Hypervalent Iodine-Mediated Fluorination of Styrene Derivatives: Stoichiometric and Catalytic Transformation to 2,2-Difluoroethylarenes

Article abstract of DOI:10.1021/acs.joc.5b01929

Fluorination of styrene derivatives with a reagent system composed of μ-oxo-bis[trifluoroacetato(phenyl)iodine] and a pyridine·HF complex gave the corresponding (2,2-difluoroethyl)arenes in good yields. Similarly, the reagent of PhI(OCOCF₃)₂ and the pyridine·HF complex acted as a fluorinating agent for styrene derivatives. The fluorination of styrene derivatives with the pyridine·HF complex underwent under catalytic conditions using 4-iodotoluene as a catalyst and m-CPBA as a terminal oxidant.

Full text of DOI:10.1021/acs.joc.5b01929

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Hypervalent Iodine-Mediated Fluorination of Styrene Derivatives:
Stoichiometric and Catalytic Transformation to 2,2-
Difluoroethylarenes
Tsugio Kitamura,* Kensuke Muta, and Juzo Oyamada
Department of Chemistry and Applied Chemistry, Graduate School of Science and Engineering, Saga University, Hojo-machi, Saga
840-8502, Japan
*
S Supporting Information
ABSTRACT: Fluorination of styrene derivatives with a reagent
system composed of μ-oxo-bis[trifluoroacetato(phenyl)iodine] and a
pyridine·HF complex gave the corresponding (2,2-difluoroethyl)arenes
in good yields. Similarly, the reagent of PhI(OCOCF ) and the
3
2
pyridine·HF complex acted as a fluorinating agent for styrene
derivatives. The fluorination of styrene derivatives with the pyridine·
HF complex underwent under catalytic conditions using 4-iodotoluene
as a catalyst and m-CPBA as a terminal oxidant.
INTRODUCTION
method deserves attention as a direct transformation method of
the vinyl group on the aromatic ring into the corresponding
,2-difluoroethyl group. Although the transformation of a vinyl
group into a 2,2-difluoroethyl group accompanies the migration
of an aryl group, as shown in Scheme 2, this method is
convenient and useful in organic synthesis. The previous
procedures for the hypervalent iodine-mediated 2,2-difluor-
oethyl group construction require (difluoroiodo)arenes or
Togni’s reagent as a hypervalent iodine-fluorinating reagent.
■
Introduction of fluorine atoms into organic molecules strongly
affects on the chemical, physical, and biological properties. The
unique properties have proven to be important in the
pharmaceutical, agrochemical, and materials industries. Espe-
cially, trifluoromethyl and the related groups have been used as
active components of pharmaceuticals and agrochemicals, and
the synthetic methods of fluoroalkylated compounds have been
widely investigated so far. Similarly, introduction of a 2,2,2-
trifluoroethyl group into organic molecules has been conducted
using several methodologies.
On the other hand, it is also expected that the 2,2-
difluoroethyl group has the ability to modify the biological
properties. Rueeger et al. reported that introduction of a 2,2-
difluoroethyl group into an indole derivative enhances the
biological activity compared with the corresponding 2,2,2-
2
1
(
Difluoroiodo)arenes must be prepared before use, and they
2
cannot be stored for a long time due to their instability.
Although Togni’s reagent is commercially available, it is
expensive. Thus, we studied to find a simple and convenient
reagent system for the construction of the 2,2-difluoroethyl
group. For this purpose, we prepared in situ a hypervalent
iodine reagent and used it for the fluorination of styrene
derivatives. This method provided a convenient and practical
fluorination reaction, giving 2,2-difluoroethyl-substituted are-
nes, and served to conduct a catalytic fluorination reaction.
