Palladium-catalysed direct arylations of heteroaromatics using more eco-compatible solvents pentan-1-ol or 3-methylbutan-1-ol

Article abstract of DOI:10.1016/j.tetlet.2011.01.084

The palladium-catalysed direct coupling of aryl halides with heteroaromatics in greener solvents than DMF or DMAc, which are often employed for such couplings, would be a considerable advantage for both industrial application and sustainable development.

Full text of DOI:10.1016/j.tetlet.2011.01.084

Tetrahedron Letters 52 (2011) 1383–1387
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Palladium-catalysed direct arylations of heteroaromatics using more
eco-compatible solvents pentan-1-ol or 3-methylbutan-1-ol
Souhila Bensaid a, Nouria Laidaoui b, Douniazad El Abed b, Soufi Kacimi c, Henri Doucet a,
⇑
a Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes ‘Catalyse et Organometalliques’, Campus de Beaulieu, 35042 Rennes, France
b Laboratoire de Réactivité et Chimie Fine, Département de Chimie, Faculté des Sciences, Université d’Oran Es-Sénia, BP. 1524, EL M’naouer, Oran 31100, Algeria
c Laboratoire de matériaux et catalyse, Faculté des sciences, Université Djillali Liabès, Sidi Bel Abbes 22000, Algeria
a r t i c l e i n f o
a b s t r a c t
Article history:
The palladium-catalysed direct coupling of aryl halides with heteroaromatics in greener solvents than
DMF or DMAc, which are often employed for such couplings, would be a considerable advantage for both
industrial application and sustainable development. We observed that a range of aryl bromides undergoe
coupling via C–H bond activation/functionalisation reaction of thiazoles or imidazoles in moderate to
good yields using pentan-1-ol or 3-methylbutan-1-ol as the solvents. Pentan-1-ol and 3-methylbutan-
1-ol are less toxic than DMF or DMAc, moreover they are bioresources as they can be obtained by fermen-
tation. Therefore, these reaction conditions are certainly more eco-compatible than those generally
employed for such couplings.
Received 15 December 2010
Revised 14 January 2011
Accepted 17 January 2011
Available online 21 January 2011
Keywords:
Heteroaromatics
Aryl bromides
C–H activation
Catalysis
Ó 2011 Elsevier Ltd. All rights reserved.
Palladium
ArMR1
+
The palladium-catalysed cross-coupling reactions between aryl
halides and heteroarenes such as thiophene, pyrroles, furans, imi-
dazoles or thiazoles represent powerful access to arylated hetero-
cycles. Negishi, Stille or Suzuki cross-coupling reactions have been
largely employed for the preparation of such compounds (Scheme
1, top).1 However, these methods are not very convenient as their
organometallic derivatives have to be prepared. Moreover, these
reactions are not environmentally attractive as they provide an
organometal or a salt (MX) as the by-product.
ArX
+
R2
R2
R2
Ar
Z
Y
Z
[Pd]
[Pd]
+ R1MX
R1M
X
Y
X
Y
M = Zn, Sn or B
X = Cl, Br, I
R2
R2
Z
Z
Y
[Pd]
base
Y = O, S or NR3
Z = CH or N
ArX
+
H
Ar
Y
Over the last years, very interesting results for the palladium-
catalysed coupling of aryl halides with heteroaromatic derivatives
via C–H bond activation have been reported and provide an eco-
nomical and attractive procedure for the preparation of such com-
pounds (Scheme 1, bottom).2,3 These coupling reactions provide
only HX associated to a base as a by-product and therefore are very
interesting both in terms of atom-economy and inert wastes. De-
spite tremendous improvement of the catalytic efficiency allowing
reactions under milder conditions or lower catalyst loadings, this
type of transformation still suffers from a major limitation with
regard to green chemistry concerning the reaction media since
the preferred solvents for these transformations are generally the
undesirable and toxic, dimethylformamide (DMF) or dimethylacet-
amide (DMAc).2–10 Therefore, the discovery of less toxic solvents
Scheme 1.
for such coupling reactions would be a considerable advantage
for sustainable development.
