,50-trifluoro-[1,10-biphenyl]-4-carbonitrile
1H NMR (400 MHz, CDCl3):
d
7.76 (d, J ¼ 8.4 Hz, 2H), 7.61 (d,
J ¼ 8.0 Hz, 2H), 7.21 (t, J ¼ 7.2 Hz, 2H), ppm. 13C NMR
d 152.8, 150.4,
142.5, 141.3, 138.8, 135.2, 132.9, 127.6, 118.4, 112.3, 111.6, 111.4, ppm.
MS (EI) m/z 233 (Mþ, 100%): 233, 213, 206, 182, 156, 111, 75, 63.
Melting Point: 104e105 ꢀC.
4.5.5. 20,30-difluoro-4-(4-propylcyclohexyl)-1,10-biphenyl
1H NMR (400 MHz, CDCl3, TMS):
d
7.46 (d, J ¼ 6.8 Hz, 2H), 7.30 (d,
J ¼ 8.0 Hz, 2H), 7.16e7.20 (m, 1H), 7.09e7.13 (m, 2H), 2.48e2.55 (m,
1H), 1.91 (t, J ¼ 16 Hz, 4H), 1.44e1.54 (m, 2H), 1.31e1.39 (m, 3H),
1.20e1.28 (m, 2H), 1.02e1.11 (m, 2H), 0.91 (t, J ¼ 8.0 Hz, 3H), ppm;
4.2. Synthesis of Ph2P(CH2CH2O)nCH3 (n ¼ 22) (L)
The ligand Ph2P(CH2CH2O)nCH3 (n ¼ 22) (L, Cp: 93 ꢀC) was
13C NMR
d 152.5, 150.1, 148.2, 146.9, 132.3, 131.5, 129.0, 127.3, 125.4,
prepared according to the reported method [54]. 1H NMR
124.2, 115.8, 44.6, 39.9, 37.2, 34.5, 33.7, 20.2, 14.6, ppm; MS (EI) m/z
314 (Mþ, 100%): 314, 271, 229, 216, 203, 149, 121, 91, 81, 55. Melting
Point: 76e77 ꢀC.
(400 MHz, D2O):
d
2.39 (t, 2H), 3.37 (s, 3H), 3.55e3.65 (m, 95H),
28.64 (d),
7.31e7.50 (m, 10H) ppm. 13C NMR (100 MHz, D2O):
d
58.75 (s), 68.16 (d), 69.88e71.70 (m), 128.17 (s), 128.30 (d), 132.40
(d), 138.08 (d) ppm. 31P NMR (400 MHz, D2O):
d
ꢁ22.70 ppm.
4.5.6. 20,30-difluoro-4-(4-pentylcyclohexyl)-1,10-biphenyl
1H NMR (400 MHz, CDCl3, TMS):
d 7.46e7.48 (m, 2H), 7.30 (d,
J ¼ 8.4 Hz, 2H), 7.14e7.20 (m, 1H), 7.09e7.13 (m, 2H), 2.48e2.55 (m,
4.3. General procedure for the Suzuki reaction
1H), 1.93 (t, J ¼ 12 Hz, 4H), 1.44e1.54 (m, 2H), 1.20e1.35 (m, 9H),
1.02e1.11 (m, 2H), 0.90 (t, J ¼ 8.0 Hz, 3H), ppm; 13C NMR
d 152.5,
A solution of PdCl2 (0.09 mg, 0.0005 mmol) and ligand L (1.2 mg,
0.001 mmol) in deoxygenated H2O (1 mL) was stirred at room
temperature for 30 min under nitrogen. Et3N (1 mmol,101 mg), aryl
bromide (0.5 mmol), arylboronic acid (0.75 mmol) were then
successively added. The reaction mixture was heated in oil bath
under nitrogen with magnetic stirring. After cooling to room
temperature, the reaction mixture was added to brine (15 mL) and
extracted three times with diethyl ether (3 ꢂ 15 mL). The solvent
was concentrated under vacuum and the product was isolated by
short chromatography on a silica gel (200e300 mesh) column.
150.0, 148.2, 146.9, 132.3, 131.5, 129.0, 127.3, 125.4, 124.1, 115.8, 44.6,
37.6, 34.5, 33.8, 32.4, 26.9, 22.9, 20.2, 14.3, ppm; MS (EI) m/z 342
(Mþ, 100%): 342, 314, 271, 229, 216, 203, 175, 151, 123, 87, 53.
Melting Point: 52e53 ꢀC.
Acknowledgments
The authors thank the financial support from the National
Natural Science Foundation of China (20976024, 20923006,
21076034), Dalian University of Technology (DUT11LK15, JG0916,
DUTTX2009102), and the Program for New Century Excellent
Talents in University.
4.4. Catalyst recycling for the Suzuki reaction
When the reaction was completed, the reaction mixture was
cooled to room temperature and extracted with 2 mL ethyl ether.
Et3N (1 mmol,101 mg), aryl bromide (0.5 mmol) and phenylboronic
acid (0.75 mmol) were added to the aqueous phase separated from
the previous catalytic run under nitrogen and reacted at 80 ꢀC.
Appendix. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jorganchem.2011.04.007.

N. Liu et al. / Journal of Organometallic Chemistry 696 (2011) 2641e2647
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