Here we report the convenient and practical construction of
3
trifluoroethylated compound. However, a direct introduction
of a 2,2-difluoroethyl group has not been conducted before. At
present, functional group transformation is a suitable strategy
for the construction of a gem-difluoroethyl moiety. The
synthesis of organic molecules bearing gem-difluoroethyl side
chains has been conducted by several methods such as (1)
fluorination of styrene derivatives using fluorinated hypervalent
iodine compounds or iodine/XeF , (2) reaction of organozinc
reagents and potassium bromodifluoroacetate, (3) fluorination
of gem-bistriflates and gem-dihalides, (4) fluorodecarboxylation
2
,2-difluoroethylarenes by a hypervalent iodine-mediated
fluorination reaction of styrene derivatives. Also, we found
that this fluorination proceeded with a catalytic amount of
iodoarenes in the presence of m-CPBA as a terminal oxidant.
4
2
5
RESULTS AND DISCUSSION
6
■
7
Stoichiometric Fluorination with Hypervalent Iodine/
HF Reagents. First, we chose styrene 1a as the model
substrate and the pyridine·HF complex (Py·HF) as the fluorine
of dicarboxylic acids, and (5) chlorodifluoromethylation
followed by the elimination of HCl and the migration of a
8
double bond. The outline is shown in Scheme 1.
Among the above methods, the fluorination reaction of
styrene-derivative-mediated hypervalent iodine can construct
aromatic compounds bearing 2,2-difluoroethyl moieties. This
Received: August 19, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b01929
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Scheme 1. Known Methods for Construction of a 2,2-
Difluoroethyl Group
together with the Py·HF reagent, the reaction of 1a in CH Cl
2
2
at 40 °C for 17 h gave (2,2-difluoroethyl)benzene (2a) in 43%
yield (entry 1). Although the use of PhI(OAc) increased the
2
yield to 59%, Koser’s salt [hydroxyl(tosyloxy)iodobenzene]
resulted in a decrease of the yield (entry 3). When a less
nucleophilic PhI(OCOCF ) was used as a promoter, the yield
3
2
was increased to 60% (entry 4). The reaction of 1a using μ-oxo-
bis[trifluoroacetato(phenyl)iodine], [(CF CO )IPh] O, gave
3
2
2
the highest yield of 2b (61%) (entry 5). PhI(OAc) and
2
PhI(OCOCF ) gave comparable yields, but PhI(OCOCF )
3
2
3 2
gave a cleaner reaction mixture. Then, we determined to use
(CF CO )IPh] O for further optimization of the reaction
[
3
2
2
conditions.
Using [(CF CO )IPh] O, HF reagents as the fluorine source
3
2
2
were screened again. The results are given in Table 2. Although
Table 2. Effects of HF Reagents and Solvents on the
a
Fluorination of Styrene 1a
b
entry
HF reagent
solvent
yield (%)
1
2
3
4
5
6
7
8
55% aq HF
TEA·5HF
TEA·3HF
KF
CH Cl2
34
46
trace
0
2
CH Cl2
2
CH Cl2
2
CH Cl2
2
Py·HF
Py·HF
Py·HF
Py·HF
DCE
52
53
24
0
1,2-DCB
toluene
Scheme 2. Hypervalent Iodine-Mediated Transformation of
Styrenes to 2,2-Difluoroethylarenes
c
other solvents
a
Conditions: 1a (0.2 mmol), [(CF CO )IPh] O (0.12 mmol), HF
reagent (2 mmol HF), and solvent (2 mL). Yield was determined by
F NMR. MeCN, DMF, DME, diglyme, and THF.
3
2
2
b
19
c
the reaction with the Py·HF reagent provided 2a in 61% yield,
5% aqueous HF and TEA·5HF reagents decreased the yields
5
to 34 and 46%, respectively (entries 1 and 2). TEA·3HF and
KF were not suitable for this fluorination (entries 3 and 4).
Next, we examined solvents using the Py·HF reagent, but the
yield was not improved (entries 5−8).
Since we found the best reagent system for the fluorination
of 1a, we further optimized the conditions. The results are
given in Table 3. When the amount of the Py·HF reagent was
increased, the yield of 2a also increased (entries 1−3). Use of 4
mmol of Py·HF reagent afforded 2a in 67% yield (entry 3).
