Direct heteroarylation of 5-bromothiophen-2-ylpyridine and of 8-bromoquinoline via palladium-catalysed C-H bond activation: Simpler access to heteroarylated nitrogen-based derivatives

Article abstract of DOI:10.1039/c3cy00150d

The palladium-catalysed direct heteroarylation of the pyridyl-containing substrates, 2-(5-bromothiophen-2-yl)pyridine and 8-bromoquinoline, proceeds in moderate to high yields with a variety of heteroarenes in the presence of 1-2 mol% of a palladium catalyst. This approach allows the access to polyheteroaromatics which are interesting building blocks as (NC)-chelate ligands. The reaction proceeds regioselectively at the C5 position of thiophenes, thiazoles, furans or pyrroles and tolerates various substituents such as formyl, acetyl, ester, nitrile or chloro on the heteroarene. Therefore, this method allows a straightforward modulation of the electron density distribution on such derivatives.

Full text of DOI:10.1039/c3cy00150d

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Direct heteroarylation of 5-bromothiophen-2-
ylpyridine and of 8-bromoquinoline via palladium-
catalysed C–H bond activation: simpler access to
heteroarylated nitrogen-based derivatives†
Cite this: DOI: 10.1039/c3cy00150d
´
Jenny Laroche, Kassem Beydoun, Veronique Guerchais* and Henri Doucet*
The palladium-catalysed direct heteroarylation of the pyridyl-containing substrates, 2-(5-bromothiophen-2-yl)-
pyridine and 8-bromoquinoline, proceeds in moderate to high yields with a variety of heteroarenes in the
presence of 1–2 mol% of a palladium catalyst. This approach allows the access to polyheteroaromatics
which are interesting building blocks as (N^C)-chelate ligands. The reaction proceeds regioselectively at
the C5 position of thiophenes, thiazoles, furans or pyrroles and tolerates various substituents such as
formyl, acetyl, ester, nitrile or chloro on the heteroarene. Therefore, this method allows a straightforward
modulation of the electron density distribution on such derivatives.
Received 4th March 2013,
Accepted 15th April 2013
DOI: 10.1039/c3cy00150d
www.rsc.org/catalysis
Introduction
Recently, the palladium-catalysed direct arylation of hetero-
aromatics has emerged as a very powerful method for the
synthesis of (hetero)arylated heteroaromatics.1–4 However, there
are still limitations for these reactions in terms of substrate
scope. For example, the coupling of substrates incorporating a
pyridine ring or its derivatives such as quinolines via C–H bond
functionalization has attracted less attention due to the possible
poisoning of palladium by coordination of the nitrogen atom.1
Nitrogen-based compounds containing heterocycles, such as
heteroaryl-thienylpyridine or -quinoline (heteroaryl = thiophene,
imidazole, indole. . .), have attracted increased interest due to
their coordination and/or physical properties5 making them
important building blocks for the preparation of opto-electronic
devices (Fig. 1).6–8 For example, (oligo)thienylpyridine has been
used to prepare single dye SAMs with multicolour fluorescence.7d
Coordination of 2-pyridyl(oligo)thiophenes to platinum(II) or
iridium(III) centres led to complexes displaying both phospho-
rescence and fluorescence properties.7e N,N-Quinoline-based
boron complexes have been used to prepare electroluminescent
devices.8a Cyclopentyldithiophene substituted by a quinoline
moiety has been incorporated in dye-sensitized solar cells.8g
Fig. 1 A simpler access to nitrogen-based ligands.
Up to now, the introduction of various heteroaryl groups
into these nitrogen-containing compounds has been achieved
using Stille, Suzuki or Negishi type couplings.7,8 To our knowl-
edge, the synthesis of such compounds using palladium-
catalysed coupling of 1 or 2 (Fig. 1) with heteroarenes via
C–H bond functionalization has not been reported so far.
The palladium-catalysed direct heteroarylation of 1 or 2
would open the access to a variety of (N,C)-chelate ligands
(precursors of five- and six-membered ring metal complexes,
see Fig. 1) or extended conjugated systems. This method would
present considerable advantages: (i) it would allow us to reduce
´
Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite de Rennes 1
´
´
‘‘Organometalliques, Materiaux et Catalyse’’, Campus de Beaulieu, 35042 Rennes,
France. E-mail: veronique.guerchais@univ-rennes1.fr, henri.doucet@univ-rennes1.fr;
Fax: +33 0223236939
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3cy00150d
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the number of steps and (ii) lower the amount of wastes 1-methyl-1H-pyrrole-2-carbaldehyde, the coupling product 9
produced. In addition, such coupling reactions are expected to was obtained in a moderate yield of 56% (Table 1, entry 6).
present a better functional group tolerance, which would allow a The direct use of furan derivatives is an important field for
straightforward modification of the heteroarene substituents.
research in green chemistry, since some of them can be
obtained from agricultural wastes rich in pentosan polymers.
Results and discussion
Table 1 Palladium-catalysed direct heteroarylations of 2-(5-bromothiophen-2-yl)-
We now report (i) conditions for the palladium-catalysed direct
regioselective arylation of 2-(5-bromothiophen-2-yl)pyridine 1
with a set of heteroarenes using a cheap base and an air stable
catalyst, (ii) the reactivity of 2-thiophen-2-ylpyridine for direct
arylation with aryl bromides, (iii) the coupling of 8-bromo-
quinoline 2 with a wide variety of heteroarenes.
pyridine 1 (Scheme 2)
Entry Heteroarene
Product
Yield (%)
71a
1
We started our investigation on the C–H functionalization of
2-(5-bromothiophen-2-yl)pyridine 1 using 2-i-butylthiazole as the
coupling partner as such heteroarenes had been previously found
to be very reactive for palladium-catalysed direct arylation.9 Since
thiophenes are electron-rich heterocycles, the oxidative addition of
bromothiophenes to the palladium centre often requires the use of
phosphine ligands. The reaction using 1 mol% PdCl(C3H5)(dppb)
as the catalyst at 150 1C proceeded towards completion in 24 h
affording 3 in 76% yield (Scheme 1). In the course of this coupling
reaction, no side-products arising upon the activation of the C–H
bond at the C3 position of the thiophene ring of 1, via coordina-
tion of the pyridine ring, were detected. This reaction performed at
120 1C under similar reaction conditions gave 3 in only 15% yield
due to a low conversion of 1.
