Solvent-free, palladium-catalyzed Suzuki-Miyaura cross-couplings of aryl chlorides with arylboronic acids

Article abstract of DOI:10.1080/00397910701412828

Pd(MeCN)2Cl2/PCy3 was found to be an efficient catalytic system for the Suzuki-Miyaura cross-couplings of aryl chlorides with arylboronic acids under solvent-free conditions. Furthermore, the presence of the conventional solvents had deleterious effect on the reaction. In the presence of Pd(MeCN)2Cl2, PCy3, and TBAF (tetra-n-butylammonium fluoride), a number of aryl chlorides including heteroaryl chlorides were coupled with arylboronic acids or heteroarylboronic acids smoothly to afford the corresponding products in moderate to excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701412828

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Solvent‐Free, Palladium‐Catalyzed
Suzuki–Miyaura Cross‐Couplings of Aryl
Chlorides with Arylboronic Acids
Jin‐Heng Li a , Chen‐Liang Deng a & Ye‐Xiang Xie a
a Key Laboratory of Chemical Biology and Traditional Chinese Medicine
Research (Ministry of Education), College of Chemistry and Chemical
Engineering, Hunan Normal University, Changsha, China
Version of record first published: 11 Jul 2007.
To cite this article: Jin‐Heng Li, Chen‐Liang Deng & Ye‐Xiang Xie (2007): Solvent‐Free, Palladium‐Catalyzed
Suzuki–Miyaura Cross‐Couplings of Aryl Chlorides with Arylboronic Acids, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:14, 2433-2448
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Synthetic Communicationsw, 37: 2433–2448, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701412828
Solvent-Free, Palladium-Catalyzed
Suzuki–Miyaura Cross-Couplings of Aryl
Chlorides with Arylboronic Acids
Jin-Heng Li, Chen-Liang Deng, and Ye-Xiang Xie
Key Laboratory of Chemical Biology and Traditional Chinese Medicine
Research (Ministry of Education), College of Chemistry and Chemical
Engineering, Hunan Normal University, Changsha, China
Abstract: Pd(MeCN)2Cl2/PCy3 was found to be an efficient catalytic system for the
Suzuki–Miyaura cross-couplings of aryl chlorides with arylboronic acids under
solvent-free conditions. Furthermore, the presence of the conventional solvents had
deleterious effect on the reaction. In the presence of Pd(MeCN)2Cl2, PCy3, and
TBAF (tetra-n-butylammonium fluoride), a number of aryl chlorides including hetero-
aryl chlorides were coupled with arylboronic acids or heteroarylboronic acids smoothly
to afford the corresponding products in moderate to excellent yields.
Keywords: arylboronic acid, aryl halide, Pd(OAc)2, Suzuki–Miyaura cross-coupling
reaction, TBAB
The palladium-catalyzed Suzuki–Miyaura cross-coupling reaction has
emerged as one of the most valuable methods for the synthesis of biaryls,
which play an important role as structural elements of many natural
products and important pharmaceuticals.[1–36] Since its invention,[8] a wide
variety of efficient palladium catalytic systems have been developed.
However, many of the palladium catalytic systems are limited to the
couplings of aryl iodide and bromides. In recent years, use of readily
available aryl chlorides in these transformations has received increasing
Received October 26, 2006
Address correspondence to Jin-Heng Li, College of Chemistry and Chemical
Engineering, Hunan Normal University, Changsha 410081, China. E-mail: jhli@
hunnu.edu.cn
2433

