Facile synthesis of 3-arylpyridine derivatives by palladacycle-catalyzed Stille cross-coupling reaction

Article abstract of DOI:10.1016/j.tet.2012.10.080

The Stille cross-coupling reaction of a variety of aryl halides (X=Cl, Br, I) with 3-alkylstannylpyridines highly catalyzed by cyclopalladated ferrocenylimine has been developed. This reaction allows formation of arylpyridine derivatives in moderate to excellent yields. Functional groups on aryl halides, such as amino, hydroxyl, keto, and aldehyde are tolerated and the reactions with arylbenzoxale substrates also proceed well.

Full text of DOI:10.1016/j.tet.2012.10.080

Tetrahedron 69 (2013) 902e909
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Facile synthesis of 3-arylpyridine derivatives by palladacycle-catalyzed
Stille cross-coupling reaction
,
b
,
,
Gaizhi Ma a, Yuting Leng a , Yusheng Wu c, Yangjie Wu a
*
*
a The College of Chemistry and Molecular Engineering, Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Zhengzhou University, Zhengzhou,
Henan 450052, PR China
b Tetranov Biopharm, LLC. 75 Daxue Road, Zhengzhou, Henan 450052, PR China
c Tetranov International Inc., 100 Jersey Avenue, Suite A340, New Brunswick, NJ 08901, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The Stille cross-coupling reaction of a variety of aryl halides (X¼Cl, Br, I) with 3-alkylstannylpyridines
highly catalyzed by cyclopalladated ferrocenylimine has been developed. This reaction allows forma-
tion of arylpyridine derivatives in moderate to excellent yields. Functional groups on aryl halides, such as
amino, hydroxyl, keto, and aldehyde are tolerated and the reactions with arylbenzoxale substrates also
proceed well.
Received 10 June 2012
Received in revised form
20 September 2012
Accepted 9 October 2012
Available online 8 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Stille cross-coupling reaction
Cyclopalladated ferrocenylimine
Catalyst
Aryl halides
Pyridine
1. Introduction
a stable Pd(II) precatalyst contributes to the high yields of coupling
reactions.8 On the other hand, in the most of the reported catalytic
Biaryl motifs particularly containing pyridyl moiety are found in
numerous herbicides,1 bioactive compounds including both natural
products and pharmaceutically interesting molecules,2 microelec-
trode array,3 conducting polymers, and liquid crystal materials.4
Over the last several decades, the Stille cross-coupling reaction
has proved to be indispensable in organic synthesis of biaryl de-
rivatives.4,5 Recently, different catalytic systems on Stille cross-
coupling were developed by several research groups.6 However,
the synthesis of arylpyridine derivatives especially the 3-
arylpyridine derivatives by Stille cross-couplings has never been
studied systematically, which probably be limited by the low re-
activity of 3-halogenated pyridines and the harsh reaction condi-
tions. In view of various applications of arylpyridine derivatives and
the shortcomings of reported synthetic methods, we tried to realize
synthesis of 3-arylpyridines using the more reactive alkyl-
stannylpyridines instead of stable halogenated pyridines.
systems of Stille cross-coupling, the reaction follows a mechanism of
Pd(0)/Pd(II) catalytic cycle.9 Asourongoingendeavortoward seeking
the new application of palladacycle (I)e(II) in the cross-coupling of
challenging substrates, herein we report a generally applicable and
efficient method for the synthesis of 3-arylpyridine derivatives via
Stille cross-coupling of 3-alkylstannylpyridines with aryl halides in
the presence of cyclopalladated ferrocenylimines (Fig. 1).
2. Results and discussion
In our initial study, we examined the effects of various catalysts,
solvents, bases, and additives in thereaction of alkylstannylpyridines
N
L
PCy2
Cyclopalladated ferrocenylimines, one type of readily prepared
complexes with good stability and convenient manipulation, have
been widely applied to the catalysis of various coupling reactions.7 It
was disclosed that slow generation of active Pd(0) complexes from
L= PCy3,
Fe
i
Pr
iPr
Pd
Cl
I
II
iPr
* Corresponding authors. Tel.: þ86 371 67767993; fax: þ86 371 6797 9408;
e-mail addresses: yutingleng@zzu.edu.cn (Y. Leng), wyj@zzu.edu.cn (Y. Wu).
