Metal-Free Assembly of Polysubstituted Pyridines from Oximes and Acroleins

Article abstract of DOI:10.1021/acs.joc.5b02624

Transition-metal-catalyzed synthesis of N-heterocycles from oximes has been previously well established. In this paper, for the first time a metal-free protocol with the combinational employment of iodine and triethylamine has been demonstrated to be effective to trigger the oxime-based synthesis of pyridines with high chemo-selectivity and wide functional group tolerance. A broad range of functional pyridines were prepared in moderate to excellent yields. While neither iodine nor triethylamine could trigger this transformation, mechanistic experiments indicated a radical pathway for the reaction. The resultant 2-aryl-substituted pyridines have been proved to be versatile building blocks in a range of transition-metal-catalyzed C-H functionalization reactions. (Chemical Equation Presented).

Full text of DOI:10.1021/acs.joc.5b02624

Article
pubs.acs.org/joc
Metal-Free Assembly of Polysubstituted Pyridines from Oximes and
Acroleins
Huawen Huang,* Jinhui Cai, Lichang Tang, Zilong Wang, Feifei Li, and Guo-Jun Deng*
Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan
University, Xiangtan 411105, China
S
* Supporting Information
ABSTRACT: Transition-metal-catalyzed synthesis of N-heterocycles from
oximes has been previously well established. In this paper, for the first time
a metal-free protocol with the combinational employment of iodine and
triethylamine has been demonstrated to be effective to trigger the oxime-
based synthesis of pyridines with high chemo-selectivity and wide functional
group tolerance. A broad range of functional pyridines were prepared in
moderate to excellent yields. While neither iodine nor triethylamine could trigger this transformation, mechanistic experiments
indicated a radical pathway for the reaction. The resultant 2-aryl-substituted pyridines have been proved to be versatile building
blocks in a range of transition-metal-catalyzed C−H functionalization reactions.
oximes,5f in which the reaction conditions are quite mild by
employing electron-deficient benzoates as the leaving groups.
Particularly, oximes bearing α-methylene have a structural
INTRODUCTION
Functionalized pyridines represent privileged heterocycles,
■
which are widely found in natural products, functional
materials, and medicinal chemicals.1 Due to their high
advantage to provide, formally, the vinyl amine (CC−N)
moiety in the assembly of pyridines.6 In previous works, Cu
significance in industrial applications, the synthesis of
catalysts were well demonstrated to play key roles in the N−O
polysubstituted pyridines from acyclic precursors has been
attracting great interest in synthetic chemistry.2
bond activation of oximes, generally leading to imino radicals or
otherwise imino-[CuIII] species as the highly active interme-
Oxime chemistry is well-known for the classic Beckmann
diates.4c In view of sustainable development, chemical
rearrangement and Semmler−Wolff reaction as well as for the
procedures under metal-free conditions are always of
significance especially in the pharmaceutical industry, and that
synthetic manifold in organic preparation and industrial
application.3 In the past decade, oxime derivatives have proved
could also bring reduced environmental disruption to water and
to be versatile building blocks with a range of transition-metal
soil.7 Given the state of iodine-catalyzed transformation8 and
catalysts, such as of Pd, Cu, Rh, and Ru, especially for the
construction of nitrogen-containing heterocycles (Scheme 1a).4
our previous work, we questioned whether a metal-free and
mild protocol could be devised for the oxime-based heterocycle
synthesis. Herein we disclose for the first time a metal-free
system for the synthesis of substituted pyridines by the
intermolecular assembly of ketoximes and α,β-unsaturated
aldehydes. In such a transformation, iodine was demonstrated
to be highly effective for the 1e− reduction of oximes (Scheme
1c), generating an imino radical which reacts with cinnamalde-
hyde with high efficiency to give functionalized pyridines.
Scheme 1. N-Containing Heterocycle Synthesis from Oxime
Esters
RESULTS AND DISCUSSION
■
We commenced our investigation using O-acetyl ketoxime 1a
and α,β-unsaturated aldehyde 2a as the model system (Table
1). Initially, a mixture of two isomers of pyridines (3a and 3a′)
was observed when adding iodine to the system (Table 1, entry
1), while the sole treatment with triethylamine gave the
pyridines with a chemoselectivity of 1:1, albeit in a low yield
(Table 1, entry 2). Delightedly, when we combined I2 with
triethylamine in the reaction system, pyridine 3a was exclusively
Besides, the homolysis of the oxime N−O bond under
microwave or UV irradiation followed by radical cyclization
was also utilized to generate several heterocycles (Scheme 1b).5
Very recently, Yu and Zhang reported a visible-light-triggered
imino radical generation for the efficient preparation of
pyridines, quinolines, and phenanthridines from O-acyl
Received: November 16, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02624
J. Org. Chem. XXXX, XXX, XXX−XXX

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a
mediated system (Scheme 2). Generally, aromatic methylox-
imes employed reacted smoothly to give the corresponding
Table 1. Optimization of Reaction Conditions
a
Scheme 2. Scope of Oximes for the Metal-Free Cyclization
b
entry
add. x
add. y
solvent
yield
3a/3a′
1
2
3
4
5
6
7
I2
none
Et3N
Et3N
Et2NH
iPr2NH
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMSO
DMF
16
9
8:1
none
1:1
I2
86
50
54
70
>99:1
>99:1
>99:1
>99:1
−
I2
I2
NIS
PhI(OAc)2
trace
trace
78
c
8
KI
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
−
d
9
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
e
10
35
f
11
80
g
12
78
h
13
50
i
14
84
15
16
17
18
19
43
40
PhCl
36
PhOMe
CH3CN
toluene
45
65
j
20
76
a
Unless otherwise noted, the reaction was performed in a sealed tube
with oxime ester (0.2 mmol, 1.0 equiv), aldehyde (0.3 mmol, 1.5
equiv), additive x (0.1 mmol, 50 mol %), additive y (0.1 mmol, 50 mol
b
%) in toluene (1.0 mL) at 120 °C for 3 h. Determined by GC analysis
c
with dodecane as an internal standard. Under an O2 atmosphere.
d
e
f
g
Using 40 mol % of I2. Using 20 mol % of I2. Under oxygen. Under
a
Reaction conditions: Oxime derivatives (0.5 mmol), enal derivatives
h
i
j
argon. At 110 °C. At 130 °C. Gram-scale reaction was conducted
(0.75 mmol), I2 (0.25 mmol), and Et3N (0.25 mmol) in 2.5 mL of
toluene at 120 °C for 3 h. Products 3a−w formed from the oximes
derived from methyl ketones, i.e., R′ = H.
