Novel introduction of a tetrafluoroethylene (-CF2CF 2-) unit into organic molecules

Article abstract of DOI:10.1055/s-0030-1258330

The reductive coupling of 4-bromo-3,3,4,4-tetrafluorobut-1-ene with 2.4 equivalents of various carbonyl compounds proceeded very smoothly in the presence of 2.4 equivalents of MeLi/LiBr-free at -78°C for two hours, giving the corresponding adducts in high

Full text of DOI:10.1055/s-0030-1258330

PAPER
33
Novel Introduction of a Tetrafluoroethylene (-CF2CF2-) Unit into Organic
Molecules
N
ovel Introduct
s
ion of
a
T
u
etrafluoroeth
t
ylene
U
o
nit into
O
rg
m
anic
M
olecule
s
u Konno,* Shinya Takano, Yoshikazu Takahashi, Hideaki Konishi, Yusuke Tanaka, Takashi Ishihara
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Fax +81(75)7247580; E-mail: konno@chem.kit.ac.jp
Received 7 September 2010; revised 15 October 2010
This observation prompted several chemists to investigate
heavily fluorinated sugars (Figure 3). For example, the
asymmetric synthesis of the tetrafluoropyranose 3 and 4
was achieved by Linclau et al.4 Very recently, Gouverneur
Abstract: The reductive coupling of 4-bromo-3,3,4,4-tetrafluo-
robut-1-ene with 2.4 equivalents of various carbonyl compounds
proceeded very smoothly in the presence of 2.4 equivalents of
MeLi/LiBr-free at –78 °C for two hours, giving the corresponding
adducts in high to excellent yields. On the other hand, trieth- and co-workers have also reported the synthesis of tet-
rafluorinated C-nucleosides 5.5
yl(1,1,2,2-tetrafluorobut-3-enyl)silane, which could be prepared by
treatment of 4-bromo-3,3,4,4-tetrafluorobut-1-ene and chlorotrieth-
ylsilane with magnesium at 0 °C for three hours, reacted with some
aldehydes in the presence of 1 mol% of tetrabutylammonium fluo-
ride, the desired adducts being obtained in good to high yields.
OH
OH
R
O
OH
CF2
O
OH
CF2
HO
O
Key words: tetrafluoroethylene, MeLi/LiBr-free, triethyl(1,1,2,2-
tetrafluorobut-3-enyl)silane, reductive coupling
F
F
HO
C
HO
C
F2
F2
F
F
3
4
5
The incorporation of a fluorine-containing fragment into
organic molecules can have a significant influence on the
material characteristics or biological activity of the mole-
cules by affecting their physicochemical and/or pharma-
cological properties.1 While the incorporation of terminal
perfluorinated moieties has been extensively studied,2 the
introduction of an internal perfluoroalkylene unit, e.g. 1
(Figure 1, n >2) is relatively rare.
Figure 3 Tetrafluorinated carbohydrate or C-nucleoside analogues
In the syntheses of these heavily fluorinated sugars,
however, intramolecular cyclization (Equation 1) was re-
quired because fluoride elimination from the in situ gen-
erated polyfluoroalkyllithium species proceeded
significantly in the intermolecular coupling reaction
(Equation 2).6 Even in the intramolecular cyclization of
the formate derivative 6, b-elimination product 7, reduc-
tion product 8, as well as methylated product 9 were also
observed (Equation 3).4
R1 (CF2)n R2
1
R1, R2 = carbon chain substituent
Figure 1 Internal perfluoroalkylene unit (n >2)
OBn
OBn
intramolecular
MeLi/LiBr (1.0 equiv)
OCHO
OCHO
In 1998, DiMagno and co-workers proposed a general
strategy for enhancing molecular recognition based on in-
creasing ‘polar hydrophobicity’, which could be achieved
by replacing polar hydrophilic groups with polar hydro-
phobic groups, e.g., a CHOH group in carbohydrates with
a CF2 group. It was found that the hexafluoropyranose 2
shown in Figure 2, has a tenfold increase in transport
across the red blood cell membrane, compared to glucose
due to enhanced affinity for the transporter protein.3
THF, –78 °C, 3 h
CF2CF2Br
CF2CF2Li
OBn
BnO
O
OH
OH
F2C CF2
CF=CF2
trace
Equation 1
OH
intermolecular
MeLi/LiBr (1.0 equiv)
electrophile
O
OH
CF2
OBn
OR
OBn
OR
F2C
C
THF, –78 °C, 3 h
F2
CF2CF2Br
CF2CF2Li
2
OBn
Figure 2 DiMagno’s partially fluorinated hexapyranose
OR
etc.
many products
CF=CF2
SYNTHESIS 2011, No. 1, pp 0033–0044
x
x
.
x
x
.2
0
1
0
Advanced online publication: 15.11.2010
DOI: 10.1055/s-0030-1258330; Art ID: F16110SS
Equation 2
© Georg Thieme Verlag Stuttgart · New York

34
T. Konno et al.
PAPER
ly, when butyllithium was used instead of MeLi/LiBr-
free, the yield of 12a was decreased from 95 to 79% (entry
8). Increasing the reaction temperature also led to a de-
crease in the yield of 12a and b-elimination product 14a
was afforded as a byproduct (entry 9).
OBn
OBn
intramolecular
MeLi/LiBr (1.0 equiv)
OCHO
OCHO
THF, –78 °C, 3 h
BnO
CF2CF2Br
BnO
CF2CF2Li
6
OBn
OBn
Table 1 Investigation of the Reaction Conditions
O
OH
CF2
OH
PhCHO (2.4 equiv)
MeLi/LiBr-free (X equiv)
F
F
BnO
C
BnO
CF=CF2
7 (2.7%)
OBn
solvent, –78 °C, 2 h
F2
Br
F
F
84%
11
F
F
F
F
F
OBn
Ph
+
+
OH
OH
H
F
F
F
F
F
OH
F
BnO
CF2CF2H
8 (1.7%)
BnO
CF2CF2Me
12a
13a
14a
9 (0.3%)
Entry MeLi/LiBr- Solvent Yielda (%)
Recovereda
Equation 3
free (equiv)
12a
trace
15
13a
14a
0
(%) of 11
1
2
3
4
5
6
7
8
9f
1.2b
Et2O
Et2O
THF
THF
THF
THF
THF
THF
THF
0
97
81
33
45
85
0
Such a synthetic difficulty in the synthesis of molecules
having a perfluoroalkylene unit, especially a tetrafluoro-
ethylene unit, prompted us to re-investigate the intermo-
lecular nucleophilic addition of (tetrafluoroalkyl)metal
species 10, derived from commercially available 4-bro-
mo-3,3,4,4-tetrafluorobut-1-ene (11), with various elec-
trophiles in detail (Scheme 1).
1.2
1
0
1.2
59
5
0
1.2c
47
4
0
1.2d
12
trace
0
2.4
95
trace
0
F2
C
F2
C
F2
C
electrophile (E+)
2.4b
50
5
7
0
0
36
0
C
E
C
Br
C
Met
F2
F2
F2
2.4e
79
0
11
10
Scheme 1 Intended program
2.4f
68
9
8
a Determined by 19F NMR.