Fig. 1. Palladacycle IeII.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.080

G. Ma et al. / Tetrahedron 69 (2013) 902e909
903
with aryl bromides. The results are summarized in Table 1. The re-
action of 3-tributylstannylpyridine with bromobenzene was carried
out with different catalysts, and the desired product was obtained in
relatively higher yields (70%) under the catalysis of cyclopalladated
decrease the reaction temperature to 80 ꢀC (Table 1, entry 14). Under
such a mild condition, comparable yield (98%) of coupling product
was isolated. Most interestingly, the cross-coupling reaction even
proceeds smoothly at room temperature albeit with moderate yield
Table 1
Effects of solvents, catalysts, bases, temperature, and additives on the reaction of tributylstannylpyridine with bromobenzenea
Bu
Bu
Br
Sn
[Pd], Solvent
Bu
+
Base, Additive, T, h
N
N
1a
3aa
2a
Entry
Solvent
Catalyst
Base
T (ꢀC)
Additive
t (h)
Yield(%)b
1
2
3
4
5
6
7
8
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
Dioxane
DME
DMF
DMF
DMF
Pd[P(Ph)3]4 (5%)
PdCl2(5%)þP(Ph)3(10%)
LiCl
LiCl
LiCl
110
110
110
110
110
110
110
110
110
110
110
110
110
80
16
16
16
16
16
16
16
16
16
16
16
16
16
12
12
16
12
12
61
50
70
73
57
65
78
18
66
25
80
99
59
98
22
65
78
80
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
I (1%)
d
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
Cs2CO3 (1.5 equiv)
CuO
CuBr
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
9
10
11
12
13
14
15
16
17c
18d
CsF
KF
DMF
DMF
DMF
DMF
CsF
CsF
CsF
CsF
CsF
80
25
80
80
I (1%)
I (1%)
I (1%)
DMF
a
Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), base (1 mmol), additive (20 mol %), catalyst I (1 mol %), solvent (2 mL), under nitrogen.
Isolated yield.
1a (0.5 mmol), 2a (0.5 mmol).
1a (0.75 mmol), 2a (0.5 mmol).
b
c
d
ferrocenylimine I in comparison with the cases using other Pd cat-
(Table 1, entry 15). However, the desirable product was obtained
with the lower yield (22%) in the absence of catalyst (Table 1, en-
try16); compared with the other ratio of 1a and 2a, the 1:1.5 ratio of
1a and 2a gave much higher yield. When 1:1 ratio of 1a and 2a,
bromobenzene remained and the part of 3-tributylstannylpyridine
was decomposed (Table 1, entries 17 and 18).
alysts, such as Pd(PPh3)4 or PdCl2 (Table 1, entries 1e3). After
screening of a variety of additives and solvents (entries 4e12), it was
revealed that the CuI and DMF seem to be optimal (Table 1, entry
12).10 Then, the impact of the bases on the efficiency of the catalysis
was investigated (Table 1, entries 11e13), and CsF turns out to be the
best option to give the desired product in 99% yield (Table 1, entry
12). Such a high activity of the catalytic system allows to further
With the optimized reaction conditions in hand, we then in-
vestigated the substrate scope of the catalysis. As shown in Table 2,
Table 2
The Stille cross-coupling reaction of alkylstannylpyridine with various aryl halidesa
Br
+
I (1mol%)
R1
R1
Sn(alkyl)3
CuI, CsF, DMF, 80ºC
N
N
alkyl=-Me,-Bu
2a-2c
1a-1s
3aa-3cc
Entry
1
Substrate 1
Substrate 2
Product
Yieldb
98
Bu
Sn Bu
Bu
Br
N
N
1a
1b
3aa
N
2a
Br
2
2a
65
3ba
(continued on next page)

904
G. Ma et al. / Tetrahedron 69 (2013) 902e909
Table 2 (continued )
Entry
Substrate 1
Substrate 2
Product
Yieldb
94
Br
3
2a
N
1c
3ca
4
5
Br
2a
2a
92
90
N
1d
3da
OCH3
Br
OCH3
N
1e
3ea
6
7
2a
2a
62
99
N
OCH
Br
3 1f
OCH3
3fa
Br
N
NH
Br
H2N
2 1g
3ga
8
2a
99
N
NH2
3ha
NH2
1h
NH2
Br
Br
NH2
9
2a
2a
99
93
N
1i
3ia
3ja
CHO
CHO
10
N
1j
COOCH3
COCH3
CF3
11
12
13
14
Br
COOCH3
COCH3
2a
73
87
75
99
N
1k
3ka
Br
2a
2a
2a
N
1l
3la
Br
Br
CF3
NO2
N
N
1m
1n
3ma
NO2
3na
CF3
Br
15
2a
65
N
F3C
CF
CF3
3 1o
3oa

G. Ma et al. / Tetrahedron 69 (2013) 902e909
905
Table 2 (continued )
Entry
Substrate 1
Substrate 2
Product
Yieldb
O
N
O
16
2a
60
N
Br
N
1p
3pa
Br
O
N
N
O
N
17
18
19
2a
2a
76
77
70
1q
1r
3qa
3ra
3sa
Br
Br
O
N
N
O
N
F
F
O
N
N
O
N
2a
1s
Sn
Br
20
21
22
95
75
N
1a
3aa=3ab
N
2b
Bu
Sn
Bu
Bu
OCH3
Br
OCH3
N
N
1c
3cc
2c
OH
Br
OH
2a
2c
89
70
N
1t
3ta
23
N
N
N
Br
3ua
a
Reaction conditions: aryl halides (0.5 mmol), alkylstannylpyridines (0.75 mmol), CsF (1.0 mmol), catalyst I (1 mol %), CuI (20 mol %), DMF (2 mL), 80 ꢀC, 12 h, under
nitrogen.
