Palladium-catalysed direct C-H activation/arylation of heteroaromatics: An environmentally attractive access to bi- or polydentate ligands

Article abstract of DOI:10.1002/ejic.200800143

Bi- or polydentate ligands based on heterocycles can be easily prepared by palladium-catalysed C-H bond activation of heteroaromatics followed by heteroarylation with heteroaryl bromides. A variety of heteroaromatics such as furans, thiophenes, pyridines, thiazoles or oxazole derivatives have been employed and moderate to good yields were generally obtained using the air-stable complex [PdCl(dppb)(C₃H₅)] as catalyst. A range of functions such as acetyl, formyl, ester or nitrile on the heteroaromatics is tolerated. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejic.200800143

FULL PAPER
DOI: 10.1002/ejic.200800143
Palladium-Catalysed Direct C-H Activation/Arylation of Heteroaromatics: An
Environmentally Attractive Access to Bi- or Polydentate Ligands
Fazia Derridj,[a] Aditya L. Gottumukkala,[b] Safia Djebbar,[a] and Henri Doucet*[b]
Keywords: Atom economy / Homogeneous catalysis / C–H activation / Heterocycles / Palladium
Bi- or polydentate ligands based on heterocycles can be eas-
ily prepared by palladium-catalysed C–H bond activation of
heteroaromatics followed by heteroarylation with heteroaryl
bromides. A variety of heteroaromatics such as furans, thio-
phenes, pyridines, thiazoles or oxazole derivatives have been
employed and moderate to good yields were generally ob-
tained using the air-stable complex [PdCl(dppb)(C3H5)] as
catalyst. A range of functions such as acetyl, formyl, ester or
nitrile on the heteroaromatics is tolerated.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
ated to a base as by-product and therefore is very interest-
ing both in terms of atom-economy and the relative inert-
ness of the wastes (Scheme 1). This procedure could there-
fore provide an economic and environmentally attractive
procedure for the preparation of bi- or polydentate li-
gands.[5] However, most of the results described so far for
this reaction were obtained for the coupling of heteroarom-
atics with aryl halides.[5] 2-Haloheteroarenes are uncommon
partners for such couplings[6–9] and only a few examples
have been described with such substrates in the literature.
For example, the direct heteroarylation of 5-bromo-2-fural-
dehyde by C–H bond activation of 2-furaldehyde has been
described by McClure and co-workers, who used PdCl2 in
conjunction with PCy3 as the catalyst and obtained the
coupling product in 64% yield.[6] The reaction of an oxazolo-
pyridine with 2-chloropyridine using Pd(OAc)2/PPh3 as
catalyst has been reported to give 2-(pyridin-2-yl)ox-
azolo[4,5-b]pyridine in 33% yield,[7a] and an improved pro-
cedure for this reaction was recently reported by Daugulis
and Chiong, who used the electron-rich and congested bu-
tyldi(1-adamantyl)phosphane ligand to obtain the coupling
product in 67% yield.[7b] A coupling reaction between 2-
bromothiophene and an indolizine leading to 3-(thiophen-
2-yl)indolizine in 55% yield has also been reported.[8] Three
examples of direct 5-heteroarylations of imidazoles via C–
H activation have also been described.[9] For example, Mi-
ura and co-workers have successfully coupled 1,2-dimethyl-
1H-imidazole with 2-bromothiazole in 41% yield using
Pd(OAc)2/PPh3 as the catalyst,[9a] and 2-bromopyridine was
coupled to an imidazo-pyrimidine in 55% yield under sim-
ilar reaction conditions.[9b] The direct arylation of a purine
at position 8 has been described by Hocek and co-
workers,[9c] who used Pd(OAc)2 as the catalyst, Cs2CO3 as
the base and CuI as an additive. Although the conditions
for this reaction are rather harsh (160 °C), the coupling
with 2-iodopyridine gave the cross-coupling product re-
Introduction
Bi- or polydentate ligands based on polyheteroaromatics
such as bipyridines or polythiophenes are useful com-
pounds for organometallic chemistry and catalysis or for
preparation of materials due to their specific coordination
and electronic properties. Palladium-catalysed Suzuki, Stille
or Negishi cross-coupling reactions between 2-halohetero-
arenes and organometallic derivatives of thiophenes, furans,
thiazoles, oxazoles or pyridines are some of the most impor-
tant methods for the synthesis of such compounds.[1–4]
However, these reactions require the preparation of an or-
ganometallic derivative of the heteroaromatic and produce
an organometallic salt (MX) as a by-product (Scheme 1).
Scheme 1.
Very interesting results regarding the coupling of aryl ha-
lides with heteroaromatic derivatives by C–H bond acti-
vation have been reported over the past few years. No prep-
aration of an organometallic derivative is required for such
couplings. Moreover, this reaction provides only HX associ-
[a] Laboratoire d’hydrométallurgie et chimie inorganique molécu-
laire, Faculté de Chimie, U.S.T.H.B.,
Bab-Ezzouar, Algeria
[b] Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Uni-
versité de Rennes, “Catalyse et Organometalliques”,
Campus de Beaulieu, 35042 Rennes, France
Fax: +33-2-2323-6939
E-mail: henri.doucet@univ-rennes1.fr
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C-H Activation/Arylation of Heteroaromatics
gioselectively in 42% yield. Finally, it should be noted that
We next examined the reactivity of 5-bromo-2-fural-
homocoupling by C–H bond activation of heteroaromatics dehyde for the palladium-catalysed coupling with a set of
using palladium or gold catalysts has also been reported.[10] heteroaromatic compounds (Scheme 2, Table 1) with
Although a few syntheses of ligands by palladium-cata- DMAc as solvent, KOAc as base and [PdCl(C3H5)-
lysed C–H bond activation of heteroaromatics followed by (dppb)][13] as catalyst. All reactions were performed at
heteroarylation have been described, the scope of the reac- 120 °C, as partial degradation of 5-bromo-2-furaldehyde
tion needs to be extended to a wider variety of heteroaro- and of some of the coupling products was observed at more
matics and also to functionalised heteroaryl halides. More- elevated temperatures. Complete conversion of 5-bromo-2-
over, higher yields for the coupling of such compounds have furaldehyde was observed under these conditions in all
to be obtained using more efficient catalysts under more cases. Similar isolated yields (71–78%) of target products
effective reaction conditions in order to obtain economi- 2–6 were obtained using methyl 2-methyl-3-furancarboxyl-
cally viable procedures.
ate, 2-butylthiophene, 2-methylthiophene, 2-chlorothio-
phene or 2-propylthiazole as reagents. The coupling is re-
gioselective in favour of the 5-arylation in all cases. Selective
5-arylation was also observed with 2-chlorothiophene, and
5-(5-chlorothiophen-2-yl)furan-2-carbaldehyde (5) was ob-
tained in 71% yield (Table 1, entry 5). The thiophene–chlo-
rine bond of this reagent was found to be unreactive under
these reaction conditions.
Results and Discussion
The classical palladium catalysts for C–H activation/
functionalisation of heteroaromatic derivatives with aryl ha-
lides or triflates are probably ligand-less palladium com-
plexes or palladium associated to monophosphanes,[5,11a]
although bi- or polydentate phosphane ligands have also
demonstrated their usefulness.[5,11b,11c,12] We therefore de-
cided to examine the reactivity of 5-bromo-2-furaldehyde
for the palladium-catalysed coupling reaction with 2-bu-
tylfuran using Pd(OAc)2 or [PdCl(C3H5)]2, DMAc (N,N-
dimethylacetamide) as solvent and KOAc as base at 120 °C
in the absence of ligand. The formation of unidentified
side-products was observed, especially in the presence of
Pd(OAc)2. We have recently reported that ligand-free
Pd(OAc)2 is a very powerful catalyst for the direct arylation
of furans, thiophenes or thiazoles Ϫ the reaction can be
performed with as little as 0.01 mol-% catalyst. However,
the efficiency of this catalyst is limited to the coupling of
very reactive substrates such as activated aryl bromides and
does not seems to be appropriate for the coupling of het-
eroaryl bromides.[11d]
Table 1. Palladium-catalysed cross-coupling with 5-bromo-2-fural-
dehyde (Scheme 2).[a]
Most of the couplings of heteroaryl derivatives with aryl
halides reported in the literature were performed at elevated
temperature (120–150 °C),[5] where a fast decomposition of
most palladium complexes generally occurs, especially when
relatively high catalyst loadings are employed. The use of
phosphane ligands seems to increase the stability and lon-
gevity of the catalyst in palladium-catalysed reactions, and
better yields of coupling products can be expected in some
cases. We therefore next performed the coupling of 5-
bromo-2-furaldehyde with 2-butylfuran using Pd(OAc)2 or
[PdCl(C3H5)]2 in combination with PPh3 or dppb. A higher
isolated yield of 1 was obtained using the bidentate phos-
phane ligand. For this reason, we have employed palladium
in combination with dppb as a catalyst to study the scope
and limitations of these couplings.
