Phosphine-free palladium-catalyzed direct arylation of imidazo[1,2-a] pyridines with aryl bromides at low catalyst loading

Article abstract of DOI:10.1021/jo300528b

Ligand-free Pd(OAc)₂ was found to catalyze very efficiently the direct arylation of imidazo[1,2-a]pyridines at C3 under very low catalyst concentration. The reaction can be performed employing as little as 0.1-0.01 mol % catalyst with electron-

Full text of DOI:10.1021/jo300528b

Note
pubs.acs.org/joc
Phosphine-Free Palladium-Catalyzed Direct Arylation of Imidazo[1,2-
a]pyridines with Aryl Bromides at Low Catalyst Loading
Hai Yan Fu,† Lu Chen,‡ and Henri Doucet*,‡
†Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu,
610064, China
‡Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite
Beaulieu, 35042 Rennes, France
́
de Rennes “Catalyse et Organometalliques”, Campus de
S
* Supporting Information
ABSTRACT: Ligand-free Pd(OAc)2 was found to catalyze very
efficiently the direct arylation of imidazo[1,2-a]pyridines at C3 under
very low catalyst concentration. The reaction can be performed
employing as little as 0.1−0.01 mol % catalyst with electron-deficient
and some electron-excessive aryl bromides.
he palladium-catalyzed direct arylation of several hetero-
aromatics via a C−H bond activation using aryl halides
coupling of several heteroaromatics using ligand-free palladium
catalyst.5b−d However, so far, such procedure has not been
employed for the direct arylation of imidazo[1,2-a]pyridines.
Here, we wish to report on the reaction of imidazo[1,2-
a]pyridines using a wide variety of electronically and sterically
diverse aryl or heteroaryl bromides using low loadings of a
phosphine-free palladium catalyst.
T
has led to successes in recent years.1−3 Such couplings are very
attractive compared to classical palladium-catalyzed reactions
such as Stille, Suzuki, or Negishi couplings,4 as they do not
require the preliminary synthesis of organometallic derivatives.
However, the major drawback of most of the reported
procedures is that they require 1−10 mol % palladium catalyst
associated with 1−20 mol % of phosphine ligands. Only a few
examples of such reactions using low catalyst loadings have
been reported to date.5 Among heterocycles, imidazo[1,2-
a]pyridines display important biological properties. For
example, Zolpidem is actually employed for the short-term
treatment of insomnia, and Miroprofen is a nonsteroidal anti-
inflammatory drug.
We decided to employ commercially available imidazo[1,2-
a]pyridine and 4-bromobenzonitrile as the test substrates for
our study (Scheme 1, Table 1). We initially examined the
influence of the nature of the base on the conversion for this
reaction using DMAc as the solvent and 0.1 mol % Pd(OAc)2
as the catalyst. In the presence of KOAc as the base, a complete
conversion of 4-bromobenzonitrile was observed, and 1 was
obtained in 93% yield (Table 1, entry 1). A similar result was
obtained in the presence of CsOAc as the base, whereas
NaOAc led only to a conversion of 88% of 4-bromobenzonitrile
(Table 1, entries 2 and 3). On the other hand, K2CO3 or
Cs2CO3 gave moderate conversions of 4-bromobenzonitrile
(Table 1, entries 4 and 5). The good performance of acetates as
the base is consistent with a concerted metalation deprotona-
tion (CMD) pathway.9 The nature of the solvent often
modifies the catalyst activity in cross-coupling reactions; thus,
we observed that NMP and DMF in the presence of 0.1 mol %
Pd(OAc)2 as the catalyst also gave 1 in high yields with
complete conversion of 4-bromobenzonitrile (Table 1, entries 6
and 7). Some solvents that can be considered as “greener” than
DMAc, NMP or DMF, have also been employed. Pentan-1-
ol10a and cyclopentyl methyl ether10b led to complete
conversions of 4-bromobenzonitrile and to good yields in 1
(Table 1, entries 10 and 11). Diethylcarbonate10c was also
found to quite efficiently promote the reaction (Table 1, entry
9). On the other hand, the reaction performed in absence of
solvent led to a poor conversion of the aryl bromide (Table 1,
So far, the direct arylation of imidazo[1,2-a]pyridines
generally requires quite high catalyst loadings (2−10 mol
%).6 For example, in 2006, Berteina-Raboin and co-workers
reported that the use of 5 mol % Pd(OAc)2 associated to 10
mol % PPh3 promotes efficiently the coupling of imidazo[1,2-
a]pyridines with aryl bromides at the 3-position.6a The same
year, Sames and co-workers employed 2.5 mol % of a palladium
complex containing an imidazolyl carbene and PPh3 as ligands
for the coupling of methyl 4-bromobenzoate with ethyl
imidazo[1,2-a]pyridine-2-carboxylate. The C3 arylated imidazo-
[1,2-a]pyridine was obtained in 51% yield.6b Therefore, the
discovery of more effective conditions for the direct coupling of
imidazo[1,2-a]pyridine derivatives with aryl bromides, espe-
cially under low catalyst loading conditions, would be a
considerable advantage for industrial applications.
