Palladium-catalyzed direct ortho C-H arylation of 2-arylpyridine derivatives with aryltrimethoxysilane

Article abstract of DOI:10.1021/jo2016168

A Pd(OAc)₂-catalyzed cross-coupling reaction between 2-arylpyridine and aryltrimethoxysilane in the presence of AgF and BQ in 1,4-dioxane was studied. After various reaction parameters (catalyst, oxidant, additive, solvent and reaction temperat

Full text of DOI:10.1021/jo2016168

NOTE
pubs.acs.org/joc
Palladium-Catalyzed Direct Ortho CꢀH Arylation of 2-Arylpyridine
Derivatives with Aryltrimethoxysilane
Wu Li, Zhangwei Yin, Xiaoqing Jiang, and Peipei Sun*
College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210097, China
S Supporting Information
b
ABSTRACT: A Pd(OAc)2-catalyzed cross-coupling reaction
between 2-arylpyridine and aryltrimethoxysilane in the presence
of AgF and BQ in 1,4-dioxane was studied. After various reaction
parameters (catalyst, oxidant, additive, solvent and reaction
temperature) were examined, the optimal conditions for the
reaction were identified. The synthesis is compatible to aryltri-
methoxysilane with both electron-withdrawing and electron-
donating groups on the aryl moiety with moderate yields. The
kinetic isotope effect (kH/kD) for the CꢀH bond activation was provided.
olyaromatic motifs are very often found in natural products
and pharmaceuticals. Polyaromatics also possess some in-
advantages such as environmental benignity, low toxicity, atomic
efficiency, and safe handling.7 Herein, we present the first direct
cross-coupling reaction between 2-arylpyridine derivatives and
trialkyloxyarylsilanes via CꢀH bond activation using a palladium
catalyst.
P
trinsic physical properties and therefore have potential applica-
tions in research fields of dyes, organic semiconductors, and
other advanced materials. Di- or triaromatic rings, especially
phenyl heterocycles, are the backbone of some of the most
efficient and selective ligands for asymmetric catalysis, especially
when atropisomery is possible.1 Thus, developing more efficient
methods to construct these building blocks has received con-
siderable attention in recent years.
As an initial experiment, we began our investigation by testing
the reaction of 2-phenylpyridine (1a) with trimethoxyphenylsi-
lane (2a) in the presence of a catalytic amount of Pd catalyst. The
screening of the reaction conditions is summarized in Table 1. It
was found that the nature of oxidant, additive, and solvent, as well
as the catalyst, may play a critical role on the reaction efficiency.
In the absence of Pd catalyst, the reaction cannot proceed at all.
Pd(OAc)2 showed evidently catalytic activity to the reaction, and
the appropriate amount of the catalyst was 10 mol %. Decreasing
the amount of Pd(OAc)2 to 5 mol % might bring about a
decrease of the yield (entry 2). Other palladium species such
as PdCl2 and Pd(PPh3)4 were substantially less effective (entries
15 and 16). Fluorine compound was beneficial to the reaction of
trialkyloxyarylsilanes due to its activation to organosilane.8 AgF
was proved to be an efficient fluoride source, while the effects of
tetra-n-butylammonium fluoride (TBAF) and NaF were poor
(entries 3ꢀ6). We envisioned that AgF might play more roles
than just a simple fluoride source; it may also serve as a co-
oxidant with benzoquinone (BQ) to oxidize a Pd(0) species back
to Pd(II) to fulfill the catalytic cycle. When 1 equiv of BQ was
presented in the reaction mixture, the desired product was
obtained in 62% yield. In the absence of BQ, almost no formation
of the desired product was observed. We therefore conclude that
BQ is also an essential reagent in the transmetalationꢀreductive
elimination step, as the related reports suggest.6a,b And yet, other
common oxidants such as Ag2O and Cu(OTf)2 were not efficient
for this transformation (entries 8ꢀ10). The different solvents
Arylꢀaryl bond formation is one of the most important tools
to make up polyaromatic structures, thanks to its ability to couple
two sophisticated moieties under mild conditions. Transition-
metal-catalyzed biaryl cross-coupling reactions, which generally
employ aryl halides and organometallics as coupling partners,
have served as the most common methods for constructing biaryl