b
Isolated yield.
the cross-coupling of various aryl bromides (1aes) with a variety of
alkylstannylpyridines (2aec) under the catalysis of I (1 mol %) is
quite general. The reaction proceeded smoothly to afford the cor-
responding cross-coupling products 3aaecc in good to excellent
isolated yields (60e99%). Neither the electronic property nor the
steric hindrance of substituents (R1) on the aromatic rings of aryl
bromide (1aes) had significant impact on the yields of the coupling
reactions (Table 2, entries 1e15), despite of slight negative effects of
strongly electron-donating (Table 2, entry 6), electron-withdrawing
(Table 2, entries 11,13) or sterically bulky (Table 2, entry 2) group on
the reactivity of the catalysis. Most importantly, the aryl bromides
having free amino group at ortho-, meta- or para-position reacted
with tributylstannylpyridine perfectly to afford the corresponding
cross-coupling products (3gaeia) in 99% yield, and having free
hydroxyl group also proceeded well to afford desired product with
89% yield (Table 2, entry 22), highlighting the excellent tolerance of
substrate functionality of the present catalytic systems. On the
other hand, the reaction of aryl bromides containing benzoxazole
skeletons gave the corresponding cross-coupling products in
moderate to good yields (Table 2, entries 16e19). Finally, the
adaptability of the present catalytic system for alkylstannylpyridine
substrates was investigated by employing 3-trimethyltannylpyr-
idine (2b) or 2-tributylstannylpyridine (2c) as the coupling reagent
to react with bromobenzene (1a) or 4-methoxybromobenzene (1c),

906
G. Ma et al. / Tetrahedron 69 (2013) 902e909
respectively. As shown in the entries 20 and 21 of Table 2, the
expected products of 3-aryl or 2-arylpyridine derivatives were
obtained with 95% and 75% yields, respectively, indicating the
relatively lower activity of 2-tributylstannylpyridine than that of
3-substituted analog. In the entry 23 of Table 2, the reaction of
2-bromopyridine with 2-alkylstannylpyridine afforded the 2,20-
bipyridine with 70% yield.
The catalytic system allows to further decrease the reaction
temperature to room temperature for aryl iodides. Corresponding
cross-coupling product was obtained with nearly the same high
yields at 80 ꢀC, 45 ꢀC, and rt (Table 3, entry 1). Subsequently, we
explored the scope of the optimal catalyst I in Stille cross-coupling
reactions of substituted aryl iodides (Table 3) at room temperature.
Thus, diversely decorated aryl iodides including strongly electron-
donating (entry 3, 87% of yield), electron-withdrawing groups
(entry 2, 96% of yield) were efficiently functionalized.
Aryl chlorides are one kind of attractive substrates due to being
less expensive and more readily available. The encouraging results
from aryl bromides and aryl iodides prompted us to check if the
coupling of aryl chlorides with alkylstannylpyridines could work at
the same catalytic system. Thus, we turned our attention to the aryl
chlorides for the palladium-catalyzed Stille cross-coupling reaction
with alkylstannylpyridines. Palladacycle II was chosen as catalyst
since it exhibited more efficient than I (Table 4, entry 1). Under
optimized reaction conditions (1 equiv of aryl chlorides, 1.5 equiv of
alkylstannylpyridine, 1 mol % catalyst II, 2 equiv of CsF, in DMF at
Table 3
The Stille cross-coupling reaction of alkylstannylpyridines with various aryl iodinesa
I (1mol%)
+
I
Sn(n-butyl)3
CuI, CsF, DMF, r.t.
