O
S
3. Conclusions
SO2Cl
SO2CF3
2a (
20 mmol)
Na2SO3, NaHCO3
H2O, 80 oC, 4 h
ONa
DMSO
25 oC, 0.5 h
O2N
O2N
In summary, we have developed a simple and effective
procedure for the practical preparation of aryl trifluoromethyl
sulfones from readily available arylsulfonyl chlorides and safe
Umemoto’s reagent II under mild conditions. By means of this, a
series of aryl trifluoromethyl sulfones could be synthesized in
high yields. Thus, this approach may lead to many aryl
trifluoromethyl sulfones which are important structural motifs of
biologically active, chiral catalysts, and functional materials. The
exploration of further applications of this method is ongoing in
our lab.
O2N
1k
3k
6.65g, 30 mmol
3.83g, 15 mmol, 75%
Scheme 2. Gram-scale synthesis of 3k.
To demonstrate the practicability and scalability of our
method, a gram-scale reaction was performed with 1k and 2a
under the optimized conditions. To our delight, the present
reaction provided 4-nitrophenyl trifluoromethyl sulfone 3k in 75%
yield (3.83 g), indicating an excellent potential application for
large scale synthesis (Scheme 2).
O
S
O
SO2Cl
step 1) Na2SO3, NaHCO3
step 2) TEMPO (2.0 equiv.)
CF3
+
N
(1)
OCF3
2a
(1.0 equiv.)
Conflicts of interest
1a
3a (
8%)
4
(54%)
There are no conflicts to declare.
OH
O
S
O
CF3
SO2Cl
step 1) Na2SO3, NaHCO3
CF3
+
(2)
step 2) hydroquinone (2.0 equiv.)
Acknowledgments
2a
(1.0 equiv.)
OH
1a
3a (
8%)
5,
detected by LC-MS
CF3
These investigations were supported by Zhejiang Jiuzhou
Pharmaceutical Co. Ltd. We thank Dr. Teruo Umemoto for
technical instruction for the reaction with his Umemoto’s reagent
and for reviewing the manuscript.
Ph
Ph
O
S
O
SO2Cl
step 1) Na2SO3, NaHCO3
step 2) DPE (2.0 equiv.)
6,
detected by LC-MS
CF3
(3)
+
O
O
S
References and notes
2a
(1.0 equiv.)
Ph
1a
3a
(6%)
Ph
Ph
(28%)
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7
Scheme 3. Experiment for mechanistic study.
To gain an insight into the reaction mechanism, several
control experiments were carried out (Scheme 3). When 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO) and hydroquinone were
added as radical scavengers, CF3 radical was trapped and the
trifluoromethylation reaction was greatly retarded (Scheme 3, eq.
1 and eq. 2) [13]. Significantly, when 1,1-diphenylethylene (DPE)
was added, phenylsulfonyl-coupling product 7 [14] was isolated
in 28% yield (Scheme 3, eq. 3). This strongly indicated that
phenylsulfonyl radical was generated in the reactions in addition
to the CF3 radical.
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O
O
S
Na2SO3
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Ph
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ONa
2a
1a
4.
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CF3
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S
SET
+
S
Ph
CF3
O
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3a
CF3
Ph
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III
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Ph
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I
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Scheme 4. Proposed mechanism.
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proposed as seen in Scheme 4. Sodium benzenesulfinate
resulting from 1a [15] undertakes counteranion-replacement with
2a to give ion pair I [16], since the sulfinate anion is much more
nucleophilic than triflate anion. Then, I provides a CF3 radical
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