2
75
3
4
62a
70
Then, we studied the scope of this reaction with various hetero-
arenes (Scheme 2 and Table 1). Good yields of 4, 5 and 7 were also
obtained for the coupling of 1 with thiophene-2-carbonitrile,
2-methyl-2(thiophen-2-yl)-1,3-dioxolane and 2-acetyl-4-chlorothio-
phene (Table 1, entries 1, 2 and 4). Lower yields of the desired
coupling products 6 and 8 were obtained using 2-chlorothiophene
and 1,2-dimethylimidazole (Table 1, entries 3 and 5). To
enlarge the scope of the reaction, we also performed the
5-arylation of a pyrrole and a furan derivative. In the presence of
5
6
62a
56
7
8
26a
29a
Scheme 1
9
88
10
55b
Conditions: PdCl(C3H5)(dppb) (0.01 equiv.), 2-(5-bromothiophen-2-yl)-
pyridine 1 (1 equiv.), heteroarene (2 equiv.), KOAc (2 equiv.), DMAc, 24 h,
b
Scheme 2
150 1C.a PdCl(C3H5)(dppb) (0.02 equiv.). Cs2CO3 (2 equiv.) as base.
c
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Table 2 Influence of the reaction conditions for the direct arylation of 2-thio-
However, a low yield of 10 was obtained using methyl 2-methyl-
furan-3-carboxylate as a substrate (Table 1, entry 7). Furan
derivatives are known to be quite unreactive heteroarenes.9
The same trend was observed in the presence of 3,5-dimethyl-
isoxazole. The coupling product 11 was obtained in only 29%
yield (Table 1, entry 8).
With the two latter heteroarenes, a dehalogenation side-reaction
of 1 occurred affording 2-thienylpyridine in good amount. On the
other hand, the reaction proceeded nicely in the presence of
imidazo[1,2-a]pyridine, leading to the desired coupling product
12 in a high 88% yield (Table 1, entry 9). Finally, we investigated
the C2 arylation of benzoxazole using the same catalyst, but in the
presence of stronger base, Cs2CO3, which promotes the deprotona-
tion of benzoxazole at the C2 position.10 The coupling product 13
was successfully formed in 55% yield (Table 1, entry 10).
We have recently reported that the iridium-coordinated
2-thiophen-2-ylpyridines of complex 14 can be directly arylated with
a variety of aryl bromides using 5 mol% Pd(OAc)2 catalyst to give 15
(Scheme 3). Arylation occurs regioselectively at the thienyl-C5
position of the cyclometallated ligands.11 Based on these results,
we have examined the reactivity of 2-thiophen-2-ylpyridine 16
towards aryl bromides using various catalytic conditions
(Scheme 4). This approach would also provide a simple access
to the family of the polyheteroaromatics described above.
We studied the coupling of 2-thienylpyridine 16 with 4-bromo-
propiophenone (Scheme 4, Table 2). The results show that the
reaction is not regioselective, as both the C3 and C5 positions of
2-thiophen-2-ylpyridine 16 were arylated. The two regioisomers,
17a and 17b, were produced in a 6: 5 ratio, whatever the reaction
conditions employed. The formation of the C5-arylated product
phen-2-ylpyridine 16 with 4-bromopropiophenone (Scheme 4)
Entry
Catalyst
Base
Solvent
Yield of 17a (%)
1
2
3
4
5
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
KOAc
DMAc
Xylene
DMAc
DMAc
Xylene
23
25
24
22
23
Cs2CO3
Cs2CO3
KOAc
KOAc
Conditions: [Pd] (0.02 equiv.), 2-thiophen-2-ylpyridine 16 (2 equiv.),
4-bromopropiophenone (1 equiv.), base (2 equiv.), 24 h, 150 1C. In all
cases, a ratio 17a : 17b of 6 : 5 was obtained.
17a is assumed to involve a concerted metallation deprotonation
mechanism;12 whereas, the formation of 17b likely arises from a
coordination assisted mechanism as a result of coordination of the
nitrogen atom of the pyridine ring to the palladium center. Such a
coordination assisted mechanism has been proposed to explain
the arylation at the C3 position of thiophene-2-carboxamides.13
It should be noted that this mechanism is inhibited for cyclo-
metallated thienylpyridine ligands in complex 14. Even when the
reaction proceeds towards completion in 36 h, it affords 17a in
only 22–25% yields using various reaction conditions (Table 2).
Then, we have investigated the influence of the nature of the
aryl bromide on the regioselectivity of the arylation reaction
(Scheme 5). Similarly, the reaction of 16 with 4-bromobenzo-
nitrile led to a mixture of the C3 and C5 arylated products 18a
and 18b. However, the regioselectivity was enhanced, as the
desired C5 arylation product 18a was obtained in 86% selectivity
and in 66% yield.
Finally, we investigated the direct coupling of 8-bromoquinoline
2 with heteroarenes, as such reactions would provide a simple
access to extended conjugated systems (Fig. 1; right).8a,g
We first determined the influence of the reaction conditions
for palladium-catalysed coupling of 2-isobutylthiazole with
8-bromoquinoline 2 (Scheme 6 and Table 3). When the reaction
was performed with 2 mol% of PdCl(C3H5)(dppb) in DMAc with
KOAc at 150 1C for 24 h, the expected coupling product 19 was
obtained in a low yield of 28% (Table 3, entry 1); while the use
of CsOAc as the base afforded an improved yield in 19 of 43%
(Table 3, entry 2). The nature of the solvent often modifies the
catalytic activity in cross-coupling reactions; thus, we changed
the solvent to DMF which is also known to be a good solvent for
Scheme 3
Scheme 4
Scheme 5
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Scheme 7
Scheme 6
was obtained. Using 5 mol% of more stable PdCl(C3H5)(dppb)
catalyst, the product 24 was obtained in 35% yield due to a
palladium C–H activation/functionalization. A relatively good
yield in 19 (Table 3, entry 3) was obtained; however, we did not
select this solvent due to the formation of several unidentified
side-products, which were not observed in DMAc. An increase
Table 4 Palladium-catalysed direct arylation of heteroarenes with 8-bromo-
of the catalyst loading to 5 mol% afforded an higher yield of 19 quinoline 2 (Scheme 7)
(72%) (Table 3, entry 4). However, in the course of this reaction,
Entry
Heteroarene
Product
Yield (%)
58
a partial homo-coupling side-reaction of 8-bromoquinoline to
form [8,80]biquinolinyl took place. Then, we examined the
efficiency of ligand free palladium catalyst Pd(OAc)2, which is also
known to be a very good catalyst system for the C–H activation of
heteroarenes.11 In order to avoid the formation of the homo-
coupling side-product, we added to the reaction mixture Bu4NBr
which can act as a stabilizing agent for palladium catalysts,
preventing them from fast aggregation. The presence of Bu4NBr
improved the yield of 19 to 78% when 5 mol% of Pd(OAc)2 catalyst
loading was used (Table 3, entries 5 and 6). On the other hand,
when 2 mol% Pd(OAc)2 was employed with or without additives,
the reaction proceeded towards completion in 24 h affording quite
similar yields of 19 (Table 3, entries 7 and 8). It should be noted
that a lower reaction temperature of 120 1C gave a poor yield of
19 due to a low conversion of 2 (Table 3, entry 9). Therefore, we
employed 2 mol% Pd(OAc)2 or PdCl(C3H5)(dppb) as a catalyst
without additives in DMAc at 150 1C for the substrate scope
investigation.