[a] Conditions: [PdCl(dppb)(C3H5)] (0.05 equiv.), 5-bromo-2-fural-
dehyde (1 equiv.), heteroarene (2 equiv.), KOAc (2 equiv.), DMAc,
20 h, 120 °C. The yields given are those of isolated product.
Scheme 2.
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The scope and limitations of this reaction with other het-
This reaction is not limited to thiophene and 2-methyl-
eroaryl bromides were investigated next. 2-Bromothiophene or 2-chlorothiophenes. For example, 2-bromo-5-formylthio-
or 2-bromo-5-methylthiophene were successfully coupled phene was also found to be a suitable reageant for this reac-
with 2-propylthiazole, benzoxazole, 2-chlorothiophene, 2- tion (Table 3, Scheme 4). Again, a variety of heteroarenes
methylthiophene or 2-chlorothiophene (Scheme 3, Table 2). weren coupled with this substrate to give the desired prod-
Slightly lower yields than for the coupling with 5-bromo-2- ucts 17–22. Only a minor influence of the nature of the
furaldehyde were obtained in some cases due to the forma- heteroarene on the yield of coupling product was observed.
tion of 2,2Ј-bithiophene (15), 5,5Ј-dimethyl-2,2Ј-bithio- Thus, the highest yields of 77 and 80% were obtained using
phene (12) or 5,5Ј-dichloro-2,2Ј-bithiophene (16) as side 2-butylfuran and 2-propylthiazole, respectively (Table 3, en-
products. However, the target products 7–14 were obtained tries 1 and 6). Less reactive heteroarenes such as 2-methyl-
regioselectively in all cases. In the presence of 5-bromo-2- thiophenes or 2-chlorothiophene gave the target products
chlorothiophene and benzothiophene, the expected product 20 and 21 in 65 and 69% yields, respectively (Table 3, en-
14 was obtained in a lower yield of 30% (Table 2, entry 8), tries 4 and 5). Formation of the homo-coupling product 23
and unidentified side products were also formed during the from 2-bromo-5-formylthiophene was also observed in low
course of this reaction. However, these reactions generally yield during the course of these reactions.
gave a very simple access to substituted thiophenes or un-
symmetrical bithiophene derivatives in one step.
As expected, the treatment of 2-acetyl-5-bromothiophene
with electron-rich heteroarenes also gave the expected coup-
Scheme 3.
Table 2. Palladium-catalysed cross-coupling with 2-bromothiophene, 2-bromo-5-methylthiophene or 2-bromo-5-chlorothiophene
(Scheme 3).[a]
[a] Conditions: [PdCl(dppb)(C3H5)] (0.05 equiv.), 2-bromothiophene, 2-bromo-5-methylthiophene or 2-bromo-5-chlorothiophene
(1 equiv.), heteroarene (2 equiv.), KOAc (2 equiv.), DMAc, 20 h. The yields given are those of isolated product. [b] The formation of 2,2Ј-
bithiophene (15) was also observed. [c] The formation of 5,5Ј-dimethyl-2,2Ј-bithiophene (12) was also observed. [d] Cs2CO3 was used as
base and DMF as solvent. [e] 1 mol-% of [PdCl(dppb)(C3H5)]. [f] The formation of 5,5Ј-dichloro-2,2Ј-bithiophene (16) was also observed.
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C-H Activation/Arylation of Heteroaromatics
Table 3. Palladium catalysed cross-coupling with 2-bromo-5-formylthiophene (Scheme 4).[a]
[a] Conditions: [PdCl(dppb)(C3H5)] (0.05 equiv.), 2-bromo-5-formylthiophene (1 equiv.), heteroarene (2 equiv.), KOAc (2 equiv.), DMAc,
20 h. The yields given are those of isolated product. The formation of 2,2Ј-bithiophene-5,5Ј-dicarbaldehyde (23) was also observed.
Scheme 4.
Table 4. Palladium-catalysed cross-coupling with 2-acetyl-5-bromothiophene (Scheme 4).[a]
[a] Conditions: [PdCl(dppb)(C3H5)] (0.05 equiv.), 2-acetyl-5-bromothiophene (1 equiv.), heteroarene (2 equiv.), KOAc (2 equiv.), DMAc,
20 h. The yields given are those of isolated product. The formation of 1-(5Ј-acetyl-2,2Ј-bithiophene-5-yl)ethanone (32) was also observed.
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F. Derridj, A. L. Gottumukkala, S. Djebbar, H. Doucet
FULL PAPER
ling products 24–31 together with a small amount of the Table 5. Palladium-catalysed cross-coupling with 2-bromo-5-meth-
ylpyridine (Scheme 5).[a]
homo-coupling product 32 (Table 4, Scheme 4). Thus, the
reaction of 2-butylfuran or methyl 2-methyl-3-furancarbox-
ylate gave 24 and 25 in 62 and 53% yields, respectively,
whereas 26 was obtained from 2-acetylfuran in a lower yield
due to the formation of unidentified side-products (Table 4,
entries 1–3). The coupling with four thiophene derivatives
was also tested with this substrate; they gave the expected
substituted bithiophenes 27–30 in good yields (Table 4, en-
tries 4–7). For example, the reaction of 2-acetyl-5-bromo-
thiophene with thiophene-2-carbonitrile gave 5Ј-acetyl-2,2Ј-
bithiophene-5-carbonitrile (29) in 64% yield (Table 4, en-
try 6). Again, a selective 5-arylation of 2-propylthiazole was
observed with 2-acetyl-5-bromothiophene to give 31 in 56%
yield (Table 4, entry 8).
Palladium chemistry involving heterocycles has several
unique characteristics that stem from the heterocycles’ in-
herently different structural and electronic properties in
comparison to the corresponding carbocyclic aryl com-
pounds. Pyridines, for example, are π-electron deficient,
while thiophenes or furans are π-electron rich. Thus, if the
oxidative addition of the aryl halide to the palladium com-
plex is the rate-limiting step of the reaction with this cata-
lyst, the reactions should be slower with thiophenes or fu-
rans than with pyridines. In fact, we generally obtained bet-
ter yields of coupling products with thiophenes or furans
than with pyridines (Table 5, Scheme 5). Using 2-bromo-5-
methylpyridine, the formation of the homo-coupling side-
product 6,6Ј-dimethyl-2,2Ј-bipyridinyl (39) was observed in
moderate to large amounts therefore only low to moderate
yields of the expected coupling products 33–38 were ob-
[a] Conditions: [PdCl(dppb)(C3H5)] (0.05 equiv.), 2-bromo-5-meth-
tained. The oxidative addition to palladium is probably rel-
ylpyridine (1 equiv.), heteroarene (2 equiv.), KOAc (2 equiv.),
DMAc, 20 h, 150 °C. The yields given are those of isolated product.
The formation of 6,6Ј-dimethyl-2,2Ј-bipyridinyl (39) was also ob-
served. [b] Cs2CO3 was used as base and DMF as solvent.
atively fast with this substrate but the coupling with the
heteroarenes is apparently slower than with 2-bromofurans
or thiophenes. This means that the side reaction that gives
the homo-coupling bipyridine product 39 is predominant in
some cases. With 2-bromo-5-methylpyridine, the best yields
of coupling products were obtained using benzothiazole or
benzoxazole as coupling partners (Table 5, entries 4 and 6, access to tridentate ligands. We observed that the expected
respectively). 2,5-diarylated thiophenes 40 and 41 were obtained directly
We also attempted to perform the diarylation of 2,5-di- in the presence of benzoxazole or 2-butylthiophene
bromothiophene as this reaction would give a very simple (Schemes 6 and 7). Finally, we tried to diarylate 1,2-dibro-
Scheme 5.