When the amount of the hypervalent iodine reagent
source for the optimization of reaction conditions. Because a
hypervalent iodine reagent was essential as a mediator in the
previous fluorination reactions of carbonyl compounds, we
started to screen the hypervalent iodine reagents. The results
are given in Table 1. When iodosylbenzene (PhIO) was used
9
Table 1. Effect of Hypervalent Iodine Reagents on the
a
Fluorination of Styrene 1a
[
(CF CO )IPh] O was increased, the highest yield (70%)
3 2 2
was obtained in the case of 0.18 mmol (entries 4 and 5). When
the reaction time was investigated, it turned out that the
reaction was complete within a short time (1 h) (entries 6 and
7
). Finally, it was found that the reaction proceeded efficiently
even at room temperature or 0 °C (entries 8 and 9).
With the optimized conditions obtained above, a variety of
styrene derivatives were tested to determine the scope of the
substrates. In these reactions, we also examined the reaction
with PhI(OCOCF ) (condition B) as a hypervalent iodine
3
2
mediator together with [(CF CO )IPh] O (condition A). The
3
2
2
results are given in Table 4. The substituted styrenes 1 include
-methylstyrene (1b), 4-tert-butylstyrene (1c), 4-fluorostyrene
1d), 4-bromostyrene (1e), 4-acetoxystyrene (1f), 2,4,6-
4
(
a
Conditions: 1a (0.2 mmol), hypervalent iodine reagent (0.24 mmol),
pyridine·HF (2 mmol HF), and CH Cl (2 mL) at 40 °C for 17 h.
Yield was determined by F NMR. With 0.12 mmol.
trimethylstyrene (1g), 3-bromostyrene (1h), and 2-bromostyr-
ene (1i). The fluorination reaction of the substituted styrenes
2
2
b
19
c
B
DOI: 10.1021/acs.joc.5b01929
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Table 3. Further Optimization of the Fluorination of Styrene
vinylpyridine, trans-stilbene, 1-vinylnaphthalene, 2-vinylnaph-
thalene, 2-(2-propenyl)naphthalene, 4-vinylbiphenyl, or 4-
methoxystyrene. In addition, this reaction cannot be applied
to styrene derivatives bearing functionalities sensitive to HF,
such as alcohols and amines, and to simple alkenes due to low
reactivity.
a
1
a
[
(CF CO )IPh] O
Py·HF (HF
mmol)
time
(h)
temp
(°C)
yield
b
3
2
2
Catalytic Fluorination with an Iodoarene Catalyst.
Although a catalytic fluorination of styrenes with an iodoarene
as a catalyst has not been studied before, the success of the
catalytic fluorination of 1,3-dicarbonyl compounds by iodoar-
entry
(mmol)
(%)
1
2
3
4
5
6
7
8
9
0.12
0.12
0.12
0.18
0.24
0.18
0.18
0.18
0.18
2
3
4
4
4
4
4
4
4
17
17
17
17
17
1
40
40
40
40
40
40
40
rt
61
65
67
70
64
70
38
73
72
10
ene catalysts suggests that the catalytic fluorination also takes
place in the case of styrenes. Thus, we examined the catalytic
fluorination by an iodoarene catalyst using 1,1-diphenylethene
(
1j) as the model substrate and Py·HF reagent as the fluorine
0.5
1
source. The results are given in Table 5. When the reaction of
1
0
Table 5. Optimization of the Catalytic Fluorination of 1,1-
a
Conditions: 1a (0.2 mmol), [(CF CO )IPh] O, Py·HF, and CH Cl
2
a
3
2
2
2
Diphenylethene
b
19
(
2 mL). Yield was determined by F NMR.