(oxime 10 mmol, 1 equiv).
generated and the yield was enhanced to 86% (Table 1, entry
3). Secondary aliphatic amines such as Et2NH and Pr2NH led
i
to reduced yields of the desired product (Table 1, entries 4 and
5), which indicates a distinct reaction pathway from the
previously reported copper-catalyzed system.6b Other iodine
reagents did not improve the yield. While NIS, being also able
to serve as a radical initiator, gave a slightly decreased yield
(Table 1, entry 6), PhI(OAc)2 and KI quenched the desired
transformation completely (Table 1, entries 7 and 8). For the
loading of I2, the employment of 0.4 equiv and 0.2 equiv of I2
afforded 3a in 78% and 35% yield, respectively (Table 1, entries
9 and 10). Then we found that the reaction received slight
collapse in the yield when treated under oxygen or argon
atmosphere (Table 1, entries 11 and 12). Then the reaction
temperature was tested, which revealed that the reaction
performed at 120 °C gave the highest yield of the pyridine
product, and a dramatic decrease in yield was observed when
the reaction temperature was reduced to 110 °C (Table 1,
entries 13 and 14). The screening of a series of solvents
indicated that polar solvents such as DMSO and DMF
disfavored the desired transformation (entries 15−19) and
that toluene was the best reaction media. Finally, gram-scale
reaction using 10 mmol of 1a was then conducted, which gave a
good yield of 3a (entry 20).
pyridines in good to excellent yields (Scheme 2, 3a−t, 63−
92%), regardless of the functional groups at the para-, meta-, or
ortho-position. A large range of functional groups on the
benzene ring such as alkyl (3b−d), phenyl (3e), methoxyl (3f),
fluoro (3g), chloro (3h, 3m, 3q, and 3s), bromo (3i and 3n),
iodo (3j), nitro (3l, 3o, and 3r), and trifluoromethyl (3p) were
all tolerated well. The electronic effects of the substituents on
the yield are elusive with the fact that methoxyl and nitro
groups showed the same efficiency (3f and 3l). However, the
steric effects of the substituents are apparent (p-Cl 87% vs o-Cl
66% and p-NO2 84% vs o-NO2 67%), and the oximes with an
iodo group afforded relatively low yield (3j). Naphthyl oxime
furnished the corresponding product 3t in moderate yield.
Heteroaromatic oximes produced furyl, thienyl, and pyridyl
products (3u−w) with a big gap in the yield, and only the
thienyl substrate among them gave an excellent yield of the
corresponding pyridine. While non-methyl oximes could also
transfer into the desired products in good yields (3x−z), very
low yield of the products could be observed when using
aliphatic methyl oximes derived from, for example, cyclo-
hexanone and cyclopropylmethylketone in the present system.
Subsequently, a range of substituted α,β-unsaturated
aldehydes were evaluated (Scheme 3). All the cinnamaldehydes
screened performed very well when the substitution group was
located at the benzene ring (Scheme 3, 4a−d). Analogously,
With the optimized conditions established, the scope and
generality of the cyclization were probed. Various substituted
acetophenone oxime acetates were first tested in the I2/Et3N-
B
DOI: 10.1021/acs.joc.5b02624
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Scheme 3. Scope of Acroleins for the Metal-Free
a
Cyclization
aldehydes likewise via reductive condensation, affording
exclusively pyridines of symmetry such as 4i′.6a,d
The resultant 2-arylpyridines were often used in the directed
C−H activation, and a large range of functional groups can be
embedded in the aryl ortho-position and meta-position.10 Our
further manipulations for the resultant pyridines started with
the palladium-catalyzed acylation of 3h (Scheme 4, i), and the
a
Scheme 4. Derivation of the Resultant 2-Arylpyridines
a
Reaction conditions: oxime derivatives (0.5 mmol), enal derivatives
(0.75 mmol), I2 (0.25 mmol), Et3N (0.25 mmol) in 2.5 mL toluene at
120 °C for 3 h.
there seems to be no steric effect among those substituents (4a
vs 4d), which, in connection of the previous observation,
indicates that the reaction probably proceeds via a radical
procedure. Notably, when we tested the 3-furylacrolein, the
corresponding adduct 4e was obtained in 90% yield. Then we
found that (E)-2-hexenal was also accommodated by the
system, which furnished the pyridine 4f in moderate yield.
Unfortunately, when the α-hydrogen of the carbonyl was
substituted by even a methyl, the reactions were dramatically
blocked, giving highly reduced yields of the products (4g,h).
Interestingly, we obtained the desired product 2-methyl-4,6-
diphenylpyridine 4i when enone 2i was used as the substrate,
albeit in a very low yield [eq 1]. However, a 4i analogue, i.e.,
a
Reaction conditions: (i) 3 (0.2 mmol), benzil (1.5 equiv), Pd(OAc)2
(3 mol %), TBHP (3 equiv), THF (0.8 mL), 100 °C, 12 h; (ii) 3a (0.2
mmol), 2-bromothiophene (2.5 equiv), [Ru(p-cymene)Cl2]2 (2.5 mol
%), KOAc (3 equiv), NMP (0.6 mL), 120 °C, 24 h; (iii) 3 (0.2 mmol),
Pd(OAc)2 (6 mol %), PhI(OAc)2 (2.5 equiv), CH3CN (1.25 mL), 100
°C, 12 h; (iv) 3a (0.2 mmol), sulfonyl chloride (3 equiv), [Ru(p-
cymene)Cl2]2 (5 mol %), K2CO3 (2 equiv), CH3CN (0.6 mL), 115
°C, 15 h.
