LETTER
Copper-Catalyzed Sulfonylation of Arylboronic Acids in Ionic Liquids
1457
Among the different ILs screened, it was observed that nign nature of the reaction allows easy application to a
there was no effect on the yield of the product on changing wide range of substrates.
the cation in the ionic liquid, whereas the change in the an-
ion influenced the reaction through the self-association of
Acknowledgment
the ionic liquid ions and other generalized polarity ef-
fects.15i Butylmethylimidazolium ([bmim]+) and dibutyl-
B.N. and R.C. thank the Council of Scientific and Industrial Rese-
methylimidazolium ([bbmim]+), cation-based ILs, gave
arch (CSIR), India, for research fellowships.
the product, phenyl p-tolylsulfone in low yields (20–
30%). The reaction in ILs with bromide anion
References and Notes
([bmim][Br]) gave no product and the reaction with
(1) (a) Ducharme, Y.; Gauthier, J. Y.; Prasit, P.; Leblanc, Y.;
[bmim][BF4] and [bmim][PF6] gave the product in low
Wang, Z.; Leger, S.; Therien, M. Int. Patent Appl., WO
yields (Table 1, entries 1–5). On the other hand, the reac-
9500501, 1995; Chem. Abstr. 1995, 124, 55954. (b) Prasit,
tion
using
butylmethylimidazolium
triflate
P.; Wang, Z.; Brideau, C.; Chan, C.-C.; Charleson, S.;
Cromlish, W.; Ethier, D.; Evans, J. F.; Hutchinson, W. F.;
Gauthier, J. Y.; Gordon, R.; Guay, J.; Gresser, M.; Kargman,
S.; Kennedy, B.; Leblanc, Y.; Leger, S.; Mancini, J.;
O’Neill, G. P.; Ouellet, M.; Percival, M. D.; Perrier, H.;
Riendeau, D.; Rodger, I.; Tagari, P.; Therien, M.; Vockers,
P.; Wong, E.; Xu, L.-J.; Young, R. N.; Zamboni, R.; Boyce,
S.; Rupniak, N.; Forrest, M.; Visco, D.; Patrick, D. Bioorg.
Med. Chem. Lett. 1999, 9, 1773. (c) Lawson, F. C.;
Mcadam, B.; Morrison, B. W.; Kapoor, S.; Kujubu, D.;
Antes, L.; Lasseter, K. C.; Quan, H.; Gertz, B. J.; Fitzgerald,
G. A. J. Pharmacol. Exp. Ther. 1999, 289, 735. (d) Ehrich,
E. W.; Dallob, A.; Lepeleire, I. D.; Hecken, A. V.; Riendeau,
D.; Yuan, W.; Porras, A.; Wittreich, J.; Seibold, J. R.;
Schepper, P. D.; Mehlisch, D. R.; Gertz, B. J. Clin.
Pharmacol. Ther. 1999, 65, 336. (e) Langman, M. J.;
Jensen, D. M.; Watson, D. J.; Harper, S. E.; Zhao, P.-L.;
Quan, H.; Bolognese, J. A.; Simon, T. J. J. Am. Med. Assoc.
1999, 282, 1929.
([bmim][OTf]) afforded the product in high yield
(Table 1, entry 6). Therefore, the effect of changing the
anion exerts more influence on the reaction when com-
pared to the effect of changing the cation. To ascertain the
superior performance of ionic liquids over the other sol-
vents, experiments were conducted using Cu(OAc)2 as the
catalyst in DMSO and dichloroethane (Table 1, entries 7
and 8). It is interesting to note that the reaction in these or-
ganic solvents gave the corresponding sulfone in low
yields with the formation of biphenyl and phenol as the
side products. However, there was no reaction in the ab-
sence of copper catalyst (Table 1, entry 9).
A variety of aryl sulfones have been synthesized employ-
ing the optimized reaction conditions as shown in Table 2.
