Synthesis of 3-arylimidazo[1,2-a]pyridines by a catalyst-free cascade process

Article abstract of DOI:10.1055/s-0030-1260669

A simple and efficient protocol to synthesize 3-arylimidazo[1,2-a]pyridines by a catalyst-free cascade process from 2-aminopyridine and 1-bromo-2-phenylacetylene or 1,1-dibromo-2-phenylethene in yields up to 86% is described. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0030-1260669

SPECIAL TOPIC
2255
Synthesis of 3-Arylimidazo[1,2-a]pyridines by a Catalyst-Free Cascade
Process
3
-Arylimidazo[
h
1,2-
a
]pyridin
i
es qing Wu, Yinyin Pan, Xiangge Zhou*
Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China
Fax +86(28)85412026; E-mail: zhouxiangge@scu.edu.cn
Received 20 April 2011
EtO2S
Abstract: A simple and efficient protocol to synthesize 3-arylimi-
dazo[1,2-a]pyridines by a catalyst-free cascade process from 2-ami-
nopyridine and 1-bromo-2-phenylacetylene or 1,1-dibromo-2-
phenylethene in yields up to 86% is described.
O
N
N
N
F
N
N
Key words: heterocycle, catalyst-free, cascade process
N
CF3
3-Aryl-substituted imidazo[1,2-a]pyridines are often used
as core structures to construct many bioactive molecules
including GABAA agonist 1,1 CXCR3 antagonists 2,2 pos-
itive allosteric modulators (PAMs) of mGluR2 3,3 and the
liver X receptor (LXR) agonists 4 (Figure 1).4 Consider-
able attention has also recently been paid to their photolu-
minescent properties.5 The normal approach to the
synthesis of 3-substituted imidazo[1,2-a]pyridine is based
on the condensation of 2-aminopyridine and a-bromoal-
dehyde; however, this method usually suffers from sub-
strate complexity or poor selectivity.3,6 An alternative
protocol was recently reported that relies on palladium-
catalyzed C–C bond cross-coupling reactions, however,
the tedious multi-step sequence involved and the consid-
erable cost of the catalyst restricts its application.7 In light
of this, a general and straightforward methodology that
can be used to prepare such molecules is still required.
CN
1
2
CF3
N
CN
N
N
N
SO2Me
N
N
O
3
4
Figure 1 Structure of bioactive 3-aryl imidazo[1,2-a]pyridines
N
Br
R1
N
NH2
R1
N
On the other hand, transition-metal-catalyzed cycloiso-
merization of propargylpyridines has gained considerable
attention over the past decade as an effective method for
creating nitrogen-fused heterocycles such as indolizin-
ones, pyrroloquinolines, pyrroloisoquinolines, as well as
indolizines.8 An elegant protocol for the synthesis of imi-
dazopyridines by the copper-catalyzed three-component
coupling reaction of 2-aminopyridine, aldehydes, and
alkynes is also reported.9 Furthermore, ynamines and yna-
mides have recently been reported to be synthesized by
the coupling of 1-bromoalkynes with nitrogen-containing
heterocycles or amides.10 Inspired by these reports, and in
a continuation of our endeavors in the synthesis of hetero-
cyclic compounds,11 we envisioned that 2-aminopyridine
could couple with 1-bromo-2-phenylacetylene to give
alkynylamine 6, which could isomerize to 7 and undergo
subsequent intramolecular nucleophilic addition in gener-
ate the desired product 3-phenylimidazo[1,2-a]pyridine 8
as shown in Scheme 1.
5
4
8
R2
R2
– HBr
H
N
N
isomerization
R2
R1
R1
NH
N
R2
6
7
Scheme 1 Proposed synthesis of 3-aryl imidazo[1,2-a]pyridines
At first, 2-aminopyridine (4a) and 1-bromo-2-phenylacet-
ylene (5a) were employed as model substrates, as indicat-
ed in Table 1. Gratifyingly, the reaction worked well in
the absence of any catalyst to give the desired product 8a
in 32% yield in 24 hours at 100 °C (Table 1, entry 1).12
The reaction conditions were then optimized. Among sev-
eral bases examined, use of the weak inorganic base
NaOAc and NaHCO3 led to better results, giving yields
65% and 66%, respectively, while use of stronger bases
such as Cs2CO3 decreased the yield to only 17% (Table 1,
entries 2–8). After studying the influence of reaction time,
SYNTHESIS 2011, No. 14, pp 2255–2260
x
x.
x
x
.
