Palladium-catalyzed direct heteroarylation of chloropyridines and chloroquinolines

Article abstract of DOI:10.1016/j.jorganchem.2008.11.032

The direct coupling of aryl chlorides with heteroarenes would be a considerable advantage for sustainable development due to their lower cost, lower mass, the wider diversity of available compounds and also because of the formation of only HCl associated

Full text of DOI:10.1016/j.jorganchem.2008.11.032

Journal of Organometallic Chemistry 694 (2009) 455–465
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Journal of Organometallic Chemistry
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Palladium-catalyzed direct heteroarylation of chloropyridines and chloroquinolines
Fazia Derridj a, Julien Roger b, Florence Geneste b, Safia Djebbar a, Henri Doucet b,
*
a Laboratoire d’hydrométallurgie et chimie inorganique moléculaire, Faculté de Chimie, U.S.T.H.B. Bab-Ezzouar, Alger, Algeria
b Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes ‘‘Catalyse et Organometalliques”, Campus de Beaulieu, 35042 Rennes, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The direct coupling of aryl chlorides with heteroarenes would be a considerable advantage for sustainable
development due to their lower cost, lower mass, the wider diversity of available compounds and also
because of the formation of only HCl associated to a base as by-product and the reduction of the number
of steps to prepare these compounds. We observed that through the use of PdCl(dppb)(C3H5) as a catalyst,
a range of heteroaryl derivatives undergoes coupling via C–H bond activation/functionalization reaction
with chloropyridines or chloroquinolines in low to high yields. This air-stable catalyst can be used with a
wide variety of substrates. The position of the chloro substituent on pyridines has a minor influence on
the yields. On the other hand, the nature on the heteroaryl derivative has a large influence. The highest
yields were obtained using benzoxazole, thiophene or thiazole derivatives. The coupling of chloropyri-
dines with furans also gave the expected products, but in low to moderate yields.
Received 8 September 2008
Received in revised form 27 October 2008
Accepted 14 November 2008
Available online 24 November 2008
Keywords:
Aryl chlorides
Catalysis
C–H activation
Heteroarenes
Palladium
Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction
reported by Zhuravlev [11a]. He observed that the coupling prod-
uct of 2-chloropyridine with an oxazolopyridine derivative could
The palladium-catalyzed cross-coupling reactions between pyr-
idyl halides and heteroarenes represent a powerful access to het-
eroarylated pyridines, which are important pharmaceutical
compounds [1]. Negishi [2], Stille [3], Kumada [4] or Suzuki [5]
cross-coupling reactions have been largely employed for the prep-
aration of such compounds. However, these methods are not very
convenient due to the limited access and various stabilities of sev-
eral heteroaromatic organometallic derivatives. Moreover, these
reactions are not environmentally attractive as they provides an
organometallic or salt (MX) as by-product. Over the last years, very
interesting results for the coupling of pyridyl halides with hetero-
aromatic derivatives by C–H bond activation have been reported
and provide an economically and environmentally attractive pro-
cedure for the preparation of such compounds [6]. However, so
far most of the results were obtained with reactive, but expensive
bromopyridines or iodopyridines [7–10]. The use of chloropyri-
dines for such coupling reactions would be a considerable advan-
tage for sustainable development due to their lower cost, lower
mass and the wider diversity of available compounds. This reaction
provides only HCl associated to a base as by-product and therefore
is very interesting both in terms of atom-economy and inert
wastes. However, for this coupling, aryl chlorides are relatively
uncommon partners [11]. This is due to the fact that the oxidative
addition of pyridyl chlorides to palladium is slower than with bro-
mides or iodides. One of the first examples of such reaction was
be obtained in 33% yield using Pd(OAc)2 (5 mol%) / PPh3 (20 mol%),
Cs2CO3 and acetone as reaction conditions. Better yields were ob-
tained using palladium associated to electron-rich monophos-
phines. For example, Daugulis and co-worker have been able to
couple 2-chloro-6-methoxypyridine with benzothiophene in 72%
yield using Pd(OAc)2 (5 mol%)/butyldi-1-adamantylphosphine
(10 mol%) as catalyst. This catalyst also gave good results for the
coupling of 2-chloropyridine with benzoxazole [11b]. A relatively
similar procedure has been described recently for the 2-arylation
of a 4-thiazolecarboxylate. Using 5–10 mol% Pd(OAc)2 and 10–
20 mol% P(biphenyl-2-yl)Cy2 as catalyst, the coupling of 2-chloro
and 3-chloropyridines gave the expected products in high yields
[11d].
If monophosphine ligands such as PPh3 or the air-sensitive
P(biphenyl-2-yl)Cy2 and butyldi-1-adamantylphosphine have
been successfully used for the direct coupling of heteroaromatics
with pyridyl chlorides, the efficiency of bidentate phosphine
ligands for such couplings has not been demonstrated. Moreover,
it should be noted that, so far, relatively few pyridyl chloride
derivatives and heteroaromatics have been employed for this
reaction [11]. For example, to our knowledge, the 2-arylation of
furans and the 5-arylation of thiazoles using pyridyl chlorides
or the reactivity of 4-chloropyridines have not been reported.
Therefore, the discovery of an effective and selective method,
using a low loading of an air-stable catalyst, for the direct cou-
pling of both electron-excessive and electron-deficient 2-, 3- or
4-pyridyl chlorides with a wide variety of heteroaromatics still
needs to be developed.
* Corresponding author. Tel.: +33 2 23 23 63 84; fax: +33 2 23 23 69 39.
E-mail address: henri.doucet@univ-rennes1.fr (H. Doucet).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.11.032

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F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
So far, most of the coupling reactions of heteroaryl derivatives
gand-free catalysts gave very low yields of target product (Table 1,
entries 1, 2, 6 or 7). In absence of catalyst no formation of product
was detected by GC (Table 1, entry 9). On the other hand, with 2-
npropylthiazole, the highest yield was obtained using KOAc as base
and DMAc as solvent (Table 1, entry 13). The reactions conducted
at 100 °C instead of 150 °C gave lower yields (Table 1, entries 5
and 14).
Therefore, for this study, DMF and Cs2CO3 were chosen as reac-
tion conditions for the 2-arylation of benzoxazole and benzothia-
zole. For the 5-arylation of thiazoles, thiophenes or furans, DMAc
and KOAc were employed as the solvent and the base. The reac-
tions were performed under argon in the presence of 2.5 mol% of
PdCl(C3H5)(dppb) as catalyst. Most of the substrates and products
are thermally stable so, in order to obtain higher yields, we have
performed the reactions at an elevated temperature: 150 °C. How-
ever, in some cases, a lower reaction temperature of 120 °C had to
be employed due to partial decomposition of the starting material
or coupling product.
