The Ullmann coupling reaction is one of the most
useful methods for the synthesis of symmetrical biaryls.
It is usually carried out with copper as the reagent.5
However, it generally requires more than a stoichiometric
amount of copper and high reaction temperatures. In
recent years, various agents, especially combination of
the transition metal and reducing agent,3b,6-9 were
used to overcome this problem. For example, Li and
Ventrakaman6a,b have reported the Pd/C and zinc-medi-
ated Ullmann-type coupling. In the presence of Pd/C and
zinc, various aromatic iodides and bromides were homo-
coupled in moderate to good yields, but it required some
additives (cosolvent or phase-transfer catalysts) to im-
prove the yield of the coupling product. Under these
reaction conditions, aryl chlorides were inert. Sasson and
co-workers6c have reported that aryl chlorides could be
coupled in the presence of Pd/C and zinc, but both the
additives (PEG-400 and NaOH) and high reaction tem-
peratures were needed. Recently, we also reported the
palladium-catalyzed Ullmann-type coupling in liquid
CO2.3b In liquid CO2, various aromatic halides including
some aromatic chlorides underwent homocoupling
smoothly in the presence of Pd/C, zinc, and H2O at room
temperature overnight. In this case, no other additive
was required (eq 1).
New Role of CO2 a s a Selective Agen t in
P a lla d iu m -Ca ta lyzed Red u ctive Ullm a n n
Cou p lin g w ith Zin c in Wa ter
J in-Heng Li,* Ye-Xiang Xie, and Du-Lin Yin
Institute of Fine Catalysis and Synthesis, College of
Chemistry and Chemical Engineering, Hunan Normal
University, Changsha 410081, China
jhli@mail.hunnu.edu.cn
Received J uly 8, 2003
Abstr a ct: Carbon dioxide was found to promote the pal-
ladium-catalyzed zinc-mediated reductive Ullmann coupling
of aryl halides. In the presence of carbon dioxide, Pd/C, and
zinc, various aromatic halides including less reactive aro-
matic chlorides were coupled to give the corresponding
homocoupling products in good yields.
In previous reports on carbon dioxide (CO2), most of
the studies concerned the use of CO2 as a raw material1
or reaction media2 in organic synthesis. Thus, the devel-
opment of new routes on applying CO2 in modern organic
synthesis is considered to be one of the most challenging
fields for the synthetic chemists. Although CO2 has been
demonstrated to be a selective agent in the previous
reports on using CO2 as either a raw material or reaction
media,1-3 there are only few successful examples in
applying CO2 only as a selective agent to shift the
reaction selectivity in organic synthesis.4 Very recently,
we found that CO2 could be used as a selective agent to
improve the diiodination of alkynes to synthesize 1,2-
diiodoalkenes, which are useful building blocks for or-
ganic chemistry.4b The results encourage us to further
investigate this role of CO2 in organic synthesis. Thus,
we first explored our recent report on the Ullmann
coupling reaction in liquid CO2, in which one of the roles
of CO2 was shown to be that of a selective agent.3b
In liquid carbon dioxide, the selectivity toward the
palladium-catalyzed Ullmann-type coupling was not very
desirable due to the formation of the reduction product
as the major side product. Moreover, the coupling of
aromatic halides bearing electron-withdrawing groups
did not occur, and CO2 was found to improve the
(5) (a) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 977. (b) Zhang, S.; Zhang, D.; Liebeskind, L. S. J .
Org. Chem. 1997, 62, 2312 and references therein.
(1) (a) Stocchi, I. M. Industrial Chemistry; Ellis Horwood: New York,
1990. (b) Inoue, S., Yamazaki, N., Eds. Organic and Bioorganic
Chemistry of Carbon Dioxide; Kodansha: Tokyo, Wiley: New York,
1982. (c) Halman, M. M. Chemical Fixation of Carbon Dioxide; CRC
Press: Boca Raton, 1993. (d) Arakawa, H.; Aresta, M.; Armor, J . N.;
Barteau, M. A.; Bechman, E. J .; Bell, A. T.; Bercaw, J . E.; Creutz, C.;
Dinjus, E.; Dixon, D. A.; Domen, K.; Dubois, D.; Eckert, J .; Fujita, E.;
Gibson, D. H.; Goddard, W. A.; Goodman, D. W.; Kelller, J .; Kubas, G.
