Electrolytic partial fluorination of organic compounds. Part 43: Highly regioselective anodic mono- and difluorination of propargyl sulfides and preparation of α-fluoroallenyl sulfides

Article abstract of DOI:10.1016/S0040-4039(01)00344-6

The anodic fluorination of aryl propargyl sulfides in DME containing a fluoride supporting electrolyte using an undivided cell provided the corresponding α-mono- and α,α-difluorinated sulfides selectively, depending on the amount of electricity passed. The α-monofluorinated sulfides were readily converted into the corresponding α-fluoroallenyl sulfides in good to moderate yields.

Full text of DOI:10.1016/S0040-4039(01)00344-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3009–3011
Electrolytic partial fluorination of organic compounds. Part 43:
Highly regioselective anodic mono- and difluorination of
propargyl sulfides and preparation of a-fluoroallenyl sulfides†
Sayed M. Riyadh, Hideki Ishii and Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502, Japan
Received 9 January 2001; revised 21 February 2001; accepted 23 February 2001
Abstract—The anodic fluorination of aryl propargyl sulfides in DME containing a fluoride supporting electrolyte using an
undivided cell provided the corresponding a-mono- and a,a-difluorinated sulfides selectively, depending on the amount of
electricity passed. The a-monofluorinated sulfides were readily converted into the corresponding a-fluoroallenyl sulfides in good
to moderate yields. © 2001 Elsevier Science Ltd. All rights reserved.
Selective direct fluorination of organic molecules is of
much importance in various fields such as medicinal
biological activities such as anticancer agent gem-
citabine,7 HIV-1 protease inhibitors,8 and phosphoty-
rosine mimetics.9 However, the construction of a
difluoromethylene group is not so easy and very often
requires a large amount of oxidizing, toxic or costly
reagents.10 On the other hand, very recently, the first
synthesis and synthetic application of a-fluoroallenyl
phosphonate have been reported.11 a-Fluoroallenyl
chemistry
organofluorine compounds, difluoromethylene com-
pounds attract much interest because the
and
material
science.2–6
Among
difluoromethylene group is isopolar and isosteric with
an ether oxygen, and recent work has revealed that
difluoromethylene compounds have a wide range of
Table 1. Anodic mono- and difluorination of aryl propargyl sulfides 1a–d
F
F
F
S
-2ne, -nH+
+
R1
S
R1
R1
S
R2
R2
R2
F -/DME
2
3
1
Run
Sulfide
Supporting electrolyte
Charge passed (F/mol)
Yield (%)
No.
R1
R2
2
3
1
2
3a
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1b
1c
H
H
H
H
H
H
H
Cl
H
H
H
H
H
H
H
H
H
Ph
Et4NF·4HF
Et4NF·4HF
Et4NF·4HF
Et3N·5HF
Et4NF·4HF
Et4NF·4HF
Et3N·3HF
Et3N·3HF
Et3N·3HF
2
4
4
4
8
10
8
8
43
64
70
77
22
0
21
5
0
5
13
0
17
70
55
75
72
65
10
a Constant potential electrolysis.
* Corresponding author. Tel./fax: +81-45-924-5406; e-mail: fuchi@echem.titech.ac.jp
†
For Part 42, see Ref. 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00344-6