First, we tested several reaction conditions for the coupling of 2-
chloropyridines with seven heteroaromatics (Table 2). 2-Chloro-6-
methylpyridine, 2-chloropyridine or 2-chloroquinoline reacted
with benzoxazole gave the target products 1–3 in 65–79% yields
(Table 2, entries 1–3). To determine the electronic influence of
the pyridine substituents on this coupling reaction, we studied
the reactivity of substituted 2-chloropyridines. The presence of
electron donating or withdrawing substituents appears to have a
minor effect on the reaction yields. 5-Trifluoromethyl-2-chloropyr-
idine and 6-methoxy-2-chloropyridine gave the expected coupling
products 4 and 5 in similar yields of 77% and 78%, respectively
(Table 2, entries 4 and 5). Then, we studied the 2-arylation of ben-
zothiazole using 2-chloropyridines. We obtained lower yields of
desired products than in the presence of benzoxazole. However,
the target compounds 6-8 were formed in all cases using either
2-chloro-6-methylpyridine, 2-chloroquinoline or 5-trifluoro-
methyl-2-chloropyridine (Table 2, entries 6–8). In the literature,
the 2-arylation of a 4-thiazolecarboxylate using pyridyl chlorides
has been reported [11d]. In order to extend the scope of this reac-
tion; we examined the 5-arylation of 2-substituted thiazoles. 2-
nPropylthiazole was coupled with 2-chloropyridine, 2-chloroquin-
oline or 6-methoxy-2-chloropyridine. As expected, the 5-arylated
thiazoles 9–11 were selectively obtained in 38–64% yields (Table
2, entries 9–11). In the same manner, two 2,4-substituted thia-
zoles: 2-ethyl-4-methylthiazole and 2-phenyl-4-methylthiazole
were reacted affording 12–14 in very similar yields (Table 2, en-
tries 12–14). Finally, the reactivity of 2-substituted thiophenes
with 2-chloro-6-methoxypyridine has been studied, and again,
with aryl chlorides via a C–H bond activation require relatively
high catalyst loadings (1–10 mol%) and have been performed at
elevated temperature (120–150 °C) [6]. At these temperatures,
when Pd(OAc)2 is employed as catalyst precursor, soluble palla-
dium(0) colloids or nanoparticles are generally formed, and then,
especially under high palladium concentrations (typically when
1–10 mol% catalyst is employed), so-called ‘‘palladium black”
forms rapidly. This ‘‘palladium black” is inactive for the coupling
of most aryl chlorides with arenes. Therefore, for the direct cou-
pling of chloropyridines with aryl chlorides, the stabilization of
monomeric palladium species or small clusters is necessary. Such
stabilization can be performed using either ammonium salts or li-
gands. Consequently, we have prepared the air-stable
PdCl(C3H5)(dppb)
complex
(dppb = 1,4-bis(diphenylphos-
phino)butane) [12]. The idea was that intermediate Pd(0) species
have to be protected by internal ligation against decomposition
pathways through under-ligation and subsequent colloid and ‘‘Pd
black” formation [13–16]. The presence of the bidentate ligand
dppb on palladium might also reduce the poisoning of the catalyst
due to the presence of heteroaromatics. We have already reported
some results for the direct coupling of heteroaromatics with aryl
and vinyl bromides [14,15] and also with aryl chlorides [9e,11c]
using this catalyst. Herein, we report that this catalyst provides a
powerful system for the cross-coupling of chloropyridine or chlo-
roquinoline derivatives with a wide variety of heteroaromatics.
2. Results and discussion
We describe here successively the reactions of 2-chloro, 3-
chloro and 4-chloropyridine derivatives with a range of heteroaro-
matics (Scheme 1, Tables 1–4). We initially examined the influence
of several reaction parameters on the yield for the coupling of 2-
chloropyridine with benzoxazole or 2-npropylthiazole (Table 1).
The best results for the reaction with benzoxazole were obtained
using Cs2CO3 associated to DMF and PdCl(C3H5)(dppb) as catalyst
at 150 °C (Table 1, entry 4). With this substrate, KOAc as base or li-
or N
or N
C
C
PdCl(C3H5)(dppb)
N or C
R
N or C
R
+
H
ArCl
Ar
Base, 120 or 150 °C, 20 h
O
O
or S
or S
1−32
Scheme 1.
Table 1
Palladium-catalyzed direct arylation of 2-chloropyridine, influence of the reaction conditions.
Entry
Heteroarene
Base
Solvent
Catalyst
Temperature (°C)
Yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Benzoxazole
Benzoxazole
Benzoxazole
Benzoxazole
Benzoxazole
Benzoxazole
Benzoxazole
Benzoxazole
KOAc
KOAc
DMF
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
Pd(OAc)2
[PdCl(C3H5)]2
[PdCl(C3H5)]2/2 PPh3
–
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
PdCl(C3H5)(dppb)
150
150
150
150
100
150
150
150
150
150
150
150
150
100
27
5
67
DMAc
DMAc
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAc
DMF
DMAc
DMAc
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
KOAc
72 (69)
25
3
2
58
0
26
2
12
Benzoxazole
2-npropylthiazole
2-npropylthiazole
2-npropylthiazole
2-npropylthiazole
2-npropylthiazole
Cs2CO3
Cs2CO3
KOAc
45 (38)
2
KOAc
a
Conditions: catalyst: [Pd] (0.025 mmol), 2-chloropyridine (1 mmol), heteroarene (1.2 mmol), base (1.2 mmol), solvent (5 mL), 20 h, GC and NMR yields, yields in
parenthesis are isolated.

F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
457
Table 2
Palladium-catalyzed arylation of 2-chloropyridines or quinolines (Scheme 1).
Entry
1
2-Chloropyridine or quinoline
Heteroarene
Product
Yield (%)a
65
N
O
N
N
Cl
O
N
N
1
2
3
69
79
N
O
N
O
N
Cl
2
N
O
N
O
N
N
Cl
N
N
3
4
5
77
78
N
O
F3C
N
O
F3C
4
Cl
Cl
N
N
O
O
N
O
N
5
O
6
7
58
54
N
S
N
S
N
N
Cl
6
N
N
S
N
N
Cl
S
N
7
8
52
N
N
S
F3C
F3C
S
N
8
Cl
9
38b
N
S
N
S
N
N
Cl
9
10
50b,c
N
S
N
S
N
N
Cl
10
(continued on next page)

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F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
Table 2 (continued)
Entry
11
2-Chloropyridine or quinoline
Heteroarene
Product
Yield (%)a
64b,c
N
S
N
S
N
O
N
N
Cl
O
11
12
52b,c
N
S
N
Cl
S
N
12
13
60b,c
N
S
N
O
N
N
Cl
Cl
S
N
O
13
14
62b,c
N
N
O
S
S
N
Ph
Ph
O
14
15
53b,c
S
S
N
O
O
N
N
Cl
Cl
O
15
16
63b,c
CN
S
S
N
CN
O
16
a
Conditions: catalyst: PdCl(C3H5)(dppb) (0.025 mmol), aryl chloride (1 mmol), heteroarene (1.2 mmol), Cs2CO3 (1.2 mmol), DMF (5 mL), 20 h, 150 °C, isolated yields.