J .; Kung, H. H.; Lyons, J . E.; Manzer, L. E.; Marks, T. J .; Morokuma,
K.; Nicholas, K. M.; Periana, R.; Que, L.; Rostrup-Nielson, J .; Sachtler,
W. M. H.; Schmidt, L. D.; Sen, A.; Somorjai, G. A.; Stair, P. C.; Stults,
B. R.; Tumas, W. Chem. Rev. 2001, 101, 953.
(2) For representative reviews, see: (a) J essop, P. G., Leitner, W.,
Eds: Chemical Synthesis using Supercritical Fluids; Wiley-VCH:
Weinheim, 1999. (b) J essop, P. G.; Ikariya, T.; Noyori, R. Chem. Rev.
1999, 99, 475. (c) Li, J .; J ia, L.; J iang, H. Chin. J . Org. Chem. 2000,
20, 293. (d) Oakes, R. S.; Clifford, A. A.; Rayner, C. M. J . Chem. Soc.,
Perkin Trans. 1 2001, 917.
(3) (a) Wittmann, K.; Wisniewski, W.; Mynott, R.; Leitner, W.;
Kranemann C. L.; Rische, T.; Eilbracht, P.; Kluwer: S.; Ernsting, J .
M.; Elsevier: C. J . Chem. Eur. J . 2001, 7, 4584 and references therein.
(b) Li, J .; Xie, Y.; Yin, D. J iang, H. Green Chem. 2002, 4, 424.
(4) (a) Peyrot F.; Martin, M.-T.; Migault, J .; Ducrocq, C. Eur. J . Org.
Chem. 2003, 172. (b) Li, J .; Xie, Y.; Yin, D. Green Chem. 2002, 4, 505.
(c) Gabriele, B.; Salerno, G.; Costa, M.; Chiusoli, G. P. Chem. Commun.
1999, 1381 and references therein.
(6) For Pd/C-catalyzed Ullmann-type couplings using Zn and water
as the reducing regent, see: (a) Ventrakaman, S.; Li, C. J . Org. Lett.
1999, 1, 1133. (b) Ventrakaman, S.; Li, C. J . Tetrahedron Lett. 2000,
41, 4831 and references therein. (c) Mukhopadhyay, S.; Rothenberg,
G.; Gitis, D.; Sasson, Y. Org. Lett. 2000, 2, 211.
(7) For Pd/C-catalyzed Ullmann-type couplings using other reducing
regents, see the following. Formate salts as the reducing regents: (a)
Mukhopadhyay, S.; Rothenberg, G.; Gitis, D.; Wiener, H.; Sasson, Y.
J . Chem. Soc., Perkin Trans. 2 1999, 2481. (b) Mukhopadhyay, S.;
Rothenberg, G.; Qafisheh, N.; Sasson, Y. Tetrahedron Lett. 2001, 42,
6117. Hydrogen gas as the reducing regents: (c) Mukhopadhyay, S.;
Rothenberg, G.; Wiener, H.; Sasson, Y. Tetrahedron 1999, 55, 14763
and references therein.
(8) For other Pd-catalyzed reductive Ullmann-type couplings, see:
(a) Kuroboshi, M.; Waki, Y.; Tanaka, H. J . Org. Chem. 2003, 68, 3938
and references therein. (b) Hassan, J .; Hathroubi, C.; Gozzi, C.;
Lamaire, M. Tetrahedron 2001, 57, 7845. (c) Hassan, J .; Penalva, V.;
Lavenot, L.; Gozzi, C.; Lemaire, M. Tetrahedron 1998, 54, 13793. (d)
Penalva, V.; Hassan, J .; Lavenot, L. Gozzi, C.; Lemaire, M. Tetrahedron
Lett. 1998, 39, 2559. (e) Hennings, D. D.; Iwama, T.; Rawel, V. H. Org.
Lett. 1999, 1, 1205.
(9) For Ni-catalyzed Ullmann-type couplings, see: (a) Takagi, K.;
Hayama, N.; Sasaki, K. Bull. Chem. Soc. J pn. 1984, 57, 1887. (b)
Meyer, G.; Rollin, Y.; Perichon, J . J . Organomet. Chem. 1987, 333, 263.
Massicot, F.; Schneider, R.; Fort, Y.; Illly-Cherrey, S.; Tillement, O.
Tetrahedron 2001, 57, 531 and references therein.
10.1021/jo0349835 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/18/2003
J . Org. Chem. 2003, 68, 9867-9869
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