2,4-bis(4-fluorophenyl)-6-methylpyridine, was also detected
with the treatment of substituted acetophenone oximes while
the desired corresponding 4j was not observed [eq 2], which
acylation product 5a was delivered in 88% yield. The arylation
of 3a was demonstrated by Ru-catalyzed ortho-dithienylation
using 2-bromothiophene, which gave the corresponding
product 6a in 81% yield (Scheme 4, ii). Moreover, Pd-
catalyzed ortho-acetoxylation of 3a and 3e furnished the
expected pyridines 7a and 7b, respectively, in good yields
(Scheme 4, iii). Finally, meta-functionalion of the pyridine 3a
was exemplified by Ru-catalyzed sulfurylation using 4-(tert-
butyl)benzene-1-sulfonyl chloride, which afforded the desired
product 8a in moderate yield (Scheme 4, iv).
indicated that the enone 2i was not involved in the cyclization.
Indeed, 4i was isolated in 38% yield in the absence of enals or
enones in the present system, in which the two-carbon moiety
of the Et3N was assembled into the pyridine 4i [eq 3]. To
further demonstrate this reasoning, Bu3N was used as the
substrate, which, as expected, gave 2-Pr-substituted pyridine 4k
in 44% GC yield [eq 4]. This observation is really interesting
while, in previous work, oximes such as 1a reacted with
C
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To get information about the reaction mechanism, some
control experiments were conducted. The addition of a radical
scavenger, such as TEMPO and BHT, to the reaction system
prevented the desired transformation completely (Scheme
5a,b). Furthermore, when we used Bn3N instead of Et3N in the
reaction system, Bn2NH and benzaldehyde were detected as the
main byproducts derived from the base (Scheme 5c).
therefore reasonable to utilize 0.5 equiv of Et3N as the electron
donor.9 For the fact that NIS could promote the reaction and
afford the pyridine product in good yield (Table 1, entry 6),
alternatively a condensation-based reaction pathway (path b)
was set out. 1,4-Dihydropyridine F may be the key
intermediate, which, on the assistance from iodine reagent,
eliminates a molecule of AcOH to afford the final pyridine.
Scheme 5. Mechanistic Study
CONCLUSION
■
In summary, we have developed a metal-free protocol for the
synthesis of polysubstituted pyridines from the O-acetyl
ketoximes and α,β-unsaturated aldehydes. The present strategy
features high chemoselectivity and excellent tolerance for a
broad range of functional groups. Moreover, the combinational
use of iodine and triethylamine has been demonstrated to be
robust to activate the N−O bond of oximes and enable the
assembly of pyridines, which also opens a new entry to oxime-
based N-heterocycle synthesis based on metal-free systems.
Further studies on the detailed mechanism and application in
the preparation of complex N-containing compounds are
currently in progress.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out under
standard conditions unless otherwise noted. Column chromatography
was performed using silica gel (200−300 mesh). H and 13C NMR
1
Based on the experimental observation, a plausible reaction
mechanism is proposed for the metal-free heterocyclization of
oximes and enals (Scheme 6). In path a as shown, I2-mediated
spectra were recorded on a 400 MHz NMR spectrometer, and the
chemical shifts are referenced to signals at 7.26 and 77.0 ppm,
respectively. Generally, chloroform was used as the solvent with TMS
as the internal standard. GC−MS data were obtained using electron
ionization. HRMS was carried out on a high-resolution mass
spectrometer (LCMS-IT-TOF). TLC was performed using commer-
cially available 100−400 mesh silica gel plates (GF254). The structure
of known compounds was further corroborated by comparing their 1H
NMR, 13C NMR, and MS data with those in the literature. Melting
points were measured with a melting point instrument without
correction. Oximes were prepared using a previous method.6b All other
reagents were obtained from commercial suppliers and used without
further purification.
Scheme 6. Plausible Reaction Mechanism for the Metal-Free
Pyridine Formation
General Procedure for the Synthesis of Pyridines. To a
mixture of acetophenone O-acetyl oxime derivative (0.5 mmol) and
enal derivative (0.75 mmol) were added successively I2 (0.25 mmol),
Et3N (0.25 mmol), and 2.5 mL of toluene. The reaction mixture was
stirred at 120 °C for 3 h and then cooled to room temperature.
Subsequently, the reaction mixture was diluted with ethyl acetate and
concentrated under reduced pressure, and the residue was separated
by column chromatography (petroleum ether/EtOAc 20:1 to 30:1) to
give the pure product.
2,4-Diphenylpyridine (3a, CAS: 26274-35-1).6b Yellow oil (92.4
mg, 80% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.74 (d, J = 4.8
Hz, 1H), 8.06 (d, J = 6.8 Hz, 2H), 7.94 (s, 1H), 7.70 (d, J = 6.8 Hz,
2H), 7.54−7.40 (m, 7H); 13C NMR (100 MHz, CDCl3, ppm) δ 158.1,
150.1, 149.3, 139.5, 138.5, 129.1, 129.00, 128.99, 128.7, 127.1, 127.0,
120.2, 118.7; MS (EI) m/z (%) 231 (100), 202, 154, 102, 77.
4-Phenyl-2-(p-tolyl)pyridine (3b).11 Yellow oil (99.2 mg, 81%
yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.72 (d, J = 4.8 Hz, 1H),
7.96 (d, J = 8.0 Hz, 2H), 7.91 (s, 1H), 7.70 (d, J = 7.2 Hz, 2H), 7.51−
7.42 (m, 4H), 7.31 (d, J = 7.6 Hz, 2H), 2.43 (s, 3H); 13C NMR (100
MHz, CDCl3, ppm) δ 158.1, 150.0, 149.3, 139.0, 138.7, 136.7, 129.5,
129.1, 129.0, 127.1, 126.9, 120.0, 118.5, 21.3; HRMS calcd for:
C18H16N [M + H]+ 246.1277, found 246.1276.
reduction of oxime 1a gives a [I+] species and imino-radical A,
which traps an electron to form the corresponding anion B.
Then Michael-type addition of the carbon-centered anion B′,
generated by 1,3-H-shift of B, would take place to the
unsaturated aldehydes to generate intermediate C, which
eliminates hydroxyl anion to furnish the dihydropyridine D.
Finally, the desired pyridine 3a is afforded through aromatiza-
tion of D with the [I+] species as the main oxidant.