Recently, a few ‘greener’ solvents have been employed for direct
arylations. For example, the arylation of oxazoles, thiazoles, inda-
zoles or indoles using water was reported by Greaney, Djakovitch
and co-workers.11 René and Fagnou developed biphasic conditions
using water and EtOAc for the direct arylation of thiophenes.12
Polyethylene glycol (PEG 20000) has been found to be a useful
solvent for the direct arylation of triazoles.13 Carbonates such as
diethylcarbonate have also been used successfully for the direct
arylation of some heteroaromatics such as oxazole or thiazole
derivatives.14 Finally, the ruthenium-catalysed direct arylation of
2-arylpyridines in carbonates or water has been recently reported
by Fischmeister, Dixneuf and co-workers.15
⇑
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).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.084

1384
S. Bensaid et al. / Tetrahedron Letters 52 (2011) 1383–1387
To our knowledge, so far, alcohols such as pentan-1-ol or 3-meth-
N
ylbutan-1-ol have not been employed as the solvents for palladium-
catalysed direct arylations. Pentan-1-ol and 3-methylbutan-1-ol are
moderately soluble in water and miscible with common organic sol-
vents. They are not considered a hazardous air pollutant solvent.
They are readily biodegradable, unlikely to accumulate in the food
chain, and practically non-toxic to fish and aquatic organisms. Pen-
tan-1-ol and 3-methylbutan-1-ol can be prepared by the reduction
of 1-valeraldehyde or 3-methylbutyraldehyde (isovaleraldehyde)
with hydrogen. They can also be obtained by fermentation and are
present in cider, mead, beer, wine, and spirits to varying degrees.
They can be isolated by fractional distillation. Overexposure to 1-
pentanol or 3-methylbutan-1-ol may cause irritation of the eyes,
skin, or respiratory passages; headache, dizziness, coughing, nausea,
vomiting or diarrhoea. However, exposure to residual amounts of
these alcohols is unlikely to have any adverse health effects, as these
alcohols are found as contaminants in some alcoholic beverages
such as cider, beer or whisky. Swallowing small amounts of primary
N
O
PdCl(C3H5)(dppb) 2 mol%
CN
O
+
pentan-1-ol or
1
3-methylbutan-1-ol,
KOAc, 150 °C, 16h
Br
CN
Scheme 2.
R2
R2
N
N
PdCl(C3H5)(dppb) 2 mol%
R1
R3
S
R1
S
+
pentan-1-ol or
3-methylbutan-1-ol,
KOAc, 150 °C
1–29
Br
R3
Scheme 3.
Table 1
Palladium-catalysed 5-arylation of 2-n-propylthiazole in pentan-1-ol (Scheme 3)19,20
Entry
Product
Entry
12
Product
NO2
N
N
CN
N
S
1
2 85%
S
13 66%
O
O
S
N
N
2
3
13
14
3 67%
S
14 79%
O
CF3
CF3
N
S
S
4 70%
15 35%
O
N
N
N
N
N
4
5
15
16
S
S
5 64%
16 80%
NC
NO2
CF3
F
S
6 85%
S
17 82%
O
N
N
S
6
7
17
18
7 50%
S
18 18%
F
N
N
S
8 81%
S
19 64%
N
N
N
N
tBu
Me
8
9
19
20
S
S
9 63%
20 70%
N
S
S
10 23%
21 82%

S. Bensaid et al. / Tetrahedron Letters 52 (2011) 1383–1387
1385
Table 1 (continued)
Entry
Product
Entry
Product
N
N
N
N
N
N
OMe
10
11
21
S
S
S
11 60%
22 15%
CN
N
S
22
23 46%b
12 78%
Conditions: PdCl(C3H5)(dppb) (0.02 mmol), aryl bromide (1 mmol), 2-n-propylthiazole (2 mmol), KOAc (2 mmol), pentan-1-ol (5 mL), 20 h, 150 °C, isolated yields.
a
The formation of isoquinoline was also observed.
amyl alcohol (an amyl alcohol is any of the 8 alcohols with the for-
N
mula C5H11OH) incidentally is not likely to cause injury. Therefore,
the use of such alcohols as solvents is in agreement with several of
the P. Anastas 12 principles of ‘green chemistry’ including principles
1, 5, 7 and 12.16
N
PdCl(C3H5)(dppb) 2 mol%
S
+
R
S
pentan-1-ol, KOAc,
150 °C, 20h
Br
R = 4-CN 73% 30
R = 2-CN 56% 31
For this study, both pentan-1-ol and 3-methylbutan-1-ol were
employed as the solvents. The reactions were performed under ar-
gon in the presence of 2 mol % of PdCl(C3H5)(dppb) as the cata-
lyst17 at 150 °C. First, we examined the coupling of benzoxazole
with 4-bromobenzonitrile. We had previously observed that, with
this catalyst, this reaction proceeds nicely in DMF or in diethylcar-
bonate.14 However, in pentan-1-ol or 3-methylbutan-1-ol, the for-
mation of complex mixtures of products was obtained, and the
desired coupling product 1 could not be isolated (Scheme 2).
