One-pot synthesis of pyridines from 3-aza-1,5-enynes

Article abstract of DOI:10.1016/j.tet.2013.10.038

Efficient one-pot transformation of 3-aza-1,5-enynes to poly-substituted pyridines in good to excellent yields has been developed. This reaction involved cyclization of 3-aza-enynes and elimination of sulfinyl acids steps.

Full text of DOI:10.1016/j.tet.2013.10.038

Tetrahedron 69 (2013) 10245e10248
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One-pot synthesis of pyridines from 3-aza-1,5-enynes
*
Xiaoyi Xin, Dongping Wang, Xincheng Li, Boshun Wan
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 July 2013
Received in revised form 7 October 2013
Accepted 14 October 2013
Available online 19 October 2013
Efficient one-pot transformation of 3-aza-1,5-enynes to poly-substituted pyridines in good to excellent
yields has been developed. This reaction involved cyclization of 3-aza-enynes and elimination of sulfinyl
acids steps.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Pyridines
Enynes
Heterocycles
Cyclization
1. Introduction
transformed into two kinds of functionalized pyrroles,3e 1,2-
dihydropyridines and 3-iodo-1,2-dihydropyridines.3f In this paper,
Pyridine derivatives are an important class of heterocycle found
in many natural products, active pharmaceuticals, and functional
materials.1 Although many methods are available for the synthesis
of pyridines,2 the development of new methods that benefit from
readily available starting materials with operational simplicity
continues to be a target of intense interest. The exploration of re-
action diversity is an important goal of synthetic organic chemistry.
3-Aza-1,5-enynes was a versatile building block having diverse
reaction patterns.3 Cacchi and co-workers reported that N-prop-
we report the transformation of 3-aza-1,5-enynes to pyridines in an
efficient one-pot manner (Scheme 1c).
argylic b-enaminones could be selectively transformed into pyri-
dines via 6-endo-dig cyclization (Scheme 1a, left) or pyrroles via 5-
exo-dig cyclization.3a The pyridines were obtained using 40 mol % of
CuBr, and an oxidation step was involved in the proposed mecha-
nism, but the oxidant source was unclear.3a Chiba and co-workers
also reported one example of N-propargylic-enaminone was
transformed to pyridine in low yield in the presence of 20 mol %
CuBr$SMe2 under 1 atm of oxygen atmosphere (Scheme 1b).3b
Electrophilic iodocyclizations of N-propargylic
b-enaminones
with molecular iodine leading to iodo-substituted pyridines has
been accomplished by Zora’s research group (Scheme 1a, right).3c
Saito and co-workers described that the similar structure, N-tosyl,
N-propargylic
b-enaminones, underwent Au(I)-catalyzed amino-
Scheme 1. Synthesis of pyridines from 3-aza-1,5-enyne frameworks.
Claisen rearrangement and heterocyclization to yield pyrroles and/
or 1,2-dihydropyridines.3d Recently, we reported that 3-aza-1,5-
enyne
1
(see Scheme 1c for structure) was selectively
2. Results and discussions
In the course of our investigation on the transformation of 3-
* Corresponding author. Tel.: þ86 411 84379260; fax: þ86 411 84379223; e-mail
address: bswan@dicp.ac.cn (B. Wan).
aza-1,5-enyne 1 to N-heterocycles,3e,f we found that treatment of
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.10.038

10246
X. Xin et al. / Tetrahedron 69 (2013) 10245e10248
the model substrate 1a (R1¼R2¼Ph, R3¼p-tolyl) in following three
steps: 1) heated in ethanol at 70 ꢀC for 16 h under argon atmo-
sphere, 2) remove of the ethanol solvent under vacuum, 3) N,N-
dimethylformamide (DMF) was added, the mixture was heated at
140 ꢀC for 4 h under argon atmosphere, pyridine 2a, was obtained
in 99% isolated yield (Table 1, entry 1). The structure of the pyridine
product was unambiguously confirmed by single-crystal X-ray
diffraction analysis of its o-CF3-substituted derivative 2e.4
the same product as 1a (entry 1), although the yield was lower even
after a longer reaction time.