In 2003, de Vries and co-workers described extremely
promising results for the Heck and Suzuki reactions using a low
loading (0.1−0.01 mol %) of ligand-free catalyst Pd(OAc)2.7,8
They demonstrated that, at elevated temperature, when
Pd(OAc)2 is employed as the catalyst precursor, soluble
palladium(0) colloids or nanoparticles are formed and that
the Heck or Suzuki reaction takes place. We have recently
reported that the use of the “de Vries conditions” allows the
Received: March 12, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo300528b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 1. Influence of the Reaction Conditions on the
Table 2. Direct Arylation of Imidazo[1,2-a]pyridine with
a
Arylation of Imidazo[1,2-a]pyridine with 4-
para-Substituted Aryl Bromides
a
Bromobenzonitrile
entry
R
ratio substrate/catalyst
product
yield (%)
Pd(OAc)2
1
COMe
COMe
CHO
CHO
CHO
CO2Me
CO2Me
NO2
NO2
CF3
1000
10000
10000
1000
1000
1000
10000
10000
1000
1000
1000
1000
1000
1000
1000
1000
2
2
92
74
80
entry
solvent
base
(mol %)
convn. (%)
2
1
DMAc
DMAc
DMAc
DMAc
DMAc
NMP
KOAc
CsOAc
NaOAc
K2CO3
Cs2CO3
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
100 (93)
98
3
3
b
2
4
3
79
c
3
88
5
3
78
4
66
6
4
93
87
88
5
45
7
4
6
100
100
75
8
5
b
7
DMF
9
5
89
8
xylene
10
11
12
13
14
15
16
6
72
80
82
b
9
diethylcarbonate
pentan-1-ol
82
F
7
10
11
100 (87)
Cl
8
c
c
cyclopentyl methyl
ether
99
Cl
8
40
t-Bu
9
78
65
63
12
13
14
15
16
17
18
No solvent
DMAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
0.1
38
86 (80)
85
MeO
NMe2
10
11
0.01
0.01
0.01
0.01
0.01
0.01
NMP
a
Conditions: Pd(OAc)2 (0.001 or 0.0001 equiv), aryl bromide (1
equiv), imidazo[1,2-a]pyridine (1.5 equiv), KOAc (2 equiv), 16 h, 150
°C. Pentan-1-ol as the solvent. Diethylcarbonate as the solvent, 130
DMF
0
b
diethylcarbonate
pentan-1-ol
0
b
c
55
23
°C.
cyclopentyl methyl
ether
d
19
20
21
22
23
24
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
0.1
0.1
0.1
1
86
omethylbromobenzene, resulting in 72−93% yields of the
products 2−6 (Table 2, entries 1−3, 6−8, and 10). In all cases,
the expected 3-arylated imidazo[1,2-a]pyridines were selectively
obtained. Again, good yields in 3 or 5 could be obtained using
diethylcarbonate or pentan-1-ol as the solvents (Table 2, entries
4, 5, and 9). 4-Fluorobromobenzene was also successfully
coupled with imidazo[1,2-a]pyridine to give 7 in 80% yield
(Table 2, entry 11). It should be noted that even 4-
chlorobromobenzene could be employed to give 8 in 82%
yield (Table 2, entry 12). In the course of this reaction, no
cleavage of the C−Cl bond was observed, allowing further
transformations. Even the use of electron-rich aryl bromide, 4-
tert-butylbromobenzene, led to 9 in a good yield of 78%, when
0.1 mol % catalyst was employed (Table 2, entry 14). On the
other hand, under these conditions, a partial conversion of 4-
bromoanisole or 4-bromo-N,N-dimethylaniline was observed,
and 10 and 11 were obtained in slightly lower yields of 65%
and 63% (Table 2, entries 15 and 16).
The meta-substituted aryl bromides, 3-bromobenzonitrile, 3-
bromobenzaldehyde, or 3-trifluoromethylbromobenzene, gave
12−14 in 71−93% yields using 0.1−0.01 mol % Pd(OAc)2
(Table 3, entries 1−5). A lower yield of 53% in 15 was obtained
in the presence of 3-chlorobromobenzene because of a partial
conversion of this aryl bromide (Table 3, entry 7). 2-
Bromonaphthalene was also found to be suitable coupling
partner and gave 16 in 82% in the presence of only 0.01 mol %
catalyst (Table 3, entry 9).
e
93 (83)
f
92 (87)
f
100 (91)
g
2
93 (87)
h
0.01
84 (77)
a
Conditions: Pd(OAc)2, 4-bromobenzonitrile (1 equiv), imidazo[1,2-
a]pyridine (1.5 equiv), base (2 equiv), 16 h, 150 °C, conversion of 4-
bromobenzonitrile; isolated yields of 1 are given in parentheses. 130
°C. 125 °C. 100 °C. Imidazo[1,2-a]pyridine (1.1 equiv). 1 h. 0.25
h. 4-Bromobenzonitrile (30 mmol), imidazo[1,2-a]pyridine (45
mmol), KOAc (60 mmol), DMAc (45 mL), 16 h, 150 °C.
b
c
d
e
f
g
h
entry 12). Then, we performed the reactions using only 0.01
mol % catalyst with these solvents (Table 1, entries 13−17).
Only DMAc and NMP gave good conversions of 4-
bromobenzonitrile. It sould be noted that the reaction can be
performed using only a slight excess of imidazo[1,2-a]pyridine
(1.1 equiv) (Table 1, entry 20) or shorter reaction times. For
example, in the presence of 0.1 or 1 mol % catalyst, conversions
of 92% and 100% were obtained after only 1 h (Table 1, entries
21 and 22). In the presence of 2 mol % Pd(OAc)2, a conversion
of 93% of 4-bromobenzonitrile was obtained after 15 min
(Table 1, entry 23). A scale up experiment was also successful,
as reactions performed on 1 or 30 mmol scale led to very
similar yields (Table 1, entries 13 and 24).
Then, imidazo[1,2-a]pyridine was coupled with several other
aryl bromides in the presence of 0.1−0.01 mol % Pd(OAc)2,
KOAc as the base in DMAc, pentan-1-ol, or diethylcarbonate
(Tables 2 and 3, Schemes 1−3). Selective 3-arylations were
observed using the para-substituted electron-deficient aryl
bromides, 4-bromoacetophenone, 4-bromobenzaldehyde,
methyl 4-bromobenzoate, 4-bromonitrobenzene, or 4-trifluor-
Then, we employed a range of ortho-substituted aryl
bromides (Scheme 1). Similar yields were obtained with 2-
bromobenzonitrile and 2-trifluoromethylbromobenzene than
with the para-substituted aryl bromides. From these two
reactants, 17 and 18 were obtained in 92 and 70% yields,
resprectively. On the other hand, ethyl 2-bromobenzoate led to
B
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The Journal of Organic Chemistry
Note
5-bromopyrimidine, with imidazo[1,2-a]pyridine in the pres-
ence of 0.1 mol % Pd(OAc)2 proceed nicely to give 22−26 in
73−92% yields (Scheme 2).
