Regioselective electrochemical monofluorination of α-sulfonyl sulfides

Article abstract of DOI:10.1055/s-2008-1078498

Highly regioselective monofluorination of α-sulfonyl sulfides was successfully carried out using anodic oxidation to provide the corresponding α-fluorinated products in moderate yields. The fluorinated products would be versatile fluorine-containing build

Full text of DOI:10.1055/s-2008-1078498

1714
LETTER
Regioselective Electrochemical Monofluorination of a-Sulfonyl Sulfides
Monofluorination
i
of
a
-S
u
r
lfonyl
S
o
ulfides katsu Nagura, Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502, Japan
Fax +81(45)9245406; E-mail: fuchi@echem.titech.ac.jp
Received 14 February 2008
Table 1 Oxidation Potentials (Edox) of a-Sulfonyl Sulfidesa
Abstract: Highly regioselective monofluorination of a-sulfonyl
sulfides was successfully carried out using anodic oxidation to pro-
vide the corresponding a-fluorinated products in moderate yields.
The fluorinated products would be versatile fluorine-containing
building blocks.
O
O
S
S
R1
R3
R2
Compd
1a
R1
R2
H
R3
Edox (vs. SCE)
1.88
Key words: sulfones, fluorine, electron transfer, oxidation, cations
Me
p-Tol
p-Tol
p-Tol
p-Tol
Me
2a
Me
F
>2.30
1.84
The development of efficient methodology for fluorina-
tion of organic molecules has been increasingly important
since a number of organofluorine compounds are known
to show unique chemical, physical, and biological proper-
ties.1 Particularly, a-fluoro sulfides have attracted much
interest since they can be readily converted to various use-
1b
Me
Me
Cl
H
1c
Me
2.06
1d
p-Tol
p-Tol
Ph
1.15
ful organofluorine compounds.2 a-Fluorination of sulfides 2d
F
Me
1.44
has been carried out using various reagents such as (dieth-
1e
H
Ph
1.45
ylamino)sulfurtrifluoride (DAST),3 1-(chloromethyl)-4-
fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluorobo-
rate) (Selectfluor),4 and IF5-Et3N-3HF.5 However, they
are still hazardous, difficult to handle, or very costly. On
the contrary, electrochemical fluorination is an ideal
method because it can be done in one step under safe con-
ditions. Previously, we successfully conducted highly re-
gioselective anodic a-monofluorination of sulfides having
various electron-withdrawing groups such as carbonyl,
ester, cyano, phosphonate, and amide groups at the a-po-
sition to the sulfur atom.6 We proposed a Pummerer-type
mechanism via fluorosulfonium ions as a key intermedi-
ate, and electron-withdrawing groups markedly promoted
the anodic fluorination.7 Considering further molecular
conversion, a sulfonyl group is a very useful electron-
withdrawing group because it can be easily substituted af-
ter the fluorination.8 With these facts in mind, we studied
electrochemical fluorination of a-sulfonyl sulfides in this
work.
1f
Ph
SPh
H
Ph
1.47
1g
1h
1i
p-Tol
p-Tol
2-Py
Ph
1.54
Me
H
Ph
1.51
Ph
1.80
a 5 mM of sulfide in 0.1 M NaClO4/MeCN, sweep rate: 100 mV/S.
other hand, the oxidation potential of the a-chloro sulfide
1c was higher than 2 V vs. SCE. Moreover, a-fluoro sul-
fide 2a has a much higher oxidation potential than 1c due
to a stronger electron-withdrawing fluorine atom com-
pared with a chlorine atom.
In contrast, an electron-donating methyl group decreased
slightly the oxidation potential as shown in the cases of 1b
and 1h. However, introduction of an easily oxidizable
phenylthio group to the a-position of sulfide 1e did not de-
crease the oxidation potential as observed in the case of
1f.
First, the oxidation potentials of the sulfides having sulfo-
nyl groups, 1a–i,9 and 2a,d were measured by cyclic vol-
tammetry in anhydrous acetonitrile.10 The oxidation
potentials (decomposition potential, Edox) are summarized
in Table 1. Except for 1d, the sulfides having a sulfonyl
group were found to be oxidized at more positive poten-
Next, we investigated anodic monofluorination of meth-
ylthiomethyl p-tolyl sulfone (1a),11 which is a well-known
useful synthetic reagent,12 under various electrolytic con-
ditions as shown in Table 2.
tials than methyl phenyl sulfide (Edox: 1.25 V vs. SCE), Desired monofluorinated product 2a was formed in mod-
owing to the electron-withdrawing sulfonyl group. Aro- erate yield at 3 F/mol of electricity under conventional an-
matic sulfides 1d–i and 2d were more easily oxidized odic fluorination conditions (0.37
M
Et3N-3HF/
compared with aliphatic sulfides 1a–c and 2a. On the acetonitrile) as reported previously (entry 1).7 In this case,
15% of starting 1a still remained although the desired flu-
orinated product was obtained in moderate yield. Then, 4
F/mol of electricity was passed under the same conditions.