We examined the scope of the heteroarylation of 8-bromo-
quinoline 2 using a set of heteroarenes (Scheme 7 and Table 4).
With 2-ethyl-4-methylthiazole, thiophene-2-carbonitrile or 2-acetyl-
thiophene and 2 mol% Pd(OAc)2, CsOAc as the base in DMAc at
150 1C, the coupling products 20, 21 and 22 were obtained in
moderate to high yields of 58%, 81% and 53%, respectively
(Table 4, entries 1–3). The use of an acetyl functional group
protected as an acetal gave a slightly higher yield of the product
23 (Table 4, entry 4). On the other hand, in the presence of
2-methylthiophene, and 2 mol% Pd(OAc)2, a very low yield in 24
1
2
3
4
5
6
7
81
53
58
35a
73
81
Table
3
Influence of the reaction conditions for the direct arylation of
2-i-butylthiazole with 8-bromoquinoline 2 (Scheme 6)
Entry Catalyst (mol%)
Solvent Base Additive Yield in 19 (%)
8
9
88b
61b
1
2
3
4
5
6
7
8
9
PdCl(C3H5)(dppb) (2) DMAc KOAc
PdCl(C3H5)(dppb) (2) DMAc CsOAc —
PdCl(C3H5)(dppb) (2) DMF
PdCl(C3H5)(dppb) (5) DMAc CsOAc
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
—
28
43
47
72
17
CsOAc —
DMAc CsOAc —
DMAc CsOAc Bu4NBr 78
DMAc CsOAc Bu4NBr 84
DMAc CsOAc —
DMAc CsOAc —
76
17a
Conditions: Pd(OAc)2 (0.02 equiv.), 8-bromoquinoline 2 (1 equiv.),
heteroarenes (2 equiv.), CsOAc (2 equiv.), DMAc, 24–27 h, 150 1C.
a
b
PdCl(C3H5)(dppb) (0.05 equiv.). Cs2CO3 (2 equiv.) as base,
PdCl(C3H5)(dppb) (0.035 equiv.).
Conditions: 8-bromoquinoline 2 (1 equiv.), 2-i-butylthiazole (2 equiv.),
base (2 equiv.), 24 h, 150 1C.a 120 1C.
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partial conversion of the 8-bromoquinoline (Table 4, entry 5). It (2 mmol) in the presence of PdCl(C3H5)(dppb) (6.1 mg,
should be noted that such 8-thienyl-substituted quinolines have 0.01 mmol or 12.2 mg, 0.02 mmol) (see Table 1) were dissolved
been employed for the synthesis of cyclometallated platinum in DMAc (4 mL) under an argon atmosphere. The reaction
complexes.14 We also studied the reactivity of some imidazole mixture was stirred in a pre-heated oil bath at 150 1C for 24 h.
derivatives such as 1,2-dimethylimidazole and imidazo[1,2-a]- After allowing the reaction mixture to cool down to room
pyridine. In both cases, the reaction proceeds nicely to give the temperature, the coupling product was obtained after evapora-
target products 25 and 26 in high yields of 73% and 81%, tion of the solvent and filtration on silica gel.
respectively (Table 4, entries 6 and 7). The C2 arylation of
benzoxazole and benzothiazole with 8-bromoquinoline was reaction of 2-(5-bromothiophen-2-yl)-pyridine
2-[5-(2-Isobutylthiazol-5-yl)-thiophen-2-yl]-pyridine (3). The
(0.240 g,
1
also examined using again the stronger base Cs2CO3.10 When 1 mmol), 2-isobutylthiazole (0.282 g, 2 mmol), KOAc (0.196 g,
benzoxazole was used in the presence of 3.5 mol% PdCl(C3H5)- 2 mmol) and PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol) in DMAc
(dppb) catalyst, the reaction proceeded nicely to give the desired for 24 h affords the product 3 in 76% (0.228 g) yield as a
coupling product 27 in high isolated yield (Table 4, entry 8). The yellow solid (mp 94–97 1C). Purification was performed using
reaction with benzothiazole, using the same reaction conditions, diethylether–pentane (3/7) as the eluent. 1H NMR (400 MHz,
led to the coupling product 28 in a lower yield of 61% (Table 4, CDCl3): d 8.55 (d, J = 4.8 Hz, 1H), 7.78 (s, 1H), 7.65 (m, 2H), 7.46
entry 9). In the course of this reaction, side-reactions to form (d, J = 3.8 Hz, 1H), 7.12 (m, 2H), 2.86 (d, J = 7.1 Hz, 2H), 2.14
quinoline and [8,80]biquinolinyl were also observed.