Table 3. Direct Arylation of Imidazo[1,2-a]pyridine with
meta-Substituted Aryl Bromides
a
The poly-heteroarylation of polybromobenzene would give a
simple access to conjugated compounds. Again, using only 0.1
mol % Pd(OAc)2 as the catalyst, 2,7-dibromofluorene or 1,4-
dibromonaphthalene were diheteroarylated with imidazo[1,2-
a]pyridine to give 27 and 28 in very high yields (Scheme 3,
top). In the presence of 9,10-dibromoanthracene, the desired
coupling product 29 was obtained in a lower yield of 59%
because of the formation of a small amount of 21 as side-
product. 1,3,5-Tribromobenzene was also successfully em-
ployed to prepare the 1,3,5-tri(heteroaryl)benzene 30 in 84%
yield (Scheme 3, bottom). Surprisingly, no mono- or di-
heteroarylated benzene derivatives were isolated in the course
of this reaction.
entry
R or ArBr
ratio substrate/catalyst prod. yield (%)
1
2
3
4
5
6
7
8
9
CN
CN
1000
10000
1000
12
12
13
13
14
14
15
16
16
93
90
71
20
83
32
53
88
82
CHO
b
CHO
1000
The reaction is not limited to the use of imidazo[1,2-
a]pyridine. Under the same reaction conditions, imidazo[1,2-
a]pyridine-6-carbonitrile was successfully coupled with 4-
bromobenzaldehyde or 2-bromonaphthalene to give 31 and
32 in 64 and 72% yields, respectively (Scheme 4).
CF3
1000
CF3
10000
1000
Cl
2-bromonaphthalene
2-bromonaphthalene
1000
10000
a
In summary, we have demonstrated that using as little as
0.1−0.01 mol % of Pd(OAc)2 as catalyst precursor, the direct 3-
arylation via C−H bond activation of imidazo[1,2-a]pyridines
proceeds in moderate to very high yields. We also observed that
some solvents considered as “greener” than DMAc can be
employed.
Conditions: Pd(OAc)2 (0.001 or 0.0001 equiv), aryl bromide (1
equiv), imidazo[1,2-a]pyridine (1.5 equiv), KOAc (2 equiv), 16 h, 150
b
°C. Diethylcarbonate as the solvent, 130 °C.
Scheme 1. Direct Arylation of Imidazo[1,2-a]pyridine with
ortho-Substituted Aryl Bromides
EXPERIMENTAL SECTION
■
General Procedure. As a typical experiment, the reaction of the
aryl bromide (1 mmol), imidazo[1,2-a]pyridine (0.177 g, 1.5 mmol) or
imidazo[1,2-a]pyridine-6-carbonitrile (0.186 g, 1.3 mmol), and KOAc
(0.196 g, 2 mmol) at 150 °C during 16 h in DMAc (4 mL) in the
presence of Pd(OAc)2 (0.224 mg, 0.001 mmol or 0.0224 mg, 0.0001
mmol; see tables or schemes), under argon affords the coupling
product after evaporation of the solvent and purification on silica gel.
4-Imidazo[1,2-a]pyridin-3-ylbenzonitrile (1). 4-Bromobenzoni-
trile (0.182 g, 1 mmol) affords 1 in 80% (0.175 g) yield; light
amorphous yellow solid; mp 175−176 °C.
19 in only 55% yield. A high reactivity of 1-bromonaphthalene
was also observed to produce 20 in 81% yield. Finally, the more
congested aryl bromide, 9-bromoanthracene, was employed.
The target product 21 was isolated in 58% yield. In the course
of this reaction, the formation of anthracene from dehaloge-
nation of 9-bromoanthracene was also observed in 10% yield. It
should be noted that these five reactions were performed using
only 0.1 mol % Pd(OAc)2 as the catalyst.
Some imidazo[1,2-a]pyridines substituted at C3 by pyr-
imidines have been found to be efficient as cyclin-dependent
kinase inhibitors.11 We observed that such heteroaryl bromides
are also suitable reactants. The coupling of 3- or 4-
bromopyridines, 3-bromoquinoline, 4-bromoisoquinoline, or
1H NMR (400 MHz, CDCl3): δ 8.33 (d, J = 6.9 Hz, 1H), 7.73 (s,
1H), 7.72 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 3H), 7.21 (t, J = 7.2
Hz, 1H), 6.85 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
146.8, 134.0, 133.7, 132.8, 127.4, 125.0, 123.7, 123.0, 118.4, 113.2,
110.9. Elemental analysis calcd (%) for C14H9N3 (219.24): C 76.70, H
4.14. Found: C 76.81, H 4.10.
4-Imidazo[1,2-a]pyridin-3-ylacetophenone (2). 4-Bromoaceto-
phenone (0.199 g, 1 mmol) affords 2 in 92% (0.217 g) yield;
amorphous white solid; mp 161−162 °C.
1H NMR (400 MHz, CDCl3): δ 8.36 (d, J = 6.9 Hz, 1H), 8.06 (d, J
= 8.2 Hz, 2H), 7.75 (s, 1H), 7.70−7.60 (m, 3H), 7.21 (t, J = 7.2 Hz,
1H), 6.84 (t, J = 7.2 Hz, 1H). 2.62 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 197.0, 146.7, 136.0, 133.8, 133.6, 129.2, 127.1, 124.7, 124.6,
Scheme 2. Direct Arylation of Imidazo[1,2-a]pyridine with Heteroaryl Bromides
C
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The Journal of Organic Chemistry
Note
Scheme 3. Direct Arylation of Imidazo[1,2-a]pyridine with Di- or Tribromobenzene Derivatives or a Dibromofluorene
1H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 6.2 Hz, 1H), 7.62 (m,
2H), 7.47−7.44 (m, 2H), 7.17−7.12 (m, 3H), 6.75 (t, J = 6.7 Hz, 1H).