KOAc and DMAc were employed as base and solvent.
Reaction temperature 120 °C.
b
c
the desired compounds 15 and 16 were formed in satisfactory
was also observed. Using 2-nbutylfuran and methyl 2-methyl-3-
furoate, 24 and 25 were formed in only 41% and 30% yields, respec-
tively (Table 3, entries 8 and 9).
yields of 53% and 63% (Table 2, entries 15 and 16). It should be
noted that quantitative conversion of the pyridyl chlorides was ob-
served in most cases.
Then, we studied the influence of position of the chloro substi-
tuent on pyridines for this reaction. Due to the electronegativity of
With 4-chloropyridine we observed behaviour similar to that of
2- or 3-chloropyridine. Satisfactory yields were also obtained using
several heteroaromatics (Table 4). Again, using benzoxazole, ben-
zothiazole or 2-npropylthiazole, the selective formation of the ex-
pected products 26–28 was observed in high yields (Table 4,
entries 1-3). Using 2-ethyl-4-methylthiazole, a low yield of 29
(34%) was produced due to a partial conversion of 4-chloropyridine
(Table 4, entry 4). Ethyl thiazole-2-carboxylate, also led to a mod-
erate yield of 37% in 30. With this substrate unidentified side-prod-
ucts were formed in the course of the reaction (Table 4, entry 5).
Here also, using similar reaction conditions, a higher yield was ob-
tained using 2-nbutylthiophene than in the presence of 2-nbutylfu-
ran (Table 4, entries 6 and 7).
the nitrogen atom, the
a and c positions of halopyridines should be
the most susceptible to the oxidative addition to Pd(0). In fact, the
reactivity of 3-chloropyridine is quite similar to 2-chloropyridine
(Table 3). Coupling reaction with benzoxazole or benzothiazole
gave 17 and 18 in 80% and 79% yields, respectively. Moreover, no
formation of side-products was observed. Four thiazole derivatives
were also employed, and again, satisfactory results were obtained
except with sterically congested 2-methyl-4tbutylthiazole (Table
3, entries 3–6). With this substrate a low yield of 33% was obtained.
2-nButylthiophene led to 23 in 61% yield (Table 3, entry 7). Furan
derivatives were found to be less reactive. The coupling reaction
was selective in favour of the 5-arylation of furans, but the forma-
tion of relatively large amount of 3,30-bipyridine as side-product
This procedure is not limited to chloropyridines. 2-Chloropyr-
imidine has been successfully coupled with benzoxazole (Scheme
2). The desired product 33 was obtained in very high yield. Finally,

F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
459
Table 3
Palladium-catalyzed arylation of 3-chloropyridine (Scheme 1).
Entry
1
Heteroarene
Temperature (°C)
Product
Yield (%)a
80b
120
N
N
O
O
N
17
2
3
4
120
120
120
79b
N
S
N
S
N
18
78
N
S
N
S
N
19
74
N
S
N
S
N
20
5
6
120
120
58
33
N
N
S
S
N
Ph
Ph
21
N
N
S
S
N
22
7
8
9
120
120
120
61
41
30
S
S
N
N
23
24
O
O
CO2Me
CO2Me
O
O
N
25
a
Conditions: catalyst: PdCl(C3H5)(dppb) (0.025 mmol), 3-chloropyridine (1 mmol), heteroarene (1.2 mmol), KOAc (1.2 mmol), DMAc (5 mL), 20 h, isolated yields.
Cs2CO3 and DMF were employed as base and solvent.
b
2-chlorobenzothiazole was reacted with benzoxazole or benzothi-
azole to give 34 and 35 in 54% and 63% yields, respectively
(Schemes 3 and 4).
quinolines with a wide variety of heteroarenes. 2-, 3- or 4-
chloropyridine derivatives have been employed successfully. The
position of the halide on the heteroaromatic appears to have a min-
or influence on the reactions yields. Several heteroaromatics were
also employed successfully. In general, better results were ob-
tained for the coupling with benzoxazole, benzothiazole, thiazoles
or thiophenes than with furans. This procedure is very simple, eco-
nomically attractive and uses commercially available ligand and
3. Conclusion
In summary, the complex PdCl(dppb)(C3H5) provides an effi-
cient catalyst for the direct coupling of chloropyridines or chloro-

460
F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
Table 4
Palladium-catalyzed arylation of 4-chloropyridine (Scheme 1).
Entry
1
Heteroarene
Temperature (°C)
Product
Yield (%)a
71b
120
N
N
O
N
O
26
27
2
3
4
120
120
120
65b
N
S
N
S
N
76
N
S
N
N
S
28
34
N
S
N
N
N
S
29
5
120
37
N
S
N
S
CO2Et
CO2Et
30
6
7
a
120
120
50
34
N
S
S
31
N
O
O
Conditions: catalyst: PdCl(C3H5)(dppb) (0.025 mmol), 4-chloropyridine hydrochloride (1 mmol), heteroarene (1.2 mmol), KOAc (2.2 mmol), DMAc (5 mL), 20 h, isolated
yields.
b
Cs2CO3 and DMF were employed as base and solvent.
N
N
N
N
O
N
O
PdCl(C3H5)(dppb) 2.5%
+
Cl
DMF, Cs2CO3, 150 °C, 20 h
N
81%
33
1 eq.
1.2 eq.
Scheme 2.
N
N
N
N
O
PdCl(C3H5)(dppb) 2.5%
+
Cl
DMF, Cs2CO3, 150 °C, 20 h
S
O
S
54%
34
1 eq.
1.2 eq.
Scheme 3.
catalyst precursors. The air-stability of this catalyst makes this pro-
cedure more convenient than those using bulky electron-rich
phosphanes that are often employed to activate aryl chlorides in
palladium-catalyzed reactions [11b,11d]. To the best of our knowl-
edge, this work represents one of the most wide-ranging study re-
ported so far for the preparation of heteroarylpyridines via a C–H
bond activation/functionalization. The only by-product is HCl asso-
ciated to AcOK or Cs2CO3 instead of metallic salts with classical

F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
461
N
N
S
N
S
N
S
PdCl(C3H5)(dppb) 2.5%
+
Cl
DMF, Cs2CO3, 150 °C, 20 h
S
63%
35
1 eq.
1.2 eq.
Scheme 4.
cross-coupling procedures. Moreover, no preparation of an organo-
metallic derivative is required, reducing the number of steps to
prepare these compounds.
4.5. 2-Pyridin-2-ylbenzoxazole (2)
The reaction of 2-chloropyridine (0.114 g, 1 mmol), benzoxaz-
ole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C affords
the corresponding product 2 in 69% (0.135 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.70 (d, J = 4.6 Hz, 1H), 8.24 (d,
J = 8.2 Hz, 1H), 7.70–7.55 (m, 2H), 7.55 (m, 1H), 7.60–7.20 (m, 3H).