Scheme 6.
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C-H Activation/Arylation of Heteroaromatics
Scheme 7.
Scheme 8.
Preparation of the [PdCl(dppb)(C3H5)] Catalyst:[13] An oven-dried
40-mL Schlenk tube equipped with a magnetic stirring bar was
charged with [Pd(C3H5)Cl]2 (182 mg, 0.5 mmol) and dppb (426 mg,
1 mmol) under an argon atmosphere. Anhydrous dichloromethane
(10 mL) was then added and the resulting solution stirred at room
temperature for twenty minutes. The solvent was removed in vacuo
mobenzene as this reaction would also allow access to an-
other class of useful ligands in one step. The coupling with
2-propylthiazole afforded 42 in 43% yield (Scheme 8).
Conclusions
and the resulting yellow powder was used without purification. 31
P
NMR (81 MHz, CDCl3): δ = 19.3 (s) ppm.
In summary, a wide variety of bi- or polydentate ligands
can be prepared easily in moderate to good yields by the
direct heteroarylation of 2-halogenated heteroaromatic de-
rivatives. Better results were generally obtained using 2-bro-
mothiophenes or a 2-bromofuran than a 2-bromopyridine
General Procedure for Coupling Reactions: In a typical experiment,
the heteroaryl bromide (1 mmol), heteroaryl (2 mmol), KOAc
(0.196 g, 2 mmol) or Cs2CO3 (0.650 g, 2 mmol; see tables) and
[PdCl(C3H5)(dppb)] (0.030 g, 0.05 mmol) were dissolved in DMAc
derivative. Several heteroaromatics can be employed as or DMF (5 mL; see tables) under argon and the reaction mixture
stirred at 120–150 °C (see tables) for 20 h. The solution was diluted
with water or with a 1  H2O/KOH solution (20 mL) for products
containing a pyridine, benzoxazole or benzimidazole moiety. The
product was then extracted three times with CH2Cl2. The combined
organic layers weres dried with MgSO4 and the solvent removed in
vacuo. The crude product was purified by silica gel column
chromatography.
coupling partners, and good yields were generally obtained
using substituted furans, thiophenes, thiazoles or oxazoles.
N-Methylbenzimidazole was found to be less reactive. It
should be noted that a range of functions such as acetyl,
formyl, ester or nitrile are tolerated. This procedure is very
simple, economically attractive and uses commercially avail-
able substrates. The air-stability of the catalyst also makes
this procedure very convenient. A large number of the prod-
ucts prepared by this method have never been described so
far, thus indicating that this procedure provides a conve-
nient access to compounds which cannot be prepared easily
by more classical cross-coupling methods. Moreover, due to
environmental considerations, such atom-economic pro-
cedures that produce inert wastes (acetic acid and potas-
sium bromide in most cases) should become increasingly
important for industrial processes.
5Ј-Butyl-2,2Ј-bifuranyl-5-carbaldehyde (1): The reaction of 5-
bromo-2-furaldehyde (0.175 g, 1 mmol), 2-butylfuran (0.248 g,
2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 1 in 72% (0.157 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 9.60 (s, 1 H), 7.31 (d, J = 3.5 Hz, 1 H), 6.83 (d, J =
3.5 Hz, 1 H), 6.67 (d, J = 3.5 Hz, 1 H), 6.15 (d, J = 3.5 Hz, 1 H),
2.71 (t, J = 7.5 Hz, 2 H), 1.72 (quint, J = 7.4 Hz, 2 H), 1.45 (sext,
J = 7.4 Hz, 2 H), 0.93 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 176.7, 159.0, 151.9, 151.2, 143.1, 123.9,
110.7, 107.5, 106.4, 29.9, 27.8, 22.2, 13.7 ppm. C13H14O3 (218.25):
calcd. C 71.54, H 6.47; found C 71.41, H 6.57. HRMS (EI) calcd.
for [M]+: m/z 218.0943; found 218.0941.
Experimental Section
General Remarks: All reactions were prformed under argon in
Schlenk tubes on a vacuum line. Analytical grade N,N-dimethyl-
Methyl 5Ј-Formyl-5-methyl-2,2Ј-bifuranyl-4-carboxylate (2): The re-
action of 5-bromo-2-furaldehyde (0.175 g, 1 mmol), methyl 2-
acetamide (DMAc) and N,N-dimethylformamide (DMF) were used methyl-3-furancarboxylate (0.280 g, 2 mmol) and KOAc (0.196 g,
as received. Potassium acetate and caesium carbonate (99%) were
obtained commercially. Commercial heteroaryl halides and het-
eroaryl derivatives were used without purification. 1H and 13C
NMR spectra were recorded with a Bruker 200 MHz spectrometer
in CDCl3 solutions. Chemical shifts are reported in ppm relative to
2 mmol) at 120 °C in dry DMAc (5 mL) in the presence of
[PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 2 in 75%
(0.176 g) isolated yield. H NMR (200 MHz, CDCl3): δ = 9.65 (s,
1 H), 7.31 (d, J = 3.5 Hz, 1 H), 7.13 (s, 1 H), 6.73 (d, J = 3.5 Hz,
1 H), 3.87 (s, 3 H), 2.68 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 177.0, 163.7, 160.7, 151.7, 150.3, 142.6, 123.0, 115.0, 109.9,
107.7, 51.6, 13.9 ppm. C12H10O5 (234.20): calcd. C 61.54, H 4.30;
1
1
CDCl3 (δ = 7.25 for H and 77.0 ppm for 13C). Flash chromatog-
raphy was performed on silica gel (230–400 mesh).
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found C 61.59, H 4.21. HRMS (EI) calcd. for [M]+: m/z 234.0528;
found 234.0518.
2-(Thiophen-2-yl)benzoxazole (8):[12b] The reaction of 2-bromothio-
phene (0.163 g, 1 mmol), benzoxazole (0.238 g, 2 mmol) and
Cs2CO3 (0.650 g, 2 mmol) at 150 °C in dry DMF (5 mL) in the
presence of [PdCl(dppb)(C3H5)] (6.1 mg, 0.01 mmol) afforded 8 in
73% (0.147 g) isolated yield. 1H NMR (200 MHz, CDCl3): δ = 7.88
(d, J = 3.6 Hz, 1 H), 7.75 (m, 1 H), 7.55 (m, 2 H), 7.37 (m, 2 H),
7.18 (t, J = 4.1 Hz, 1 H) ppm.
5-(5-Butylthiophen-2-yl)furan-2-carbaldehyde (3): The reaction of 5-
bromo-2-furaldehyde (0.175 g, 1 mmol), 2-butylthiophene (0.280 g,
2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 3 in 78% (0.183 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 9.60 (s, 1 H), 7.37 (d, J = 3.5 Hz, 1 H), 7.27 (d, J =
3.5 Hz, 1 H), 6.80 (d, J = 3.5 Hz, 1 H), 6.60 (d, J = 3.5 Hz, 1 H),
2.86 (t, J = 7.5 Hz, 2 H), 1.72 (quint, J = 7.4 Hz, 2 H), 1.47 (sext,
J = 7.4 Hz, 2 H), 0.95 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 176.5, 155.2, 151.1, 149.0, 128.8, 126.1,
125.3, 123.0, 106.6, 33.4, 29.7, 22.0, 13.7 ppm. C13H14O2S (234.32):
calcd. C 66.64, H 6.02; found C 66.50, H 6.10. HRMS (EI) calcd.
for [M]+: m/z 234.0715; found 234.0719.