Additionally, one molecule of Et3N as the base could provide
two electrons and decays into Et2N+CHCH3, which would
be further hydrolyzed into secondary amine and aldehyde. It is
2-(4-(tert-Butyl)phenyl)-4-phenylpyridine (3c, CAS: 1188087-46-
8).12 Yellow oil (123.4 mg, 86% yield); H NMR (400 MHz, CDCl3,
1
ppm) δ 8.73 (d, J = 4.8 Hz, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.92 (s,
1H), 7.70 (d, J = 7.2 Hz, 2H), 7.54−7.43 (m, 6H), 1.38 (s, 9H); 13C
NMR (100 MHz, CDCl3, ppm) δ 157.9, 152.1, 149.9, 149.0, 138.5,
D
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136.6, 129.0, 128.8, 126.9, 126.6, 125.6, 119.8, 118. 3, 34.6, 31.2; MS
(EI) m/z (%) 211 (100), 196, 181, 154, 57.
2-(3-Methoxyphenyl)-4-phenylpyridine (3m). Yellow oil (109.6
mg, 84% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.74 (d, J = 4.8
Hz, 1H), 7.93 (s, 1H), 7.72−7.57 (m, 4H), 7.55−7.35 (m, 5H), 6.99
(d, J = 7.6 Hz, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm)
δ 160.0, 157.7, 149.9, 149.1, 140.8, 138.3, 129.6, 129.0, 128.9, 126.9,
120.2, 119.3, 118.7, 115.0, 112.2, 55.2; HRMS calcd for: C18H16ON
[M + H]+ 262.1224, found 262.1226.
2-(3-Bromophenyl)-4-phenylpyridine (3n). Yellow solid (123.6
mg, 80% yield); mp = 57−59 °C; 1H NMR (400 MHz, CDCl3, ppm)
δ 8.74 (d, J = 5.2 Hz, 1H), 8.22 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.90
(s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.60−7.43 (m, 5H), 7.37 (t, J = 7.8
Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 156.5, 150.2, 149.5,
141.5, 138.2, 131.9, 130.2, 130.1, 129.1, 128.5, 127.1, 125.5, 123.0,
120.8, 118.8; HRMS calcd for: C17H13BrN [M + H]+ 310.0220, found
310.0226.
2-(4-Isobutylphenyl)-4-phenylpyridine (3d). Yellow oil (124.8 mg,
87% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.71 (d, J = 4.8 Hz,
1H), 7.96 (d, J = 7.2 Hz, 2H), 7.91 (s, 1H), 7.68 (d, J = 7.2 Hz, 2H),
7.52−7.41 (m, 4H), 7.27 (d, J = 7.6 Hz, 2H), 2.54 (d, J = 6.8 Hz, 2H),
1.97−1.85 (m, 1H), 0.93 (d, J = 6.4 Hz, 6H); 13C NMR (100 MHz,
CDCl3, ppm) δ 158.1, 150.0, 149.2, 142.8, 138.6, 136.9, 129.5, 129.0,
128.9, 127.0, 126.7, 119.9, 118.4, 45.2, 30.2, 22.3; HRMS calcd for:
C21H22N [M + H]+ 288.1743, found 288.1747.
2-([1,1′-Biphenyl]-4-yl)-4-phenylpyridine (3e). White solid (139.7
1
mg, 91% yield); mp = 101−103 °C; H NMR (400 MHz, CDCl3,
ppm) δ 8.76 (d, J = 5.2 Hz, 1H), 8.15 (d, J = 8.4 Hz, 2H), 7.99 (s,
1H), 7.76−7.67 (m, 6H), 7.55−7.34 (m, 7H); 13C NMR (100 MHz,
CDCl3, ppm) δ 157.6, 150.1, 149.4, 141.8, 140.6, 138.5, 138.3, 129.13,
129.06, 128.8, 127.5, 127.4, 127.1, 126.4, 120.3, 118.7, 110.0; HRMS
calcd for: C23H18N [M + H]+ 308.1434, found 308.1431.
2-(3-Nitrophenyl)-4-phenylpyridine (3o, CAS: 1426022-18-5).6b
White solid (117.3 mg, 85% yield); mp = 117−118 °C; 1H NMR (400
MHz, CDCl3, ppm) δ 8.92 (s, 1H), 8.78 (d, J = 4.8 Hz, 1H), 8.45 (d, J
= 7.6 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H), 8.00 (s, 1H), 7.70 (q, J = 8.4
Hz, 3H), 7.56−7.48 (m, 4H); 13C NMR (100 MHz, CDCl3, ppm) δ
155.4, 150.4, 149.9, 148.8, 141.1, 138.0, 132.8, 129.7, 129.4, 129.2,
127.1, 123.6, 121.9, 121.4, 118.8; MS (EI) m/z (%) 276 (100), 246,
202, 115, 77.
2-(4-Methoxyphenyl)-4-phenylpyridine (3f, CAS: 1426022094).6b
1
Yellow solid (108.3 mg, 83% yield); mp = 65−66 °C; H NMR (400
MHz, CDCl3, ppm) δ 8.70 (d, J = 4.8 Hz, 1H), 8.02 (d, J = 8.4 Hz,
2H), 7.88 (s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.53−7.40 (m, 4H), 7.02
(d, J = 8.8 Hz, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm)
δ 160.5, 157.7, 149.9, 149.2, 138.7, 132.1, 129.1, 128.9, 128.3, 127.0,
119.6, 118.0, 114.1, 55.3; MS (EI) m/z (%) 261 (100), 246, 218, 96,
77.
4-Phenyl-2-(3-(trifluoromethyl)phenyl)pyridine (3p). Yellow oil
1
(122.6 mg, 82% yield); H NMR (400 MHz, CDCl3, ppm) δ 8.77
2-(4-Fluorophenyl)-4-phenylpyridine (3g, CAS: 1188022-73-2).
Yellow oil (93.4 mg, 75% yield); 1H NMR (400 MHz, CDCl3, ppm) δ
8.72 (d, J = 4.8 Hz, 1H), 8.05 (q, J = 4.5 Hz, 2H), 7.88 (s, 1H), 7.69
(d, J = 6.8 Hz, 2H), 7.54−7.42 (m, 4H), 7.18 (t, J = 8.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 163.5 (d, J = 246.9 Hz), 156.9,
150.0, 149.3, 138.3, 135.5 (d, J = 3.1 Hz), 129.1, 129.0, 128.8 (d, J =
8.3 Hz), 127.0, 120.1, 118.3, 115.6 (d, J = 21.5 Hz); HRMS calcd for:
C17H13FN [M + H]+ 250.1027, found 250.1029.