Gassman et al. have already reported the reductive cou-
pling of perfluoroalkyl iodide with various aldehydes, ke-
tones, and esters.2d Our initial studies on the reductive
coupling of 4-bromo-3,3,4,4-tetrafluorobut-1-ene (11)
and benzaldehyde were carried out by examining their re-
action conditions (Table 1). Thus, treatment of 11 and 2.4
equivalents of benzaldehyde with 1.2 equivalents of
methyllithium/lithium bromide in diethyl ether at –78 °C
for two hours did not give any of the desired product 12a;
the starting bromide 11 was recovered quantitatively (en-
try 1). The use of lithium bromide free methyllithium
(MeLi/LiBr-free) instead brought about a slight increase
in the yield, the desired alcohol 12a being obtained in only
15% yield, together with 1% of the reduction product 13a,
although a large amount of the starting material still re-
mained unreacted (entry 2). Switching the solvent from
diethyl ether to tetrahydrofuran improved the yield of 12a
from 15 to 59% (entry 3). Although the prolonged reac-
tion time as well as the addition of Lewis acid did not lead
to satisfactory results (entries 4 and 5), the use of 2.4
equivalents of MeLi/LiBr-free resulted in a complete con-
sumption of the starting material, the desired adduct 12a
being obtained almost quantitatively (entry 6). In this
case, the employment of MeLi/LiBr-free was found to be
crucial because the reaction in the presence of 2.4 equiva-
lents of MeLi/LiBr in tetrahydrofuran gave 12a in only
50% yield, together with 5% of 13a (Entry 7). Additional-
b Commercially available MeLi/LiBr (Et2O soln) was used.
c Stirred for 4 h.
d BF3·OEt2 (2.4 equiv) was used.
e n-BuLi (hexane soln) was used instead of MeLi/LiBr-free.
f Carried out at –40 °C.
With the optimum reaction conditions in hand (Table 1,
entry 6), we next investigated the reaction of 11 with var-
ious electrophiles. The results are summarized in Table 2.
As shown in entries 2–4, the position of the substituent on
the benzene ring of the aldehyde did not influence the re-
action at all. Additionally, aldehydes having an electron-
donating group, such as Me, OMe, on the benzene ring
could participate well in the coupling reaction (entries 2
and 5), whereas an electron-withdrawing group, such as
CF3, CN, or NO2, on the benzene ring of the aromatic al-
dehydes led to a significant decrease in the yield (entries
7–9). Other aldehydes, like furfural as well as cinnamal-
dehyde, were also found to be good electrophiles, the cor-
responding alcohols being afforded in high yields (entries
10 and 11). As described in entries 12–15, treatment of 11
with various aliphatic aldehydes, such as propanal, hepta-
nal, cyclohexanecarboxaldehyde, and pivalaldehyde, fur-
nished the coupling products, 12l–o in excellent yields.
Furthermore, the reaction with various ketones took place
very smoothly to give the corresponding alcohols 12p,q in
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Novel Introduction of a Tetrafluoroethylene Unit into Organic Molecules
35
good to high yields (entries 16 and 17). The non-activated being obtained in 40% yield (entry 18). On the other hand,
imine, such as N-benzylbenzaldehyde imine, was found to the reductive coupling with a chiral sulfinimine proceeded
be less reactive in this reaction, none of the desired prod- very smoothly to give the corresponding amine in good
uct was afforded at all. However, the use of boron trifluo- yield as a diastereomeric mixture in a ratio of 90:10 of
ride–diethyl ether complex as a Lewis acid led to a (Rs,S)/(Rs,R).7
significant improvement of the yield, the desired amine
Table 2 The Reductive Coupling of 11 with Various Electrophiles
F
F
F
F
MeLi/LiBr-free (2.4 equiv)
THF, –78 °C, 2 h
+
electrophile
(2.4 equiv)
E
Br
F
F
F
F
11
12
Entry
Product
Yielda (%)
19F NMR
Isolated
86
F
F
1
2
95
F
F
OH
12a
12b
12c
12d
12e
12f
12g
12h
12i
OMe
F
F
quant.
77
78
63
80
63
37
30
F
F
F
F
OH
F
F
3
4
5
6
7
8
9
quant.
77
OMe
F
OH
F
F
F
OH OMe
Me
Cl
F
F
89
F
F
F
F
F
F
OH
F
F
69
F
OH
CF3
CN
NO2
F
F
–
F
OH
F
F
35
F
OH
F
F
F
trace
OH
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36
T. Konno et al.
PAPER
Table 2 The Reductive Coupling of 11 with Various Electrophiles (continued)
F
F
F
F
MeLi/LiBr-free (2.4 equiv)
THF, –78 °C, 2 h
+
electrophile
(2.4 equiv)
Br
E
F
F
F
F
11
12
Entry
Product
Yielda (%)
19F NMR
Isolated
77
F
F
O
10
11
12
13
84
95
97
87
F
F
F
F
F
OH
12j
12k
12l
F
Ph
74
F
F
OH
F
Et
57b
61
F
OH
F
F
n-C6H13
F
F
OH
12m
F
F
14
15
16
17
18
quant.
95
78
84
56
78
34
F
F
F
OH
12n
12o
F
t-Bu
F
F
F
OH
F
Me
64
F
F
F
F
OH
12p
12q
F
quant.
40c
F
OH
F
F
F
F
F
F
NHBn
12r
F
F
19
70
61d
HN
O
S
t-Bu
12s
a In all cases, the products were isolated after treatment of the crude materials with excess NaBH4 in order to reduce the unreacted electrophile.
b The low isolated yield was due to the high volatility of the product.
c BF3·OEt2 (2.4 equiv) was used.
d Diastereomeric ratio: (Rs,S)/(Rs,R) 90:10.
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Novel Introduction of a Tetrafluoroethylene Unit into Organic Molecules
37
Table 3 Investigation of the Reaction Conditions
PhCHO (1.0 equiv)
F
F
F
F
F
F
TBAF (x mol%)
Ph
Ph
+
SiEt3
THF, temp, 12 h
F
F
F
F
F
F
OH
OSiEt3
15
(1.2 equiv)
12a
16a
TBAF (2.0 equiv)
THF, 0 °C, 2 h
Entry
TBAF (mol%)
Temp (°C)
Yielda (%) of 12a and 16a
1
1.0
1.0
1.0
0.5
r.t.
0
78
2
91 (89)b
70
3
–20
0
4
66
a Determined by 19F NMR.
b Isolated yield of 12a after treatment of the resultant mixture of 12a and 16a with 2.0 equiv of TBAF.
Next our interest was directed toward triethyl(1,1,2,2-tet- of tetrabutylammonium fluoride were found to be fruitless
rafluorobut-3-enyl)silane (15) as an another reagent for (entries 3 and 4).
the introduction of the tetrafluoroethylene unit because of
With the optimal reaction conditions (Table 3, entry 2),
the accumulated studies on the coupling reaction of tri-
we continued the investigation of the coupling reaction
methyl(trifluoromethyl)silane with various carbonyl com-
using various electrophiles. The results are summarized in
pounds in the presence of a catalytic amount of fluoride
Table 4.
ion.8 After several attempts, a synthetic method was estab-
As shown in entries 4–6, the aromatic aldehydes with an
electron-withdrawing group, such as Cl, CF3, and CN, on
lished; thus, treatment of 1.2 equivalents of 11 with 1.0
equivalents of chlorotriethylsilane in the presence of 1.2
the benzene ring, were found to be good electrophiles in
equivalents of magnesium in tetrahydrofuran at 0 °C for
the reaction, the desired alcohols 12f–h, being obtained in
high yields. On the other hand, an electron-donating
group, such as OMe and Me, on the benzene ring led to a
significant decrease of the yield (entries 2 and 3). Espe-
cially, the reaction with anisaldehyde proceeded very
sluggishly and any trace of the desired product was not de-
tected at all. An aliphatic aldehyde was somewhat less re-
active and the desired product was obtained in moderate
yield even when the reaction was carried out at room tem-
perature (entry 8). Furthermore, various ketones are also
less reactive (entries 9–12). Even an aryl ketone having a
strongly electron-withdrawing group, such as a NO2
group, on the benzene ring afforded the product in moder-
ate yield (entry 10). Acid chloride, as well as ester, did not
give any products at all (entries 13 and 14).
three hours gave the desired product 15 in 79% 19F NMR
yield (Scheme 2).