(m, 1H), 1.02 (d, J = 6.6 Hz, 6H). 13C NMR (100 MHz, CDCl3):
d 169.2, 151.8, 149.4, 143.9, 138.0, 136.4, 135.2, 131.5, 125.6,
124.7, 121.8, 118.2, 42.2, 29.5, 22.0. Elemental analysis calcd
(%) for C16H16N2S2 (300.44): C, 63.96; H, 5.37%; found: C,
Conclusion
In summary, we have demonstrated that the palladium-catalysed 64.11; H, 5.48%.
direct heteroarylation of 2-(5-bromothiophen-2-yl)pyridine 1 and
50-Pyridin-2-yl-[2,20]bithiophenyl-5-carbonitrile (4). The reac-
8-bromoquinoline 2 proceeds with a variety of heteroarenes. It tion of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g, 1 mmol),
should be noted that this protocol, which employs a moderate thiophene-2-carbonitrile (0.218 g, 2 mmol), KOAc (0.196 g,
loading of air stable catalysts, is applicable to a wide range of 2 mmol) and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) in DMAc
heteroarenes. This procedure allowed us to synthesize in one step for 24 h affords the product 4 in 71% (0.190 g) yield as a bright
new heteroarylated-(thienyl)pyridine and -quinoline derivatives. yellow solid (mp 186–189 1C). Purification was performed using
Moreover, we found that this method tolerates several functional diethylether–pentane (3/7) as the eluent. 1H NMR (400 MHz,
groups on the incorporated heteroaryl group. In addition, the CDCl3): d 8.59 (d, J = 4.5 Hz, 1H), 7.70 (m, 2H), 7.54 (d, J = 3.9 Hz,
major by-products of these couplings are KBr or CsBr/AcOH instead 1H), 7.50 (d, J = 3.9 Hz, 1H), 7.28 (d, J = 3.9 Hz, 1H), 7.20 (m, 2H).
of metallic salts obtained using more classical coupling procedures, 13C NMR (100 MHz, CDCl3): d 151.6, 149.7, 146.3, 144.6, 138.3,
making this process economically viable and environmentally 136.8, 136.4, 126.7, 125.1, 123.6, 122.5, 118.7, 114.1, 107.7.
attractive. Therefore, this method will open up new perspectives Elemental analysis calcd (%) for C14H8N2S2 (268.36): C, 62.66;
for the design of nitrogen-based building blocks, which are useful H, 3.00%; found: C, 62.78; H, 3.14%.
due to their potential coordination and photophysical properties.
2-[50-(2-Methyl-[1,3]dioxolan-2-yl)-[2,20]bithiophenyl-5-yl]-pyridine
(5). The reaction of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g,
1 mmol), 2-methyl-2-thiophen-2-yl-[1,3]dioxolane (0.340 g, 2 mmol),
KOAc (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol)
in DMAc for 24 h affords the product 5 in 75% (0.247 g) yield as
Experimental section
General remarks
All the reactions were performed under argon using a Schlenk a light green solid (mp 118–121 1C). Purification was performed
tube apparatus and pre-dried glassware. All chemical reactants using diethylether–pentane (1/4) as the eluent. 1H NMR
were obtained from commercial sources and used without (400 MHz, CDCl3): d 8.54 (d, J = 4.6 Hz, 1H), 7.63 (m, 2H),
further purification. DMAc of analytical grade (99%) was not 7.46 (d, J = 3.7 Hz, 1H), 7.14 (m, 2H), 7.09 (d, J = 3.7 Hz, 1H),
distilled before use. KOAc 99+, CsOAc 99+ and Cs2CO3 99% 6.96 (d, J = 3.7 Hz, 1H), 4.03 (m, 4H), 1.79 (s, 3H). 13C NMR
were used. Flash chromatography was performed on silica gel (100 MHz, CDCl3): d 152.2, 149.5, 146.7, 143.3, 139.2, 136.9,
(230–400 mesh). Thin-layer chromatography was carried out 136.5, 125.0, 124.9, 124.3, 123.7, 121.8, 118.4, 107.0, 65.0, 27.4.
using Merck silica gel GF254 plates. Chromatograms were Elemental analysis calcd (%) for C17H15NO2S2 (329.44): C,
recorded using a SHIMADZU GCMS-GP2010S gas chromato- 61.98; H, 4.59%; found: C, 61.99; H, 4.44%.
graph mass spectrometer. 1H NMR and 13C NMR were recorded
2-(50-Chloro-[2,20]bithiophenyl-5-yl)-pyridine (6). The reac-
on Bruker Avance-300, -400, -500. The chemical shifts are tion of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g, 1 mmol),
reported in ppm (d) relative to CDCl3 (1H: 7.26 and 13C: 77.0).
2-chlorothiophene (0.237 g, 2 mmol), KOAc (0.196 g, 2 mmol)
and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) in DMAc for 24 h
affords the product 6 in 62% (0.172 g) yield as a light green solid (mp
133–136 1C). Purification was performed using diethylether–pentane
Representative procedure for the heteroarylation of
2-(5-bromothiophen-2-yl)pyridine 1
As a typical experiment, 2-(5-bromothiophen-2-yl)pyridine 1 (1 mmol), (1/49) as the eluent. 1H NMR (400 MHz, CDCl3): d 8.57 (d, J = 4.6 Hz,
heteroaryl partner (2 mmol), KOAc or Cs2CO3 (see Table 1) 1H), 7.69 (m, 2H), 7.45 (d, J = 3.8 Hz, 1H), 7.16 (t, J = 4.6 Hz, 1H),
c
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7.10 (d, J = 3.8 Hz, 1H), 7.01 (d, J = 3.8 Hz, 1H), 6.86 (d, J = 158.8, 152.2, 149.6, 147.2, 143.6, 136.6, 134.4, 125.0, 123.6, 122.0,
3.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 152.1, 149.6, 143.8, 118.6, 115.2, 106.0, 51.4, 13.8. Elemental analysis calcd (%) for
138.3, 136.6, 136.1, 129.1, 127.0, 125.0, 124.5, 123.1, 122.0,
C16H13NO3S (299.35): C, 64.20; H, 4.38%; found: C, 64.17;
118.5. Elemental analysis calcd (%) for C13H8ClNS2 (277.79): H, 4.30%.
C, 56.21; H, 2.90%; found: C, 56.10; H, 2.98%.
2-[5-(3,5-Dimethylisoxazol-4-yl)-thiophen-2-yl]-pyridine (11).