2
0
1
1
Advanced online publication: 15.06.2011
DOI: 10.1055/s-0030-1260669; Art ID: C42011SS
© Georg Thieme Verlag Stuttgart · New York

2256
Z. Wu et al.
SPECIAL TOPIC
it was found that 24 hours was optimal for the catalysis; 8f–j). Figure 2 shows the X-ray crystal structure of the
only 50% yield was obtained after 12 hours (Table 1, en- product 8c.
try 9). Further investigations revealed that the yield in-
creased to 76% at an elevated temperature of 120 °C
(Table 1, entry 10). It is worth mentioning that the reac-
tion also worked well in dimethylsulfoxide (DMSO) or
xylene, although slightly lower yields were obtained
(Table 1, entries 11 and 12).
Table 1 Optimization of the Reaction Conditionsa
N
NH2
N
+
Br
N
Figure 2 X-ray crystal structure of the product 8c
4a
5a
8a
Entry Solvent
Additives
–
Temp (°C) Time (h) Yield (%)b
Table 2 Synthesis of 3-Aryl Imidazo[1,2-a]pyridines from Substi-
tuted 1-Bromo-2-phenylacetylenesa
1
2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
Xylene
100
100
100
100
100
100
100
100
100
120
120
120
24
24
24
24
24
24
24
24
12
24
24
24
32
50
17
65
66
19
38
39
50
76
70
69
N
K2CO3
Cs2CO3
NaOAc
NaHCO3
Et3N
R1
N
NH2
NaHCO3
3
R1
+
Br
DMF, 120 °C, 24 h
R2
R2
N
4
5
4
8
5
Entry
Product
Yield (%)b
6
N
7
pyridine
HOAc
N
N
1
2
8a
76
8
9
NaHCO3
NaHCO3
NaHCO3
NaHCO3
N
10
11
12
8b
8c
61
86
a Reaction conditions: 2-aminopyridine (0.5 mmol), 1-bromo-2-phe-
nylacetylene (0.6 mmol), solvent (0.5 mL).
b Isolated yield.
N
N
N
N
3
Next, under the optimized conditions, the scope of this
new protocol was investigated. Table 2 lists the results of
the reactions between a range of substituted 2-aminopy-
ridines and 1-bromo-2-phenylacetylenes.
Cl
N
In general, substituted 1-bromo-2-phenylacetylenes bear-
ing either electron-donating or electron-withdrawing
groups were able to react with 2-aminopyridine in moder-
ate to good yields ranging from 61 to 86%; electron-with-
drawing substituents were found to be beneficial to the
reaction (Table 2, entries 8a–e). For example, 1-bromo-2-
(4-chlorophenyl)acetylene gave the desired product in
86% yield, whereas only 61% yield was obtained in the
case of 1-bromo-2-(4-methylphenyl)acetylene. This result
might, in part, be caused by the fact that electron-rich sub-
strates were unfavorable for the nucleophilic addition step
proposed in Scheme 1. Substituents on the 2-aminopy-
ridines had less influence on the results, with yields using
such substrates ranging from 62 to 71% (Table 2, entries
4
5
8d
8e
82
70
Br
N
OMe
Synthesis 2011, No. 14, 2255–2260 © Thieme Stuttgart · New York

SPECIAL TOPIC
3-Arylimidazo[1,2-a]pyridines
2257
Table 2 Synthesis of 3-Aryl Imidazo[1,2-a]pyridines from Substi-
conditions and the convenient availability of the starting
materials, this approach is a necessary complement to the
other existing methods for producing substituted imida-
zo[1,2-a]pyridines. Further studies and applications of
this methodology are currently underway in our laborato-
ry.
tuted 1-Bromo-2-phenylacetylenesa (continued)
N
R1
N
NH2
NaHCO3
R1
+
Br
DMF, 120 °C, 24 h
R2
R2
N
5
4
8
Table 3 Synthesis of 3-Aryl Imidazo[1,2-a]pyridines from Substi-
tuted 1,1-Dibromo-2-phenylethenesa
Entry
Product
Yield (%)b
N
R1
NH2
N
Br
N
R1
NaHCO3
+
N
Br
R2
N
DMF, 120 °C, 48 h
6
8f
63
R2
4
9
8
Entry
1
Product
Yield (%)b
N
N
N
N
N
N
76
7
8
8g
8h
8i
69
71
68
62
8a
(trace)c
N
N
2
3
8b
8c
58
80
N
N
N
F
9
N
N
N
Cl
Cl
10
8j
N
N
4
5
6
7
8d
8e
8f
77
71
63
69
a Reaction conditions: 2-aminopyridine (0.5 mmol), 1-bromo-2-phe-
nylacetylene (0.6 mmol), NaHCO3 (1 mmol), DMF (0.5 mL), 120 °C,
24 h.