3-(4-Chlorophenyl)-imidazo[1,2-a]pyridine (8).6c 4-Bromo-
chlorobenzene (0.191 g, 1 mmol) affords 8 in 82% (0.187 g) yield.
1H NMR (400 MHz, CDCl3): δ 8.20 (m, 1H), 7.62 (m, 2H), 7.41
(m, 4H), 7.14 (m, 1H), 6.75 (m, 1H).
Scheme 4. Direct Arylation of Imidazo[1,2-a]pyridine-6-
carbonitrile with Aryl Bromides
3-(4-t-Butylphenyl)-imidazo[1,2-a]pyridine (9). 4-tert-Butyl-
bromobenzene (0.213 g, 1 mmol) affords 9 in 78% (0.195 g) yield;
amorphous white solid; mp 143−145 °C.
1H NMR (400 MHz, CDCl3): δ 8.34 (d, J = 6.9 Hz, 1H), 7.67 (s,
1H), 7.65 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 8.2
Hz, 2H), 7.17 (t, J = 7.2 Hz, 1H), 6.77 (t, J = 6.8 Hz, 1H), 1.38 (s,
9H). 13C NMR (100 MHz, CDCl3): δ 151.2, 145.9, 132.2, 127.7,
126.3, 126.1, 125.6, 123.9, 123.4, 118.1, 112.3, 34.7, 31.2. Elemental
analysis calcd (%) for C17H18N2 (250.34): C 81.56, H 7.25. Found: C
81.69, H 7.36.
3-(4-Methoxyphenyl)-imidazo[1,2-a]pyridine (10).13 4-Bro-
moanisole (0.187 g, 1 mmol) affords 10 in 65% (0.146 g) yield.
1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 6.8 Hz, 1H), 7.62−7.59
(m, 2H), 7.42 (d, J = 8.8 Hz, 2H), 7.12 (t, J = 8.0 Hz, 1H), 7.00 (d, J =
8.0 Hz, 2H), 6.73 (t, J = 6.8 Hz, 1H), 3.83 (s, 6H).
(4-Imidazo[1,2-a]pyridin-3-yl-phenyl)-dimethylamine (11).
4-Bromo-N,N-dimethylaniline (0.200 g, 1 mmol) affords 11 in 63%
(0.149 g) yield; amorphous yellow solid; mp 137−139 °C.
1H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 6.9 Hz, 1H), 7.52−7.48
(m, 2H), 7.28 (d, J = 8.2 Hz, 2H), 7.02 (t, J = 7.2 Hz, 1H), 6.72 (d, J =
8.2 Hz, 2H), 6.63 (t, J = 7.2 Hz, 1H), 2.91 (s, 6H). 13C NMR (100
MHz, CDCl3): δ 150.1, 145.4, 131.3, 129.1, 126.0, 123.4, 123.3, 117.8,
116.4, 112.5, 111.9, 40.2. Elemental analysis calcd (%) for C15H15N3
(237.30): C 75.92, H 6.37. Found: C 75.68, H 6.30.
123.2, 118.3, 113.0, 26.5. Elemental analysis calcd (%) for C15H12N2O
(236.27): C 76.25, H 5.12. Found: C 76.21, H 5.04.
4-Imidazo[1,2-a]pyridin-3-ylbenzaldehyde (3). 4-Bromoben-
zaldehyde (0.185 g, 1 mmol) affords 3 in 80% (0.178 g) yield;
amorphous light yellow solid; mp 110−111 °C.
1H NMR (300 MHz, CDCl3): δ 9.96 (s, 1H), 8.35 (d, J = 6.9 Hz,
1H), 7.92 (d, J = 8.2 Hz, 2H), 7.74 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H),
7.61 (d, J = 8.2 Hz, 2H), 7.18 (t, J = 7.2 Hz, 1H), 6.81 (t, J = 7.2 Hz,
1H). 13C NMR (75 MHz, CDCl3): δ 191.1, 146.8, 135.1, 135.0, 133.9,
130.4, 127.2, 124.9, 124.3, 123.2, 118.3, 113.1. Elemental analysis calcd
(%) for C14H10N2O (222.24): C 75.66, H 4.54. Found: C 75.50, H
4.62.
Methyl 4-Imidazo[1,2-a]pyridin-3-ylbenzoate (4). Methyl 4-
bromobenzoate (0.215 g, 1 mmol) affords 4 in 93% (0.235 g) yield;
amorphous white solid; mp 147−149 °C.
3-Imidazo[1,2-a]pyridin-3-ylbenzonitrile (12). 3-Bromobenzo-
nitrile (0.182 g, 1 mmol) affords 12 in 93% (0.204 g) yield;
amorphous white solid; mp 138−140 °C.
1H NMR (300 MHz, CDCl3): δ 8.40 (d, J = 6.9 Hz, 1H), 8.18 (d, J
= 8.2 Hz, 2H), 7.79 (s, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.68 (d, J = 8.2
Hz, 2H), 7.23 (t, J = 7.2 Hz, 1H), 6.89 (t, J = 7.2 Hz, 1H), 3.90 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 166.6, 146.8, 133.8, 133.6, 130.5,
129.4, 127.2, 124.8, 123.4, 118.5, 113.0, 52.3. Elemental analysis calcd
(%) for C15H12N2O2 (252.27): C 71.42, H 4.79. Found: C 71.30, H
4.64.
1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 6.9 Hz, 1H), 7.73 (s,
1H), 7.69 (d, J = 8.2 Hz, 1H), 7.63 (s, 1H), 7.60−7.49 (m, 3H), 7.14
(t, J = 7.2 Hz, 1H), 6.78 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 146.3, 133.2, 131.5, 130.9, 130.5, 130.5, 129.9, 124.7, 123.0,
122.6, 118.1, 117.9, 113.2, 112.9. Elemental analysis calcd (%) for
C14H9N3 (219.24): C 76.70, H 4.14. Found: C 76.68, H 4.07.
