Perfluoroalkylation of α-methylstyrene using titanium oxide as a photocatalyst

Article abstract of DOI:10.1246/cl.2007.1042

A redox system for fluoroalkylation with perfluoroalkyl iodide using TiO₂ as a photocatalyst was developed. Photoirradiation of perfluoroalkyl iodide and α-methylstyrene in CH₃CN in the presence of TiO₂ and NaBF₄

Full text of DOI:10.1246/cl.2007.1042

1
042
Chemistry Letters Vol.36, No.8 (2007)
Perfluoroalkylation of ꢀ-Methylstyrene Using Titanium Oxide as a Photocatalyst
Ã
Mari Iizuka, Shoju Fukushima, and Masato Yoshida
School of Medicine, Shimane University, Izumo 693-8501
(Received June 5, 2007; CL-070604; E-mail: yoshidam@med.shimane-u.ac.jp)
A redox system for fluoroalkylation with perfluoroalkyl io-
[CF (CF ) I ] / [CF (CF ) I ]
3
2 5
t
3
2 5
0
dide using TiO2 as a photocatalyst was developed. Photoirradia-
tion of perfluoroalkyl iodide and ꢀ-methylstyrene in CH3CN in
the presence of TiO2 and NaBF4 gave ꢀ-fluoroalkylstyrene.
1.0
0.80
(
a)
0
0
.60
.40
Perfluoroalkyl iodide is well known as a source of perfluoro-
alkyl radical. These radicals are produced from the iodide ther-
1
mally, photochemically, or by the use of radical initiator.
A one-electron reduction of the iodide is an alternative way to
0
.20
(c)
(b)
2
produce perfluoroalkyl radical. Free-radical chain iodoperfluo-
roalkylation of olefins using the iodide with the olefin is the most
important method for the introduction of perfluoroalkyl group
0
2
4
6
8
10 time / h
1
Figure 1. Photochenical decomposition of CF3(CF2)5I. Condi-
tions: (a) CF3(CF2)5I (1.25 mmol), TiO2 (40 mg) in CH3CN
30 mL); (b) CF3(CF2)5I (1.25 mmol), TiO2 (40 mg) in CH3CN
25 mL) and MeOH (5 mL); (c) CF3(CF2)5I (1.25 mmol), TiO2
40 mg), NaBF4 (0.5 mmol) in CH3CN (25 mL) and MeOH
5 mL).
into organic molecules. However, in the reaction with ꢀ-meth-
ylstyrene, the produced benzyl type radical is too stable to
(
(
(
(
abstract the iodine from perfluoroalkyl iodide promoting the
3
radical chain reaction (Scheme 1).
We have been exploring the synthetic utility of the reaction
of perfluoroalkyl iodide with ꢀ-methylstyrene. In the course of
our work, we have discorvered TiO2-catalyzed perfuoroalkyla-
tion of ꢀ-methylstyrene with perfluoroalkyl iodide. The results
are described in this communication (Scheme 2).
(Figure 1a). Interestingly, in the presence of 5 mL of MeOH, a
smooth decomposition began to proceed after an induction
period (Figure 1b). Photoirradiation of TiO excites the electrons
2
The photochemical decomposition of perfluoroalkyl iodide
in the presence of TiO2 was examined. Light of more than
from the valence band to the conduction band, leaving holes in
the valence band. However, these electrons did not achieve the
reduction of the iodide, since the recombination between the
electrons and the holes was probably much faster (Scheme 3,
eq 1). In the presence of MeOH, the holes should react with
MeOH before recombination (Scheme 3, eq 2), and the electrons
therefore acted to reduce the iodide to give perfluoroalkyl
radicals (Scheme 3, eq 3). The decomposition of the iodide
350-nm wavelength was irradiated to the solution of CF3(CF2)5I
(
1.25 mmol) in 30-mL CH3CN in the presence of TiO2 (ST-01;
Ishihara Sangyo Co., Ltd.) using a metal halide lamp under a
N2 atmosphere, and the decay of the iodide was monitored
by HPLC. HPLC analysis was performed by a Shimadzu
SPD-6A liquid chromatograph equipped with a Cosmosil 5C18
2
(
4:6 Â 250 mm , Nacalai Tesque reverse phase column) with
was further accelerated by the addition of NaBF (Figure 1c).
4
MeOH/H2O (80/20 in volume) as eluent. The photochemical
decomposition of perfluoroalkyl iodide did not proceed smooth-
ly even in the presence of TiO2; for 9 h irradiation, 82% of
the iodide was left unchanged, as determined by HPLC
The enhancement of the efficiency of CF (CF ) I decomposition
3
2 5
may be explained by the suppression of back electron transfer
4
to the radical cation.
On the basis of these results, the introduction of perfluoro-
alkyl radicals thus produced into organic molecules was investi-
gated. A solution of perfluoroalkyl iodide and ꢀ-methylstyrene
in CH3CN in the presence of TiO2 was photoirradiated under
similar conditions. Perfluoroalkylated olefins (1 and 2), the
alcohol 3, the methoxylated compound 4 (Chart 1) and other
miscellaneous fluoroalkylated products were detected by
GC-MS analysis. The distribution of the products was heavily
