Use of Task-Specific Ionic liquid for selective electrocatalytic fluorination

Article abstract of DOI:10.1021/ol9028836

[Chemical equation presented] Highly selective indirect anodic fluorination of organic compounds was successfully carried out for the first time by using a task-specific ionic liquid of iodoarene as a mediator in ionic liquid hydrogen fluoride salts.

Full text of DOI:10.1021/ol9028836

ORGANIC
LETTERS
2
010
Vol. 12, No. 3
44-646
Use of Task-Specific Ionic Liquid for
Selective Electrocatalytic Fluorination
6
Takahiro Sawamura, Shunsuke Kuribayashi, Shinsuke Inagi, and
Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology, 4259 Nagatsuta,
Midori-ku, Yokohama 226-8502, Japan
fuchi@echem.titech.ac.jp
Received December 15, 2009
ABSTRACT
Highly selective indirect anodic fluorination of organic compounds was successfully carried out for the first time by using a task-specific ionic
liquid of iodoarene as a mediator in ionic liquid hydrogen fluoride salts.
In the context of green sustainable chemistry, ionic liquids
ILs) have become popular as volatile organic solvent-free
containing ionic liquid hydrogen fluoride (HF) salts as a
supporting electrolyte and fluorine source. However, severe
3
(
media for organic synthesis and electrochemical and separa-
tion processes, due to their inherent features such as
negligible vapor pressure, low flammability, high thermal
passivation of the anode (formation of a polymeric film on
the anode, which suppresses anodic current) occurred often.
3
To suppress anodic passivation, we have recently developed
solvent-free electrochemical fluorination in neat ionic liquid
1
stability, high ionic conductivity, and reusability. Recent
4
developments in the design of organic salts have made it
possible to create task-specific ionic liquids (TSILs), in which
a functional group is covalently attached to the cation or the
HF salts. However, even in such HF-based IL electrolytic
systems, anode passivation still takes place, depending on
5
the substrates involved. One solution to the passivation
2
anion or both. This has enabled the supply of various
problem is to employ indirect electrolysis using mediators.
functionalities to conventional IL media for application in
many fields of chemistry, especially in organic synthesis and
catalysis chemistry.
We have developed a method for the electrochemical
fluorination of organic compounds in organic solvents
2
For example, a hypervalent iodoarene difluoride (ArIF )
(
2) (a) Ohno, H., Ed. Electrochemical Aspects of Ionic Liquids; John
Wiely & Sons, Inc.: Hoboken, NJ, 2005. (b) Bates, E. D.; Mayton, R. D.;
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Tajima, T. ACS Symposioum Series 911. Fluorine-Containing Synthons;
Soloshonok, V., Ed.; 2005; Chapter 15. (c) Fuchigami, T.; Tajima, T. ACS
Symposioum Series 949. Current Fluoroorganic Chemistry. New Synthetic
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honok, V., Ed., 2007; Chapter 5.
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1
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10.1021/ol9028836  2010 American Chemical Society
Published on Web 01/05/2010