Br
b Isolated yield.
N
N
In an endeavor to expand the application of this protocol,
we tried to use 1,1-dibromo-2-phenylethenes directly as
substrates in this reaction, which were known to be able to
form 1-bromo-2-phenylacetylenes through use of the
Ramirez and Corey–Fuchs procedures.13,14 To our delight,
all the substituted 1,1-dibromo-2-phenylethenes worked
well under the standard conditions, and afforded compa-
rable yields with 1-bromo-2-phenylacetylenes, as shown
in Table 3.
O
N
N
In summary, we have developed a novel synthetic proto-
col for the efficient assembly of 3-aryl imidazo[1,2-a]py-
ridines by a catalyst-free cascade process. The efficiency
and substituent-tolerance of this procedure have been
demonstrated by synthesizing a number of functionalized
imidazo[1,2-a]pyridines. Considering the simple reaction
N
N
8g
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2258
Z. Wu et al.
SPECIAL TOPIC
Table 3 Synthesis of 3-Aryl Imidazo[1,2-a]pyridines from Substi-
Table 3 Synthesis of 3-Aryl Imidazo[1,2-a]pyridines from Substi-
tuted 1,1-Dibromo-2-phenylethenesa (continued)
tuted 1,1-Dibromo-2-phenylethenesa (continued)
N
N
R1
R1
NH2
NH2
N
N
Br
Br
R1
R1
NaHCO3
NaHCO3
+
+
N
N
Br
Br
R2
R2
DMF, 120 °C, 48 h
DMF, 120 °C, 48 h
R2
R2
4
4
9
9
8
8
Entry
8
Product
Yield (%)b
Entry
16
Product
Yield (%)b
N
N
N
MeO
N
8h
71
8p
30
O
N
N
N
N
F
9
8i
8j
68
62
17
18
8q
8r
33
60
N
N
N
N
Cl
10
N
Cl
N
a Reaction conditions: 2-aminopyridine (0.5 mmol), 1,1-dibromo-2-
phenylethene (0.6 mmol), NaHCO3 (1 mmol), DMF (0.5 mL),
120 °C, 48 h.
11
12
8k
76
63
b Isolated yield.
c In the absence of NaHCO3.
F
N
N
Unless otherwise noted, all reagents were purchased from commer-
cial suppliers and used without further purification. Analytical thin
layer chromatography (TLC) was performed using Merck silica gel
GF254 plates. Column chromatography was performed using silica
gel (200–300 mesh) eluting with EtOAc and petroleum ether (60–
90 °C). All products were characterized by NMR and MS analyses.
1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra
were recorded at 100 MHz (Bruker DPX) with CDCl3 as solvent.
Chemical shifts (d) are reported in ppm using TMS as internal stan-
dard.
8l
OMe
N
N
N
N
N
N
13
14
15
8m
8n
8o
63
27
63
Synthesis of 3-Aryl Imidazo[1,2-a]pyridines; Typical Procedure
A mixture of 2-aminopyridine (0.5 mmol), 1-bromo-2-phenylacet-
ylene (0.6 mmol), NaHCO3 (1 mmol), and DMF (0.5 mL) was heat-
ed at 120 °C for 24 h. The mixture was then allowed to cool to r.t.,
diluted with H2O (15 mL) and then extracted with EtOAc
(3 × 20 mL). The organic extracts were combined and then dried
over anhydrous Na2SO4. After evaporation of the solvent, the resi-
due was purified by silica gel column chromatography to afford the
corresponding product.
Cl
3-Phenylimidazo[1,2-a]pyridine (8a)
Yellow oil.
1H NMR (400 MHz, CDCl3): d = 8.32 (d, J = 6.8 Hz, 1 H), 7.69–
7.65 (m, 2 H), 7.55–7.47 (m, 4 H), 7.39 (t, J = 7.2 Hz, 1 H), 7.17 (t,
J = 8.0 Hz, 1 H), 6.77 (t, J = 6.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 145.03, 131.32, 128.22, 127.19,
127.01, 124.71, 123.31, 122.32, 117.15, 111.57.