2434
J.-H. Li, C.-L. Deng, and Y.-X. Xie
attention, and a number of effective catalytic systems have been provided for
this purpose.[2–7,9–25] Among these processes, sterically hindered and
electron-rich ligands played crucial roles in the couplings of these challenging
substrates. One of the notable examples is the use of bulky trialkypho-
sphines.[19–25] For example, treatment of p-chlorotoluene (1a) with phenyl-
boronic acid (2a), Pd2(dba)3, trialkyphosphine, Cs2CO3, and dioxane at
808C for 5 h afforded the corresponding product 3 in 75% yield (PCy3) or
85% yield [P(t-Bu)3] (Eq. (1) in Scheme 1).[19–24] Very recently, Kudo and
coworkers applied Pd2(dba)3/PCy3 in the synthesis of nitrogen heterocycles
from the reactions of heteroarylboronic acids with either aryl halides or
heteroaryl halides (Eq. (2).[25] However, harmful solvents (THF or dioxane)
were still required, as in the other cases.[20–26] In view of economic cost and
the environment, the development of the palladium-catalyzed Suzuki–
Miyaura cross-coupling reactions of aryl chlorides performed under solvent-
free conditions is still significant. However, few protocols on the solvent-
free, palladium-catalyzed Suzuki–Miyaura cross-coupling reaction have
been reported.[33–36] In addition, these protocols are limited to the couplings
of aryl iodides and bromides and often use microwave irradiation. Here, we
report that the combination of PdCl2(MeCN)2 with PCy3 and tetra-n-butylam-
monium fluoride (TBAF) is an efficient system for the cross-couplings of aryl
chlorides, including heteroaryl chlorides with arylboronic acids or heteroaryl-
boronic acids, under solvent-free conditions Eq. (3). Moreover, we found that
conventional solvents have deleterious effects on the reaction.
The coupling of p-chlorotoluene (1a) with phenylboronic acid (2a) was
chosen as a model reaction to screen suitable reaction conditions, and the
results are summarized in Table 1. Very recently, we reported that the combi-
nation of PdCl2(MeCN)2/P(o-tol)3/TBAF was an efficient system for the
Hiyama cross-coupling reactions of aryl halides with aryltrimethoxysilanes
Scheme 1.

Palladium-Catalyzed Suzuki–Miyaura Reaction
2435
under solvent-free conditions.[37] Thus, we expected to apply the system in the
solvent-free Suzuki–Miyaura cross-coupling reaction. However, the system
was less effective for the reaction (Table 1, entry 1). In the presence of
PdCl2(MeCN)2 (3 mol%), P(o-tol)3 (6 mol%), and TBAF (3 equiv),
treatment of substrate 1a with 2a at 85–908C for 5 h afforded a low yield
of the corresponding product 3. To our delight, employing PCy3 as the
Table 1. Palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of p-chloro-
toluene (1a) with phenylboronic acid (2a)a
Entry
Pd
Ligand
Base
Solvent
Yield (%)b
1
2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
Pd2(dba)3
P(o-tol)3
PCy3
PPh3
P(n-Bu)3
—
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
Cs2CO3
TBAOH
KF
—
—
13
91
16
35
25
60
82
84
65
78
74
51
40
59
26
13
80
16
30
28
8
3
—
—
4
5
—
—
6c
7
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
—
—
8
Pd(OAc)2
PdCl2
Pd2(dba)3
9
—
10
11
12
13
14
15
16
17
18
19
20
21d
22e
23f
Dioxane
Dioxane
THF
DMF
Acetone
MeCN
H2O
PEG-400
—
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
—
—
TBAF
TBAF
TBAF
—
—
Trace
92
—
aReaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), Pd (3 mol%), ligand (6 mol%),
.
TBAF 3H2O (3 equiv), and solvent (1 mL) at 85–908C for 5 h.
bIsolated yield.
cPCy3 (3 mol%).
dAt room temperature.
ePd (0.1 mol%).
fReaction condition: 1a (5 mmol), 2a (6 mmol), Pd (3 mol%), ligand (6 mol%),
.
TBAF 3H2O (3 equiv) at 85–908C for 24 h.