4. Experimental
4.1. General remarks
All reactions were run under argon in Schlenk tubes using vac-
uum lines. DMF or DMAc analytical grade were not distilled before
use. Cesium carbonate or potassium acetate (99+) were used. Com-
mercial aryl chlorides and heteroarene derivatives were used with-
out purification. 1H and 13C spectrum were recorded with a Bruker
200 MHz spectrometer in CDCl3 solutions. Chemical shift are re-
ported in ppm relative to CDCl3 (7.25 for 1H NMR and 77.0 for
13C NMR). Flash chromatography was performed on silica gel
(230–400 mesh). Cyclic voltammetric experiments were carried
out using an EDAQ potentiostat unit, with the EChem software
package. A platinum wire working electrode, a platinum wire aux-
iliary electrode, and a saturated calomel reference electrode (SCE)
were used in a standard three-electrode configuration. Electro-
chemical measurements were performed in dimethylformamide,
4.6. 2-Benzoxazol-2-ylquinoline (3)
The reaction of 2-chloroquinoline (0.164 g, 1 mmol), benzoxaz-
ole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C affords
the corresponding product 3 in 79% (0.194 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.46 (d, J = 8.2 Hz, 1 H), 8.37 (d,
J = 8.2 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H),
7.88 (m, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.76 (m, 1H), 7.66 (t,
J = 7.8 Hz, 1H), 7.43 (m, 2H).
4.7. 2-(5-Trifluoromethylpyridin-2-yl)-benzoxazole (4)
The reaction of 2-chloro-5-(trifluoromethyl)pyridine (0.182 g,
1 mmol), benzoxazole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF
at 150 °C affords the corresponding product 4 in 77% (0.203 g) iso-
lated yield.
containing 0.1 M tetrabutylammonium tetrafluoroborate, at
a
100 mV sꢀ1 scan rate, under a dinitrogen atmosphere.
4.2. Preparation of the PdCl(dppb)(C3H5) catalyst [12]
1H NMR (200 MHz, CDCl3) d 9.02 (s, 1H), 8.43 (d, J = 8.0 Hz, 1H),
8.09 (d, J = 8.0 Hz, 1H), 7.81 (m, 1H), 7.64 (m, 1H), 7.50–7.30 (m,
2H).
An oven-dried 40 mL Schlenk tube equipped with a magnetic
stirring bar under argon atmosphere, was charged with
[Pd(C3H5)Cl]2 (182 mg, 0.5 mmol) and dppb (426 mg, 1 mmol).
10 mL of anhydrous dichloromethane were added, then the solu-
tion was stirred at room temperature for twenty minutes. The sol-
vent was removed in vacuum. The yellow powder was used
without purification. 31P NMR (81 MHz, CDCl3) d = 19.3 (s).
13C NMR (50 MHz, CDCl3) d 159.9, 150.9, 148.8, 147.0 (q,
J = 4.0 Hz), 141.4, 134.3 (q, J = 3.5 Hz), 127.7 (q, J = 33.4 Hz),
126.6, 125.2, 122.9 (q, J = 272.4 Hz), 122.8, 120.8, 111.2.
Anal. Calc. for C13H7F3N2O: C, 59.10; H, 2.67. Found: C, 59.14; H,
2.84%.
4.3. General procedure for coupling reactions
4.8. 2-(6-Methoxypyridin-2-yl)-benzoxazole (5)
In a typical experiment, the aryl chloride (1 mmol), heteroarene
derivative (1.2 mmol), Cs2CO3 (0.390 g, 1.2 mmol) or KOAc
(0.118 g, 1.2 mmol) and PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol)
were dissolved in DMF or DMAc (5 mL) under an argon atmo-
sphere. The reaction mixture was stirred at 120 or 150 °C (see ta-
bles) for 20 h. The solution was diluted with an H2O/KOH
solution 1 M (20 mL), then the product was extracted three times
with CH2Cl2. The combined organic layer was dried over MgSO4
and the solvent was removed in vacuo. The crude product was
purified by silica gel column chromatography.
The reaction of 2-chloro-6-methoxypyridine (0.144 g, 1 mmol),
benzoxazole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C
affords the corresponding product 5 in 78% (0.177 g) isolated
yield.
1H NMR (200 MHz, CDCl3) d 7.89 (d, J = 8.2 Hz, 1H), 7.83 (m, 1H),
7.68 (t, J = 7.8 Hz, 1H), 7.63 (m, 1H), 7.36 (m, 2H), 6.86 (d, J = 8.2 Hz,
1H), 4.10 (s, 3H).
13C NMR (50 MHz, CDCl3) d 164.7, 162.1, 151.3, 143.8, 142.3,
139.5, 126.1, 125.2, 121.0, 117.3, 114.2, 111.4, 54.2.
Anal. Calc. for C13H10N2O: C, 69.02; H, 4.46. Found: C, 69.20; H,
4.57%.
4.4. 2-(6-Methylpyridin-2-yl)-benzoxazole (1)
The reaction of 2-chloro-6-methylpyridine (0.128 g, 1 mmol),
benzoxazole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C af-
fords the corresponding product 1 in 65% (0.137 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 7.98 (d, J = 8.2 Hz, 1H), 7.62 (m, 1H),
7.45 (t, J = 7.8 Hz, 1H), 7.42 (m, 1H), 7.15 (m, 2H), 6.99 (d, J = 8.2 Hz,
1H), 2.47 (s, 3H).
4.9. 2-(6-Methylpyridin-2-yl)-benzothiazole (6)
The reaction of 2-chloro-6-methylpyridine (0.128 g, 1 mmol),
benzothiazole (0.162 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C af-
fords the corresponding product 6 in 58% (0.131 g) isolated yield.

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1H NMR (200 MHz, CDCl3) d 8.18 (d, J = 8.2 Hz, 1H), 8.10 (d,
at 120 °C affords the corresponding product 11 in 64% (0.150 g)
J = 8.2 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.52
(t, J = 7.8 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H),
2.66 (s, 3H).
isolated yield.
1H NMR (200 MHz, CDCl3) d 8.06 (s, 1H), 7.52 (t, J = 7.8 Hz, 1H),
7.15 (d, J = 8.2 Hz, 1H), 6.59 (d, J = 8.2 Hz, 1H), 3.95 (s, 3H), 2.97 (t,
J = 7.5 Hz, 2H), 1.83 (sext., J = 7.5 Hz, 2H), 1.02 (t, J = 7.5 Hz, 3H).
13C NMR (50 MHz, CDCl3) d 173.0, 164.0, 148.6, 139.7, 139.5,
139.4, 112.4, 109.8, 53.7, 36.0, 23.8, 14.1.