(d, J = 4.8 Hz, 1H), 8.34 (s, 1H), 8.25 (d, J = 7.2 Hz, 1H), 7.95 (s,
1H), 7.71 (d, J = 6.8 Hz, 3H), 7.62 (t, J = 7.5 Hz, 1H), 7.56−7.46 (m,
4H); 13C NMR (100 MHz, CDCl3, ppm) δ 156.3, 150.2, 149.6, 140.1,
138.1, 131.1 (q, J = 32 Hz), 130.1, 129.17, 129.15, 129.1, 127.0, 125.5
(q, J = 3.8 Hz), 124.2 (q, J = 270.7 Hz), 123.8 (q, J = 3.9 Hz), 120.8,
118.6; HRMS calcd for: C18H13F3N [M + H]+ 300.0990, found
300.0995.
2-(2-Chlorophenyl)-4-phenylpyridine (3q). Yellow solid (87.5 mg,
66% yield); mp = 60−62 °C; 1H NMR (400 MHz, CDCl3) δ 8.77 (d,
J = 5.2 Hz, 1H), 7.88 (s, 1H), 7.72−7.62 (m, 3H), 7.56−7.42 (m, 5H),
7.41−7.33 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 157.3, 149.9,
148.4, 139.2, 138.1, 132.2, 131.5, 130.1, 129.6, 129.12, 129.10, 127.1,
127.0, 122.9, 120.4; HRMS calcd for: C17H13ClN [M + H]+ 266.0729,
found 266.0731.
2-(4-Chlorophenyl)-4-phenylpyridine (3h).11 Yellow oil (115.3 mg,
87% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.73 (d, J = 5.2 Hz,
1H), 8.01 (d, J = 8.4 Hz, 2H), 7.90 (s, 1H), 7.69 (d, J = 7.2 Hz, 2H),
7.54−7.46 (m, 6H); 13C NMR (100 MHz, CDCl3, ppm) δ 156.8,
150.1, 149.5, 138.3, 137.9, 135.2, 129.1, 128.9, 128.3, 127.1, 120.5,
118.5; HRMS calcd for: C17H13NCl [M + H]+ 266.0731, found
266.0730.
2-(2-Nitrophenyl)-4-phenylpyridine (3r). Yellow solid (113.2 mg,
2-(4-Bromophenyl)-4-phenylpyridine (3i, CAS: 504413-43-8).6b
1
82% yield); mp = 98−100 °C; H NMR (400 MHz, CDCl3, ppm) δ
1
Yellow solid (122.1 mg, 79% yield); mp = 84−86 °C; H NMR (400
8.70 (d, J = 4.8 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 5.2 Hz,
5H), 7.59−7.47 (m, 5H); 13C NMR (100 MHz, CDCl3, ppm) δ 156.0,
150.0, 149.42, 149.36, 137.8, 135.4, 132.4, 131.3, 129.3, 129.23,
129.16, 127.1, 124.4, 120.9, 120.7; HRMS calcd for: C17H13O2N2 [M +
H]+ 277.0967, found 277.0972.
MHz, CDCl3, ppm) δ 8.74 (d, J = 4.8 Hz, 1H), 7.95 (d, J = 8.4 Hz,
2H), 7.91 (s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H),
7.54−7.43 (m, 4H); 13C NMR (100 MHz, CDCl3, ppm) δ 156.8,
150.1, 149.6, 138.33, 138.27, 131.9, 129.18, 129.16, 128.6, 127.1,
123.6, 120.6, 118.5; MS (EI) m/z (%) 309 (100), 229, 205, 154, 77.
2-(4-Iodophenyl)-4-phenylpyridine (3j, CAS: 1426022-12-9).6b
Yellow solid (121.4 mg, 68% yield); mp = 94−96 °C; 1H NMR
(400 MHz, CDCl3, ppm) δ 8.73 (d, J = 4.8 Hz, 1H), 7.90 (s, 1H),
7.86−7.70 (m, 4H), 7.69 (d, J = 7.2 Hz, 2H), 7.54−7.49 (m, 4H); 13C
NMR (100 MHz, CDCl3, ppm) δ 157.0, 150.2, 149.5, 138.9, 138.3,
137.9, 129.1, 128.7, 127.1, 120.6, 118.4, 95.4; MS (EI) m/z (%) 357
(100), 230, 152, 115, 77.
2-(3,4-Dichlorophenyl)-4-phenylpyridine (3s, CAS: 1426022-20-
9).6b White solid (137.5 mg, 92% yield); mp = 104−106 °C;1H NMR
(400 MHz, CDCl3, ppm) δ 8.74 (d, J = 4.8 Hz, 1H), 8.19 (s, 1H), 7.91
(d, J = 10.0 Hz, 2H), 7.69 (d, J = 7.2 Hz, 2H), 7.58−7.47 (m, 5H); 13C
NMR (100 MHz, CDCl3, ppm) δ 155.5, 150.2, 149.7, 139.3, 138.1,
133.2, 133.1, 130.7, 129.3, 129.2, 128.9, 127.1, 126.1, 121.0, 118.5; MS
(EI) m/z (%) 299 (100), 264, 228, 154, 77.
2-(Naphthalen-1-yl)-4-phenylpyridine (3t). Yellow solid (88.52
1
mg, 63% yield); mp = 103−105 °C; H NMR (400 MHz, CDCl3,
2-(4-(Methylsulfonyl)phenyl)-4-phenylpyridine (3k). Light yellow
solid (122.1 mg, 79% yield); mp = 136−138 °C; 1H NMR (400 MHz,
CDCl3, ppm) δ 8.79 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 2H), 8.07
(d, J = 8.4 Hz, 2H), 7.99 (s, 1H), 7.70 (d, J = 6.8 Hz, 2H), 7.56−7.47
(m, 4H), 3.11 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 155.8,
150.4, 149.8, 144.6, 140.6, 138.0, 129.3, 129.2, 127.9, 127.8, 127.0,
121.4, 119.3, 44.5; HRMS calcd for: C18H16NO2S [M + H]+ 310.0896,
found 310.0895.
