Synthesis of 2-aryl-3,3,3-trifluoropropanoic acids using electrochemical carboxylation of (1-bromo-2,2,2-trifluoroethyl)arenes and its application to the synthesis of β,β,β-trifluorinated non-steroidal anti-inflammatory drugs

Article abstract of DOI:10.1016/j.tet.2009.11.053

Electrochemical carboxylation of (1-bromo-2,2,2-trifluoroethyl)arenes resulted in an efficient fixation of carbon dioxide to give the corresponding 2-aryl-3,3,3-trifluoropropanoic acids in good yields, and the present reactions were successfully applied to the synthesis of β,β,β-trifluorinated non-steroidal anti-inflammatory drugs (NSAIDs).

Full text of DOI:10.1016/j.tet.2009.11.053

Tetrahedron 66 (2010) 473–479
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 2-aryl-3,3,3-trifluoropropanoic acids using electrochemical
carboxylation of (1-bromo-2,2,2-trifluoroethyl)arenes and its application to the
synthesis of
b,
b,
b-trifluorinated non-steroidal anti-inflammatory drugs
*
Yusuke Yamauchi, Shoji Hara, Hisanori Senboku
Laboratory of Organic Reaction, Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 October 2009
Received in revised form 11 November 2009
Accepted 12 November 2009
Available online 15 November 2009
Electrochemical carboxylation of (1-bromo-2,2,2-trifluoroethyl)arenes resulted in an efficient fixation of
carbon dioxide to give the corresponding 2-aryl-3,3,3-trifluoropropanoic acids in good yields, and the
present reactions were successfully applied to the synthesis of
b
,b
,b
-trifluorinated non-steroidal anti-
inflammatory drugs (NSAIDs).
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Electrochemical reduction
Fixation of carbon dioxide
Carboxylic acids
Fluorine containing compounds
NSAIDs
1. Introduction
and (perfluoroalkyl)alkenes with a nickel catalyst9 was reported
to proceed with C–F bond cleavage to yield the corresponding
The use of carbon dioxide (CO2) as a carbon source for chemical
reaction is important and an attractive research topic in organic
synthesis.1 One useful and effective method for the reaction of CO2
and organic compounds with a C–C bond formation involves an
electrochemical process. Electrochemical fixation of CO2 into or-
ganic molecules gives carboxylic acids. The fixation can be readily
accomplished in high yields under neutral and mild conditions
even under an atmospheric pressure of carbon dioxide when
a reactive metal, such as magnesium or aluminum, is used as an
anode in the electrolysis.2,3 We have already reported the syn-
thesis of useful carboxylic acids by electrochemical carboxylation
(EC) of various organic compounds.4 On the other hand, it is well
known that fluorine-containing organic compounds have unique
chemical and physical properties. The introduction of fluorine
atoms into biologically-active compounds is also known to cause
remarkable modification of their original activities.5 Therefore,
considerable attention has been paid to efficient and selective
preparation methods of organofluorine compounds.6 However,
little attention has been paid to EC to afford fluorinated carboxylic
acids. Fluorinated benzoic acids were synthesized by EC of tri-
fluorinated carboxylic acids. We also reported EC of
toluenes10 and pentafluoroethylarenes11 to obtain
phenylacetic acids and 2-aryl-2,3,3,3-tetrafluoropropanoic acids,
respectively. Their applications to the synthesis of -fluorinated
and -tetrafluorinated non-steroidal anti-inflammatory
a
,
a
-difluoro-
a
-fluoro-
a
a,b,b,b
drugs (NSAIDs) were also successfully carried out.10,11 Although
there have been several reports on EC of (1-haroethyl)arenes
(1-arylethyl halides) and their application to the synthesis of
NSAIDs,2a,3a,12 to the best of our knowledge, our reports on EC
using (1-haroethyl)arenes having fluorine atoms in an ethyl
moiety10,11 are the only examples and no further EC has been
reported. We recently found that 2-aryl-3,3,3-trifluoropropanoic
acids could be easily synthesized by efficient EC of (1-bromo-2,2,2-
trifluoroethyl)arenes, and its application to the synthesis of tri-
fluorinated NSAIDs was successfully carried out. We report herein
the synthesis of
b,b,b-trifluorinated NSAIDs by EC of (1-bromo-
2,2,2-trifluoroethyl)arenes.
2. Results and discussion
fluoromethyl or fluoroarylhalides.3a,7 EC of -trifluorotoluene8
a,a,a
2.1. Screening of reaction conditions
(1-Bromo-2,2,2-trifluoroethyl)benzene (3), a model substrate,
could be easily prepared as shown in Scheme 1. Reduction of
* Corresponding author. Tel./fax: þ81 11 706 6555.
E-mail address: senboku@eng.hokudai.ac.jp (H. Senboku).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.053

474
Y. Yamauchi et al. / Tetrahedron 66 (2010) 473–479
equipped with a Pt plate cathode (2ꢂ2 cm2) and a Zn plate anode
O
OH
CF3
Br
(2ꢂ2 cm2) (Scheme 2). This acceptable yield of 4 prompted us to
NBS, (PhO)3P
NaBH4
CF3
CF3
apply the present EC to synthesis of b,b,b-trifluorinated NSAIDs.
MeOH
77%
CH2Cl2
63%
1
2
3
2.2. Synthesis of b,b,b-trifluorinated NSAIDs by
electrochemical carboxylation
Scheme 1. Synthesis of (1-bromo-2,2,2-trifluoroethyl)benzene 3.
2.2.1. Introduction. Several 2-arylpropanoic acids are known to
inhibit various types of inflammation and are used as NSAIDs. On
the other hand, it was mentioned above that introduction of fluo-
rine atoms into biologically-active compounds often causes re-
markable modification of their original activities. Actually, it has
commercially available 2,2,2-trifluoroacetophenone (1) with
NaBH4 in MeOH gave the corresponding alcohol 2 in 77% yield.
Treatment of 2 with N-bromosuccinimide and triphenylphosphite
in CH2Cl2 gave (1-bromo-2,2,2-trifluoroethyl)benzene (3) in 63%
yield.
13
been reported that
of the balance of COX-1/COX-2 inhibitions and that the resulting
-fluorinated NSAIDs show a little anti-cancer activity.14 For these
reasons, -fluorinated NSAIDs having a 2-aryl-2-fluoropropanoic
a-fluorination of NSAIDs results in modification
Firstly, screening of reaction conditions, including temperature,
current density, electricity, and anode material, in EC was carried
out using 3 as a substrate and the results are shown in Table 1.
When a constant current electrolysis (10 mA/cm2) of 3 in DMF
containing 0.1 M Bu4NBF4 was carried out with 4 F/mol of elec-
tricity by using an undivided cell equipped with a Pt cathode and an
Mg anode in the presence of CO2 at 0 ꢀC, expected 3,3,3-trifluoro-2-
phenylpropanoic acid (4) was obtained in only 22% yield (entry 1).