R
N
N
R
Entry
1
Substrate R
Product
Yieldb
91c/90d/93b
I
N
1u
3aa
NO2
I
I
2
3
4
NO2
OCH3
CH3
96
87
95
86
N
1v
1w
1x
3na
OCH3
I
N
3ea
CH3
N
3da
CO2CH3
I
CO2CH3
5
1y
N
3ka
a
Reaction conditions: aryl iodine (0.5 mmol), alkylstannylpyridine (0.75 mmol), CsF (1.0 mmol), catalyst I (1 mol %), CuI (20 mol %), DMF (2 mL), room temperature, 12 h,
under nitrogen.
b
Isolated yield.
c
80 ꢀC.
d
45 ꢀC.
Table 4
The Stille cross-coupling reaction of alkylstannylpyridines with various aryl chloridesa
II (1mol%)
CuI, CsF, DMF, 110oC
Cl
+
Sn(n-butyl)3
R
N
N
R
Entry
1
Substrate R
Product
Yieldb
5c/10d/46e/92b
Cl
N
1z
NO2
3aa
NO2
2
98
Cl
1
N
3na

G. Ma et al. / Tetrahedron 69 (2013) 902e909
907
Table 4 (continued )
Entry
Substrate R
Product
Yieldb
92
OCH3
CH3
3
4
Cl
OCH3
N
1
3ea
90
95
Cl
CH3
1
N
3da
H3C
H3C
Cl
5
N
1&
3ca
a
Reaction conditions: aryl chlorides (0.5 mmol), alkylstannylpyridines (0.75 mmol), CsF (1.0 mmol), catalyst II (1 mol %), CuI (20 mol %), DMF (2 mL), 110 ꢀC, 12 h, under
nitrogen.
b
c
Isolated yield.
Catalyst I (1 mol %), 80 ꢀC.
Catalyst I (1 mol %), 110 ꢀC.
Catalyst II (1 mol %), 80 ꢀC.
d
e
110 ꢀC), aryl chlorides with both electron-donating and electron-
withdrawing substituents at para- and ortho-positions were suc-
cessfully converted into the corresponding expected products in
90e98% yields (Table 4, entries 2e5).
Me3SnCl (15.00 mmol) in THF (10.0 mL) was added dropwise and
stirred at ꢁ78 ꢀC for another 3 h. The resulting deep-red solution
was warmed to room temperature over night and a heavy pre-
cipitate formed. Hydrolysis was achieved with a saturated aqueous
solution of NH4Cl. Subsequent treatments (Et2O extraction, drying
on anhydrous Na2SO4, concentration and flash chromatography)
afforded pure product.
3. Conclusion
In summary, we have described a mild, simple, and generally
efficient catalytic system for the reaction of 3-alkylstannylpyridines
with aryl halides (e.g., Cl, Br, I) by using cyclopalladated ferroce-
nylimine as the catalyst (I, II). A wide range of substrates could be
used to this system. Aryl halides with electron-donating, electron-
neutral, and electron-withdrawing substituents all work well giv-
ing moderate to excellent yields. In case of 2-arylbenzoxazole
bromides as substrates, the moderate yields were obtained. Fur-
ther studies on extending the application of this reaction in organic
synthesis are ongoing in our laboratory.
4.3. General procedure for the reaction of alkylstannylpyr-
idines with aryl halides
Aryl halide (0.5 mmol), base (1 mmol), CuI (20 mol %), alkyl-
stannylpyridine (0.75 mmol), and catalyst (1 mol %) were dissolved
in DMF (2 mL) in a 10 mL vial and heated at a specific temperature
under N2 for 12 h. After the reaction was complete, and then
quenched with water. The mixture was diluted with ethyl acetate
(10 mL), filtered through a pad of Celite, and followed by extraction
with ethyl acetate for three times. The combined organic layer was
dried over anhydrous Na2SO4, filtered, and evaporated under re-
duced pressure. The residual was purified by flash chromatography
on silica gel (ethyl acetate/hexane) to give the desired product.