The cross-coupling reaction is quite simple and can be ap-
plied to different arylboronic acids. The individual reac-
tions were not further optimized for the reaction
conditions, reaction times or temperature. The use of aryl-
boronic acids with electron-donating and electron-with-
drawing substituents was equally efficient for the
coupling reaction with sodium p-toluenesulfinate. The
corresponding diaryl sulfones were obtained in good
yields. This extends the scope of further functionalization
on the aromatic ring of resulting sulfones. The reaction
with trifluoromethylphenylboronic acid gave the corre-
sponding sulfone in high yield (Table 2, entries 1–6). In
spite of the presence of an electron-donating substituent at
the ortho position, o-tolylboronic acid reacted smoothly to
give the corresponding sulfone in good yield (Table 2, en-
try 7). Reaction using sodium methyl sulfinate as reaction
partners with various arylboronic acids led to similar re-
sults forming aryl sulfones in good yields (Table 2, entries
8–11). Finally, upon completion of the reaction, the ionic
liquid phase containing [bmim][OTf] and Cu(OAc)2 was
almost quantitatively recovered by simple extraction of
the product with Et2O. The recovered ionic liquid phase
containing the catalyst was reused for several cycles with
consistent activity (Table 2, entries 1 and 4).
(2) (a) Richards, I. C.; Thomas, P. S. Pestic. Sci. 1990, 30, 275.
(b) Wolf, W. M. J. Mol. Struct. 1999, 474, 113. (c) Otzen,
T.; Wempe, E. G.; Kunz, B.; Bartels, R.; Yvetot, G. L.;
Hansel, W.; Schaper, K.-J.; Seydel, J. K. J. Med. Chem.
2004, 47, 240.
(3) Faucher, A.-M.; White, P. W.; Brochu, C.; Maitre, C. G.;
Rancourt, J.; Fazal, G. J. Med. Chem. 2004, 47, 18.
(4) Oae, S. Organic Sulfur Chemistry; CRC Press: Boca Raton
FL, 1992, Chap. 4.
(5) Simpkins, N. S. Sulfones in Organic Synthesis in
Tetrahedron Organic Chemistry Series, Vol. 10; Baldwin, J.
E.; Magnus, P. D., Eds.; Pergamon: Oxford, 1993, Chap. 2.
(6) (a) Graybill, B. M. J. Org. Chem. 1967, 32, 2931. (b) Ueda,
M.; Uchiyama, K.; Kano, T. Synthesis 1984, 323.
(7) (a) Oae, S. Organic Sulfur Chemistry; CRC Press: Boca
Raton FL, 1992, Chap. 6. (b) Nara, S. J.; Harjani, J. R.;
Salunkhe, M. M. J. Org. Chem. 2001, 66, 8616. (c) Frost,
C. G.; Hartley, J. P.; Whittle, A. J. Synlett 2001, 830.
(d) Bandgar, B. P.; Kasture, S. P. Synth. Commun. 2001, 31,
1065.
(8) (a) Narkevitch, V.; Schenk, K.; Vogel, P. Angew. Chem. Int.
Ed. 2000, 39, 1806. (b) Narkevitch, V.; Megevand, S.;
Schenk, K.; Vogel, P. J. Org. Chem. 2001, 66, 5080.
(c) Bouchez, L.; Vogel, P. Synthesis 2002, 225. (d) Huang,
X.-G.; Vogel, P. Synthesis 2002, 232. (e) Narkevitch, V.;
Vogel, P.; Schenk, K. Helv. Chim. Acta 2002, 85, 1674.
(f) Bouchez, L. C.; Dubbaka, S. R.; Turks, M.; Vogel, P. J.
Org. Chem. 2004, 69, 6413. (g) Bouchez, L. C.; Turks, M.;
Bubbaka, S. R.; Fonquerne, F.; Craita, C.; Laclef, S.; Vogel,
P. Tetrahedron 2005, 61, 11473. (h) Bouchez, L. C.; Craita,
C.; Vogel, P. Org. Lett. 2005, 7, 897.
In conclusion, a facile, recyclable, and clean synthesis of
alkylaryl and diaryl sulfones using catalytic amount of
Cu(OAc)2 in ionic liquids at room temperature in short re-
action times without any additive has been developed via
cross-coupling of arylboronic acids with sodium sulfinate
salts. The simplicity of operation, mild conditions, easy
recyclability of the catalyst and the environmentally be-
(9) Gilman, H.; Beaver, N. J.; Meyers, C. H. J. Am. Chem. Soc.
1925, 47, 2047.
(10) Baarschers, W. H. Can. J. Chem. 1976, 54, 3056.
Synlett 2008, No. 10, 1455–1458 © Thieme Stuttgart · New York