The reactions at lower reaction temperature resulted in increases of
the yield of 4 to 60% at ꢁ40 ꢀC (entries 2–5). Although no im-
provement in yield was realized by screening of current density and
electricity (entries 6–9), the yield of 4 was improved up to 70% by
changing the anode metal from Mg to Zn (entry 10). Concentration
effect of the substrate 3 was also examined in EC using a Zn anode
(entries 11–12). However, no further improvement in yield was
realized. From these screenings, trifluoro-2-phenylpropanoic acid 4
was finally obtained in 66% isolated yield by EC of bromide 3 under
optimized conditions as shown in Scheme 2 using an undivided cell
a
a
acid moiety are suitable target molecules for organic synthesis, and
several successful syntheses have been reported.10,15 However, to
the best of our knowledge, little attention has been paid to the
synthesis of b,b,b
-trifluoro-NSAIDs,16 of which biological activities
would also be anticipaited.
2.2.2. Preparation of bromides 9 as precursors of b,b,b-trifluorinated
NSAIDs. Preparation of 1-bromo-2,2,2-trifluoroethylarenes 9 as
precursors of -trifluoro-NSAIDs was carried out as shown in
b,b,b
Scheme 3. Aryl Grignard reagents, generated from the corre-
sponding aryl halides 517 and magnesium in ether, were reacted
with Weinreb amide 618 to give the corresponding aryl tri-
fluoromethyl ketones 7. Reduction of 7 with NaBH4 in MeOH gave
alcohols 8. 1-Bromo-2,2,2-trifluoroethylarenes 9 were successfully
obtained by treatment of alcohols 8 with (a) CBr4 and Ph3P in tol-
uene19 for 8a and 8c or with (b) NBS and (PhO)3P in CH2Cl213 for 8b
and 8d.
Table 1
Screening of reaction conditions in EC of 3a
O
1) Mg, Et2O
NaBH4
MeOH
Br
CO2H
CF3
Ar
X
CO2
Pt
M
O
Ar
CF3
2)
CF3
5a-d
OMe
0.1 M Bu4NBF4 in DMF
5b: p- / o- = 79 / 21
F3C
N
7a: 70%
7b:
7c: 77%
7d: 68%
6
Me
3
4
Entry Temperature Current Density Electricity Anode Material Yieldb
[ꢀC]
[mA/cm2]
[F/mol]
(M)
[%]
Br
OH
1
2
3
4
5
6
7
8
0
10
10
10
10
10
5
20
10
10
10
10
10
4
4
4
4
4
4
4
3
5
4
4
4
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Mg
Zn
22
33
40
60
58
56
23
41
44
70
37
55
(a) CBr4, PPh3, toluene
or (b) NBS, P(OPh)3, CH2Cl2
ꢁ10
ꢁ20
ꢁ40
ꢁ60
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
Ar
CF3
Ar
CF3
8a: 95%
9a: 66% by (a)
9b: 60% by (b)
9c: 70% by (a)
9d: 60% by (b)
8b: 45% in 2 steps
8c: 92%
8d: 91%
9
10
11c
12d
Zn
Zn
PhO
a: X = Br, Ar =
b: X = I, Ar =
a
All reactions were carried out using 1 mmol of bromide 3 in DMF (10 mL).
Yields were determined by 19F NMR.
Reaction was carried out using 2 mmol of bromide 3 in DMF (10 mL).
Reaction was carried out using 0.5 mmol of bromide 3 in DMF (10 mL).
i-Bu
b
c
d
c: X = Br, Ar =
d: X = Br, Ar =
Ph
MeO
F
Br
CO2H
CF3
CO2
,
Zn
Pt
Scheme 3. Synthesis of 1-bromo-2,2,2-trifluoroethylarenes 9.
CF3
2.2.3. Synthesis of
b,b,b-trifluorofenoprofen. EC of 1-(1-bromo-
0.1 M Bu4NBF4 in DMF
10 mA/cm2 , 4 F/mol
2,2,2-trifluoroethyl)-3-phenoxybenzene (9a) under optimized
conditions as described above resulted in efficient fixation of CO2 at
the benzylic position with a reductive cleavage of a C–Br bond to
3
4
-40 °C
Isolated yield 66%
Scheme 2. EC of (1-bromo-2,2,2-trifluoroethyl)benzene 3 under optimized conditions.
achieve synthesis of
b,b,b-trifluorofenoprofen (10) in 70% yield

Y. Yamauchi et al. / Tetrahedron 66 (2010) 473–479
475
along with recovery of 17% of 9a (entry 1 in Table 2). When 5 F/mol
of electricity was supplied, the yield of 10 was slightly increased to
80% (entry 2). It should be noted that a small amount of difluoro-
styrene derivative 11 was observed in both cases in 3% and 4% 19F
NMR yields, respectively. Its formation was easily confirmed by
a comparison of 1H and 19F NMR spectra of crude products with
reported ones of similar difluorostyrenes.20 Thus, one proton
ꢁ60 ꢀC, the yield of 12 was improved to 57% along with a decrease
in the yield of 13 to 9% (entry 2). Finally, EC of 9b at ꢁ60 ꢀC with 6 F/
mol of electricity gave carboxylic acid 12 in 62% 19F NMR yield
(entry 3). Since other carboxylic acids were detected by 19F NMR,
the desired carboxylic acid was isolated as its methyl ester. Thus,
treatment of crude products with trimethylsilyldiazomethane22 in
benzene and MeOH gave methyl ester of 12, which was purified by
column chromatography to give methyl 3,3,3-trifluoro-2-(4-iso-
appeared at
d
5.24 (1H, dd, J¼25.6 and 3.6 Hz) ppm in 1H NMR and
two fluorine atoms also appeared in 19F NMR at
d
ꢁ83.99 (1F, dd,
butylphenyl)propanoate, b,b,b-trifluoroibuprofen methyl ester (14)
in 42% isolated yield in two steps (Scheme 4).
