Redox system for perfluoroalkylation of arenes and α-methylstyrene derivatives using titanium oxide as photocatalyst

Article abstract of DOI:10.1016/j.jfluchem.2009.07.010

Photoirradiation of titanium oxide (TiO₂) excites the electrons from the valence band to the conduction band, leaving holes in the valence band. Using these holes and electrons, it is possible to perform one-electron oxidations and reductions. We developed a method for the photocatalytic perfluoroalkylation of aromatic rings such as benzene and its derivatives, naphthalene and benzofuran with perfluoroalkyl iodide by the combination of reduction and oxidation reactions with TiO₂. Perfluoroalkyl iodide was reduced to a perfluoroalkyl radical by the excited electrons in the conduction band of TiO₂, and the resulting radical reacted with an aromatic ring to form an arenium radical that was successively oxidized to a cation by the holes in the valence band of TiO₂. Similarly, the photocatalytic reaction of α-methylstyrene with perfluoroalkyl iodide afforded perfluoroalkylated α-methylstyrene, in which the perfluoroalkyl group is on a methyl carbon.

Full text of DOI:10.1016/j.jfluchem.2009.07.010

Journal of Fluorine Chemistry 130 (2009) 926–932
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Redox system for perfluoroalkylation of arenes and
using titanium oxide as photocatalyst
a-methylstyrene derivatives
*
Mari Iizuka, Masato Yoshida
School of Medicine, Shimane University, Izumo 693-8501, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Photoirradiation of titanium oxide (TiO2) excites the electrons from the valence band to the conduction
band, leaving holes in the valence band. Using these holes and electrons, it is possible to perform one-
electron oxidations and reductions. We developed a method for the photocatalytic perfluoroalkylation of
aromatic rings such as benzene and its derivatives, naphthalene and benzofuran with perfluoroalkyl
iodide by the combination of reduction and oxidation reactions with TiO2. Perfluoroalkyl iodide was
reduced to a perfluoroalkyl radical by the excited electrons in the conduction band of TiO2, and the
resulting radical reacted with an aromatic ring to form an arenium radical that was successively oxidized
Received 15 June 2009
Received in revised form 14 July 2009
Accepted 14 July 2009
Available online 24 July 2009
Keywords:
Perfluoroalkyl iodide
Perfluoroalkylation
Titanium oxide
Photocatalyst
Radical
to a cation by the holes in the valence band of TiO2. Similarly, the photocatalytic reaction of
a-
methylstyrene with perfluoroalkyl iodide afforded perfluoroalkylated
perfluoroalkyl group is on a methyl carbon.
a-methylstyrene, in which the
ß 2009 Elsevier B.V. All rights reserved.
1. Introduction
and holes for one-electron reductions and oxidations, respectively.
However, studies on the use of TiO2 as a photocatalyst for carbon–
carbon bond formation have been scarcely done [10]; especially no
TiO2-photocatalytic carbon–carbon bond formation reaction for
syntheses of organofluorine compounds has been reported thus far
except for our preliminary communication [11]. Here, we report
Perfluoroalkyl iodide is a well-known source for the introduc-
tion of perfluoroalkyl groups into organic molecules. From a
perfluoroalkyl iodide, a perfluoroalkyl radical is relatively easy to
produce thermally, photochemically or through the use of a radical
initiator [1–3]. One-electron reduction of the iodide is an
alternative method of producing perfluoroalkyl radical. A method
using Na2S2O4 developed by Huang and co-workers [4] and a
method using SmI2 [5] are useful for the reduction of the iodide.