4.10. 2-Benzothiazol-2-ylquinoline (7)
The reaction of 2-chloroquinoline (0.164 g, 1 mmol), benzothia-
zole (0.162 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C affords
the corresponding product 7 in 54% (0.142 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.87 (d, J = 8.2 Hz, 1H), 8.51 (d,
J = 8.2 Hz, 1H), 8.40–8.10 (m, 3H), 7.99 (d, J = 8.2 Hz, 1H), 7.88 (t,
J = 7.8 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.62-7.40 (m, 2H).
Anal. Calc. for C12H14N2OS: C, 61.51; H, 6.02. Found: C, 61.45; H,
6.10%.
4.15. 2-(2-Ethyl-4-methylthiazol-5-yl)-quinoline (12)
The reaction of 2-chloroquinoline (0.164 g, 1 mmol), 2-ethyl-4-
methylthiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C af-
fords the corresponding product 12 in 52% (0.132 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.18 (d, J = 7.8 Hz, 1H), 8.09 (d,
J = 7.8 Hz, 1H), 7.80-7.60 (m, 3H), 7.53 (t, J = 7.8 Hz, 1H), 3.04 (q,
J = 7.4 Hz, 2H), 2.78 (s, 3H), 1.45 (t, J = 7.8 Hz, 3H).
4.11. 2-(5-Trifluoromethylpyridin-2-yl)-benzothiazole (8)
The reaction of 2-chloro-5-(trifluoromethyl)pyridine (0.182 g,
1 mmol), benzothiazole (0.162 g, 1.2 mmol) and Cs2CO3 (0.390 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF
at 150 °C affords the corresponding product 8 in 52% (0.146 g) iso-
lated yield.
13C NMR (50 MHz, CDCl3) d 173.0, 152.4, 150.4, 148.5, 137.0,
132.5, 130.4, 129.7, 127.9, 126.9, 126.8, 120.6, 27.5, 18.0, 14.7.
Anal. Calc. for C15H14N2S: C, 70.83; H, 5.55. Found: C, 70.68; H,
5.54%.
1H NMR (200 MHz, CDCl3) d 8.96 (s, 1H), 8.52 (d, J = 8.3 Hz, 1H),
8.14 (d, J = 8.2 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H), 8.00 (d, J = 8.2 Hz,
1H), 7.57 (t, J = 7.8 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H).
13C NMR (50 MHz, CDCl3) d 167.9, 154.8, 154.6, 147.0 (q,
J = 4.0 Hz), 136.8, 134.7 (q, J = 3.5 Hz), 127.7 (q, J = 33.4 Hz),
127.4, 127.0, 124.4, 122.9 (q, J = 272.4 Hz), 122.6, 120.8.
Anal. Calc. for C13H7F3N2S: C, 55.71; H, 2.52. Found: C, 55.94; H,
2.60%.
4.16. 2-(2-Ethyl-4-methylthiazol-5-yl)-6-methoxypyridine (13)
The reaction of 2-chloro-6-methoxypyridine (0.144 g, 1 mmol),
2-ethyl-4-methylthiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc
at 120 °C affords the corresponding product 13 in 60% (0.141 g)
isolated yield.
4.12. 2-(2-Propylthiazol-5-yl)-pyridine (9)
1H NMR (200 MHz, CDCl3) d 7.55 (t, J = 7.8 Hz, 1H), 7.05 (d,
J = 8.2 Hz, 1H), 6.60 (d, J = 8.2 Hz, 1H), 3.95 (s, 3H), 3.00 (q,
J = 7.5 Hz, 2H), 2.69 (s, 3H), 1.39 (t, J = 7.5 Hz, 3H).
13C NMR (50 MHz, CDCl3) d 171.8, 163.7, 149.6, 149.5, 139.4,
132.1, 114.6, 109.1, 53.8, 27.4, 18.2, 14.7.
The reaction of 2-chloropyridine (0.113 g, 1 mmol), 2-npropyl-
thiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 150 °C affords
the corresponding product 9 in 38% (0.078 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.58 (d, J = 4.7 Hz, 1H), 8.10 (s, 1H),
7.73 (t, J = 7.8 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.19 (dd, J = 7.8 and
4.7 Hz, 1H), 3.02 (t, J = 7.5 Hz, 2H), 1.87 (sext., J = 7.5 Hz, 2H), 1.06
(t, J = 7.5 Hz, 3H).
Anal. Calc. for C12H14N2OS: C, 61.51; H, 6.02. Found: C, 61.40; H,
6.01%.
4.17. 2-Methoxy-6-(4-methyl-2-phenylthiazol-5-yl)-pyridine (14)
13C NMR (50 MHz, CDCl3) d 173.3, 150.9, 149.8, 139.3, 139.2,
136.7, 122.3, 119.5, 35.7, 23.3, 13.7.
Anal. Calc. for C11H12N2S: C, 64.67; H, 5.92. Found: C, 64.57; H,
5.91%.
The reaction of 2-chloro-6-methoxypyridine (0.144 g, 1 mmol),
2-phenyl-4-methylthiazole (0.210 g, 1.2 mmol) and KOAc (0.118 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc
at 120 °C affords the corresponding product 14 in 62% (0.175 g)
isolated yield.
4.13. 2-(2-Propylthiazol-5-yl)-quinoline (10)
1H NMR (200 MHz, CDCl3)
d 8.00–7.95 (m, 2H), 7.57 (t,
J = 7.8 Hz, 1H), 7.45–7.35 (m, 3H), 7.12 (d, J = 8.2 Hz, 1H), 6.64 (d,
J = 8.2 Hz, 1H), 4.00 (s, 3H), 2.79 (s, 3H).
The reaction of 2-chloroquinoline (0.164 g, 1 mmol), 2-npropyl-
thiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C affords
the corresponding product 10 in 50% (0.127 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.22 (s, 1H), 8.14 (d, J = 7.8 Hz, 1H),
8.07 (d, J = 7.8 Hz, 1H), 7.80–7.60 (m, 3H), 7.50 (t, J = 7.8 Hz, 1H),
3.04 (t, J = 7.5 Hz, 2H), 1.90 (sext., J = 7.5 Hz, 2H), 1.07 (t,
J = 7.8 Hz, 3H).
13C NMR (50 MHz, CDCl3) d 166.2, 163.8, 151.1, 149.4, 139.4,
134.1, 133.6, 130.4, 129.3, 126.8, 114.7, 109.5, 53.9, 18.6.
Anal. Calc. for C16H14N2OS: C, 68.06; H, 5.00. Found: C, 68.10; H,
4.87%.
4.18. 2-(5-Butylthiophen-2-yl)-6-methoxypyridine (15)
13C NMR (50 MHz, CDCl3) d 174.7, 151.1, 148.6, 140.7, 140.4,
137.1, 130.4, 129.6, 128.0, 127.6, 127.0, 118.2, 36.2, 23.8, 14.1.
Anal. Calc. for C15H14N2S: C, 70.83; H, 5.55. Found: C, 70.90; H
5.41%.