2436
J.-H. Li, C.-L. Deng, and Y.-X. Xie
ligand provided the target product 3 in a 91% yield (Table 1, entry 2). Other
phosphine ligands including PPh3 and P(n-Bu)3 were then evaluated, and they
were inferior to PCy3 (Table 1, entries 3 and 4). Identical results were
observed without the aid of any ligands (Table 1, entry 5). We also found
that the loading of PCy3 affected the reaction. The yield decreased to 60%
when the loading of PCy3 was reduced to 3 mol% (Table 1, entries 2 and
6). Encouraged by these results, we then examined other Pd catalysts
including Pd2(dba)3,[19–25] Pd(OAc)2, and PdCl2 under solvent-free con-
ditions (Table 1, entries 7–9). However, the Pd catalysts were less effective
than PdCl2(MeCN)2. For example, the yield of 3 was reduced to 82% when
substrate 1a reacted with 2a, Pd2(dba)3 (3 mol%), PCy3 (6 mol%), and
TBAF (3 equiv) (Table 1, entry 7). To obtain the optimized reaction con-
ditions, a series of solvents, including THF, DMF, dioxane, acetone, MeCN,
H2O, and PEG-400, were next tested (Table 1, entries 10–17). The results
demonstrated that these solvents suppressed the coupling process. For
example, the coupling performed in dioxane, the reported effective
solvent,[19–25] decreased the yield of 3 to some extent using either
Pd2(dba)3 (78%) or PdCl2(MeCN)2 (74%) as the catalyst (Table 1, entries
10 and 11). The effects of both ligand and base on the reaction were also inves-
tigated. The use of other bases, such as Cs2CO3, TBAOH (tetra-n-butylammo-
nium hydroxide), and KF, decreased the yield of the target product 3
dramatically (Table 1, entries 18–20). Finally, attempts to perform the
reaction at room temperature or at 0.1 mol% loading of Pd were unsuccessful
(Table 1, entries 21 and 22). Noteworthy is that the process is suitable for the
reaction of 5 mol of 1a (Table 1, entry 23). We also attempted to recover and
reuse the PdCl2(MeCN)2/P(cy)3/TBAF system; however, only a 45% yield of
3 was isolated in the second run.
As shown in Table 2, a wide range of aryl chlorides 1a–1h, whether
electron rich or electron deficient, all work well with arylboronic acids
2a–2f, PdCl2(MeCN)2 (3 mol%), PCy3 (6 mol%), and TBAF (3 equiv)
under solvent-free conditions to provide the target products in moderate to
excellent yields. For example, the deactivated chloride 1f was reacted with
2a, 2b, or 2d–2f to give the corresponding products 13–17 in 84%, 80%,
58%, 62%, and 51% yields, respectively (entries 10–14). For the challenging
aryl chlorides 1g and 1h, moderate to good yields were still achieved under the
same conditions (entries 15 and 16). We also disclosed that the presence of the
bulky ortho substitutes in the aromatic rings of aryl chlorides did not impede
effective coupling, but incorporation of the bulky ortho substitutes to arylboro-
nic acids decreased the yields. For example, the bulky chloride 1i reacted with
2a to produced the corresponding product 19 in 78% yield (Table 2, entry 16),
whereas only 51% yield of 17 was isolated from the coupling of 1f with
boronic acid 2f bearing an ortho-methyl group (Table 2, entry 14).
The application of these optimized reaction conditions to the synthesis
of heterocycles was also studied (Table 3).[25–32] To our delight, both het-
eroaryl-aryls and heteroaryl-heteroaryls could be synthesized by this

Palladium-Catalyzed Suzuki–Miyaura Reaction
2437
Table 2. PdCl2(MeCN)2/PCy3-catalyzed Suzuki–Miyaura cross-couplings of aryl
chlorides (1) with arylboronic acids (2) under solvent-free conditionsa
Entry
1
Aryl halide
Arylboronic acid
Yield (%)b
100 (4)
2
3
(1b)
(1b)
98 (5)
81 (6)
4
5
6
(1b)
(1b)
95 (7)
100 (8)
98 (9)
(2a)
(2a)
7
8
94 (10)
83 (11)
(1d)
9
(2a)
(2a)
90 (12)
10
84 (13)
11
12
13
14
(1f)
(1f)
(1f)
(1f)
(2b)
(2d)
(2e)
(2f)
80 (14)
58 (15)
62 (16)
51 (17)
(continued)