Furthermore, electrochemical reduction of the iodide to produce
perfluoroalkyl radicals has been well investigated [6]. On the other
hand, reports of the perfluoroalkylation of organic molecules with
the iodide via a perfluoroalkyl cation are scarce due to the high
electronegativity of fluorine [7]. Therefore, electrophilic perfluo-
roalkylation of organic molecules via a radical intermediate is
expected to be a useful method for introducing a perfluoroalkyl
group into organic molecules [8]. We investigated the perfluor-
oalkylation of electron-rich compounds (H-Do) with the iodide via
a cationic intermediate by a combination of reduction and
subsequent oxidation using titanium oxide (TiO2) as shown in
Scheme 1. Recently, the use of TiO2 as a photocatalyst has received
considerable attention [9]. Photoirradiation of TiO2 excites
electrons from the valence band to the conduction band, leaving
holes in the valence band. It may be possible to use these electrons
the development of
a new redox system using TiO2 as a
photocatalyst to perform perfluoroalkylations that result in
carbon–carbon bond formation. The electrons in the conduction
band of TiO2 reduce perfluoroalkyl iodide to form a perfluoroalkyl
radical and iodide ion. The resulting radical reacts with an organic
molecule to provide a new radical species, which is successively
oxidized to the corresponding cationic intermediate as shown in
Scheme 1.
* Corresponding author.
Scheme 1.
E-mail address: yoshidam@med.shimane-u.ac.jp (M. Yoshida).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.07.010

M. Iizuka, M. Yoshida / Journal of Fluorine Chemistry 130 (2009) 926–932
927
Scheme 2.
In this paper, we describe the perfluoroalkylation of aromatic
rings (Scheme 2(a)), -methylstyrene (Scheme 2(b)) and their
related compounds with perfluoroalkyl iodide under TiO2-photo-
catalytic conditions.
to disperse TiO2, the solution was photoirradiated for 64 h using
two metal halide lamps (National Sky-beam MT-70) that irradiated
the reaction vessel from both sides. During the photoirradiation of
64 h, the color of TiO2 changed from white to blue gray, and the
iodide was consumed completely as determined by HPLC. After
removal of TiO2 by filtration, the solvent and unreacted p-xylene
were removed by rotary evaporation, and the residue was
dissolved in ether (50 mL). The resulting ether solution was
washed with 10% aq Na2S2O3 (50 mL) and then brine (50 mL), and
dried over MgSO4. The ether was removed under reduced pressure
to give crude 1a. The crude product was purified by column
chromatography on silica gel with hexane as eluent to give 1a
(462 mg, 44% yield based on the iodide, colorless oil) in its pure
form.
a
2. Experimental
1H, 13C, and 19F NMR spectra were acquired with a JEOL JNM-
ECA500 (1H: 500 MHz; 13C: 125 MHz; 19F: 470 MHz) or AL400 (1H:
400 MHz; 13C: 100 MHz; 19F: 376 MHz) spectrometer in CDCl3.
Fluorine chemical shifts were determined using PhCF3 as an
internal standard and are given in ppm downfield from an external
standard of CF3COOH (dF of PhCF3 = 12.6). Mass spectra were
obtained with a Hewlett PACARD 5890 GC/5972 MSD or a JEOL JMS
AX-505H spectrometer equipped with a JEOL JMA 5000 mass data
system using an electron-impact (EI) ionization technique at 70 eV.
HPLC analysis was performed with a Shimadzu SPD-6A liquid
1a: 1H NMR (CDCl3,
J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.30 (s, 1H); 19F NMR (CDCl3,
d): 2.36 (s, 3H), 2.43 (brs, 3H), 7.16 (d,
d
): À5.04 (3F), À30.00 (2F), À44.62 (2F), À45.48 (2F), À46.60 (2F),
À49.84 (2F); MS (m/z): 424 (M+), 155.
Similarly, 1b was obtained from the reaction of nonafluorobutyl
iodide with p-xylene.
chromatograph
equipped
with
a
Cosmosil
5C18
(4.6 mm  250 mm, Nacalai Tesque, reverse-phase column) with
CH3OH/H2O (80/20 by volume) as eluent. Perfluorobutyl and
perfluorohexyl iodides were obtained from Tokyo Kasei Kogyo Co.,
1b: 19F NMR(CDCl3,
d
): À5.73 (3F), À31.18 (2F), À46.52 (2F),
À50.83 (2F); MS (m/z): 324 (M+), 155.