3010
S. M. Riyadh et al. / Tetrahedron Letters 42 (2001) 3009–3011
sulfides should be useful as a fluorobuilding block.
However, there has been no report on a-fluoroallenyl
sulfides so far. Previously, we have found that an
electron-withdrawing group markedly facilitated anodic
a-fluorination of sulfides.12 An acetylenic group is an
electron-withdrawing group; however, to the best of
our knowledge, no anodic partial fluorination of
sulfides having an acetylenic group has been reported.
Consequently, MeCN electrolytic solutions were not
suitable for the formation of 2a and 3a. On the other
hand, DME was suitable because it did not cause anode
passivation although excess amount of electricity is
necessary due to the simultaneous oxidation of DME
during electrolysis. Therefore, a solvent effect of DME
on the anodic fluorination is notable.
We extended this anodic fluorination to other deriva-
tives 1b,c. In all cases, a,a-difluorinated sulfides 3b,c
were predominantly (run 8) or exclusively (run 9)
formed. The difluorinated products 3b,c were readily
isolated by column chromatography.17 In the case of
1c, neither phenyl fluorination nor acetylenic fluorina-
tion occurred and a,a-difluorinated product 3c was
obtained exclusively. Therefore, this fluorination is
highly regioselective.
In this paper, we report the first successful regioselec-
tive anodic mono- and difluorination of aryl propargyl
sulfides 1 using various fluoride salts in DME and the
transformation of monofluoropropargyl sulfides to a-
fluoroallenyl sulfides.
At first, we carried out the anodic fluorination of
phenyl propargyl sulfide 1a using constant current elec-
trolysis under various conditions.13 The results are sum-
marized in Table 1.
Although a-monofluorinated sulfide 2a was formed in
good yield, its complete isolation was unsuccessful due
to its instability. Therefore, we attempted to convert 2a
into a more stable derivative. Thus, a solution of a
crude product 2a was basified by addition of an ethanol
solution of sodium ethoxide, and the resulting stable
a-fluoroallenyl sulfide 4a18 was easily isolated in good
yield as shown in Scheme 1. p-Chlorophenyl derivative
4b was similarly obtained in moderate yield from 1b.
Although MeCN was not suitable for the fluorination
(the yield of 2a was up to 25%) due to anode passiva-
tion, DME was found to be very effective irrespective
of the supporting fluoride salts. When twice the theoret-
ical amount of electricity (4F/mol) was passed in DME,
a-monofluorinated sulfide 2a was selectively formed in
good yield (run 4). A fluorine atom was regioselectively
introduced into the position a to the sulfur atom.
Fluorination at the acetylenic group or phenyl ring did
not take place at all. However, a,a-difluorinated sulfide
3a was also formed as a by-product. On the other hand,
constant potential anodic oxidation of 1a at 1.5 V
versus SSCE provided 2a predominantly in good yield
(run 3).14
Since a-fluoroallenyl sulfides 4 have multifunctional
groups, they may be highly useful building blocks simi-
larly to a-fluoroallenyl phosphonates.10
In order to disclose the role of an acetylenic group,
anodic fluorination of allyl phenyl sulfide was
attempted. However, many complicated fluorinated
products were formed. Therefore, a strongly electron-
withdrawing acetylenic group is essential for this
regioselective anodic fluorination (Scheme 2).
In order to obtain a,a-difluorinated product 3a selec-
tively, a large excess amount of electricity was passed.
As shown in Table 1, 3a was formed as a main product
(runs 5 and 7).15 Longer electrolysis resulted in exclu-
sive formation of 3a although the yield decreased (run
6). Previously, we found that Et4NF·4HF/MeCN was
effective for a,a-difluorination of sulfides having vari-
ous electron-withdrawing groups but Et3N·3HF/MeCN
was not suitable.16 In contrast, only poor yield (14%) of
3a was obtained in Et4NF·4HF/MeCN but the use of
Et3N·3HF/DME provided 3a in good yield of 75%.
N-Fluoropyridinium salts are known to be good fluori-
nating reagents.19 The chemical fluorination of phenyl
propargyl sulfide 1a, as a model compound, was also
attempted. However, treatment of 1a with various N-
fluoropyridinium triflates in dichloromethane at either
room temperature or under refluxing resulted in no
F
F
F
-2e, -H+
+
Ar
S
Ar
S
Ar
S
F- / DME
4F/mol
1a: Ar = C6H5
1b: Ar = p-ClC6H4
2a (77%)
2b (54%)
3a (17%)
3b (12%)
F
F
F
H+
EtONa
EtOH
Ar
S
Ar
S
Ar
C
S
C
CH2
CH
4a (70%)
3a (50%)
Scheme 1.

S. M. Riyadh et al. / Tetrahedron Letters 42 (2001) 3009–3011
3011
-2e, -H+
Ph
S
Many Fluorinated Products
F-/ DME
Scheme 2.
Y
+
Ph
S
CH2Cl2
Fluorinated Products
N
F
X
X
r.t. or reflux
TfO-
Scheme 3.
formation of fluorinated products as shown in Scheme
3.20 Therefore, electrochemical fluorination proved to
be superior to the conventional chemical method.
13. Constant current electrolysis (5 mA/cm2) of 1a (1 or 5
mmol) was carried out at platinum electrodes (3×3 cm2)
at ambient temperature in DME (30 or 60 ml) containing
0.37 M fluoride salt using an undivided cell under a
nitrogen atmosphere. After electrolysis, the supporting
electrolyte was removed by silica gel short column chro-
matography. The yields of the products 2a and 3a were
estimated by 19F NMR spectroscopy. Compound 2a was
converted to a-fluoroallenyl sulfide 4a, which was easily
isolated by silica gel preparative thin-layer chromato-
graphy.
In summary, we have successfully carried out for the
first time selective anodic mono- and difluorination of
aryl propargyl sulfides, and the monofluorinated prod-
ucts were readily transformed into stable a-fluoroallenyl
sulfides. Further studies of the synthetic application of
allenes are in progress. The fluorinated products
obtained here are proposed to be highly useful building
blocks.
14. After electrolysis, the electrolytic solution was passed
through silica gel short column chromatography using
ethyl acetate and the eluent was concentrated to give 2a.
Compound 2b was obtained similarly. Compound 2a:
References
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