However, 1a was not consumed completely and the yield
SYNLETT 2008, No. 11, pp 1714–1718
Advanced online publication: 11.06.2008
DOI: 10.1055/s-2008-1078498; Art ID: U01008ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
8

LETTER
Monofluorination of a-Sulfonyl Sulfides
Table 3 Fluorination of a-Sulfonyl Sulfides
1715
Table 2 Fluorination of Methylthiomethyl p-Tolyl Sulfone (1a)
F–
F–
Et4NF-4HF, DME
Pt/Pt
10 mA/cm2
Pt/Pt
O
O
O O
10 mA/cm2
– 2e, – H+
O
O
O
O
S
S
S
S
S
S
S
S
R1
R3
R1
R3
– 2e, – H+
F
F
R2
R2
1a–i
1a
(0.1 M)
2a
2a–i
Compd R1
R2
R3
Product
Charge passed Yield
(F/mol)
Entry Solvent Supporting electrolyte Charge passed
(F/mol)
Yield
(%)a
(%)a
1a
1b
1c
1d
1e
1f
Me
Me
H
p-Tol 2a
2
2
2
2
2
2
2
2
4
58
1
2
3
4
5
6
MeCN Et3N-3HF (0.37 M)
MeCN Et4NF-4HF (0.15 M)
CH2Cl2 Et3N-3HF
3
4
2
2
2
2
55
Me p-Tol 2b
42b
12c
44
64
Me
Cl
H
p-Tol 2c
30
p-Tol
Ph
Me
Ph
2d
2e
2f
CH2Cl2 Et4NF-4HF
0
H
52
DME
DME
Et3N-3HF
23
Ph
SPh Ph
Ph
51
Et4NF-4HF
66 (58)
a Determined by 19F NMR. Isolated yield is shown in parentheses.
1g
1h
1i
p-Tol
H
2g
2h
2i
52
p-Tol Me Ph
2-Py Ph
45
of 2a did not increase. Since Et3N-3HF is rather easily ox-
idized, Et3N-3HF seems to be oxidized simultaneously
during the anodic oxidation of 1a. Therefore, anodically
more stable Et4NF-4HF was employed instead of Et3N-
3HF for the anodic fluorination (entry 2). When 4 F/mol
of electricity was passed, the stating 1a was completely
consumed and the yield of 2a was increased to 64%.
H
55
a Isolated yield.
b a-(Fluoromethylthio)ethyl p-tolyl sulfone: p-TolSO2CHMeSCH2F
(4) was formed in 26% yield.
c Starting material (65%) was recovered.
with the recovered starting material (13%) and many
byproducts. Therefore, electrochemical fluorination is
much more efficient for the preparation of a-fluoro-a-sul-
fonyl sulfides compared with a chemical method.
In our previous reports, anodic difluorination of sulfides
having an electron-withdrawing group such as ester, phos-
phonate, and cyano groups at a to the sulfur atom was suc-
cessfully carried out with high current efficiencies using a
Et4NF-4HF as a fluorine source in acetonitrile.13 Howev-
er, difluorinated product was not obtained at all under the
similar conditions (entry 2). This is as due to the high ox-
idation potential of monofluorinated product 2a
(Edox > 2.30 V vs. SCE), which prevented the further oxi-
dation of 2a.
We extended this fluorination system to other sulfides 1b–
i.11 The results are summarized in Table 3. The desired
monofluorinated products were obtained exclusively in
moderate yields in the cases of 1d–i. Since the oxidation
potential of a-fluoro-a-(p-tolylthio)methyl methyl sul-
fone (2d) is more positive by ca. 0.3 V compared with 1d,
difluorinated product was not obtained in the anodic fluo-
rination of 1d. It seems that the oxidation of 1d proceeded
efficiently in Et4NF-4HF/DME system and 1d was com-
pletely consumed at the theoretical amounts of electricity.
Consequently, oxidation of 2d did not occur. We also
tried difluorination of 1d in Et4NF-4HF/MeCN system
which is suitable for anodic difluorination.13 After 4 F/
mol of charge was passed, difluorination product 3 was
obtained in 11% yield along with monofluorinated prod-
uct 2d (7%) and byproducts such as (p-TolS)2 (43%).