5-(5-Methylthiophen-2-yl)-2-propylthiazole (9): The reaction of 2-
bromo-5-methylthiophene (0.177 g, 1 mmol), 2-propylthiazole
(0.254 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
0.05 mmol) afforded 9 in 63% (0.141 g) isolated yield. 1H NMR
(200 MHz, CDCl3): δ = 7.63 (s, 1 H), 6.93 (d, J = 4.5 Hz, 1 H),
6.68 (d, J = 4.5 Hz, 1 H), 2.97 (t, J = 7.5 Hz, 2 H), 2.50 (s, 3 H),
1.86 (sext, J = 7.5 Hz, 2 H), 1.04 (t, J = 7.5 Hz, 3 H) ppm. 13C
(50 MHz, CDCl3): δ = 169.6, 139.9, 137.2, 131.9, 131.1, 125.9,
125.1, 35.4, 23.3, 15.3, 13.6 ppm. C11H13NS2 (223.36): calcd. C
59.15, H 5.87; found C 59.07, H 5.94. HRMS (EI) calcd. for
[M]+: m/z 223.0489; found 223.0490.
2-(5-Methylthiophen-2-yl)benzoxazole (10):[14] The reaction of 2-
bromo-5-methylthiophene (0.177 g, 1 mmol), benzoxazole (0.238 g,
2 mmol) and Cs2CO3 (0.650 g, 2 mmol) at 150 °C in dry DMF
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 10 in 80% (0.172 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 7.72 (m, 2 H), 7.53 (m, 1 H), 7.34 (m, 2 H), 6.85 (m,
1 H), 2.59 (s, 3 H). 13C (50 MHz, CDCl3): δ = 159.0, 150.3, 145.7,
142.0, 130.2, 127.0, 126.7, 124.7, 124.5, 119.5, 110.2, 15.6 ppm.
5-(5-Methylthiophen-2-yl)furan-2-carbaldehyde (4): The reaction of
5-bromo-2-furaldehyde (0.175 g, 1 mmol), 2-methylthiophene
(0.196 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
0.05 mmol) afforded 4 in 75% (0.144 g) isolated yield. 1H NMR
(200 MHz, CDCl3): δ = 9.59 (s, 1 H), 7.34 (d, J = 3.5 Hz, 1 H),
7.27 (d, J = 3.5 Hz, 1 H), 6.77 (d, J = 3.5 Hz, 1 H), 6.59 (d, J =
3.5 Hz, 1 H), 2.54 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ =
177.1, 155.6, 151.1, 143.7, 129.7, 127.0, 126.9, 124.0, 107.2,
15.9 ppm. C10H8O2S (192.24): calcd. C 62.48, H 4.19; found C
62.34, H 4.07. HRMS (EI) calcd. for [M]+: m/z 192.0245; found
192.0250.
5Ј-Chloro-5-methyl-2,2Ј-bithiophene (11): The reaction of 2-bromo-
5-methylthiophene (0.177 g, 1 mmol), 2-chlorothiophene (0.238 g,
2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 11 in 51% (0.109 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 6.90 (d, J = 3.2 Hz, 1 H), 6.86 (d, J = 3.2 Hz, 1 H),
6.82 (d, J = 3.2 Hz, 1 H), 6.68 (d, J = 3.2 Hz, 1 H), 2.50 (s, 3 H)
ppm. 13C NMR (50 MHz, CDCl3): δ = 139.6, 136.4, 134.1, 127.9,
127.2, 126.4, 124.2, 122.5, 15.8 ppm. C9H7ClS2 (214.74): calcd. C
50.34, H 3.29; found C 50.51, H 3.52. HRMS (EI) calcd. for
[M]+: m/z 213.9678; found 213.9670.
5,5Ј-Dimethyl-2,2Ј-bithiophene (12):[15] The reaction of 2-bromo-5-
methylthiophene (0.177 g, 1 mmol), 2-methylthiophene (0.196 g,
2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 12 in 78% (0.152 g) isolated yield. This compound was
also obtained as side product of the reactions with 2-bromo-5-
methylthiophene and 2-propylthiazole, 2-chlorothiophene or
benzoxazole. 1H NMR (200 MHz, CDCl3): δ = 6.89 (d, J = 3.2 Hz,
2 H), 6.65 (d, J = 3.2 Hz, 2 H), 2.49 (s, 6 H) ppm.
5-(5-Chlorothiophen-2-yl)furan-2-carbaldehyde (5): The reaction of
5-bromo-2-furaldehyde (0.175 g, 1 mmol), 2-chlorothiophene
(0.237 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
0.05 mmol) afforded 5 in 71% (0.151 g) isolated yield. 1H NMR
(200 MHz, CDCl3): δ = 9.62 (s, 1 H), 7.30 (m, 2 H), 6.94 (d, J =
4.0 Hz, 1 H), 6.63 (d, J = 3.7 Hz, 1 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 176.8, 153.5, 151.5, 132.5, 130.1, 127.3, 125.3, 123.4,
107.5 ppm. C9H5ClO2S (212.65): calcd. C 50.83, H 2.37; found C
50.71, H 2.51. HRMS (EI) calcd. for [M]+: m/z 211.9699; found
211.9698.
5-(2-Propylthiazol-5-yl)furan-2-carbaldehyde (6): The reaction of 5-
bromo-2-furaldehyde (0.175 g, 1 mmol), 2-propylthiazole (0.254 g,
2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 6 in 80% (0.177 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 9.64 (s, 1 H), 8.05 (s, 1 H), 7.30 (d, J = 3.5 Hz, 1 H),
6.69 (d, J = 3.5 Hz, 1 H), 3.03 (t, J = 7.5 Hz, 2 H), 1.85 (sext, J =
7.5 Hz, 2 H), 1.05 (t, J = 7.5 Hz, 3 H) ppm. 13C (50 MHz, CDCl3):
δ = 177.4, 173.4, 152.6, 152.3, 141.2, 123.7, 118.3, 109.3, 35.9, 23.7,
14.0 ppm. C11H11NO2S (221.28): calcd. C 59.71, H 5.01; found C
59.94, H 4.87. HRMS (EI) calcd. for [M]+: m/z 221.0510; found
221.0507.
5Ј-Butyl-5-chloro-2,2Ј-bithiophene (13): The reaction of 2-bromo-5-
chlorothiophene (0.198 g, 1 mmol), 2-butylthiophene (0.280 g,
2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 13 in 61% (0.157 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 6.92 (d, J = 3.7 Hz, 1 H), 6.86 (d, J = 3.7 Hz, 1 H),
6.82 (d, J = 3.7 Hz, 1 H), 6.69 (d, J = 3.7 Hz, 1 H), 2.81 (t, J =
7.5 Hz, 2 H), 1.65 (quint, J = 7.4 Hz, 2 H), 1.42 (sext, J = 7.4 Hz,
2 H), 0.96 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 146.2, 137.0, 134.2, 127.2, 125.2, 124.0, 122.5, 122.4, 34.1, 30.3,
22.6, 14.3 ppm. C12H13ClS2 (256.82): calcd. C 56.12, H 5.10; found
C 56.31, H 5.24. HRMS (EI) calcd. for [M]+: m/z 256.0147; found
256.0150.
2-Propyl-5-(thiophen-2-yl)thiazole (7): The reaction of 2-bromothio-
phene (0.163 g, 1 mmol), 2-propylthiazole (0.254 g, 2 mmol) and
KOAc (0.196 g, 2 mmol) at 150 °C in dry DMAc (5 mL) in the
presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 7 in
56% (0.117 g) isolated yield. 1H NMR (200 MHz, CDCl3): δ = 7.71
(s, 1 H), 7.24 (d, J = 5.2 Hz, 1 H), 7.14 (m, 1 H), 7.05 (m, 1 H),
2.97 (t, J = 7.5 Hz, 2 H), 1.86 (sext, J = 7.5 Hz, 2 H), 1.04 (t, J =
7.5 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 170.7, 138.3,
133.9, 131.9, 128.2, 125.7, 125.5, 35.9, 23.7, 14.1 ppm. C10H11NS2
(209.33): calcd. C 57.38, H 5.30; found C 57.48, H 5.30. HRMS
(EI) calcd. for [M]+: m/z 209.0333; found 209.0330.