J¼31.3, and 3.6 Hz) and ꢁ81.70 (1F, dd, J¼31.3, and 25.6 Hz) ppm. It
is likely that the formation of 11 is caused by the elimination of
a fluoride anion at the
anion generated by electroreductive cleavage of a C–Br bond. Ac-
tually, it is well known that -trifluoroethyl carbanion species
b-position from the corresponding benzyl
CO2Me
CF3
Br
CO2
Pt
Zn ,
TMSCHN2
b,b,b
CF3
mostly release a fluoride ion spontaneously to give difluoro-
alkenes.21 When a similar EC of 9a was carried out at a higher
temperature, 0 ꢀC, the elimination of a fluoride ion was advanced to
result in an increase in the yield of 11 and decrease in the yield of 10
(entry 3). On the other hand, it has been reported by us that
a similar EC of 1-pentafluoroethyl-3-phenoxybenzene took place
benzene-MeOH
0.1 M Bu4NBF4 in DMF
10 mA/cm2 , 6 F/mol
i-Bu
i-Bu
9b
14
Isolated yield 42%
-60 °C
Scheme 4. Synthesis of b,b,b-trifluoroibuprofen methyl ester (14).
efficiently even at 0 ꢀC to give
yield without formation of trifluorostyrene.11 These results in-
dicated that a fluorine atom at the benzylic position in -tri-
a,b,b,b-tetrafluorofenoprofen in 82%
We also investigated the synthesis of two other
b,b,b-tri-
fluorinated NSAIDs. Similar EC of 2-(1-bromo-2,2,2-trifluoroethyl)-
6-methoxynaphthalene (9c) under 5 mA/cm2 of constant current
with 3 F/mol of electricity at ꢁ40 ꢀC followed by esterification with
trimethylsiliydiazomethane successfully afforded the desired
methyl 3,3,3-trifluoro-2-(6-methoxynaphthalen-2-yl)propanoate,
b,b,b
fluoroethyl carbanion species plays an important role in its stability,
although we do not have any explanation for this effect at present.
2.2.4. Synthesis of methyl esters of b,b,b-trifluoroibuprofen, -naproxen,
b,
b,
b-trifluoronaproxen methyl ester (15) in 48% yield in two steps.
and -flurbiprofen. EC of 1-(1-bromo-2,2,2-trifluoroethyl)-4-iso-
butylbenzene (9b) under conditions similar to those for entry 1 in
Table 2 surprisingly gave desired carboxylic acid 12 in poor yield
along with undesired 2,2-difluorostyrene 13 in 19% yield (entry 1 in
Table 3). When the reaction was carried out at a lower temperature,
Inasimilarmanner, methyl3,3,3-trifluoro-2-(2-fluorobiphenyl-4-yl)-
propanoate,
b,b,b-trifluoroflurbiprofen methyl ester (16) could
also be obtained in 59% yield by EC of 9d under 5 mA/cm2 of
constant current with 4 F/mol of electricity at ꢁ40 ꢀC followed
by a similar esterification (Scheme 5).23
Table 2
Synthesis of
b
,b
,
b-trifluorofenoprofen (10) by EC of trifluoroethylarene 9a
Br
CO2H
CO2
Pt
Zn
,
F
PhO
PhO
PhO
+
CF3
CF3
F
0.1 M Bu4NBF4 in DMF
10 mA/cm2
9a
10
11
Entry
Electricity [F/mol]
Temperature [ꢀC]
Yield [%]
Recovered 9ab [%]
10a
11b
1
2
3
4
5
4
ꢁ40
ꢁ40
0
70
80
54
3
4
35
17
7
2
a
Isolated yield.
b
Determined by 19F NMR.
Table 3
Synthesis of
b
,b
,
b-trifluoroibuprofen (12) by EC of 9b
Br
CO2H
CF3
CO2
Pt
Zn ,
F
+
CF3
F
0.1 M Bu4NBF4 in DMF
10 mA/cm2
i-Bu
i-Bu
i-Bu
9b
12
13
Entry
Electricity [F/mol]
Temperature [ꢀC]
Yielda [%]
Recovered 9ba [%]
12
13
1
2
3
4
4
6
ꢁ40
ꢁ60
ꢁ60
36
57
62
19
8
6
10
11
7
a
Determined by 19F NMR.

476
Y. Yamauchi et al. / Tetrahedron 66 (2010) 473–479
Br
CO2Me
CF3
CO2
TMSCHN2
Pt
Zn ,
CF3
benzene-MeOH
0.1 M Bu4NBF4 in DMF
5 mA/cm2, 3 F/mol
MeO
MeO
9c
15
-40 °C
isolated yield 48%
Br
CO2Me
CF3
CO2
TMSCHN2
Pt
Zn ,
F
F
CF3
benzene-MeOH
0.1 M Bu4NBF4 in DMF
5 mA/cm2, 4 F/mol
Ph
Ph
9d
16
-40 °C
isolated yield 59%
Scheme 5. Synthesis of
b,
b,
b-trifluoronaproxen methyl ester (15) and
b,
b,
b-trifluoroflurbiprofen methyl ester (16).
At Cathode
Br
CO2
CO2
+ 2e
-Br
CF3
CF3
CF3
R
R
R
A
B
At Anode
Zn
Zn2+
+
2e
CO2
CF3
Zn
CO2ZnBr
Zn2+
+
CF3
B
and / or
R
R
2
D
C
Scheme 6. Probable reaction mechanism.
Br
2.3. Reaction mechanism
+2e
-Br
F
-F
CF3
CF2
R
R
R
A probable reaction mechanism is shown in Scheme 6. At the
cathode, two-electron reduction of the substrate results in C–Br
bond cleavage at the benzylic position to generate benzylic anion A
as an intermediate. In cyclic voltammetry of the typical benzyl
bromide 3 used as a substrate, an irreversible reduction peak ap-
pears at ꢁ1.9 V Ag/Agþ and these results indicate that electro-
chemical reduction of the benzyl bromide would take place easily
and smoothly. The anion A attacks CO2 to give carboxylate ion B. On
the other hand, at the anode, dissolution of zinc takes place to
produce zinc ion, which captures carboxylate ion B to give zinc
carboxylate C and/or D. Acid treatment in workup gives the cor-
responding carboxylic acid.
F
F
A
Scheme 7. Probable reaction mechanism affording difluoroalkene.
3. Conclusion
In conclusion, we have succeeded in synthesis of 2-aryl-3,3,3-
trifluoropropanoic acids by the electrochemical reduction of
(1-bromo-2,2,2-trifluoroethyl)arenes in the presence of CO2 using
a Pt cathode and a Zn anode. This new method was also shown to
be effective for the synthesis of b,b,b-trifluorinated non-steroidal
anti-inflammatory drugs.
As mentioned earlier, b,b,b-trifluoroethyl anion is mostly known
to release a fluoride ion spontaneously to give difluoroalkenes.21 In
the present EC, benzyl anion A thus generated has fluorine atoms at
the neighboring carbon of an anion center. Elimination of a fluoride
ion would proceed competitively to give difluorostyrene as a by-
product, resulting in a decrease in yield of the expected product.
When the EC of 9a was carried out at 0 ꢀC, the elimination of
a fluoride ion producing difluorostyrene 11 was advanced in contrast
to the reaction at ꢁ40 ꢀC (Table 1). On the other hand, the reaction at
ꢁ60 ꢀC could suppress the elimination, resulting in an increase in
the yield of acid 10. These results indicated that the elimination of
a fluoride ion from anion A would depend on its thermal conditions
and would be closely related to its stability21 (Scheme 7).
