Electrolytic partial fluorination of organic compounds. Part 50: Highly selective anodic mono- and difluorination of 4-phenylthiomethyl-1,3-dioxolan-2-one and its synthetic application

Article abstract of DOI:10.1016/S0040-4039(01)00869-3

Anodic fluorination of 4-phenylthiomethyl-1,3-dioxolan-2-ones was successfully carried out to provide the corresponding α-mono- and α,α-difluorinated products selectively, depending on the amount of the electricity passed. The fluorination was also greatly affected by solvents, temperature and current densities. The fluorinated products were readily converted into the corresponding fluorinated allyl alcohol and diols by treatment with an alkaline solution.

Full text of DOI:10.1016/S0040-4039(01)00869-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4861–4863
Electrolytic partial fluorination of organic compounds. Part 50:
Highly selective anodic mono- and difluorination of
4-phenylthiomethyl-1,3-dioxolan-2-one and its
synthetic application†
Katsutoshi Suzuki, Hideki Ishii and Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502, Japan
Received 25 April 2001; revised 14 May 2001; accepted 18 May 2001
Abstract—Anodic fluorination of 4-phenylthiomethyl-1,3-dioxolan-2-ones was successfully carried out to provide the corresponding
a-mono- and a,a-difluorinated products selectively, depending on the amount of the electricity passed. The fluorination was also
greatly affected by solvents, temperature and current densities. The fluorinated products were readily converted into the corresponding
fluorinated allyl alcohol and diols by treatment with an alkaline solution. © 2001 Elsevier Science Ltd. All rights reserved.
However, their preparation is still limited.3 Recently,
Fluorine-containing allyl alcohols and 1,2-diols are use-
electrochemical partial fluorination of organic com-
pounds has been shown to be a new powerful method
ful building blocks for the preparation of valuable
organofluorine compounds such as fluorinated sugars.2
Table 1. Anodic fluorination of 4-phenylthiomethyl-1,3-dioxolan-2-one (1)
O
O
O
-2ne-, -nH+
F -
O
O
+
O
O
O
O
SPh
SPh
SPh
F
F
F
1
2
3
Run Solvent
Supporting electrolyte Electricity (F mol−1
)
Temp. (°C)
Current density (mA cm−2
)
Yield (%)a
2
3
1
2
3
4
5
6
7
8
MeCN
CH2Cl2
CH2Cl2
DME
DME
DME
DME
DME
DME
DME
Et3N·3HF
Et3N·3HF
Et3N·3HF
Et3N·5HF
Et4NF·4HF
Et3N·3HF
Et3N·3HF
Et3N·3HF
Et3N·3HF
Et3N·3HF
Et3N·3HF
2
2
4
2
2
2
8
8
20
20
20
20
20
20
20
40
40
40
40
10
10
10
10
10
10
10
10
10
40
40
0
48
6
24
22
22
40
73
17
0
4
26
5
1
0
8
Trace
40
68
65
9
10
11
48
48
16
Trace
9
DME/MeCN
(50/50)
a Isolated yield.
* Corresponding author. Tel./fax: +81-45-924-5406; e-mail: fuchi@echem.titech.ac.jp
†
For Part 49, see: Ref. 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00869-3