Ltd. and purified by distillation over Na2S2O3 if necessary.
a-
Methylstyrene was obtained from Tokyo Kasei Kogyo Co., Ltd. and
purified by distillation if necessary. 3,4-Dihydro-1-methylnaphta-
lene was prepared from 1-methyl-1-hydroxy-1,2,3,4-tetrahydro-
2.1.2. Perfluoroalkylation of naphthalene
Similarly,
a solution of perfluorohexyl iodide (1.114 g,
naphthalene, which was synthesized from
a-tetralone (Aldrich
2.5 mmol) and naphthalene (5.0 mmol) was photoirradiated for
30 h under a nitrogen atmosphere with stirring to disperse TiO2.
The color of the TiO2 changed from white to blue gray. After 30 h of
photoirradiation, about 2.12 mmol of the iodide was consumed as
determined by HPLC. After removal of TiO2 by filtration, the solvent
was removed by rotary evaporation, and the residue was dissolved
in 50 mL of ether. The resulting ether solution was washed with
10% aq Na2S2O3 (50 mL) and then brine (50 mL), and dried over
MgSO4. The ether was removed under reduced pressure. The
residue was purified by column chromatography on silica gel with
hexane as eluent to give a mixture of 1-tridecafluorohexyl-
naphthalene (2) and 2-tridecafluorohexylnaphthalene (358 mg,
44% yield based on the consumed iodide, 6/1 mixture as
determined by 19F NMR, colorless oil). Unreacted naphthalene
was recovered later during the purification by column chromato-
graphy.
Chemicals) via Grignard reaction. Commercially available
a
aromatic compounds such as p-xylene, 1,4-dichlorobenzene,
naphthalene and benzofuran were used without further purifica-
tion. The solvent for the reaction, CH3CN, was distilled over CaH2
just prior to use. TiO2 (ST-01; Ishihara Sangyo Co., Ltd.) was used
for all photocatalytic reactions in this study.
2.1. Photocatalytic aromatic perfluoroalkylation with
perfluoroalkyl iodide
Perfluoroalkylated p-xylene (1a and 1b) [12], naphthalene (2)
[13,14], and benzofuran (3) [15] were prepared by the following
procedures.
2: 1H NMR (CDCl3,
8.06 (m, 1H), 8.23 (m, 1H); 19F NMR (CDCl3,
d): 7.59 (m, 3H), 7.83 (m, 1H), 7.92 (m, 1H),
d
): À5.01 (3F), À28.69
(2F), À44.61 (2F), À45.74 (2F), À46.94 (2F), À50.35 (2F); MS (m/z):
446 (M+), 177.
2.1.3. Perfluoroalkylation of benzofuran
The reaction of perfluorohexyl iodide (1.114 g, 2.5 mmol) with
benzofuran (5.0 mmol) was performed using the same procedure
as the perfluoroalkylation of p-xylene. After 50 h of photoirradia-
tion, 1.97 mmol of the iodide was consumed as determined by
HPLC. After removal of TiO2 by filtration from the reaction mixture,
the solvent was removed by rotary evaporation, and the residue
2.1.1. Perfluoroalkylation of p-xylene
TiO2 (80 mg) was dispersed in CH3CN (54 mL) and sonicated for
10 min. To the resulting disperse system, CH3OH (6 mL), NaBF4
(110 mg), perfluorohexyl iodide (1.114 g, 2.5 mmol) and p-xylene
(25 mmol) were added. Under a nitrogen atmosphere with stirring

928
M. Iizuka, M. Yoshida / Journal of Fluorine Chemistry 130 (2009) 926–932
was dissolved in 50 mL of ether. The resulting ether solution was
washed with 10% aq Na2S2O3 (50 mL) and then brine (50 mL), and
dried over MgSO4. The ether was removed by rotary evaporation,
and then the unreacted benzofuran was removed under reduced
pressure using a vacuum pump. The residue was purified by
column chromatography on silica gel with hexane as eluent to give
3 (298 mg, 43% yield based on the consumed iodide, colorless oil).
In this reaction, almost no regioisomers were produced.
dried over MgSO4. The ether was removed under reduced pressure.
The residue was purified by column chromatography on silica gel
with hexane as eluent, and 3-methyl-2-phenyl-4,4,5,5,6,6,7,7,
8,8,9,9,9-tridecafluorononene (5) (376 mg, 49% yield based on the
consumed iodide, colorless oil) was obtained.