unions.2 As a potential green and efficient process to construct
complicated structures from simple and commercially available
chemicals, the development of methods for direct transformation
of a CꢀH bond into a CꢀC bond continues to be an important
challenge in organic synthesis and catalysis in recent years.3
These reactions generally involve directing-group-assisted acti-
vation of sp2 CꢀH bonds of ortho aromatic CꢀH bonds. Many
directing groups, such as acetyl, acetamino, carboxylic acid,
oxazolyl, pyridyl, hydroxyl, imino, and cyano moieties, have been
used for CꢀH bond activation.4 Mechanistic studies indicated
that aromatic CꢀH bonds can be activated via a five-membered
metallacycles. An attractive one among many approaches is
cross-coupling of a CꢀH bond with an organometallic reagent
under oxidative conditions.5 Although many groups have re-
ported palladium-catalyzed direct arylation or alkylation to
aromatic CꢀH bond with organometallic compounds, especially
organoboronic acids or organotin compounds,6 there are still
very few studies on the direct coupling using organosilanes by
CꢀH functionalization even though this method possesses
Received: August 3, 2011
Published: September 13, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo2016168 J. Org. Chem. 2011, 76, 8543–8548
|

The Journal of Organic Chemistry
NOTE
Table 1. Optimization of the Reaction Conditionsa
group such as cyano or ester group gave the desired products, though
the yields were not very high (entries 19ꢀ22). This palladium-
catalyzed arylation had very good regioselectivity, and no diary-
lated products or other byproducts were isolated.
A possible mechanism for the present palladium(II)-catalyzed
ortho arylation of 2-phenylpyridine (1a) via CꢀH bond activa-
tion is proposed, as shown in Scheme 1. First, the reaction of
Pd(OAc)2 with 2-phenylpyridine (1a) afforded a cyclopalladated
intermediate 4, which was actually confirmed by many related
reports.6b,9 This intermediate reacted with the in situ generated
pentavalent silicate to form the (aryl)(2-phenylpyridine)palladi-
um(II) species 5 in which benzoquinone could act as a ligand to
coordinate with palladium.9a,10 The subsequent reductive elim-
ination liberated the arylated 2-phenylpyridine, and the released
palladium(0) was reoxidized by Ag(I) and p-benzoquinone to
regenerate palladium(II), which would continue the catalytic
cycle. The high regioselectivity could also provide strong evi-
dence to support this step.
entry catalyst (mol %) solvent
additive (equiv)
yield (%)
1
2
3
4
5
6
7
8
9
none
dioxane AgF (2.0)/BQ (1.0)
0
Pd(OAc)2 (5.0) dioxane AgF (2.0)/BQ (1.0)
Pd(OAc)2 (10.0) dioxane AgF (2.0)/BQ (1.0)
Pd(OAc)2 (10.0) dioxane TBAF (2.0)/BQ (1.0)
Pd(OAc)2 (10.0) dioxane NaF (2.0)/BQ (1.0)
Pd(OAc)2 (10.0) dioxane BQ (1.0)
29
62 (25)b
20
0
0
Pd(OAc)2 (10.0) dioxane AgF (2.0)
trace
trace
trace
Pd(OAc)2 (10.0) dioxane Ag2O (2.0)/BQ (1.0)
Pd(OAc)2 (10.0) dioxane AgF (2.0)/Ag2O (1.0)
The kinetic isotope effect was investigated by using 2-
(o-deuteriophenyl)pyridine (1a-D) to react with 2a to form
3aa and 3aa-D (Scheme 2). The kH/kD ratio for the CꢀH bond
activation when (trimethoxy) phenylsilane (2a) was used was
10 Pd(OAc)2 (10.0) dioxane AgF (2.0)/Cu(OTf)2 (1.0) 23
11 Pd(OAc)2 (10.0) H2O
AgF (2.0)/BQ (1.0)
0
12 Pd(OAc)2 (10.0) toluene AgF (2.0)/BQ (1.0)
trace
trace
trace
trace
47
1
determined to be 1.02 (compared with the standard H NMR
13 Pd(OAc)2 (10.0) DMF
14 Pd(OAc)2 (10.0) NMP
AgF (2.0)/BQ (1.0)
AgF (2.0)/BQ (1.0)
spectrum of 3aa). This indicated that the palladium(II)-catalyzed
CꢀH bond cleavage of 2-phenylpyridine (1a) did not occur in
the rate determining step. Thus, the reaction of the palladacycle
with trialkyloxyarylsilanes was still a viable option for the rate-
determining step, similar to the reaction of 2-phenylpyridine with
arylboronic compound.9a
In conclusion, we have developed a new catalytic system for
the arylation of pyridine derivatives with arylsiloxanes through
the CꢀH functionalization reaction, which allows efficient
synthesis of a variety of pyridine derivatives. It was also a new
example of the direct coupling using organosilanes by CꢀH
functionalization.