Synthesis 2011, No. 14, 2255–2260 © Thieme Stuttgart · New York

SPECIAL TOPIC
3-Arylimidazo[1,2-a]pyridines
2259
MS (EI): m/z = 194 [M+].
6-Methyl-3-phenylimidazo[1,2-a]pyridine (8h)
Yellow oil.
3-(4-Methylphenyl)imidazo[1,2-a]pyridine (8b)
Yellow oil.
1H NMR (400 MHz, CDCl3): d = 8.22 (d, J = 7.2 Hz, 1 H), 7.59 (d,
J = 9.2 Hz, 1 H), 7.58 (s, 1 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.24 (d,
J = 8.0 Hz, 2 H), 7.11–7.06 (m, 1 H), 6.71 (t, J = 7.2 Hz, 1 H), 2.34
(s, 3 H).
13C NMR (100 MHz, CDCl3): d = 144.94, 137.13, 131.21, 128.88,
126.97, 125.28, 124.72, 123.00, 122.34, 117.16, 111.37, 20.29.
MS (EI): m/z = 208 [M+].
1H NMR (400 MHz, CDCl3): d = 8.10 (s, 1 H), 7.63 (s, 1 H), 7.58–
7.49 (m, 5 H), 7.42 (t, J = 7.2 Hz, 1 H), 7.05 (d, J = 9.2 Hz, 1 H),
2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 145.22, 132.34, 129.54, 129.21,
128.06, 127.44, 125.41, 122.17, 120.93, 117.51, 18.38.
MS (EI): m/z = 208 [M+].
6-Fluoro-3-phenylimidazo[1,2-a]pyridine (8i)
Yellow oil.
1H NMR (400 MHz, CDCl3): d = 8.18 (m, 1 H), 7.64 (s, 1 H), 7.58–
7.54 (m, 1 H), 7.45–7.44 (m, 4 H), 7.37–7.35 (m, 1 H), 7.05 (t, J =
7.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 153.75, 151.40, 142.76, 132.64,
128.36, 127.77, 127.52, 126.82, 126.03, 117.68, 117.59, 115.42,
115.16, 109.21, 108.80.
3-(4-Chlorophenyl)imidazo[1,2-a]pyridine (8c)
White solid.
1H NMR (400 MHz, CDCl3): d = 8.29 (d, J = 6.8 Hz, 1 H), 7.69 (d,
J = 7.2 Hz, 2 H), 7.49 (s, 4 H), 7.24–7.20 (m, 1 H), 6.85 (t, J =
6.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 146.24, 134.03, 132.69, 129.50,
129.19, 127.72, 124.50, 123.15, 118.31, 112.83.
MS (EI): m/z = 212 [M+].
MS (EI): m/z = 228 [M+].
6-Chloro-3-phenylimidazo[1,2-a]pyridine (8j)
White solid.
3-(4-Bromophenyl)imidazo[1,2-a]pyridine (8d)
White solid.
1H NMR (400 MHz, CDCl3): d = 8.21 (d, J = 6.8 Hz, 1 H), 7.62–
7.56 (m, 4 H), 7.37 (d, J = 8.4 Hz, 2 H), 7.17–7.12 (m, 1 H), 6.78 (t,
J = 6.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 145.28, 131.64, 131.46, 128.43,
127.16, 123.54, 122.13, 121.14, 117.34, 111.87.
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1 H), 7.62 (s, 1 H), 7.55
(d, J = 9.6 Hz, 1 H), 7.46 (d, J = 4.4 Hz, 4 H), 7.39–7.34 (m, 1 H),
7.09 (d, J = 9.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 143.36, 132.24, 128.38, 127.62,
127.55, 127.04, 125.27, 124.61, 120.21, 120.01, 117.55.
MS (EI): m/z = 228 [M+].
MS (EI): m/z = 273 [M+].
3-(4-Fluorophenyl)imidazo[1,2-a]pyridine (8k)
White solid.
3-(3-Methoxylphenyl)imidazo[1,2-a]pyridine (8e)
White solid.
1H NMR (400 MHz, CDCl3): d = 8.15 (d, J = 6.8 Hz, 1 H), 7.59 (d,
J = 8.8 Hz, 2 H), 7.44–7.41 (m, 2 H), 7.14–7.08 (m, 3 H), 6.74 (t,
J = 6.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 162.73, 160.26, 145.00, 131.45,
129.02, 128.94, 124.30, 123.64, 123.26, 122.06, 117.24, 115.43,
115.21, 111.64.
