Angewandte
Chemie
substitution. This first reaction is presumably the slower step
and may be considered as an initiation process that generates
trifluoromethanesulfonic acid and sulfoxide 3. The acid thus
formed may then lead to sulfoxide 3 by the intermediate 6, as
shown in our earlier work.[11] The second part of the
mechanism is presumed to be analogous to the one proposed
process for routine laboratory applications. We are currently
applying this methodology to more elaborate aromatic
compounds, especially biphenyl derivatives, to synthesize
new and hopefully more reactive reagents.
by Shreeve and co-workers (Scheme 2). At this point, the Experimental Section
General procedure for the synthesis of sulfonium compounds as
requisite two equivalents of acid necessary for the twofold
protonation of potassium trifluoromethanesulfinate (to give
6) are produced by the propagation reaction. Some exper-
imental observations are in favor of this mechanism. The
reaction is inhibited by a base such as 2,6-di-tert-butyl-4-
methylpyridine. Moreover, in some cases, small quantities of
sulfoxide are isolated from the reaction mixture. This last
point will be discussed later. The global equation shows that
trifluoromethanesulfonic acid does not appear in the reaction
equation. The stoichiometry used for the reagents (one
equivalent for each) may appear to be in contradiction with
this equation. Nevertheless, these conditions gave the best
results with respect to the yield of isolated product.[14]
In addition to the aromatic starting material, fine analysis
of the crude mixture has revealed the presence of small
quantities of aryl trifluoromethyl sulfoxides 3 (as mentioned
above), but also reduced aryl trifluoromethyl sulfides, in
larger quantities. Part of the aryl trifluoromethyl sulfoxide
seems to be reduced in situ, presumably by trifluoromethane-
sulfonic anhydride. This reagent is better known for its
oxidative properties,[13a,15] but some examples of its reducing
power have been reported.[13b,16] To the best of our knowledge,
no explanation has been proposed yet for this behavior.[17]
This reduction process is peculiarly illustrated by the
formation of trifluoromethylthio-substituted sulfonium 7 by
treatment of sulfoxide 4 with an excess of neat trifluorome-
thanesulfonic anhydride (Scheme 5).
exemplified by the preparation of 1b: Benzene (1.14 mL, 12.8 mmol,
1 equiv) and trifluoromethanesulfonic anhydride (2.14 mL,
12.8 mmol, 1 equiv) were added under argon to a suspension of
potassium trifluoromethanesulfinate (2.2 g, 12.8 mmol) in dichloro-
methane (2 mL, 64 mmol, 5equiv). The reaction mixture is filtered
after 16 h, diluted with CH2Cl2 (30 mL), washed with water (3
10 mL), dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
using dichloromethane/methanol (90:10) as the eluent to give 1.76 g
(70%) of a slightly colored powder. Recrystallization from pentane/
ethyl acetate (2:8) afforded 1.5g (60%) of 1b as a white solid.
M.p. 99.6–1008C; 1H NMR (CDCl3, 200 MHz): d = 8.27 (d, J =
8.8 Hz, 4H), 7.8 ppm (d, 4H); 19F NMR (CDCl3, 188 MHz): d =
À50.7 (m, 3F, SCF3), À79.0 ppm (m, 3F, SO2CF3); 13C NMR
(CDCl3, 75MHz): d = 145.0, 134.6, 132.7, 123.0 (q, J = 328.2, CF3),
120.6 (q, J = 320.0, CF3), 114.8 ppm; pos. ESI MS: (m/z): 323 [M+];
elemental analysis (%) calcd for C14H8Cl2F6O3S2: C 35.53, H 1.70;
found: C 35.51, H 1.69.[18]
Received: October 25, 2005
Published online: January 17, 2006
Keywords: electrophiles · reaction mechanisms ·
.
sulfonium salts · trifluoromethyl substituents
[1] a) R. E. Banks, B. E. Smart, J. C. Tatlow in Organofluorine
Chemistry, Principles and Commercial Applications, Plenum,
New York, 1994; b) B. E. Smart, J. Fluorine Chem. 2001, 109, 3 –
11.
[2] a) K. L. Kirk in Biochemistry of Halogenated Organic Com-
pounds (Ed.: E. Frieden), Plenum, New York, 1991; b) F. M. D.
Ismail, J. Fluorine Chem. 2002, 118, 27 – 33; c) H.-J. Böhm, D.
Banner, S. Bendels, M. Kansy, B. Kuhn, K. Müller, U. Obst-
Sander, M. Stahl, ChemBioChem 2004, 5, 637 – 643.
[3] P. Jeschke, ChemBioChem 2004, 5, 570 – 589.
[4] P. Kirsch in Modern Fluoroorganic Chemistry: Synthesis, Reac-
tivity, Applications, Wiley-VCH, Weinheim, 2004.
[5] a) J. T. Welch, S. Eswarakrishnan in Fluorine in Bioorganic
Chemistry, Wiley, New York, 1991; b) T. Hiyama in Organo-
fluorine Compounds, Chemistry and Applications, Springer,
Berlin, 2000; c) M.A. McClinton, D. A. McClinton, Tetrahedron
1992, 48, 6555 – 6666.
[6] T. Umemoto, Chem. Rev. 1997, 97, 1757 – 1777.
[7] L. M. Yagupolskii, N. V. Kondratenko, G. N. Timofeeva, J. Org.
Chem. USSR 1984, 20, 103 – 105.
[8] J. J. Yang, R. L. Kirchmeier, J. M. Shreeve, J. Org. Chem. 1998,
63, 2656 – 2660.
[9] a) T. Umemoto, S. Ishihara, J. Am. Chem. Soc. 1993, 115, 2156 –
2164; b) T. Umemoto, S. Ishihara, J. Fluorine Chem. 1998, 92,
181 – 187.
Scheme 5. Preparation of sulfonium 7 in neat Tf2O.
We suppose that in the first step one equivalent of
sulfoxide is reduced to its corresponding sulfide, which can
further react with an activated form of the sulfoxide to
generate the observed sulfonium 7 (see Scheme 2). We have
no experimental evidence for such a mechanism, except the
isolation (besides 7) of nonpolar sulfide derivatives, which
result from the reduction of phenyltrifluoromethyl sulfoxide 4
in the reaction medium. Nevertheless, this reaction consti-
tutes a new route to interesting sulfonium derivatives and can
be generalized to prepare various aryl trifluoromethyl
sulfoxides.
[10] T. Umemoto, S. Ishihara, Tetrahedron Lett. 1990, 31, 3579 – 3582.
[11] C. Wakselman, M. Tordeux, C. Freslon, L. Saint-Jalmes, Synlett
2001, 4, 550 – 552.
[12] Sodium or potassium trifluoromethanesulfinate could be inter-
changeably used without influence on the yield.
In summary, we have developed a very short and efficient
synthesis of aryl trifluoromethyl sulfonium salts, important
electrophilic trifluoromethylating reagents. Our strategy
allows the preparation of target compounds in a one-pot
[13] a) G. Maas, P. Stang, J. Org. Chem. 1981, 46, 1606 – 1610; b) T.
Netscher, P. Bohrer, Tetrahedron Lett. 1996, 37, 8359 – 8362.
Angew. Chem. Int. Ed. 2006, 45, 1279 –1282
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