Mg (1.2 equiv)
Et3SiCl (1.0 equiv)
F
F
F
F
Br
SiEt3
THF, 0 °C, 3 h
F
F
F
F
11
15
19F NMR yield: 79%
(1.2 equiv)
Scheme 2 Preparation of triethyl(1,1,2,2-tetrafluorobut-3-enyl)si-
lane
We next examined the fluoride-catalyzed nucleophilic ad-
dition of 15 with various carbonyl compounds. Thus,
treatment of 1.2 equivalents of 15 and 1.0 equivalents of
benzaldehyde with 1 mol% of tetrabutylammonium fluo-
ride at room temperature for 12 hours gave the corre-
sponding alcohol 12a and the silyl ether 16a in 78%
combined yield (Table 3, entry 1). As shown in entry 2,
decreasing the temperature from room temperature to 0 °C
led to a significant improvement in the yield, the desired
material was obtained in 91% yield. Without isolation,
treatment of the reaction mixture with 2.0 equivalents of
tetrabutylammonium fluoride in tetrahydrofuran at 0 °C
for two hours resulted in smooth desilylation, the alcohol
12a was obtained in 89% isolated yield over two steps. On
the other hand, the reaction at –20 °C or 0.5 mol% loading
As synthetic applications of the coupling products 12, the
carbon elongation at the other side of tetrafluoroethylene
unit was carried out (Scheme 3). Thus, treatment of 12a
and 12l with excess ozone in dichloromethane at –78 °C
for three hours, followed by the addition of dimethyl sul-
fide into the reaction mixture, gave tetrafluorinated fura-
nose derivatives 17a and 17l as a diastereomeric mixture
in 67% and 64% yields, respectively. Thus-obtained fura-
nose derivatives were subjected to an excess amount of
Grignard reagent in tetrahydrofuran at reflux temperature
for 12 hours, the corresponding unsymmetric 1,4-diols
18a and 18l were obtained 85 and 96% yields, respective-
ly.9
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38
T. Konno et al.
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Table 4 The Fluoride-Catalyzed Nucleophilic Addition
F
F
F
F
1) TBAF (1 mol%)
THF, 0 °C, 12 h
SiEt3
E
electrophile
(1.0 equiv)
+
2) TBAF (2.0 equiv)
THF, 0 °C, 2 h
F
F
F
F
12
15
(1.2 equiv)
Entry
Product
Yield (%)
19F NMR
Isolated
82
F
F
1
2
89
F
F
F
F
F
F
F
OH
12a
12b
12e
12f
12g
12h
12i
OMe
F
F
a
a
–
–
F
OH
F
F
3
4
5
6
7
65
96
74
88
22
56
84
58
62
21
F
OH
Cl
F
F
F
OH
CF3
CN
NO2
F
F
F
OH
F
F
F
OH
F
F
F
F
F
OH
F
F
n-C6H13
8
9
52
0
42b
F
OH
12m
F
F
F
0
F
F
OH
12p
12t
NO2
F
10
41
37
F
F
OH
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Novel Introduction of a Tetrafluoroethylene Unit into Organic Molecules
39
Table 4 The Fluoride-Catalyzed Nucleophilic Addition (continued)
F
F
F
F
1) TBAF (1 mol%)
THF, 0 °C, 12 h
SiEt3
E
electrophile
(1.0 equiv)
+
2) TBAF (2.0 equiv)
THF, 0 °C, 2 h
F
F
F
F
12
15
(1.2 equiv)
Entry
Product
Yield (%)
19F NMR
Isolated
–
F
F
11
12
5
0
F
F
F
OH
12q
12u
O
F
F
F
0
0
0
OMe
F
OH
F
F
F
F
13c
14c
0
0
F
F
O
12v
O
F
OMe
O
12w
a Not determined.
b Carried out at r.t.
c Carried out in the presence of 1.2 equiv of TBAF.
1) O3, CH2Cl2, –78 °C, 3 h
2) MeSMe
into unsymmetric 1,4-diols via ozonolysis and followed
by a Grignard reaction.
O
F2
C
HO
R1
R1
OH
C
C
C
F2
F2 F2
In this way, we have established novel synthetic ap-
proaches to various types of molecules having a tetrafluo-
roethylene unit.
R
R
1 = Ph (12a)
1 = Et (12l)
17a 67% (dr = ca. 7:3)
17l 64% (dr = ca. 2:1)
4-MeC6H4MgBr (6.0 equiv)
(for 12a)
or
PhMgBr (6.0 equiv)
(for 12l)
Infrared spectra were taken on a Jasco FT/IR-4100typeA spectro-
photometer as film on a NaCl plate. 1H and 13C NMR spectra were
measured with a Bruker DRX-500 NMR spectrometer and a Jeol
JNM- AL 400 NMR spectrometer in CDCl3 soln with TMS as an in-
ternal reference. A Jeol JNM-EX90A (84.21 MHz) FT-NMR spec-
trometer and a Jeol JNM-AL 400 NMR spectrometer were used for
determining the yield of the products with hexafluorobenzene
(C6F6). 19F NMR (376.05 MHz) spectra were measured with a Jeol
JNM-AL 400 NMR spectrometer in CDCl3 soln with CFCl3 as an
internal standard. 31P NMR (161.70 MHz) spectra were measured
with a Jeol JNM-AL 400 NMR spectrometer in CDCl3 soln with
Ph3P as an external standard. 13C and 31P NMR spectra were proton
decoupled. HRMS were taken on a Hitachi M-80B mass spectrom-
eter by EI, CI, and FAB methods.
OH
F2
C
R1
OH
R2
C
THF, reflux, 12 h
F2
18a 85% (dr = ca 1:1)
18l 96% (dr = ca 11:1)
Scheme 3 Synthetic applications of 12a and 12l
In summary, we have demonstrated the reductive cou-
pling of 11 with various electrophiles in the presence of
MeLi/LiBr-free. As a result, various carbonyl compounds
could participate in the reaction very well to give the cor-
responding adducts 12 in high to excellent yields. We also
synthesized the tetrafluoroethylene unit containing silyl
compound 15 as a novel synthetic reagent. Though 15 is
much less reactive than the lithium reagent, the reaction
with aromatic aldehydes with an electron-withdrawing
group, such as CF3 and CN, took place very smoothly,
compared with the reaction with the lithium reagent. Thus-
obtained tetrafluorinated alcohols 12 could be converted
All chemicals were of reagent grade and, if necessary, were purified
in the usual manner prior to use. TLC was performed on aluminum
sheets coated with Merck silica gel 60 F254 plates, and column chro-
matography was carried out using Wacogel C-200 as adsorbent.
2,2,3,3-Tetrafluoro-1-phenylpent-4-en-1-ol (12a); Typical Pro-
cedure
To a soln of 11 (0.062 g, 0.3 mmol) in THF (0.6 mL) was added
benzaldehyde (0.073 mL, 0.072 mmol) at –78 °C. After ca. 10 min,
Synthesis 2011, No. 1, 33–44 © Thieme Stuttgart · New York

40
T. Konno et al.
PAPER
2,2,3,3-Tetrafluoro-1-(2-methoxyphenyl)pent-4-en-1-ol (12d)
IR (neat): 3451, 3008, 2944, 2843, 1708, 1650, 1603, 1590, 1495,
1465, 1442, 1420, 1356, 1289, 1248, 1181, 1118, 1026, 987, 857,
829, 809 cm–1.