2438
J.-H. Li, C.-L. Deng, and Y.-X. Xie
Table 2. Continued
Entry
15
Aryl halide
Arylboronic acid
Yield (%)b
(2a)
93 (18)
16
(2a)
78 (19)
aReaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), PdCl2(MeCN)2 (3 mol%), PCy3
.
(6 mol%), and TBAF 3H2O (3 equiv) at 85–908C for 5 h.
bIsolated yield.
process. The reactions between aryl halides 1b and 1d with heteroarylboro-
nic acids 2g–2i, respectively, were first tested. In the presence of
PdCl2(MeCN)2 (3 mol%), PCy3 (6 mol%), and TBAF (3 equiv), the corre-
sponding heteroaryl-aryl products 20–24 were generated in good to
excellent yields. We then examined another route to synthesize heteroaryl-
aryls: the couplings of heteroaryl chlorides with arylboronic acids. Satisfac-
tory results were also obtained from the reactions of heteroaryl chlorides 1i–
1l with 2a, 2c, or 2d under the same reaction conditions. For example, het-
eroaryl chloride 1k coupled with arylboronic acids 2a–2c including a chal-
lenging boronic acid 2c provided the corresponding products 27–29 in
100%, 58%, and 93% yields, respectively (entries 8–10). Gratifyingly,
these optimized reaction conditions were also effective for the reactions in
which both of the reaction partners are heterocycles. Treatment of substate
1k with oxygen-containing heteroarylboronic acid 2g or sulfur-containing
heteroarylboronic acid 2h, PdCl2(MeCN)2, PCy3, and TBAF afforded the
corresponding products 30 and 31 in good yields. The results also
indicated that the reaction between 2-chloropyrazine 1l and 2h was carried
out smoothly to give the desired product 33 in a 95% yield. A moderate
yield of the target product 34 was still provided when 2-chloropyrazine
(1l) was reacted with nitrogen-containing heteroarylboronic acid (2i) under
the same reaction conditions.
In summary, we have demonstrated a homogeneous PdCl2(MeCN)2/
PCy3/TBAF system for the solvent-free cross-coupling of aryl chlorides
with arylboronic acids. Compared with the results of Fu and Chen,[19–25]
several interesting features are obvious for the current reaction: First, the
.
reaction is carried out under homogeneous conditions (TBAF 3H2O: mp
58–608C). Second, no harmful organic solvents such as dioxane or THF
were required. On the contrary, the solvents have deleterious effects on the

Palladium-Catalyzed Suzuki–Miyaura Reaction
2439
Table 3. Synthesis of heterocycles via the solvent-free PdCl2(MeCN)2/PCy3-
catalyzed Suzuki–Miyaura cross-couplingsa
Entry
1
Aryl halide
Arylboronic acids
Yield (%)b
88 (20)
2
(1b)
(1b)
100 (21)
3
4
85 (22)
80 (23)
(2g)
5
6
(1d)
(2h)
(2a)
73 (24)
63 (25)
7
(2a)
(2a)
69 (26)
8
9
100 (27)
58 (28)
(1k)
10
11
12
13
(1k)
(1k)
(1k)
(2d)
(2g)
(2h)
(2a)
93 (29)
99 (30)
86 (31)
100 (32)
14
15
(1l)
(1l)
(2h)
(2i)
95 (33)
65 (34)
aReaction condition: 1 (0.5 mmol), 2 (0.6 mmol), PdCl2(MeCN)2 (3 mol%), PCy3
.
(6 mol%), and TBAF 3H2O (3 equiv) at 85–908C for 5 h.
bIsolated yield.

2440
J.-H. Li, C.-L. Deng, and Y.-X. Xie
present reaction. Finally, the protocol not only works well for aryl chlorides
bearing different substitutes but also is general for the synthesis of biaryls,
heteroary-aryls, and heteroaryl-heterobiaryls including oxygen, sulfur, and
nitrogen heterocycles. Further applications of the system in other transform-
ations are under way.
EXPERIMENTAL
Typical Procedure
A mixture of aryl halide 1 (0.5 mmol), arylboronic acid 2 (0.6 mmol),
PdCl2(MeCN)2 (3 mol%), PCy3 (6 mol%), and TBAF (3 equiv) was stirred
at 85–908C for 5 h until the starting material was completely consumed as
monitored by thin-layer chromatography (TLC). After the mixture was
dissolved in ethyl acetate, filtered, washed with H2O, extracted by diethyl
ether, and evaporated, the residue was then purified by flash column chromato-
graphy (hexane or hexane/ethyl acetate) to afford the corresponding coupled
product. The spectral data of all the known compounds 3–27, 30, 32, and 33
were in agreement with those reported.[9–31,39–46]
4-Methyl-biphenyl (3)[9–25]
1H NMR (400 MHz, CDCl3) d: 7.59 (t, J ¼ 7.6 Hz, 2H), 7.49 (d, J ¼ 8.0 Hz,
2H), 7.42 (t, J ¼ 7.6 Hz, 2H), 7.31 (t, J ¼ 7.6 Hz, 1H), 7.24 (d, J ¼ 8.0 Hz,
2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) d: 141.1, 138.3, 137.0,
129.5, 128.7, 127.3, 127.2, 127.0, 21.1.
4-Nitro-biphenyl (4)[9–25]
1H NMR (400 MHz, CDCl3) d: 8.30 (d, J ¼ 8.8 Hz, 2H), 7.74 (d, J ¼ 8.8 Hz,
2H), 7.64 (d, J ¼ 6.9 Hz, 2H), 7.52–7.44 (m, 3H); 13C NMR (100 MHz,
CDCl3) d: 147.6, 147.1, 138.8, 129.2, 128.91, 127.8, 127.4, 124.1.
4-Methyl-40-nitro-biphenyl (5)[9–25]
1H NMR (400 MHz, CDCl3) d: 8.27 (d, J ¼ 8.8 Hz, 2H), 7.71 (d, J ¼ 8.8 Hz,
2H), 7.53 (d, J ¼ 8.4 Hz, 2H), 7.30 (d, J ¼ 7.8 Hz, 2H), 2.42 (s, 3H); 13C
NMR (100 MHz, CDCl3) d: 147.5, 146.7, 139.0, 135.7, 129.8, 127.4, 127.1,
124.0, 21.2.