2-(5-Chlorothiophen-2-yl)benzothiazole (14):[16] The reaction of 2-
bromo-5-chlorothiophene (0.198 g, 1 mmol), benzothiazole
2556
www.eurjic.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2008, 2550–2559

C-H Activation/Arylation of Heteroaromatics
(0.270 g, 2 mmol) and Cs2CO3 (0.650 g, 2 mmol) at 120 °C in dry
(0.237 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMF (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
0.05 mmol) afforded 14 in 30% (0.076 g) isolated yield. H NMR
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
0.05 mmol) afforded 21 in 69% (0.158 g) isolated yield. H NMR
1
1
(200 MHz, CDCl3): δ = 8.02 (d, J = 8.3 Hz, 1 H), 7.86 (d, J =
8.3 Hz, 1 H), 7.55–7.30 (m, 3 H), 6.97 (d, J = 3.8 Hz, 1 H) ppm.
(200 MHz, CDCl3): δ = 9.87 (s, 1 H), 7.67 (d, J = 4.0 Hz, 1 H),
7.17 (d, J = 4.0 Hz, 1 H), 7.13 (d, J = 3.9 Hz, 1 H), 6.90 (d, J =
3.9 Hz, 1 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 182.4, 145.9,
141.9, 137.2, 134.5, 131.7, 127.4, 125.2, 124.2 ppm. C9H5ClOS2
(228.72): calcd. C 47.26, H 2.20; found C 47.02, H 2.31. HRMS
(EI) calcd. for [M]+: m/z 227.9470; found 227.9479.
2,2Ј-Bithiophene (15): This compound was obtained as a side prod-
uct from several reactions with 2-bromothiophene. 1H NMR
(200 MHz, CDCl3): δ = 7.16 (d, J = 5.2 Hz, 2 H), 7.15 (d, J =
3.7 Hz, 2 H), 6.97 (dd, J = 5.2 and 3.7 Hz, 2 H) ppm.
5-(2-Propylthiazol-5-yl)thiophene-2-carbaldehyde (22): The reaction
of 2-bromo-5-formylthiophene (0.191 g, 1 mmol), 2-propylthiazole
(0.254 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
5,5Ј-Dichloro-2,2Ј-bithiophene (16):[17] This compound was ob-
tained as a side product from the reactions with 2-bromo-5-chloro-
1
thiophene. H NMR (200 MHz, CDCl3): δ = 6.87 (d, J = 3.8 Hz,
2 H), 6.83 (d, J = 3.8 Hz, 2 H) ppm.
1
0.05 mmol) afforded 22 in 80% (0.190 g) isolated yield. H NMR
5-(5-Butylfuran-2-yl)thiophene-2-carbaldehyde (17): The reaction of
2-bromo-5-formylthiophene (0.191 g, 1 mmol), 2-butylfuran
(0.248 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
(200 MHz, CDCl3): δ = 9.88 (s, 1 H), 7.88 (s, 1 H), 7.69 (d, J =
3.9 Hz, 1 H), 7.24 (d, J = 3.9 Hz, 1 H), 3.00 (t, J = 7.6 Hz, 2 H),
1.84 (sext, J = 7.6 Hz, 2 H), 1.05 (t, J = 7.6 Hz, 3 H) ppm. 13C
(50 MHz, CDCl3): δ = 182.9, 173.1, 143.7, 142.8, 140.6, 137.5,
130.9, 126.1, 36.0, 23.7, 14.1 ppm. C11H11NOS2 (237.34): calcd. C
55.67, H 4.67; found C 55.78, H 4.80. HRMS (EI) calcd. for
[M]+: m/z 237.0282; found 237.0287.
-2,2Ј-Bithiophene-5,5Ј-dicarbaldehyde (23):[10c] This compound was
obtained as a side product from the reactions with 2-bromo-5-for-
mylthiophene. 1H NMR (200 MHz, CDCl3): δ = 9.94 (s, 2 H), 7.75
(d, J = 3.9 Hz, 2 H), 7.44 (d, J = 3.9 Hz, 2 H) ppm.
1
0.05 mmol) afforded 17 in 77% (0.181 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 9.85 (s, 1 H), 7.67 (d, J = 4.0 Hz, 1 H),
7.23 (d, J = 4.0 Hz, 1 H), 6.67 (d, J = 2.9 Hz, 1 H), 6.12 (d, J =
2.9 Hz, 1 H), 2.70 (t, J = 7.5 Hz, 2 H), 1.69 (quint, J = 7.4 Hz, 2
H), 1.45 (sext, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.5 Hz, 3 H) ppm. 13
C
NMR (50 MHz, CDCl3): δ = 182.5, 158.5, 146.4, 143.4, 140.6,
137.4, 121.8, 109.8, 107.7, 29.9, 27.7, 22.2, 13.7 ppm. C13H14O2S
(234.32): calcd. C 66.64, H 6.02; found C 66.80, H 5.89. HRMS
(EI) calcd. for [M]+: m/z 234.0715; found 234.0719.
1-[5-(5-Butylfuran-2-yl)thiophen-2-yl]ethanone (24): The reaction of
2-acetyl-5-bromothiophene (0.205 g, 1 mmol), 2-butylfuran
(0.248 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
Methyl 5-(5-Formylthiophen-2-yl)-2-methylfuran-3-carboxylate (18):
The reaction of 2-bromo-5-formylthiophene (0.191 g, 1 mmol),
methyl 2-methyl-3-furancarboxylate (0.280 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) at 120 °C in dry DMAc (5 mL) in the presence
of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 18 in 57%
1
0.05 mmol) afforded 24 in 62% (0.154 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.58 (d, J = 4.0 Hz, 1 H), 7.16 (d, J =
4.0 Hz, 1 H), 6.58 (d, J = 2.9 Hz, 1 H), 6.08 (d, J = 2.9 Hz, 1 H),
2.67 (t, J = 7.5 Hz, 2 H), 2.53 (s, 3 H), 1.67 (quint, J = 7.4 Hz, 2
1
(0.143 g) isolated yield. H NMR (200 MHz, CDCl3): δ = 9.86 (s,
1 H), 7.67 (d, J = 4.0 Hz, 1 H), 7.29 (d, J = 4.0 Hz, 1 H), 6.94 (s,
1 H), 3.85 (s, 3 H), 2.64 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 183.0, 164.1, 160.6, 146.5, 142.2, 142.0, 137.6, 123.6, 116.2,
109.5, 52.1, 14.4 ppm. C12H10O4S (250.27): calcd. C 57.59, H 4.03;
found C 57.67, H 3.94. HRMS (EI) calcd. for [M]+: m/z 250.0300;
found 250.0303.
H), 1.42 (sext, J = 7.4 Hz, 2 H), 0.95 (t, J = 7.5 Hz, 3 H) ppm. 13
C
NMR (50 MHz, CDCl3): δ = 190.3, 157.9, 146.6, 142.1, 141.2,
133.3, 121.7, 108.9, 107.5, 29.9, 27.7, 26.4, 22.1, 13.7 ppm.
C14H16O2S (248.34): calcd. C 67.71, H 6.49; found C 67.78, H 6.68.
HRMS (EI) calcd. for [M]+: m/z 248.0871; found 248.0876.
Methyl 5-(5-Acetylthiophen-2-yl)-2-methylfuran-3-carboxylate (25):
The reaction of 2-acetyl-5-bromothiophene (0.205 g, 1 mmol),
methyl 2-methyl-3-furancarboxylate (0.280 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) at 120 °C in dry DMAc (5 mL) in the presence
of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 25 in 53%
5Ј-Butyl-2,2Ј-bithiophene-5-carbaldehyde (19): The reaction of 2-
bromo-5-formylthiophene (0.191 g, 1 mmol), 2-butylthiophene
(0.280 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
1
0.05 mmol) afforded 19 in 67% (0.168 g) isolated yield. H NMR
1
(0.140 g) isolated yield. H NMR (200 MHz, CDCl3): δ = 7.60 (d,
(200 MHz, CDCl3): δ = 9.84 (s, 1 H), 7.65 (d, J = 3.9 Hz, 1 H),
7.19 (d, J = 3.9 Hz, 1 H), 7.17 (d, J = 3.9 Hz, 1 H), 6.75 (d, J =
3.6 Hz, 1 H), 2.83 (t, J = 7.5 Hz, 2 H), 1.72 (quint, J = 7.4 Hz, 2
J = 4.0 Hz, 1 H), 7.22 (d, J = 4.0 Hz, 1 H), 6.90 (s, 1 H), 3.86 (s,
3 H), 2.65 (s, 3 H), 2.56 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 190.3, 163.7, 159.7, 146.2, 142.5, 140.3, 133.1, 123.1, 115.5,
108.2, 51.5, 26.5, 13.8 ppm. C13H12O4S (264.30): calcd. C 59.08, H
4.58; found C 59.20, H 4.49. HRMS (EI) calcd. for [M]+: m/z
264.0456; found 264.0452.