The reaction of 2-chloro-6-methoxypyridine (0.144 g, 1 mmol),
2-nbutylthiophene (0.168 g, 1.2 mmol) and KOAc (0.118 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc
at 120 °C affords the corresponding product 15 in 53% (0.131 g)
isolated yield.
4.14. 2-Methoxy-6-(2-propylthiazol-5-yl)-pyridine (11)
1H NMR (200 MHz, CDCl3) d 7.55 (t, J = 7.9 Hz, 1H), 7.42 (d,
J = 3.6 Hz, 1H), 7.18 (d, J = 7.4 Hz, 1H), 6.78 (d, J = 3.6 Hz, 1H),
6.58 (d, J = 7.4 Hz, 1H), 4.01 (s, 3H), 2.85 (t, J = 7.5 Hz, 2H), 1.65
(quint., J = 7.4 Hz, 2H), 1.41 (sext., J = 7.4 Hz, 2H), 0.97 (t,
J = 7.4 Hz, 3H).
The reaction of 2-chloro-6-methoxypyridine (0.144 g, 1 mmol),
2-npropylthiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc

F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
463
13C NMR (50 MHz, CDCl3) d 163.9, 150.8, 148.5, 142.6, 139.4,
125.5, 124.6, 111.2, 108.7, 53.7, 34.2, 30.5, 22.6, 14.3.
Anal. Calc. for C14H17NOS: C, 67.98; H, 6.93. Found: C, 67.87; H,
7.04%.
Anal. Calc. for C11H12N2S: C, 64.67; H, 5.92. Found: C, 64.80; H,
5.81%.
4.24. 3-(4-Methyl-2-phenylthiazol-5-yl)-pyridine (21)
4.19. 5-(6-Methoxypyridin-2-yl)-thiophene-2-carbonitrile (16)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), 2-phenyl-4-
methylthiazole (0.210 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C
affords the corresponding product 21 in 58% (0.146 g) isolated
yield.
The reaction of 2-chloro-6-methoxypyridine (0.144 g, 1 mmol),
thiophene-2-carbonitrile (0.131 g, 1.2 mmol) and KOAc (0.118 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc
at 120 °C affords the corresponding product 16 in 63% (0.136 g)
isolated yield.
1H NMR (200 MHz, CDCl3) d 8.75 (s, 1H), 8.58 (d, J = 4.1 Hz, 1H),
7.96–7.85 (m, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.50–7.20 (m, 4H), 2.55
(s, 3H).
1H NMR (200 MHz, CDCl3) d 7.63 (t, J = 7.4 Hz, 1H), 7.58 (d,
J = 4.0 Hz, 1H), 7.48 (d, J = 4.0 Hz, 1H), 7.27 (d, J = 7.4 Hz, 1H),
6.74 (d, J = 7.4 Hz, 1H), 4.00 (s, 3H).
13C NMR (50 MHz, CDCl3) d 166.5, 150.5, 150.1, 149.2, 136.6,
133.8, 130.6, 129.4, 128.9, 128.6, 126.8, 123.9, 16.7.
Anal. Calc. for C15H12N2S: C, 71.40; H, 4.79. Found: C, 71.42; H,
4.89%.
13C NMR (50 MHz, CDCl3) d 164.1, 152.8, 148.3, 139.8, 138.6,
123.8, 115.1, 112.3, 111.8, 110.4, 54.0.
Anal. Calc. for C11H8N2OS: C, 61.09; H, 3.73. Found: C, 61.01; H,
3.68%.
4.25. 3-(4-tert-Butyl-2-methylthiazol-5-yl)-pyridine (22)
4.20. 2-Pyridin-3-ylbenzooxazole (17)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), 2-methyl-
4-tbutylthiazole (0.187 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C
affords the corresponding product 22 in 33% (0.077 g) isolated
yield.
The reaction of 3-chloropyridine (0.113 g, 1 mmol), benzoxaz-
ole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 120 °C affords
the corresponding product 17 in 80% (0.157 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 9.48 (s, 1H), 8.77 (d, J = 4.2 Hz, 1H),
8.52 (d, J = 8.2 Hz, 1H), 7.81 (m, 1H), 7.62 (m, 1H), 7.54–7.30 (m,
3H).
1H NMR (200 MHz, CDCl3) d 8.63 (s, 2H), 7.69 (d, J = 7.2 Hz, 1H),
7.32 (dd, J = 7.2 and 4.8 Hz, 1H), 2.68 (s, 3H), 1.23 (s, 9H).
13C NMR (50 MHz, CDCl3) d 163.4, 160.7, 151.6, 149.5, 138.6,
132.2, 129.9, 122.5, 32.1, 30.1, 19.4.
Anal. Calc. for C13H16N2S: C, 67.20; H, 6.94. Found: C, 67.35; H,
6.80%.
4.21. 2-Pyridin-3-ylbenzothiazole (18)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), benzothia-
zole (0.156 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C affords
the corresponding product 18 in 79% (0.168 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 9.30 (s, 1H), 8.71 (d, J = 4.2 Hz, 1H),
8.36 (d, J = 8.1 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 8.2 Hz,
1H), 7.60–7.30 (m, 3H).
4.26. 3-(5-Butylthiophen-2-yl)-pyridine (23)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), 2-nbutylthi-
ophene (0.168 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C affords
the corresponding product 23 in 61% (0.133 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.85 (s, 1H), 8.49 (d, J = 4.8 Hz, 1H),
7.82 (d, J = 7.8 Hz, 1H), 7.28 (dd, J = 7.8 and 4.8 Hz, 1H), 7.20 (d,
J = 3.8 Hz, 2H), 6.80 (d, J = 3.8 Hz, 2H), 2.86 (t, J = 7.5 Hz, 2H), 1.75
(quint., J = 7.5 Hz, 2H), 1.41 (sext., J = 7.5 Hz, 2H), 0.97 (t,
J = 7.5 Hz, 3H).
4.22. 3-(2-Propylthiazol-5-yl)-pyridine (19)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), 2-npropyl-
thiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C affords
the corresponding product 19 in 78% (0.159 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.80 (s, 1H), 8.55 (d, J = 4.2 Hz, 1H),
7.87 (s, 1H), 7.84 (d, J = 7.2 Hz, 1H), 7.33 (dd, J = 7.2 and 4.2 Hz, 1H),
3.01 (t, J = 7.5 Hz, 2H), 1.86 (sext., J = 7.5 Hz, 2H), 1.05 (t, J = 7.5 Hz,
3H).
13C NMR (50 MHz, CDCl3) d 147.9, 147.1, 146.6, 137.6, 132.4,
130.7, 125.3, 123.9, 123.6, 33.7, 29.9, 22.1, 13.8.
Anal. Calc. for C13H15NS: C, 71.84; H, 6.96. Found: C,71.97; H,
6.99%.
4.27. 3-(5-Butylfuran-2-yl)-pyridine (24)
13C NMR (50 MHz, CDCl3) d 172.3, 149.4, 147.9, 139.1, 134.9,
134.0, 128.3, 124.1, 36.0, 23.7, 14.1.