4. Experimental section
4.1. General
Melting points were measured on a Yanagimoto micro melting
point apparatus and are uncorrected. IR spectra were determined
with a JASCO FT/IR-410 spectrometer in neat form unless otherwise
stated. 1H (400 MHz), 13C (100 MHz), and 19F (372.5 MHz) NMR
spectra were recorded in CDCl3 with a JEOL ECX-400P FTNMR
spectrometer. The chemical shifts,
d, are given in ppm with

Y. Yamauchi et al. / Tetrahedron 66 (2010) 473–479
477
tetramethylsilane (1H, 13C) and CFCl3
(
19F) as references, re-
stirring at room temperature for 1 h, the reaction mixturewas poured
into 1 M HCl (200 mL). The resulting aqueous solution was extracted
withEt2O (3ꢂ30 mL)and the etherealsolutionwasdried overMgSO4.
Evaporation of the solvent followed by purification with column
chromatography gave 1-aryl-2,2,2-trifluoroethanol 2 or 8.
spectively. J values are in Hertz. MS spectra were determined using
a JEOL JMS-T100GC (EI) and Thermo Scientific Exactive (ESI). Elec-
trochemical reactions were carried out using Constant Current
Power Supply (model 5944), Metronix Corp. Tokyo. CV was mea-
sured by Hokuto Denko HSV-100 with a Pt wire (4 1 mm) and Ag/
Agþ as a working electrode and a reference electrode, respectively.
Column chromatography was carried out using Kanto Kagaku Silica
gel 60 N with hexane/EtOAc as an eluent. All reagents and solvents
were commercially available and were used as received without
further purification. 1-Bromo-3-phenoxybenzene (5a)17a and 1-
iodo-4-isobutylbenzene (5b, a 79/21 mixture of p-/o- isomers)17b,c
were prepared by the reported procedure.
4.3.1. 2,2,2-Trifluoro-1-phenylethanol (2)24,25. Isolated Yield: 77%.
1H NMR (400 MHz):
d
2.57 (d, J¼4.4 Hz, 1H), 4.99–5.06 (m, 1H),
7.40–7.49 (m, 5H). 19F NMR (372.5 MHz):
d
ꢁ78.97 (d, J¼6.7 Hz, 3F).
4.3.2. 2,2,2-Trifluoro-1-(3-phenoxyphenyl)ethanol (8a)25. Isolated
Yield: 95%. 1H NMR (400 MHz):
2.50 (d, J¼4.6 Hz, 1H), 4.97–5.04
(m, 1H), 7.01–7.05 (m, 3H), 7.11–7.16 (m, 2H), 7.21 (d, J¼7.8 Hz, 1H),
7.33–7.40 (m, 3H). 13C NMR (100 MHz):
72.4 (q, J¼32.4 Hz), 117.7,
119.1, 119.6, 122.0, 123.7, 124.1 (q, J¼282.1 Hz), 129.9, 130.0, 135.8,
156.6, 157.5. 19F NMR (372.5 MHz):
ꢁ78.96 (d, J¼6.7 Hz, 3F).
d
d
4.2. Preparation of aryl trifluoromethyl ketones: general
procedure
d
To a flask that was charged with Mg (267 mg, 11 mmol) in dry
Et2O (10 mL) under N2 was dropwise added a solution of aryl halide 5
(10 mmol) in dry Et2O (5 mL) and a few drops of 1,2-dibromoethane.
After the addition was completed, the mixture was refluxed for 1 h.
The reaction mixture was then cooled to 0 ꢀC and then Winereb
amide 618 (10 mmol) was added. After stirring at room temperature
for 2 h, the reaction mixture was poured into 150 mL of 1 M HCl. The
aqueous solution was extracted with Et2O (3ꢂ30 mL) and dried over
MgSO4. Evaporation of the solvent and purification with column
chromatography gave aryl trifluoromethyl ketone 7. In the case of
reaction of 5b, which is a mixture of regioisomers (p-/o-¼79/21),
isolation of the product 7b was not carried out at this stage since it is
difficult to separate 7b and its regioisomer (p-/o-¼92/8 by 1H NMR).
4.3.3. 2,2,2-Trifluoro-1-(4-isobutylphenyl)ethanol (8b). Isolated Yield:
45% from 5b (two steps). IR (neat): 3398, 2957, 1270,1171, 1129 cmꢁ1
1H NMR (400 MHz):
0.90 (d, J¼6.6 Hz, 6H), 1.81–1.92 (m, 1H), 2.48
.
d
(d, J¼4.6 Hz, 1H), 2.49 (d, J¼7.3 Hz, 2H), 4.96–5.03 (m, 1H), 7.19 (d,
J¼8.2 Hz, 2H), 7.38 (d, J¼8.2 Hz, 2H). 13C NMR (100 MHz):
d 22.3, 30.1,
45.1, 72.8 (q, J¼32.4 Hz), 124.3 (q, J¼281.7 Hz), 127.2, 129.4, 131.2,
143.3. 19F NMR (372.5 MHz):
d
ꢁ78.98 (d, J¼6.7 Hz, 3F). HRMS (EI):
m/z [M]þ calcd for C12H15F3O 232.1075. Found 232.1075.
4.3.4. 2,2,2-Trifluoro-1-(6-methoxynaphthalen-2-yl)ethanol
(8c)26. Isolated Yield: 89%. Mp: 99–100 ꢀC IR (KBr): 3262, 2941,
1632, 1610, 1490, 1392, 1268, 1175, 1129, 860, 690 cmꢁ1 1H NMR
.
(400 MHz):
d
2.59 (d, J¼4.5 Hz, 1H), 3.94 (s, 3H), 5.13–5.20 (m, 1H),
7.15 (d, J¼2.4 Hz, 1H), 7.19 (dd, J¼9.0, 2.4 Hz, 1H), 7.54 (d, J¼8.6 Hz,
4.2.1. 2,2,2-Trifluoro-1-(3-phenoxyphenyl)ethanone (7a). Isolated
Yield: 70%. IR: 3071, 1721, 1581, 1489, 1444, 1245, 1204, 1146, 872,
1H), 7.77 (d, J¼8.7 Hz, 1H), 7.78 (d, J¼8.7 Hz, 1H), 7.88 (s, 1H). 19F
NMR (372.5 MHz):
d
ꢁ78.73 (d, J¼6.7 Hz, 3F).