4. Experimental section
4.1. General
1H NMR, 13C NMR spectra were recorded on a Bruker DPX-400
spectrometer with CDCl3 as the solvent and TMS as an internal
standard. Melting points were measured using a WC-1 microscopic
apparatus and are uncorrected. GC analysis was performed on
Agilent 4890D gas chromatograph. Mass spectra were measured on
an LC-MSD-Trap-XCT instrument. High resolution mass spectra
were measured with ESI. Elemental analyses were determined with
a Carlo Erba elemental analyzer. Dichloromethane, ethyl acetate,
and hexane (analytical grade) were used for column chromatog-
raphy without further purification. Other solvents were purified
according to the standard methods. Other chemicals were obtained
from commercial sources and used as-received unless otherwise
noted.
4.3.1. 3-Phenylpyridine (3aa).12 Oil liquid; 1H NMR (400 MHz,
CDCl3):
d
¼8.86 (s,1H), 8.59 (s,1H), 7.88 (d, J¼7.92 Hz,1H), 7.59e7.57
(m, 2H), 7.48 (t, J¼7.28 Hz, 2H), 7.43e7.35 (m, 2H); 13C NMR
(100 MHz, CDCl3):
d¼123.6, 127.2, 128.1, 129.1, 134.4, 137.8, 148.4.
4.3.2. 3-(Naphthalen-1-yl)-pyridine (3ba). Oil liquid; 1H NMR
(400 MHz, CDCl3):
d
¼8.76 (s, 1H), 8.68 (s, 1H), 7.91 (t, J¼7.6 Hz, 2H),
7.80 (d, J¼8.04 Hz, 2H), 7.52 (m, 2H), 7.43 (m, 3H); 13C NMR
(100 MHz, CDCl3):
128.6, 131.5, 133.8, 136.3, 137.4, 148.6, 150.6; HRMS-ESI (m/z):
[MþH]þ calcd for C15H12Nþ: 206.0964, found: 206.0967.
d
¼123.2, 125.3, 125.44, 126.1, 126.6, 127.4, 128.5,
4.3.3. 3-(o-Tolyl)pyridine (3ca).13 Oil liquid; 1H NMR (400 MHz,
CDCl3):
d
¼8.61 (s, 2H), 7.64 (d, J¼7.68 Hz, 1H), 7.34e7.24 (m, 4H),
4.2. General procedure for the synthesis of
alkylstannylpyridines11
7.21 (d, J¼7.00 Hz, 1H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
¼20.4, 123.1, 126.1, 128.1, 129.9, 130.6, 135.6, 136.5, 137.5, 138.1,
148.1, 149.9; HRMS-ESI (m/z): [MþH]þ calcd for C12H12Nþ:
To a solution of n-BuLi (15.00 mmol) in diethyl ether (30.0 mL) at
ꢁ78 ꢀC was added dropwise to a solution of bromopyridine
(15.00 mmol) in diethyl ether (25.0 mL). The resulting solution was
stirred at ꢁ78 ꢀC for 2 h. And then, the solution of Bu3SnCl or
170.0964, found: 170.0968.
4.3.4. 3-(p-Tolyl)pyridine (3da). Yellow solid, mp 34e35 ꢀC; 1H
NMR (400 MHz, CDCl3):
d¼8.90 (s, 1H), 8.63 (d, J¼1.2 Hz, 1H), 7.89

908
G. Ma et al. / Tetrahedron 69 (2013) 902e909
(d, J¼7.88 Hz, 1H), 7.52 (d, J¼8.04 Hz, 2H), 7.33 (d, J¼7.96 Hz, 2H),
7.30 (s, 1H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3):
126.9, 129.8, 129.8, 134.1, 134.9, 138.0, 148.2; HRMS-ESI (m/z):
[MþH]þ calcd for C12H12Nþ: 170.0964, found: 170.0968.
197.5; HRMS-ESI (m/z): [MþH]þ calcd for C13H12NOþ: 198.0913,
d¼21.2, 123.6,
found: 198.0918.
4.3.13. 3-(4-(Trifluoromethyl)phenyl)pyridine (3ma).20 Yellow solid,
mp 59e60 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.90 (s, 1H), 8.70 (s,
4.3.5. 3-(4-Methoxyphenyl)pyridine (3ea).14 Yellow solid, mp
1H), 7.91e7.94 (m, 1H), 7.75 (dd, J¼20.76, 9.96 Hz, 4H), 7.43e7.46
57e58 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.82 (s, 1H), 8.54 (d,
(m, 1H); 13C NMR (100 MHz, CDCl3);
d
¼123.8, 126.0, 126.9, 125.1,
J¼4.08 Hz, 1H), 7.83 (dt, J¼7.88, 1.88 Hz, 1H), 7.52 (d, J¼8.72 Hz, 2H),
127.5, 134.5, 141.4, 148.3, 149.4; HRMS-ESI (m/z): [MþH]þ calcd for
7.32e7.35 (m, 1H), 7.01 (d, J¼8.72 Hz, 2H), 3.86 (s, 3H); 13C NMR
C12H9F3Nþ: 224.0682, found: 224.0683.