Anal. Calc. for C11H12N2S: C, 64.67; H, 5.92. Found: C, 64.57; H,
5.99%.
The reaction of 3-chloropyridine (0.113 g, 1 mmol), 2-nbutylfu-
ran (0.149 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C affords
the corresponding product 24 in 41% (0.083 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.90 (s, 1H), 8.52–8.40 (m, 1H), 7.89
(d, J = 5.9 Hz, 1H), 7.28 (m, 1H), 6.65 (d, J = 3.0 Hz, 1H), 6.10 (d,
J = 3.0 Hz, 1H), 2.71 (t, J = 7.6 Hz, 2H), 1.70 (quint., J = 7.5 Hz, 2H),
1.45 (sext., J = 7.5 Hz, 2H), 0.97 (t, J = 7.5 Hz, 3H).
4.23. 3-(2-Ethyl-4-methylthiazol-5-yl)-pyridine (20)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), 2-ethyl-4-
methylthiazole (0.153 g, 1.2 mmol) and KOAc (0.118 g, 1.2 mmol)
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc at 120 °C af-
fords the corresponding product 20 in 74% (0.151 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.69 (s, 1H), 8.56 (d, J = 4.8 Hz, 1H),
7.70 (d, J = 7.2 Hz, 1H), 7.37 (dd, J = 7.2 and 4.8 Hz, 1H), 3.01 (q,
J = 7.5 Hz, 2H), 2.47 (s, 3H), 1.41 (t, J = 7.5 Hz, 3H).
4.28. Methyl 2-methyl-5-pyridyl-3-furoate (25)
The reaction of 3-chloropyridine (0.113 g, 1 mmol), methyl 2-
methyl-3-furoate (0.168 g, 1.2 mmol) and KOAc (0.118 g,
1.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc
at 120 °C affords the corresponding product 25 in 30% (0.065 g)
isolated yield.
13C NMR (50 MHz, CDCl3) d 171.7, 150.1, 148.9, 148.7, 136.6,
129.2, 127.3, 123.8, 27.4, 16.4, 14.7.

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F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
1H NMR (200 MHz, CDCl3) d 9.00–8.80 (m, 1H), 8.60–8.40 (m,
1H NMR (200 MHz, CDCl3) d 8.70 (d, J = 6.3 Hz, 2H), 8.29 (s, 1H),
7.52 (d, J = 6.3 Hz, 2H), 3.22 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H).
13C NMR (50 MHz, CDCl3) d 194.9, 167.6, 151.2, 143.6, 142.3,
138.3, 121.5, 32.1, 8.3.
Anal. Calc. for C11H10N2O2S: C, 56.39; H, 4.30. Found C, 56.21; H,
4.41%.
1H), 7.92 (d, J = 7.8 Hz, 1H), 7.40–7.25 (m, 1H), 7.00 (s, 1H), 3.87
(s, 3H), 2.68 (s, 3H).
13C NMR (50 MHz, CDCl3) d 164.6, 160.1, 149.3, 148.9, 145.6,
131.1, 126.5, 124.0, 115.8, 107.4, 52.0, 14.3.
Anal. Calc. for C12H11NO3: C, 66.35; H, 5.10. Found: C, 66.18; H,
5.21%.
4.34. 4-(5-Butylthiophen-2-yl)-pyridine (31)
4.29. 2-Pyridin-4-ylbenzoxazole (26)
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), 2-nbutylthiophene (0.168 g, 1.2 mmol) and KOAc
(0.216 g, 2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol)
in DMAc at 120 °C affords the corresponding product 31 in 50%
(0.109 g) isolated yield.
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), benzoxazole (0.143 g, 1.2 mmol) and Cs2CO3 (0.715 g,
2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF
at 120 °C affords the corresponding product 26 in 71% (0.139 g)
isolated yield.
1H NMR (200 MHz, CDCl3) d 8.70–8.40 (m, 2H), 7.43 (d,
J = 6.4 Hz, 2H), 7.34 (d, J = 3.8 Hz, 1H), 6.82 (d, J = 3.8 Hz, 1H),
2.86 (t, J = 7.5 Hz, 2H), 1.75 (quint., J = 7.5 Hz, 2H), 1.41 (sext.,
J = 7.5 Hz, 2H), 0.97 (t, J = 7.5 Hz, 3H).
1H NMR (200 MHz, CDCl3) d 8.83 (d, J = 7.0 Hz, 2H), 8.10 (d,
J = 7.0 Hz, 2H), 7.81 (m, 1H), 7.64 (m, 1H), 7.50–7.30 (m, 3H).
4.30. 2-Pyridin-4-ylbenzothiazole (27)
13C NMR (50 MHz, CDCl3) d 150.6, 149.0, 142.1, 138.7, 126.0,
125.6, 119.9, 34.0, 30.4, 22.6, 14.2.
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), benzothiazole (0.162 g, 1.2 mmol) and Cs2CO3 (0.715 g,
2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF
at 150 °C affords the corresponding product 27 in 65% (0.138 g)
isolated yield.
Anal. Calc. for C13H15NS: C, 71.84; H, 6.96. Found: C, 71.70; H,
6.79%.
4.35. 4-(5-Butylfuran-2-yl)-pyridine (32)
1H NMR (200 MHz, CDCl3) d 8.79 (d, J = 6.5 Hz, 2H), 8.14 (d,
J = 8.2 Hz, 1H), 7.98-7.90 (m, 3H), 7.55 (t, J = 7.8 Hz, 1H), 7.47 (t,
J = 7.8 Hz, 1H).
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), 2-nbutylfuran (0.149 g, 1.2 mmol) and KOAc (0.216 g,
2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMAc
at 120 °C affords the corresponding product 32 in 34% (0.069 g)
isolated yield.
4.31. 4-(2-Propylthiazol-5-yl)-pyridine (28)
1H NMR (200 MHz, CDCl3) d 8.65–8.40 (m, 2H), 7.48 (d,
J = 6.3 Hz, 2H), 6.80 (d, J = 3.8 Hz, 1H), 6.14 (d, J = 3.8 Hz, 1H),
2.72 (t, J = 7.5 Hz, 2H), 1.75 (quint., J = 7.5 Hz, 2H), 1.41 (sext.,
J = 7.5 Hz, 2H), 0.97 (t, J = 7.5 Hz, 3H).
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), 2-npropylthiazole (0.153 g, 1.2 mmol) and KOAc
(0.216 g, 2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol)
in DMAc at 120 °C affords the corresponding product 28 in 76%
(0.155 g) isolated yield.
13C NMR (50 MHz, CDCl3) d 159.1, 150.3, 138.2, 122.5, 117.7,
110.2, 108.0, 30.5, 28.3, 22.7, 14.2.