1H NMR (400 MHz, CDCl3): d = 8.37 (d, J = 7.2 Hz, 1 H), 7.70 (s,
1 H), 7.68 (d, J = 9.2 Hz, 1 H), 7.45 (t, J = 8.0 Hz, 1 H), 7.21–7.14
(m, 2 H), 7.08 (s, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 6.82 (t, J = 6.8 Hz,
1 H), 3.86 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 160.21, 146.17, 132.58, 130.57,
130.31, 125.61, 124.27, 123.53, 120.26, 118.26, 113.75, 113.54,
112.57, 55.39.
MS (EI): m/z = 212 [M+].
3-(4-Methoxylphenyl)imidazo[1,2-a]pyridine (8l)
White solid.
MS (EI): m/z = 224 [M+].
1H NMR (400 MHz, CDCl3): d = 8.25 (d, J = 6.8 Hz, 1 H), 7.66 (d,
J = 8.8 Hz, 1 H), 7.63 (s, 1 H), 7.47 (d, J = 8.8 Hz, 2 H), 7.18–7.14
(m, 1 H), 7.05 (d, J = 8.8 Hz, 2 H), 6.79 (t, J = 6.8 Hz, 1 H), 3.87 (s,
3 H).
13C NMR (100 MHz, CDCl3): d = 159.59, 145.78, 132.01, 129.62,
125.49, 123.91, 123.26, 121.54, 118.15, 114.67, 112.34, 55.39.
8-Methyl-3-phenylimidazo[1,2-a]pyridine (8f)
White solid.
1H NMR (400 MHz, CDCl3): d = 8.20 (d, J = 7.2 Hz, 1 H), 7.68 (s,
1 H), 7.55–7.47 (m, 4 H), 7.41 (t, J = 7.2 Hz, 1 H), 6.99 (d, J =
6.8 Hz, 1 H), 6.72 (t, J = 6.8 Hz, 1 H), 2.65 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 146.49, 131.79, 129.57, 129.19,
128.06, 127.90, 126.15, 123.12, 121.27, 112.60, 17.10.
MS (EI): m/z = 224 [M+].
MS (EI): m/z = 208 [M+].
3-(3-Methylphenyl)imidazo[1,2-a]pyridine (8m)
Yellow oil.
7-Methyl-3-phenylimidazo[1,2-a]pyridine (8g)
Yellow oil.
1H NMR (400 MHz, CDCl3): d = 8.12 (d, J = 7.2 Hz, 1 H), 7.52 (s,
1 H), 7.45–7.37 (m, 4 H), 7.32–7.27 (m, 2 H), 6.54 (d, J = 6.8 Hz,
1 H), 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 145.56, 134.19, 131.07, 128.44,
128.15, 126.91, 126.79, 124.16, 121.55, 115.47, 114.14, 20.18.
1H NMR (400 MHz, CDCl3): d = 8.24 (d, J = 6.8 Hz, 1 H), 7.59 (s,
1 H), 7.58 (d, J = 6.8 Hz, 1 H), 7.32–7.25 (m, 3 H), 7.14 (d, J =
6.8 Hz, 1 H), 7.10–7.06 (m, 1 H), 6.71 (t, J = 6.8 Hz, 1 H), 2.34 (s,
3 H).
13C NMR (100 MHz, CDCl3): d = 145.00, 137.98, 131.34, 128.13,
128.06, 127.94, 127.66, 124.81, 123.98, 123.12, 122.41, 117.14,
111.42, 20.45.
MS (EI): m/z = 208 [M+].
MS (EI): m/z = 208 [M+].
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Z. Wu et al.
SPECIAL TOPIC
3-(2-Chlorophenyl)imidazo[1,2-a]pyridine (8n)
White solid.
References
(1) Goodacre, S. C.; Street, L. J.; Hallett, D. J.; Crawforth, J. M.;
Kelly, S.; Owens, A. P.; Blackaby, W. P.; Lewis, R. T.;
Stanley, J.; Smith, A. J.; Ferris, P.; Sohal, B.; Cook, S. M.;
Pike, A.; Brown, N.; Wafford, K. A.; Marshall, G.; Castro, J.