Then, we examined the reactivity of thiazole derivatives in
these solvents. Greaney and co-workers had observed that the di-
rect 5-arylation of thiazoles proceeds nicely ‘on water’ using
5 mol % PdCl2(dppf)/10 mol % PPh3 as the catalyst and silver car-
bonate as the additive.11a We had also obtained good results for
this reaction in diethylcarbonate.14b Employing 2-n-propylthiazole
and 4-bromobenzonitrile as the coupling partners, at 150 °C for
20 h, in the presence of KOAc as the base and 2 mol %
PdCl(C3H5)(dppb) as the catalyst in pentan-1-ol, the corresponding
5-arylation product 2 was obtained in good yield (Scheme 3 and
Table 1, entry 1). Next, we studied the scope of this reaction. The
reaction of other para-substituted electron-deficient aryl bromides
such as 4-bromopropiophenone, 4-bromoacetophenone, 4-bromo-
benzaldehyde or 4-bromonitrobenzene with 2-n-propylthiazole
R
Scheme 4.
S
O
PdCl(C3H5)(dppb) 2 mol%
+
pentan-1-ol, KOAc,
150 °C, 20h
Br
CN
S
CN
O
12% 32
Scheme 5.
gave the expected products 3–6 in 64–85% yields (Table 2, entries
2–5). Surprisingly, even deactivated aryl bromides 4-tert-butylb-
romobenzene or 4-bromoanisole gave the desired coupling
products 9 and 11 in relatively good yields (Table 1, entries 8
and 10). As expected, the meta-substituted aryl bromides,
Table 2
Palladium-catalysed 5-arylation of 2-ethyl-4-methylthiazole in pentan-1-ol (Scheme 3)19,20
Entry
Product
Entry
4
Product
CN
O
CF3
F
N
N
1
S
S
S
24 82%
27 75%
O
N
N
N
N
2
3
5
6
S
25 30%
28 77%
N
S
S
29 70%
26 67%
Conditions: PdCl(C3H5)(dppb) (0.02 mmol), aryl bromide (1 mmol), 2-ethyl-4-methylthiazole (2 mmol), KOAc (2 mmol), pentan-1-ol (5 mL), 20 h, 150 °C, isolated yields.

1386
S. Bensaid et al. / Tetrahedron Letters 52 (2011) 1383–1387
N
We also studied this reaction using 4-methylthiazole (Scheme
4). With this substrate, we could have observed the formation of
the 2- or the 5-arylation products. In DMAc as the solvent using
KOAc as the base, regioselective arylation on carbon C5 was
observed.5d The use of pentan-1-ol as the solvent for such cou-
plings preserves the regiochemical outcome of the arylation at
the 5-position, and the products 30 and 31 were formed in quite
good yields.
N
+
N
Y
PdCl(C3H5)(dppb) 2 mol%
N
pentan-1-ol, KOAc,
150 °C, 20h
Y
Br
Y = CH 78% 33
Y = N 76% 34
On the other hand, thiophenes or furans were found to give very
low yields in coupling products when pentan-1-ol was employed
as the solvent. For example, the coupling of 4-bromobenzonitrile
with 2-propionylthiophene gave the desired product 32 in only
12% yield (Scheme 5). In DMAc, much better yields could be
obtained.8g
The reactivity of 1,2-dimethylimidazole in pentan-1-ol was
found to be quite similar to the reactivity of thiazoles. The reaction
of 2-bromonaphthalene or 3-bromoquinoline gave 33 and 34 in
good yields (Scheme 6).
Finally, we examined if another amyl alcohol, 3-methylbutan-1-
ol, could be employed for palladium-catalysed direct arylations
(Table 3). As expected, the reaction of 2-n-propylthiazole with a
set of aryl bromides in 3-methylbutan-1-ol also proceeds nicely,
and gave similar yields than those obtained in pentan-1-ol.
In summary, we report here that a range of aryl bromides
undergoe palladium-catalysed coupling via C–H bond activation/
functionalisation reaction with thiazoles or 1,2-dimethylimidazole
in moderate to good yields using pentan-1-ol or 3-methylbutan-1-
ol as the solvents. These solvents, which are commercially avail-
able on a large scale at an affordable price, can be considered as
green alternatives to DMF or DMAc, which are generally employed
as the solvents for these transformations. For all these reactions,
pentan-1-ol and 3-methylbutan-1-ol 99% were used without any
purification. It should be noted that a wide variety of functional
groups on the aryl bromide such as formyl, acetyl, propionyl, nitro,
nitrile or fluoro are tolerated in these solvents.