ð1Þ
Next, we explored the scope and generality of this reaction, and
the results are given in Table 1. Aryl R1 groups bearing different
substituents, including electron-neutral groups (entry 1), -donating
groups (entries 2e4), -withdrawing groups (entry 5), and halogen
groups (entries 6e8) were well tolerated, and the desired products
were isolated with moderate to high yields (60e99%). For 2-CF3
(entry 5, 69%) and 2-Br (entry 8, 60%) substituted substrate, the
yields were lower even the reaction time was prolonged, this
mainly reasoned from steric hindrance. A fused ring was also
suitable for this process, although a relatively low yield was ob-
tained (75%, entry 9). However, alkyl R1 substituents were not
tolerated (Eqs. 1 and 2), even at elevated temperature (140 ꢀC) and
prolonged time, the product were previously reported 1,2-
dihydropyridines 3v and w.3f These results indicated that an aryl
R1 is crucial in this system. Both aryl- and alkyl-substituted alkyne
(R2) units in the substrate were well tolerated (entries 10e18). We
noted that alkyl-substituted alkyl substrates also reacted in good
yields (entries 16e18). The electronic properties of the sulfonyl
group (R3) had a small impact on the yield (entries 1, 19, 20, the
products of 1s and t were same to 1a). Moreover, the C]C bond is
not limited to the (E)-geometry, substrate 1u (entry 21) afforded
ð2Þ
A plausible reaction mechanism is depicted in Scheme 2. In step
1, aza-Claisen rearrangement of 1 followed by 6p-electrocyclization
leads to 1,2-dihydropyridines 3.3f Then elimination of sulfinic acids5
from 3 followed a proposed E1-like mechanism: dissociation of aryl
sulfinic anion generates a carbon cation D, aryl sulfinic anion ab-
stracts a proton furnishes pyridine product 2.
Table 1
Scope of the synthesis of pyridinesa
Entry
1
R1
R2
R3
Yield (%)b
1
2
3
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
Ph
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-CF3C6H4
4-FC6H4
2-ClC6H4
2-BrC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
Ph
99 (2a)
96 (2b)
99 (2c)
91 (2d)
69 (2e)
95 (2f)
88 (2g)
60 (2h)
75 (2i)
95 (2j)
95 (2k)
92 (2l)
86 (2m)
96 (2n)
83 (2o)
90 (2p)
87 (2q)
90 (2r)
93 (2a)
91 (2a)
44 (2a)
4
5c
6
7
8c
9c
1-Naphthyl
Ph
10
11
12
13
14
15
16c,d
17c,d
18d,e
19
20
21d
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
nPr
Scheme 2. Proposed mechanism.
To verify the process from 1,2-dihydropyridines 3 to pyridines 2,
we treated the isolated 1,2-dihydropyridines 3a3f as the starting
material with the same conditions as used for 1a in step 3 (Eq. 3). As
expected, the same product, pyridine 2a, was obtained in the same
yield (99%) as the standard conditions (Table 1, entry 1).
nBu
Cy
Ph
Ph
1s
1t
2-ClC6H4
4-MeC6H4
1uf
Ph
a
Reaction conditions: 1 (0.2 mmol) of in ethanol (2.0 mL) was heated at 70 ꢀC for
16 h under argon atmosphere, then ethanol was removed under vacuum and DMF
was added, the mixture was heated at 140 ꢀC for 4 h under argon atmosphere unless
otherwise noted.
b
Isolated yields.
Step 3: 24 h.
Step 1: 100 ꢀC.
c
ð3Þ
d
e
Step 3: 36 h.
f
The double bond configuration of the reactant is (Z).

X. Xin et al. / Tetrahedron 69 (2013) 10245e10248
10247
3. Conclusion
128.7, 128.2,128.1,124.6,123.9, 53.3, 52.7, 21.6; HRMS Calculated for
C
22H19NO4Na [MþNa]þ 384.1212, found 384.1211.
In summary, we have developed an efficient one-pot method for
the synthesis of pyridines from 3-aza-1,5-enynes with high yields.