L.; Atack, J. R. J. Med. Chem. 2006, 49, 35.
(2) Li, A.; Johnson, M. G.; Liu, J.; Chen, X.; Du, X.; Mihalic, J.
T.; Deignan, J.; Gustin, D. J.; Duquette, J.; Fu, Z.; Zhu, L.;
Marcus, A. P.; Bergeron, P.; McGee, L. R.; Danao, J.;
Lemon, B.; Carabeo, T.; Sullivan, T.; Ma, J.; Tang, L.; Tonn,
G.; Collins, T. L.; Medina, J. C. Bioorg. Med. Chem. Lett.
2008, 18, 688.
(3) Tresadern, G.; Cid, J. M.; Macdonald, G. J.; Vega, J. A.;
Lucas, A. I.; García, A.; Matesanz, E.; Linares, M. L.;
Oehlrich, D.; Lavreysen, H.; Biesmans, I.; Trabanco, A. A.
Bioorg. Med. Chem. Lett. 2010, 20, 175.
(4) Singhaus, R. R.; Bernotas, R. C.; Steffan, R.; Matelan, E.;
Quinet, E.; Nambi, P.; Feingold, I.; Huselton, C.;
Wilhelmsson, A.; Goos-Nilsson, A.; Wrobel, J. Bioorg.
Med. Chem. Lett. 2010, 20, 521.
1H NMR (400 MHz, CDCl3): d = 7.77 (d, J = 6.8 Hz, 1 H), 7.64 (s,
1 H), 7.62 (d, J = 8.8 Hz, 1 H), 7.50 (d, J = 7.2 Hz, 1 H), 7.41–7.30
(m, 3 H), 7.30–7.15 (m, 1 H), 6.76 (t, J = 6.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 144.79, 133.66, 132.57, 131.75,
129.30, 129.20, 127.08, 126.20, 123.51, 123.40, 121.88, 116.96,
111.23.
MS (EI): m/z = 228 [M+].
5-Methyl-3-phenylimidazo[1,2-a]pyridine (8o)
White solid.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 8.8 Hz, 1 H), 7.44 (s,
1 H), 7.34–7.28 (m, 5 H), 7.03–6.99 (m, 1 H), 6.40 (d, J = 6.8 Hz,
1 H), 2.97 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 145.97, 135.37, 133.36, 130.90,
130.57, 127.40, 126.37, 125.19, 123.25, 115.06, 112.25, 20.76.
MS (EI): m/z = 208 [M+].
(5) (a) Aginagalde, M.; Vara, Y.; Arrieta, A.; Zangi, R.;
Cebolla, V. L.; Delgado-Camon, A.; Cossio, F. P. J. Org.
Chem. 2010, 75, 2776. (b) Takizawa, S.; Nishida, J.;
Yamashita, Y. J. Photopolym. Sci. Technol. 2008, 21, 355.
(6) Muzalevskiy, V. M.; Nenajdenko, V. G.; Shastin, A. V.;
Balenkova, E. S.; Haufe, G. Synthesis 2009, 2249.
(7) (a) Enguehard, C.; Renou, J.; Collot, V.; Hervet, M.; Rault,
S.; Gueiffier, A. J. Org. Chem. 2000, 65, 6572.
Methyl 3-Phenylimidazo[1,2-a]pyridine-6-carboxylate (8p)
White solid.
1H NMR (400 MHz, CDCl3): d = 8.99 (s, 1 H), 7.70 (d, J = 9.2 Hz,
1 H), 7.68 (s, 1 H), 7.62 (d, J = 9.2 Hz, 1 H), 7.51–7.46 (m, 4 H),
7.41–7.37 (m, 1 H), 3.85 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 164.40, 145.40, 132.93, 128.45,
127.73, 127.27, 126.75, 125.96, 122.86, 116.53, 115.76, 51.45.
MS (EI): m/z = 252 [M+].
(b) Koubachi, J.; Kazzouli, S. E.; Raboin, S. B.; Mouaddib,
A.; Guillaumet, G. Synlett 2006, 3237.
(8) For some recent examples, see: (a) Seregin, I. V.;
Schammel, A. W.; Gevorgyan, V. Org. Lett. 2007, 9, 3433.
(b) Chernyak, D.; Skontos, C.; Gevorgyan, V. Org. Lett.