754 cmꢁ1.1H NMR (400 MHz):
d
7.02–7.06 (m, 2H), 7.16–7.21 (m,1H),
7.31–7.42 (m, 3H), 7.50 (t, J¼8.0 Hz,1H), 7.68 (s,1H), 7.78 (d, J¼7.8 Hz,
1H). 13C NMR (100 MHz):
116.5 (q, J¼291.2 Hz), 119.2 (q, J¼1.9 Hz),
4.3.5. 2,2,2-Trifluoro-1-(3-fluoro-4-phenylphenyl)ethanol
d
(8d). Isolated Yield: 91%. Mp: 63–64 ꢀC. IR (KBr): 3389, 2939, 1582,
119.4,124.4,124.5 (q, J¼2.4 Hz),125.4,130.1,130.5,131.3,155.9,158.2,
1489, 1422, 1255, 1132, 824, 698 cmꢁ1. 1H NMR (400 MHz):
d 2.68
179.9 (q, J¼35.3 Hz). 19F NMR (372.5 MHz):
d
ꢁ72.04 (s, 3F). HRMS
(d, J¼4.6 Hz, 1H), 5.04–5.11 (m, 1H), 7.31–7.57 (m, 8H). 13C NMR
(EI): m/z [M]þ calcd for C14H9F3O2 266.0555. Found 266.0555.
(100 MHz):
d
71.9 (qd, J¼32.2, 1.4 Hz), 115.2 (d, J¼24.8 Hz), 123.4 (d,
J¼2.9 Hz), 124.0 (q, J¼282.3 Hz), 128.0, 128.5, 128.9 (d, J¼3.1 Hz),
130.2 (d, J¼13.6 Hz), 130.9 (d, J¼3.8 Hz), 134.8, 134.9, 159.5 (d,
4.2.2. 2,2,2-Trifluoro-1-(6-methoxynaphthalen-2-yl)ethanone
(7c). Isolated Yield: 77%. Mp: 64–66 ꢀC IR (KBr): 2941, 1698, 1624,
J¼248.9 Hz). 19F NMR (372.5 MHz):
d
ꢁ78.91 (d, J¼6.7 Hz, 3F),
1484, 1401, 1269, 1167, 1027, 902 cmꢁ1. 1H NMR (400 MHz):
d
3.97
ꢁ117.53 (m, 1F). HRMS (EI): m/z [M]þ calcd for C14H10F4O 270.0668.
(s, 3H), 7.17 (d, J¼2.4 Hz, 1H), 7.23–7.27 (m, 1H), 7.82 (d, J¼8.9 Hz,
Found 270.0668.
1H), 7.90 (d, J¼9.1 Hz, 1H), 8.05 (d, J¼8.7 Hz, 1H), 8.54 (s, 1H). 13C
NMR (100 MHz):
d
55.4, 105.8, 117.0 (q, J¼291.6 Hz), 120.4, 125.0 (q,
4.3.6. Preparation of 1-bromo-2,2,2-trifluoroethylarenes: method
J¼1.7 Hz), 125.0, 127.5, 127.6, 131.8, 132.9 (q, J¼2.6 Hz), 138.4, 161.0,
A
13. To a solution of 1-aryl-2,2,2-trifluoroethanol (2, 8b or 8d,
180.0 (q, J¼34.6 Hz). 19F NMR (372.5 MHz):
d
ꢁ71.16 (s, 3F). HRMS
5 mmol) in CH2Cl2 (10 mL) was added N-bromosuccinimide (1.78 g,
10 mmol) and triphenylphosphite (3.10 g, 10 mmol), and then the
mixture was stirred at 40 ꢀC for 12 h. After evaporation of the
solvent, ether (100 mL) was added to the residue and the insoluble
solid was removed by filtration through Celite. Evaporation
followed by purification with column chromatography gave
1-bromo-2,2,2-trifluoroethylarene 3, 9b, or 9d.
(EI): m/z [M]þ calcd for C13H19F3O2 254.0555. Found 254.0553.
4.2.3. 2,2,2-Trifluoro-1-(3-fluoro-4-phenylphenyl)ethanone
(7d). Isolated Yield: 68%. Mp: 54–56 ꢀC IR (KBr): 3078, 1714, 1614,
1425, 1209, 1132, 848, 753, 739, 719, 699 cmꢁ1. 1H NMR (400 MHz):
d
7.43–7.54 (m, 3H), 7.58–7.62 (m, 2H), 7.65 (d, J¼7.8 Hz, 1H), 7.87 (d,
J¼10.9 Hz, 1H), 7.94 (d, J¼8.2 Hz, 1H). 13C NMR (100 MHz):
d 116.5 (q,
J¼290.9 Hz), 117.5 (dq, J¼25.8, 1.9 Hz), 125.9–126.1 (m), 128.6, 128.9
(d, J¼3.6 Hz), 129.0, 130.1 (d, J¼7.2 Hz), 131.3 (d, J¼3.6 Hz), 133.8 (d,
J¼1.4 Hz),136.4(d, J¼13.8 Hz),159.5(d, J¼251.1 Hz),178.9(qd, J¼35.5,
4.3.7. 1-(1-Bromo-2,2,2-trifluoroethyl)benzene (3). Isolated Yield:
63%. IR (neat): 3072, 1259, 1166, 1112, 697 cmꢁ1 1H NMR
.
(400 MHz):
d
5.12 (q, J¼7.5 Hz, 1H), 7.37–7.44 (m, 3H), 7.48–7.54 (m,
2.2 Hz).19F NMR (372.5 MHz):
d
ꢁ72.10 (s, 3F), ꢁ115.69 (m,1F). HRMS
2H). 13C NMR (100 MHz):
d
47.1 (q, J¼33.9 Hz),123.5 (q, J¼277.8 Hz),
(EI): m/z [M]þ calcd for C14H8F4O 268.0511. Found 268.0508.
128.9, 129.1, 130.0, 132.8. 19F NMR (372.5 MHz):
d
ꢁ71.06 (d,
J¼7.5 Hz, 3F). HRMS (EI): m/z [M]þ calcd for C8H6BrF3 237.9605.
4.3. Preparation of 1-aryl-2,2,2-trifluoroethanol: general
procedure
Found 237.9604.
4.3.8. 1-(1-Bromo-2,2,2-trifluoroethyl)-4-isobutylbenzene
To a solution of aryl trifluoromethyl ketone (1 or 7, 10 mmol) in
MeOH (10 mL) was added NaBH4 (378 mg, 10 mmol) at 0 ꢀC. After
(9b). Isolated Yield: 60%. IR (neat): 2958, 2916, 1260, 1160, 1112,
678 cmꢁ1
.
1H NMR (400 MHz):
d
0.91 (d, J¼6.8 Hz, 6H), 1.81–1.93

478
Y. Yamauchi et al. / Tetrahedron 66 (2010) 473–479
(m, 1H), 2.49 (d, J¼7.3 Hz, 1H), 5.11 (q, J¼7.5 Hz, 1H), 7.16 (d,
with Et2O (3ꢂ30 mL). The combined ethereal solution was washed
with satd brine and dried over MgSO4. Evaporation of the solvent
gave an almost pure 2-aryl-3,3,3-trifluoropropanoic acid 4 or 10.