1-(3-Chloro-50-pyridin-2-yl-[2,20]bithiophenyl-5-yl)-ethanone (7). The reaction of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g,
The reaction of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g, 1 mmol), 3,5-dimethylisoxazole (0.194 g, 2 mmol), KOAc
1 mmol), 1-(4-chloro-thiophen-2-yl)-ethanone (0.321 g, 2 mmol), (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol)
KOAc (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (6.1 mg, in DMAc for 24 h affords the product 11 in 29% (0.074 g) yield
0.01 mmol) in DMAc for 24 h affords the product 7 in 70% as a light green solid (mp 122–125 1C). Purification was
(0.223 g) yield as an orange solid (mp 163–166 1C). Purification performed using diethylether–pentane (1/4) as the eluent.
was performed using diethylether–pentane (1/4) as the eluent. 1H NMR (400 MHz, CDCl3): d 8.58 (d, J = 4.5 Hz, 1H), 7.69
1H NMR (400 MHz, CDCl3): d 8.59 (d, J = 4.6 Hz, 1H), 7.66 (m, 2H), 7.56 (d, J = 3.8 Hz, 1H), 7.17 (t, J = 5.1 Hz, 1H), 7.03
(m, 2H), 7.55 (m, 3H), 7.18 (t, J = 6.5 Hz, 1H), 2.53 (s, 3H). (d, J = 3.8 Hz, 1H), 2.56 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz,
13C NMR (100 MHz, CDCl3): d 189.4, 151.8, 149.7, 146.9, 139.6, CDCl3): d 165.9, 158.5, 152.2, 149.6, 144.6, 136.7, 133.5, 126.9,
138.8, 136.7, 134.7, 133.8, 128.6, 124.6, 122.5, 121.8, 118.9, 26.2. 124.7, 122.1, 118.5, 110.7, 12.2, 11.3. Elemental analysis calcd
Elemental analysis calcd (%) for C15H10ClNOS2 (319.83): C, (%) for C14H12N2OS (256.32): C, 65.60; H, 4.72%; found: C,
56.33; H, 3.15%; found: C, 56.47; H, 3.04%.
65.41; H, 4.66%.
2-[5-(2,3-Dimethylimidazol-4-yl)-thiophen-2-yl]-pyridine (8).
3-(5-Pyridin-2-ylthiophen-2-yl)-imidazo[1,2-a]pyridine (12).
The reaction of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g, The reaction of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g,
1 mmol), 1,2-dimethylimidazole (0.192 g, 2 mmol), KOAc 1 mmol), imidazo[1,2-a]pyridine (0.236 g, 2 mmol), KOAc
(0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol)
in DMAc for 24 h affords the product 8 in 62% (0.158 g) yield as in DMAc for 24 h affords the product 12 in 88% (0.244 g) yield
a brown solid (mp 120–123 1C). Purification was performed as a brown solid (mp 95–98 1C). Purification was performed
using methanol–dichloromethane (1/49) as the eluent. 1H NMR using methanol–dichloromethane (1/99) as the eluent. 1H NMR
(400 MHz, CDCl3): d 8.56 (d, J = 4.8 Hz, 1H), 7.67 (m, 2H), 7.54 (400 MHz, CDCl3): d 8.57 (m, 2H), 7.86 (s, 1H), 7.72 (m, 3H),
(d, J = 3.8 Hz, 1H), 7.15 (t, J = 4.8 Hz, 1H), 7.12 (s, 1H), 7.04 (d, J = 7.64 (d, J = 3.8 Hz, 1H), 7.31 (d, J = 3.8 Hz, 1H), 7.19 (m, 2H),
3.8 Hz, 1H), 3.65 (s, 3H), 2.44 (s, 3H). 13C NMR (100 MHz, 6.91 (t, J = 6.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 152.1,
CDCl3): d 152.2, 149.5, 146.7, 144.5, 136.6, 133.5, 127.4, 126.7, 149.7, 146.6, 144.5, 136.7, 133.7, 132.1, 126.2, 124.9, 124.6,
126.5, 124.7, 121.9, 118.4, 31.5, 13.7. Elemental analysis calcd 124.2, 122.2, 119.7, 118.6, 118.3, 113.1. Elemental analysis calcd
(%) for C14H13N3S (255.34): C, 65.85; H, 5.13%; found: C, 65.74; (%) for C16H11N3S (277.34): C, 69.29; H, 4.00%; found: C, 69.42;
H, 5.12%.
1-Methyl-5-(5-pyridin-2-ylthiophen-2-yl)-pyrrole-2-carbaldehyde
H, 3.88%.
2-(5-Pyridin-2-ylthiophen-2-yl)-benzoxazole (13). The reac-
(9). The reaction of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g, tion of 2-(5-bromothiophen-2-yl)-pyridine 1 (0.240 g, 1 mmol),
1 mmol), 1-methylpyrrole-2-carbaldehyde (0.218 g, 2 mmol), benzoxazole (0.238 g, 2 mmol), Cs2CO3 (0.652 g, 2 mmol) and
KOAc (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (6.1 mg, PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol) in DMAc for 24 h affords
0.01 mmol) in DMAc for 24 h affords the product 9 in 56% the product 13 in 55% (0.153 g) yield as an orange solid (mp
(0.150 g) yield as a brown solid (mp 113–116 1C). Purification 182–185 1C). Purification was performed using diethylether–
1
was performed using diethylether–pentane (1/4) as the eluent. pentane (3/7) as the eluent. H NMR (400 MHz, CDCl3): d 8.62
1H NMR (400 MHz, CDCl3): d 9.57 (s, 1H), 8.59 (d, J = 4.6 Hz, (d, J = 4.6 Hz, 1H), 7.91 (d, J = 3.9 Hz, 1H), 7.71 (m, 3H), 7.63
1H), 7.72 (m, 3H), 7.58 (d, J = 3.8 Hz, 1H) 7.23 (d, J = 3.8 Hz, 1H), (d, J = 3.9 Hz, 1H), 7.55 (m, 1H), 7.35 (m, 2H), 7.21 (m, 1H). 13
C
6.96 (d, J = 4.1 Hz, 1H), 6.50 (d, J = 4.1 Hz, 1H), 4.15 (s, 3H). NMR (100 MHz, CDCl3): d 158.9, 151.6, 150.5, 149.8, 149.4,
13C NMR (100 MHz, CDCl3): d 179.5, 151.9, 149.5, 146.1, 137.1, 142.1, 136.8, 130.7, 130.6, 125.3, 125.2, 124.7, 122.8, 119.9,
136.6, 134.0, 133.4, 128.0, 124.6, 124.3, 122.2, 118.5, 111.3, 34.4. 119.1, 110.4. Elemental analysis calcd (%) for C16H10N2OS
Elemental analysis calcd (%) for C15H12N2OS (268.33): C, 67.14; (278.33): C, 69.04; H, 3.62%; found: C, 69.18; H, 3.45%.
H, 4.51%; found: C, 67.20; H, 4.45%.