1H NMR (200 MHz, CDCl3) d 8.61 (d, J = 6.4 Hz, 2H), 8.00 (s, 1H),
7.40 (d, J = 6.4 Hz, 2H), 3.01 (t, J = 7.5 Hz, 2H), 1.88 (sext., J = 7.5 Hz,
2H), 1.04 (t, J = 7.5 Hz, 3H).
Anal. Calc. for C13H15NO: C, 77.58; H, 7.51. Found: C, 77.41; H,
7.47%.
13C NMR (50 MHz, CDCl3) d 173.4, 150.9, 140.3, 139.5, 135.9,
121.0, 36.1, 23.7, 14.0.
4.36. 2-Pyrimidin-2-ylbenzoxazole (33)
Anal. Calc. for C11H12N2S: C, 64.67; H, 5.92. Found: C, 64.80; H,
5.81%.
The reaction of 2-chloropyrimidine (0.115 g, 1 mmol), benzox-
azole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C affords
the corresponding product 33 in 81% (0.160 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.91 (d, J = 7.3 Hz, 2H), 7.82 (d,
J = 7.8 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.50–7.30 (m, 3H).
13C NMR (50 MHz, CDCl3) d 158.5, 157.0, 154.2, 150.2, 140.6,
126.0, 124.3, 120.9, 120.5, 110.4.
4.32. 4-(2-Ethyl-4-methylthiazol-5-yl)-pyridine (29)
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), 2-ethyl-4-methylthiazole (0.153 g, 1.2 mmol) and KOAc
(0.216 g, 2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol)
in DMAc at 120 °C affords the corresponding product 29 in 34%
(0.069 g) isolated yield.
Anal. Calc. for C11H7N3O: C, 67.00; H, 3.58. Found: C, 67.11; H,
3.67%.
1H NMR (200 MHz, CDCl3) d 8.64 (d, J = 6.4 Hz, 2H), 7.33 (d,
J = 6.4 Hz, 2H), 3.01 (q, J = 7.6 Hz, 2H), 2.53 (s, 3H), 1.41 (t,
J = 7.6 Hz, 3H).
4.37. 2-Benzothiazol-2-ylbenzoxazole (34)
13C NMR (50 MHz, CDCl3) d 172.3, 150.5, 149.7, 140.8, 128.5,
123.5, 27.4, 17.0, 14.6.
The reaction of 2-chlorobenzothiazole (0.170 g, 1 mmol), benz-
oxazole (0.143 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol) with
PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C affords
the corresponding product 34 in 54% (0.136 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 8.26 (d, J = 8.2 Hz, 1H), 8.01 (d,
J = 8.2 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.72 (d, J = 8.2 Hz, 1H),
7.60 (t, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.50–7.40 (m, 2H).
Anal. Calc. for C11H12N2S: C, 64.67; H, 5.92. Found: C, 64.50; H,
5.99%.
4.33. 5-Pyridin-4-ylthiazole-2-carboxylic acid ethyl ester (30)
The reaction of 4-chloropyridine hydrochloride (0.150 g,
1 mmol), ethyl thiazole-2-carboxylate (0.189 g, 1.2 mmol) and
KOAc (0.216 g, 2.2 mmol) with PdCl(C3H5)(dppb) (0.015 g,
0.025 mmol) in DMAc at 120 °C affords the corresponding product
30 in 37% (0.087 g) isolated yield.
4.38. [2,20]Bibenzothiazolyl (35)
The reaction of 2-chlorobenzothiazole (0.170 g, 1 mmol), ben-
zothiazole (0.162 g, 1.2 mmol) and Cs2CO3 (0.390 g, 1.2 mmol)

F. Derridj et al. / Journal of Organometallic Chemistry 694 (2009) 455–465
465
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(g) H. Schirok, J. Org. Chem. 71 (2006) 5538;
with PdCl(C3H5)(dppb) (0.015 g, 0.025 mmol) in DMF at 150 °C af-
fords the corresponding product 35 in 63% (0.169 g) isolated yield.
1H NMR (200 MHz, CDCl3) d 7.80 (d, J = 8.0 Hz, 1H), 7.73 (d,
J = 8.0 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.28 (t, J = 7.8 Hz, 1H).
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4.39. Cyclic voltammetry
Compounds 3 and 4 exhibited in cyclic voltammetry a revers-
ible wave at –1.55VSCE and –1.47VSCE, corresponding to the forma-
tion of
a radical anion, as previously reported for similar
benzothiazole and benzoxazole derivatives [17]. The substitution
of the pyridine group by a quinoline in 3 and the introduction of
an electron-attracting substituent on the pyridine ring in 4 ren-
dered the nucleus more easily reducible, as seen by the cathodic
shift of the reduction potentials (ꢀ1.87VSCE for 2). The electronic
effect in 4 also affected the second reduction wave, observed at a
less cathodic potential than other analogues (ꢀ2.47VSCE for 1 and
–2.05VSCE for 4).
(b) J. Koubachi, S. El Kazzouli, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet,
Synlett (2006) 3237;
(c) A. Battace, M. Lemhadri, T. Zair, H. Doucet, M. Santelli, Adv. Synth. Catal.
349 (2007) 2507;
(d) P. Amaladass, J.A. Clement, A.K. Mohanakrishnan, Tetrahedron 63 (2007)
10363;
CAS Registry No.: 1, 64819-72-3; 2, 32959-62-9; 3, 24613-96-5;
6, 22201-26-9; 7, 24613-99-8; 17, 2295-42-3; 18, 2612-72-8; 24,
925459-37-6; 26, 2295-47-8; 27, 2295-38-7; 34, 31704-13-9; 35,
35, 4271-09-4.
(e) X. Wang, D.V. Gribkov, D. Sames, J. Org. Chem. 72 (2007) 1476;
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[8] (a) For examples of palladium-catalyzed bimolecular direct arylation of
heteroaromatics by using aryl iodides: B.S. Lane, D. Sames, Org. Lett.
(2004) 2897;
6
(b) I. Cerna, R. Pohl, B. Klepetarova, M. Hocek, Org. Lett. 8 (2006) 5389;
(c) B.B. Toure, B.S. Lane, D. Sames, Org. Lett. 8 (2006) 1979;
Acknowledgments
(d) G.L. Turner, J.A. Morris, M.F. Greaney, Angew. Chem., Int. Ed. 46 (2007)
7996;
We thank ‘‘CNRS” and ‘‘Rennes Metropole” for financial support.
(e) M. Irie, S. Takami, J. Phys. Org. Chem. 20 (2007) 894;
(f) J. Priego, S. Gutierrez, R. Ferritto, H.B. Broughton, Synlett (2007) 2957.
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heteroaromatics by using aryl chlorides: Y. Aoyagi, A. Inoue, I. Koizumi, R.
Hashimoto, K. Tokunaga, K. Gohma, J. Komatsu, K. Sekine, A. Miyafuji, J. Kunoh,
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heteroaromatics by using aryl chlorides, see: M. Smet, J. Van Dijk, W. Dehaen,
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