J¼8.2 Hz, 2H), 7.40 (d, J¼8.2 Hz, 2H). 13C NMR (100 MHz):
d 22.2,
30.1, 45.1, 47.2 (q, J¼34.1 Hz), 123.5 (q, J¼277.8 Hz), 128.9, 129.6,
130.1, 144.0. 19F NMR (372.5 MHz):
d
ꢁ71.09 (d, J¼7.5 Hz, 3F). HRMS
(EI): m/z [M]þ calcd for C12H14BrF3 294.0231. Found 294.0227.
4.4.2. In the case of reaction of 9b, 9c, or 9d. The combined ethereal
solution was dried over MgSO4 and was evaporated to give a crude
product. To a solution of the crude product in benzene (7 mL) and
MeOH (2 mL) was added 2 M solution of trimethylsilyldiazo-
methane22 in Et2O (1 mL) and the resulting solution was stirred at
room temperature for 30 min. Evaporation followed by purification
with column chromatography afforded methyl 2-aryl-3,3,3-tri-
fluoropropanoate 14, 15 or 16.
4.3.9. 2-Fluoro-4-(1-bromo-2,2,2-trifluoroethyl)biphenyl
(9d). Isolated Yield: 60%. Mp: 53–54 ꢀC IR (KBr): 3063, 1422, 1256,
1168, 1105, 782, 688 cmꢁ1. 1H NMR (400 MHz):
d
5.15 (q, J¼7.4 Hz,
1H), 7.32–7.50 (m, 6H), 7.53–7.57 (m, 2H). 13C NMR (100 MHz):
d
45.9 (qd, J¼34.3, 1.9 Hz), 117.1 (dq, J¼25.3, 1.0 Hz), 123.3 (q,
J¼278.0 Hz), 125.1 (dq, J¼3.3, 1.0 Hz), 128.3, 128.6, 128.9 (d,
J¼3.1 Hz), 130.9 (d, J¼13.6 Hz), 131.1 (d, J¼4.1 Hz), 133.6 (dq, J¼7.9,
1.0 Hz), 134.6 (d, J¼1.4 Hz), 159.4 (d, J¼249.9 Hz). 19F NMR
4.4.3. 3,3,3-Trifluoro-2-phenylpropanoic acid (4)27. Isolated Yield:
(372.5 MHz):
d
ꢁ70.96 (d, J¼7.4 Hz, 3F), ꢁ116.77 (m, 1F). HRMS (EI):
66%. 1H NMR (400 MHz):
d
4.37 (q, J¼8.5 Hz, 1H), 7.39–7.48 (m, 5H).
m/z [M]þ calcd for C14H9BrF4 331.9824. Found 331.9822.
19F NMR (372.5 MHz):
d
ꢁ68.26 (d, J¼8.5 Hz, 3F).
4.3.10. Preparation of 1-bromo-2,2,2-trifluoroethylarenes: method
B
4.4.4. 3,3,3-Trifluoro-2-(3-phenoxyphenyl)propanoic acid (10). Isolated
Yield: 80%. IR (neat): 3065, 2925, 1731, 1586, 1489, 1258, 1163, 1119,
19. To a solution of triphenylphosphine (1.31 g, 5 mmol) in toluene
(5 mL) was added a solution of 1-aryl-2,2,2-trifluoroethanol (8a or
8c, 5 mmol) and carbon tetrabromide (1.66 g, 5 mmol) in toluene
(10 mL). The mixture was then stirred at 60 ꢀC for 15 h. After the
solid had been removed by filtration, the filtrate was diluted with
Et2O (100 mL), washed with satd NaHCO3 (2ꢂ40 mL), and dried
over MgSO4. Evaporation of the solvent and purification with col-
umn chromatography gave 1-bromo-2,2,2-trifluoroethylarene 9a
or 9c.
909, 735 cmꢁ1.1H NMR (400 MHz):
d
4.32 (q, J¼8.5 Hz,1H), 7.00–7.05
(m, 3H), 7.11–7.20 (m, 3H), 7.32–7.39 (m, 3H). 13C NMR (100 MHz):
55.1 (q, J¼29.3 Hz), 119.2, 119.3, 119.8, 123.3 (d, J¼280.2 Hz), 123.9,
123.9,129.9,130.3 (q, J¼1.7 Hz),130.3,156.4,157.9,171.8 (q, J¼2.6 Hz).
d
19F NMR (372.5 MHz):
d
ꢁ68.09 (d, J¼8.5 Hz, 3F). HRMS (ESI): m/z
[MꢁCOOH]þ calcd for C14H10F3O 251.0689. Found 251.0696.
4.4.5. Methyl 3,3,3-trifluoro-2-(4-isobutylphenyl)propanoate (14).
Isolated Yield: 42% (two steps). IR: (neat) 2958, 1754, 1359, 1261,
4.3.11. 1-(1-Bromo-2,2,2-trifluoroethyl)-3-phenoxybenzene
1156, 1111, 1013 cmꢁ1. 1H NMR (400 MHz):
d
0.90 (d, J¼6.6 Hz, 6H),
(9a). Isolated Yield: 66%. IR (neat): 3064, 1580, 1469, 1236,
1.80–1.92 (m, 1H), 2.48 (d, J¼7.2 Hz, 1H), 3.77 (s, 3H), 4.29 (q,
894 cmꢁ1. 1H NMR (400 MHz):
d
5.12 (q, J¼7.5 Hz, 1H), 6.99–7.054
J¼8.6 Hz, 1H), 7.16 (d, J¼8.1 Hz, 2H), 7.33 (d, J¼8.1 Hz, 2H). 13C NMR
(m, 3H), 7.13–7.18 (m, 2H), 7.21–7.24 (m, 1H), 7.32–7.40 (m, 3H). 13C
(100 MHz):
d
22.3, 30.1, 45.0, 52.8, 55.0 (q, J¼28.8 Hz), 123.7 (q,
NMR (100 MHz):
d
46.5 (q, J¼34.3 Hz), 119.2, 119.3, 119.8, 123.3 (q,
J¼279.7 Hz), 126.5 (q, J¼1.9 Hz), 129.1, 129.6, 143.0, 166.8 (q,
J¼277.6 Hz), 123.6, 123.9, 129.9, 130.2, 134.5, 156.3, 157.7. 19F NMR
J¼2.9 Hz). 19F NMR (372.5 MHz):
d
ꢁ68.47 (d, J¼8.6 Hz, 3F). HRMS
(372.5 MHz):
d
ꢁ71.01 (d, J¼7.4 Hz, 3F). HRMS (EI): m/z [M]þ calcd
(EI): m/z [M]þ calcd for C14H17F3O2 274.1181. Found 274.1181.
for C14H10BrF3O 329.9867. Found 329.9867.