Scheme 6.
3-bromobenzonitrile, 3-bromonitrobenzene or 3-bromoacetophe-
none, also gave the target compounds 12–14 in good yields (Table
2, entries 11–13).
Ortho-substituents on aryl halides generally have a more impor-
tant influence on the yields of palladium-catalysed reactions due to
their steric and/or coordination properties.18 2-Bromobenzonitrile
and 2-fluorobromobenzene gave 17 and 19 in good yields; whereas
a low conversion of the aryl bromide and a poor yield of 18 was ob-
tained when 2-bromobenzaldehyde was employed as the reactant
(Table 1, entries 16–18).
Pyridines, quinolines or pyrimidines are among the most com-
mon heterocyclic motifs found in pharmaceutically active com-
pounds. Therefore, preparative methods of biheteroaryl
derivatives containing such heterocycles remain an essential re-
search topic in organic synthesis. The reaction of 3-bromopyridine
or 3-bromoquinoline with 2-n-propylthiazole in pentan-1-ol gave
the expected coupling products 20 and 21 in 70% and 82% yields,
respectively. On the other hand, the use of 5-bromopyrimidine
and 4-bromoisoquinoline led to the formation of the 5-arylated
thiazoles 22 and 23 in low to moderate yields (Table 1, entries
19–22). In the course of the reaction with 4-bromoisoquinoline, a
dehalogenation side-reaction to form isoquinoline was observed.
Then, in order to determine the influence of a 4-substituent on thi-
azole on the reaction rates using this procedure, 2-ethyl-4-methylthi-
azole was employed as the reactant (Scheme 3 and Table 2). Five
electron-deficient aryl bromides and 3-bromopyridine have been
employed, and in most cases the desired products 24–29 were
formed in good to high yields. Again, the use of 4-trifluoromethyl-
bromobenzene gave a low yield of 30% in 25 (Table 2, entry 2).
Acknowledgements
We thank the Centre National de la Recherche Scientifique and
‘Rennes Metropole’ for providing financial support.
Table 3
Palladium-catalysed 5-arylation of 2-n-propylthiazole in 3-methylbutan-1-ol (Scheme 3)19,20
Entry
Product
Entry
5
Product
NC
N
N
CN
N
N
S
1
28 0%
S
17 82%
N
NO2
S
2
3
6
7
S
68 1%
21 72%
O
N
N
N
S
N
N
22 13%
S
S
14 76%
4
16 74%
Conditions: PdCl(C3H5)(dppb) (0.02 mmol), aryl bromide (1 mmol), 2-n-propylthiazole (2 mmol), KOAc (2 mmol), 3-methylbutan-1-ol (5 mL), 20 h, 150 °C, isolated yields.

S. Bensaid et al. / Tetrahedron Letters 52 (2011) 1383–1387
1387
Clement, J. A.; Mohanakrishnan, A. K. Tetrahedron 2007, 63, 10363–10371; (c)
Pozgan, F.; Roger, J.; Doucet, H. ChemSusChem 2008, 1, 404–407; (d) Derridj, F.;
Gottumukkala, A. L.; Djebbar, S.; Doucet, H. Eur. J. Inorg. Chem. 2008, 2550–
2559; (e) Nakano, M.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1851–
1854; (f) Dong, J. J.; Roger, J.; Doucet, H. Tetrahedron Lett. 2009, 50, 2778–2781;
References and notes
1. Li, J. J.; Gribble, G. W. Palladium in Heterocyclic Chemistry Part III; Pergamon:
Amsterdam, 2000; (b)Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York, 2002; p 213; (c)
Kondolff, I.; Doucet, H.; Santelli, M. Synlett 2005, 2057–2061.
2. Ohta, A.; Akita, Y.; Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuji, A.; Nakata, T.;
Tani, N.; Aoyagi, Y. Heterocycles 1990, 31, 1951–1958.
ˇ
(g) Roger, J.; Pozgan, F.; Doucet, H. Green Chem. 2009, 11, 425–432; (h) Liégault,
B.; Petrov, I.; Gorlesky, S. I.; Fagnou, K. J. Org. Chem. 2010, 75, 1047–1060; (i)
Derridj, F.; Roger, J.; Djebbar, S.; Doucet, H. Org. Lett. 2010, 12, 4320–4323.