5: 1H NMR (CDCl3,
(s, 1H), 5.53 (s, 1H), 7.31–7.36 (m, 5H); 13C NMR (CDCl3,
40.52 (t, JCCF = 21.7 Hz), 117.90, 126.39, 127.75, 128.45, 142.10,
145.24; 19F NMR (CDCl3,
): À5.01 (3F), À37.43 and À40.83 (ABq,
d
): 1.46 (d, J = 5.6 Hz, 3H), 3.54 (m, 1H), 5.43
): 15.10,
d
3: 1H NMR (CDCl3,
7.59 (m, 1H), 7.69 (m, 1H); 19F NMR (CDCl3,
d
): 7.25 (m, 1H), 7.35 (m, 1H), 7.46 (m, 1H),
d
d
): À5.01 (3F), À36.04
JFF = 277 Hz, 2F), À44.04 and À44.20 (ABq, JFF = 277 Hz, 2F), À46.05
(2F), À46.15 (2F), À46.89 (2F), À47.02 (2F), À50.36 (2F); MS (m/z):
(2F), À47.02 (2F), À50.36 (2F); HRMS (m/z): M+ calcd for C16H11F13
,
436 (M+), 167.
450.0653; found, 450.0632.
2.2. Photocatalytic perfluoroalkylation of
and its derivatives
a-methylstyrene
2.2.3. Reaction with 3,4-dihydro-1-methylnaphthalene
When the photocatalytic reaction of perfluorohexyl iodide with
3,4-dihydro-1-methylnaphthalene was performed using a proce-
2.2.1. Reaction with
a
-methylstyrene
dure similar to that described in the case of the reaction with a-
TiO2 (80 mg) was dispersed in CH3CN (58 mL) and sonicated for
10 min. To the resulting disperse system, CH3OH (2 mL), NaBF4
methylstyrene, further reaction occured between 2-tridecafluor-
ohexyl-1,3,4-trihydro-1-methylenenaphthalene (6), which was
the initial product of the reaction, and perfluoroalkyl radical.
Therefore, the photochemical reaction of 3,4-dihydro-1-methyl-
naphthalene was performed as follows. TiO2 (40 mg) was
dispersed in CH3CN (27 mL) and sonicated for 10 min. To the
resulting disperse system, CH3OH (3 mL), NaBF4 (55 mg), per-
fluorohexyl iodide (445 g, 1.0 mmol) and 3,4-dihydro-1-methyl-
naphtalene (432 mg, 3.0 mmol) were added. The solution was
similarly photoirradiated for 16 h. The color of the TiO2 changed
from white to blue gray. After 16 h of photoirradiation, about
0.33 mmol of the iodide remained unreacted as determined by
HPLC. After removal of TiO2 by filtration, the solvent was
evaporated and the residue was dissolved in 50 mL of ether. The
resulting ether solution was washed with 10% aq Na2S2O3 (50 mL)
and then brine (50 mL), and dried over MgSO4. The ether was
removed under reduced pressure. From the residue, 2-trideca-
fluorohexyl-1,3,4-trihydro-1-methylenenaphthalene (6) (135 mg,
44% yield based on the consumed iodide, colorless oil) was
obtained by column chromatography on silica gel with hexane as
an eluent.
(110 mg), perfluorohexyl iodide (1.114 g, 2.5 mmol) and
a-
methylstyrene (600 mg, 5.1 mmol) were added. Under a nitrogen
atmosphere with stirring to disperse TiO2, the solution was
photoirradiated for 45 h using two metal halide lamps (National
Sky-beam MT-70) that irradiated the reaction vessel from both
sides. The color of the TiO2 changed from white to blue gray. After
45 h of photoirradiation, 1.92 mmol of the iodide was consumed as
determined by HPLC. After removal of the TiO2 by filtration, the
solvent and unreacted
a-methylstyrene were removed by rotary
evaporation, and the residue was dissolved in 50 mL of ether. The
resulting ether solution was washed with 10% aq Na2S2O3 (50 mL)
and then brine (50 mL), and dried over MgSO4. The ether was
removed under reduced pressure. The residue was subjected to
column chromatography on silica gel with hexane as eluent. 2-
Phenyl-4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluorononene (441 mg, 52%
yield based on the consumed iodide, colorless oil) was obtained as
a mixture of 1-nonene (4a [16]) and 2-nonene (4b [16]) in the ratio
of 13/1 as determined by 19F NMR. The mixture was again
subjected to column chromatography on silica gel with hexane as
eluent. First, a small amount of 4b was eluted. Then, the main
product 4a was eluted and obtained in its pure form.