2-(4-Nitrophenyl)-4-phenylpyridine (3l). Yellow solid (115.9 mg,
84% yield); mp = 152−154 °C; 1H NMR (400 MHz, CDCl3, ppm) δ
8.80 (d, J = 4.8 Hz, 1H), 8.36 (d, J = 8.8 Hz, 2H), 8.25 (d, J = 8.8 Hz,
2H), 8.01 (s, 1H), 7.71 (d, J = 6.8 Hz, 2H), 7.58−7.50 (m, 4H); 13C
NMR (100 MHz, CDCl3, ppm) δ 155.5, 150.5, 149.8, 148.2, 145.4,
138.0, 129.4, 129.3, 127.8, 127.1, 124.0, 121.6, 119.4; HRMS calcd for:
C17H13O2N2 [M + H]+ 277.0972, found 277.0970.
ppm) δ 8.85 (d, J = 5.2 Hz, 1H), 8.14 (d, J = 7.6 Hz, 1H), 7.94 (d, J =
8.0 Hz, 2H), 7.83 (s, 1H), 7.72 (d, J = 7.2 Hz, 2H), 7.67 (d, J = 6.8 Hz,
1H), 7.58 (t, J = 7.5 Hz, 2H), 7.53−7.44 (m, 5H); 13C NMR (100
MHz, CDCl3, ppm) δ 159.7, 149.9, 148.9, 138.5, 138.2, 133.9, 131.2,
129.14, 129.12, 128.9, 128.4, 127.5, 127.1, 126.5, 125.9, 125.6, 125.3,
123.0, 120.0; HRMS calcd for: C21H16N [M + H]+ 282.1274, found
282.1277.
2-(Furan-2-yl)-4-phenylpyridine (3u).6b Yellow oil (33.2 mg, 30%
yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.64 (d, J = 5.2 Hz, 1H),
7.93 (s, 1H), 7.70 (d, J = 7.2 Hz, 2H), 7.56−7.48 (m, 4H), 7.39 (d, J =
4.0 Hz, 1H), 7.14 (d, J = 2.8 Hz, 1H), 6.57 (s, 1H); 13C NMR (100
MHz, CDCl3, ppm) δ 153.5, 149.9, 149.7, 149.3, 143.4, 138.2, 129.2,
129.1, 127.0, 120.0, 116.6, 112.1, 109.0; MS (EI) m/z (%) 221 (100),
192, 165, 154, 125.
E
DOI: 10.1021/acs.joc.5b02624
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4-Phenyl-2-(thiophen-2-yl)pyridine (3v).13 Yellow oil (103.1 mg,
87% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.61 (d, J = 5.2 Hz,
1H), 7.86 (s, 1H), 7.67 (d, J = 4.8 Hz, 3H), 7.52−7.40 (m, 4H), 7.36
(d, J = 5.2 Hz, 1H), 7.14 (t, J = 4.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3, ppm) δ 152.9, 149.8, 149.1, 144.7, 138.1, 128.98, 128.96,
127.9, 127.5, 126.9, 124.6, 119.9, 116.7; MS (EI) m/z (%) 237 (100),
204, 165, 127, 77.
CDCl3, ppm) δ 158.0, 151.5, 150.0, 143.8, 139.3, 138.3, 129.1, 128.7,
127.0, 116.3, 114.7, 112.1, 108.7; MS (EI) m/z (%) 221 (100), 192,
165, 96, 77.
2-Phenyl-4-propylpyridine (4f, CAS: 53911-34-5).15 Yellow oil
(49.3 mg, 50% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.59 (d, J
= 4.8 Hz, 1H), 7.99 (d, J = 7.6 Hz, 2H), 7.56 (s, 1H), 7.50−7.37(m,
3H), 7.09 (d, J = 4.4 Hz, 1H), 2.67 (t, J = 7.4 Hz, 2H), 1.78−1.66 (m,
2H), 0.99 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ
157.3, 152.5, 149.3, 139.4, 128.8, 128.7, 127.0, 122.5, 121.0, 37.5, 23.5,
13.7; MS (EI) m/z (%) 197 (100), 182, 169, 154, 77.
4-Phenyl-2,3′-bipyridine (3w). Yellow oil (48.7 mg, 42% yield); 1H
NMR (400 MHz, CDCl3, ppm) δ 9.26 (s, 1H), 8.77 (d, J = 5.2 Hz,
1H), 8.67 (s, 1H), 8.39 (d, J = 8.0 Hz, 1H), 7.95 (s, 1H), 7.70 (d, J =
6.8 Hz, 2H), 7.53−7.41 (m, 5H); 13C NMR (100 MHz, CDCl3, ppm)
δ 155.4, 150.4, 149.9, 149.6, 148.2, 138.1, 135.0, 134.5, 129.3, 129.2,
127.0, 123.6, 120.9, 118.8; HRMS calcd for: C16H13N2 [M + H]+
233.1071, found 233.1073.
5-Methyl-2,4-diphenylpyridine (4g, CAS: 83575-92-2).16 Yellow
1
oil (24.5 mg, 20% yield); H NMR (400 MHz, CDCl3, ppm) δ 8.03
(d, J = 7.2 Hz, 2H), 7.73 (s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.54−7.40
(m, 6H), 7.34 (s, 1H), 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3,
ppm) δ 158.8, 157.6, 149.7, 138.8, 129.0, 128.9, 128.8, 128.7, 127.2,
127.1, 119.9, 116.2, 110.0, 24.7; MS (EI) m/z (%) 245 (100), 230,
202, 168, 77.
3-Methyl-2,4-diphenylpyridine (3x, CAS: 875228-76-5).6b Yellow
1
oil (95.6 mg, 78% yield); H NMR (400 MHz, CDCl3, ppm) δ 8.56
(d, J = 4.8 Hz, 1H), 7.56 (d, J = 7.2 Hz, 2H), 7.49−7.37 (m, 8H), 7.15
(d, J = 4.8 Hz, 1H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm)
δ 159.7, 150.8, 146.3, 141.0, 139.8, 129.0, 128.6, 128.4, 128.3, 128.1,
127.8, 123.1, 17.9; MS (EI) m/z (%) 245 (100), 166, 139, 115, 77.