9. For recent examples of direct arylations of pyrroles or indoles: (a) Bellina, F.;
Cauteruccio, S.; Rossi, R. Eur. J. Org. Chem. 2006, 1379–1382; (b) Wang, X.;
Gribkov, D. V.; Sames, D. J. Org. Chem. 2007, 72, 1476–1479; (c) Lebrasseur, N.;
Larrosa, I. J. Am. Chem. Soc. 2008, 130, 2926–2927; (d) Fall, Y.; Doucet, H.;
Santelli, M. ChemSusChem 2009, 2, 153–157; (e) Roger, J.; Pozgan, F.; Doucet, H.
Adv. Synth. Catal. 2010, 352, 696–710.
3. (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174–238; (b)
Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200–205; (c) Campeau, L.-C.; Stuart, D.
R.; Fagnou, K. Aldrichimica Acta 2007, 40, 35–41; (d) Seregin, I. V.; Gevoryan, V.
Chem. Soc. Rev. 2007, 36, 1173–1193; (e) Li, B.-J.; Yang, S.-D.; Shi, Z.-J. Synlett
2008, 949–957; (f) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269–10310; (g)
Ackermann, L.; Vincente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792–
9826; (h) Roger, J.; Gottumukkala, A. L.; Doucet, H. ChemCatChem 2010, 2, 20–
40.
4. For recent examples of direct 2-arylations or vinylations of oxazoles: (a)
Hoarau, C.; Du Fou de Kerdaniel, A.; Bracq, N.; Grandclaudon, P.; Couture, A.;
Marsais, F. Tetrahedron Lett. 2005, 46, 8573–8577; (b) Chiong, H. A.; Daugulis,
O. Org. Lett. 2007, 9, 1449–1451; (c) Sanchez, R. S.; Zhuravlev, F. A. J. Am. Chem.
Soc. 2007, 129, 5824–5825; (d) Besselievre, F.; Mahuteau-Betzer, F.; Grierson,
D. S.; Piguel, S. J. Org. Chem. 2008, 73, 3278–3280; (e) Verrier, C.; Martin, T.;
Hoarau, C.; Marsais, F. J. Org. Chem. 2008, 73, 7383–7386; (f) Yoshizumi, T.;
Satoh, T.; Hirano, K.; Matsuo, D.; Orita, A.; Otera, J.; Miura, M. Tetrahedron Lett.
2009, 50, 3273–3276; (g) Verrier, C.; Hoarau, C.; Marsais, F. Org. Biomol. Chem.
2009, 7, 647–650; (h) Strotman, N. A.; Chobanian, H. R.; Guo, Y.; He, J.; Wilson,
J. E. Org. Lett. 2010, 32, 3578–3581.
10. For recent examples of direct arylations of isoxazoles: Fall, Y.; Reynaud, C.;
Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2009, 4041–4050.
11. For direct arylations using water as the solvent: (a) Turner, G. L.; Morris, J. A.;
Greaney, M. F. Angew. Chem., Int. Ed. 2007, 46, 7996–8000; (b) Ohnmacht, S. A.;
Mamone, P.; Culshaw, A. J.; Greaney, M. F. Chem. Commun. 2008, 1241–1243;
(c) Ferrer Flegeau, E.; Popkin, M. E.; Greaney, M. F. Org. Lett. 2008, 10, 2717–
2720; (d) Ohnmacht, S. A.; Culshaw, A. J.; Greaney, M. F. Org. Lett. 2010, 12,
224–226; (e) Joucla, L.; Batail, N.; Djakovitch, L. Adv. Synth. Catal. 2010, 352,
2929–2936.
12. René, O.; Fagnou, K. Org. Lett. 2010, 12, 2116–2119.
13. Ackermann, L.; Vicente, R. Org. Lett. 2009, 11, 4922–4925.
14. (a) Roger, J.; Verrier, C.; Le Goff, R.; Hoarau, C.; Doucet, H. ChemSusChem 2009,
2, 951–956; (b) Dong, J. J.; Roger, J.; Verrier, C.; Martin, T.; Le Goff, R.; Hoarau,
C.; Doucet, H. Green Chem. 2010, 12, 2053–2063.
15. (a) Arockiam, P.; Poirier, V.; Fischmeister, C.; Bruneau, C.; Dixneuf, P. H. Green
Chem. 2009, 11, 1871–1875; (b)Angew. Chem., Int. Ed. 2010, 49, 6629–6632.
16. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford
University Press: New York, 1998. pp. 30; (b) Welton, T. Chem. Rev. 1999, 99,
2071–2084; (c) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686–
694.
5. For recent examples of direct 2- or 5-arylations of thiazoles: (a) Gottumukkala,
A. L.; Doucet, H. Eur. J. Inorg. Chem. 2007, 3629–3632; (b) Campeau, L.-C.;
Bertrand-Laperle, M.; Leclerc, J.-P.; Villemure, E.; Gorelsky, S.; Fagnou, K. J. Am.
Chem. Soc. 2008, 130, 3276–3277; (c) Martin, T.; Verrier, C.; Hoarau, C.; Marsais,
ˇ
F. Org. Lett. 2008, 10, 2909–2912; (d) Roger, J.; Pozgan, F.; Doucet, H. J. Org.
Chem. 2009, 74, 1179–1186; (e) Derridj, F.; Roger, J.; Geneste, F.; Djebbar, S.;
Doucet, H. J. Organomet. Chem. 2009, 694, 455–465.
17. Cantat, T.; Génin, E.; Giroud, C.; Meyer, G.; Jutand, A. J. Organomet. Chem. 2003,
687, 365–376.
6. For recent examples of direct arylations of imidazoles: (a) Bellina, F.;
Cauteruccio, S.; Mannina, L.; Rossi, R.; Viel, S. Eur. J. Org. Chem. 2006, 693–
703; (b) Cerna, I.; Pohl, R.; Klepetarova, B.; Hocek, M. Org. Lett. 2006, 8, 5389–
5392; (c) Bellina, F.; Calandri, C.; Cauteruccio, S.; Rossi, R. Tetrahedron 2007, 63,
1970–1980; (d) Bellina, F.; Cauteruccio, S.; Di Flore, A.; Rossi, R. Eur. J. Org.
Chem. 2008, 5436–5445; (e) Bellina, F.; Cauteruccio, S.; Di Flore, A.; Marchietti,
C.; Rossi, R. Tetrahedron 2008, 64, 6060–6072; (f) Roger, J.; Doucet, H.
Tetrahedron 2009, 65, 9772–9781.
7. For recent examples of direct arylations of furans: (a) Parisien, M.; Valette, D.;
Fagnou, K. J. Org. Chem. 2005, 70, 7578–7584; (b) Beccalli, E. M.; Broggini, G.;
Martinelli, M.; Sottocornola, S. Synthesis 2008, 136–140; (c) Gottumukkala, A.
L.; Doucet, H. Adv. Synth. Catal. 2008, 350, 2183–2188; (d) Liégaut, B.; Lapointe,
D.; Caron, L.; Vlassova, A.; Fagnou, K. J. Org. Chem. 2009, 74, 1826–1834; (e)
18. (a) Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001, 1980–1982; (b)
Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Synthesis 2004, 1281–1289.
19. General procedure for coupling reactions: In a typical experiment, the aryl
bromide (1 mmol), heteroaromatic derivative (2 mmol), KOAc (0.196 g,
2 mmol) and PdCl(C3H5)(dppb)17 (0.012 g, 0.02 mmol) were dissolved in
pentan-1-ol or 3-methylbutanol (5 mL) (see tables) in a Schlenk tube under
an argon atmosphere. The reaction mixture was stirred at 150 for 20 h. The
solvent was removed in vacuo, then the crude mixture was purified by silica
gel column chromatography.
20. All compounds gave satisfactory 1H, 13C and elementary analysis: 1H NMR
(200 MHz, CDCl3) of new compounds: 13 d 8.42 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H),
7.91 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 3.06 (t, J = 7.5 Hz,
2H), 1.83 (sext., J = 7.5 Hz, 2H), 1.10 (t, J = 7.5 Hz, 3H). 27 d 7.70 (s, 1H), 7.68–
7.45 (m, 3H), 3.06 (q, J = 7.5 Hz, 2H), 2.53 (s, 3H), 1.42 (t, J = 7.5 Hz, 3H). 31 d
8.85 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.70–7.48 (m, 3H), 2.47 (s, 3H).
ˇ
Dong, J. J.; Roger, J.; Pozgan, F.; Doucet, H. Green Chem. 2009, 11, 1832–1846; (f)
Ionita, M.; Roger, J.; Doucet, H. ChemSusChem 2010, 3, 367–376.
8. For recent examples of direct arylations of thiophenes: (a) David, E.; Pellet-
Rostaing, S.; Lemaire, M. Tetrahedron 2007, 63, 8999–9006; (b) Amaladass, P.;