4.2.4. Dimethyl 4-phenyl-6-(p-tolyl)pyridine-2,3-dicarboxylate
The mechanism of containing an aza-Claisen rearrangement, 6
p-
(2d). Unknown compound, colorless oil; 1H NMR (400 MHz,
electrocyclization, and elimination of aryl sulfinic acid was pro-
posed. This work provides an alternate access to construct pyri-
dines directly from available building blocks.
CDCl3)
d
7.98 (d, J¼7.9 Hz, 2H), 7.85 (s, 1H), 7.44 (s, 5H), 7.29 (d,
J¼7.8 Hz, 2H), 4.02 (s, 3H), 3.73 (s, 3H), 2.41 (s, 3H); 13C NMR
(100 MHz, CDCl3)
d 167.0, 164.8, 156.9, 148.9, 145.3, 139.3, 136.5,
133.9, 128.7, 128.1, 127.8, 127.4, 127.1, 126.3, 122.3, 52.2, 51.7, 20.4;
HRMS Calculated for C22H19NO4Na [MþNa]þ 384.1212, found
384.1205.
4. Experimental section
4.1. General method
4.2.5. Dimethyl 4-phenyl-6-(2-(trifluoromethyl)phenyl)pyridine-2,3-
dicarboxylate (2e). Unknown compound, white solid, mp
All reactions were carried out under an atmosphere of argon
using standard Schlenk techniques. Solvents were treated prior
to use according to the standard methods. Column chromatog-
raphy was carried out on silica gel (300e400 mesh) using
a forced flow of eluent at 0.3e0.5 bar pressure. For TLC, silica gel
GF254 was used and visualized by fluorescence quenching under
UV light. NMR spectra were recorded at room temperature in
CDCl3 on 400 MHz Bruker DRX-400 or 500 MHz Bruker DRX-500
NMR spectrometers. The chemical shifts for 1H NMR were
recorded in parts per million downfield from tetramethylsilane
(TMS) with the solvent resonance as the internal standard
(7.26 ppm for CDCl3). The chemical shifts for 13C NMR were
recorded in ppm downfield using the central peak of CDCl3
(77.16 ppm) as the internal standard. Coupling constants (J) are
reported in Hertz and refer to apparent peak multiplications. The
abbreviations s, d, t, q, and m stand for singlet, doublet, triplet,
quartet, and multiplet in that order. HRMS data were obtained
with Micromass HPLCeQ-TOF mass spectrometer.
154e155 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.79 (d, J¼7.8 Hz, 1H),
7.67e7.62 (m, 2H), 7.59e7.53 (m, 2H), 7.45 (s, 5H), 4.00 (s, 3H), 3.77
(s, 3H); 13C NMR (100 MHz, CDCl3)
167.8, 165.4, 158.3, 149.3, 145.6,
d
138.4, 136.9, 132.0, 131.9, 129.7, 129.4, 129.3, 128.9, 128.3, 127.7,
127.6, 126.7 (q, J¼5.2 Hz), 124.1 (d, J¼273.9 Hz), 53.5, 52.9; 19F NMR
(377 MHz, CDCl3)
d
ꢁ56.91; HRMS Calculated for C22H16NO4F3Na
[MþNa]þ 438.0929, found 438.0950.
4.2.6. Dimethyl
6-(4-fluorophenyl)-4-phenylpyridine-2,3-dicarb-
oxylate (2f). Unknown compound, colorless oil; 1H NMR (400 MHz,
CDCl3)
d
8.07 (dd, J¼8.5, 5.5 Hz, 2H), 7.82 (s,1H), 7.44 (m, 5H), 7.17 (t,
J¼8.6 Hz, 2H), 4.01 (s, 3H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
167.8, 165.7, 164.2 (d, J¼250.3 Hz), 156.9, 150.2, 146.4, 137.3, 133.9,
133.8, 129.4 (d, J¼8.6 Hz), 129.2, 128.8, 128.1, 123.4, 116.0 (d,
J¼21.8 Hz), 53.3, 52.8; 19F NMR (377 MHz, CDCl3)
d
ꢁ111.63; HRMS
Calculated for C21H16NO4FNa [MþNa]þ 388.0961, found 388.0965.