a
Table 4. Scope of Substrates
b
entry
iodoarene
oxidant
time (h) yield (%)
1
2
3
4
5
6
7
8
9
2-MeOC H I
m-CPBA
17
17
17
17
17
17
17
17
17
17
17
17
3
48
0
6
4
2-MeOC H I
NaClO·5H O
6
4
2
2-MeOC H I
30% H O2
0
6
4
2
2-MeOC H I
t-BuOOH
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
0
6
4
2,4,6-(MeO) C H I
1
3
6
2
4-MeOC H I
6
6
4
2,4,6-Me C H I
45
42
49
0
3
6
2
2-MeC H I
6
4
4-MeC H I
6
4
1
0
c
1
1
4-MeC H I
49
47
49
50
6
4
d
1
2
4-MeC H I
6 4
1
3
4-MeC H I
6 4
1
4
4-MeC H I
0.5
6
4
a
Conditions: 1j (0.5 mmol), ArI (0.1 mmol), Py·HF (10 mmol HF),
b
and an oxidant (0.75 mmol) in CH Cl (2 mL) at rt. Yields were
2
2
determined by 19F NMR. Reaction was carried out at 40 °C. m-
c
d
CPBA (1.0 mmol) was used.
1j with Py·HF was conducted in the presence of 1-iodo-2-
methoxybenzene (20 mol %) and m-CPBA as a terminal
oxidant at room temperature for 17 h, the desired difluorinated
product 2j was obtained in 48% yield (entry 1). Although other
oxidants such as NaClO·5H O, 30% H O , and t-BuOOH were
a
Condition A: 1 (0.2 mmol), [(CF CO )IPh] O (0.18 mmol), Py·HF
3
2
2
(
4 mmol HF), and CH Cl (2 mL) at rt for 1 h. Condition B: 1 (0.2
2 2
mmol), PhI(OCOCF ) (0.36 mmol), Py·HF (4 mmol HF), and
3
2
2
2
2
19
CH Cl (2 mL) at rt for 1 h. Yields were determined by F NMR.
2
2
examined in the fluorination reaction, as for neither of the
cases, no difluorinated product 2j was obtained (entries 2−4).
Next, we screened an iodoarene catalyst. We conducted the
fluorination reaction using 2-iodo-1,3,5-trimethoxybenzene and
1-iodo-4-methoxybenzene as the catalyst, but the yield of 2j was
very low (entries 5 and 6). When 2-iodo-1,3,5-trimethylben-
zene, 1-iodo-2-methylbenzene, and 1-iodo-4-methylbenzene
were used as the catalyst, the product was obtained in good
yields (42−49%) (entries 7−9). However, the absence of the
iodoarene catalyst did not provide the product 2j at all (entry
10). Increasing the reaction temperature to 40 °C and the
amount of m-CPBA gave almost the same result (47−49%
yield) (entries 11 and 12). Although the reaction time was
shortened to 3 and 0.5 h, there was almost no difference in the
yield of 2j. Then, we decided on the optimal time in 0.5 h.
b
c
For 2 h. For 8 h.
1
2
b−1i generated the corresponding 2,2-difluoroethylarenes
b−2i in good to high yields under both conditions A and B.
The reaction of 1,1-diphenylethene (1j) and 2-phenylpropene
(
1k) afforded 1,1-difluoro-1,2-diphenylethane (2j) and 2,2-
difluoro-1-phenylpropane (2k) in high yields. In the reaction of
,2-dihydronaphthalene (1l), the ring-contracted product, 1-
1
(
difluoromethyl)indane (2l), was obtained in 32−43% yield.
Most products were volatile and had bad separation, with
iodobenzene formed from [(CF CO )IPh] O. Accordingly, the
3
2
2
yields of volatile products were low when they were isolated by
column chromatography on silica gel. However, the desired
fluorination reaction was not observed in the case of 2-
C
DOI: 10.1021/acs.joc.5b01929
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6
a
The catalytic fluorination by 4-iodotoluene was examined
with several styrene derivatives in order to determine the scope
of the substrates. Table 6 shows that the catalytic fluorination
(2,2-Difluoroethyl)benzene (2a). Using condition A, the
fluorinated product 2a was obtained in 73% yield as determined by
19
F NMR of the crude reaction mixture. Due to the volatility, the
identity of the product was confirmed by H and F NMR and
GCMS: H NMR (400 MHz, CDCl ) δ 3.13 (dt, J = 4, 17 Hz, 2H),
1
19
1
3
Table 6. Catalytic Fluorination of Styrenes 1 with 2-
19
5
.93 (tt, J = 4, 56 Hz, 1H), 7.24−7.35 (m, 5H); F NMR (376 MHz,
a
Iodotoluene
6a
CDCl ) δ −115.0 (dt, J = 18, 57 Hz) [lit. −115.3 (dt, J = 17.5, 57
3
+
+
Hz)]; MS (EI) m/z 142 (M ), 91 (PhCH ); HRMS (EI, double
2
+
focusing) m/z [M ] calcd for C H F 142.0594; found 142.0592.