Palladium-Catalyzed Suzuki–Miyaura Reaction
4-Nitro-20,60-dimethylbiphenyl (6)[25]
2441
1H NMR (300 MHz, CDCl3) d: 8.31 (d, J ¼ 9.0 Hz, 2H), 7.35 (d, J ¼ 8.7 Hz,
2H), 7.25–7.20 (m, 1H), 7.15–7.13 (m, 2H), 2.02 (s, 6H); 13C NMR (75 MHz,
CDCl3) d: 148.4, 146.8, 139.5, 135.3, 130.7, 128.0, 127.6, 123.8, 20.7.
4-Nitro-40-methoxybiphenyl (7)[38]
1H NMR (300 MHz, CDCl3) d: 8.25 (d, J ¼ 9.0 Hz, 2H), 7.68 (d, J ¼ 9.0 Hz,
2H), 7.57 (d, J ¼ 9.0 Hz, 2H), 7.02 (d, J ¼ 8.7 Hz, 2H); 13C NMR (75 MHz,
CDCl3) d: 160.4, 147.2, 146.5, 131.0, 128.5, 127.0, 124.1, 114.6, 55.4.
4-Nitro-40-fluorobiphenyl (8)[38]
1H NMR (400 MHz, CDCl3) d: 8.30 (d, J ¼ 8.8 Hz, 2H), 7.70 (d, J ¼ 8.8 Hz,
2H), 7.59 (dd, J ¼ 5.6 Hz, 5.6 Hz, 2H), 7.20 (t, J ¼ 8.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d: 164.6, 162.1, 146.5, 134.9, 129.1 (d, J ¼ 8.6 Hz, 1C),
127.6, 124.2, 116.2 (d, J ¼ 21.7 Hz, 1C).
1-Biphenyl-4-yl-ethanone (9)[9–25]
1H NMR (300 MHz, CDCl3) d: 8.04 (d, J ¼ 8.4 Hz, 2H), 7.69 (d, J ¼ 8.4 Hz,
2H), 7.64 (d, J ¼ 7.6 Hz, 2H), 7.50–7.40 (m, 3H), 2.64 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 198.1, 146.1, 140.2, 136.2, 130.1, 129.2, 128.6, 127.6,
118.5, 27.0.
Biphenyl (10)[39]
1H NMR (300 MHz, CDCl3) d: 7.59 (d, J ¼ 8.4 Hz, 4H), 7.43 (t, J ¼ 7.2 Hz,
4H), 7.36 (t, J ¼ 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d: 141.6, 129.1,
127.6, 127.5.
2-Methyl-biphenyl (11)[9–25]
1H NMR (400 MHz, CDCl3) d: 7.40 (t, J ¼ 7.2 Hz, 2H), 7.32 (t, J ¼ 6.8 Hz,
3H), 7.25–7.23 (m, 4H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) d: 141.9,
135.3, 130.3, 129.8, 129.2, 128.0, 127.2, 126.7, 125.7, 125.6, 20.4.