15 PdCl2 (10.0)
dioxane AgF (2.0)/BQ (1.0)
16 Pd(PPh3)4 (10.0) dioxane AgF (2.0)/BQ (1.0)
a Reaction conditions: 2-phenylpyridine (1a) (1.0 mmol), trimethox-
yphenylsilane (2a) (2.0 mmol), catalyst (10 mol %), additive (2.0 mmol),
oxidant (1.0 mmol), and solvent (4.0 mL) at 110 °C for 24 h. b Reaction
proceeded at 80 °C.
were also screened, and dioxane was shown to be most suitable
for this transformation, while no reactions occurred in H2O,
toluene, DMF, and NMP (entries 11ꢀ14). Low reaction tem-
perature led to the low conversion (entry 3). When the reaction
was carried out at 80 °C, a low yield of 25% was given, but a yield
of 62% was obtained while the reaction proceeded at 110 °C. As
the temperature was further increased to 120 °C, no obvious
increase of the yield was observed. The reaction could finish in
24 h. Thus, the reaction efficiently proceeded when 10 mol %
of Pd(OAc)2 was used as a catalyst in combination with AgF
(2 equiv) and BQ (1 equiv) in dioxane at 110 °C.
With the optimized reaction conditions in hand, different
trialkyloxyarylsilanes were surveyed (Table 2). In general, the
reactions of arylsilanes with electron-donating groups in the
aromatic ring gave higher yields than those with the electron-
deficient groups. But when the polycyclic arylsilane such as
trimethoxy(naphthalen-1-yl)silane was used, only trace corre-
sponding product was obtained, which may be attributed to the
steric hindrance of the polycyclic group (entry 23). It is worth
pointing out that the chloro group on the aromatic ring could
remain in the product. The tolerance of the reaction for CꢀCl bond
in arylsilanes ensures that it could be further transformed into
different functionalities (entries 6 and 18). The reactions of
2-arylpyridine derivatives with several substituents on the phenyl
ring were also studied. In the presence of o-, m-, and p-methyl, as well
as p-methoxyl on the phenyl ring, the reaction gave the desired
products with moderate yields. Unfortunately, almost no targeted
products were isolated as a strong electron-withdrawing group nitro
was substituted on the phenyl ring (entries 24 and 25), while the
reaction of 2-arylpyridines with moderate electron-withdrawing
’ EXPERIMENTAL SECTION
General Methods. All reactions were run in oven-dried flasks
under nitrogen. Unless otherwise noted, reagents were commercially
1
available and were used without purification. H NMR and 13C NMR
spectra were recorded in CDCl3 [using (CH3)4Si (for 1H, δ = 0.00; for
13C, δ = 77.00) as internal standard]. The following abbreviations were
used to explain the multiplicities: s = singlet, d = doublet, t = triplet, m =
multiplet. Melting points are uncorrected.
General Experimental Procedures and Characterizations.
A seal tube (15 mL) initially fitted with a septum containing Pd(OAc)2
(22 mg, 0.10 mmol), silver(I) fluoride (253 mg, 2.00 mmol), and BQ
(108 mg, 1.00 mmol) was evacuated and purged with nitrogen gas three
times. 1,4-Dioxane (4 mL), arylpyrimidines (1.00 mmol), and trimethy-
loxyarylsilanes (2.0 mmol) were added to the system, and the reaction
mixture was stirred at 110 °C for 24 h. The mixture was filtered through a
short Celite pad and washed with dichloromethane several times. The
filtrate was concentrated by vacuum and separated on a silica gel column
using hexane/EtOAc as eluent to give the corresponding pure ortho-
arylated 2-phenylpyridine derivatives.