Therefore, the oxidation of 1d is possible, however, not
efficient.
Dichloromethane was not suitable as a solvent for the
fluorination reaction (entries 3 and 4). Particularly, when
Et4NF-4HF was used, unidentified insoluble product was
formed on the surface of the anode resulting in no forma-
tion of 2a. Next, we used dimethoxyethane (DME) as a
solvent (entries 5 and 6). When Et3N-3HF was used, fluo-
rination did not proceed efficiently. However, when
Et4NF-4HF was employed, 1a was mostly consumed at
theoretical amount of electricity (2 F/mol) for monofluori-
nation, and 2a was formed in good yield. Previously, we
demonstrated that DME enhances the nucleophilicity of a
fluoride ion,14 which resulted in increase of the yield. In
all cases except for entry 4, byproducts such as MeSSMe
were obtained. This suggests that the oxidative degrada-
tion of 1a occurred simultaneously during anodic fluori-
nation, which resulted in the moderate yield of 2a. Thus,
we found that Et4NF-4HF/DME is the best system for the
fluorination. In contrast, fluorination of 1a using NaH and
Selectfluor provided 2a in extremely low yield (9%) along
Previously, we reported the fluorination of dithioacetals
of aldehydes.15 In these cases, fluorodesulfurization took
place selectively and no a-fluorination occured. In con-
trast, fluorodesulfurization did not take place at all in the
case of a,a-di(phenylthio)methyl phenyl sulfone (1f). We
also disclosed that the use of a bromide ion was effective
for fluorodesulfurization.16 Therefore, we tried indirect
Synlett 2008, No. 11, 1714–1718 © Thieme Stuttgart · New York

1716
H. Nagura, T. Fuchigami
LETTER
– 2e
Table 4 Oxidation of Monofluorinated a-Sulfonyl Sulfides
O
O
O
O O
O
Br–
Br+
MCPBA (2.2 equiv)
S
S
S
S
R1
R2
O
O
O
F
O
R1
R2
O
O
CH2Cl2
r.t., over night
PhS
S
PhS
S
+
PhS
PhS
S
F
F
Ph
Ph
Et3N·3HF,
Ph
CH2Cl2 (0.22 M)
1.5 F/mol
Pt/Pt
F
H
PhS
H
Compd
2a
R1
R2
Product
5a
Yield (%)a
1f
(20 mM)
2e
0%
2f
36%
3 mA/cm2
Me
p-Tol
Ph
90
determined by 19F NMR
2e
Ph
5e
85
Scheme 1 Indirect electrolysis of a,a-di(phenylthio)methyl phenyl
sulfone (1f) using Br– mediator
2g
p-Tol
2-Py
Ph
5g
Quant.
30
2i
Ph
5i
O
O
S
S
S
F–
bHF
F–
aH3C
p-Tol
a Isolated yield.
O
O
Me
O
–
S
S
1b
aH3C
p-Tol
This seems to be as due to its high oxidation potential (Ed:
2.06 V vs. SCE).
– e
Me bH
O
S
A
–
aHF
aH2C
p-Tol
In order to demonstrate further molecular conversion of
the fluorinated products, the oxidation of monofluorinated
products 2a, 2e, 2g, and 2i was demonstrated by using m-
chloroperbenzoic acid (MCPBA, Table 4).18 Desired sul-
fones (5a, 5e, and 5g) were formed in excellent yields.
However, 4i was obtained in low yield since other oxida-
tion products such as sulfoxide and N-oxide were formed
as byproducts. Thus prepared a-fluoro disulfones 4 are
known to be useful synthetic equivalents for the monoflu-
oromethide species since Shibata et al. successfully used
a-fluoro disulfone for asymmetric monofluoromethyla-
tion.19 a-Fluoro disulfones have been prepared by the re-
action of disulfones with hazardous fluorine gas or a
costly reagent, Selectfluor.19 In contrast, our new synthet-
ic method is quite safe and can be applied to large-scale
experiments.
Me bH
O
O
O
O
S
S
F–
S
S
1a
aH3C
p-Tol
aH3C
p-Tol
– e
–
bHF
Hb bH
bH
B
Scheme 2 Regioselectivity of deprotonation of anodically formed
cation radical intermediates of 1b and 1a
electrolysis of 1f by using Et4NBr (1 mM) as a bromide
ion mediator (Scheme 1). However, the fluorodesulfur-
ization product 2e was not detected at all and 2f was
formed in 36% yield (determined by 19F NMR). Deproto-
nation of the cation radical intermediate of 1f seems to be
enhanced by the strong electron-withdrawing effect of the
sulfone group, which provides 2f predominantly.