4862
K. Suzuki et al. / Tetrahedron Letters 42 (2001) 4861–4863
for selective fluorination.4 We have reported selective
anodic fluorination of various organo sulfur com-
pounds.5 With these in mind, we studied anodic fluori-
nation of 4-phenylthiomethyl-1,3-dioxolan-2-ones (1) in
order to synthesize fluorine-containing allyl alcohols
and diols.
Further anodic oxidation at 40°C provided difluori-
nated product 39 preferentially (run 9). In order to
increase the yield of 3, the applied current density was
increased from 10 mA cm−2 to 40 mA cm−2 (run 10).
Expectedly, the yield increased markedly to 70% and 3
was obtained predominantly. Thus, it was found that
the electrolysis at a higher current density and higher
temperature was suitable for the difluorination of 1.
Although, DME was suitable for anodic fluorination of
1, a large excess amount of electricity was necessary for
the formation of the difluorinated product 3 due to the
simultaneous oxidation of DME. Next, we used a
mixed solvent of DME/MeCN for the anodic fluorina-
tion in order to decrease the amount of the necessary
electricity. Eventually, the required electricity was
reduced to one-third by using DME/MeCN (50:50) and
the desired difluorinated product 3 was obtained in an
acceptable yield (run 11).
At first, we carried out anodic fluorination of 1 at
platinum electrodes in an undivided cell under different
conditions using various fluoride salts as a supporting
electrolyte and a fluorine source.6 Constant current was
applied. The results are summarized in Table 1.
As shown in Table 1, no fluorinated product was
formed in MeCN (run 1). In contrast, monofluorinated
product 2 was obtained in moderate yield in CH2Cl2
(run 2). However, further oxidation of 2 resulted in a
drastic decrease in the yield of 2 and the corresponding
difluorinated product 3 was formed (run 3). On the
other hand, the use of dimethoxyethane (DME) pro-
vided monofluorinated product 2 in reasonable yields
regardless of the supporting fluoride salts (runs 4–6). In
these cases, a large amount of the starting material 1
was recovered. Among the electrolytes used, Et3N·3HF
gave the best product selectivity (run 6). In order to
increase the yield of 2, the electrolysis of 1 was carried
out by using Et3N·3HF/DME until the starting 1 was
consumed. Thus, the product yield increased consider-
ably when 8 F/mol of charge was passed (run 7).
Finally, deprotection of the carbonate group of 2 and 3
was attempted. Alkaline hydrolysis of 2 resulted in
decomposition of 2. Therefore, 2 was converted into the
corresponding sulfone and then alkaline hydrolysis was
carried out at room temperature to provide the corre-
sponding allyl alcohol derivative 410 quantitatively
(79% yield from 2) as shown in Scheme 2.
On the other hand, difluorinated compound 3 was
directly converted into the corresponding diol 511 by
alkaline hydrolysis at room temperature as shown in
Scheme 3.
Next, the electrolysis was investigated at a higher tem-
perature. Interestingly, the anodic fluorination of 1 at
40°C gave monofluoro product 2 selectively in good
yield (73%) (run 8). The increase of the yield of 2 can be
accounted as follows. We have already proposed a
Pummerer type mechanism for the anodic fluorination
of sulfides.7 Therefore, the anodic fluorination of 1
seems to proceed similarly as shown in Scheme 1.
The compound 3 was also readily converted into the
corresponding difluoro sulfonyl diol derivative 612 by
the oxidation of 3 with mCPBA followed by alkaline
hydrolysis at room temperature as shown in Scheme 4.
O
HO
OH
NaOH (1.5eq)
O
O
F
SPh
F
Elimination of hydrogen fluoride from the fluorosulfo-
nium intermediate A should be facilitated at a higher
temperature. Thus, we could obtain the desired
monofluorinated product 2 in good yield. The product
2 was found to be a diastereoisomeric mixture (7:3).8
SPh
F
50% aq. MeOH
r.t.
F
3
5
(73%)
Scheme 3.
O
O
O
O
-2 e -, F -
F -
-HF
O
O
O
O
O
O
O
O
SPh
SPh
SPh
F
SPh
(A)
1
2
F
Scheme 1.
O
O
HO
NaOH (1.5eq)
mCPBA (2.4eq)
O
O
O
O
SO2Ph
CH2Cl2
r.t.
SPh
SO2Ph
EtOH
r.t.
F
2
4
F
F
(100%)
(79%)
Scheme 2.