4.2.7. Dimethyl
oxylate (2g). Unknown compound, white solid, mp 97e98 ꢀC; 1H
NMR (400 MHz, CDCl3)
7.87 (s, 1H), 7.68 (d, J¼7.0 Hz, 1H), 7.47 (m,
6H), 7.42e7.33 (m, 2H), 4.01 (s, 3H), 3.77 (s, 3H); 13C NMR
(100 MHz, CDCl3) 167.9, 165.5, 157.3, 149.1, 137.7, 137.0, 132.4,
6-(2-chlorophenyl)-4-phenylpyridine-2,3-dicarb-
4.2. General procedure for the syntheses of pyridines 2
d
In a Schlenk tube equipped with a magnetic stirrer bar, starting
material 1 (0.2 mmol) and ethanol (2 mL) were added. The resulting
mixture was stirred at 70 ꢀC under argon protection for 16 h. The
solvent ethanol was removed under vacuum and then DMF (1 mL)
was added, the mixture was heated at 140 ꢀC for 4 h under argon
atmosphere. The solvent was removed under vacuum. The residue
was directly purified by flash chromatography (eluent: 50:1e10:1
petroleum ether/ethyl acetate) to give the desired pyridine 2.
d
132.0,131.9,130.5,130.3,129.4,129.3,128.9,128.5,128.3,127.4, 53.5,
52.9; HRMS Calculated for C21H16NO4NaCl [MþNa]þ 404.0666,
found 404.0654.
4.2.8. Dimethyl
oxylate (2h). Unknown compound, white solid, mp 108e109 ꢀC; 1H
NMR (400 MHz, CDCl3)
7.81 (s, 1H), 7.65 (d, J¼8.0 Hz, 1H), 7.60 (d,
J¼7.6 Hz, 1H), 7.51e7.35 (m, 6H), 7.26 (t, J¼8.5 Hz, 1H), 3.98 (s, 3H),
3.74 (s, 3H); 13C NMR (100 MHz, CDCl3)
167.9, 165.5, 158.7, 149.0,
6-(2-bromophenyl)-4-phenylpyridine-2,3-dicarb-
d
4.2.1. Dimethyl 4,6-diphenylpyridine-2,3-dicarboxylate
d
(2a). Unknown compound, colorless oil; 1H NMR (500 MHz,
145.8, 139.8, 137.0, 133.6, 131.9, 130.7, 129.5, 129.3, 128.9, 128.5,
128.3, 128.0, 121.9, 53.5, 52.9; HRMS Calculated for C21H16NO4NaBr
[MþNa]þ 448.0160, found 448.0150.
CDCl3)
d
8.10e8.04 (m, 2H), 7.87 (s, 1H), 7.52e7.42 (m, 8H), 4.02 (s,
167.9, 165.8, 158.0,
3H), 3.73 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
150.1, 146.5, 137.8, 137.5, 130.1, 129.2, 129.1, 128.8, 128.7, 128.2, 127.5,
123.8, 53.3, 52.7; HRMS Calculated for C21H17NO4Na [MþNa]þ
370.1055, found 370.1057.
4.2.9. Dimethyl 6-(naphthalen-1-yl)-4-phenylpyridine-2,3-dicarb-
oxylate (2i). Unknown compound, white solid, mp 136e137 ꢀC; 1H
NMR (500 MHz, CDCl3)
d
8.11 (dd, J¼5.5, 4.2 Hz, 1H), 7.95 (d,
4.2.2. Dimethyl 4-phenyl-6-(o-tolyl)pyridine-2,3-dicarboxylate
J¼8.2 Hz, 1H), 7.93e7.90 (m, 1H), 7.78 (s, 1H), 7.67 (dd, J¼7.1, 1.2 Hz,
(2b). Unknown compound, colorless oil; 1H NMR (400 MHz,
1H), 7.56 (dd, J¼8.2, 7.1 Hz, 1H), 7.54e7.50 (m, 2H), 7.50e7.45 (m,
CDCl3)
d
7.58 (s, 1H), 7.43 (s, 6H), 7.33e7.22 (m, 3H), 3.97 (s, 3H),
167.0, 164.7,
5H), 4.01 (s, 3H), 3.79 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 168.0,
3.74 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
165.8,160.0,149.7,146.2,137.2,136.9,134.1,131.2,130.0,129.3,129.1,
128.9, 128.6, 128.5, 128.3, 128.2, 127.1, 126.3, 125.4, 125.3, 53.5 52.9;
HRMS Calculated for C25H19NO4Na [MþNa]þ 420.1212, found
420.1213.