3-Imidazo[1,2-a]pyridin-3-ylbenzaldehyde (13). 3-Bromoben-
zaldehyde (0.185 g, 1 mmol) affords 13 in 71% (0.158 g) yield;
amorphous gray solid; mp 41−42 °C.
3-(4-Nitrophenyl)-imidazo[1,2-a]pyridine (5).12 4-Bromonitro-
benzene (0.202 g, 1 mmol) affords 5 in 88% (0.210 g) yield.
1H NMR (400 MHz, CDCl3): δ 8.35 (d, J = 6.8 Hz, 1H), 8.31 (d, J
= 8.0 Hz, 2H), 7.78 (s, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.23 (t, J = 7.2
Hz, 1H), 6.88 (t, J = 6.4 Hz, 1H).
1H NMR (400 MHz, CDCl3): δ 10.09 (s, 1H), 8.32 (d, J = 6.9 Hz,
1H), 8.07 (s, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.2 Hz, 1H),
7.77 (s, 1H), 7.75−7.63 (m, 2H), 7.24 (t, J = 7.2 Hz, 1H), 6.86 (t, J =
7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 191.7, 146.4, 137.2,
133.6, 133.0, 130.4, 130.1, 129.5, 128.3, 124.9, 124.3, 123.1, 118.4,
113.2. Elemental analysis calcd (%) for C14H10N2O (222.24): C 75.66,
H 4.54. Found: C 75.57, H 4.50.
3-(4-Trifluoromethylphenyl)-imidazo[1,2-a]pyridine (6). 4-
Trifluoromethylbromobenzene (0.225 g, 1 mmol) affords 6 in 72%
(0.189 g) yield; amorphous white yellow solid; mp 150−151 °C.
1H NMR (300 MHz, CDCl3): δ 8.32 (d, J = 6.9 Hz, 1H), 7.77−7.56
(m, 6H), 7.22 (t, J = 7.2 Hz, 1H), 6.83 (t, J = 7.2 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 146.6, 133.5, 132.9, 129.8 (q, J = 32.9 Hz), 127.7,
126.1 (q, J = 3.9 Hz), 124.7, 124.2, 123.9 (q, J = 272.3 Hz), 123.1,
118.4, 113.0. Elemental analysis calcd (%) for C14H9F3N2 (262.23): C
64.12, H 3.46. Found: C 64.24, H 3.35.
3-(3-Trifluoromethylphenyl)-imidazo[1,2-a]pyridine (14). 3-
Trifluoromethylbromobenzene (0.225 g, 1 mmol) affords 14 in 83%
(0.218 g) yield; amorphous white solid; mp 79−80 °C.
3-(4-Fluorophenyl)-imidazo[1,2-a]pyridine (7).13 4-Bromo-
fluorobenzene (0.175 g, 1 mmol) affords 7 in 80% (0.170 g) yield.
1H NMR (400 MHz, CDCl3): δ 8.27 (d, J = 7.9 Hz, 1H), 7.79 (s,
1H), 7.75−7.60 (m, 5H), 7.20 (t, J = 7.2 Hz, 1H), 6.83 (t, J = 7.2 Hz,
D
dx.doi.org/10.1021/jo300528b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1H). 13C NMR (100 MHz, CDCl3): δ 146.5, 133.3, 131.7 (q, J = 32.4
Hz), 131.0, 130.2, 129.8, 124.7 (q, J = 3.9 Hz), 124.6, 124.4 (q, J = 3.9
Hz), 124.2, 123.9 (q, J = 272.8 Hz), 123.0, 118.5, 113.1. Elemental
analysis calcd (%) for C14H9F3N2 (262.23): C 64.12, H 3.46. Found: C
64.02, H 3.54.
3-Pyridin-3-ylimidazo[1,2-a]pyridine (22). 3-Bromopyridine
(0.158 g, 1 mmol) affords 22 in 92% (0.179 g) yield; amorphous
gray solid; mp 38−39 °C.
1H NMR (400 MHz, CDCl3): δ 8.84 (s, 1H), 8.65 (d, J = 3.5 Hz,
1H), 8.27 (d, J = 6.7 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.75 (s, 1H),
7.70 (d, J = 9.2 Hz, 1H), 7.45 (t, J = 7.0 Hz, 1H), 7.24 (t, J = 7.2 Hz,
1H), 6.86 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 149.2,
148.8, 146.6, 135.1, 133.3, 125.6, 124.8, 123.9, 122.9, 122.3, 118.5,
113.1. Elemental analysis calcd (%) for C12H9N3 (195.22): C 73.83, H
4.65. Found: C 73.94, H 4.51.
3-(3-Chlorophenyl)-imidazo[1,2-a]pyridine (15). 3-Bromo-
chlorobenzene (0.191 g, 1 mmol) affords 15 in 53% (0.121 g) yield;
clear oil.
1H NMR (300 MHz, CDCl3): δ 8.26 (d, J = 6.9 Hz, 1H), 7.66 (s,
1H), 7.62 (d, J = 8.2 Hz, 1H), 7.49 (s, 1H), 7.42−7.28 (m, 3H), 7.16
(t, J = 7.0 Hz, 1H), 6.78 (t, J = 7.0 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ 146.2, 135.0, 133.0, 130.9, 130.3, 128.0, 127.6, 125.7, 124.4,
124.1, 123.0, 118.2, 112.7. Elemental analysis calcd (%) for C13H9ClN2
(228.68): C 68.28, H 3.97. Found: C 68.34, H 3.80.
3-Pyridin-4-ylimidazo[1,2-a]pyridine (23). 4-Bromopyridine
hydrochloride (0.194 g, 1 mmol) affords 23 in 91% (0.177 g) yield;
amorphous light yellow solid; mp 126−128 °C.
1H NMR (400 MHz, CDCl3): δ 8.37 (d, J = 8.1 Hz, 1H), 8.06 (d, J
= 6.8 Hz, 2H), 7.76 (s, 1H), 7.68−7.62 (m, 3H), 7.21 (t, J = 7.2 Hz,
1H), 6.84 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 150.6,
147.2, 136.8, 134.4, 125.2, 123.4, 123.0, 120.9, 118.5, 113.3. Elemental
analysis calcd (%) for C12H9N3 (195.22): C 73.83, H 4.65. Found: C
73.74, H 4.50.