In conclusion, we successfully carried out selective
monofluorination of a-sulfonyl sulfides by using an elec-
trochemical methodology. This electrochemical method
is more efficient for the preparation of a-fluoro-a-sulfonyl
sulfides compared with the chemical method using NaH
and Selectfluor. The fluorinated products are expected to
be useful fluorine-containing building blocks as exempli-
fied by the oxidative conversion of a-fluoro-a-sulfonyl
sulfides to the corresponding a-fluorinated disulfones,
which are useful as a monofluoromethylation regent.
Their other synthetic application is also currently under
way.
On the other hand, anodic fluorination of 1-(methyl-
thio)ethyl p-tolyl sulfone (1b) provided two monofluori-
nated products, a-fluoro-a-methylthioethyl p-tolyl
sulfone (2b) and (a-fluoromethylthio)ethyl p-tolyl sul-
fone (4) in 42% and 26% yields, respectively. It is well
known that the regioselectivity of anodic substitutions of
heteroatom compounds like amines and sulfides is gener-
ally controlled by kinetic acidity of an a-proton of their
cation radicals.17 In the case of anodic fluorination of 1b,
the introduction of an electron-donating methyl group to
the a-position to the sulfur atom of 1a decreases the kinet-
ic acidity of the a-methyne proton (bH, Scheme 2). There-
Acknowledgment
b
fore, the elimination of H of cation radical intermediate
A becomes much slower compared with that of cation rad- The authors thank Ms. M. Ishikawa of Center for Advanced Mate-
rials Analysis (Suzukakedai), Technical Department, Tokyo Insti-
tute of Technology, for HRMS analysis and Morita Chemical
Industries Co. Ltd. for generous gifts of Et3N-3HF and Et4NF-4HF.
ical intermediate B (Scheme 2). Consequently, elimina-
tion of aH of cation radical intermediate A also takes place
simultaneously.
The fluorination of 1-chloro-1-methylthiomethyl p-tolyl
References and Notes
sulfone (1c) did not proceed well and 65% of 1c was re-
covered. Even when 3 F/mol of electricity was passed, the
yield of 2c did not increase and 57% of 1c was recovered.
(1) (a) Biomedicinal Aspects of Fluorine Chemistry; Filler, R.;
Kobayashi, Y., Eds.; Kodansha and Elsevier Biomedical:
Tokyo, 1982. (b) Welch, J. T.; Eswarakrishnan, S. Fluorine
in Bioorganic Chemistry; Wiley: New York, 1991.
Synlett 2008, No. 11, 1714–1718 © Thieme Stuttgart · New York

LETTER
Monofluorination of a-Sulfonyl Sulfides
(11) Anodic Fluorination of Sulfides
1717
(2) (a) Furuta, S.; Hiyama, T. Tetrahedron Lett. 1996, 37, 7983.
(b) Murakami, S.; Fuchigami, T. Synlett 2006, 1015.
(c) Nagura, H.; Murakami, S.; Fuchigami, T. Tetrahedron
2007, 63, 10237.
(3) Solas, D.; Hale, R. L.; Patel, D. V. J. Org. Chem. 1996, 61,
1537.
(4) Banks, R. E.; Lawrence, N. J.; Popplewell, A. L. J. Chem.
Soc., Chem.Commun. 1994, 343.
(5) Ayuba, S.; Yoneda, N.; Fukuhara, T.; Hara, S. Bull. Chem.
Typical anodic fluorination conditions are as follows:
Electrolysis was conducted with a platinum anode and
cathode [4 cm2 (2 × 2 cm)] in 0.15 M Et4NF-4HF/DME (10
mL) containing 1.0 mmol of sulfides using an undivided cell
at ambient temperature. After the starting sulfide was mostly
consumed (monitored by SiO2 TLC), the electrolysis
solution was passed through a short column of SiO2
(CHCl3). The solvent was then removed by evaporation and
residue was purified by column chromatography on SiO2
(hexane–EtOAc, 10:1 to 5:1 or CHCl3) to provide the
desired fluorinated product.
Soc. Jpn. 2002, 75, 1597.
(6) (a) Fuchigami, T.; Shimojo, M.; Konno, A. J. Org. Chem.
1995, 60, 3459. (b) Cao, Y.; Hidaka, A.; Tajima, T.;
Fuchigami, T. J. Org. Chem. 2005, 70, 9614. (c) Tajima,
T.; Nakajima, A.; Fuchigami, T. J. Org. Chem. 2006, 71,
1436. (d) Zagipa, B.; Hidaka, A.; Cao, Y.; Fuchigami, T.