6: 1H NMR (CDCl3,
3.02 (m, 1H), 3.44 (m, 1H), 5.22 (s, 1H), 5.71 (s, 1H), 7.17 (m, 1H),
7.23 (m, 2H), 7.56 (m, 1H); 13C NMR (CDCl3,
): 22.78, 26.13, 43.00
(t, JCCF = 20.6 Hz), 116.41, 124.84, 126.36, 128.08, 128.45, 134.26,
136.14, 147.46; 19F NMR (CDCl3,
d): 2.14 (m, 1H), 2.32 (m, 1H), 2.80 (m, 1H),
d
d
): À5.39 (3F), À35.06 and À39.92
(ABq, JFF = 278 Hz, 2F), À44.81 (2F), À46.47 (2F), À47.35 (2F),
À50.71 (2F); HRMS (m/z): M+ calcd for C17H11F13, 462.0653; found,
462.0696.
4a: 1H NMR (CDCl3,
(s, 1H), 7.29–7.39 (m, 5H); 19F NMR (CDCl3,
d): 3.29 (t, JHF = 18 Hz, 2H), 5.41 (s, 1H), 5.64
d
): À5.38 (3F), À36.90
(2F), À46.37 (2F), À47.43 (2F), À47.60 (2F), À50.70 (2F); MS (m/z):
436 (M+), 167, 117, 115, 103.
4b: 1H NMR (CDCl3,
d
): 2.28 (s, 3H), 5.75 (t; JHF = 16 Hz, 1H),
7.29–7.39 (m, 5H); 19F NMR (CDCl3,
d
): À5.41 (3F), À30.00 (2F),
À46.21 (2F), À47.50 (2F), À47.99 (2F), À50.71 (2F); MS (m/z): 436
(M+), 167, 147, 127.
3. Results and discussion
2.2.2. Reaction with 2-phenyl-2-butene
3.1. Photocatalytic aromatic perfluoroalkylation
The reaction of perfluorohexyl iodide (1.114 g, 2.5 mmol) with
2-phenyl-2-butene (660 mg, 5.0 mmol) was performed using the
same procedure as the perfluoroalkylation of p-xylene. After 22 h
of photoirradiation, 1.70 mmol of the iodide was consumed as
determined by HPLC. After removal of TiO2 by filtration from the
reaction mixture, the solvent and unreacted 2-phenyl-2-butene
were removed by rotary evaporation, and the residue was
dissolved in 50 mL of ether. The resulting ether solution was
washed with 10% aq Na2S2O3 (50 mL) and then brine (50 mL), and
The photochemical perfluoroalkylation of an aromatic ring with
perfluoroalkyl iodide was examined under the various conditions
shown in Table 1; the reaction was monitored by HPLC and GC–MS.
Under a N2 atmosphere, a solution of CF3(CF2)5I (1.25 mmol) and p-
xylene (25 mmol) in 30 mL CH3CN was irradiated with light having
a wavelength of more than 350 nm using a metal halide lamp.
However, the reaction was very slow under the conditions, and
more than 90% of the iodide remained unreacted after 20 h of

M. Iizuka, M. Yoshida / Journal of Fluorine Chemistry 130 (2009) 926–932
929
Table 1
Photochemical reaction of perfluorohexyl iodide with p-xylene in the presence or absence of TiO2.
.
Run
Additive
Solvent
Conversion of CF3(CF2)5I/%a
Yield of Ar(CF2)5CF3/%b
1
2
3
4
5
6
None
CH3CN (30 mL)
7
8
Trace
TiO2 (40 mg)
CH3CN (30 mL)
Trace
TiO2 (40 mg)
CH3CN (27 mL), –CH3OH (3 mL)
CH3CN (27 mL), –CH3OH (3 mL)
CH3CN (27 mL), –C2H5OH (3 mL)
CH3CN (27 mL), –2-PrOH (3 mL)
44
67
64
8
20 (45)
46 (69)
32 (50)
Trace
TiO2 (40 mg), NaBF4 (55 mg)
TiO2 (40 mg), NaBF4 (55 mg)
TiO2 (40 mg), NaBF4 (55 mg)
a
Determined by HPLC.
b
Yields were determined by HPLC based on CF3(CF2)5I. The yields based on consumed CF3(CF2)5I are shown in parentheses.
photoirradiation as determined by HPLC analysis (Table 1, run 1).