H), 1.45 (sext, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.5 Hz, 3 H) ppm. 13
C
NMR (50 MHz, CDCl3): δ = 182.4, 148.6, 147.8, 140.9, 137.5,
133.3, 125.9, 125.4, 123.3, 33.5, 29.8, 22.0, 13.7 ppm. C13H14OS2
(250.38): calcd. C 62.36, H 5.64; found C 62.10, H 5.81. HRMS
(EI) calcd. for [M]+: m/z 250.0486; found 250.0481.
1-[5-(5-Acetylfuran-2-yl)thiophen-2-yl]ethanone (26): The reaction
of 2-acetyl-5-bromothiophene (0.205 g, 1 mmol), 2-acetylfuran
(0.220 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
5Ј-Butyl-2,2Ј-bithiophene-5-carbaldehyde (20):[18] The reaction of 2-
bromo-5-formylthiophene (0.191 g, 1 mmol), 2-methylthiophene
(0.196 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
1
0.05 mmol) afforded 26 in 32% (0.075 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.65 (d, J = 4.0 Hz, 1 H), 7.47 (d, J =
4.0 Hz, 1 H), 7.27 (d, J = 3.7 Hz, 1 H), 7.79 (d, J = 3.7 Hz, 1 H),
2.59 (s, 3 H), 2.54 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ =
190.9, 186.8, 152.7, 151.9, 144.8, 139.7, 133.4, 126.0, 119.5, 110.2,
27.2, 26.5 ppm. C12H10O3S (234.27): calcd. C 61.52, H 4.30; found
1
0.05 mmol) afforded 20 in 65% (0.135 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 9.86 (s, 1 H), 7.66 (d, J = 3.9 Hz, 1 H),
7.19 (d, J = 3.9 Hz, 1 H), 7.17 (d, J = 3.9 Hz, 1 H), 6.75 (d, J =
3.6 Hz, 1 H), 2.52 (s, 3 H) ppm.
5Ј-Chloro-2,2Ј-bithiophene-5-carbaldehyde (21): The reaction of 2- C 61.30, H 4.21. HRMS (EI) calcd. for [M]+: m/z 234.0351; found
bromo-5-formylthiophene (0.191 g, 1 mmol), 2-chlorothiophene 234.0347.
Eur. J. Inorg. Chem. 2008, 2550–2559
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
2557

F. Derridj, A. L. Gottumukkala, S. Djebbar, H. Doucet
FULL PAPER
1-(5Ј-Butyl-2,2Ј-bithiophene-5-yl)ethanone (27): The reaction of 2-
acetyl-5-bromothiophene (0.205 g, 1 mmol), 2-butylthiophene
(0.280 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
afforded 33 in 32% (0.069 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 7.58 (t, J = 7.6 Hz, 1 H), 7.45 (d, J = 8.2 Hz, 1 H),
7.00 (m, 2 H), 6.12 (d, J = 2.9 Hz, 1 H), 2.77 (t, J = 7.5 Hz, 2 H),
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 2.58 (s, 3 H), 1.67 (quint, J = 7.4 Hz, 2 H), 1.42 (sext, J = 7.4 Hz,
1
0.05 mmol) afforded 27 in 83% (0.219 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.54 (d, J = 4.0 Hz, 1 H), 7.11 (d, J =
2 H), 0.95 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 158.7, 158.2, 152.5, 149.6, 137.1, 121.4, 115.7, 109.7, 107.7,
3.6 Hz, 1 H), 7.05 (d, J = 4.0 Hz, 1 H), 6.70 (d, J = 3.6 Hz, 1 H), 30.5, 28.4, 25.1, 22.7, 14.3 ppm. C14H17NO (215.29): calcd. C
2.79 (t, J = 7.5 Hz, 2 H), 2.51 (s, 3 H), 1.62 (quint, J = 7.4 Hz, 2
78.10, H 7.96; found C 78.23, H 7.81. HRMS (EI) calcd. for
H), 1.43 (sext, J = 7.4 Hz, 2 H), 0.94 (t, J = 7.5 Hz, 3 H) ppm. 13
C
[M]+: m/z 215.1310; found 215.1307.
NMR (50 MHz, CDCl3): δ = 190.1, 147.7, 146.3, 141.4, 133.5,
133.3, 125.3, 125.1, 123.1, 33.4, 29.7, 26.2, 22.0, 13.6 ppm.
C14H16OS2 (264.41): calcd. C 63.59, H 6.10; found C 63.40, H 6.21.
HRMS (EI) calcd. for [M]+: m/z 264.0643; found 264.0651.
2-(5-Butylthiophen-2-yl)-6-methyl-pyridine (34): The reaction of 2-
bromo-5-methylpyridine (0.172 g, 1 mmol), 2-butylthiophene
(0.280 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
1
1-(5Ј-Methyl-2,2Ј-bithiophene-5-yl)ethanone (28):[19] The reaction of
2-acetyl-5-bromothiophene (0.205 g, 1 mmol), 2-methylthiophene
(0.196 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
0.05 mmol) afforded 34 in 34% (0.079 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.54 (t, J = 7.6 Hz, 1 H), 7.43 (d, J =
8.2 Hz, 1 H), 7.40 (d, J = 2.8 Hz, 1 H), 6.97 (d, J = 8.2 Hz, 1 H),
6.79 (d, J = 2.8 Hz, 1 H), 2.86 (t, J = 7.5 Hz, 2 H), 2.58 (s, 3 H),
1.70 (quint, J = 7.4 Hz, 2 H), 1.42 (sext, J = 7.4 Hz, 2 H), 0.96 (t,
J = 7.5 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 158.6,
152.7, 148.6, 142.8, 137.1, 125.5, 124.6, 121.3, 115.8, 34.2, 30.5,
25.0, 22.6, 14.3 ppm. C14H17NS (231.36): calcd. C 72.68, H 7.41;
found C 72.71, H 7.50. HRMS (EI) calcd. for [M]+: m/z 231.1082;
found 231.1086.
1
0.05 mmol) afforded 28 in 67% (0.149 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.56 (d, J = 4.0 Hz, 1 H), 7.11 (d, J =
3.6 Hz, 1 H), 7.07 (d, J = 4.0 Hz, 1 H), 6.71 (d, J = 3.6 Hz, 1 H),
2.53 (s, 3 H), 2.51 (s, 3 H) ppm.
5Ј-Acetyl-2,2Ј-bithiophene-5-carbonitrile (29):[19] The reaction of 2-
acetyl-5-bromothiophene (0.205 g, 1 mmol), thiophene-2-car-
bonitrile (0.218 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C
in dry DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)]
(30.5 mg, 0.05 mmol) afforded 29 in 64% (0.149 g) isolated yield.
1H NMR (200 MHz, CDCl3): δ = 7.63 (d, J = 4.0 Hz, 1 H), 7.57
(d, J = 4.0 Hz, 1 H), 7.28 (m, 2 H), 2.58 (s, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 190.8, 145.2, 143.6, 142.7, 138.8, 133.6,
126.8, 125.7, 114.1, 109.9, 27.1 ppm.