J. Fluorine Chem. 2006, 127, 552. (e) Tajima, T.;
Nakajima, A.; Doi, Y.; Fuchigami, T. Angew. Chem. Int. Ed.
2007, 46, 3550.
(7) Fuchigami, T.; Konno, A.; Nakagawa, K.; Shimojo, M.
J. Org. Chem. 1994, 59, 5937.
(8) (a) Trost, B. M.; Ghadiri, M. R. J. Am. Chem. Soc. 1984, 106,
7260. (b) Trost, B. M. Bull. Chem. Soc. Jpn. 1988, 61, 107.
(c) Najera, C.; Jus, M. Tetrahedron 1999, 55, 10547.
(9) Preparation of a,a-Di(phenylthio)methyl Phenyl Sulfone
(1f)
a-Fluoro-a-methylthiomethyl p-Tolyl Sulfone (2a)
1H NMR (270 MHz, CDCl3): d = 7.84 (d, J = 8.2 Hz, 2 H),
7.40 (d, J = 8.2 Hz, 2 H), 5.99 (d, J = 47.6 Hz, 1 H), 2.47 (s,
3 H), 2.43 (d, J = 2.1 Hz, 3 H). 13C NMR (68 MHz, CDCl3):
d = 145.98, 132.23, 129.84, 129.41, 106.12 (d, J = 262.7
Hz), 21.79, 12.45 (d, J = 2.2 Hz). 19F NMR (254 MHz,
CDCl3, TFA): d = –82.0 (d, J = 47.6 Hz). HRMS–FAB: m/z
[M + Na+] calcd for C9H11FO2S2Na: 257.0082; found:
257.0086.
a-Fluoro-a-methylthioethyl p-Tolyl Sulfone (2b)
1H NMR (270 MHz, CDCl3): d = 7.84 (d, J = 8.1 Hz, 2 H),
7.38 (d, J = 8.1 Hz, 2 H), 2.47 (s, 3 H), 2.38 (s, 3 H), 1.80 (d,
J = 19.6 Hz, 3 H). 13C NMR (68 MHz, CDCl3): d = 145.63,
130.94, 130.26 (d, J = 1.1 Hz), 129.59, 112.88 (d, J = 261.0
A solution of methyl phenyl sulfone (1.58 g, 10.1 mmol) in
dry THF (40 mL) was treated with n-BuLi (6.25 mL, 1.6 M
hexane solution) at –78 °C under a nitrogen atmosphere.
After stirring of the solution for 10 min at –78 °C, a solution
of diphenyl disulfide (1.08 g, 5.0 mmol) in dry THF (10 mL)
was added slowly at –78 °C. After additional 3 h of stirring,
the solution was treated with 1 M aq HCl (50 mL) and
extracted with EtOAc (2 × 100 mL). The combined extracts
were washed with brine and dried over anhyd Na2SO4. After
the removal of the solvent by evaporation, the residue was
purified by column chromatography on SiO2 (hexane–
EtOAc, 6:1) to yield 0.93 g (50%) of a,a-di(phenyl-
thio)methyl phenyl sulfone (1f). 1H NMR (270 MHz,
CDCl3): d = 8.00–7.96 (m, 2 H), 7.69–7.63 (m, 1 H), 7.56–
7.50 (m, 2 H), 7.40–7.23 (m, 10 H) 5.12 (s, 1 H). 13C NMR
(68 MHz, CDCl3): d = 136.70, 134.05, 134.02, 131.74,
129.90, 129.16, 129.08, 128.75, 80.78. HRMS (EI): m/z
[M+] calcd for C19H16O2S3: 372.0312; found: 372.0314.
Preparation of Phenyl 2-Pyridylthiomethyl Sulfone (1i)
A solution of 0.61 g (5.5 mmol) of 2-mercaptpyridine in dry
MeCN (10 mL) under a nitrogen atmosphere and cooled to 0
°C was treated with NaH (0.20 g, 5.0 mmol; 60% in liquid
paraffin) in dry MeCN (10 mL). The solution was stirred for
0.5 h at 0 °C, after which time chloromethyl phenyl sulfone
(0.87 g, 4.6 mmol) in dry MeCN (10 mL) was added. After
additional 5 h under reflux, the solution was treated with
H2O (30 mL) and extracted with EtOAc (2 × 30 mL). The
combined extracts were washed with brine and dried over
anhyd Na2SO4. After removal of the solvent by evaporation,
the residue was purified by column chromatography on SiO2
(hexane–EtOAc, 4:1) to yield 0.87 g (71%) of phenyl 2-
pyridylthiomethyl sulfone (1i). 1H NMR (270 MHz, CDCl3):
d = 8.20–8.18 (m, 1 H), 7.93–7.90 (m, 2 H), 7.49–7.36 (m, 4
H), 7.09–7.05 (m, 1 H), 6.95–6.91 (m, 1 H), 4.99 (s, 2 H).