mediator was prepared by anodic oxidation of iodoarene
derivatives in HF salt/acetonitrile and applied to the elec-
electron-withdrawing group (EWG) was also converted to
the monofluorinated product in good yield by using the TSIL
mediator. Deprotonation of the R-position of sulfur (rate-
determining step ) involves the elimination of trivalent
iodoarene with indirect electrolysis, as shown in the plausible
reaction mechanism (Scheme 2). It is known that the
6a
trochemical fluorodesulfurization of dithioacetal compounds
6b
7
and fluorination of R-dicarbonyl compounds. Although the
former fluorination was the first successful example of the
catalytic use of hypervalent iodoarene for organic synthesis,
the fluorinated products had to be separated from the
mediator, and the mediator could not be reused. This is a
severe drawback from an atom-economical perspective.
Therefore, hybridization of mediator systems and TSILs is
well worth investigation. In this paper, we report on the first
electrochemical mediatory application of a TSIL having an
iodoarene moiety. The effect of the TSIL mediator on
electrochemical fluorination in a HF-based IL and the
reusability of the system were also investigated.
1
2
elimination rate of trivalent iodoarene is extremely high (10
8
times higher than that of iodine ). On the other hand, in the
case of direct electrolysis, the leaving group is fluoride (see
Supporting Information, Scheme S1). Hence, indirect reaction
with the hypervalent iodoarene mediator proceeded efficiently
to yield the desired monofluorinated product.
Scheme 1. Indirect Anodic Fluorination of 2 in HF Salt
The iodoarene mediator TSIL with an imidazolium cation
(
1) was prepared through ammonium cation formation and
subsequent anion exchange. TSIL mediator 1 was readily
soluble in several ionic liquids and was not extracted from
the ILs by nonpolar organic solvents such as diethyl ether.
Cyclic voltammetry measurements of 1 (0.1 mM) in 0.1 M
Et
4
NF-4HF/acetonitrile displayed an oxidation peak at 1.91
V vs saturated calomel electrode (SCE), which is similar to
6
a
that of the iodoarene devoid of an IL moiety.
Scheme 2
.
Plausible Mechanism of Indirect Anodic Fluorination
Using a TSIL Mediator
In a general indirect anodic reaction, a divided cell is used
for the mediator system to prevent cathodic reduction of the
oxidized species once generated at the anode. TSIL mediator
1
bears a bulky component; therefore, it can remain in the
vicinity of the anode surface in the viscous HF-based IL and
encounter the substrate before reduction at the cathode, even
in a simple undivided cell. First, the indirect anodic
R-fluorination of 2-pyrimidylsulfide 2a in the absence and
presence of a catalytic amount (10 mol %) of TSIL mediator
1
3
was carried out in HF-based IL (Et N-3HF) in an undivided
cell (Scheme 1). After passage of 4 F/mol charge, the yield
of the R-fluorinated product (3a) was low (31%) in the
absence of 1, due to the high viscosity of Et
3
N-3HF and the
low basicity of the fluoride ion in Et N-3HF. In sharp
3
contrast, the use of TSIL mediator 1 significantly enhanced
the yield of 3a (87%). Sulfide 2b with a CN group as an
(
4) (a) Hasegawa, M.; Ishii, H.; Cao, Y.; Fuchigami, T. J. Electrochem.
Soc. 2006, 153, D162–D166. (b) Hasegawa, M.; Fuchigami, T. Green Chem.
003, 5, 512–515. (c) Inagi, S.; Sawamura, T.; Fuchigami, T. Electrochem.
To elucidate the mediation system, potentiostatic elec-
ox
trolysis (1.80 V vs SCE) was carried out for 2a (E
V vs SCE). In the presence of TSIL mediator 1 (E
p
) 2.23
) 1.91
2
ox
Commun. 2008, 10, 1158–1160. (d) Sawamura, T.; Inagi, S.; Fuchigami,
T. J. Electrochem. Soc. 2009, 156, E26-E28. (e) Inagi, S.; Hayashi, S.;
Fuchigami, T. Chem. Commun. 2009, 1718–1720. (f) Hayashi, S.; Inagi,
S.; Fuchigami, T. Macromolecules 2009, 42, 3755–3760.
p
V vs SCE), 3a was obtained in 18% yield after passage of
F/mol charge, whereas no fluorinated product was obtained
in the absence of 1, which indicates that the fluorination of
1
(5) (a) Childs, V.; Christensen, L.; Klink, F. W.; Kolpin, C. F. in: Lund,
H.; Baizer, M. M.; Eds.; Organic Electrochemistry, 3rd ed.; Marcel Dekker:
New York, 1991; Chapter 26. (b) Shaaban, M. R.; Ishii, H.; Fuchigami, T
J. Org. Chem. 2000, 65, 8685–8689.
2
a with TSIL mediator 1 proceeded via an indirect process.
(
6) (a) Fuchigami, T.; Fujita, T. J. Org. Chem. 1994, 59, 7190–7192.
(7) Fuchigami, T.; Yamamoto, K.; Konno, A. Tetrahedron 1991, 47,
(
b) Hara, S.; Hatakeyama, T.; Chen, S.-Q.; Ishi-i, K.; Yoshida, M;
Sawaguchi, M.; Fukuhara, T.; Yoneda, N. J. Fluorine Chem. 1998, 87, 189–
92.
625–634.
(8) Okuyama, T.; Takano, T.; Sueda, T.; Ochiai, M. J. Am. Chem. Soc.
1995, 117, 3360–3367.
1
Org. Lett., Vol. 12, No. 3, 2010
645