2-(Biphenyl-2-yl)pyridine (3aa).9b Light yellow oil. 1H NMR (CDCl3,
400 MHz):δ 8.67 (d, J = 2.4Hz, 1H), 7.73ꢀ7.74 (m, 1H), 7.49ꢀ7.50 (m,
3H), 7.42 (t, J = 7.3 Hz, 1H), 7.26ꢀ7.29 (m, 3H), 7.19ꢀ7.20 (m, 2H),
7.12 (t, J = 5.6 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100
MHz): δ 159.3, 149.4, 148.5, 141.8, 141.3, 140.6, 139.5, 135.2, 134.9,
128.2, 127.6, 126.7, 125.4, 121.4, 120.9.
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NOTE
Table 2. Reaction Results of 2-Arylpyridine Derivatives with Trialkyloxyarylsilanesa
a All of the reactions were carried out using pyridine derivatives 1 (1.0 mmol), trialkyloxyarylsilanes 2 (2.0 mmol), Pd(OAc)2 (10 mol %), AgF (2.0 mmol),
and BQ (1.0 mmol) in dioxane (4.0 mL) at 110 °C for 24 h.
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NOTE
2-[2-(4-Methylphenyl)]phenylpyridine (3ab).11 Light yellow oil. 1H
NMR (CDCl3, 400 MHz): δ 8.67 (d, J = 3.2 Hz, 1H), 7.70ꢀ7.71 (m,
1H), 7.40ꢀ7.47 (m, 4H), 7.13 (t, J = 5.6 Hz, 1H), 7.06ꢀ7.07 (m, 4H),
6.92 (d, J = 7.8 Hz, 1H), 2.34 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ
158.9, 149.1, 141.1, 140.3, 139.2, 134.9, 130.2, 129.4, 128.2, 127.7, 126.4,
125.1, 121.0, 22.4.
(d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100
MHz): δ 159.0, 149.5, 139.8, 139.4, 139.3, 135.6, 132.8, 131.0, 128.3,
127.9, 126.8, 125.3, 121.6.
1
2-(3-Methylbiphenyl-2-yl)pyridine (3ba).13 Colorless oil. H NMR
(CDCl3, 400 MHz): δ 8.61 (d, J = 4.8 Hz, 1H), 7.43ꢀ7.45 (m, 1H), 7.33
(d, J = 8.0 Hz, 1H), 7.24ꢀ7.26 (m, 2H), 7.09ꢀ7.12 (m, 3H), 7.04ꢀ7.08
(m, 3H), 6.86 (d, J = 8.0 Hz, 1H), 2.17 (s, 3H) 13C NMR (CDCl3, 100
MHz): δ 159.6, 148.8, 141.7, 141.3, 139.3, 136.7, 135.7, 129.6, 129.4,
128.0, 127.6, 127.5, 126.2, 125.6, 121.3, 20.5.
2-[2-(3-Methylphenyl)]phenylpyridine (3ac).12 White solid. Mp =
88ꢀ89 °C (lit.12 mp 90ꢀ91 °C). 1H NMR (CDCl3, 400 MHz): δ 8.66
(d, J = 4.5 Hz, 1H), 7.70ꢀ7.71 (m, 1H), 7.41ꢀ7.49 (m, 4H), 7.10ꢀ7.15
(m, 2H), 7.03ꢀ7.05 (m, 2H), 6.92 (d, J = 8.0 Hz, 2H), 2.27 (s, 3H). 13C
NMR (CDCl3, 100 MHz): δ 159.7, 149.1, 141.2, 137.8, 131.9, 130.3,
127.9, 127.6, 126.8, 125.5, 120.9, 115.7, 113.2, 22.7.
2-(4-Methylbiphenyl-2-yl)pyridine (3ca).9b Yellow oil. 1H NMR
(CDCl3, 400 MHz): δ 8.62 (d, J = 4.4 Hz, 1H), 7.51 (s, 1H), 7.28ꢀ7.36
(m, 2H), 7.24ꢀ7.25 (m, 1H), 7.19ꢀ7.21 (m, 3H), 7.07ꢀ7.13 (m, 3H),
6.84 (d, J = 8.0 Hz, 1H), 2.43 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ
159.1, 149.1, 141.0, 138.9, 137.5, 137.1, 134.8, 130.8, 130.2, 129.4, 129.0,
127.7, 126.2, 125.2, 121.0, 20.8.
2-[2-(4-Methoxyphenyl)]phenylpyridine (3ad).11 Light yellow oil.
