ORGANIC
LETTERS
1999
Vol. 1, No. 7
1133-1135
Carbon−Carbon Bond Formation via
Palladium-Catalyzed Reductive Coupling
in Air
Sripathy Venkatraman and Chao-Jun Li*
Department of Chemistry, Tulane UniVersity, New Orleans, Louisiana 70118
Received August 20, 1999
ABSTRACT
Palladium-catalyzed reactions in general are known to be carried out under an inert atmosphere because the palladium intermediates in the
catalytic cycle are often known to be sensitive to oxygen. Herein we report a novel palladium-catalyzed Ullmann-type reductive coupling of
aryl halides under an air atmosphere and in aqueous acetone.
Palladium-catalyzed reductive couplings are among the most
important carbon-carbon bond-forming reactions in modern
synthetic organic chemistry.1 Such reactions include the
π-allyl chemistry (also asymmetric),2 the Stille coupling,3
the Heck reaction,4 the Suzuki reactions,5 the Sonogashira
coupling,6 and many others. These reactions are generally
air sensitive. In addition to the requirement of an inert gas
atmosphere, these reactions are often carried out in the
presence of a phosphine compound (which serves as the
coordinating ligand to stabilize the reactive palladium
intermediate). In the course of our quest for novel method-
ologies in aqueous media,7 we came across this unusual
condition wherein the palladium catalyst seemed to be stable
in air.8 The validity of the reaction was further confirmed
when carried out under an oxygen atmosphere.
As the first step, we wish to report the palladium-catalyzed
zinc-mediated aryl halide coupling in air at an ambient
temperature (Scheme 1). Conventionally, reductive aryl
Scheme 1
(1) For representative reviews, see: Trost, B. M. Tetrahedron 1977, 33,
2615. Tsuji, J. Top. Curr. Chem. 1980, 91, 29. Kumada, M. Pure Appl.
Chem. 1980, 52, 669. Negishi, E. I. Acc. Chem. Res. 1982, 15, 340. Tsuji,
J. Organic Synthesis with Palladium Compounds; Springer-Verlag: Berlin,
1980; Baeckvall, J. E. Pure Appl. Chem. 1983, 55, 1669. Heck, R. H.
Palladium Reagents for Organic Synthesis; Academic Press: New York,
1985. Oppolzer, W. Angew. Chem. 1989, 101, 39. Trost, B. M. Acc. Chem.
Res. 1990, 23, 34. Larock, R. C. AdV. Met.-Org. Chem. 1994, 3, 97.
(2) For representative reviews, see: Trost. B. M. Acc. Chem. Res. 1980,
13, 385.
(3) For representative reviews, see: Stille, J. F. Angew. Chem., Int. Ed.
Engl. 1986, 25, 508.
(4) For representative reviews, see: Heck, R. H. Acc. Chem. Res. 1979,
12, 146. Overman, L. E. Pure Appl. Chem. 1994, 66, 1423.
(5) For a representative review, see: Miyaura, N.; Suzuki, A. Chem.
ReV. 1995, 95, 2457.
halide couplings9 are carried out by using the Ullmann
conditions,10 where copper is used in stoichiometric quanti-
ties.11 Generally, the Ullmann coupling is also carried out
at a high temperature, often above 200 °C.12
(8) After initial submission this work, an air-stable and polymer-supported
palladium-catalyzed Suzuki reaction was reported, see: Zhang, T. Y.; Allen,
M. J. Tetrahedron Lett. 1999, 40, 5813. For a Heck-type reaction with
arenediazonium salts, see: Brunner, H.; Le Cousturier de Courcy, N.; Genet,
J.-P. Tetrahedron Lett. 1999, 40, 4815.
(9) For representative reviews, see: Bringmann, G.; Walter, R.; Weirich,
R. Angew. Chem., Int. Ed. Engl. 1990, 29, 977. Sainsbury, M. Tetrahedron
1980, 36, 3327.
(6) For a representative review, see: Sonogashira, K. In ComprehensiVe
Organic Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991.
(7) Li, C. J. Chem. ReV. 1992, 92, 2023. Li, C. J.; Chan, T. H. Organic
Reaction in Aqueous Media; John Wiley & Sons: New York, 1997. See
also: Organic Synthesis in Water; Grieco, P. A., Ed.; Thomson Science:
Glasgow, 1998.
(10) For representative reviews, see: Fanta, P. E. Chem. ReV. 1946, 38,
139; 1964, 64, 613; Synthesis 1974, 9. Goshaev, M.; Otroshchenko, O. S.;
Sadykov, A. S. Russ. Chem. Soc. ReV. 1972, 41, 1046. See also: Posner,
G. H. An Introduction to Synthesis Using Organocopper Reagents; John
Wiley: New York, 1980. Nelson, T. D.; Meyers, A. I. J. Org. Chem. 1994,
59, 2655.
10.1021/ol9909740 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/10/1999