3-Naphthalen-2-yl-imidazo[1,2-a]pyridine (16). 2-Bromo-
naphthalene (0.207 g, 1 mmol) affords 16 in 88% (0.215 g) yield;
amorphous light yellow oil.
1H NMR (400 MHz, CDCl3): δ 8.36 (d, J = 6.9 Hz, 1H), 7.96 (s,
1H), 7.92 (d, J = 8.2 Hz, 1H), 7.88−7.80 (m, 2H), 7.77 (s, 1H), 7.68
(d, J = 8.8 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.55−7.45 (m, 2H), 7.17
(t, J = 8.0 Hz, 1H), 6.77 (t, J = 6.4 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 146.0, 133.4, 132.7, 132.6, 128.8, 127.8, 127.6, 126.6, 126.5,
126.4, 126.3, 125.5, 124.2, 123.2, 118.1, 112.5. Elemental analysis calcd
(%) for C17H12N2 (244.29): C 83.58, H 4.95. Found: C 83.70, H 4.99.
2-Imidazo[1,2-a]pyridin-3-ylbenzonitrile (17). 2-Bromobenzo-
nitrile (0.182 g, 1 mmol) affords 17 in 92% (0.202 g) yield;
amorphous white solid; 146−147 °C.
4-Imidazo[1,2-a]pyridin-3-ylisoquinoline (24). 4-Bromoisoqui-
noline (0.208 g, 1 mmol) affords 24 in 90% (0.221 g) yield;
amorphous white solid; mp 168−169 °C.
1H NMR (400 MHz, CDCl3): δ 9.36 (s, 1H), 8.65 (s, 1H), 8.12−
8.07 (m, 1H), 7.84 (s, 1H), 7.79−7.60 (m, 4H), 7.57−7.50 (m, 1H),
7.25 (t, J = 7.8 Hz, 1H), 6.76 (t, J = 6.7 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 153.5, 146.4, 144.6, 134.6, 134.4, 131.3, 128.4, 128.3, 127.8,
124.6, 124.1, 123.8, 120.3, 120.2, 118.2, 112.5. Elemental analysis calcd
(%) for C16H11N3 (245.28): C 78.35, H 4.52. Found: C 78.32, H 4.57.
3-Imidazo[1,2-a]pyridin-3-ylquinoline (25). 3-Bromoquinoline
(0.208 g, 1 mmol) affords 25 in 73% (0.179 g) yield; amorphous white
yellow solid; mp 146−148 °C.
1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 6.9 Hz, 1H), 7.86 (s,
1H), 7.81 (d, J = 8.2 Hz, 1H), 7.75−7.63 (m, 2H), 7.59 (d, J = 8.2 Hz,
1H), 7.49 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 6.82 (t, J = 6.8
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 146.5, 134.7, 134.1, 133.1,
132.4, 129.8, 128.6, 125.1, 123.3, 121.2, 118.2, 117.6, 112.9, 112.3.
Elemental analysis calcd (%) for C14H9N3 (219.24): C 76.70, H 4.14.
Found: C 76.89, H 4.21.
3-(2-Trifluoromethylphenyl)-imidazo[1,2-a]pyridine (18). 2-
Trifluoromethylbromobenzene (0.225 g, 1 mmol) affords 18 in 70%
(0.184 g) yield; amorphous white solid; mp 103−104 °C.
1H NMR (300 MHz, CDCl3): δ 7.85 (d, J = 7.6 Hz, 1H), 7.75−7.55
(m, 5H), 7.46 (d, J = 7.2 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 6.73 (t, J =
6.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 145.6, 133.9, 133.1,
132.0, 131.1 (q, J = 30.2 Hz), 129.4, 127.5, 126.8 (q, J = 5.0 Hz),
124.3, 123.5, 123.1 (q, J = 273.5 Hz), 121.7, 117.8, 112.4. Elemental
analysis calcd (%) for C14H9F3N2 (262.23): C 64.12, H 3.46. Found: C
64.05, H 3.56.
1H NMR (400 MHz, CDCl3): δ 9.09 (s, 1H), 8.34 (d, J = 6.9 Hz,
1H), 8.29 (s, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.84 (d, J = 7.5 Hz, 1H),
7.83 (s, 1H), 7.74 (t, J = 7.2 Hz, 1H), 7.70 (d, J = 7.0 Hz, 1H), 7.59 (t,
J = 7.2 Hz, 1H), 7.24 (t, J = 7.2 Hz, 1H), 6.86 (t, J = 7.2 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ 149.9, 147.5, 146.7, 133.9, 133.7, 130.0,
129.5, 127.9, 127.8, 127.5, 124.9, 123.0, 122.7, 122.5, 118.6, 113.2.
Elemental analysis calcd (%) for C16H11N3 (245.28): C 78.35, H 4.52.
Found: C 78.46, H 4.80.
3-Pyrimidin-5-ylimidazo[1,2-a]pyridine (26). 5-Bromopyrimi-
dine (0.159 g, 1 mmol) affords 26 in 88% (0.172 g) yield; amorphous
white solid; mp 196−197 °C.
1H NMR (400 MHz, CDCl3): δ 9.21 (s, 1H), 8.94 (s, 2H), 8.23 (d,
J = 6.5 Hz, 1H), 7.78 (s, 1H), 7.69 (d, J = 8.9 Hz, 1H), 7.26 (t, J = 7.2
Hz, 1H), 6.89 (t, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
157.7, 155.2, 147.1, 134.1, 125.4, 124.3, 122.6, 118.7, 118.6, 113.6.
Elemental analysis calcd (%) for C11H8N4 (196.21): C 67.34, H 4.11.
Found: C 67.51, H 4.04.