13C NMR (68 MHz, CDCl3): d = 152.78, 148.80, 137.37,
136.22, 133.50, 128.94, 128.31, 122.12, 120.44, 52.39.
HRMS–FAB: m/z [M + H+] calcd for C12H12NO2S2:
266.0309; found: 266.0313.
Hz), 22.51 (d, J = 20.1 Hz), 21.73, 12.87 (d, J = 5.6 Hz). 19
F
NMR (254 MHz, CDCl3, TFA): d = –56.9 (q, J = 19.6 Hz).
HRMS–FAB: m/z [M + Na+] calcd for C10H13FO2S2Na:
271.0239; found: 271.0247.
a-Chloro-a-Fluoro-a-methylthiomethyl p-Tolyl Sulfone
(2c)
1H NMR (270 MHz, CDCl3): d = 7.91 (d, J = 8.6 Hz, 2 H),
7.41 (d, J = 8.6 Hz, 2 H), 2.57 (d, J = 1.3 Hz, 3 H), 2.49 (s,
3 H). 13C NMR (68 MHz, CDCl3): d = 146.73, 131.25 (d,
J = 1.1 Hz), 129.68, 128.94, 122.31 (d, J = 322.5Hz), 21.94,
15.84 (d, J = 3.4 Hz). 19F NMR (254 MHz, CDCl3, TFA):
d = –15.8 (s). HRMS–FAB: m/z [M + Na+] calcd for
C9H10ClFO2S2Na: 290.9692; found: 290.9689.
a-Fluoro-a-(p-tolylthio)methyl Methyl Sulfone (2d)
1H NMR (270 MHz, CDCl3): d = 7.53 (d, J = 7.9 Hz, 2 H),
7.21 (d, J = 7.9 Hz, 2 H), 6.13 (d, J = 51.1 Hz, 1 H), 2.97 (d,
J = 1.5 Hz, 3 H), 2.38 (s, 3 H). 13C NMR (68 MHz, CDCl3):
d = 140.53, 134.54, 134.52, 130.38, 110.26 (d, J = 262.7
Hz), 37.48, 21.37. 19F NMR (254 MHz, CDCl3, TFA):
d = –71.7 (d, J = 51.1 Hz). HRMS (EI): m/z [M+] calcd for
C9H11FO2S2: 234.0184; found: 234.0185.
a-Fluoro-a-phenylthiomethyl Phenyl Sulfone (2e)
1H NMR (270 MHz, CDCl3): d = 8.01–7.98 (m, 2 H), 7.76–
7.71 (m, 1 H), 7.63–7.56 (m, 4 H), 7.41–7.35 (m, 3 H), 6.20
(d, J = 50.9 Hz, 1 H). 13C NMR (68 MHz, CDCl3):
d = 136.74 (d, J = 1.7 Hz), 134.86, 133.94, 133.91, 129.83
(d, J = 1.1 Hz), 129.68, 129.52, 129.20, 110.66 (d, J = 264.9
Hz). 19F NMR (254 MHz, CDCl3, TFA): d = –69.0 (d,
J = 50.9, 7.4 Hz). HRMS (EI): m/z [M+] calcd for
C13H11FO2S2: 282.0184; found: 282.0179.
a-Fluoro-a,a-di(phenylthio)methyl Phenyl Sulfone (2f)
1H NMR (270 MHz, CDCl3): d = 7.96–7.93 (m, 2 H), 7.69–
7.64 (m, 1 H), 7.54–7.45 (m, 2 H), 7.42–7.24 (m, 10 H). 13
C
NMR (68 MHz, CDCl3): d = 136.70 (d, J = 1.1 Hz), 134.59,
134.49, 130.82 (d, J = 1.1Hz), 130.16, 129.19, 128.69,
127.16, 120.26 (d, J = 314.7 Hz). 19F NMR (254 MHz,
CDCl3, TFA): d = –28.6 (s). HRMS–FAB: m/z [M + Na+]
calcd for C19H15FO2S3Na: 413.0116; found: 413.0122.
a-Fluoro-a-(p-tolylthio)methyl Phenyl Sulfone (2g)
1H NMR (270 MHz, CDCl3): d = 7.99 (m, 2 H), 7.76–7.70
(m, 1 H), 7.60 (m, 2 H), 7.47 (d, J = 8.1 Hz, 2 H), 7.17 (d,
(10) Cyclic voltammetry was carried out at a Pt electrode
(0.5 × 0.5 cm2) using a Hokutodenko HA-501 Potentiostat/
Galvanostat.