8
8 2
1
1
1
-(2,2-Difluoroethyl)-4-methylbenzene (2b). Using condi-
tion A, the fluorinated product 2b was obtained in 50% yield as
determined by 19F NMR of the crude reaction mixture. Due to the
1
19
volatility, the identity of the product was confirmed by H and
F
1
NMR: H NMR (400 MHz, CDCl ) δ 2.32 (s, 3H), 3.07 (dt, J = 4, 17
Hz, 2H), 5.86 (tt, J = 4, 57 Hz, 1H), 7.12 (s, 4H); F NMR (376
MHz, CDCl ) δ −115.1 (dt, J = 18, 57 Hz); MS (EI) m/z 156 (M ),
05 (MeC H CH ); HRMS (EI, double focusing) m/z [M ] calcd
3
19
+
3
+
+
1
6 4 2
for C H F 156.0751; found 156.0751.
9
10 2
1
-(2,2-Difluoroethyl)-4-(1,1-dimethylethyl)benzene (2c).
Using condition B, the fluorinated product 2c was obtained in 53%
yield as determined by 19F NMR of the crude reaction mixture.
Further separation by column chromatography on silica gel gave 26
a
Conditions: 1 (0.5 mmol), 4-MeC H I (0.1 mmol), Py·HF (10 mmol
6
4
mg (ca. 95% of purity) of 2c in the reaction for 17 h using 1c (1
HF), and m-CPBA (0.75 mmol) in CH Cl (3 mL) at rt for 0.5 h.
1
2
2
mmol): H NMR (400 MHz, CDCl ) δ 1.31 (s, 9H), 3.11 (dt, J = 4,
Yields were determined by 1 F NMR.
9
3
1
7 Hz, 2H), 5.91 (tt, J = 4, 56 Hz, 1H), 7.18 (d, J = 8 Hz, 2H), 7.36 (d,
13
1
J = 8 Hz, 2H); C{ H} NMR (100 MHz, CDCl ) δ 31.3, 34.5, 40.4
3
1
9
(t, J = 22 Hz), 116.8 (t, J = 240 Hz), 125.6, 129.33, 129.39, 129.43; F
provides 2,2-difluoroethylarenes 2 in 31−66% yields. Although
the catalytic efficiency in the fluorination of styrenes 1 is not
high, the present results indicate that the fluorination of 1
proceeds moderately even under the catalytic conditions using
NMR (376 MHz, CDCl ) δ −114.9 (dt, J = 17, 56 Hz); HRMS (EI,
3
+
double focusing) m/z [M ] calcd for C H F 198.1220; found
12
16 2
1
98.1221.
-(2,2-Difluoroethyl)-4-fluorobenzene (2d). Using condition
11
1
4
-iodotoluene.