4.4.6. Methyl 3,3,3-trifluoro-2-(6-methoxynaphthalen-2-yl)propa-
noate (15). Isolated Yield: 48% (two steps). Mp: 107–109 ꢀC IR
(KBr): 2972, 1754, 1607, 1443, 1354, 1258, 1154, 1108, 857 cmꢁ1. 1H
4.3.12. 1-(1-Bromo-2,2,2-trifluoroethyl)-6-methoxynaphthalene
(9c). Isolated Yield: 70%. Mp: 78–79 ꢀC. IR (KBr): 2961, 1631, 1255,
1175, 1107, 1029 cmꢁ1. 1H NMR (400 MHz):
d
3.93 (s, 3H), 5.28 (q,
NMR (400 MHz):
d
3.78 (s, 3H), 3.93 (s, 3H), 4.45 (q, J¼8.5 Hz, 1H),
J¼7.5 Hz, 1H), 7.13–7.17 (m, 1H), 7.19 (dd, J¼9.1, 2.6 Hz, 1H), 7.58 (d,
7.12–7.15 (m, 1H), 7.18 (dd, J¼9.1, 2.6 Hz, 1H), 7.48 (d, J¼8.4 Hz, 1H),
J¼8.5 Hz, 1H), 7.76 (t, J¼8.2 Hz, 1H), 7.86 (s, 1H). 13C NMR
7.76 (dd, J¼8.9, 3.8 Hz, 2H), 7.83 (s, 1H). 13C NMR (100 MHz):
d 52.9,
(100 MHz):
d
47.7 (q, J¼34.3 Hz), 55.3, 105.6, 119.8, 123.5 (q,
55.2 (q, J¼29.1 Hz), 55.3, 105.5, 119.6,123.8 (q, J¼280.0 Hz),124.2 (q,
J¼278.5 Hz), 126.1, 127.6, 127.7, 128.1, 128.8, 129.7, 135.1, 158.8. 19F
J¼1.9 Hz), 126.7, 127.6, 128.6, 129.0, 129.6, 134.7, 158.4, 166.8 (q,
NMR (372.5 MHz):
calcd for C13H10BrF3O 317.9867. Found 317.9868.
d
ꢁ70.75 (d, J¼7.5 Hz, 3F). HRMS (EI): m/z [M]þ
J¼2.9 Hz). 19F NMR (372.5 MHz):
d
ꢁ68.20 (d, J¼8.5 Hz, 3F). HRMS
(EI): m/z [M]þ calcd for C15H13F3O3 298.0817. Found 298.0816.
4.4. Synthesis of 2-aryl-3,3,3-trifluoropropanoic acid by
electrochemical carboxylation of 1-bromo-2,2,2-
trifluoroethylarene followed by esterification: general
procedure
4.4.7. Methyl 2-(2-fluoro-3-phenylphenyl)-3,3,3-trifluoropropanoate
(16). Isolated Yield: 59% (two steps). IR (neat): 2958, 1754, 1271,
1164, 1112, 1014 cmꢁ1
.
1H NMR (400 MHz):
d
3.82 (s, 3H), 4.36 (q,
J¼8.5 Hz, 1H), 7.26–7.32 (m, 3H), 7.37–7.42 (m, 1H), 7.43–7.50 (m,
2H), 7.52–7.56 (m, 2H). 13C NMR (100 MHz):
d
53.1, 54.7 (qd, J¼29.6,
A
solution of 1-bromo-2,2,2-trifluoroethylarene (3 or 9,
1.4 Hz), 117.3 (d, J¼24.8 Hz), 123.4 (q, J¼280.0 Hz), 125.6 (d,
J¼3.6 Hz), 128.1, 128.5, 128.9 (d, J¼3.1 Hz), 130.0 (qd, J¼8.1, 1.9 Hz),
130.2 (d, J¼13.8 Hz), 131.2 (d, J¼4.1 Hz), 134.8 (d, J¼1.2 Hz), 159.6 (d,
1.0 mmol) in anhyd DMF (10 mL) containing Bu4NBF4 (0.1 M) was
electrolyzed at 0 ꢀC with a constant current (5 or 10 mA/cm2)
under an atmospheric pressure of bubbling carbon dioxide (flow
rate of CO2; ca. 50 mL/min). An undivided cell equipped with a Pt
plate cathode (2ꢂ2 cm2) and a Zn plate anode (2ꢂ2 cm2) was
used for the electrolysis. After an appropriate amount of elec-
tricity was passed (shown in schemes), the electrolyzed solution
was poured into 1 M HCl (100 mL) and then extracted with Et2O
(3ꢂ30 mL).
J¼249.4 Hz), 166.1 (q, J¼2.6 Hz). 19F NMR (372.5 MHz):
d
ꢁ68.11 (d,
J¼8.5 Hz, 3F), ꢁ117.01 (m, 1F). HRMS (EI): m/z [M]þ calcd for
C16H12F4O2 312.0773. Found 312.0768.
Acknowledgements
H.S. thanks The Akiyama Foundation for partial financial
support of this research. The support by the Global COE Program
(Project No. B01: Catalysis as the Basis for Innovation in Materials
Science) from the Ministry of Education, Culture, Sports, Science
and Technology, Japan to Y.Y. is acknowledged. We also thank Ms.
4.4.1. In the case of reaction of 3 or 9a. The combined ethereal
solution was washed with satd NaHCO3 (3ꢂ40 mL). The resulting
aqueous solution was acidified with 3 M HCl and then extracted

Y. Yamauchi et al. / Tetrahedron 66 (2010) 473–479
479
12. Representative papers; (a) Folest, J.-C.; Duprilot, J.-M.; Pe´richon, J. Tetrahedron
Lett. 1985, 26, 2633; (b) Fauvarque, J. F.; Jutand, A.; Francois, M. Nouv. J.
Chim. 1986, 10, 119; (c) Chaussard, J.; Troupel, M.; Robin, Y.; Jacob, G.; Juhasz,
J. P. J. Appl. Electrochem. 1989, 19, 345; (d) Isse, A. A.; Gennaro, A. Chem.
Commun. 2002, 2798; (e) Stepanov, A. A.; Volodin, Yu. Yu.; Grachev, M. K.;
Kurochkina, G. I.; Syrtsev, A. N.; Grinberg, V. A. Russ. J. Electrochem. 2002, 38,
1346; (f) Damodar, J.; Krishna Mohan, S.; Khaja Lateef, S.; Jayarama Reddy, S.
Synth. Commun. 2005, 35, 1143; (g) Ramesh Raju, R.; Khaja Lateef, S.; Krishna
Mohan, S.; Jayarama Reddy, S. Arkivoc 2006, 76; (h) Scialdone, O.; Galia, A.;
Errante, G.; Isse, A. A.; Gennaro, A.; Filardo, G. Electrochim. Acta 2008, 53,
2514.
S. Oka, Ms. A. Tokumitsu, and Mr. N Owada, Equipment Manage-
ment Center, Creative Research Institution Sousei, Hokkaido Uni-
versity, for mass analyses.