1H NMR (CDCl3): d = 3.65 (br s, 1 H), 3.86 (s, 3 H), 5.42 (dd,
J = 19.57, 6.39 Hz, 1 H), 5.65 (d, J = 11.80 Hz, 1 H), 5.87 (dt,
J = 17.38, 2.2 Hz, 1 H), 6.07 (ddt, J = 11.80, 17.38, 11.80 Hz, 1 H),
6.93–7.03 (m, 2 H), 7.33–7.38 (m, 2 H).
13C NMR (CDCl3): d = 55.69, 68.90 (dd, J = 28.92, 23.09 Hz),
111.20, 112.77–113.62 (m), 115.25–116.20 (m), 117.74–118.74
(m), 123.07–123.26 (m), 127.30 (t, J = 24.00 Hz), 129.83 (d,
J = 1.61 Hz), 130.13, 157.69.
to this mixture was added dropwise 1.06 M MeLi/LiBr-free (0.75
mL, 0.72 mmol) and the mixture was stirred at this temperature for
2 h. The reaction was quenched with aq NH4Cl and then it was ex-
tracted with Et2O (3 ×). The combined organic layers were dried
(anhyd Na2SO4), then filtered, and concentrated in vacuo. The resi-
due was dissolved in EtOH, and to this mixture was added excess
NaBH4 at 0 °C. The soln was allowed to reach r.t., and stirred for
several hours. The reaction was quenched with aq NH4Cl and it was
extracted with EtOAc (3 ×). The combined organic layers were
dried (anhyd Na2SO4), then filtered and concentrated in vacuo. The
residue was purified by column chromatography (silica gel, hex-
ane–EtOAc, 5:1) to give the corresponding alcohol 12a (0.062 g,
0.26 mmol, 86%).
19F NMR (CDCl3, CFCl3): d = –113.46 (dd, J = 260.98, 12.41 Hz, 1
F), –115.12 (ddd, J = 258.72, 11.80, 4.89 Hz, 1 F), –120.06 (dt,
J = 270.76, 6.21 Hz, 1 F), –127.93 (dd, J = 270.76, 19.57 Hz, 1 F).
HRMS (FAB): m/z [M+] calcd for C12H12F4O2: 264.0773; found:
264.0773.
IR (neat): 3423, 3068, 3037, 2925, 1958, 1814, 1707, 1650, 1496,
1456, 1420, 1238, 1180, 1105, 1010, 968, 848, 811 cm–1.
1H NMR (CDCl3): d = 2.51 (br s, 1 H), 5.16 (dd, J = 16.66, 6.39 Hz,
1 H), 5.66 (d, J = 11.47 Hz, 1 H), 5.85 (dm, J = 17.38 Hz, 1 H), 6.01
(ddt, J = 11.47, 17.38, 11.47 Hz, 1 H), 7.39–7.47 (m, 5 H).
13C NMR (CDCl3): d = 71.74–72.25 (m), 113.01 (q, J = 33.6 Hz),
115.04–116.00 (m), 117.61–118.48 (m), 123.43–123.62 (m),
126.89 (t, J = 24.00 Hz), 128.04, 128.36, 129.18, 135.18.
19F NMR (CDCl3, CFCl3): d = –112.98 (dd, J = 263.61, 11.47 Hz, 1
F), –113.91 (dd, J = 263.61, 11.47 Hz, 1 F), –120.10 (d, J = 274.01
Hz, 1 F), –127.63 (dd, J = 274.01, 16.66 Hz, 1 F).
2,2,3,3-Tetrafluoro-1-(4-methylphenyl)pent-4-en-1-ol (12e)
IR (neat): 3433, 3032, 2925, 1914, 1650, 1616, 1516, 1420, 1244,
1181, 1110, 1010, 986, 910, 837, 785, 760, 734, 705, 491 cm–1.
1H NMR (CDCl3): d = 2.40 (s, 3 H), 2.73 (br s, 1 H), 5.09 (dd,
J = 17.24, 7.19 Hz, 1 H), 5.66 (d, J = 11.12 Hz, 1 H), 5.86 (dd,
J = 17.28, 2.00 Hz, 1 H), 6.027 (ddt, J = 11.12, 17.28, 11.12 Hz, 1
H), 7.22 (d, J = 8.39 Hz, 2 H), 7.35 (d, J = 7.99 Hz, 2 H).
HRMS (FAB): m/z [M+] calcd for C11H10F4O: 234.0668; found:
234.0667.
13C NMR (CDCl3): d = 21.12, 71.78 (dd, J = 28.92, 22.29 Hz),
112.66–113.49 (m), 115.03–115.97 (m), 117.66–118.45 (m),
123.39 (t, J = 9.94 Hz), 126.96 (t, J = 23.95 Hz), 127.91, 129.05,
130.36, 132.17 (d, J = 1.71 Hz), 139.08.
19F NMR (CDCl3, CFCl3): d = –113.02 (dd, J = 263.61, 11.12 Hz,
1 F), –113.95 (dd, J = 263.61, 11.12 Hz, 1 F), –120.30 (dt,
J = 273.39, 6.02 Hz, 1 F), –127.62 (dd, J = 273.01, 17.24 Hz, 1 F).
2,2,3,3-Tetrafluoro-1-(4-methoxyphenyl)pent-4-en-1-ol (12b)
IR (neat): 3449, 3006, 2938, 2842, 1614, 1587, 1515, 1465, 1444,
1420, 1305, 1253, 1178, 1108, 1031, 986, 969, 842 cm–1.
1H NMR (CDCl3): d = 2.63 (s, 1 H), 3.81 (s, 3 H), 5.08 (ddd,
J = 14.82, 7.19, 2.80 Hz, 1 H), 5.65 (d, J = 11.75 Hz, 1 H), 5.83 (dt,
J = 17.38, 2.20 Hz, 1 H), 6.00 (ddt, J = 11.75, 17.38, 11.75 Hz, 1
H), 6.91 (d, J = 8.79 Hz, 2 H), 7.37 (d, J = 7.99 Hz, 2 H).
13C NMR (CDCl3): d = 55.23, 71.33–71.84 (m), 112.60–113.50
(m), 114.07 (d, J = 5.02 Hz), 115.17–115.98 (m), 118.08 (td,
J = 33.08, 11.55 Hz), 123.41 (t, J = 9.94 Hz), 126.98 (t, J = 23.95
Hz), 129.31, 160.18.
19F NMR (CDCl3, CFCl3): d = –113.01 (dd, J = 263.61, 11.75 Hz, 1
F), –113.98 (dd, J = 263.61, 11.75 Hz, 1 F), –120.51 (dd,
J = 273.39, 4.87 Hz, 1 F), –127.60 (dd, J = 273.39, 14.82 Hz, 1 F).
HRMS (FAB): m/z [M+] calcd for C12H12F4O: 248.0824; found:
248.0822.
1-(4-Chlorophenyl)-2,2,3,3-tetrafluoropent-4-en-1-ol (12f)
IR (neat): 3433, 2925, 1911, 1650, 1599, 1493, 1420, 1237, 1181,
1111, 1015, 969, 849, 828, 783, 733, 682 cm–1.
1H NMR (CDCl3): d = 3.01 (s, 1 H), 4.97 (dd, J = 16.66, 7.59 Hz, 1
H), 5.54 (d, J = 10.87 Hz, 1 H), 5.72 (dt, J = 17.28, 2.6 Hz, 1 H),
5.87 (ddt, J = 10.87, 17.28, 10.87 Hz, 1 H), 7.22 (s, 4 H).