159.7, 148.44, 144.6, 137.7, 136.2, 135.3, 130.2, 128.9, 128.2, 127.8,
127.6,127.2, 126.8,126.5,125.2, 52.3, 51.8, 19.5; HRMS Calculated for
C
22H19NO4Na [MþNa]þ 384.1212, found 384.1216.
4.2.3. Dimethyl 4-phenyl-6-(m-tolyl)pyridine-2,3-dicarboxylate
4.2.10. Dimethyl 6-phenyl-4-(o-tolyl)pyridine-2,3-dicarboxylate
(2c). Unknown compound, colorless oil; 1H NMR (400 MHz,
(2j). Unknown compound, colorless oil; 1H NMR (400 MHz,
CDCl3)
(m, 5H), 7.35 (t, J¼7.6 Hz, 1H), 7.24 (d, J¼8.7 Hz, 1H), 4.00 (s, 3H),
3.71 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3)
168.0, 165.8,
158.2, 150.0, 146.3, 138.8, 137.7, 137.5, 130.9, 129.1, 128.9, 128.8,
d
7.88 (s, 1H), 7.84 (s, 1H), 7.82 (d, J¼7.8 Hz, 1H), 7.49e7.39
CDCl3)
7.36e7.21 (m, 3H), 7.15 (d, J¼7.4 Hz, 1H), 4.02 (s, 3H), 3.61 (s, 3H),
2.16 (s, 3H); 13C NMR (100 MHz, CDCl3)
167.3, 165.9, 157.7, 150.5,
146.5,137.7, 136.7, 135.6,130.3,130.1, 129.3,129.1, 128.9,128.6,127.5,
d
8.07 (dd, J¼7.9, 1.6 Hz, 2H), 7.78 (s, 1H), 7.53e7.43 (m, 3H),
d
d

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X. Xin et al. / Tetrahedron 69 (2013) 10245e10248
125.6, 123.9, 53.3, 52.5, 20.1; HRMS Calculated for C22H19NO4Na
14.0; HRMS Calculated for C18H19NO4Na [MþNa]þ 336.1212, found
[MþNa]þ 384.1212, found 384.1207.
336.1206.
4.2.11. Dimethyl 6-phenyl-4-(m-tolyl)pyridine-2,3-dicarboxylate
4.2.17. Dimethyl 4-butyl-6-phenylpyridine-2,3-dicarboxylate
(2k). Unknown compound, colorless oil; 1H NMR (400 MHz,
(2q). Unknown compound, colorless oil; 1H NMR (500 MHz,
CDCl3)
(t, J¼6.9 Hz, 1H), 7.24 (m, 3H), 4.02 (s, 3H), 3.75 (s, 3H), 2.41 (s, 3H);
13C NMR (100 MHz, CDCl3)
168.0, 165.8, 157.9, 150.2, 146.3, 138.6,
137.8, 137.4, 130.0, 129.9, 129.0, 128.8, 128.7, 128.6, 127.5, 125.2,
123.8, 53.2, 52.7, 21.5; HRMS Calculated for C22H19NO4Na [MþNa]þ
384.1212, found 384.1202.
d
8.07 (d, J¼6.9 Hz, 2H), 7.87 (s, 1H), 7.53e7.41 (m, 3H), 7.34
CDCl3) d 8.05e7.98 (m, 2H), 7.73 (s, 1H), 7.50e7.41 (m, 3H), 3.98 (s,
3H), 3.95 (s, 3H), 2.76e2.72 (m, 2H), 1.70e1.60 (m, 2H), 1.44e1.36
d
(m, 2H), 0.94 (t, J¼7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 168.1,
166.0, 157.9, 151.8, 146.4, 138.0, 129.9, 129.2, 129.0, 127.4, 123.6, 53.1,
52.8, 33.0, 32.6, 22.6, 13.9; HRMS Calculated for C19H21NO4Na
[MþNa]þ 350.1368, found 350.1374.