Representative procedure for the arylation of 2-(thiophen-2-yl)-
Methyl 2-methyl-5-(5-pyridin-2-yl-thiophen-2-yl)-furan-3-
pyridine 16
carboxylate (10). The reaction of 2-(5-bromothiophen-2-yl)-pyridine
1 (0.240 g, 1 mmol), methyl 2-methylfuran-3-carboxylate (0.280 g, As a typical experiment, the aryl bromide (1 mmol), 2-(thio-
2 mmol), KOAc (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (12.2 mg, phen-2-yl)pyridine 16 (2 mmol), and KOAc (2 mmol) in the
0.02 mmol) in DMAc for 24 h affords the product 10 in 26% presence of PdCl(C3H5)(dppb) (0.02 mmol) were dissolved in
(0.078 g) yield as brown oil. Purification was performed using DMAc (4 mL) under an argon atmosphere. The reaction mixture
diethylether–pentane (3/7) as the eluent. 1H NMR (400 MHz, was stirred in an oil bath pre-heated at 150 1C for 16 or 24 h.
CDCl3): d 8.57 (d, J = 4.5 Hz, 1H), 7.66 (m, 2H), 7.50 (d, J = 3.8 Hz, After allowing the reaction mixture to cool down to room
1H), 7.24 (d, J = 3.8 Hz, 1H), 7.14 (t, J = 5.7 Hz, 1H), 6.78 (s, 1H), temperature, the coupling product was obtained after evapora-
3.85 (s, 3H), 2.64 (s, 3H). 13C NMR (100 MHz, CDCl3): d 164.2, tion of the solvent and filtration on silica gel.
c
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1-[4-(5-Pyridin-2-ylthiophen-2-yl)-phenyl]-propan-1-one (17a) 7.59 (t, J = 8.0 Hz, 1H), 7.47 (dd, J = 8.0, 3.8 Hz, 1H), 2.95 (d, J =
and 1-[4-(2-pyridin-2-ylthiophen-3-yl)-phenyl]-propan-1-one (17b). 7.1 Hz, 2H), 2.23 (m, 1H), 1.06 (d, J = 6.6 Hz, 6H). 13C NMR
The reaction of 4-bromopropiophenone (0.212 g, 1 mmol), (125 MHz, CDCl3): d 172.9, 149.4, 144.1, 140.6, 136.4, 133.2,
2-(thiophen-2-yl)pyridine 16 (0.322 g, 2 mmol), KOAc (0.196 g, 130.8, 128.7, 127.6, 127.4, 126.4, 121.4, 42.3, 29.8, 22.5.
2 mmol) and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) in DMAc Elemental analysis calcd (%) for C16H16N2S (268.38): C, 71.60;
for 24 h affords the products 17a and 17b in a 6 : 5 (17a : 17b) H, 6.01%; found: C, 71.78; H, 5.89%.
ratio and in 23% (0.067 g) and 14% (0.041 g) isolated yields as
8-(2-Ethyl-4-methylthiazol-5-yl)-quinoline (20). The reaction
light yellow solids (mp 80–83 1C and 138–141 1C, respectively). of 8-bromoquinoline 2 (0.208 g, 1 mmol), 2-ethyl-4-methylthia-
Purification was performed using diethylether–pentane (1/4) as zole (0.254 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and Pd(OAc)2
the eluent. 17a: 1H NMR (500 MHz, CDCl3): d 8.58 (d, J = 4.6 Hz, (4.5 mg, 0.02 mmol) in DMAc for 24 h affords the product 20 in
1H), 7.99 (d, J = 7.9 Hz, 2H), 7.74 (d, J = 7.9 Hz, 2H), 7.70 58% (0.193 g) yield as a brown oil. Purification was performed
(m, 2H), 7.56 (d, J = 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.16 using diethylether only as the eluent. 1H NMR (400 MHz,
(t, J = 5.5 Hz, 1H), 3.01 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H). CDCl3): d 8.91 (d, J = 4.1 Hz, 1H), 8.14 (d, J = 8.2 Hz, 1H),
13C NMR (125 MHz, CDCl3): d 199.9, 152.1, 149.6, 145.4, 144.5, 7.79 (d, J = 8.1 Hz, 1H), 7.69 (d, J = 7.3 Hz, 1H), 7.53 (t, J = 7.6 Hz,
138.3, 136.6, 135.7, 128.7, 125.5, 125.4, 125.3, 122.1, 118.6, 31.7, 1H), 7.39 (dd, J = 8.2, 4.1 Hz, 1H), 3.01 (q, J = 7.6 Hz, 2H), 2.34
8.2. Elemental analysis calcd (%) for C18H15NOS (293.38): C, (s, 3H), 1.40 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3):
73.69; H, 5.15%; found: C, 73.79; H, 5.24%. 17b: 1H NMR d 172.4, 150.5, 149.7, 146.6, 136.7, 132.1, 129.0, 128.6, 127.2,
(500 MHz, CDCl3): d 8.59 (d, J = 4.6 Hz, 1H), 7.97 (d, J = 126.4, 121.6, 27.2, 16.9, 14.5. Elemental analysis calcd (%) for
7.5 Hz, 2H), 7.46 (d, J = 7.5 Hz, 2H), 7.44–7.40 (m, 2H),
C15H14N2S (254.35): C, 70.83; H, 5.55%; found: C, 70.70;
7.12–7.08 (m, 2H), 6.99 (d, J = 8.0 Hz, 1H), 3.01 (q, J = 7.5 Hz, H, 5.42%.
2H), 1.24 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3): d 200.4,
5-Quinolin-8-ylthiophene-2-carbonitrile (21). The reaction of
152.6, 149.7, 141.5, 140.1, 138.6, 136.0, 135.8, 130.7, 129.3, 8-bromoquinoline 2 (0.208 g, 1 mmol), thiophene-2-carbonitrile
128.4, 126.9, 122.2, 122.0, 31.8, 8.2.
