ORGANIC
LETTERS
2002
Vol. 4, No. 17
2997-3000
An Amphiphilic Resin-Supported
Palladium Catalyst for High-Throughput
Cross-Coupling in Water
Yasuhiro Uozumi* and Yasushi Nakai
Institute for Molecular Science and The Graduate UniVersity for AdVanced Studies,
Nishi-Gonaka 38, Myodaiji, Okazaki 444-8585, Japan
Received June 26, 2002
ABSTRACT
The Suzuki−Miyaura coupling of aryl halides (8 varieties) and aryl- or vinylboronic acids (12 varieties) took place in water in the presence of
a palladium complex of an amphiphilic polystyrene−poly(ethylene glycol) copolymer resin-supported N-anchored 2-aza-1,3-bis(diphenylphosphino)-
propane ligand and potassium carbonate to give uniform and quantitative yields of the corresponding biaryls (96 varieties).
High-throughput synthesis by solution-phase catalysis has
been recognized as a useful methodology with the advent
of efficient methods for compound purification. One ap-
proach employs supported catalysts that can be readily
removed by filtration.1 A number of supported palladium
complexes, in particular palladium-phosphine complexes,
have been designed and prepared to combine the advantages
of both homogeneous and heterogeneous catalysts in one
system.2 This class of supported palladium catalysts would
solve the basic problems of homogeneous catalysts, namely,
the separation and recycling of the catalysts. These palladium
complex catalysts also have the advantage of preventing
contamination of the ligand residue in the products.
oped amphiphilic resin-supported palladium complexes with
a view toward using them for catalytic reactions in water.4
Thus, for example, π-allylic substitution, carbonylation, and
Suzuki-Miyaura cross-coupling have been achieved in water
using a palladium complex immobilized by coordination with
a triarylphosphine anchored on an amphiphilic polystyrene-
poly(ethylene glycol) graft copolymer (PS-PEG-tap) (Figure
1).5
Recently, dendrimer- and polymer-supported chelating
ligands bearing a 2-aza-1,3-bis(diphenylphosphino)propane
moiety were designed, prepared, and complexed to palladium
(3) For reviews, see: (a) Li, C.-J.; Chan, T.-H. Organic Reactions in
Aqueous Media; Wiley: New York, 1997. (b) Grieco, P. A. Organic
Synthesis in Water; Kluwer Academic Publishers: Dordrecht, The Neth-
erlands, 1997.
On the other hand, organic reactions in water have recently
received much attention, because water is a readily available,
safe, and environmentally benign solvent.3 We have devel-
(4) (a) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron Lett. 1997, 38,
3557. (b) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64,
3384. (c) Uozumi, Y.; Watanabe, T. J. Org. Chem. 1999, 64, 6921. (d)
Danjo, H.; Tanaka, D.; Hayashi, T.; Uozumi, Y. Tetrahedron 1999, 55,
14341. (e) Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001, 123, 2919.
(5) (a) Bayer, E.; Rapp, W. In Chemistry of Peptides and Proteins;
Voelter, W., Bayer, E., Ovchinikov, Y. A., Iwanov, V. T., Eds.; Walter de
Gruter: Berlin, 1986; Vol. 3, p 3. (b) Rapp, W. In Combinatorial Peptide
and Nonpeptide Libraries; Jung, G., Ed.; VCH: Weinheim, Germany, 1996;
p 425. (c) Du, X.; Armstrong, R. W. J. Org. Chem. 1997, 62, 5678. (d)
Gooding, O. W.; Baudert, S.; Deegan, T. L.; Heisler, K.; Labadie, J. W.;
Newcomb, W. S.; Porco, J. A., Jr.; Eikeren, P. J. Comb. Chem. 1999, 1,
113.
(1) For reviews, see: (a) Bailey, D. C.; Langer, S. H. Chem. ReV. 1981,
81, 109. (b) Shuttleworth, S. J.; Allin, S. M.; Sharma, P. K. Synthesis 1997,
1217. (c) Burgess, K.; Porte, A. M. AdV. Catal. Processes 1997, 2, 69. (d)
Shuttleworth, S. J.; Allin, S. M.; Wilson, R. D.; Nasturica, D. Synthesis
2000, 1035.
(2) For reviews, see: (a) Uozumi, Y.; Hayashi, T. In Handbook of
Combinatorial Chemistry; Nicolaou, K. C., Hanko, R., Hartwig, W, Eds.:
Wiley-VCH: Weinheim, Germany, 2002; Chapter 19, pp 531-584. (b)
Do¨rwald, F. Z. Organic Synthesis on Solid Phase; Wiley-VCH: Weinheim,
Germany, 2000.
10.1021/ol0264298 CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/27/2002