2442
J.-H. Li, C.-L. Deng, and Y.-X. Xie
3,5-Dimethyl-biphenyl (12)[40]
1H NMR (400 MHz, CDCl3) d: 7.59 (d, J ¼ 8.4 Hz, 2H), 7.44–7.40 (m, 2H),
7.31–7.28 (m, 1H), 7.19 (d, J ¼ 8.4 Hz, 2H), 6.98 (d, J ¼ 9.2 Hz, 1H), 2.35
(s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) d: 141.5, 138.1, 128.9,
128.7, 127.9, 127.2, 127.1, 125.1, 21.4.
4-Methoxy-biphenyl (13)[9–25]
1H NMR (300 MHz, CDCl3) d: 7.54 (t, J ¼ 8.4 Hz, 4H), 7.42 (t, J ¼ 7.8 Hz,
2H), 7.31 (t, J ¼ 7.5, 1H), 6.98 (d, J ¼ 9.0, 2H), 3.86 (s, 3H); 13C NMR
(100 MHz, CDCl3) d: 159.1, 140.8, 133.7, 128.7, 128.1, 126.7, 126.6,
114.2, 55.3.
4-Methyl-40-methoxy-biphenyl (14)[9–25]
1H NMR (400 MHz, CDCl3) d: 7.50 (d, J ¼ 8.8 Hz, 2H), 7.44 (d, J ¼ 8.4 Hz,
2H), 7.22 (d, J ¼ 8.0 Hz, 2H), 6.95 (d, J ¼ 8.8 Hz, 2H), 3.83 (s, 3H), 2.37
(s, 3H); 13C NMR (100 MHz, CDCl3) d: 158.9, 137.9, 136.3, 133.7, 129.4,
127.9, 126.5, 114.1, 55.3, 21.0.
4,40-Dimethoxy-biphenyl (15)[39]
1H NMR (300 MHz, CDCl3) d: 7.48 (d, J ¼ 8.4 Hz, 4H), 6.95 (d, J ¼ 8.87 Hz,
4H), 3.84 (s, 6H); 13C NMR (100 MHz, CDCl3) d: 158.7, 133.5, 127.7,
114.1, 59.3.
4-Fluoro-40-methoxy-biphenyl (16)[9–25]
1H NMR (300 MHz, CDCl3) d: 7.50–7.45 (m, 4H), 7.09 (t, J ¼ 8.4 Hz, 2H),
6.96 (d, J ¼ 8.7 Hz, 2H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3) d: 163.7,
160.4, 159.0, 132.7, 128.2 (d, J ¼ 9.3 Hz, 1C), 128.0, 115.5 (d, J ¼ 28.2 Hz,
1C), 114.2, 55.3.
2-Methyl-4’-methoxy-biphenyl (17)[9–25]
1H NMR (400 MHz, CDCl3) d: 7.26–7.22 (m, 6H), 6.95 (d, J ¼ 8.4 Hz, 2H),
3.85 (s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) d: 158.5, 141.5, 135.5,
134.3, 130.3, 130.2, 129.9, 127.0, 125.8, 113.5, 55.3, 20.6.