Methyl 2-imidazo[1,2-a]pyridin-3-yl-benzoate (19). Methyl 2-
bromobenzoate (0.215 g, 1 mmol) affords 19 in 55% (0.139 g) yield;
amorphous light yellow solid; 72−74 °C.
1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 7.5 Hz, 1H), 7.73 (d, J
= 6.0 Hz, 1H), 7.65−7.43 (m, 4H), 7.48 (d, J = 7.2 Hz, 1H), 7.18 (t, J
= 7.2 Hz, 1H), 6.73 (t, J = 6.6 Hz, 1H), 3.54 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 167.1, 145.7, 132.8, 132.6, 132.5, 131.1, 131.0, 129.2,
129.0, 124.6, 124.1, 123.7, 117.9, 112.0, 52.2. Elemental analysis calcd
(%) for C15H12N2O2 (252.27): C 71.42, H 4.79. Found: C 71.51, H
4.89.
2,7-Bis(imidazo[1,2-a]pyridine)-fluorene (27). 2,7-Dibromo-
fluorene (0.324 g, 1 mmol), imidazo[1,2-a]pyridine (0.354 g, 3
mmol), and KOAc (0.392 g, 4 mmol) at 150 °C during 16 h in DMAc
(4 mL) in the presence of Pd(OAc)2 (0.224 mg, 0.001 mmol) affords
27 in 82% (0.328 g) yield; amorphous orange solid, mp 229−231 °C.
1H NMR (400 MHz, CDCl3): δ 8.40 (d, J = 6.0 Hz, 2H), 7.94 (d, J
= 7.2 Hz, 2H), 7.76 (s, 4H), 7.69 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 7.6
Hz, 2H), 7.21 (t, J = 7.6 Hz, 2H), 6.83 (t, J = 6.2 Hz, 2H), 4.07 (s,
2H). 13C NMR (100 MHz, CDCl3): δ 146.2, 144.3, 141.1, 132.6,
127.9, 126.8, 125.9, 124.6, 124.2, 123.4, 120.7, 118.3, 112.6, 37.0.
Elemental analysis calcd (%) for C27H20N4 (400.47): C 80.98, H 5.03.
Found: C 80.99, H 5.14.
3-Naphthalen-1-ylimidazo[1,2-a]pyridine (20).13 1-Bromo-
naphthalene (0.207 g, 1 mmol) affords 20 in 81% (0.198 g) yield.
1H NMR (400 MHz, CDCl3): δ 7.93 (m, 2H), 7.77 (s, 1H), 7.72
(d, J = 10.8 Hz, 1H), 7.66 (d, J = 6.8 Hz, 1H), 7.56 (s, 2H), 7.49 (m,
2H), 7.37 (m, 1H), 7.17 (t, J = 7.5 Hz, 1H), 6.64 (t, J = 6.6 Hz, 1H).
3-Anthracen-9-ylimidazo[1,2-a]pyridine (21). 9-Bromoanthra-
cene (0.257 g, 1 mmol) affords 21 in 58% (0.171 g) yield; amorphous
white solid; mp 208−209 °C.
1,4-Bis(imidazo[1,2-a]pyridine)-naphthalene (28). 1,4-Dibro-
monaphthalene (0.286 g, 1 mmol), imidazo[1,2-a]pyridine (0.354 g, 3
mmol), and KOAc (0.392 g, 4 mmol) at 150 °C during 16 h in DMAc
(4 mL) in the presence of Pd(OAc)2 (0.224 mg, 0.001 mmol) affords
28 in 88% (0.317 g) yield; amorphous light yellow solid; mp 246−247
°C.
1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 8.01 (d, J = 8.4 Hz,
2H), 7.83 (s, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H),
7.41 (t, J = 7.5 Hz, 2H), 7.29 (t, J = 7.5 Hz, 2H), 7.22 (d, J = 6.8 Hz,
1H), 7.17 (t, J = 6.4 Hz, 1H), 6.54 (t, J = 6.8 Hz, 1H). 13C NMR (100
MHz, CDCl3): δ 146.0, 135.5, 131.8, 131.5, 129.1, 128.8, 126.7, 125.6,
125.5, 124.3, 124.1, 122.0, 120.6, 118.0, 112.3. Elemental analysis calcd
(%) for C21H14N2 (294.35): C 85.69, H 4.79. Found: C 85.80, H 4.65.
1H NMR (400 MHz, CDCl3): δ 7.82 (s, 2H), 7.79 (d, J = 8.0 Hz,
2H), 7.73 (d, J = 8.6 Hz, 2H), 7.69 (s, 2H), 7.66−7.60 (m, 2H), 7.47−
7.41 (m, 2H), 7.21 (t, J = 7.2 Hz, 2H), 6.72 (t, J = 7.2 Hz, 2H). 13C
NMR (100 MHz, CDCl3): δ 145.9, 134.1, 132.4, 128.5, 127.8, 127.3,
E
dx.doi.org/10.1021/jo300528b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
125.9, 124.4, 123.9, 123.0, 118.0, 112.4. Elemental analysis calcd (%)
for C24H16N4 (360.41): C 79.98, H 4.47. Found: C 79.87, H 4.37.
9,10-Bis(imidazo[1,2-a]pyridine)-anthracene (29). 9,10-Dibro-
moanthracene (0.336 g, 1 mmol), imidazo[1,2-a]pyridine (0.354 g, 3
mmol), and KOAc (0.392 g, 4 mmol) at 150 °C during 16 h in DMAc
(4 mL) in the presence of Pd(OAc)2 (0.224 mg, 0.001 mmol) affords
29 in 59% (0.242 g) yield; amorphous yellow solid; mp 376−378 °C.
1H NMR (400 MHz, CDCl3): δ 7.98 (s, 2H), 7.85 (d, J = 9.0 Hz,
2H), 7.65−7.60 (m, 4H), 7.42−7.35 (m, 6H), 7.28 (t, J = 7.8 Hz, 2H),
6.70 (t, J = 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 146.1, 136.5,
131.8, 126.9, 126.2, 124.9, 124.7, 124.0, 120.3, 118.0, 112.7. Elemental
analysis calcd (%) for C28H18N4 (410.47): C 81.93, H 4.42. Found: C
81.80, H 4.54.