4.2.12. Dimethyl 6-phenyl-4-(p-tolyl)pyridine-2,3-dicarboxylate
4.2.18. Dimethyl 4-cyclohexyl-6-phenylpyridine-2,3-dicarboxyla-te
(2l). Unknown compound, colorless oil; 1H NMR (400 MHz,
(2r). Unknown compound, colorless oil; 1H NMR (400 MHz, CDCl3)
CDCl3)
(d, J¼8.0 Hz, 2H), 7.26 (d, J¼8.1 Hz, 2H), 4.01 (s, 3H), 3.76 (s, 3H),
2.41 (s, 3H); 13C NMR (100 MHz, CDCl3)
168.1, 165.8, 157.9, 150.1,
146.3,139.3,137.8,134.5,130.0,129.6,129.0,128.1,127.5,123.8,110.1,
53.3, 52.7, 21.4; HRMS Calculated for C22H19NO4Na [MþNa]þ
384.1212, found 384.1221.
d
8.06 (d, J¼6.9 Hz, 2H), 7.86 (s, 1H), 7.52e7.41 (m, 3H), 7.34
d
8.01 (d, J¼6.7 Hz, 2H), 7.80 (s,1H), 7.47 (m, 3H), 3.98 (s, 6H (2CH3)),
2.69 (t, J¼10.4 Hz, 1H), 1.90 (dd, J¼25.2, 12.1 Hz, 4H), 1.79 (d,
d
J¼12.3 Hz, 1H), 1.54e1.24 (m, 5H); 13C NMR (100 MHz, CDCl3)
d 168.4, 166.0, 158.2, 156.1, 145.7, 138.3, 129.8, 129.3, 129.0, 127.5,
120.9, 53.2, 52.9, 41.5, 33.7, 26.6, 26.0; HRMS Calculated for
C
21H23NO4Na [MþNa]þ 376.1525, found 376.1512.
4.2.13. Dimethyl 4-(4-methoxyphenyl)-6-phenylpyridine-2,3-
Acknowledgements
dicarboxylate (2m). Unknown compound, white solid, mp
96e97 ꢀC; 1H NMR (400 MHz, CDCl3)
d
8.07 (d, J¼6.9 Hz, 2H), 7.86
We are grateful to the National Natural Science Foundation of
China (21172218) for financial support.
(s, 1H), 7.53e7.43 (m, 3H), 7.40 (d, J¼8.7 Hz, 2H), 6.99 (d, J¼8.7 Hz,
2H), 4.02 (s, 3H), 3.86 (s, 3H), 3.78 (s, 3H); 13C NMR (100 MHz,
CDCl3)
d 168.2, 165.9, 160.5, 158.0, 149.7, 137.9, 130.0, 129.7, 129.6,
Supplementary data
129.1, 128.8, 127.5, 123.8, 114.4, 110.1, 55.5, 53.3, 52.8; HRMS Cal-
culated for C22H19NO5Na [MþNa]þ 400.1161, found 400.1143.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.10.038.
4.2.14. Dimethyl
4-(4-fluorophenyl)-6-phenylpyridine-2,3-dicar-
boxylate (2n). Unknown compound, colorless oil; 1H NMR
(400 MHz, CDCl3)
d
8.07 (d, J¼6.9 Hz, 2H), 7.84 (s, 1H), 7.45 (m, 5H),
References and notes
7.16 (t, J¼8.5 Hz, 2H), 4.02 (s, 3H), 3.75 (s, 3H); 13C NMR (100 MHz,
1. (a) Pozharskii, A. F.; Soldatenkov, A.; Katritzky, A. R. Heterocycles in Life and So-
ciety: an Introduction to Heterocyclic Chemistry, Biochemistry and Applications;
Wiley: Hoboken, NJ, 2011; (b) McAteer, C. H.; Balasubramanian, M.; Murugan, R.
In Comprehensive Heterocyclic Chemistry III; FRS, A. R. K., Ramsden, C. A., Scriven,
E. F. V., Taylor, R. J. K., Eds.; Elsevier: Amsterdam, The Netherlands, 2008; Vol. 7,
pp 309e336; (c) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435.
