use of cheaper metals, such as copper6 and nickel, as the
-8
9
Reusable Copper-Catalyzed Cross-Coupling
Reactions of Aryl Halides with Organotins in
Inexpensive Ionic Liquids
catalysts is an alternative strategy besides the recovery as well
as reuse of the expensive palladium catalysts. Although copper
as the cocatalyst for the palladium-catalyzed Stille cross-
couplings has been reported in many papers, little attention
has been attracted on the use of copper as catalyst alone for the
reaction. Moreover, many copper-mediated protocols required
2
4
Jin-Heng Li,* Bo-Xiao Tang, Li-Ming Tao, Ye-Xiang Xie,
Yun Liang, and Man-Bo Zhang*
5-8
5
,6
stoichiometric amounts of copper. Kang and co-workers first
demonstrated that the Stille couplings catalyzed by 10 mol %
of CuI alone were conducted smoothly in moderate to high
Key Laboratory of Chemical Biology & Traditional Chinese
Medicine Research (Ministry of Education), College of
Chemistry and Chemical Engineering, Hunan Normal
UniVersity, Changsha 410081, China
7
yields with the aid of sodium chlorides. However, the scope
was limited to aryl iodides and vinyl iodides, and organostan-
nanes must be added slowly by a syringe pump to improve the
yields. The other copper-catalyzed Stille methods were also
jhli@hunnu.edu.cn; manbozhang@163.com
8a
ReceiVed June 14, 2006
focused on the activated organohalides, such as acyl chlorides,
8
b
ally bromides, proparyl bromides, and hypervalent iodine
8
c
compounds. Thus, the development of an effective copper
catalytic system extended the scope to aryl bromides, and aryl
chlorides is still a challenging area. Here, we report an effective
Cu2O nanoparticles/P(o-tol)3 catalytic system for cross-couplings
of aryl halides including aryl chlorides with organotins in TBAB.
Importantly, the Cu2O/P(o-tol)3/TBAB system can be recovered
2 3
A combination of Cu O nanoparticles with P(o-tol) shows
highly catalytic activity for the Stille cross-coupling reaction.
A series of copper catalysts and ligands were evaluated, and
(
3) For very recent papers on the palladium-catalyzed Stille cross-
couplings, see (a) Calo, V.; Nacci, A.; Monopoli, A.; Montingelli, F. J.
Org. Chem. 2005, 70, 6040. (b) Garcia-Martinez, J. C.; Lezutekong, R.;
Crooks, R. M. J. Am. Chem. Soc. 2005, 127, 5097. (c) Li, J.-H.; Liang, Y.;
Wang, D.-P.; Liu, W.-J.; Xie, Y.-X.; Yin, D.-L. J. Org. Chem. 2005, 70,
832. (d) Herve, A.; Rodriguez, A. L.; Fouquet, E. J. Org. Chem. 2005,
0, 1953. (e) Gallagher, W. P.; Maleczka, R. E., Jr. J. Org. Chem. 2005,
2 3
Cu O nanoparticles combined with P(o-tol) provided the best
results. In the presence of Cu
2
O nanoparticles and P(o-tol) ,
3
a variety of aryl halides including aryl chlorides underwent
the Stille reaction with organotins smoothly in moderate to
2
7
excellent yields using inexpensive TBAB (n-Bu
4
NBr) as the
/TBAB
70, 841. (f) Su, W.; Urgaonkar, S.; McLaughlin, P. A.; Verkade, J. G. J.
Am. Chem. Soc. 2004, 126, 16433. (g) Chiappe, C.; Pieraccini, D.; Zhao,
D.; Fei, Z.; Dyson, P. J. AdV. Synth. Catal. 2006, 348, 68. (h) Li, J.-H.;
Liang, Y.; Xie, Y.-X. Tetrahedron 2005, 61, 7289. (i) Gajare, A. S.; Jensen,
R. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Synlett 2005, 144.
medium. It is noteworthy that the Cu O/P(o-tol)
2
3
system can be recovered and reused at least three times
without any loss of catalytic activity among the reactions of
aryl iodides and activated aryl bromides.
(4) For representative papers on the use of copper as the cocatalyst for
the palladium-catalyzed Stille cross-couplings, see (a) Mee, S. P. H.; Lee,
V.; Baldwin, J. E. Chem.sEur. J. 2005, 11, 3294. (b) Mazzola, R. D., Jr.;
Giese, S.; Benson, C. L.; West, F. G. J. Org. Chem. 2004, 69, 220. (c)
Casado, A. L.; Espinet, P. Organometallics 2003, 22, 1305. (d) Dubbaka,
S. R.; Vogel, P. J. Am. Chem. Soc. 2003, 125, 15292. (e) Kim, W.-S.; Kim,
H.-J.; Cho, C.-G. J. Am. Chem. Soc. 2003, 125, 14288. (f) Gallagher, W.