Synlett 2008, No. 11, 1714–1718 © Thieme Stuttgart · New York

1718
H. Nagura, T. Fuchigami
LETTER
(13) Konno, A.; Fuchigami, T. J. Org. Chem. 1997, 62, 8579.
(14) (a) Hill, S. E.; Feller, D.; Glemdening, E. D. J. Phys. Chem.
A 1998, 102, 3813. (b) Ishii, H.; Yamada, N.; Fuchigami, T.
Tetrahedron 2001, 57, 9067.
(15) Yoshiyama, T.; Fuchigami, T. Chem. Lett. 1992, 21, 1995.
(16) Fuchigami, T.; Sano, M. J. Electroanal. Chem. 1996, 414,
81.
J = 8.1 Hz, 2 H), 6.15 (d, J = 50.8 Hz, 1 H), 2.36 (s, 3H).
13C NMR (68 MHz, CDCl3): d = 140.19, 134.82, 134.23,
134.20, 130.27, 129.81 (d, J = 1.1 Hz), 129.19, 125.54 (d,
J = 1.1 Hz), 110.79 (d, J = 264.4 Hz), 21.36. 19F NMR (254
MHz, CDCl3, TFA): d = –69.6 (d, J = 50.8 Hz). HRMS–
FAB): m/z [M + Na+] calcd for C14H13FO2S2Na: 319.0239;
found: 319.0237.
a-Fluoro-a-(p-tolylthio)ethyl Phenyl Sulfone (2h)
1H NMR (270 MHz, CDCl3): d = 8.00–7.97 (m, 2 H), 7.71–
7.43 (m, 5 H), 7.16–7.12 (m, 2 H), 2.35 (s, 3 H), 1.72 (d,
J = 19.3 Hz, 3 H). 13C NMR (68 MHz, CDCl3): d = 140.62,
136.67 (d, J = 2.2 Hz), 134.48, 130.62, 130.60, 129.91,
129.49, 128.83, 123.37, 115.78 (d, J = 260.5 Hz), 21.22 (d,
J = 21.8 Hz). 19F NMR (254 MHz, CDCl3, TFA): d = –40.52
(q, J = 19.3 Hz). HRMS (EI): m/z [M+] calcd for
(17) (a) Yoon, U. C.; Mariano, P. S. Acc. Chem. Res. 1992, 25,
233. (b) Fuchigami, T.; Ichikawa, S. J. Org. Chem. 1994,
59, 607.
(18) Typical Procedure for Oxidation of Sulfides 2a,e,g,i
m-Chloroperbenzoic acid (2.2 equiv) was added to a solution
of sulfide in CH2Cl2 at 0 °C. The solution was stirred over
night at r.t., treated with sat. aq NaHCO3 and extracted with
two portions of CH2Cl2. The combined extracts were washed
with brine and dried over anhyd Na2SO4. After the removal
of the solvent by evaporation, the residue was purified by
column chromatography on SiO2 (CHCl3) to provide a pure
disulfone.
C15H15FO2S2: 310.0497; found: 310.0490.
a-Fluoro-a-(2-pyridylthio)methyl Phenyl Sulfone (2i)
1H NMR (270 MHz, CDCl3): d = 8.45–8.43 (m, 1 H),
8.06v8.03 (m, 2 H), 7.77–7.12 (m, 1 H), 7.71 (d, J = 48.1 Hz,
1 H), 7.64–7.56 (m, 3 H), 7.23 (m, 1 H), 7.16–7.12 (m, 1 H).
13C NMR (68 MHz, CDCl3): d = 151.57 (d, J = 2.2 Hz),
149.58, 137.22, 134.84, 129.59, 129.18, 123.06, 123.02,
121.79, 106.01 (d, J = 259.9 Hz). 19F NMR (254 MHz,
CDCl3, TFA): d = –77.3 (d, J = 48.1 Hz). HRMS–FAB):
m/z [M + H+] calcd for C12H11FNO2S2: 284.0215; found:
284.0219.
a,a-Difluoro-a-(p-tolylthio)methyl Methyl Sulfone (3)
1H NMR (270 MHz, CDCl3): d = 7.59–7.56 (m, 2 H), 7.23–
7.21 (m, 2 H), 3.03 (s, 3 H), 2.39 (s, 3 H). 13C NMR (68
MHz, CDCl3): d = 141.69, 137.21 (t, J = 1.1 Hz), 130.14,
127.81 (t, J = 323.1 Hz), 119.06, 35.72, 21.51. 19 F NMR
(254 MHz, CDCl3, TFA): d = –5.14. HRMS (EI): m/z [M+]
calcd for C9H10F2O2S2: 252.0090; found: 252.0083.