(100 MHz, CDCl3):
d
¼55.4, 114.5, 123.5, 128.2, 130.2, 133.9, 147.9,
148.0, 159.7; HRMS-ESI (m/z): [MþH]þ calcd for C12H12NOþ:
4.3.14. 3-(4-Nitrophenyl)pyridine
(3na). Yellow
solid,
mp
186.0913, found: 186.0915.
142e143 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.94 (s, 1H), 8.73 (d,
J¼3.28 Hz, 1H), 8.37 (d, J¼8.68 Hz, 2H), 7.96 (s, J¼7.92 Hz, 1H), 7.78
4.3.6. 3-(3-Methoxyphenyl)pyridine (3fa). Oil liquid; 1H NMR
(d, J¼8.72 Hz, 2H), 7.49e7.46 (m, 1H); 13C NMR (100 MHz, CDCl3):
(400 MHz, CDCl3):
J¼7.84 Hz,1H), 7.41e7.34 (m, 2H), 7.16 (d, J¼7.64 Hz,1H), 7.10 (s,1H),
6.96e6.94 (m, 1H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
¼8.85 (s, 1H), 8.59 (d, J¼2.16 Hz, 1H), 7.86 (d,
d
¼123.9, 124.4, 127.9, 127.9, 134.5, 134.6, 144.3, 147.6, 148.3, 149.9;
HRMS-ESI (m/z): [MþH]þ calcd for C11H9N2Oþ2 : 201.0659, found:
d
¼55.3,
201.0661.
112.9, 113.4, 119.6, 123.5, 130.1, 134.4, 136.5, 139.3, 148.3, 148.6,
160.1; HRMS-ESI (m/z): [MþH]þ calcd for C12H12NOþ: 186.0913,
found: 186.0915.
4.3.15. 3-[3,5-Bis(trifluoromethyl)phenyl]pyridine (3oa). Yellow solid,
mp 62e63 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.89 (s,1H), 8.72 (s,1H),
8.01 (s, 2H), 7.92 (s, 2H), 7.47e7.44 (m, 1H); 13C NMR (100 MHz,
4.3.7. 3-(2-Aminophenyl)pyridine (3ga).15 Oil liquid; 1H NMR
CDCl3):
d
¼29.7, 30.8, 119.1, 121.8, 123.9, 124.5, 127.3, 132.4, 132.7,
(400 MHz, CDCl3):
d
¼8.69 (s, 1H), 8.56 (d, J¼2.68 Hz, 1H), 7.78 (d,
134.6, 140.1, 148.2, 150.1; HRMS-ESI (m/z): [MþH]þ calcd for
J¼7.52 Hz, 1H), 7.34 (t, J¼6.56 Hz, 1H), 7.17 (t, J¼7.36 Hz, 1H), 7.07 (d,
J¼7.20 Hz, 1H), 6.83 (t, J¼7.24 Hz, 1H), 6.76 (d, J¼7.84 Hz, 1H), 3.72
C13H8F6Nþ: 292.0555, found: 292.0562.
(s, 2H); 13C NMR (100 MHz, CDCl3):
d¼115.9, 118.9, 123.6, 129.4,
4.3.16. 2-[3-(Pyridin-3-yl)phenyl]benzoxazole (3pa). Yellow solid,
130.6, 135.3, 136.6, 143.8, 148.4, 150.1; HRMS-ESI (m/z): [MþH]þ
mp 102e103 ꢀC; 1H NMR (400 MHz, CDCl3):
(d, J¼3.80 Hz, 1H), 8.50 (s, 1H), 8.30 (d, J¼7.76 Hz, 1H), 7.89
(d, J¼7.84 Hz, 1H), 7.80e7.81 (m, 1H), 7.76 (d, J¼7.80 Hz, 1H),
7.67e7.60 (m, 2H), 7.43e7.37 (m, 3H); 13C NMR (100 MHz, CDCl3):
d
¼8.96 (s, 1H), 8.66
calcd for C11H11Nþ2 : 171.0917, found: 171.0918.
