ORGANIC
LETTERS
2002
Vol. 4, No. 25
4423-4425
An Efficient Copper Catalyst for the
Formation of Sulfones from Sulfinic
Acid Salts and Aryl Iodides
Jeremy M. Baskin and Zhaoyin Wang*
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research,
P.O. Box 1005, Pointe Claire-DorVal, Que´bec, Canada H9R 4P8
Received September 17, 2002
ABSTRACT
A novel copper-catalyzed method for the coupling of sulfinic acid salts and aryl iodides is described. A variety of methyl and diaryl sulfones
have been formed in excellent yields.
Aryl sulfones are important compounds in the practice of
medicinal chemistry. The functional group is found in
numerous drugs, including the recently developed selective
COX-2 inhibitor Vioxx.1 The common methods for preparing
these sulfones include the oxidation of sulfides2 or the
sulfonylation of arenes using aryl sulfonyl halides or aryl
sulfonic acids in the presence of a strong acid catalyst.3
Though these methods are attractive for their simplicity, they
are incompatible with numerous functional groups, including
olefins, amines, and some nitrogen heterocycles.
conditions. Indeed, there has been a report by Suzuki wherein
aryl iodides were treated with 1.6 equiv of an aryl sulfinate
and 1.5 equiv of CuI in DMF at 110 °C to yield diaryl
sulfones.4,5 The use of stoichiometric amounts of copper
complicates the workup of large-scale reactions.
In contrast to the development of catalytic C-O and C-N
bond-forming technology,6 there have been fewer reports on
transition metal-catalyzed C-S bond formation.7 The major-
(4) Suzuki, H.; Abe, H. Tetrahedron Lett. 1995, 36, 6239-6242.
(5) For a report on SNAr reactions between sulfinates and electron-
deficient aryl fluorides, see: Ulman, A.; Urankar, E. J. Org. Chem. 1989,
54, 4691-4692.
A metal-mediated cross-coupling of sulfinic acid salts with
aryl halides would represent a mild alternative to these
(6) (a) Muci, A. R.; Buchwald, S. L. Practical Palladium Catalysts for
C-N and C-O Bond Formation. In Topics in Current Chemistry; Miyaura,
N., Ed.; Springer-Verlag: Berlin, 2002; Vol. 219, p 133. (b) Klapars, A.;
Antilla, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123,
7727-7729. (c) Kiyomori, A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron
Lett. 1999, 40, 2657-2660. (d) Wolter, M.; Nordmann, G.; Job, G. E.;
Buchwald, S. L. Org. Lett. 2002, 4, 973-976. (e) Marcoux, J.-F.; Doye,
S.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 10539-10540. (f) Klapars,
A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421-7428.
(7) (a) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett. 2002,
4, 2803-2806. (b) Kondo, T.; Motsudo, T. Chem. ReV. 2000, 100, 3205-
3220. (c) Rane, A. M.; Miranda, E. I.; Soderquist, J. A. Tetrohedron Lett.
1994, 35, 3225-3226. (d) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852-
860. (e) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11598-
11599. (f) Baranano, D.; Hatwig, J. F.; J Am. Chem. Soc. 1995, 117, 2937-
2938. (g) Mann, G.; Baranano, D.; Hartwig, J. F.; Rheingold, A. L.; Guzei,
* To whom correspondence should be addressed.
(1) Prasit, P.; Wang, Z.; Brideau, C.; Chan, C.-C.; Charleson, S.;
Cromlish, W.; Ethier, D.; Evans, J. F.; Ford-Hutchinson, A. W.; Gauthier,
J. Y.; Gordon, R.; Guay, J.; Gresser, M.; Kargman, S.; Kennedy, B.; Leblanc,
Y.; Le´ger, S.; Mancini, J.; O’Neill, G. P.; Ouellet, M.; Percival, M. D.;
Perrier, H.; Riendeau, D.; Rodger, I.; Tagari, P.; The´rien, M.; Vickers, P.;
Wong, E.; Xu, L.-J.; Young, R.-N.; Zamboni, R. Bioorg. Med. Chem. Lett.
1999, 9, 1773-1778.
(2) Schank, K. In The Chemistry of Sulfones and Sulfoxides; Patai, S.,
Rappoport, Z., Stirling, C. J. M., Eds.; Wiley: New York, 1988; Chapter
7.
(3) (a) Truce, W. E.; Klinger, T. C.; Brand, W. W. In Organic Chemistry
of Sulfur; Oae, S., Ed.; Plenum Press: New York, 1977. (b) Ueda, M.;
Uchiyama, K.; Kano, T. Synthesis 1984, 323. (c) Graybill, B. M. J. Org.
Chem. 1967, 32, 2931.
10.1021/ol0269190 CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/12/2002