(0.218 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and Pd(OAc)2
4-(5-(Pyridin-2-yl)thiophen-2yl)benzonitrile (18a). The reac- (4.5 mg, 0.02 mmol) in DMAc for 26 h affords the product 21
tion of 4-bromobenzonitrile (0.182 g, 1 mmol), 2-(thiophen-2-yl)- in 81% (0.191 g) yield as a bright yellow solid (mp 131–134 1C).
pyridine 16 (0.322 g, 2 mmol), KOAc (0.196 g, 2 mmol) and Purification was done using dichloromethane–pentane (8/2) as
PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) in DMAc for 16 h the eluent. 1H NMR (400 MHz, CDCl3): d 9.01 (d, J = 4.1 Hz, 1H),
affords the product 18a in 66% (0.173 g) isolated yield as a 8.22 (d, J = 8.2 Hz, 1H), 8.17 (d, J = 7.4 Hz, 1H), 7.83 (d, J =
yellow solid (mp 195–198 1C). Purification was performed using 8.1 Hz, 1H), 7.70 (d, J = 4.1 Hz, 1H), 7.62 (m, 2H), 7.51 (dd,
diethylether–pentane (1/4) as the eluent. 1H NMR (500 MHz, J = 8.2, 4.1 Hz, 1H). 13C NMR (125 MHz, CDCl3): d 149.4, 146.0,
CDCl3): d 8.60 (d, J = 4.5 Hz, 1H), 7.75 (d, J = 8.5 Hz, 2H), 7.71 143.7, 136.7, 136.0, 130.6, 128.8, 128.7, 127.5, 126.5, 124.9,
(d, J = 7.2 Hz, 1H), 7.70–7.65 (m, 3H), 7.58 (d, J = 3.9 Hz, 1H), 121.8, 115.4, 112.2. Elemental analysis calcd (%) for C14H8N2S
7.42 (d, J = 3.9 Hz, 1H), 7.19 (t, J = 5.5 Hz, 1H). 13C NMR (236.29): C, 71.16; H, 3.41%; found: C, 71.14; H, 3.49%.
(125 MHz, CDCl3): d 151.9, 149.7, 146.3, 143.4, 138.5, 136.8,
1-(5-Quinolin-8-ylthiophen-2-yl)-ethanone (22). The reaction
132.8, 126.0, 125.9, 125.5, 122.4, 118.8, 118.7, 110.8. Elemental of 8-bromoquinoline 2 (0.208 g, 1 mmol), 2-acetylthiophene
analysis calcd (%) for C16H10N2S (262.33): C, 73.26; H, 3.84%; (0.252 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and Pd(OAc)2
found: C, 73.36; H, 3.89%.
(4.5 mg, 0.02 mmol) in DMAc for 26 h affords the product 22
in 53% (0.134 g) yield as a white solid (mp 132–135 1C).
Purification was performed using diethylether–pentane (1/4)
Representative procedure for the heteroarylation of
8-bromoquinoline 2
1
as the eluent. H NMR (400 MHz, CDCl3): d 9.04 (d, J = 4.1 Hz,
As a typical experiment, 8-bromoquinoline 2 (1 mmol), hetero- 1H), 8.21 (d, J = 8.2 Hz, 1H), 8.14 (d, J = 7.5 Hz, 1H), 7.83 (d, J =
aryl partner (2 mmol), CsOAc (2 mmol) in the presence of 8.1 Hz, 1H), 7.77 (d, J = 4.1 Hz, 1H), 7.75 (d, J = 4.1 Hz, 1H), 7.60
Pd(OAc)2 or PdCl(C3H5)(dppb) were dissolved in DMAc (4 mL) (t, J = 7.5 Hz, 1H), 7.49 (dd, J = 8.2, 4.1 Hz, 1H), 2.62 (s, 3H). 13
C
under an argon atmosphere. The reaction mixture was stirred NMR (75 MHz, CDCl3): d 191.3, 149.8, 147.8, 145.3, 144.5, 136.4,
in an oil bath pre-heated at 150 1C for 24–27 h. After allowing 131.9, 131.8, 128.7, 128.6, 128.3, 127.1, 126.3, 121.5, 20.7.
the reaction mixture to cool down to room temperature, the Elemental analysis calcd (%) for C15H11NOS (253.32): C,
coupling product was obtained after evaporation of the solvent 71.12; H, 4.38%; found: C, 71.05; H, 4.48%.
and filtration on silica gel.
8-[5-(2-Methyl-[1,3]dioxolan-2-yl)-thiophen-2-yl]-quinoline (23).
8-(2-Isobutylthiazol-5-yl)-quinoline (19). The reaction of The reaction of 8-bromoquinoline 2 (0.208 g, 1 mmol), 2-methyl-
8-bromoquinoline 2 (0.208 g, 1 mmol), 2-isobutylthiazole 2-thiophen-2-yl-[1,3]dioxolane (0.340 g, 2 mmol), CsOAc (0.384 g,
(0.282 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and Pd(OAc)2 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol) in DMAc for 26 h
(4.5 mg, 0.02 mmol) in DMAc for 24 h affords the product 19 affords the product 23 in 58% (0.172 g) yield as a light brown
in 76% (0.204 g) yield as a yellow oil. Purification was per- solid (mp 101–104 1C). Purification was performed using
formed using diethylether–pentane (2/3) as the eluent. 1H NMR diethylether–pentane (1/4) as the eluent. 1H NMR (400 MHz,
(400 MHz, CDCl3): d 9.01 (d, J = 3.8 Hz, 1H), 8.31 (s, 1H), 8.19 CDCl3): d 9.02 (d, J = 4.1 Hz, 1H), 8.17 (d, J = 8.2 Hz, 1H), 8.05
(d, J = 8.0 Hz, 1H), 8.10 (d, J = 7.3 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), (d, J = 7.4 Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 4.1 Hz, 1H),
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7.55 (t, J = 7.5 Hz, 1H), 7.43 (dd, J = 8.2, 4.1 Hz, 1H), 7.10 (d, J = 13C NMR (100 MHz, CDCl3): d 162.2, 151.8, 150.9, 145.8, 142.2,
4.1 Hz, 1H), 4.08 (m, 4H), 1.87 (s, 3H). 13C NMR (75 MHz, 136.5, 132.6, 131.6, 128.7, 126.3, 125.9, 125.3, 124.3, 121.6,
CDCl3): d 149.5, 149.4, 144.5, 139.3, 136.3, 132.9, 128.7, 127.6, 120.7, 110.7. Elemental analysis calcd (%) for C16H10N2O
127.1, 126.4, 123.8, 121.2, 107.5, 65.0, 27.8. Elemental analysis (246.26): C, 78.03; H, 4.09%; found: C, 78.10; H, 4.14%.
calcd (%) for C17H15NO2S (297.37): C, 68.66; H, 5.08%; found:
C, 68.79; H, 5.30%.