A, the fluorinated product 2d was obtained in 73% yield as determined
by 19F NMR of the crude reaction mixture. Due to the volatility, the
CONCLUSION
1
19
1
identity of the product was confirmed by H and F NMR: H NMR
400 MHz, CDCl ) δ 3.07 (dt, J = 4, 17 Hz, 2H), 5.86 (tt, J = 4, 56
■
(
We have disclosed that the reaction of styrene derivatives 1
with a hypervalent iodine reagent and a pyridine·HF reagent
takes place under mild conditions to give (2,2-difluoroethyl)-
arenes 2 in good yields. Since the fluorination of styrenes 2
involves 1,2-aryl migration, the present reaction formally
provides the method for introducing a 2,2-difluoroethyl group
into arenes. Due to the advantages of convenient preparation of
fluorinating reagents and efficiency of the reaction, this method
is useful for the introduction of a potentially valuable
difluoroethyl group into the aromatic ring. Moreover, it has
been proven that the present fluorination also proceeds by
iodoarene catalysts. Therefore, the present method for
transformation of styrenes to (2,2-difluoroethyl)arenes should
be considered a convenient and mild alternative to other
fluorinating reactions.
3
19
Hz, 1H), 6.97−7.19 (m, 4H); F NMR (376 MHz, CDCl ) δ −115.4,
−
(
3
+
115.5 (dt, J = 18, 56 Hz); MS (EI) m/z 160 (M ), 109
FC H CH ); HRMS (EI, double focusing) m/z [M ] calcd for
+
+
6 4 2
C H F 160.0500; found 160.0499.
8
7 3
4a
1-Bromo-4-(2,2-difluoroethyl)benzene (2e). Using condition
A, the fluorinated product 2e was obtained in 85% yield as determined
by 19F NMR of the crude reaction mixture. The product 2e was
isolated in 29% yield (64 mg) by column chromatography on silica gel.
Further separation by column chromatography on silica gel gave 64
mg (ca. 90% of purity) of 2e in the reaction for 17 h using 1e (1
1
mmol): H NMR (400 MHz, CDCl ) δ 3.09 (dt, J = 4, 17 Hz, 2H),
3
5
2
.90 (tt, J = 4, 56 Hz, 1H), 7.12 (d, J = 8 Hz, 2H), 7.46 (d, J = 8 Hz,
H); 13C{ H} NMR (100 MHz, CDCl ) δ 40.2 (t, J = 22 Hz), 116.0
1
3
19
(t, J = 240 Hz), 121.6, 131.3, 131.5, 131.8; F NMR (376 MHz,
CDCl ) δ −115.4 (dt, J = 17, 56 Hz).
3
1-Acetoxy-4-(2,2-difluoroethyl)benzene (2f). Using condition
B, the fluorinated product 2f was obtained in 46% yield as determined
by F NMR of the crude reaction mixture. Further separation by
EXPERIMENTAL SECTION
19
■
General Procedure for the Fluorination of Styrenes 1.
Condition A: To a 15 mL Teflon test tube were placed
column chromatography on silica gel gave 44 mg (ca. 95% of purity)
of 2f in the reaction for 17 h using 1f (1 mmol): H NMR (400 MHz,
1
[
(CF CO )IPh] O (117 mg, 0.18 mmol), Py·HF (114 mg, 4
CDCl
Hz, 1H), 7.05 (d, J = 7 Hz, 2H), 7.25 (d, J = 7 Hz, 2H); C{ H}
NMR (100 MHz, CDCl ) δ 21.0, 40.2 (t, J = 22 Hz), 116.3 (t, J = 240
Hz), 121.8, 129.9, 130.8, 150.0, 169.4; F NMR (376 MHz, CDCl ) δ
3
3
) δ 2.29 (s, 3H), 3.12 (dt, J = 4, 17 Hz, 2H), 5.90 (tt, J = 4, 56
3
2
2
1
3
1
mmol), and CH Cl (1 mL), and the mixture was stirred for 15 min
at room temperature. After styrene 1 (0.2 mmol) and CH Cl (1 mL)
were added, the test tube was capped with a rubber septum. The
mixture was stirred at room temperature for 1 h. The reaction mixture
2
2
2
2
3
19
+
−115.2 (dt, J = 17, 56 Hz); HRMS (EI, double focusing) m/z [M ]
was quenched with a saturated NaHCO solution and extracted with
calcd for C H O F 200.0649; found 200.0650.