2-(5-Chlorothiophen-2-yl)-6-methylpyridine (35): The reaction of 2-
bromo-5-methylpyridine (0.172 g, 1 mmol), 2-chlorothiophene
(0.237 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
1
0.05 mmol) afforded 35 in 37% (0.078 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.56 (t, J = 7.6 Hz, 1 H), 7.37 (d, J =
8.2 Hz, 1 H), 7.29 (d, J = 3.9 Hz, 1 H), 7.02 (d, J = 8.2 Hz, 1 H),
6.91 (d, J = 3.9 Hz, 1 H), 2.56 (s, 3 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 158.9, 151.5, 144.3, 137.2, 132.4, 127.5, 123.6, 122.2,
115.4, 24.9 ppm. C10H8ClNS (209.70): calcd. C 57.28, H 3.85;
found C 57.40, H 3.91. HRMS (EI) calcd. for [M]+: m/z 209.0066;
found 209.0063.
1-(5Ј-Chloro-2,2Ј-bithiophene-5-yl)ethanone (30): The reaction of 2-
acetyl-5-bromothiophene (0.205 g, 1 mmol), 2-chlorothiophene
(0.237 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
1
0.05 mmol) afforded 30 in 57% (0.138 g) isolated yield. H NMR
2-(6-Methylpyridin-2-yl)benzothiazole (36): The reaction of 2-
bromo-5-methylpyridine (0.172 g, 1 mmol), benzothiazole (0.270 g,
2 mmol) and Cs2CO3 (0.650 g, 2 mmol) at 150 °C in dry DMF
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 36 in 54% (0.122 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 8.19 (d, J = 8.0 Hz, 1 H), 8.11 (d, J = 8.0 Hz, 1 H),
7.97 (d, J = 8.0 Hz, 1 H), 7.75 (t, J = 7.6 Hz, 1 H), 7.52 (t, J =
7.6 Hz, 1 H), 7.42 (t, J = 7.6 Hz, 1 H), 7.26 (d, J = 8.0 Hz, 1 H),
2.67 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 159.2, 154.8,
151.1, 137.6, 136.6, 126.6, 125.9, 125.4, 123.9, 122.5, 122.4, 118.2,
24.8 ppm. HRMS (EI) calcd. for [M]+: m/z 226.0565; found
226.0564.
1-Methyl-2-(6-methylpyridin-2-yl)-1H-benzimidazole (37):[20] The
reaction of 2-bromo-5-methylpyridine (0.172 g, 1 mmol), N-methyl-
benzimidazole (0.264 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at
150 °C in dry DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)]
(30.5 mg, 0.05 mmol) afforded 37 in 31% (0.069 g) isolated yield.
1H NMR (200 MHz, CDCl3): δ = 8.18 (d, J = 8.0 Hz, 1 H), 7.80
(m, 1 H), 7.75 (t, J = 7.6 Hz, 1 H), 7.44 (m, 1 H), 7.32 (m, 2 H),
7.23 (d, J = 8.0 Hz, 1 H), 4.30 (s, 3 H), 2.67 (s, 3 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 157.4, 150.5, 142.5, 137.2, 137.0,
123.2, 123.1, 122.4, 122.0, 121.7, 119.9, 109.8, 32.7, 24.5 ppm.
(200 MHz, CDCl3): δ = 7.58 (d, J = 4.0 Hz, 1 H), 7.09 (m, 2 H),
6.88 (d, J = 4.0 Hz, 1 H), 2.56 (s, 3 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 190.3, 144.5, 142.7, 134.8, 133.2, 131.0, 127.3, 124.7,
124.1, 26.5 ppm. C10H7ClOS2 (242.75): calcd. C 49.48, H 2.91;
found C 49.60, H 2.87. HRMS (EI) calcd. for [M]+: m/z 241.9627;
found 241.9627.
1-[5-(2-Propylthiazol-5-yl)thiophen-2-yl]ethanone (31): The reaction
of 2-acetyl-5-bromothiophene (0.205 g, 1 mmol), 2-propylthiazole
(0.254 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry
DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg,
1
0.05 mmol) afforded 31 in 56% (0.141 g) isolated yield. H NMR
(200 MHz, CDCl3): δ = 7.82 (s, 1 H), 7.58 (d, J = 4.0 Hz, 1 H),
7.12 (d, J = 4.0 Hz, 1 H), 2.97 (t, J = 7.5 Hz, 2 H), 2.54 (s, 3 H),
1.83 (sext, J = 7.4 Hz, 2 H), 1.03 (t, J = 7.5 Hz, 3 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 190.2, 171.9, 143.0, 141.7, 139.5,
133.0, 130.6, 125.4, 35.4, 26.4, 23.1, 13.5 ppm. C12H13NOS2
(251.37): calcd. C 57.34, H 5.21; found C 57.34, H 5.30. HRMS
(EI) calcd. for [M]+: m/z 251.0439; found 251.0434.
1-(5Ј-Acetyl-2,2Ј-bithiophene-5-yl)ethanone (32):[10c] This com-
pound was obtained as a side product from the reactions with 2-
acetyl-5-bromothiophene. 1H NMR (200 MHz, CDCl3): δ = 7.59
(d, J = 3.2 Hz, 2 H), 7.32 (d, J = 3.2 Hz, 2 H), 2.58 (s, 6 H) ppm.
2-(6-Methylpyridin-2-yl)benzoxazole (38):[12b] The reaction of 2-
2-(5-Butylfuran-2-yl)-6-methyl-pyridine (33): The reaction of 2- bromo-5-methylpyridine (0.172 g, 1 mmol), benzoxazole (0.238 g,
bromo-5-methylpyridine (0.172 g, 1 mmol), 2-butylfuran (0.248 g, 2 mmol) and Cs2CO3 (0.650 g, 2 mmol) at 150 °C in dry DMF
2 mmol) and KOAc (0.196 g, 2 mmol) at 150 °C in dry DMAc (5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 38 in 78% (0.164 g) isolated yield. 1H NMR (200 MHz,
2558
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2008, 2550–2559

C-H Activation/Arylation of Heteroaromatics
Z. Yu, Tetrahedron 2006, 62, 1806; f) X. Chang, M.-Y. Kim,
Y.-J. Kim, H. S. Huh, S. W. Lee, Dalton Trans. 2007, 792.
For examples of palladium-catalysed Negishi coupling, see: a)
J. Jensen, N. Skjaerbaek, P. Vedso, Synthesis 2001, 128; b) D. R.
Gauthier Jr, R. H. Szumigala Jr, P. G. Dormer, J. D. Arm-
strong III, R. P. Volante, P. J. Reider, Org. Lett. 2002, 4, 375; c)
A. Lützen, M. Hapke, H. Staats, J. Bunzen, Eur. J. Org. Chem.
2003, 3948; d) M. R. Reeder, H. E. Gleaves, S. A. Hoover, R. J.
Imbordino, J. J. Pangborn, Org. Proc. Res. Dev. 2003, 7, 696;
e) W.-L. Jia, Q.-D. Liu, R. Wang, S. Wang, Organometallics
2003, 22, 4070; f) F. López-Calahorra, M. Martínez-Rubio, D.
Velasco, E. Brillas, L. Julia, Tetrahedron 2006, 60, 285.
a) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731;
b) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107,
174; c) T. Satoh, M. Miura, Chem. Lett. 2007, 36, 200; d) H.
Doucet, J. C. Hierso, Curr. Opin. Drug Discov. Devel. 2007, 10,
672; e) L.-C. Campeau, D. R. Stuart, K. Fagnou, Aldrichim.
Acta 2007, 40, 35.
CDCl3): δ = 8.14 (d, J = 8.0 Hz, 1 H), 7.80 (m, 1 H), 7.73 (t, J =
8.0 Hz, 1 H), 7.64 (m, 1 H), 7.37 (m, 2 H), 7.10 (d, J = 8.0 Hz, 1
H), 2.70 (s, 3 H) ppm.
[4]
6,6Ј-Dimethyl-2,2Ј-bipyridine (39): This compound was obtained as
a side product from the reactions with 2-bromo-5-methylpyridine.
1H NMR (200 MHz, CDCl3): δ = 8.19 (d, J = 8.2 Hz, 2 H), 7.70
(t, J = 7.6 Hz, 2 H), 7.16 (d, J = 8.2 Hz, 2 H), 2.64 (s, 6 H) ppm.
