In 1963, Castro and Stephens reported the coupling of an
alkynylcopper reagent and aryl halides to produce arylalkynes.8
Sonogashira showed the coupling of aryl halides and alkynes
without use of stoichiometric amounts of copper reagent in
1975.9 The most commonly used catalytic system in the
Sonogashira reaction requires CuI as the cocatalyst with
palladium and a phosphine ligand, amines, solvent, and the
desired aryl halides and terminal alkynes.10 Similar reaction
types have been reported that used alkynyl metal reagents
containing Mg,11 Zn,12 B,13 Al,14 Si,15 or Sn16 as the alkyne
source instead of terminal alkynes. Among the alkynyl metals,
trimethylsilylacetylene has been widely used as one of the
protected alkynes in the synthesis of asymmetrically disubsti-
tuted arylalkynes,17 and another protected alkyne, 2-methyl-
but-3-yn-2-ol, was also used.18 However, they have some
drawbacks. When alkynyl metal reagents are used, the reactions
always produce stoichiometric amounts of metal waste, raising
environmental problems. In the case of 2-methylbut-3-yn-2-ol,
the range of usable substrates is low because a strong base is
required. In the case of terminal acetylene as the alkyne source,
the homocoupled product occurred as a byproduct in the
presence of the copper cocatalyst19 or this side product
sometimes formed from the desired product in the absence of
copper.20
Palladium-Catalyzed Decarboxylative Coupling of
Alkynyl Carboxylic Acids and Aryl Halides
Jeongju Moon, Mihee Jang, and Sunwoo Lee*
Department of Chemistry, Chonnam National UniVersity, 300
Yongbong-dong, Buk-gu, Gwangju, 500-757, Republic of Korea
ReceiVed October 26, 2008
2-Octynoic acid and phenylpropiolic acid were employed for
the palladium-catalyzed decarboxylative coupling reaction
and with a variety of aryl halides. The former needed 1,4-
bis(diphenylphosphino)butane (dppb) as a ligand and the
latter tri-tert-butylphosphine (PtBu3), and both required 2
equiv of tetra-n-butylammonium fluoride (TBAF) for full
conversion. These reactions showed high reactivities and
tolerance of functional groups such as vinyl, ester, ether,
ketone, and amine.
Many improved versions of the Sonogashira reactions have
been reported, including, for example, copper-free,21 amine-
(7) (a) Boydston, A. J.; Yin, Y.; Pagenkopf, B. L. J. Am. Chem. Soc. 2004,
126, 3724–3725.
(8) Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 28, 3313–3315.
(9) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16,
4467–4470.
(10) (a) Hierso, J.-c.; Fihri, A.; Amardeil, R.; Meunier, P. Org. Lett. 2004,
6, 3473–3476. (b) Adjabeng, G.; Brenstrum, T.; Frampton, C. S.; Roberson,
A. J.; Hillhouse, J.; NcNulty, J.; Capretta, A. J. Org. Chem. 2004, 69, 5082–
5086.
(11) (a) Dang, H. P.; Linstrumelle, G. Tetrahedron Lett. 1978, 19, 191–194.
(b) Kamikawa, T.; Uozumi, Y.; Hayashi, T. Tetrahedron Lett. 1996, 37, 3161–
3164.
(12) (a) King, A. O.; Negishi, E,-i.; Villain, F. J., Jr.; Silveira, A., Jr. J. Org.
Chem. 1978, 43, 358–360. (b) Shi, J.; Zeng, X.; Negishi, E.-i. Org. Lett. 2003,
5, 1825–1828.
(13) (a) Fu¨rstner, A.; Seidel, G. Tetrahedron 1995, 51, 11165–11176. (b)
Castanet, A. S.; Colobert, F.; Schlama, T. Org. Lett. 2000, 2, 3559–3561. (c)
Oh, C. H.; Jung, S. H. Tetrahedron Lett. 2000, 41, 8513–8516. (d) Kabalka,
G. W.; Al-Masum, M.; Mereddy, A. R.; Dadush, E. Tetrahedron Lett. 2006, 47,
1133–1136.
(14) (a) Takai, K.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1980, 21, 2531–
2534. (b) Pe´rez, I.; Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc. 2001,
123, 4155–4160.