Acceleration of the reaction was not observed even when TiO2
photocatalyst was used in CH3CN (Table 1, run 2). Interestingly,
using a solvent system of CH3CN (27 mL) and methanol (3 mL) was
found to make the reaction proceed smoothly (Table 1, run 3). The
addition of NaBF4 to the solvent system further accelerated the
reaction, and 67% of the iodide was consumed in the reaction
performed under these conditions (Table 1, run 4). Such an effect of
additives is also reported in the case of the TiO2-catalyzed
photooxygenation of 1,1-diarylethenes performed in the presence
of MgClO4 [17]. The products of the reaction were analyzed by GC–
MS, and perfluorohexylated p-xylene (1a) was detected as the
main product. The maximum yield (69%) based on the consump-
tion of perfluorohexyl iodide was obtained in run 4 in Table 1. In a
solvent system of CH3CN with ethanol, aromatic perfluoroalkyla-
tion giving 1a proceeded similarly (Table 1, run 5). However, no
effect of 2-propanol on the photocatalytic reaction was observed
(Table 1, run 6).
Scheme 3. Photoirradiation of TiO2 excites the electrons from the
valence band to the conduction band, leaving holes in the
valence band (Scheme 3, Eq. (1)). However, these excited
electrons did not reduce the iodide as
a result of the
recombination of the electrons with the holes (Scheme 3, Eq.
(1)), which was probably much faster than the reaction with the
iodide (Scheme 3, Eq. (2)). In the presence of methanol, the holes
are expected to react with methanol (Scheme 3, Eq. (3)) before
recombination of the holes with the electrons can occur, and as
a result, the excited electrons were able to reduce the iodide
to a perfluoroalkyl radical. The resulting perfluoroalkyl radical
reacted with p-xylene to form an arenium radical, which was
successively oxidized to an arenium cation by the holes (Scheme
3, Eq. (4)). Overall, the success of this aromatic perfluoroalkyla-
tion depends on the balance of the oxidation–reduction
reactions; methanol and NaBF4 may act as modulators to
maintain this balance.
Furthermore, the TiO2-photocatalytic aromatic perfluoroalk-
ylations of p-xylene, benzene and 1,4-dichlorobenzene with
perfluoroalkyl iodide were examined in a mixed solvent system
of CH3CN/CH3OH (9/1 by volume) in the presence of NaBF4. The
Perfluoroalkyl substituted p-xylene (1a) was obtained cleanly
under the conditions in run 4 in Table 1. As the most plausible
mechanism for the production of 1a, we propose that shown in
Scheme 3.

930
M. Iizuka, M. Yoshida / Journal of Fluorine Chemistry 130 (2009) 926–932
Table 2
[14,18]. When perfluorohexyl iodide (1.25 mmol) was reacted with
a mixture of p-xylene (12.5 mmol), benzene (12.5 mmol) and 1,4-
dichlorobenzene (12.5 mmol), the molar ratio between the
produced arenes (X = CH3/H) was 1.7/1.0. Almost no perfluo-
rohexylated 1,4-dichlorobenzene was obtained in this reaction.
These results can be explained as follows. There are two
possible reaction pathways for the intermediate perfluoroalkyl
radical (Scheme 4). The first route is the reaction of the radical on
the surface of TiO2. The other route is the diffusion of the radical
into the solvent and subsequent reaction with an arene to produce
a perfluoroalkylated arenium radical. The arenium radical in the
bulk solution encounters again to TiO2 to be oxidized by the holes
in the TiO2. Based on the maximum yield obtained for the reaction
of p-xylene, at least 70% of the perfluoroalkyl radical should diffuse
from the surface of TiO2. In the case of electron-deficient 1,4-
dichlorobenzene, the electrophilic perfluoroalkyl radical after
diffusion into solution may react with something beside the arene
to produce fluorine-containing side products before it reacts with
the arene. Thus, the yield of the perfluoroalkylation in 1,4-
dichlorobenzene is expected to be low. Only CF3(CF2)5H was
TiO2-photocatalytic perfluoroalkylations of benzenes.