2,3,4-Triphenylpyridine (3y, CAS: 130318-01-3).6b White solid
5-Methyl-2-phenylpyridine (4h, CAS: 27012-22-2).17 Yellow oil
1
(21.1 mg, 25% yield); H NMR (400 MHz, CDCl3, ppm) δ 8.53 (s,
1H), 7.97 (d, J = 7.2 Hz, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 7.6
Hz, 1H), 7.47 (t, J = 7.4 Hz, 2H), 7.39 (t, J = 7.2 Hz, 1H), 2.38 (s,
3H); 13C NMR (100 MHz, CDCl3, ppm) δ 154.8, 150.0, 139.4, 137.3,
131.6, 128.7, 128.6, 126.7, 120.0, 18.1; MS (EI) m/z (%) 169 (100),
154, 141, 115, 77.
1
(135.1 mg, 88% yield); mp = 178−179 °C; H NMR (400 MHz,
CDCl3, ppm) δ 8.74 (d, J = 4.8 Hz, 1H), 7.35 (d, J = 4.8 Hz, 1H), 7.27
(d, J = 6.0 Hz, 3H), 7.21−7.18 (m, 5H), 7.12−7.02 (m, 5H), 6.88 (d, J
= 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 158.4, 149.9,
148.2, 140.7, 139.4, 137.7, 134.4, 131.4, 129.9, 129.3, 127.9, 127.7,
127.6, 127.34, 127.32, 126.6, 123.6; MS (EI) m/z (%) 307 (100), 202,
176, 152, 77.
2-Methyl-4,6-diphenylpyridine (4i, CAS: 1912-16-9).6b Yellow oil
(46.6 mg, 38% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.04 (d, J
= 7.2 Hz, 2H), 7.74 (s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.53−7.40 (m,
6H), 7.35 (s, 1H), 2.73 (s, 3H) ; 13C NMR (100 MHz, CDCl3, ppm) δ
158.8, 157.6, 149.7, 139.7, 138.8, 129.0, 128.9, 128.8, 128.7, 127.2,
127.1, 119.9, 116.2, 24.7; MS (EI) m/z (%) 245 (100), 230, 202, 168,
77.
4-Phenyl-5,6-dihydrobenzo[h]quinoline (3z, CAS: 95545-95-2).6b
White solid (98.95 mg, 77% yield); mp = 102−103 °C; 1H NMR (400
MHz, CDCl3) δ 8.58 (d, J = 4.8 Hz, 1H), 8.37 (d, J = 7.6 Hz, 1H),
7.53−7.30 (m, 7H), 7.22 (d, J = 7.2 Hz, 1H), 7.14 (d, J = 4.8 Hz, 1H),
2.93 (t, J = 6.6 Hz, 2H), 2.83 (t, J = 6.6 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 153.0, 148.6, 147.1, 138.9, 138.1, 134.8, 129.5, 129.1,
128.7, 128.4, 128.0, 127.5, 127.2, 125.5, 123.3, 28.1, 25.5; MS (EI) m/
z (%) 257 (100), 226, 151, 127, 77.
(5-Chloro-2-(4-phenylpyridin-2-yl)phenyl)(phenyl)methanone
1
(5a). Yellow oil (64.9 mg, 88% yield); H NMR (400 MHz, CDCl3,
ppm) δ 8.40 (d, J = 5.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.70 (d, J =
7.2 Hz, 3H), 7.62−7.53(m, 4H), 7.49−7.38 (m, 4H), 7.29 (t, J = 7.4
Hz, 3H). 13C NMR (100 MHz, CDCl3, ppm) δ 196.4, 156.1, 149.5,
148.9, 141.1, 138.0, 137.9, 137.3, 134.9, 132.7, 130.2, 130.0, 129.4,
129.13, 129.07, 128.9, 128.2, 126.9, 120.7, 120.2; HRMS calcd for:
C24H17ClNO [M + H]+ 370.0993, found 370.0993.
2-(2,6-Di(thiophen-2-yl)phenyl)-4-phenylpyridine (6a). Yellow oil
(64 mg, 81% yield);1H NMR (400 MHz, CDCl3, ppm) δ 8.59 (d, J =
5.2 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.49 (t, J = 7.8 Hz, 1H), 7.44−
7.35 (m, 7H), 7.15 (d, J = 4.8 Hz, 2H), 6.83 (t, J = 4.2 Hz, 2H), 6.74
(d, J = 3.6 Hz, 2H). 13C NMR (100 MHz, CDCl3, ppm) δ 158.8,
149.1, 148.2, 142.6, 138.4, 138.1, 134.8, 130.1, 128.97, 128.96, 128.4,
127.3, 127.0, 126.8, 125.9, 124.4, 120.2; HRMS calcd for: C25H18NS2
[M + H]+396.0875, found 396.0870.
2-(4-Phenylpyridin-2-yl)phenyl acetate (7a). Yellow oil (43.4 mg,
75% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.61 (d, J = 5.2 Hz,
1H), 8.23 (s, 1H), 7.66 (d, J = 7.2 Hz, 2H), 7.54−7.46 (m, 4H), 7.28
(t, J = 8.2 Hz, 2H), 6.97 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H),
2.21 (s, 3H). 13C NMR (100 MHz, CDCl3, ppm) δ 168.7, 160.1,
155.2, 150.1, 149.0, 146.7, 137.9, 130.6, 129.5, 129.3, 126.9, 122.3,
120.2, 116.1, 114.4, 113.8, 21.3; HRMS calcd for: C19H16NO2 [M +
H]+ 290.1176, found 290.1175.
4-(4-Methoxyphenyl)-2-phenylpyridine (4a, CAS: 1350737-69-
7).6b Yellow solid (103.1 mg, 79% yield); mp = 75−77 °C; 1H
NMR (400 MHz, CDCl3, ppm) δ 8.70 (d, J = 4.8 Hz, 1H), 8.04 (d, J =
7.2 Hz, 2H), 7.90 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.58−7.35 (m,
4H), 7.04 (d, J = 8.4 Hz, 2H), 3.88 (s, 3H); 13C NMR (100 MHz,
CDCl3, ppm) δ 160.5, 157.9, 149.9, 148.7, 139.5, 130.6, 128.9, 128.7,
128.2, 127.0, 119.7, 118.2, 114.5, 55.3; MS (EI) m/z (%) 261 (100),
246, 230, 189, 77.