CDCl3)
d
167.8, 165.7, 163.3 (d, J¼249.4 Hz), 158.1, 149.0, 146.4, 137.6,
133.4, 130.2, 130.1, 129.1, 128.7, 127.5, 123.7, 115.9 (d, J¼21.8 Hz),
53.3, 52.8; 19F NMR (377 MHz, CDCl3)
d
ꢁ112.58; HRMS Calculated
for C21H16NO4FNa [MþNa]þ 388.0961, found 388.0967.
2. Reviews for construct pyridine cores: (a) Henry, G. D. Tetrahedron 2004, 60,
6043; (b) Keller, P. A. In Comprehensive Heterocyclic Chemistry III; FRS, A. R. K.,
Ramsden, C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier: Amsterdam, The
Netherlands, 2008; Vol. 7, pp 217e308; (c) Hill, M. D. Chem.dEur. J. 2010, 16,
12052; (d) Gulevich, A. V.; Dudnik, A. S.; Chernyak, N.; Gevorgyan, V. Chem. Rev.
2013, 113, 3084.
3. (a) Cacchi, S.; Fabrizi, G.; Filisti, E. Org. Lett. 2008, 10, 2629; (b) Toh, K. K.; Wang,
Y. F.; Ng, E. P. J.; Chiba, S. J. Am. Chem. Soc. 2011, 133, 13942; (c) Zora, M.; Kar-
abiyikoglu, S. In Abstracts of Papers; 243th National Meeting of American Chemical
Society, San Diego, California; March 25e29, 2012; American Chemical Society:
Washington, DC, 2012; ORGN 844; (d) Saito, A.; Konishi, T.; Hanzawa, Y. Org. Lett.
2010, 12, 372; (e) Xin, X. Y.; Wang, D. P.; Li, X. C.; Wan, B. S. Angew. Chem., Int. Ed.
2012, 51, 1693; (f) Xin, X. Y.; Wang, D. P.; Wu, F.; Li, X. C.; Wan, B. S. J. Org. Chem.
2013, 78, 4065.
4. CCDC 911162 contains the supplementary crystallographic data for 2e in this
paper. These data can be obtained Data Centre via www.ddcd.cam.ac.uk/data_
request/cif.
5. For examples of sulfinic acids elimination, see: (a) Donohoe, T. J.; Bower, J. F.;
Baker, D. B.; Basutto, J. A.; Chan, L. K. M.; Gallagher, P. Chem. Commun. 2011, 47,
10611; (b) Petasis, N. A.; Butkevich, A. N. J. Organomet. Chem. 2009, 694, 1747.
4.2.15. Dimethyl
4-(4-chlorophenyl)-6-phenylpyridine-2,3-dicar-
boxylate (2o). Unknown compound, white solid, mp 120e121 ꢀC;
1H NMR (400 MHz, CDCl3)
d
8.07 (d, J¼6.7 Hz, 2H), 7.83 (s, 1H),
7.53e7.42 (m, 5H), 7.38 (d, J¼8.5 Hz, 2H), 4.02 (s, 3H), 3.76 (s, 3H);
13C NMR (100 MHz, CDCl3)
167.7, 165.7, 158.2, 148.9, 146.5, 137.6,
d
135.9, 135.6, 130.3, 129.6, 129.2, 129.1, 128.6, 127.5, 123.6, 53.4, 52.9;
HRMS Calculated for C21H16NO4NaCl [MþNa]þ 404.0666, found
404.0649.
4.2.16. Dimethyl 6-phenyl-4-propylpyridine-2,3-dicarboxylate
(2p). Unknown compound, colorless oil; 1H NMR (400 MHz,
CDCl3)
d
8.02 (d, J¼7.0 Hz, 2H), 7.73 (s, 1H), 7.51e7.40 (m, 3H), 3.98
(s, 3H), 3.96 (s, 3H), 2.79e2.65 (m, 2H), 1.76e1.64 (m, 2H), 0.99 (t,
J¼7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 168.1, 166.0, 157.9, 151.5,
138.0, 129.9, 129.2, 129.0, 127.4, 123.6, 110.1, 53.2, 52.8, 35.2, 23.7,