.
Run
x of
n of
Molar ratio,
Yield of
ArH
CF3(CF2)nI
ArH/CF3(CF2)nI
Ar(CF2)nCF3/%a
1
2
3
4
5
6
7
CH3
CH3
CH3
CH3
CH3
H
5
5
5
5
3
5
5
2
10
20
30
10
10
10
28
58
72
72
56
51
13
Cl
a
Determined by HPLC based on CF3(CF2)nI.
results are shown in Table 2. Photoirradiation was continued until
the iodide was almost completely consumed, which required more
than 45 h. The photochemical reactions were performed using
various molar ratios of p-xylene and perfluorohexyl iodide
(Table 2, runs 1–4). When the reaction was carried out using
2 mol amt. of p-xylene to the iodide, the yield of 1a was poor
(Table 2, run 1). The yield of 1a was improved to about 70% by using
more than 20 mol amt. of p-xylene (Table 2, runs 2–4). Similarly,
perfluorobutylated p-xylene (1b) was also obtained in 56% yield
(Table 2, run 5). Unfortunately, trifluoromethylation using this
protocol with trifluoromethyl iodide was unsuccessful, and almost
all of the iodide remained unreacted. The reduction potential of
trifluoromethyl iodide is known to be higher than that of
perfluorohexyl or butyl iodide [6]. The effectiveness of the TiO2
photocatalyst as a reducing agent may not be sufficient for the
successful reaction of trifluoromethyl iodide using this method.
The reaction of perfluorohexyl iodide with benzene or 1,4-
dichlorobenzene was also examined (Table 2, runs 6 and 7).
Perfluorohexylbenzene was obtained in 51% yield (Table 2, run 6)
but the yield of the perfluorohexylated 1,4-dichlorobenzene was
poor (Table 2, run 7), even when the reaction was carried out in the
presence of 10 mol amt. of 1,4-dichlorobenzene. The reactivity of
these arenes in the production of perfluorohexylated arenes was
consistent with the electrophilicity of the perfluoroalkyl radical
characterized among the fluorine-containing side products by 19
F
NMR analysis of the solution for the reaction, which showed the
characteristic doublet signal of CF2–H coupling.
This methodology was applied to the practical preparation of
perfluoroalkylated arenes such as p-xylene, naphthalene and
benzofuran as described in Section 2, and these arenes were
obtained in moderate isolated yields. The reactivity of perfluo-
roalkyl radical with naphthalene is much higher than even that
with electron-rich benzenes such as toluene or anisole [14].
Therefore, in the perfluoroalkylation of naphthalene, 2 mol amt.
of naphthalene was sufficient to effectively trap the diffusing
perfluoroalkyl radical. Similarly, perfluoroalkylation of benzo-
furan proceeded effectively for the reaction of the iodide with
2 mol amt. of benzofuran. In these reactions, the desired
perfluoroalkylated products were easily separated from the
starting arenes. Thus, TiO2-photocatalitic reactions of perfluo-
roalkyl iodide with electron-rich aromatic compound are
proposed as a practical method for introducing perfluoroalkyl
groups to the aromatic ring.
3.2. Preparation of perfluoroalkylated
the methyl carbon
a-methylstyrene on
This methodology for reduction and successive oxidation was
further investigated in regards to the practical preparation of
perfluoroalkylated
a-methylstyrene, in which the perfluoroalkyl
group is on the methyl carbon, as shown in Scheme 2(b). Free-
radical chain iodoperfluoroalkylation of olefins using a perfluor-
oalkyl iodide is the most important method for the introduction of
perfluoroalkyl groups into organic molecules [1–3]. Triethylborane
is a superior radical initiator for iodoperfluoroalkylation [19].