13C NMR (CDCl3): d = 71.32 (dd, J = 28.92, 23.19 Hz), 112.33–
113.49 (m), 114.85–115.97 (m), 117.94 (q, J = 34.1 Hz), 123.75 (t,
J = 9.89 Hz), 126.64 (t, J = 24.00 Hz), 128.53, 129.39, 133.54 (d,
J = 1.61 Hz), 135.09.
19F NMR (CDCl3, CFCl3): d = –112.77 (dd, J = 263.61, 10.87 Hz, 1
F), –113.61 (dd, J = 263.61, 10.87 Hz, 1 F), –120.02 (dd,
J = 276.02, 7.14 Hz, 1 F), –127.23 (dd, J = 273.39, 16.66 Hz, 1 F).
HRMS (FAB): m/z [M+] calcd for C12H12F4O2: 264.0773; found:
264.0769.
2,2,3,3-Tetrafluoro-1-(3-methoxyphenyl)pent-4-en-1-ol (12c)
IR (neat): 3444, 3006, 2942, 2840, 1934, 1712, 1659, 1603, 1492,
1467, 1438, 1420, 1261, 1184, 1105, 987, 908 cm–1.
1H NMR (CDCl3): d = 2.62 (br s, 1 H), 3.81 (s, 3 H), 5.10 (dd,
J = 17.06, 6.79 Hz, 1 H), 5.66 (d, J = 11.19 Hz, 1 H), 5.85 (dt,
J = 16.79, 2.2 Hz, 1 H), 6.01 (ddt, J = 11.80, 17.39, 11.80 Hz, 1 H),
6.91–6.94 (m, 1 H), 7.02 (d, J = 7.59 Hz, 2 H), 7.30 (t, J = 7.79 Hz,
1 H).
13C NMR (CDCl3): d = 55.23, 71.89 (dd, J = 28.92, 23.19 Hz),
112.47–113.51 (m), 114.81–115.97 (m), 117.57–118.45 (m),
120.43, 123.50 (t, J = 9.49 Hz), 126.92 (t, J = 24.00 Hz), 129.34,
136.63, 159.51.
19F NMR (CDCl3, CFCl3): d = –113.02 (dd, J = 263.61, 11.80 Hz, 1
F), –114.00 (dd, J = 263.61, 11.80 Hz, 1 F), –119.99 (d, J = 273.39
Hz, 1 F), –127.68 (dt, J = 273.39, 17.06 Hz, 1 F).
HRMS (FAB): m/z [M+] calcd for C11H9ClF4O: 268.0278; found:
268.0280.
2,2,3,3-Tetrafluoro-1-[4-(trifluoromethyl)phenyl]pent-4-en-1-
ol (12g)
IR (neat): 3619, 3434, 2925, 1623, 1420, 1326, 1246, 1171, 1133,
1069, 1019, 979, 858, 789, 477 cm–1.
1H NMR (CDCl3): d = 2.60 (br s, 1 H), 5.25 (dd, J = 16.86, 6.79 Hz,
1 H), 5.70 (d, J = 11.55 Hz, 1 H), 5.87 (dd, J = 16.89, 2.4 Hz, 1 H),
6.02 (ddt, J = 11.55, 16.89, 11.55 Hz, 1 H), 7.63 (dd, J = 25.58, 8.39
Hz, 4 H).
13C NMR (CDCl3): d = 71.45 (dd, J = 28.92, 23.09 Hz), 112.18–
113.59 (m), 114.71–116.06 (m), 117.28–118.54 (m), 122.55,
HRMS (FAB): m/z [M+] calcd for C12H12F4O2: 264.0773; found:
264.0777.
Synthesis 2011, No. 1, 33–44 © Thieme Stuttgart · New York

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Novel Introduction of a Tetrafluoroethylene Unit into Organic Molecules
41
124.03 (td, J = 9.14, 1.61 Hz), 125.26 (q, J = 3.58 Hz), 126.50 (t,
J = 24.00 Hz), 128.48, 131.31 (q, J = 32.53 Hz), 138.81.
HRMS (FAB): m/z [M+] calcd for C9H8F4O2: 224.0460; found:
224.0458.
19F NMR (CDCl3, CFCl3): d = –63.25 (s, 3 F), –112.70 (dd,
J = 263.61, 11.55 Hz, 1 F), –113.49 (dd, J = 263.61, 11.55 Hz, 1 F),
–119.41 (dd, J = 273.39, 7.52 Hz, 1 F), –127.35 (ddd, J = 270.76,
16.86, 4.89 Hz, 1 F).
HRMS (FAB): m/z [M+] calcd for C12H9F7O: 302.0542; found:
302.0552.
4,4,5,5-Tetrafluoro-1-phenylhepta-1,6-dien-3-ol (12k)
IR (neat): 3397, 3029, 2924, 1653, 1578, 1496, 1450, 1420, 1237,
1184, 1109, 1010, 967, 863 cm–1.
1H NMR (CDCl3): d = 2.47 (d, J = 5.20 Hz, 1 H), 4.77 (td,
J = 14.53, 6.79 Hz, 1 H), 5.70 (d, J = 11.70 Hz, 1 H), 5.89 (dt,
J = 17.29, 2.00 Hz, 1 H), 6.07 (ddt, J = 11.70, 17.29, 11.70 Hz, 1
H), 6.29 (dd, J = 15.79, 6.79 Hz, 1 H), 6.81 (d, J = 15.79 Hz, 1 H),
7.29–7.32 (m, 1 H), 7.36 (t, J = 7.39 Hz, 2 H), 7.43 (d, J = 7.19 Hz,
2 H).
13C NMR (CDCl3): d = 71.18 (dd, J = 27.31, 24.8 Hz), 112.68–
113.44 (m), 115.17–115.99 (m), 117.65–118.53 (m), 121.86 (d,
J = 3.21 Hz), 123.67 (t, J = 9.54 Hz), 126.97 (t, J = 23.95 Hz),
126.82, 128.45, 128.65, 135.58 (d, J = 32.23 Hz).
19F NMR (CDCl3, CFCl3): d = –113.22 (dd, J = 258.72, 11.70 Hz, 1
F), –113.96 (dd, J = 263.61, 7.14 Hz, 1 F), –122.46 (dd, J = 273.39,
7.14 Hz, 1 F), –126.48 (dd, J = 273.01, 14.53 Hz, 1 F).
1-(4-Cyanophenyl)-2,2,3,3-tetrafluoropent-4-en-1-ol (12h)
IR (neat): 3434, 2927, 2234, 1931, 1727, 1650, 1612, 1506, 1420,
1241, 1177, 1108, 1011, 989, 859, 834, 789, 736, 703, 568 cm–1.
1H NMR (CDCl3): d = 3.00 (br s, 1 H), 5.24 (dd, J = 14.21, 5.99 Hz,
1 H), 5.70 (d, J = 11.40 Hz, 1 H), 5.86 (dt, J = 17.38, 2.00 Hz, 1 H),
6.02 (ddt, J = 11.40, 17.38, 11.40 Hz, 1 H), 7.59 (d, J = 7.99 Hz, 2
H), 7.67 (d, J = 7.19 Hz, 2 H).
13C NMR (CDCl3): d = 71.18 (dd, J = 28.92, 23.19 Hz), 112.12–
113.487 (m), 114.65–115.97 (m), 117.23–118.14 (m), 118.39,
124.02 (t, J = 9.54 Hz), 126.45 (t, J = 23.95 Hz), 128.84, 131.96,
140.36.