1H NMR (CDCl3, 400 MHz): δ 8.65 (d, J = 4.8 Hz, 1H), 7.68ꢀ7.70 (m,
1H), 7.43ꢀ7.46 (m, 4H), 7.08ꢀ7.13 (m, 3H), 6.91 (d, J = 8.0 Hz, 1H),
6.78 (d, J = 8.0 Hz, 2H), 3.79 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ
159.4, 158.3, 149.4, 140.2, 139.3, 135.3, 133.7, 130.8, 130.5, 130.4, 128.5,
127.3, 125.4, 121.3, 113.5, 55.2.
1
2-(30-Methyl-4-methylbiphenyl-2-yl)pyridine (3cc). Yellow oil. H
NMR (CDCl3, 400 MHz): δ 8.66 (d, J = 4.4 Hz, 1H), 7.55 (s, 1H),
7.35ꢀ7.41 (m, 2H), 7.28 (d, J = 8.5 Hz, 1H), 7.10 (t, J = 7.2 Hz, 2H),
7.03 (d, J = 8.8 Hz, 2H), 6.90 (t, J = 7.2 Hz, 2H), 2.47 (s, 3H), 2.28 (s,
3H). 13C NMR (CDCl3, 100 MHz): δ 159.2, 149.1, 141.2, 140.8, 139.1,
137.7, 135.3, 130.5, 130.4, 128.6, 127.9, 127.6, 127.5, 126.9, 125.5, 121.4,
22.7, 21.4. HRMS (ESI): calcd for C19H17N[H] 260.1439, found
260.1440.
2-[2-(3-Methoxyphenyl)]phenylpyridine (3ae).11 Light yellow oil.
1H NMR (CDCl3, 400 MHz): δ 8.66 (d, J = 4.6 Hz, 1H), 7.71ꢀ7.73 (m,
1H), 7.48ꢀ7.50 (m, 3H), 7.42ꢀ7.44 (m, 1H), 7.12ꢀ7.19 (m, 2H), 6.95
(d, J = 8.0 Hz, 1H), 6.79 (d, J = 8.0 Hz, 2H), 6.70 (s, 1H), 3.65 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 159.0, 158.9, 149.1, 142.4, 140.2,
139.2, 135.0, 130.0, 130.1, 128.8, 128.2, 127.4, 125.1, 121.9, 121.1, 114.6,
112.6, 54.8.
2-(40-Methoxy-4-methylbiphenyl-2-yl)pyridine (3 cd).13 Colorless
1
solid. Mp: 86ꢀ87 °C (lit.13 mp 88ꢀ89 °C). H NMR (CDCl3, 400
2-[2-(4-Chlorophenyl)]phenylpyridine (3af).9b Light yellow solid.
Mp: 95ꢀ96 °C (lit.9b mp 96.1ꢀ97.6 °C). 1H NMR (CDCl3, 400 MHz):
δ 8.65 (d, J = 4.4 Hz, 1H), 7.69ꢀ7.71 (m, 1H), 7.51ꢀ7.48 (m, 3H),
7.41ꢀ7.43 (m, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.15ꢀ7.16 (m, 1H), 7.10
MHz): δ 8.66 (d, J = 4.8 Hz, 1H), 7.53 (s, 1H), 7.39 (t, J = 6.4 Hz, 1H),
7.32 (d, J = 7.8 Hz, 1H), 7.27 ꢀ7.29 (m, 1H), 7.12ꢀ7.14 (m, 1H), 7.06
(d, J = 8.4 Hz, 2H), 6.89 (d, J = 7.8 Hz, 1H), 6.77 (d, J = 8.4 Hz, 2H), 3.80
(s, 3H), 2.46 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 159.5, 158.4,
149.4, 139.1, 137.4, 137.1, 135.2, 133.7, 131.1, 130.7, 130.4, 129.3, 125.5,
121.3, 113.5, 55.2, 21.1.
Scheme 1. Proposed Reaction Mechanism
2-(30-Methoxy-4-methylbiphenyl-2-yl)pyridine (3ce). Yellow oil. 1H
NMR (CDCl3, 400 MHz): δ 8.67 (d, J = 4.4 Hz, 1H), 7.55 (s, 1H), 7.42
(t, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.12
(t, J = 7.6 Hz, 2H), 6.92 (d, J = 8.0 Hz, 1H), 6.75ꢀ6.78 (m, 2H), 6.68 (s,
1H), 3.56 (s, 3H), 2.47 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 159.1,
158.9, 149.0, 142.3, 138.9, 137.4, 137.2, 134.9, 130.7, 130.0, 129.0, 128.7,
125.1, 121.9, 121.0, 114.7, 112.4, 54.8, 22.4. HRMS (ESI): calcd for
C19H17NO[H] 276.1388, found 276.1396.