influenced by the conditions.
H3C
CH3
CF3(CF2)n •
+
C
CH2–(CF2)nCF3
•
Ph
Ph
CF (CF )
I
CH3
CH (CF ) CF
3
3
2 n
Ph
2
2 n
CF3(CF2)n •
I
Scheme 1.
h
ν
TiO
2
electrons (e–)
+
+
holes (h+)
(1)
(2)
h+
e–
h
ν, TiO2
CH2(CF2)nCF3
+•
CH3
3
(CH OH)
CH OH
3
CF3(CF2)n I
+
Ph
Ph
CF
3
(CF
)
2 n
I
CF
3
2
(CF )
n
•
I–
(3)
Scheme 2.
Scheme 3.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.8 (2007)
1043
I–
CH3
CH2(CF2)5CF3 CH2(CF2)5CF3
CH
CF3(CF2)5 •
+
CH2(CF2)5CF3
Ph
CF3(CF2)5 I
(
CF ) CF
2 5 3
CH3
OH
3
Ph
Ph
OCH
3
Ph
CH3
H
1
2
3
4
e–
Ph
TiO2
Chart 1.
h
ν
Ph
•
C
CH2–(CF2)5CF3
Table 1. Preparation of fluoroalkylated olefin
3
CH OH
H C
h+
3
h
ν
, TiO2 (40 mg),
NaBF4 (0.5 mmol)
CH3
CH (CF ) CF
2 2 5 3
CF3(CF2)5I
1.25 mmol)
+
CH OH) •+
(
3
Ph
+
C
(
Ar
CH3CN–CH3OH
Ar
CH2–(CF2)5CF3
– H+
Solevnt
systema
Ar
/mmol
Conversion of
iodide/%
H C
3
Run
Time/h
Yield/%b
1
2
3
4
5
6
7
8d
9
30/0
29/1
27/3
25/5
25/3
27/3
27/3
27/3
27/3
Ph (1.25)
Ph (1.25)
Ph (1.25)
Ph (1.25)
Ph(1.25)
18
18
18
18
42
18
42
18
18
33
56
22 (66)
48 (86)
50 (72)
43 (61)
54c
CH (CF ) CF
3
2
2 5
69
Ph
71
97
Scheme 4.
Ph (2.50)
Ph (2.50)
Ph (2.50)
4-MeC6H5
67
46 (71)
67
TiO2 as a photocatalyst. A plausible reaction mechanism is
shown in Scheme 4. Electrons and holes are produced on the
surface of TiO2. Owing to the electrons, perfluoroalkyl iodide
is reduced to perfluoroalkyl radicals and iode anions. The pro-
duced radicals add to ꢀ-methylstyrene to give the corresponding
benzyl type radical. This stable radical cannot abstract the iodine
from perfluoroalkyl iodide, and is oxidized to the cation by
the holes. Thus, this fluoroalkylation is achieved on the balance
of the oxidation–reduction. MeOH and NaBF4 may act as
modulators to keep the balance successfully.
100
72
54 (74)
46 (56)
83
(
2.50)
2-MeC6H5
2.50)
4-ClC6H5
2.50)
Ph (2.50)
1
1
1
0
27/3
27/3
27/3
18
18
18
76
62
70
54 (71)
30 (47)
37 (53)
(
1
(
2e
a
b
The ratio of CH3CN/MeOH is shown. The characterization of 1
was performed by comparison with the spectral data for authentic
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (417) from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT)
of the Japanese Government.
3
samples. Yield was determined by HPLC based on CF3(CF2)5I us-
ing m-nitrotoluene as an internal standard. Yield based on consumed
CF3 (CF2)5I is shown in parentheses. Produced 1 should undergo
c
reaction with CF3(CF2)5I to be converted into further fluoroalkylat-
d
ed products under these conditions. LiBF4 instead of NaBF4 was
References and Notes
e
used in this run. Perfluorobutylation with CF3(CF2)3I was investi-
gated in this run.
1
M. Yoshida, N. Kamigata, H. Sawada, M. Nakayama, J.
Fluorine Chem. 1990, 49, 1; W. R. Dolbier, Jr., Chem.
Rev. 1996, 96, 1557; N. O. Brace, J. Fluorine Chem. 1999,
93, 1; N. O. Brace, J. Fluorine Chem. 1999, 96, 101.
Electrochemically: C. P. Andrieux, L. G e´ lis, M. Medebielle,
J. Pinson, J.-M. Sav e´ ant, J. Am. Chem. Soc. 1990, 112, 3509.
one-electron reduction with Na2 S2O4: W.-Y. Huang, J.
Fluorine Chem. 1992, 58, 1. one-electron reduction with
SmI2: M. Yoshida, D. Suzuki, M. Iyoda, J. Chem. Soc.,
Perkin Trans. 1, 1997, 643.
Here, we focused our attention on the selective preparation
of 1. The results obtained under various conditions are summa-
rized in Table 1.
2
MeOH was essential to make this reaction proceed smoothly
(
ꢀ
(
Table 1; Runs 1–4). This methodology was applied to various
-methylstyrenes possessing substituents on the aromatic ring
Table 1; Runs 9–11), or perfluorobutylation of ꢀ-methylstyrene
using CF3(CF2)3I (Table 1; Run 12). Unfortunately, an attempt-
ed run for trifluoromethylation with CF3I was unsuccessful, and
almost all of the CF3I remained unchanged.
3
M. Yoshida, M. Ohkoshi, N. Aoki, Y. Ohnuma, M. Iyoda,
Tetrahedron Lett. 1999, 40, 5731; M. Yoshida, M. Ohkoshi,
T. Muraoka, H. Matsuyama, M. Iyoda, Bull. Chem. Soc. Jpn.
2002, 75, 1833.
H. Maeda, H. Miyamoto, K. Mizuno, Chem. Lett. 2004, 33,
462.
Recently, much attention has been given to TiO2 as a photo-
5
catalyst. However, application to organic synthesis, especially
4
5
to carbon–carbon bond formation, has little been reported thus
far. Now, we have developed a new redox system for perfluor-
oalkylation leading to carbon–carbon bond formation using
M. R. Hoffmann, S. T. Martin, W. Choi, D. W. Bahnemann,
Chem. Rev. 1995, 95, 69.
Published on the web (Advance View) July 14, 2007; doi:10.1246/cl.2007.1042