HRMS (FAB): m/z [M+] calcd for C13H12F4O: 260.0824; found:
260.0825.
19F NMR (CDCl3, CFCl3): d = –112.99 (dd, J = 31.96, 11.40 Hz, 2
F), –119.17 (d, J = 270.76 Hz, 1 F), –126.91 (dd, J = 276.02, 14.21
Hz, 1 F).
HRMS (FAB): m/z [M + H]+ calcd for C12H10F4NO: 260.0698;
found: 260.0703.
3,3,4,4-Tetrafluorohept-6-en-3-ol (12l)
This compound is so volatile that it could not be isolated in a pure
form. The isolated mixture contained 12l and a small amount of
EtOAc.
1H NMR (CDCl3): d = 1.02 (t, J = 7.39 Hz, 3 H), 1.50–1.70 (m, 1
H), 1.71–1.89 (m, 1 H), 2.86 (d, J = 7.19 Hz, 1 H), 3.92 (dt, 16.85,
7.59 Hz, 1 H), 5.63 (d, J = 11.70 Hz, 1 H), 5.82 (dt, J = 17.38, 2.20
Hz, 1 H), 6.01 (ddt, J = 17.38, 11.70, 11.70 Hz, 1 H).
13C NMR (CDCl3): d = 9.93, 71.54 (dd, J = 28.11, 23.19 Hz),
113.16–119.50 (m, 2 C), 123.51 (t, J = 9.89 Hz), 127.54 (t,
J = 23.95 Hz).
19F NMR (CDCl3): d = –128.12 (dd, J = 273.39, 16.85 Hz, 1 F),
–122.94 (dd, J = 273.39, 7.14 Hz, 1 F), –114.07 (ddd, J = 268.50,
263.61, 11.70 Hz, 2 F).
2,2,3,3-Tetrafluoro-1-(4-nitrophenyl)pent-4-en-1-ol (12i)
IR (neat): 3493, 3116, 2928, 2858, 1709, 1650, 1608, 1524, 1421,
1350, 1318, 1242, 1180, 1109, 1014, 988, 862, 833, 795, 728, 698,
485 cm–1.
1H NMR (CDCl3): d = 3.08 (br s, 1 H), 5.32 (dd, J = 14.45, 6.79 Hz,
1 H), 5.71 (d, J = 11.40 Hz, 1 H), 5.90 (dt, J = 17.38, 14.99 Hz, 1
H), 6.02 (ddt, J = 11.40, 17.38, 11.40 Hz, 1 H), 7.65 (d, J = 8.79 Hz,
2 H), 8.22 (d, J = 8.79 Hz, 2 H).
13C NMR (CDCl3): d = 71.09 (dd, J = 28.92, 23.09 Hz), 112.05–
113.54 (m), 114.58–116.02 (m), 117.16–118.50 (m), 123.33,
124.20 (t, J = 9.49 Hz), 126.31 (t, J = 23.95 Hz), 127.94, 128.55,
129.06, 141.99 (d, J = 1.61 Hz), 148.26.
HRMS (CI): m/z [M + H]+ calcd for C7H11F4O: 187.0746; found:
187.0750.
19F NMR (CDCl3, CFCl3): d = –112.91 (dd, J = 17.30, 11.40 Hz, 2
F), –119.08 (dd, J = 276.02, 7.14 Hz, 1 F), –126.82 (dd, J = 280.53,
14.45 Hz, 1 F).
HRMS (FAB): m/z [M + H]+ calcd for C11H10F4NO3: 280.0599;
found: 280.0599.
3,3,4,4-Tetrafluoroundec-1-en-5-ol (12m)
IR (neat): 3389, 2961, 2931, 2860, 1467, 1420, 1261, 1188, 1097,
1015, 981, 958, 869, 803, 730, 460 cm–1.
1H NMR (CDCl3): d = 0.87–0.91 (m, 3 H), 1.30–1.35 (m, 11 H),
4.04 (dd, J = 15.99, 7.19 Hz, 1 H), 5.68 (d, J = 10.79 Hz, 1 H), 5.87
(dt, J = 17.58, 2.00 Hz, 1 H), 6.04 (ddt, J = 11.22, 17.38, 11.22 Hz,
1 H).
13C NMR (CDCl3): d = 13.96 (d, J = 2.41 Hz), 22.55 (d, J = 1.61
Hz), 28.95 (d, J = 1.61 Hz), 29.34, 31.65 (d, J = 1.71 Hz), 70.00
(dd, J = 27.31, 23.90 Hz), 112.86–114.04 (m), 115.34–116.58 (m),
117.82–119.12 (m), 123.26 (t, J = 9.89 Hz), 127.20 (t, J = 24.4 Hz).
19F NMR (CDCl3, CFCl3): d = –113.92 (t, J = 10.91 Hz, 2 F),
–122.84 (dd, J = 273.39, 7.14 Hz, 1 F), –128.41 (dd, J = 276.02,
14.67 Hz, 1 F).
HRMS (FAB): m/z [M + H]+ calcd for C11H19F4O: 243.1374; found:
243.1377.
2,2,3,3-Tetrafluoro-1-(furan-2-yl)pent-4-en-1-ol (12j)
IR (neat): 3409, 2926, 1650, 1503, 1421, 1237, 1187, 1150, 1111,
1014, 981, 926, 887, 802, 745, 597, 478 cm–1.
1H NMR (CDCl3): d = 2.57 (d, J = 7.59 Hz, 1 H), 5.17 (quint,
J = 7.99 Hz, 1 H), 5.66 (d, J = 11.22 Hz, 1 H), 5.84 (dd, J = 17.18,
2.00 Hz, 1 H), 5.98 (ddt, J = 11.22, 17.18, 11.22 Hz, 1 H), 6.41 (dd,
J = 3.20, 2.00 Hz, 1 H), 6.50 (d, J = 3.20 Hz, 1 H), 7.46 (d, J = 2.00
Hz, 1 H).
13C NMR (CDCl3): d = 65.55 (dd, J = 28.92, 24.00 Hz), 66.99 (dd,
J = 28.11, 23.90 Hz), 109.79 (t, J = 3.31 Hz), 111.075, 111.53 (q,
J = 1.67 Hz), 112.20, 112.52, 112.85, 114.73–115.661 (m), 117.65
(td, J = 33.48, 2.51 Hz), 122.07 (t, J = 9.94 Hz), 123.65 (t, J = 9.89
Hz), 125.15–125.96 (m), 127.09–127.66 (m), 142.11–142.25 (m),
143.27 (dd, J = 10.74, 4.92 Hz), 144.24 (dd, J = 9.04, 4.12 Hz),
147.93–148.04 (m).
19F NMR (CDCl3, CFCl3): d = –113.67 (dd, J = 263.61, 11.22 Hz, 1
F), –115.18 (dd, J = 266.24, 11.22 Hz, 1 F), –122.01 (dt, J = 270.76,
7.34 Hz, 1 F), –126.49 (dd, J = 270.76, 17.18 Hz, 1 F).
1-Cyclohexyl-2,2,3,3-tetrafluoropent-4-en-1-ol (12n)
IR (neat): 3607, 3443, 2930, 2856, 2673, 1651, 1453, 1420, 1304,
1256, 1193, 1105, 986, 958, 933, 918, 896, 873, 847, 794, 731, 676,
458 cm–1.
1H NMR (CDCl3): d = 1.14–1.44 (m, 5 H), 1.66 (s, 2 H), 1.82 (dd,
J = 24.38, 13.19 Hz, 5 H), 3.89 (d, J = 20.37 Hz, 1 H), 5.67 (d,
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T. Konno et al.