2010, 12, 3242. (c) Xia, Y.; Dudnik, A. S.; Li, Y.;
Gevorgyan, V. Org. Lett. 2010, 12, 5538. (d) Chernyak, D.;
Gevorgyan, V. Org. Lett. 2010, 12, 5558. (e) Kim, I.; Kim,
K. Org. Lett. 2010, 12, 2500.
3-(1-Naphthalenyl)imidazo[1,2-a]pyridine (8q)
White solid.
1H NMR (400 MHz, CDCl3): d = 7.91–7.86 (m, 2 H), 7.71 (s, 1 H),
7.68–7.62 (m, 2 H), 7.52–7.42 (m, 4 H), 7.36 (t, J = 6.8 Hz, 1 H),
7.16 (t, J = 8.0 Hz, 1 H), 6.64 (t, J = 6.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 144.78, 132.88, 132.69, 130.99,
128.60, 128.11, 127.69, 125.94, 125.37, 125.22, 124.59, 124.17,
123.35, 123.07, 122.64, 116.96, 111.28.
(9) Chernyak, N.; Gevorgyan, V. Angew. Chem. Int. Ed. 2010,
49, 2743.
(10) (a) Laroche, C.; Li, J.; Freyer, M. W.; Kerwin, S. M. J. Org.
Chem. 2008, 73, 6462. (b) Istrate, F. M.; Buzas, A. K.;
Jurberg, I. D.; Odabachian, Y.; Gagosz, F. Org. Lett. 2008,
10, 925. (c) Coste, A.; Couty, F.; Evano, G. Org. Lett. 2009,
11, 4454. (d) Burley, G. A.; Davies, D. L.; Griffith, G. A.;
Lee, M.; Singh, K. J. Org. Chem. 2010, 75, 980.
(11) (a) Wang, Y.; Wu, Z.; Wang, L.; Li, Z.; Zhou, X. Chem. Eur.
J. 2009, 15, 8971. (b) Liang, L.; Li, Z.; Zhou, X. Org. Lett.
2009, 11, 3294. (c) Wu, Z.; Jiang, Z.; Wu, D.; Xiang, H.;
Zhou, X. Eur. J. Org. Chem. 2010, 1854. (d) Wu, Z.; Zhou,
L.; Jiang, Z.; Wu, D.; Li, Z.; Zhou, X. Eur. J. Org. Chem.
2010, 4971. (e) Yu, L.; Jiang, X.; Wang, L.; Li, Z.; Wu, D.;
Zhou, X. Eur. J. Org. Chem. 2010, 5560.
MS (EI): m/z = 244 [M+].
7-Methyl-3-(4-chlorophenyl)imidazo[1,2-a]pyridine (8r)
White solid.
1H NMR (400 MHz, CDCl3): d = 8.15 (d, J = 6.8 Hz, 1 H), 7.60 (s,
1 H), 7.45 (s, 4 H), 7.41–7.40 (m, 1 H), 6.65 (d, J = 7.2 Hz, 1 H),
2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 146.80, 135.41, 133.70, 132.51,
129.43, 128.96, 127.98, 124.00, 122.38, 116.66, 115.41, 21.23.
MS (EI): m/z = 242 [M+].
(12) For examples of the construction of heterocycles from
alkyne derivatives, see: (a) Huh, D. H.; Ryu, H.; Kim, Y. G.
Tetrahedron 2004, 60, 9857. (b) Shen, W.; Kohn, T.; Fu, Z.;
Jiao, X. Y.; Lai, S.; Schmitt, M. Tetrahedron Lett. 2008, 49,
7284. (c) Tao, K.; Zheng, J.; Liu, Z.; Shen, W.; Zhang, J.
Tetrahedron Lett. 2010, 51, 3246.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis
Acknowledgment
(13) For the synthesis of 1,1-dibromoalkenes, see: (a) Ramirez,
F.; Desai, N. B.; McKelvie, N. J. Am. Chem. Soc. 1962, 84,
1745. (b) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972,
3769.
(14) For dehydrobromination of 1,1-dibromoalkenes under basic
conditions, see: Okutani, M.; Mori, Y. J. Org. Chem. 2009,
74, 442; and references therein.
This project was sponsored by Natural Science Foundation of China
(Nos. 20901052, 21072132), Sichuan Provincial Foundation
(08ZQ026–041) and Ministry of Education (NCET-10–0581). We
also thank Analytic and Testing Centre of Sichuan University for
the NMR spectral determination.
Synthesis 2011, No. 14, 2255–2260 © Thieme Stuttgart · New York