4.3.8. 3-(3-Aminophenyl)pyridine (3ha).16 Yellow solid, mp
69e70 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.80 (d, J¼1.44 Hz, 1H),
d
¼110.7, 120.1, 123.7, 124.8, 125.4, 126.3, 127.1, 128.1, 129.8,
8.55 (d, J¼4.20 Hz, 1H), 7.81 (dt, J¼7.92 Hz, 1.68 Hz, 1H), 7.29e7.32
(m, 1H), 7.23 (t, J¼7.80 Hz, 1H), 6.93 (d, J¼7.64 Hz, 1H), 6.86e6.85
(m, 1H), 8.70 (dd, J¼2.00 Hz, 7.96 Hz, 1H), 3.91 (s, 2H); 13C NMR
130.1, 134.5, 135.7, 138.7, 142.0, 148.3, 149.1, 150.8, 162.6; HRMS-
ESI (m/z): [MþH]þ calcd for C18H13N2Oþ: 273.1022, found:
273.1027.
(100 MHz, CDCl3):
138.8, 147.3, 148.1, 148.2.
d
¼113.5, 114.7, 117.2, 123.5, 130.0, 134.3, 136.9,
4.3.17. 6-(Pyridin-3-yl)-2-(4-methylphenyl)benzoxazole (3qa). Yellow
solid, mp 133e134 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.92 (s,1H), 8.63
4.3.9. 3-(4-Aminophenyl)pyridine
(3ia).17 Yellow
solid,
mp
(s, 1H), 8.17 (d, J¼8.08 Hz, 2H), 7.94 (d, J¼7.80 Hz, 1H), 7.84 (d,
J¼8.2 Hz, 1H), 7.78 (s, 1H), 7.58e7.56 (m, 1H), 7.43e7.40 (m, 1H), 7.35
108e109 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.79 (d, J¼1.44 Hz, 1H),
8.50 (d, J¼4.04 Hz, 1H), 7.80 (d, J¼7.88 Hz, 1H), 7.40 (d, J¼8.56 Hz,
(d, J¼8.00 Hz, 2H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3):
¼30.9,
d
2H), 7.23e7.32 (m, 1H), 6.78 (d, J¼8.36 Hz, 2H), 3.79 (s, 2H); 13C
109.1, 120.2, 123.7, 124.0, 124.1, 127.6, 129.7, 134.6, 135.1, 142.4, 148.4,
148.5, 151.3, 164.1; HRMS-ESI (m/z): [MþH]þ calcd for C19H15N2Oþ:
287.1179, found: 287.1180.
NMR (100 MHz, CDCl3):
d
¼115.5, 123.4, 127.8, 128.0, 133.4, 136.5,
146.60, 147.4, 147.7; HRMS-ESI (m/z): [MþH]þ calcd for C11H11N2þ:
171.0917, found: 171.0919.
4.3.18. 6-(Pyridin-3-yl)-2-phenylbenzoxazole (3ra). Yellow solid,
4.3.10. 4-(Pyridin-3-yl)benzaldehyde (3ja). White solid, mp
mp 98e99 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.91 (s, 1H), 8.62 (d,
50e51 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼10.09 (s, 1H), 8.90 (d,
J¼4.04 Hz, 1H), 8.27e8.25 (m, 2H), 7.90 (d, J¼7.88 Hz, 1H), 7.83 (d,
J¼1.76 Hz, 1H), 8.68e8.66 (m, 1H), 8.00 (d, J¼8.24 Hz, 2H), 7.93 (d,
J¼8.20 Hz, 1H), 7.76 (s, 1H), 7.57e7.52 (m, 4H), 7.40e7.38 (m, 1H);
J¼7.88 Hz, 1H), 7.76 (d, J¼8.20 Hz, 2H), 7.41e7.44 (m, 1H); 13C NMR
13C NMR (100 MHz, CDCl3):
129.0, 131.8, 134.6, 135.3, 136.3, 142.1, 148.5, 148.6, 151.4, 163.8;
HRMS-ESI (m/z): [MþH]þ calcd for C18H13N2Oþ: 273.1022, found:
273.1027.
d
¼109.2, 120.4, 123.7, 124.1, 126.9, 127.7,
(100 MHz, CDCl3):
d
¼123.8, 127.8, 127.8, 130.5, 130.5, 134.6, 135.3,
135.8, 143.8, 148.4, 149.6, 191.8; HRMS-ESI (m/z): [MþH]þ calcd for
C12H10NOþ: 184.0757, found: 184.0758.