1,3,5-Tris(imidazo[1,2-a]pyridine)-benzene (30). 1,3,5-Tribro-
mobenzene (0.315 g, 1 mmol), imidazo[1,2-a]pyridine (0.708 g, 6
mmol), and KOAc (0.588 g, 6 mmol) at 150 °C during 16 h in DMAc
(4 mL) in the presence of Pd(OAc)2 (0.224 mg, 0.001 mmol) affords
affords 30 in 84% (0.358 g) yield; amorphous gray solid; mp 249−250
°C.
Chem., Int. Ed. 2009, 48, 9792. (g) Fischmeister, C.; Doucet, H. Green
Chem. 2011, 13, 741.
(2) For selected recent contributions on direct arylations or
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A. L.; Derridj, F.; Djebbar, S.; Doucet, H. Tetrahedron Lett. 2008, 49,
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2010, 12, 4320. (c) Roger, J.; Pozgan, F.; Doucet, H. Adv. Synth. Catal.
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2010, 352, 696.
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Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuji, A.; Nakata, T.; Tani,
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ligand-less palladium catalysts: (a) Parisien, M.; Valette, D.; Fagnou, K.
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2009, 65, 9772.
1H NMR (400 MHz, CDCl3): δ 8.39 (d, J = 5.9 Hz, 3H), 7.80 (s,
3H), 7.78 (s, 3H), 7.67 (d, J = 8.8 Hz, 3H), 7.21 (t, J = 7.2 Hz, 3H).
6.85 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 146.5, 133.2,
131.7, 126.3, 124.7, 124.3, 123.1, 118.4, 113.1. Elemental analysis calcd
(%) for C27H18N6 (426.47): C 76.04, H 4.25. Found: C 76.10, H 4.21.
3-(4-Formylphenyl)-imidazo[1,2-a]pyridine-6-carbonitrile
(31). 4-Bromobenzaldehyde (0.185 g, 1 mmol) affords 31 in 64%
(0.158 g) yield; amorphous white solid; mp 231−233 °C.
(6) For examples of direct arylations at C3 of imidazo[1,2-a]pyridine:
(a) Koubachi, J.; El Kazzouli, S.; Berteina-Raboin, S.; Mouaddib, A.;
Guillaumet, G. Synlett 2006, 3237. (b) Toure, B. B.; Lane, B. S.;
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Sames, D. Org. Lett. 2006, 8, 1979. (c) Kumar, P. V.; Lin, W.-S.; Shen,
J.-S.; Nandi, D.; Lee, H. M. Organometallics 2011, 30, 5160.
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Quinet, E.; Nambi, P.; Feingold, I.; Huselton, C.; Wilhelmsson, A.;
Goos-Nilsson, A.; Wrobel, J. Bioorg. Med. Chem. Lett. 2010, 20, 521.
(e) Koubachi, J.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G.
Tetrahedron 2010, 66, 1937.
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39, 1118.
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H. Tetrahedron Lett. 2011, 52, 1383. (b) Beydoun, K.; Doucet, H.
ChemSusChem 2011, 4, 526. (c) Dong, J. J.; Roger, J.; Verrier, C.;
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2053.
1H NMR (400 MHz, CDCl3): δ 10.10 (s, 1H), 8.80 (s, 1H), 8.09
(d, J = 8.3 Hz, 2H), 7.93 (s, 1H), 7.80 (d, J = 9.3 Hz, 1H), 7.74 (d, J =
8.3 Hz, 2H), 7.37 (d, J = 9.3 Hz, 1H). 13C NMR (100 MHz, CDCl3):
δ 191.1, 145.8, 136.3, 135.8, 133.5, 130.9, 129.7, 128.2, 125.9, 124.6,
119.6, 116.3, 99.7. Elemental analysis calcd (%) for C15H9N3O
(247.25): C 72.87, H 3.67. Found: C 72.98, H 3.54.
3-Naphthalen-2-ylimidazo[1,2-a]pyridine-6-carbonitrile
(32). 2-Bromonaphthalene (0.207 g, 1 mmol) affords 32 in 72%
(0.194 g) yield; amorphous white solid; mp 112−114 °C.
1H NMR (400 MHz, CDCl3): δ 8.76 (s, 1H), 7.97 (d, J = 8.0 Hz,
1H), 7.94 (s, 1H), 7.90−7.80 (m, 3H), 7.71 (d, J = 9.3 Hz, 1H), 7.60−
7.50 (m, 3H), 7.25 (d, J = 9.3 Hz, 1H). 13C NMR (100 MHz, CDCl3):
δ 145.0, 134.7, 133.4, 133.1, 129.8, 129.5, 128.0, 127.8, 127.3, 127.0,
127.1, 125.2, 124.7, 123.8, 119.2, 116.5, 98.9. Elemental analysis calcd
(%) for C18H11N3 (269.30): C 80.28, H 4.12. Found: C 80.14, H 4.00.
ASSOCIATED CONTENT
■
(11) Byth, K. F.; Culshaw, J. D.; Green, S.; Oakes, S.; Thomas, A. P.
Bioorg. Med. Chem. Lett. 2004, 14, 2245.
(12) Liebscher, J.; Feist, K. J. Prakt. Chem. 1988, 330, 175.
S
* Supporting Information
1H and 13C NMR spectra of new compounds and 1H spectra of
known compounds. This material is available free of charge via
the Internet at http://pubs.acs.org
(13) Wu, Z.; Pan, Y.; Zhou, X. Synthesis 2011, 2255.
AUTHOR INFORMATION
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Corresponding Author
*E-mail: henri.doucet@univ-rennes1.fr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We are grateful to the Chinese Scholarship Council for grants
to H.Y.F. and L.C. We thank CNRS and “Rennes Metropole”
for providing financial support.
REFERENCES
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dx.doi.org/10.1021/jo300528b | J. Org. Chem. XXXX, XXX, XXX−XXX