8-Benzothiazol-2-ylquinoline (28). The reaction of 8-bromo-
quinoline 2 (0.208 g, 1 mmol), benzothiazole (0.270 g, 2 mmol),
8-(5-Methylthiophen-2-yl)-quinoline (24). The reaction of Cs2CO3 (0.652 g, 2 mmol) and PdCl(C3H5)(dppb) (21.4 mg,
8-bromoquinoline 2 (0.208 g, 1 mmol), 2-methylthiophene 0.035 mmol) in DMAc for 24 h affords the product 28 in 61%
(0.196 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and PdCl(C3H5)- (0.160 g) yield as a light green solid (mp 150–153 1C). Purifica-
(dppb) (30.6 mg, 0.05 mmol) in DMAc for 22 h affords the tion was performed using ethylacetate–pentane (1/4) as the
1
product 24 in 35% (0.079 g) yield as a brown oil. Purification eluent. H NMR (400 MHz, CDCl3): d 9.09 (m, 2H), 8.27 (d, J =
was performed using diethylether–pentane (1/99) as the eluent. 8.2 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.97
1H NMR (400 MHz, CDCl3): d 9.01 (d, J = 4.1 Hz, 1H), 8.17 (d, J = (d, J = 7.3 Hz, 1H), 7.73 (t, J = 7.7 Hz, 1H), 7.52 (m, 2H), 7.40
8.2 Hz, 1H), 8.02 (d, J = 7.3 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.57 (t, J = 7.3 Hz, 1H). 13C NMR (100 MHz, CDCl3): d 163.8, 152.4,
(t, J = 3.5 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.44 (dd, J = 8.2, 149.8, 145.1, 138.4, 137.0, 131.5, 130.7, 130.4, 128.7, 126.9,
4.1 Hz, 1H), 6.83 (d, J = 3.5 Hz, 1H), 2.58 (s, 3H). 13C NMR 126.2, 125.1, 123.3, 121.8, 121.7. Elemental analysis calcd (%)
(75 MHz, CDCl3): d 149.4, 144.7, 142.6, 137.4, 136.4, 133.4, for C16H10N2S (262.33): C, 73.26; H, 3.84%; found: C, 73.18;
128.8, 127.5, 126.7, 126.5, 125.0, 121.1, 15.4. Elemental analysis H, 3.71%.
calcd (%) for C14H11NS (225.31): C, 74.63; H, 4.92%; found: C,
74.78; H, 5.08%.
Acknowledgements
8-(2,3-Dimethylimidazol-4-yl)-quinoline (25). The reaction of
K. B. is grateful to CNRS and ‘‘Conseil regional de Bretagne’’ for
a grant. We thank the CNRS and ‘‘Rennes Metropole’’ for
providing financial support.
8-bromoquinoline 2 (0.208 g, 1 mmol), 1,2-dimethylimidazole
(0.192 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and Pd(OAc)2
(4.5 mg, 0.02 mmol) in DMAc for 26 h affords the product 25
in 73% (0.163 g) yield as a brown oil. Purification was per-
formed using methanol–dichloromethane (1/99) as the eluent.
1H NMR (400 MHz, CDCl3): d 8.94 (d, J = 4.1 Hz, 1H), 8.21 (d, J =
8.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.71 (d, J = 8.2 Hz, 1H), 7.58
(t, J = 7.1 Hz 1H), 7.44 (dd, J = 8.2, 4.1 Hz, 1H), 7.06 (s, 1H), 3.36
(s, 3H), 2.50 (s, 3H). 13C NMR (100 MHz, CDCl3): d 150.4, 146.6,
145.9, 136.3, 132.2, 131.7, 130.0, 128.8, 128.6, 126.9, 126.3,
121.3, 32.0, 13.7. Elemental analysis calcd (%) for C14H13N3
(223.27): C, 75.31; H, 5.87%; found: C, 75.50; H, 6.04%.
8-Imidazo[1,2-a]pyridin-3-ylquinoline (26). The reaction of
8-bromoquinoline 2 (0.208 g, 1 mmol), imidazo[1,2-a]pyridine
(0.236 g, 2 mmol), CsOAc (0.384 g, 2 mmol) and Pd(OAc)2
(4.5 mg, 0.02 mmol) in DMAc for 26 h affords the product 26
in 81% (0.198 g) yield as a brown oil. Purification was per-
formed using methanol–dichloromethane (1/19) as the eluent.
1H NMR (400 MHz, CDCl3): d 8.86 (m, 1H), 8.23 (d, J = 8.2 Hz,
1H), 7.93 (d, J = 8.2 Hz, 1H), 7.86 (m, 2H), 7.83 (d, J = 6.8 Hz,
1H), 7.68 (m, 2H), 7.46 (dd, J = 8.2, 4.1 Hz, 1H), 7.20 (t, J =
6.8 Hz, 1H), 6.69 (t, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3):
d 150.3, 146.4, 146.0, 136.5, 134.2, 131.8, 128.9, 128.8, 128.7,
126.6, 125.7, 124.2, 124.1, 121.5, 117.8, 111.3. Elemental analysis
calcd (%) for C16H11N3 (245.28): C, 78.35; H, 4.52%; found: C,
78.40; H, 4.67%.
Notes and references
1 For reviews: (a) D. Alberico, M. E. Scott and M. Lautens,
Chem. Rev., 2007, 107, 174; (b) T. Satoh and M. Miura, Chem.
Lett., 2007, 200; (c) I. V. Seregin and V. Gevoryan, Chem. Soc.
Rev., 2007, 36, 1173; (d) B.-J. Li, S.-D. Yang and Z.-J. Shi,
Synlett, 2008, 949; (e) F. Bellina and R. Rossi, Tetrahedron,
2009, 65, 10269; ( f ) L. Ackermann, R. Vicente and A. Kapdi,
Angew. Chem., Int. Ed., 2009, 48, 9792; (g) J. Roger,
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quinoline 2 (0.208 g, 1 mmol), benzoxazole (0.238 g, 2 mmol),
Cs2CO3 (0.652 g, 2 mmol) and PdCl(C3H5)(dppb) (21.4 mg,
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was performed using diethylether–pentane (1/1) as the eluent.
1H NMR (400 MHz, CDCl3): d 9.16 (d, J = 4.1 Hz, 1H), 8.50 (d, J =
7.3 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 8.2 Hz, 1H), 7.92
(m, 1H), 7.67 (m, 2H), 7.49 (dd, J = 8.2, 4.1 Hz, 1H), 7.4 (m, 2H).
c
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This journal is The Royal Society of Chemistry 2013
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