PAPER
J = 11.60 Hz, 1 H), 5.88 (dt, J = 17.38, 2.4 Hz, 1 H), 6.04 (ddt,
J = 11.60, 17.38, 11.60 Hz, 1 H).
HRMS (FAB): m/z [M+] calcd for C10H14F4O: 226.0981; found:
226.0975.
13C NMR (CDCl3): d = 25.92 (d, J = 14.86 Hz), 26.33, 30.14 (d,
J = 1.71 Hz), 38.04, 72.93 (dd, J = 27.31, 21.49 Hz), 113.12 (dd,
J = 36.55, 33.03 Hz), 114.32 (t, J = 33.03 Hz), 115.61 (dd,
J = 35.54, 33.03 Hz), 116.87 (t, J = 33.03 Hz), 118.09 (dd,
J = 35.54, 33.03 Hz), 119.44 (d, J = 66.16 Hz), 123.26 (t, J = 9.49
Hz), 127.16 (t, J = 24.4 Hz).
19F NMR (CDCl3, CFCl3): d = –114.77 (dd, J = 22.19, 11.60 Hz, 2
F), –120.65 (d, J = 275.64 Hz, 1 F), –125.59 (dd, J = 273.01, 20.37
Hz, 1 F).
N-Benzyl-2,2,3,3-tetrafluoro-1-phenylpent-4-enylamine (12r)
IR (neat): 3364, 3086, 3064, 3027, 2929, 2843, 1957, 1646, 1602,
1584, 1494, 1471, 1454, 1416, 1358, 1329, 1267, 1226, 1207, 1157,
1090, 972, 960, 912, 867, 827, 797, 750, 694, 633, 580 cm–1.
1H NMR (CDCl3): d = 1.94 (s, 1 H), 3.37 (d, J = 13.19 Hz, 1 H),
3.60 (d, J = 13.19 Hz, 1 H), 4.06 (dd, J = 17.45, 9.59 Hz, 1 H), 5.39
(d, J = 11.12 Hz, 1 H), 5.62 (d, J = 17.38 Hz, 1 H), 5.85 (ddt,
J = 11.12, 17.38, 11.12 Hz, 1 H), 7.11–7.24 (m, 10 H).
13C NMR (CDCl3): d = 50.75, 61.79 (dd, J = 25.70, 20.58 Hz),
113.19 (t, J = 33.48 Hz), 114.33 (t, J = 32.63 Hz), 115.67 (t,
J = 33.94 Hz), 116.88 (td, J = 32.68, 3.31 Hz), 118.16 (t, J = 33.89
Hz), 119.42 (t, J = 33.03 Hz), 127.19, 127.49 (t, J = 24.00 Hz),
128.22–128.55 (m), 129.09, 134.35, 134.96, 139.14, 161.90.
19F NMR (CDCl3, CFCl3): d = –112.38 (dd, J = 260.98, 11.12 Hz, 1
F), –113.41 (dd, J = 260.98, 11.12 Hz, 1 F), –116.47 (dt, J = 270.76,
4.89 Hz, 1 F), –123.80 (dd, J = 270.76, 17.45 Hz, 1 F).
HRMS (FAB): m/z [M + H]+ calcd for C11H17F4O: 241.1217; found:
241.1204.
4,4,5,5-Tetrafluoro-2,2-dimethylhept-6-en-3-ol (12o)
IR (neat): 3609, 3490, 2964, 2880, 1714, 1651, 1483, 1469, 1420,
1371, 1266, 1238, 1188, 1112, 985, 959, 909, 885, 796, 758, 733,
721, 449 cm–1.
1H NMR (CDCl3): d = 1.08 (s, 9 H), 1.92 (d, J = 8.39 Hz, 1 H), 3.76
(dd, J = 24.42, 7.59 Hz, 1 H), 5.66 (d, J = 10.82 Hz, 1 H), 5.86 (dt,
J = 17.58, 2.00 Hz, 1 H), 6.05 (ddt, J = 10.82, 17.58, 10.82 Hz, 1
H).
HRMS (FAB): m/z [M + H]+ calcd for C18H18F4N: 324.1377; found:
324.1368.
(R)-N-(2,2,3,4-Tetrafluoro-1-phenylpent-4-enyl)-2-methylpro-
pane-2-sulfinamide (12s)
Obtained as a mixture of diastereomers, ratio 90:10. A part of the
major isomer could be isolated in a pure form, however, the minor
isomer could not be obtained in a pure form. For the minor isomer,
only identified peaks in the NMR spectra are shown.
13C NMR (CDCl3): d = 26.48, 26.53 (t, J = 1.66 Hz), 35.33, 53.37,
74.98 (dd, J = 28.11, 21.49 Hz), 113.17 (t, J = 33.89 Hz), 115.13–
115.99 (m), 117.70–118.48 (m), 120.62 (t, J = 31.83 Hz), 123.07 (t,
J = 9.54 Hz), 127.40 (t, J = 24.35 Hz).
19F NMR (CDCl3, CFCl3): d = –114.16 (dd, J = 261.35, 10.82 Hz, 1
F), –115.22 (dd, J = 261.35, 10.82 Hz, 1 F), –115.78 (d, J = 273.39,
Hz, 1 F), –128.90 (dd, J = 273.39, 24.42 Hz, 1 F).
Major Isomer (Rs,S)
White solid; mp 83 °C.
HRMS (FAB): m/z [M + H]+ calcd for C9H15F4O: 215.1061; found:
215.1059.
IR (KBr): 3423, 3321, 2963, 1458, 1419, 1367, 1222, 1185, 1098,
1073, 1007, 982, 960, 875, 847, 828, 802, 745, 730, 719, 701, 642,
543, 485, 433 cm–1.
1H NMR (CDCl3): d = 1.22 (s, 9 H), 3.69 (d, J = 7.19 Hz, 1 H), 4.88
(td, J = 13.47, 7.59 Hz, 1 H), 5.58 (d, J = 11.25 Hz, 1 H), 5.73 (d,
J = 17.38 Hz, 1 H), 5.84 (ddt, J = 11.25, 17.38, 11.25 Hz, 1 H), 7.36
(d, J = 2.40 Hz, 5 H).
13C NMR (CDCl3): d = 22.70, 56.85, 60.26 (dd, J = 24.00, 21.49
Hz), 112.79 (t, J = 34.69 Hz), 113.54 (t, J = 33.89 Hz), 115.28 (t,
J = 34.34 Hz), 116.10 (t, J = 33.88 Hz), 117.76 (t, J = 34.29 Hz),
118.65 (t, J = 33.88 Hz), 123.81 (t, J = 9.54 Hz), 126.39 (t, J = 24.4
Hz), 128.30, 128.80, 129.11, 134.91 (d, J = 4.22 Hz).
19F NMR (CDCl3, CFCl3): d = –112.41 (t, J = 11.25 Hz, 2 F),
–117.65 (dd, J = 273.39, 13.47 Hz, 1 F), –120.42 (dd, J = 273.01,
13.47 Hz, 1 F).
3,3,4,5-Tetrafluoro-2-phenylhex-5-en-2-ol (12p)
IR (neat): 3611, 3484, 3095, 3063, 3031, 3004, 2946, 1958, 1905,
1815, 1713, 1650, 1605, 1497, 1449, 1419, 1382, 1350, 1236, 1182,
1114, 1029, 1012, 980, 915, 810, 762, 728, 700, 671, 649, 623 cm–1.