Palladium-Catalyzed Suzuki–Miyaura Reaction
2,6-Dimethyl-biphenyl (18)[9–25]
2443
1H NMR (400 MHz, CDCl3) d: 7.43 (t, J ¼ 7.6 Hz, 2H), 7.36–7.30 (m, 1H),
7.15–7.11 (m, 5H), 2.03 (s, 6H); 13C NMR (100 MHz, CDCl3) d: 141.1,
136.1, 129.0, 128.8, 128.4, 127.3, 127.0, 126.6, 20.9.
2,4-Dimethoxy-biphenyl (19)[41]
1H NMR (300 MHz, CDCl3) d: 7.53 (d, J ¼ 8.1 Hz, 2H), 7.40 (t, J ¼ 7.5 Hz,
2H), 7.34 (t, J ¼ 9.0 Hz, 1H), 6.95–6.82 (m, 3H); 13C NMR (75 MHz, CDCl3)
d: 153.6, 138.3, 129.4, 128.0, 127.0, 116.6, 116.0, 113.0, 112.8, 112.5,
56.2, 55.8.
2-(4-Nitrophenyl)furan (20)[42]
1H NMR (400 MHz, CDCl3) d: 8.24 (d, J ¼ 8.8 Hz, 2H), 7.78 (d, J ¼ 7.8 Hz,
2H), 7.57 (d, J ¼ 1.2 Hz, 1H), 6.87 (d, J ¼ 2.4 Hz, 1H), 6.55 (t, J ¼ 3.6 Hz,
1H); 13C NMR (100 MHz, CDCl3) d: 151.7, 146.4, 144.1, 136.4, 124.3,
123.3, 112.4, 108.6.
2-(4-Nitrophenyl)thiophene (21)[42]
1H NMR (400 MHz, CDCl3) d: 8.23 (d, J ¼ 8.8 Hz, 2H), 7.74 (d, J ¼ 9.6 Hz,
2H), 7.48 (d, J ¼ 4.0 Hz, 1H), 7.44 (d, J ¼ 5.2 Hz, 1H), 7.15 (t, J ¼ 4.4 Hz,
1H); 13C NMR (100 MHz, CDCl3) d: 146.6, 141.6, 140.6, 128.7, 127.7,
126.0, 125.7, 124.4.
4-(4-Nitrophenyl)pyridine (22)[25]
1H NMR (400 MHz, CDCl3) d: 8.75 (d, J ¼ 6.0 Hz, 2H), 8.36 (d, J ¼ 8.8 Hz,
2H), 7.81 (d, J ¼ 8.8 Hz, 2H), 7.55 (d, J ¼ 6.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d: 150.6, 148.1, 145.7, 144.4, 127.9, 124.3, 121.7.
2-Phenylfuran (23)[43]
1H NMR (300 MHz, CDCl3) d: 7.67 (d, J ¼ 8.8 Hz, 1H), 7.60 (d, J ¼ 8.8 Hz,
2H), 7.46–7.34 (m, 5H); 13C NMR (75 MHz, CDCl3) d: 142.0, 128.7, 128.6,
127.3, 127.2, 127.1, 123.7, 111.6.

2444
J.-H. Li, C.-L. Deng, and Y.-X. Xie
2-Phenylthiophene (24)[44]
1H NMR (400 MHz, CDCl3) d: 7.61–7.57 (m, 2H), 7.35 (t, J ¼ 7.6 Hz, 2H),
7.29–7.23 (m, 2H), 7.05 (t, J ¼ 4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) d:
144.4, 134.3, 128.8, 127.9, 127.4, 125.9, 124.7, 123.0.
2-Phenylpyridine (25)[44]
1H NMR (400 MHz, CDCl3) d: 8.59 (d, J ¼ 4.8 Hz, 1H), 7.99 (d, J ¼ 6.8 Hz,
2H), 7.78–7.71 (m, 2H), 7.48 (t, J ¼ 8.8 Hz, 2H), 7.42 (t, J ¼ 7.2 Hz, 1H),
7.26–7.21 (m, 1H); 13C NMR (100 MHz, CDCl3) d: 157.4, 149.6, 139.3,
136.7, 128.9, 128.7, 126.9, 122.1, 120.5.
3-Phenylpyridine (26)[44]
1H NMR (400 MHz, CDCl3) d: 8.85 (s, 1H), 8.59 (d, J ¼ 6.4 Hz, 1H), 7.88
(d, J ¼ 12.0 Hz, 1H), 7.60 (d, J ¼ 8.4 Hz, 2H), 7.49 (t, J ¼ 7.2 Hz, 2H),
7.43–7.35 (m, 2H); 13C NMR (100 MHz, CDCl3) d: 148.4, 148.3, 137.8,
136.6, 134.3, 129.0, 128.1, 127.1, 123.5.
5-Phenylpyrimidine (27)[25]
1H NMR (400 MHz, CDCl3) d: 9.21 (s, 1H), 8.96 (s, 2H), 7.58 (d, J ¼ 8.8 Hz,
2H), 7.53 (t, J ¼ 8.8 Hz, 2H), 7.47 (t, J ¼ 7.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d: 157.3, 154.8, 134.2, 134.1, 129.3, 128.9, 126.7.
5-(2,6-Dimethylphenyl)pyrimidine (28)
White solid, mp 50–528C (uncorrected). 1H NMR (400 MHz, CDCl3) d: 9.23
(s, 1H), 8.60 (s, 2H), 7.26 (t, J ¼ 8.0 Hz, 1H), 7.17 (d, J ¼ 8.4 Hz, 2H), 2.06
(s, 6H); 13C NMR (100 MHz, CDCl3) d: 157.3, 157.1, 136.4, 134.6, 133.8,
128.7, 127.8, 21.0; LRMS (EI, 20 eV) m/z (%): 184 (Mþ, 100); HRMS
(EI) for C12H12N2 (Mþ): calcd. 184.1001, found 184.1000.
5-(4-Methoxyphenyl)pyrimidine (29)
White solid, mp 91–938C (uncorrected). 1H NMR (400 MHz, CDCl3) d: 9.16
(s, 1H), 8.92 (s, 2H), 7.53 (d, J ¼ 8.4 Hz, 2H), 7.05 (d, J ¼ 8.4 Hz, 2H), 3.88
(s, 3H); 13C NMR (100 MHz, CDCl3) d: 160.3, 156.8, 154.3, 133.8, 128.0,

