nium (1) and S-(trifluoromethyl)diphenylsulfonium salts (2)
constitute an important subset of these reagents (Figure 1).
Scheme 1. Preparation of
S-(Difluoromethyl)dibenzothiophenium
Trifluoromethanesulfonate
Figure 1. Electrophilic trifluoromethylating agents.
They are known to be powerful electrophilic trifluoromethy-
lation agents, which are successfully used for the trifluo-
romethylation of a wide range of substrates differing in
reactivity.6 However, neither S-(difluoromethyl)dibenzothiophe-
nium nor S-(difluoromethyl)diphenylsulfonium salts have
been previously reported. Our aim was to explore the
chemistry of these compounds and ascertain their use as
electrophilic difluoromethylating reagents. Herein, we wish
to report the results of our studies toward the synthesis of
S-(difluoromethyl)dibenzothiophenium triflate and S-(dif-
luoromethyl)diphenylsulfonium tetrafluoroborate and dem-
onstrate the effectiveness of these reagents in electrophilic
difluoromethylation reactions.
cation. This is supported by the fact that after the solvent
was removed a quantitative amount of dibenzothiophene (9)
was recovered. To support the formation of the S-(difluo-
romethyl)dibenzothiophenium cation, the cyclization reaction
was repeated at -80 °C and the reaction mixture was
monitored by low-temperature 19F NMR. Under these
circumstances, no trace of difluoromethyl trifluoromethane-
sulfonate was detected. However, a doublet observed at
-101.7 ppm in the 19F NMR having J ) 56.8 Hz as the
coupling constant indicates the formation of an S-(difluo-
romethyl)dibenzothiophenium cation. In 2 h at - 80 °C, the
conversion was 15% relative to the sulfoxide. Apart from
the doublet and the starting material’s signals, no other
signals were observed in the 19F NMR spectrum.
To compare the reactivity of the S-difluoromethyl(diben-
zothiophenium) cation to that of the S-trifluoromethyl-
(dibenzothiophenium) cation, any report of the reaction of
the latter with a triflate anion was checked in the literature.
It was found that in the case of S-(trifluoromethyl)diben-
zothiophenium triflate a high temperature of 200 °C is
required to transfer the trifluoromethyl group to the triflate
anion.6b
Having established the instability of S-(difluoromethyl)-
dibenzothiophenium triflate at room temperature (the cation
is too reactive towards the anion), a different approach was
pursued.6f Considering the fact that in the case of S-
trifluoromethyl sulfonium cations the S-(trifluoromethyl)-
diphenylthiophenium salts (2) are less reactive than the
appropriate S-(trifluoromethyl)dibenzothiophenium ones (1),
we decided to prepare an S-(difluoromethyl)diphenylsulfo-
nium derivative.
2-[(Difluoromethyl)sulfinyl]bromobenzene (6) was reacted
in benzene with triflic anhydride at 0-5 °C. Aside from the
unreacted sulfoxide, a significant amount of difluoromethyl
trifluoromethanesulfonate was identified by 19F NMR, after
2 h of stirring. A multiplet at -98 ppm having a pattern
Our first target was the preparation of S-(difluoromethyl)-
dibenzothiophenium triflate (8) (Scheme 1). 2-[(Difluorom-
ethyl)sulfanyl]biphenyl (5) was prepared by reacting 2-bro-
mothiophenol (3) with difluorochloromethane followed by
Suzuki coupling of the resulting sulfide (4)7 with phenyl-
boronic acid. 2-[Difluoromethyl(sulfinyl)]biphenyl (7) was
obtained from the oxidation of the sulfide with m-chlorop-
erbenzoic acid. An alternative reaction pathway consisting
of oxidation of 2-(difluoromethylsulfanyl)bromobenzene (4)
followed by Suzuki reaction also proved to be successful.
However, in the latter case, the overall yield was lower.
Cyclization of the sulfoxide (7) was carried out by addition
of triflic anhydride to the solution in dichloromethane at 0
°C.6b The reaction mixture was allowed to warm to room
temperature, and after 2 h of stirring, it was analyzed by 19
F
NMR. Surprisingly, in spite of the fact that only a trace
amount of sulfoxide (7) was detected, difluoromethyl trif-
luoromethanesulfonate (10) was identified as a major product
instead of the expected sulfonium compound (8). Formation
of the difluoromethyl ester of triflic acid can be explained
by the in situ difluoromethylation of the trifluoromethylsul-
fonyl anion by the S-(difluoromethyl)dibenzothiophenium
(6) (a) Yagupol’skii, L. M.; Kondratenko, N. Y.; Timofeeva, G. N. Zh.
Org. Khim. 1984, 20, 115-118. (b) Umemoto, T.; Ishihara, S. J. Am. Chem.
Soc. 1993, 115, 2156-2164. (c) Umemoto, T.; Ishihara, S.; Adachi, K. J.
Fluorine Chem. 1995, 74, 77-82. (d) Umemoto, T.; Ishihara, S. J. Fluorine
Chem. 1999, 98, 75-81. (e) Umemoto, T.; Adachi, K. J. Org. Chem. 1994,
59, 5692-5699. (f) Yang, J. J.; Kirchmeier, R. L.; Shreeve, J. M. J. Org.
Chem. 1998, 63, 2656-2660. (g) Ma, J.-A.; Cahard, D. J. Org. Chem. 2003,
68, 8726-8729.
(7) Endel’man, E. S.; Danilenko, V. S.; Trinus, F. P.; Yufa, P. A.;
Fadeicheva, A. G.; Muravov, I. I.; Fialkov, Y. A.; Yagupol’skii, L. M.
Khim.-Farm. Zh. 1973, 7, 15-19.
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