2-(5-Methylbiphenyl-2-yl)pyridine (3da).9b Yellow oil. 1H NMR
(CDCl3, 400 MHz): δ 8.64 (d, J = 4.4 Hz, 1H), 7.62 (d, J = 7.8 Hz,
1H), 7.36ꢀ7.40 (m, 2H), 7.24ꢀ7.32 (m, 4H), 7.16ꢀ7.19 (m, 2H),
7.11ꢀ7.12 (m, 1H), 6.87 (d, J = 7.8 Hz, 1H), 2.47 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 159.1, 149.0, 141.2, 140.2, 138.1, 134.9, 130.9,
130.2, 129.4, 128.2, 127.7, 127.3, 126.3, 125.1, 120.9, 20.9.
2-(40-Methoxy-5-methylbiphenyl-2-yl)pyridine (3dd).11 Yellow oil.
1H NMR (CDCl3, 400 MHz): δ 8.64 (d, J = 3.8 Hz, 1H), 7.60 (d, J = 7.8
Hz, 1H), 7.38 (t, J = 8.8 Hz, 2H), 7.25 (s, 1H), 7.12ꢀ7.07 (m, 3H), 6.88
(d, J = 7.8 Hz, 1H), 6.78 (d, J = 8.6 Hz, 2H), 3.81 (s, 3H), 2.46 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 158.0, 156.3, 141.3, 140.5, 130.6,
130.5, 129.9, 129.6, 127.0, 119.7, 116.0, 115.9, 113.1, 55.2, 21.2.
Scheme 2. Kinetic Isotope Effect
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NOTE
2-(30-Methoxy-5-methylbiphenyl-2-yl)pyridine (3de). Yellow oil. 1H
NMR (CDCl3, 400 MHz): δ 8.64 (d, J = 4.0 Hz, 1H), 7.66 (d, J = 8.4 Hz,
1H), 7.36 (t, J = 7.8 Hz, 1H), 7.07ꢀ7.10 (m, 5H), 7.00ꢀ7.03 (m, 1H),
132.8, 131.6, 130.8, 130.7, 130.4, 128.2, 125.4, 121.8, 113.7, 61.1, 55.2, 14.3;
HRMS (ESI): calcd for C21H19NO3[H] 334.1430, found 334.1443.
6.85 (s, 1H), 6.72 (d, J = 8.0 Hz, 1H), 3.90 (s, 3H), 2.35 (s, 3H). 13
C
’ ASSOCIATED CONTENT
NMR (CDCl3, 100 MHz): δ 159.3, 158.8, 149.0, 141.7, 138.1, 136.3,
134.8, 131.9, 131.6, 129.2, 128.6, 125.1, 120.6, 115.4, 112.8, 55.1, 20.5.
HRMS (ESI): calcd for C19H17NO[H] 276.1388, found 276.1392.
2-(5-Methoxybiphenyl-2-yl)pyridine (3ea).13 Colorless solid. Mp:
66ꢀ67 °C (lit.13 mp 68.5ꢀ69.5 °C). 1H NMR (CDCl3, 400 MHz): δ
8.60 (d, J = 4.8 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.33ꢀ7.35 (m, 1H),
7.23ꢀ7.25 (m, 3H), 7.16ꢀ7.18 (m, 2H), 7.06ꢀ7.07 (m, 1H), 7.00 (d,
J = 8.5 Hz, 1H), 6.95 (s, 1H), 6.80 (d, J = 7.8 Hz, 1H), 3.88 (s, 3H). 13C
NMR (CDCl3, 100 MHz): δ 158.6, 157.8, 148.2, 141.0, 140.3, 134.2,
130.9, 128.6, 127.1, 125.9, 124.4, 119.9, 114.7, 112.3, 54.4.
1
Supporting Information. H NMR and 13C NMR spectra
S
b
for all compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: sunpeipei@njnu.edu.cn.