The reusability of the IL system was investigated after
simple extraction of the product with diethyl ether. The
recovered IL still contained the TSIL mediator and was
reused for subsequent runs, maintaining a good yield of 3a
through the fourth run (87-84%).
Finally, indirect anodic fluorodesulfurization of cyclic
dithioacetal (8) was investigated in the TSIL mediator system
(Scheme 3). Even in the case of fluorodesulfurization, the
mediator system worked sufficiently to afford the difluo-
romethylene product (9) in excellent yield.
In conclusion, a novel indirect electrochemical fluorination
system was developed by employing a task-specific ionic
liquid (TSIL) with an iodoarene moiety as the mediator in a
HF-based IL. The mobility of the novel mediator bearing
an IL moiety was reduced in viscous IL, which enabled the
indirect electrochemical fluorination efficiently in a simple
undivided cell. This is a significant advantage compared with
conventional mediatory systems. Mediator 1 improved the
reaction efficiency for a variety of electrochemical fluorina-
tions and remained intact in the ILs after the extraction
process to be reused for subsequent runs. Thus, volatile
organic solvent-free indirect electrochemical fluorination of
various organic compounds was achieved using a reusable
iodoarene mediator bearing an IL moiety. Application of the
TSIL mediator 1 to another oxidative reaction in an IL is
now under investigation in our laboratory.
Table 1. Indirect Anodic Fluorination of 4 and 5
a
entry
compound
EWG
X
yield (%)
1
2
3
4
5
6
a
4a
4b
4c
5a
5b
5c
COOMe
COOMe
COOMe
CN
CN
CN
H
55 (6a)
70 (6b)
69 (6c)
42 (7a)
79 (7b)
75 (7c)
Cl
Br
H
Cl
Br
Determined by 19F NMR.
Scheme 3. Indirect Anodic Fluorodesulfurization of 8
The indirect electrolysis in IL was also applicable to the
fluorination of R-(phenyl)acetate (4) and R-(phenyl)aceto-
nitrile (5). Direct electrochemical oxidation of these com-
pounds is difficult, due to their high oxidation potentials (e.g.,
ox
E
p
of 5b: 2.68 V vs SCE). Furthermore, in conventional
HF salt/acetonitrile solution, the benzylic cation generated
by oxidation preferentially reacts with acetonitrile and causes
9
acetoamidation instead of fluorination. Table 1 shows the
results of the indirect anodic fluorination of 4 and 5 in
anodically stable Et N-5HF with TSIL mediator 1. The
3
corresponding monofluorinated products (6 and 7, respec-
tively) were obtained in good to moderate yields. The
introduction of chlorine and bromine at the para-position of
the benzene ring effectively increased the electrophilicity of
the benzylic cation intermediate, which resulted in an increase
of the product yields. In sharp contrast, Noel et al. quite
recently reported the electrochemical fluorination of alkyl
Acknowledgment. We would like to thank Prof. Hideo
Togo of Chiba University for his valuable suggestions for
the preparation of the TSIL. This study was supported by a
Grant-in-Aid for Scientific Research (No. 17073008) on
Priority Area “Science of Ionic Liquids” (Area Number 452),
a Grant-in-Aid for Scientific Research (B) (No. 20350071),
and the Tokyo Ohka Foundation for the Promotion of Science
and Technology together with the Society of Iodine Science.
One of the authors (T.S.) also thanks the Japan Society for
the Promotion of Science (JSPS) for financial support of his
research fellowship.
1
0
3
phenylacetates in ionic liquid Et N-4HF. Although the
corresponding R-fluorinated products were obtained as major
products, many byproducts, such as hydrolysis products, R,R-
difluoro products, and aromatic fluorinated products, were
formed. Therefore, indirect electrolysis using the mediator
is far superior to direct electrolysis.
Supporting Information Available: Experimental section
and scheme showing the mechanism of direct electrolysis.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
9) Laurent, E.; Marquet, B.; Tardivel, R.; Thiebault, H. Tetrahedron
Lett. 1987, 28, 2359–2362.
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Chem. 2008, 129, 185–192.
(
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