However, in the reaction with
a-methylstyrene, the produced
benzyl-type radical is very stable against iodine abstraction from
the perfluoroalkyl iodide and the iodoperfluoroalkylation does not
proceed (Scheme 5) [13,20,21]. We have been investigating ways
Scheme 4.
Scheme 5.

M. Iizuka, M. Yoshida / Journal of Fluorine Chemistry 130 (2009) 926–932
931
Scheme 6.
Scheme 7.
for the produced benzyl-type radical to undergo further reaction
for the preparation of fluoroalkylated compounds [13,21], and
found a new way to convert the radical to a cation (Scheme 6). The
system consists of three steps: one-electron reduction of
perfluoroalkyl iodide, the addition of the radical to the olefin
and one-electron oxidation of the produced benzyl-type radical to
the cation. The reduction and oxidation were carried out by the
excited electrons and the holes produced in the TiO2 photocatalyst.
commercially available ketones and methyl magnesium iodide.
Thus, this reaction is expected to be a useful method for the
practical preparation of novel fluorinated 2-aryl-1-alkenes. To
demonstrate the usefulness of this technique, we prepared
fluoroalkylated ring compound (6) from
a-tetralone (see Scheme
A solution of perfluoroalkyl iodide and
a
-methylstyrene in
8(b) and Section 2).
CH3CN in dispersion of TiO2 was photoirradiated under
a
Here, we have demonstrated a new system using TiO2 as a
photocatalyst to produce perfluoroalkyl radical that results in
conditions similar to those for the aromatic perfluoroalkylations
shown in Table 1. As was reported in our preliminary commu-
nication, perfluoroalkylated olefins (4a and 4b), the alcohol 7, the
methoxylated compound 8 and other miscellaneous fluoroalky-
lated products were detected by GC–MS analysis [11]. These
products are thought to be produced via the cationic intermediate,
which can likely provide access to various organofluorine
compounds (Scheme 7). Interestingly, olefin 4a was produced
preferentially over 4b from the cation, although this result was
inconsistent with the Saytzeff orientation.
perfluoroalkylation of aromatic rings and
a-methylstyrene deri-
vatives. Among the various examples for perfluoroalkylation with
perfluoroalkyl iodide [3–5,14,19 and the references cited therein],
the methodology described here has an important feature to lead
to substantial substitution reaction on organic molecule by
fluoroalkyl group. In the reactions with aromatic rings, rear-
omatization of the arenium radicals proceeded effectively, and
fluoroalkylated aromatic compounds were obtained as clean
products. In the reactions with
a-methylstyrene derivatives, the
In this paper, we focused on the practical preparation of olefin
4a and related olefins that have high potential as building blocks
for the synthesis of fluorine compounds and as starting materials
usual addition products of perfluoroalkyl group with iodine and
hydrogen atoms to the double bond were not obtained, but
fluoroalkyl substituted terminal alkenes were obtained as main
products. These are, in our opinions, due to efficient oxidation of
the intermediate fluoroalkylated radicals to the corresponding
cations by the holes in TiO2. Further, TiO2 is cheap, easy to handle,
and non-toxic. Thus, this redox system using TiO2 is expected to be
practical methodology for introducing perfluoroalkyl group to
organic molecules.
for new types of polymers. Through the use of this reaction with
b-
substituted -methylstyrene, namely, 2-phenyl-2-butene synthe-
a
sized from ethyl phenyl ketone, perfluorohexylated 2-phenyl-1-
alkene 5 was prepared in moderate yield (see Scheme 8(a) and
Section 2). The various 2-aryl-2-alkenes used as substrates for this
reaction are synthesized via the reaction of the corresponding
Scheme 8.

932
M. Iizuka, M. Yoshida / Journal of Fluorine Chemistry 130 (2009) 926–932
[8] For recent examples: Y. Itoh, K. Mikami, Tetrahedron Lett. 62 (2006) 7199;
Acknowledgements
V. Petrik, D. Cahard, Tetrahedron Lett. 48 (2007) 3327, and the references cited
therein.
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (417) and a Grant-in-Aid for Scientific
Research (C) from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT) of the Japanese Government. The
authors thank Mr. S. Fukushima of the Center for Integrated
Research in Science, Shimane University for MS measurements.
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