4.3.11. 3-(4-(Methoxycarbonyl)phenyl)pyridine (3ka).18 Yellow solid,
4.3.19. 6-(Pyridin-3-yl)-2-(4-fluorophenyl)benzoxazole (3sa). White
mp 96e97 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.86 (s, 1H), 8.62 (s,
solid, mp 133e134 ꢀC; 1H NMR (400 MHz, CDCl3):
d¼8.92 (s, 1H),
1H), 8.11 (d, J¼8.28 Hz, 2H), 7.88 (d, J¼7.92 Hz, 1H), 7.63 (d,
8.64 (s, 1H), 8.30e8.23 (m, 2H), 7.93 (d, J¼7.40 Hz, 1H), 7.85
(d, J¼8.28 Hz, 1H), 7.78 (s, 1H), 7.58 (d, J¼8.16 Hz, 1H), 7.41e7.43
(m, 1H), 7.24 (s, 1H), 7.22 (s, 1H); 13C NMR (100 MHz, CDCl3):
J¼8.32 Hz, 2H), 7.38e7.35 (m, 1H), 3.92 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
¼52.3, 123.7, 127.1, 130.4, 134.5, 142.2, 148.4, 149.3, 166.7;
HRMS-ESI (m/z): [MþH]þ calcd for C13H12NOþ2 : 214.0863, found:
d
¼109.2, 116.2, 116.4, 120.4, 123.7, 124.2, 129.9, 130.0, 134.6,
214.0866.
135.4, 136.3, 142.1, 148.5, 148.7, 151.4, 163.0, 163.7, 166.2; HRMS-
ESI (m/z): [MþH]þ calcd for C18H12FN2Oþ: 291.0928, found:
291.0936.
4.3.12. 1-[4-(Pyridin-3-yl)phenyl]ethanone (3la).19 Yellow solid, mp
74e75 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼8.89 (s, 1H), 8.66 (s, 1H),
8.07 (d, J¼7.96 Hz, 2H), 7.91 (d, J¼7.52 Hz, 1H), 7.68 (d, J¼7.92 Hz,
4.3.20. 2-(4-Methoxyphenyl)pyridine (3cc).21 Yellow solid, mp
2H), 7.40e7.42 (m, 1H), 2.65 (s, 3H); 13C NMR (100 MHz, CDCl3):
38e39 ꢀC; 1H NMR (400 MHz, CDCl3):
J¼8.80 Hz, 2H), 7.68e7.70 (m, 2H), 7.18e7.17 (m, 1H), 7.01e6.99 (m,
d
¼8.65e8.66 (m, 1H), 7.95 (d,
d¼26.7, 123.7, 127.3, 129.1, 134.5, 135.4, 136.5, 142.3, 148.3, 149.3,

G. Ma et al. / Tetrahedron 69 (2013) 902e909
909
2H), 3.87 (s, 3H); 1H NMR (100 MHz, CDCl3):
121.4, 128.2, 136.7, 149.5, 157.1, 160.4.
d¼55.4, 114.1, 119.8,
2002, 41, 4176; (d) Es-pinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004,
43, 4704.
6. (a) Jin, M.-J.; Lee, D.-H. Angew. Chem., Int. Ed. 2010, 49, 1119; (b) Hajipour, A. R.;
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Tetrahedron 2011, 67, 6191.
4.3.21. 3-(4-Hydroxyphenyl)pyridine (3ta).22 White solid, mp
203e205 ꢀC.
4.3.22. 2,20-Bipyridine (3ua).23 White solid, mp 70e72 ꢀC; 1H NMR
(400 MHz, CDCl3)
8.37e8.39 (m, 2H), 8.68e8.69 (m, 2H).
d
¼7.31e7.28 (m, 2H), 7.81e7.78 (m, 2H),
8. Ren, G.-R.; Cui, X.-L.; Yang, E.-B.; Yang, F.; Wu., Y. J. Tetrahedron 2010, 66, 4022.
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Acknowledgements
We are grateful to the National Natural Science Foundation of
China (No. 20772114, 21172200) and the Innovation Fund for Out-
standing Scholar of Henan Province (No. 0621001100) for financial
support of this research. We thank Professor Ding Kuiling for
valuable discussion and comments on this paper.
13. Jin, Z.; Gu, X. P.; Qiu, L. L.; Wu, G. P.; Song, H. B.; Fang, J. X. J. Organomet. Chem.
2011, 696, 859.
14. Ye, M. C.; Gao, G. L.; Edmunds, A. J. F.; Worthington, P. A.; Morris, J. A.; Yu, J. Q.
J. Am. Chem. Soc. 2011, 133, 19090.
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