a-(Fluoromethylthio)ethyl p-Tolyl Sulfone (4)
a-Fluoro-a-methylsulfonylmethyl p-Tolyl Sulfone (5a)
1H NMR (270 MHz, CDCl3): d = 7.90 (d, J = 8.1 Hz, 2 H),
7.45 (d, J = 8.1 Hz, 2 H), 5.59 (d, J = 45.3 Hz, 1 H), 3.24 (d,
J = 1.0 Hz, 3 H), 2.51 (s, 3 H). 13C NMR (68 MHz, CDCl3):
d = 147.59, 131.57, 130.30, 130.00 (d, J = 1.1 Hz), 105.07
(d, J = 263.3 Hz), 39.47, 22.02. 19F NMR (254 MHz, CDCl3,
TFA): d = –96.8 (d, J = 45.3 Hz). HRMS (EI): m/z [M+]
calcd for C9H11FO4S2: 266.0083; found: 266.0077.
a-Fluoro-a-(p-tolyl sulfonyl)methyl Phenyl Sulfone (5g)
1H NMR (270 MHz, CDCl3): d = 7.99 (m, 2 H), 7.86 (d,
J = 8.1 Hz, 2 H), 7.80–7.74 (m, 1 H), 7.62 (m, 2 H), 7.40 (d,
J = 8.1 Hz, 2 H), 5.70 (d, J = 45.7 Hz, 1 H), 2.49 (s, 3 H).
13C NMR (68 MHz, CDCl3): d = 147.18, 135.56, 135.17,
132.06, 130.10, 130.08, 130.06, 129.36, 105.59 (d, J = 265.5
Hz), 22.0. 19F NMR (254 MHz, CDCl3, TFA): d = –92.9 (d,
J = 45.7 Hz). HRMS (EI): m/z [M+] calcd for C14H13FO4S2:
328.0239; found: 328.0240.
a-Fluoro-a-(2-pyridylsulfonyl)methyl Phenyl Sulfone (5i)
1H NMR (270 MHz, CDCl3): d = 8.80 (m, 1 H), 8.10–7.62
(m, 8 H), 6.50 (d, J = 45.3 Hz, 1 H). 13C NMR (68 MHz,
CDCl3): d = 154.47, 150.60, 138.50, 135.71, 134.84, 130.29,
129.31, 128.64, 124.14, 103.05 (d, J = 264.9 Hz). 19F NMR
(254 MHz, CDCl3, TFA): d = –96.5 (d, J = 45.3 Hz). HRMS
(EI): m/z [M + H+] calcd for C12H11FNO4S2: 316.0114;
found: 316.0096.
1H NMR (270 MHz, CDCl3): d = 7.80 (d, J = 8.1 Hz, 2 H),
7.38 (d, J = 8.1 Hz, 2 H), 5.84 (dd, J = 54.4, 10.6 Hz, 1 H),
5.59 (dd, J = 54.4, 10.6 Hz, 1 H), 4.20 (qd, J = 7.3, 1.5 Hz, 1
H), 2.47 (s, 3 H), 1.59 (d, J = 7.3 Hz, 3 H). 13C NMR (68
MHz, CDCl3): d = 145.27, 132.29, 129.68, 129.61, 85.43 (d,
J = 216.3 Hz), 61.33 (d, J = 2.2 Hz), 21.75, 16.15. 19F NMR
(254 MHz, CDCl3, TFA): d = –111.6 (t, J = 54.4 Hz).
HRMS–FAB: m/z [M + Na+] calcd for C10H13FO2S2Na:
271.0239; found: 271.0241.
(12) (a) Ogura, K.; Tsuruda, T.; Takahashi, H.; Iida, H.
Tetrahedron Lett. 1986, 27, 3665. (b) Simpkins, N. S.
Tetrahedron Lett. 1988, 29, 6787. (c) Tsunoda, T.; Nagaku,
M.; Nagino, C.; Kawamura, Y.; Ozaki, F.; Hioki, H.; Ito, S.
Tetrahedron Lett. 1995, 36, 2531. (d) Matsumoto, S.; Ishii,
M.; Kimura, K.; Ogura, K. Bull. Chem. Soc. Jpn. 2004, 77,
1897.
(19) Fukuzumi, T.; Shibata, N.; Sugiura, M.; Yasui, H.;
Nakamura, S.; Toru, T. Angew. Chem. Int. Ed. 2006, 45,
4973.
Synlett 2008, No. 11, 1714–1718 © Thieme Stuttgart · New York