K. Suzuki et al. / Tetrahedron Letters 42 (2001) 4861–4863
4863
O
O
HO
OH
F
NaOH (1.5eq)
mCPBA (1.2eq)
O
O
F
O
O
F
SOPh
F
CH2Cl2
r.t.
SPh
F
50% aq. MeOH
r.t.
SOPh
F
6
3
(87%)
(98%)
Scheme 4.
The products 4–6 have multi-functional groups. There-
fore, they seem to be useful fluorinated building
blocks.13
converted to 4, 5 and 6, which were easily isolated by
silica gel chromatography.
7. Fuchigami, T.; Konno, A.; Nakagawa, K.; Shimojo, M.
J. Org. Chem. 1994, 59, 5937.
In conclusion, we successfully carried out selective
anodic mono- and difluorination of 4-phenylth-
iomethyl-1,3-dioxolan-2-one and the fluorinated prod-
ucts were easily converted into monofluoro allyl alcohol
and difluorodiol derivatives in good yields.
8. 2 (more polar isomer): 1H NMR (CDCl3): l 7.54–7.35
(m, 5H), 5.90 (dd, J=53.5 Hz, 2.7 Hz), 5.00–4.91 (m,
1H), 4.56–4.36 (m, 2H); 13C NMR (CDCl3): l 153.6;
136.3; 130.6; 129.2; 129.0; 99.3 (d, J=225.4 Hz); 75.4 (d,
J=26.2 Hz); 64.8 (d, J=3.3 Hz); 19F NMR (CDCl3): l
−88.96 (dd, J=53.6, 16.8 Hz); MS (m/z) 228 (M+).
HRMS calcd for C10H9FO3S: 228.0256; found: 228.0252.
1
2 (less polar isomer): H NMR (CDCl3): l 7.55–7.35 (m,
References
5H), 5.76 (dd, J=51.7 Hz, 5.9 Hz), 4.92–4.80 (m, 1H),
4.57–4.38 (m, 2H); 13C NMR (CDCl3): l 153.8; 133.3;
133.1; 129.2; 129.4; 129.2; 99.6 (d, J=226.5 Hz); 75.7 (d,
J=25.1 Hz); 65.6 (d, J=3.3 Hz); 19F NMR (CDCl3): l
−83.73 (dd, J=51.8, 13.0 Hz); MS (m/z) 228 (M+).
HRMS calcd for C10H9FO3S: 228.0256; found: 228.0252.
1. Fuchigami, T.; Tetsu, M.; Tajima, T.; Ishii, H. Synlett, in
press.
2. (a) Hiyama, T. Organofluorine Compounds. Chemistry and
Applications; Springer: Berlin, 2000; (b) Progress and
Application of Fluorinated Bioactive Compounds; Taguchi,
T., Ed.; CMC: Tokyo, 2000; (c) Welch, J. T.; Eswarakr-
ishnan, S. Fluorine in Bioorganic Chemistry; Wiley: New
York, 1991.
3. (a) Hiyama, T.; Obayashi, M.; Sawahata, M. Tetrahedron
Lett. 1983, 24, 4113 or 4135; (b) Martin, S.; Sauvetre, R.;
Normant, J. Tetrahedron Lett. 1983, 24, 5615; (c)
Taguchi, T.; Morikawa, T.; Kitagawa, O.; Mishima, T.;
Kobayashi, Y. Chem. Pharm. Bull. 1985, 33, 5137; (d)
Tellier, F.; Sauvetre, R. J. Fluorine Chem. 1995, 70, 265;
(e) Cirkva, V.; Paleta, O. J. Fluorine Chem. 1991, 94, 141.
4. (a) Fuchigami, T. Organic Electrochemistry, 4th ed.;
Lund, H.; Hammerich, O., Eds.; Marcel Dekker: New
York, 2001; Chapter 25; (b) Fuchigami, T. In Advances in
Electron-Transfer Chemistry; Mariano, P. S., Ed.; JAI
Press: CT, 1999; Vol. 6, p. 41.
1
9. 3: H NMR (CDCl3): l 7.64–7.41 (m, 5H), 4.86–4.61 (m,
1H), 4.58–4.50 (m, 2H); 13C NMR (CDCl3): l 153.2;
136.6; 130.8; 129.6; 125.8; 123.8; 74.8 (dd, J=32.9, 28.0
Hz); 64.3; 19F NMR (CDCl3): l −14.83–11.14 (m); MS
(m/z) 246 (M+). HRMS calcd for C10H8F2O3S: 246.0162;
found: 246.0162.
10. 4: 1H NMR (CDCl3): l 7.96–7.55 (m, 5H), 6.40 (dt,
J=32.4, 6.2 Hz), 4.36 (dd, J=6.2, 2.7 Hz); 13C NMR
(CDCl3): l 134.5; 129.4; 128.6; 126.1; 116.5 (d, J=5.0
Hz); 55.5 (d, J=3.9 Hz); 19F NMR (CDCl3): l −47.72 (d,
J=31.5); HRMS calcd for C9H9FO3S: 216.0256; found:
216.0249.
1
11. 5: H NMR (CDCl3): l 7.61–7.33 (m, 5H), 4.06–3.99 (m,
1H), 3.89–3.79 (m, 2H); 13C NMR (CDCl3): l 136.4;
130.0; 129.0; 128.7; 116.3 (d, J=22.3 Hz); 73.9 (t, J=26.8
Hz); 61.3 Hz; 19F NMR (CDCl3): l −9.12–8.05 (m);
−5.54 to 4.52 (m); MS (m/z) 220 (M+). HRMS calcd for
C9H10F2O2S: 220.0370; found: 220.0349.
5. Shaaban, M. R.; Ishii, H.; Fuchigami, T. J. Org. Chem.
2000, 8685 and references cited therein.
6. Constant current electrolysis (10 or 40 mA cm−2) of 1 (1
mmol) was carried out at platinum electrodes (2×2 cm2)
at 20 or 40°C in DME, MeCN or CH2Cl2 (10 ml) and
DME/MeCN (5 ml/5 ml) containing 0.3 M fluoride salt
using an undivided cell under a nitrogen atmosphere.
After electrolysis, the supporting electrolyte was. removed
by silica gel short column chromatography. The products
2 and 3 were isolated by silica gel column chromatogra-
phy (hexane:EtOAc=9:1). Compounds 2 and 3 were
12. 6: H NMR (CDCl3): l 7.63–7.54 (m, 5H), 4.19 (m, 1H),
1
3.90 (m, 2H); 13C NMR (CDCl3): l 134.6; 132.5; 129.0;
126.6; 116.5 (d, J=4.4 Hz); 68.6 (dd, J=26.7, 21.2 Hz);
60.0 (t, J=5.0 Hz); 19F NMR (CDCl3): l −40.84 (dd,
J=227.4, 7.4 Hz); −32.20 (dd, J=225.6, 11.2 Hz);
HRMS calcd for C9H10F2O3S: 236.0319; found: 236.0316.
13. Itoh, T.; Sakabe, K.; Kudo, K.; Ohara, H.; Takagi, Y.;
Kihara, H.; Zagatti, P.; Renou, M. J. Org. Chem. 1999,
64, 252.