4-(4-Nitrophenyl)-2-phenylpyridine (4b, CAS: 1062144-59-5).14
White solid (99.4 mg, 72% yield); mp = 136−138 °C; 1H NMR (400
MHz, CDCl3, ppm) δ 8.82 (d, J = 4.8 Hz, 1H), 8.38 (d, J = 8.4 Hz,
2H), 8.06 (d, J = 7.2 Hz, 2H), 7.94 (s, 1H), 7.85 (d, J = 8.4 Hz, 2H),
7.60−7.42 (m, 4H); 13C NMR (100 MHz, CDCl3, ppm) δ 158.5,
150.4, 148.2, 146.9, 144.9, 138.9, 129.4, 128.9, 128.0, 127.0, 124.3,
120.2, 118.7; MS (EI) m/z (%) 276 (100), 230, 202, 101, 77.
4-(4-Fluorophenyl)-2-phenylpyridine (4c).11 Yellow oil (108.3 mg,
87% yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.74 (d, J = 5.2 Hz,
1H), 8.05 (d, J = 7.2 Hz, 2H), 7.88 (s, 1H), 7.67 (q, J = 4.5 Hz, 2H),
7.54−7.39 (m, 4H), 7.20 (t, J = 8.5 Hz, 2H); 13C NMR (100 MHz,
CDCl3, ppm) δ 163.3 (d, J = 247.6 Hz), 158.0, 150.0, 148.0, 139.2,
134.4 (d, J = 2.8 Hz), 129.0, 128.7 (d, J = 7.9 Hz), 128.6, 126.9, 119.9,
118.3, 116.0 (d, J = 21.5 Hz); MS (EI) m/z (%) 249 (100), 220, 172,
154, 125.
4-(4-Phenylpyridin-2-yl)-[1,1′-biphenyl]-3-yl Acetate (7b). Yellow
1
oil (62.1 mg, 85% yield); H NMR (400 MHz, CDCl3, ppm) δ 8.62
(d, J = 5.2 Hz, 1H), 8.29 (s, 1H), 7.69−7.64 (m, 5H), 7.56−7.49 (m,
4H), 7.45 (t, J = 7.4 Hz, 2H), 7.37 (t, J = 7.4 Hz, 1H), 7.25 (d, J = 3.6
Hz, 1H), 6.92 (d, J = 3.6 Hz, 1H), 2.26 (s, 3H). 13C NMR (100 MHz,
CDCl3, ppm) δ 168.8, 160.5, 155.2, 150.1, 149.4, 146.7, 143.6, 139.4,
138.0, 129.5, 129.3, 128.8, 128.1, 127.0, 126.9, 122.0, 120.1, 114.4,
112.7, 110.0, 21.4; HRMS calcd for: C25H18NO2 [M − H]+ 364.1343,
found 364.1342.
4-(2-Methoxyphenyl)-2-phenylpyridine (4d, CAS: 1426022-44-
7).6b Yellow oil (105.7 mg, 81% yield); 1H NMR (400 MHz,
CDCl3, ppm) δ 8.72 (d, J = 4.8 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.91
(s, 1H), 7.51−7.35 (m, 6H), 7.12−6.97 (m, 2H), 3.86 (s, 3H); 13C
NMR (100 MHz, CDCl3, ppm) δ 157.2, 156.5, 149.2, 147.1, 139.6,
130.4, 130.0, 128.7, 128.6, 127.9, 127.0, 122.8, 121.3, 121.0, 111.4,
55.5; MS (EI) m/z (%) 261 (100), 230, 189, 154, 77.
2-(3-((4-(tert-Butyl)phenyl)sulfonyl)phenyl)-4-phenylpyridine
1
(8a). Yellow oil (51.2 mg, 60% yield); H NMR (400 MHz, CDCl3,
4-(Furan-2-yl)-2-phenylpyridine (4e).6b Yellow oil (99.5 mg, 90%
yield); 1H NMR (400 MHz, CDCl3, ppm) δ 8.69 (d, J = 5.2 Hz, 1H),
8.04 (d, J = 7.2 Hz, 2H), 7.98 (s, 1H), 7.58 (s, 1H), 7.52−7.42 (m,
4H), 6.95 (d, J = 3.2 Hz, 1H), 6.56 (s, 1H); 13C NMR (100 MHz,
ppm) δ 8.75 (d, J = 5.2 Hz, 1H), 8.60 (s, 1H), 8.32 (d, J = 7.6 Hz,
1H), 8.00 (d, J = 7.6 Hz, 1H), 7.97 (s, 1H), 7.91 (d, J = 8.4 Hz, 2H),
7.71 (d, J = 7.2 Hz, 2H), 7.64 (t, J = 7.8 Hz, 1H), 7.56−7.47 (m, 6H),
1.30 (s, 9H). 13C NMR (100 MHz, CDCl3, ppm) δ 157.1, 155.9,
F
DOI: 10.1021/acs.joc.5b02624
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The Journal of Organic Chemistry
Article
150.2, 149.9, 142.6, 140.7, 138.5, 138.0, 131.6, 129.8, 129.33, 129.27,
128.0, 127.6, 127.1, 126.3, 126.0, 121.1, 118.9, 35.2, 31.0; HRMS calcd
for: C27H26NO2S [M + H]+ 428.1679, found 428.1680.
(10) (a) Zhou, W.; Li, H.-J.; Wang, L. Org. Lett. 2012, 14, 4594.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02624.
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S
Copies of proton and carbon NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: hwhuang@xtu.edu.cn. Fax: (+86)-731-58292251.
*E-mail: gjdeng@xtu.edu.cn. Fax: (+86)-731-58292251.
Notes
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(16) Corriu, R. J. P.; Moreau, J. J. E.; Pataud-Sat, M. J. Org. Chem.
1990, 55, 2878.
(17) Schinkel, M.; Wallbaum, J.; Kozhushkov, S. I.; Marek, I.;
Ackermann, L. Org. Lett. 2013, 15, 4482.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We are grateful for financial support from the National Natural
Science Foundation of China (21372187, 21572194) and the
Program for Innovative Research Cultivation Team in
University of Ministry of Education of China (1337304).
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DOI: 10.1021/acs.joc.5b02624
J. Org. Chem. XXXX, XXX, XXX−XXX