References and notes
1. Recent reviews: (a) Sakakura, T.; Choi, J.-C.; Yasuda, H. Chem. Rev. 2007, 107,
2365; (b) Louie, J. Curr. Org. Chem. 2005, 9, 605; (c) Aresta, M.; Dibenedettob, A.
Dalton Trans. 2007, 2975.
2. (a) Silvestri, G.; Gambino, S.;Filardo, G.; Gulotta, A. Angew. Chem., Int. Ed. Engl.1984,
23, 979; (b) Silvestri, G.; Gambino, S.; Filardo, G. Acta Chem. Scand. 1991, 45, 987.
3. (a) Sock, O.; Troupel, M.; Pe´richon, J. Tetrahedron Lett. 1985, 26, 1509; (b)
13. Okano, T.; Sugiura, H.; Fumoto, M.; Matsubara, H.; Kusukawa, T.; Makoto, F.
J. Fluorine Chem. 2002, 114, 91.
14. Takeuchi, Y.; Fujisawa, H.; Fujiwara, T.; Matsuura, M.; Komatsu, H.; Ueno, S.;
Matsuzaki, T. Chem. Pharm. Bull. 2005, 53, 1062.
´
´
´
15. (a) Schlosser, M.; Michel, D.; Guo, Z.-W.; Sih, C. J. Tetrahedron 1996, 52, 8257; (b)
Goj, O.; Kotila, S.; Haufe, G. Tetrahedron 1996, 52, 12761; (c) Rozen, S.; Hagooly,
A.; Harduf, R. J. Org. Chem. 2001, 66, 7464; (d) Laurent, E.; Marquet, B.; Roze, C.;
Ventalon, F. J. Fluorine Chem. 1998, 87, 215; (e) Fujisawa, H.; Fujiwara, T.;
Takeuchi, Y.; Omata, K. Chem. Pharm. Bull. 2005, 53, 524; (f) Bellezza, F.; Cipi-
ciani, A.; Ricci, G.; Ruzziconi, R. Tetrahedron 2005, 61, 8005.
Chaussard, J.; Folest, J. C.; Nedelec, J. Y.; Perichon, J.; Sibille, S.; Troupel, M.
Synthesis 1990, 369.
4. (a) Kamekawa, H.; Senboku, H.; Tokuda, M. Electrochim. Acta 1997, 42, 2117; (b)
Tokuda, M.; Yoshikawa, A.; Suginome, H.; Senboku, H. Synthesis 1997, 1143; (c)
Kamekawa, H.; Kudo, H.; Senboku, H.; Tokuda, M. Chem. Lett. 1997, 26, 917; (d)
Kamekawa, H.; Senboku, H.; Tokuda, M. Tetrahedron Lett. 1998, 39, 1591; (e)
Senboku, H.; Fujimura, Y.; Kamekawa, H.; Tokuda, M. Electrochim. Acta 2000, 45,
2995; (f) Senboku, H.; Komatsu, H.; Fujimura, Y.; Tokuda, M. Synlett 2001, 418;
(g) Senboku, H.; Kanaya, H.; Fujimura, Y.; Tokuda, M. J. Electroanal. Chem. 2001,
507, 82; (h) Senboku, H.; Kanaya, H.; Tokuda, M. Synlett 2002, 140; (i)
Chowdhury, M. A.; Senboku, H.; Tokuda, M. Tetrahedron 2004, 60, 475; (j)
Kuang, C.; Yang, Q.; Senboku, H.; Tokuda, M. Chem. Lett. 2005, 34, 528; (k)
Senboku, H.; Yamauchi, Y.; Fukuhara, T.; Hara, S. Electrochemistry 2006, 74, 612.
5. (a) Uneyama, K. Organofluorine Chemistry; Oxford: Blackwell, 2006; (b) Welch,
J. T. Tetrahedron 1987, 43, 3123; (c) Hiyama, T. In Organofluorine Compounds;
Yamamoto, H., Ed.; Springer: Berlin, 2000.
16. (a) Shi, G.-Q.; Huang, X.-H.; Hong, F. J. Org. Chem. 1996, 61, 3200; (b) Jiang, B.;
Xu, Y. J. Org. Chem. 1991, 56, 7336; (c) Middleton, W. J.; Bingham, E. M. J. Fluorine
Chem. 1983, 22, 561.
¨
17. (a) Orn, U.; Eriksson, L.; Jakobsson, E.; Bergman, Å Acta Chem. Scand. 1996, 50,
802; (b) Sy, W.-W.; Lodge, B. A. Tetrahedron Lett. 1989, 30, 3769; (c) Luoni, G.;
McGuigan, C.; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J. Bioorg. Med.
Chem. Lett. 2005, 15, 3791.
18. Graham, S. L.; Scholz, T. H. J. Org. Chem. 1991, 56, 4260.
19. Ullmann, J.; Hanack, M. Synthesis 1989, 685.
20. Nguyen, B. V.; Burton, D. J. J. Org. Chem. 1997, 62, 7758.
21. Uneyama, K.; Katagiri, T.; Amii, H. Acc. Chem. Res. 2008, 41, 817 and references
cited therein.
22. Hashimoto, N.; Aoyama, T.; Shioiri, T. Chem. Pharm. Bull. 1984, 29, 1475.
23. In both cases, small amounts of the corresponding difluorostyrenes were also
observed by 1H and 19F NMR of crude products.
6. (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications;
Wiley-VCH: Weinheim, 2004; (b) Advances in Organic Synthesis; Atta-Ur-, R.,
Laali, K. K., Eds.; Bentham Science: Hilversum, 2006; Vol. 2.
7. Heintz, M.; Sock, O.; Saboureau, C.; Pe´richon, J. Tetrahedron 1988, 44, 1631.
8. Saboureau, C.; Troupel, M.; Sibille, S.; Perichon, J. J. Chem. Soc., Chem. Commun.
´
24. Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S. J. Org. Chem. 1991, 56, 984.
1989, 1138.
´
25. Sibille, S.; Mcharek, S.; Perichon, J. Tetrahedron 1989, 45, 1423.
9. Chiozza, E.; Desigaud, M.; Greiner, J.; Dunach, E. Tetrahedron Lett. 1998, 39, 4831.
10. Yamauchi, Y.; Fukuhara, T.; Hara, S.; Senboku, H. Synlett 2008, 438.
11. Yamauchi, Y.; Sakai, K.; Fukuhara, T.; Hara, S.; Senboku, H. Synthesis 2009, 3375.
26. Inschauspe, D.; Sortais, J.-B.; Billard, T.; Langlois, B. R. Synlett 2003, 233.
27. Ne´meth, G.; Ra´ko´ czy, E.; Simig, G. J. Fluorine Chem. 1996, 76, 91.
´