Palladium-Catalyzed Suzuki–Miyaura Reaction
2445
126.4, 114.8, 55.3; LRMS (EI, 20 eV) m/z (%): 186 (Mþ, 100); HRMS (EI)
for C11H10N2O (Mþ): calcd. 186.0793, found 186.0791.
5-(Furan-2-yl)pyrimidine (30)[45]
1H NMR (400 MHz, CDCl3) d: 9.10 (s, 1H), 9.01 (s 2H), 7.59 (d, J ¼ 1.6 Hz,
1H), 6.85 (d, J ¼ 3.6 Hz, 1H), 6.55 (t, J ¼ 1.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d: 157.0, 151.3, 147.9, 144.0, 125.0, 112.1, 107.9.
5-(Thiophen-2-yl)pyrimidine (31)
1
White solid, mp 77.2–78.08C (uncorrected). H NMR (400 MHz, CDCl3) d:
9.13 (s, 1H), 8.96 (s, 1H), 7.46 (d, J ¼ 6.0 Hz, 2H), 7.43 (d, J ¼ 5.2 Hz,
1H), 7.18 (t, J ¼ 3.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d: 157.2, 153.4,
136.2, 128.6 (2C), 127.3, 125.2; LRMS (EI, 20 eV) m/z (%): 162 (Mþ,
100); HRMS (EI) for C8H6N2S (Mþ): calcd. 162.0252, found 162.0251.
2-Phenylpyrazine (32)[46]
1H NMR (400 MHz, CDCl3) d: 9.04 (d, J ¼ 1.6 Hz, 2H), 8.65 (s, 1H), 8.52
(d, J ¼ 2.4 Hz, 1H), 8.02 (d, J ¼ 8.0 Hz, 2H), 7.51 (t, J ¼ 7.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d: 152.8, 144.2, 142.9, 142.2, 136.3, 129.9, 129.0,
126.9.
2-(Thiophen-2-yl)pyrazine (33)[45]
1H NMR (400 MHz, CDCl3) d: 8.96 (s, 1H), 8.51 (s, 1H), 8.40 (s, 1H), 7.69
(d, J ¼ 4.0 Hz, 1H), 7.49 (d, J ¼ 5.6 Hz, 1H), 7.16 (t, J ¼ 4.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d: 148.5, 143.9, 142.3, 141.3, 140.6, 129.0, 128.4,
125.7.
2-(Pyridin-4-yl)pyrazine (34)
1
Slight yellow solid, mp 87.6–88.48C (uncorrected). H NMR (400 MHz,
CDCl3) d: 9.11 (s, 1H), 8.79 (d, J ¼ 6.0 Hz, 2H), 8.72 (s, 1H), 8.64 (s, 1H),
7.93 (d, J ¼ 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) d: 150.7, 150.1,
144.7, 144.6, 143.5, 142.3, 120.9; LRMS (EI, 20 eV) m/z (%): 157 (Mþ,
100); HRMS (EI) for C9H7N3 (Mþ): calcd. 157.0640, found 157.0640.

2446
J.-H. Li, C.-L. Deng, and Y.-X. Xie
ACKNOWLEDGMENT
The authors thank the National Natural Science Foundation of China (No.
20572020), Fok Ying Dong Education Foundation (No. 101012), the Key
Project of Chinese Ministry of Education (No. 206102), Scientific Research
Fund of Hunan Provincial Education Department (No. 05B038), and Hunan
Provincial Natural Science Foundation of China (No. 05JJ1002) for
financial support.
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