Palladium-catalyzed carbon-carbon bond formation reactions
are very useful methods for constructing higher molecules such
as materials and drugs for modern chemical and medical
applications.1 There are several types of reactions that depend
on a variety of organometallic nucleophiles, such as the Kumada,
Negishi, Stille, Suzuki, Hiyama, Sonogashira, and other related
couplings.2 Among them, the Sonogashira reaction, cross
coupling of aryl halides or alkenyl halides and terminal alkynes,
has been widely used as a powerful tool for the formation of sp
carbon and sp2 carbon bonds.3 Arylalkynes and alkenylalkynes
are important structures in pharmaceuticals,4 natural products,5
and polymers.6 In particular, much attention has been given to
π-extended molecules in the electrochemical and optical fields.7
(1) Negishi, E.-i., Ed. Handbook of Organopalladium Chemistry for Organic
Synthesis; Wiley-Interscience: New York, 2002.
(2) de Meijere, A., Diederich, F., Eds. Metal-Catalyzed Cross-Coupling
Reactions, 2nd Ed.; Wiley-VCH: Germany, 2004.
(15) (a) Nishihara, Y.; Ikegashira, K.; Mori, A.; Hiyama, T. Chem. Lett. 1997,
1233–1234. (b) Chang, S.; Yang, S. H.; Lee, P. H. Tetrahedron Lett. 2001, 42,
4833–4835. (c) Chang, H.-K.; Datta, S.; Das, A.; Odedra, A.; Liu, R.-S. Angew.
Chem., Int. Ed. 2007, 46, 4744–4747.
(3) (a) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46–49. (b) Negishi,
E.-i.; Anastasia, L. Chem. ReV. 2003, 103, 1979–2017. (c) Nicolaou, K. C.;
Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4442–4489.
(4) (a) Mitzel, F.; FitzGerald, S.; Beeby, A.; Faust, R. Eur. J. Org. Chem.
2004, 113, 6–1142. (b) Falcone, D.; Li, J.; Kale, A.; Jones, G. B. Bioorg. Med.
Chem. Lett. 2008, 18, 934–937.
(16) (a) Stille, J. K.; Simpson, J. H. J. Am. Chem. Soc. 1987, 109, 2138–
2152. (b) Mukai, C.; Miyakoshi, N.; Hanaoka, M. J. Org. Chem. 2001, 66, 5875–
5880.
(17) (a) Sommer, W. J.; Weck, M. AdV. Synth. Catal. 2006, 348, 2101–
2113. (b) Lo, P. K.; Li, K. F.; Wong, M. S.; Cheah, K. W. J. Org. Chem. 2007,
72, 6672–6679. (c) Li, G.; Huan, X.; Zhang, L. Angew. Chem., Int. Ed. 2008,
47, 346–349. (d) Doi, T.; Orita, A.; Matsuo, D.; Saijo, R.; Otera, J. Synlett 2008,
55–60. (e) Girrardot, C.; Lemercier, G.; Mulatier, J.-C.; Andraud, C.; Chauvin,
J.; Baldeck, P. L. Tetrahedron Lett. 2008, 49, 1753–1758.
(18) (a) Bleicher, L.; Cosford, N. D. P. Synlett 1995, 1115–1116. (b)
Melissaris, A. P.; Litt, M. H. J. Org. Chem. 1994, 59, 5818–5821. (c) Ma, L.;
Hu, Q.-S.; Pu, L. Tetrahedron: Asymmetry 1996, 7, 3103–3106. (d) Novak, Z.;
Nemes, P.; Kotschy, A. Org. Lett. 2004, 6, 4917–4920. (e) Csekei, M.; Novak,
Z.; Kotschy, A. Tetrahedron 2008, 64, 8992–8996.
(5) Boukouvalas, J.; Cote, S.; Ndzi, B. Tetrahedron Lett. 2007, 48, 105–
107.
(6) (a) Shimizu, H.; Fujimoto, K.; Furusyo, M.; Maeda, H.; Nanai, Y.;
Mizuno, K.; Inouye, M. J. Org. Chem. 2007, 72, 1530–1533. (b) Moon, J. H.;
McDaniel, W.; MacLean, P.; Hancock, L. F. Angew. Chem., Int. Ed. 2007, 46,
8223–8225. (c) Sessions, L. b.; Cohen, B. R.; Grubbs, R. B. Macromolecules
2007, 40, 1926–1933. (d) Dutta, T.; Woody, K. B.; Watson, M. D. J. Am. Chem.
Soc. 2008, 130, 452–453.
10.1021/jo802290r CCC: $40.75
Published on Web 12/19/2008
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1403–1406 1403