2-(30-Methyl-5-methoxybiphenyl-2-yl)pyridine (3ec). Yellow oil. 1H
NMR (CDCl3, 400 MHz): δ 8.62 (d, J = 4.5 Hz, 1H), 7.67 (d, J = 8.5 Hz,
1H), 7.38 (t, J = 8.0 Hz, 1H), 7.01ꢀ7.12 (m, 5H), 6.92ꢀ6.96 (m, 2H),
6.84 (d, J = 8.0 Hz, 1H), 3.90 (s, 3H), 2.28 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 159.2, 149.1, 141.2, 140.8, 139.1, 137.7, 135.4, 130.5,
130.4, 128.6, 127.9, 127.6, 127.5, 126.9, 125.5, 121.4, 55.4, 22.7. HRMS
(ESI): calcd for C19H17NO[H] 276.1388, found 276.1390.
’ ACKNOWLEDGMENT
This work was supported by the National Natural Science
Foundation of China (Project 20972068), the Leading Academic
Discipline Program, 211 Project for Nanjing Normal University
(the third phase), and the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions.
2-(30-Methoxy-5-methoxybiphenyl-2-yl)pyridine (3ee). Yellow oil.
1H NMR (CDCl3, 400 MHz): δ 8.63 (d, J = 4.7 Hz, 1H), 7.68 (d, J = 8.4
Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.09 (t, J = 7.8
Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 7.00 (s, 1H), 6.87 (d, J = 8.0, 1H),
6.79ꢀ6.82 (m, 2H), 6.72 (s, 1H), 3.91 (s, 3H), 3.67 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 159.4, 158.9, 158.6, 148.9, 142.4, 141.5, 134.9,
131.9, 131.6, 128.8, 125.1, 121.8, 120.7, 115.3, 114.6, 113.1, 112.7, 55.2,
54.8. HRMS (ESI): calcd for C19H17NO2[H] 292.1338, found 292.1329.
2-(40-Chloro-5-methoxybiphenyl-2-yl)pyridine (3ef). Colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.59 (d, J = 4.2 Hz, 1H), 7.62 (d, J = 8.5
Hz, 1H), 7.34ꢀ7.42 (m, 2H), 7.19 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0
Hz, 2H), 6.99ꢀ7.01 (m, 1H), 6.89 (s, 1H), 6.82 (d, J = 8.0 Hz, 1H), 3.87
(s, 3H). 13C NMR (CDCl3, 100 MHz): δ 159.8, 158.6, 149.3, 140.7,
139.8, 135.6, 133.0, 132.0, 130.9, 128.3, 125.3, 121.2, 115.8, 113.4, 55.5.
HRMS (ESI): calcd for C18H14ClNO[H] 296.0842, found 296.0844.
2-(5-Cyanobiphenyl-2-yl)pyridine (3fa). Yellow oil. 1H NMR (CDCl3,
400 MHz): δ 8.67 (d, J = 4.4 Hz, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.73ꢀ7.75
(m, 2H), 7.41 (t, J = 8.0 Hz, 1H), 7.27ꢀ7.28 (m, 3H), 7.13ꢀ7.18 (m, 3H),
6.88 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 157.3, 149.8,
143.7, 141.8, 139.1, 135.6, 134.1, 131.4, 130.9, 129.4, 128.5, 127.7, 125.2,
122.3, 118.6, 112.3. HRMS (ESI): calcd for C18H12N2[H] 257.1079, found
257.1079.
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1
2-(40-Methoxy-5-cyanobiphenyl-2-yl)pyridine (3fd). Yellow oil. H
NMR (CDCl3, 400 MHz): δ 8.66 (d, J = 4.4 Hz, 1H), 7.78 (d, J = 8.0 Hz,
1H), 7.70ꢀ7.71 (m, 2H), 7.45 (t, J = 7.8 Hz, 1H), 7.16 ꢀ7.20 (m, 1H),
7.04 (d, J = 7.8 Hz, 2H), 6.90 (d, J = 8.0 Hz, 1H), 6.80 (d, J = 8.4 Hz, 2H),
3.80 (s,3H); 13C NMR (CDCl3, 100 MHz): δ 159.2, 157.5, 149.8, 143.5,
141.4, 135.6, 134.0, 131.4, 130.6, 128.6, 125.4, 122.2, 118.7, 113.9, 113.6,
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1
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149.5, 143.4, 140.4, 135.4, 131.7, 130.7, 130.4, 129.6, 128.6, 128.2, 127.6,
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8547
dx.doi.org/10.1021/jo2016168 |J. Org. Chem. 2011, 76, 8543–8548

The Journal of Organic Chemistry
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8548
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