3
10 10
2 2
ether (10 mL × 3). The combined organic layer was washed with
1-(2,2-Difluoroethyl)-2,4,6-trimethylbenzene (2g). Using con-
brine, dried over anhydrous Na SO , and concentrated under reduced
dition B, the fluorinated product 2g was obtained in 68% yield as
2
4
19
19
pressure. The yield of the product was determined by F NMR using
hexafluorobenzene as an internal standard. Condition B: The reaction
was conducted in the same procedure as condition A except for using
PhI(OCOCF ) (160 mg, 0.36 mmol) instead of [(CF CO )IPh] O.
determined by F NMR of the crude reaction mixture. Further
separation by column chromatography on silica gel gave 9.2 mg (ca.
1
90% of purity) of 2g in the reaction for 17 h using 1g (1 mmol): H
NMR (400 MHz, CDCl ) δ 2.26 (s, 3H), 2.31 (s, 6H), 3.20 (dt, J = 4,
3
2
3
2
2
3
13
1
The product isolation was conducted by the reaction of 1 (1 mmol)
for 17 h. The product was separated by column chromatography on
silica gel (eluent: hexane).
17 Hz, 2H), 5.88 (tt, J = 4, 57 Hz, 1H), 6.88 (s, 2H); C{ H} NMR
(100 MHz, CDCl ) δ 20.3, 20.8, 34.2 (t, J = 22 Hz), 116.6 (t, J = 240
3
19
Hz), 126.5, 129.2, 136.9, 137.5; F NMR (376 MHz, CDCl ) δ
3
D
DOI: 10.1021/acs.joc.5b01929
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
−
113.6 (dt, J = 17, 57 Hz); HRMS (EI, double focusing) m/z [M+]
calcd for C H F 184.1064; found 184.1061.
AUTHOR INFORMATION
Corresponding Author
Phone/Fax: +81-952-28-8550. E-mail: kitamura@cc.saga-u.ac.
■
11
14 2
4
a
1
-Bromo-3-(2,2-difluoroethyl)benzene (2h). Using condition
*
B, the fluorinated product 2h was obtained in 85% yield as determined
by F NMR of the crude reaction mixture. Further separation by
column chromatography on silica gel gave 93 mg (ca. 90% of purity)
of 2h in the reaction for 17 h using 1h (1 mmol): H NMR (400
MHz, CDCl ) δ 3.11 (dt, J = 4, 17 Hz, 2H), 5.92 (tt, J = 4, 56 Hz,
1
9
jp.
Notes
1
The authors declare no competing financial interest.
3
13
1
1
H), 7.17−7.21 (m, 2H), 7.42−7.44 (m, 2H); C{ H} NMR (100
ACKNOWLEDGMENTS
MHz, CDCl ) δ 40.4 (t, J = 22 Hz), 116.1 (t, J = 240 Hz), 122.6,
■
3
19
1
28.5, 130.2, 130.6, 132.8, 134.5; F NMR (376 MHz, CDCl ) δ
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan (25410048).
3
−
115.3 (dt, J = 17, 56 Hz).
-Bromo-2-(2,2-difluoroethyl)benzene (2i). Using condition B,
the fluorinated product 2i was obtained in 75% yield as determined by
1
1
9
F NMR of the crude reaction mixture. Further separation by column
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■
2
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1
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(
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3
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29.3, 132.3, 132.8, 132.9; F NMR (376 MHz, CDCl ) δ −115.5 (dt,
3
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8
7
2
1
2
1
,1-Difluoro-1,2-diphenylethane (2j). Using condition B, the
19
fluorinated product 2j was obtained in 94% yield as determined by
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9
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3
1
3
2
,2-Difluoropropylbenzene (2k). Using condition A, the
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(
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9
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1
19
1
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3
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9
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7
5
.25−7.32 m, 5H); F NMR (376 MHz, CDCl ) δ − 89.3 (dt, J = 16,
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2 Hz); MS (EI) m/z 156 (M ), 91 (PhCH ); HRMS (EI, double
2
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9
10 2
4
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6
(
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1
19
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3
(
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3
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9 9
1
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2
2
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19
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