ORGANIC
LETTERS
2
005
Vol. 7, No. 22
083-5085
Palladium-Catalyzed Coupling Reactions
of Bromothiophenes at the C H Bond
5
−
Adjacent to the Sulfur Atom with a New
Activator System, AgNO /KF
3
Kei Kobayashi, Atsushi Sugie, Masabumi Takahashi, Kentaro Masui, and
Atsunori Mori*
Chemical Resources Laboratory, Tokyo Institute of Technology, R1-4 4259 Nagatsuta,
Yokohama 226-8503, Japan
Received August 26, 2005
ABSTRACT
Bromothiophene derivatives react with aryl iodides catalyzed by a palladium complex in the presence of a silver(I) nitrate/potassium fluoride
system to induce coupling at the C H bond, while the carbon bromine bond is intact. The produced coupling product bearing the C Br bond
allows further palladium-catalyzed C C bond-forming reactions in reasonable yields.
−
−
−
−
C-H substitution reactions of aromatic compounds with
organic halides are of great interest in organic synthesis
compared with those of the related coupling reaction with
metallic reagents, which are prepared from the corresponding
halide. By contrast, the direct reaction at the C-H bond
would be more suitable for the synthesis of the derivatives
where the carbon-bromine bond was intact. Our concern
has accordingly turned to the cross coupling of bro-
mothiophene derivatives at the C-H bond to introduce a
substituent into the thiophene ring. The C-H coupling of
bromothiophene, if successful, further transforms the ob-
tained coupling product by the reaction at the C-Br bond.
The combination of coupling reactions at C-H and C-Br
would open a new synthetic strategy for substituted thiophenes,
which attracts remarkable attention in the design of advanced
organic materials showing characteristics of liquid crystal,
1
library of various functional groups as well as the reaction
2
would enhance atom efficiency of the synthesis. We have
recently reported that homocoupling of thiophene derivatives
3
takesplaceatthecarbon-hydrogenbondtoformbithiophenes.
4
light emission, and organic semiconductors. Herein, we
The reaction was effectively promoted by the addition of
silver(I) fluoride. Homocoupling was found to occur at the
C-H bond even when the reaction was carried out with
report that a new class of the activator system, silver(I)
nitrate-potassium fluoride, undergoes palladium-catalyzed
C-H substitution reactions of bromothiophene derivatives
highly efficiently.
2-bromothiophene to afford the corresponding bithiophene,
The reaction of 2-bromothiophene (1a) and 4-methoxy-
1-iodobenzene (2a) was carried out with silver(I) fluoride
in the presence of a palladium catalyst. The corresponding
(
1) Metal-Catalyzed Cross-Coupling Reaction; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: Weinheim, 1998.
2) (a) Mori, A.; Sekiguchi, A.; Masui, K.; Shimada, T.; Horie, M.;
Osakada, K.; Kawamoto, M.; Ikeda, T. J. Am. Chem. Soc. 2003, 125, 1700.
b) Pivsa-Art, S.; Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Bull.
(
(
Chem. Soc. Jpn. 1998, 71, 467. (c) Yokooji, A.; Okazawa, T.; Satoh, T.;
Miura, M.; Nomura, M. Tetrahedron 2003, 59, 5685. (d) Kondo, Y.;
Komine, T. Sakamoto, T. Org. Lett. 2000, 2, 3111. (e) Sezen, B.; Sames,
D. J. Am. Chem. Soc. 2003, 125, 5274. (f) Sezen, B.; Sames, D. J. Am.
Chem. Soc. 2003, 125, 10580. (g) Sezen, B.; Sames, D. Org. Lett. 2003, 5,
(4) (a) Masui, K.; Mori, A.; Okano, K.; Takamura, K.; Kinoshita, M.;
Ikeda, T. Org. Lett. 2004, 6, 2011. (b) Briehn, C. A.; Schiedel, M.-S.;
Bonsen, E. M.; Schuhmann, W.; B a¨ uerle, P. Angew. Chem., Int. Ed. 2001,
40, 4680. (c) Facchetti, A.; Yoon, M.-H.; Stern, C. L.; Katz, H. E.; Marks,
T. J. Angew. Chem,. Int. Ed. 2003, 42, 3900. (d) Yamamoto, T.; Arai, M.;
Kokubo, H.; Sasaki, S. Macromolecules 2003, 36, 7986. (e) McCullough,
R. D. AdV. Mater. 1998, 10, 93. (f) Tour, J. M. Chem. ReV. 1996, 96, 537.
3
607. (h) Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211.
3) Masui, K.; Ikegami, H.; Mori, A. J. Am. Chem. Soc. 2004, 126, 5074.
(
1
0.1021/ol052063y CCC: $30.25
© 2005 American Chemical Society
Published on Web 10/01/2005