P.; Terstiege, I.; Maleczka, R. E., Jr. J. Am. Chem. Soc. 2001, 123, 3194.
(g) Han, X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600.
(h) Paterson, I.; Lombart, H.-G.; Allerton, C. Org. Lett. 1999, 1, 19. (i)
Hoshino, M.; Degenkolb, P.; Curran, D. P. J. Org. Chem. 1997, 62, 8341.
The Stille cross-coupling reaction is an important transforma-
tion in organic synthesis because its products, in particular
1
biarys, play an important role as structural elements of many
natural products and biologically active compounds as well as
useful intermediates in synthetic organic chemisty. Among
these efficient Stille protocols, palladium combined with a ligand
2
(j) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S. J.
(
usually a phosphine ligand) is generally employed as the
Org. Chem. 1994, 59, 5905. (k) Liebeskind, L. S.; Fengl, R. W. J. Org.
Chem. 1990, 55, 5359.
2
-4
catalytic system.
However, the cost of these palladium
(
5) For reviews on copper-catalyzed coupling reactions, see (a) Siemsen,
P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39, 2632.
b) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem.
catalysts is considerably expensive. In terms of economy, the
(
(
1) Bringmann, G.; Gunther, C.; Ochse, M.; Schupp O.; Tasler, S. In
ReV. 2002, 102, 1359. (c) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
ReV. 2004, 248, 2337. (d) Ley, S. V.; Thomas, A. W. Angew. Chem., Int.
Ed. 2003, 42, 5400.
(6) For representative papers on the Stille reaction mediated by stoichio-
metric amounts of copper catalysts, see (a) Allred, G. D.; Liebeskind, L. S.
J. Am. Chem. Soc. 1996, 118, 2748 and references therein. (b) Wipf, P.
Synthesis 1993, 537. (c) Falck, J. R.; Bhatt, R. K.; Ye J. J. Am. Chem. Soc.
1995, 117, 5973.
(7) Kang, S.-K.; Kim, J.-S.; Choi, S.-C. J. Org. Chem. 1997, 62, 4208.
(8) For papers on the copper-catalyzed Stille reactions of the activated
organohalides, such as acyl chlorides, ally bromides, proparyl bromides,
and hypervalent iodine compounds, see (a) Wang, Y.; Burton, D. J. Org.
Lett. 2006, 8, 1109. (b) Mohapatra, S.; Bandyopadhyay, A.; Barma, D. K.;
Capdevila, J. H.; Falck, J. R. Org. Lett. 2003, 5, 4759. (c) Kang, S.-K.;
Yamaguchi, T.; Kim, T.-H.; Ho, P.-S. J. Org. Chem. 1996, 61, 9082.
(9) For a representative paper on the nickel-catalyzed Stille reactions,
see Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 510.
Progress in the Chemistry of Organic Natural Products; Herz, W., Falk,
H., Kirby, G. W., Moore, R. E., Eds.; Springer: New York, 2001; Vol. 82,
pp 1-293.
(2) For reviews, see the following: (a) Hegedus, L. S. In Organometallics
in Synthesis; Schlosser, M., Ed.; J. Wiley & Sons: Chichester, U.K., 2002;
p 1123. (b) Handbook of Organopalladium Chemistry for Organic Synthesis;
Negishi, E., Ed.; Wiley-Interscience: New York, 2002. (c). Diederich, F.;
Stang, P. J. Metal-Catalyzed Cross-coupling Reactions; Wiley-VCH:
Weinheim, Germany, 1998. (d) Miyaura, N. Cross-Coupling Reaction;
Springer: Berlin, 2002. (e) de Meijere, A.; Diederich, F. Metal-Catalyzed
Cross-coupling Reactions; Wiley-VCH: Weinheim, Germany, 2004. (f)
Wang D.-P.; Zhang, X.-D.; Liang, Y.; Li, J.-H. Chin. J. Org. Chem. 2006,
2
6, 19. (g) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (h)
Hassan, J.; S e´ vignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. ReV.
002, 102, 1359. (i) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed.
004, 43, 4704.
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10.1021/jo061220j CCC: $33.50 © 2006 American Chemical Society
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J. Org. Chem. 2006, 71, 7488-7490
Published on Web 08/16/2006