2,5-Bis(benzoxazole)thiophene (40):[12b] The reaction of 2,5-dibro-
mothiophene (0.242 g, 1 mmol), benzoxazole (0.476 g, 4 mmol) and
Cs2CO3 (1.300 g, 4 mmol) at 150 °C in dry DMAc (5 mL) in the
presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 40
[5]
1
in 51% (0.162 g) isolated yield. H NMR (200 MHz, CDCl3): δ =
7.98 (s, 2 H), 7.80 (m, 2 H), 7.60 (m, 2 H), 7.42 (m, 4 H) ppm.
5,5ЈЈ-Dibutyl[2,2Ј;5Ј,2ЈЈ]terthiophene (41): The reaction of 2,5-di-
bromothiophene (0.242 g, 1 mmol), 2-butylthiophene (0.560 g,
4 mmol) and KOAc (0.392 g, 4 mmol) at 150 °C in dry DMAc
(5 mL) in the presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol)
afforded 41 in 53% (0.191 g) isolated yield. 1H NMR (200 MHz,
CDCl3): δ = 7.01 (s, 4 H), 6.72 (s, 2 H), 2.84 (t, J = 7.5 Hz, 4 H),
1.72 (quint, J = 7.4 Hz, 4 H), 1.44 (sext, J = 7.4 Hz, 4 H), 1.00 (t,
J = 7.5 Hz, 6 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 145.7,
136.6, 135.1, 125.2, 123.9, 123.6, 34.2, 30.3, 22.7, 14.3 ppm.
C20H24S3 (360.60): calcd. C 66.61, H 6.71; found C 66.45, H 6.92.
HRMS (EI) calcd. for [M]+: m/z 360.1040; found 360.1042.
[6]
[7]
[8]
[9]
M. S. McClure, B. Glover, E. McSorley, A. Millar, M. H.
Osterhout, F. Roschangar, Org. Lett. 2001, 3, 1677.
a) F. A. Zhuralev, Tetrahedron Lett. 2006, 47, 2929; b) H. A.
Chiong, O. Daugulis, Org. Lett. 2007, 9, 1449.
C.-H. Park, V. Ryabova, I. V. Seregin, A. W. Sromek, V. Gevor-
gyan, Org. Lett. 2004, 6, 1159–1162.
a) S. Pivsa-Art, T. Satoh, Y. Kawamura, M. Miura, M. No-
mura, Bull. Chem. Soc. Jpn. 1998, 71, 467; b) D. S. Ermolat’ev,
V. N. G i m énez, E. V. Babaev, E. van der Eycken, J. Comb.
ˇ
Chem. 2006, 8, 659; c) I. Cernˇa, R. Pohl, B. Klepetárˇová, M.
1,2-Bis(2-propylthiazol-5-yl)benzene (42): The reaction of 1,2-dibro-
mobenzene (0.236 g, 1 mmol), 2-propylthiazole (0.508 g, 4 mmol)
and KOAc (0.392 g, 4 mmol) at 150 °C in dry DMAc (5 mL) in the
presence of [PdCl(dppb)(C3H5)] (30.5 mg, 0.05 mmol) afforded 42
Hocek, Org. Lett. 2006, 8, 5389–5392.
[10]
[11]
a) T. Itahara, M. Hashimoto, H. Yumisashi, Synthesis 1984,
255; b) A. Srinivasan, V. M. Reddy, S. J. Narayanan, B. Sridevi,
S. K. Pushpan, M. Ravikumar, T. K. Chandrashekar, Angew.
Chem. Int. Ed. Engl. 1997, 36, 2598; c) K. Matsui, H. Ikegami,
A. Mori, J. Am. Chem. Soc. 2004, 126, 5074; d) M. Takahashi,
K. Masui, H. Sekiguchi, N. Kobayashi, A. Mori, M. Funah-
ashi, N. Tamaoki, J. Am. Chem. Soc. 2006, 128, 10930; e) A.
Kar, N. Mangu, H. M. Kaiser, M. Beller, M. K. Tse, Chem.
Commun. 2008, 386.
1
in 43% (0.141 g) isolated yield. H NMR (200 MHz, CDCl3): δ =
7.60–7.30 (m, 6 H), 2.93 (t, J = 7.6 Hz, 4 H), 1.81 (sext, J = 7.6 Hz,
4 H), 1.00 (t, J = 7.6 Hz, 6 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 172.3, 141.0, 135.6, 130.9, 128.5, 124.9, 35.3, 23.2, 13.5 ppm.
HRMS (EI) calcd. for [M]+: m/z 328.1068; found 328.1083.
a) J. Roger, H. Doucet, Org. Biomol. Chem. 2008, 6, 169; b) A.
Battace, M. Lemhadri, T. Zair, H. Doucet, M. Santelli, Organo-
metallics 2007, 26, 472; c) A. Battace, M. Lemhadri, T. Zair,
H. Doucet, M. Santelli, Adv. Synth. Catal. 2007, 349, 2507; d)
Acknowledgments
A. G. is grateful to Egide for a grant. We thank the Centre National
de la Recherche Scientifique (CNRS) and Rennes Metropole for
providing financial support.
F. Pozgan, J. Roger, H. Doucet, Chem. Sus. Chem. 2008, in
ˇ
press.
[12] a) A. L. Gottumukkala, H. Doucet, Eur. J. Inorg. Chem. 2007,
3626; b) F. Derridj, S. Djebbar, O. Benali-Baitich, H. Doucet,
J. Organomet. Chem. 2008, 693, 135.
[1] J. J. Li, G. W. Gribble, Palladium in Heterocyclic Chemistry, Per-
gamon, Amsterdam, 2000.
[13]
T. Cantat, E. Génin, C. Giroud, G. Meyer, A. Jutand, J. Or-
ganomet. Chem. 2003, 687, 365.
J. Garmatter, A. E. Siegrist, Helv. Chim. Acta 1974, 57, 945.
A. Kar, N. Mangu, H. M. Kaiser, M. Beller, M. K. Tse, Chem.
Commun. 2008, 386.
R. Royer, J. P. Lechartier, P. Demerseman, Bull. Soc. Chim. Fr.
1973, 11, 3017.
R. F. Curtis, G. T. Phillips, Tetrahedron 1967, 23, 4419.
M. D’Auria, A. De Mico, F. D’Onofrio, G. Piancatelli, J. Org.
Chem. 1987, 52, 5243.
[2] For examples of palladium-catalysed Suzuki coupling, see: a)
P. Gros, A. Doudouh, Y. Fort, Tetrahedron Lett. 2004, 45, 6239;
b) N. Kudo, M. Perseghini, G. C. Fu, Angew. Chem. Int. Ed.
2006, 45, 1282; c) K. L. Billingsley, K. W. Anderson, S. L.
Buchwald, Angew. Chem. Int. Ed. 2006, 45, 3484; d) I. Kon-
dolff, H. Doucet, M. Santelli, J. Mol. Catal. A 2007, 269, 110;
e) K. Billingsley, S. L. Buchwald, J. Am. Chem. Soc. 2007, 129,
3358.
[3] For examples of palladium-catalysed Stille coupling, see: a) M.
Benaglia, F. Ponzini, C. R. Woods, J. S. Siegel, Org. Lett. 2001,
3, 967; b) J. Mathieu, P. Gros, Y. Fort, Tetrahedron Lett. 2001,
42, 1879; c) R. Zong, R. P. Thummel, J. Am. Chem. Soc. 2004,
126, 10800; d) Y. Miyata, T. Nishinaga, K. Komatsu, J. Org.
Chem. 2005, 70, 1147; e) W. Lu, L.-H. Zhang, X.-S. Ye, J. Su,
[14]
[15]
[16]
[17]
[18]
[19]
[20]
R. E. Atkinson, F. E. Hardy, J. Chem. Soc. B: Phys. Org. 1971,
357.
W. Chen, C. Xi, Y. Wu, J. Organomet. Chem. 2007, 692, 4381.
Received: February 7, 2008
Published Online: April 29, 2008
Eur. J. Inorg. Chem. 2008, 2550–2559
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
2559