1H NMR (CDCl3): d = 1.82 (s, 3 H), 2.58 (s, 1 H), 5.51 (d, J = 12.00
Hz, 1 H), 5.70 (dt, J = 17.19, 2.4 Hz, 1 H), 5.89 (ddt, J = 12.00,
17.19, 12.00 Hz, 1 H), 7.36–7.42 (m, 3 H), 7.59 (d, J = 7.59 Hz, 2
H).
13C NMR (CDCl3): d = 25.01, 75.74 (d, J = 49.6 Hz), 113.24–
114.25 (m), 115.74–116.85 (m), 118.24–119.43 (m), 126.25,
127.48, 127.71, 127.99 (d, J = 13.25 Hz).
19F NMR (CDCl3, CFCl3): d = –107.93 (dd, J = 263.61, 12.00 Hz, 1
F), –109.87 (dd, J = 263.61, 12.00 Hz, 1 F), –118.29 (d, J = 276.02
Hz, 1 F), –119.56 (d, J = 275.64 Hz, 1 F).
HRMS (FAB): m/z [M + Na]+ calcd for C12H12F4NaO: 271.0722;
Minor Isomer (Rs,R)
19F NMR (CDCl3, CFCl3): d = –112.14 (d, J = 7.98 Hz, 2 F),
–119.51 (dd, J = 270.76, 13.54 Hz, 1 F), –120.53 (dd, J = 270.76,
13.54 Hz, 1 F).
HRMS (FAB): m/z [M + H]+ calcd for C15H20F4NOS: 338.1203;
found: 338.1207.
found: 271.0721.
1-(1,1,2,2-Tetrafluorobut-3-enyl)cyclohexanol (12q)
IR (neat): 3677, 3606, 3465, 3108, 3056, 2941, 2865, 2673, 1914,
1703, 1651, 1452, 1419, 1383, 1358, 1322, 1291, 1255, 1182, 1109,
975, 912, 879, 870, 847, 824, 778, 737, 693, 636, 502 cm–1.
1H NMR (CDCl3): d = 1.16–1.26 (m, 1 H), 1.58–1.85 (m, 10 H),
5.62 (d, J = 11.70 Hz, 1 H), 5.81 (dt, J = 17.38, 2.2 Hz, 1 H), 6.07
(ddt, J = 11.70, 17.38, 11.70 Hz, 1 H).
13C NMR (CDCl3): d = 20.47, 25.15, 30.25–30.35 (m), 41.94, 74.42
(td, J = 23.54, 1.71 Hz), 113.64–114.73 (m), 116.13–117.30 (m),
118.62–119.86 (m), 122.17 (t, J = 9.94 Hz), 128.17 (t, J = 23.95
Hz).
Triethyl(1,1,2,2-tetrafluorobut-3-en-1-yl)silane (15)
To a soln of Mg (0.087 g, 3.6 mmol) in THF (7.2 mL) was added a
Et3SiCl (0.543 g, 3.6 mmol) at 0 °C. After ca. 5 min, to this mixture
was added dropwise 11 (0.620 g, 3.0 mmol) and it was stirred at this
temperature for 3 h. To the mixture was added excess hexane (30
mL) and then it was filtered; it was then concentrated in vacuo (79%
by 19F NMR). The residue was purified by column chromatography
(silica gel, hexane only) to give 15.
19F NMR (CDCl3, CFCl3): d = –110.88 (d, J = 11.70 Hz, 2 F),
–125.029 (s, 2 F).
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Novel Introduction of a Tetrafluoroethylene Unit into Organic Molecules
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IR (neat): 3108, 2960, 2884, 2742, 1912, 1653, 1461, 1419, 1383,
1243, 1091, 1029, 981, 955, 919, 889, 802, 741, 604, 579, 491, 408
cm–1.
1H NMR (CDCl3): d = 0.84 (t, J = 7.59 Hz, 6 H), 1.04 (t, J = 7.59
Hz, 9 H), 5.65 (q, J = 11.63 Hz, 1 H), 5.81 (d, J = 17.29 Hz, 1 H),
5.99 (ddt, J = 11.63, 17.29, 11.63 Hz, 1 H).
13C NMR (CDCl3): d = 1.41, 6.64 (d, J = 11.65 Hz), 115.09 (t,
J = 31.43 Hz), 117.51 (t, J = 31.43 Hz), 119.92 (t, J = 31.43 Hz),
121.17 (t, J = 51.25 Hz), 123.03–123.22 (m), 123.86 (t, J = 51.25
Hz), 126.04, 126.87 (t, J = 25.65 Hz).
5-Ethyl-3,3,4,4-tetrafluorotetrahydrofuran-1-ol (17l)
Isolated as an isomeric mixture in a ratio of ca. 2:1.
1H NMR (CDCl3): d = 1.04 (t, J = 7.59 Hz, 3 H), 1.65–1.83 (m, 2
H), 3.87–4.27 (m, 2 H), 5.36 (d, J = 6.39 Hz, 1 H).
19F NMR (CDCl3, CFCl3): d = –135.17 (dd, 241.80, 16.92 Hz, 1 F),
–130.07 (dd, J = 241.80, 4.89 Hz, 1 F), –128.13 (dd, J = 246.31,
7.52 Hz, 1 F), –119.28 (d, J = 239.17 Hz, 1 F).
HRMS (EI): m/z [M + H]+ calcd for C6H9F4O2 189.0539; found:
189.0539.
19F NMR (CDCl3, CFCl3): d = –110.99 (d, J = 11.63 Hz, 2 F),
–122.05 (s, 2 F).
2,2,3,3-Tetrafluoro-1-(4-methylphenyl)-4-phenylbutane-1,4-
diol (18a); Typical Procedure
To a soln of 17a (0.1 mmol) in THF (0.5 mL) was dropwise added
0.55 M 4-MeC6H4MgBr in THF [0.73 mL, 4.0 equiv which was pre-
pared from 4-bromotoluene (2.0 mmol) and Mg (2.0 mmol) at r.t.
for 1 h] at r.t. Then the mixture was stirred at reflux overnight. The
reaction was quenched with sat. NH4Cl and after separation of the
two layers, the aqueous soln was washed with Et2O (2 ×) and the
combined organic layers were washed with brine, dried (Na2SO4),
and concentrated in vacuo. The resulting mixture was purified by
column chromatography (silica gel, hexane–EtOAc, 2:1) to obtain
the corresponding diol.
1H NMR (CDCl3): d = 1.64 (s, 1 H), 2.32 (d, J = 39.17 Hz, 3 H),
3.11 (d, J = 44.76 Hz, 1 H), 5.23 (t, J = 17.98 Hz, 1 H), 6.72 (d,
J = 8.39 Hz, 1 H), 7.04 (d, J = 7.99 Hz, 1 H), 7.15–7.26 (m, 1 H),
7.36–7.41 (m, 3 H).
HRMS (EI+): m/z [M+] calcd for C10H18F4Si: 242.1114; found:
242.1110.
3,3,4,5-Tetrafluoro-2-(4-nitrophenyl)hex-5-en-2-ol (12t); Typi-
cal Procedure
To a soln of 15 (0.087 g, 0.36 mmol) in THF (0.3 mL) was added 4-
nitroacetophenone (0.050 g, 0.030 mmol) at 0 °C. After ca. 10 min,
to this mixture was added dropwise 0.1 M TBAF (0.03 mL, 1
mol%) and it was stirred at this temperature for 12 h. The reaction
was quenched with H2O and then it was extracted with Et2O (3 ×).
The combined organic layers were dried (anhyd Na2SO4), then fil-
tered, and concentrated in vacuo. To the residue was added 1.0 M
TBAF (0.60 mL, 0.6 mmol) at 0 °C. The mixture was stirred for 2 h
and quenched with H2O and then it was extracted with Et2O (3 ×).
The combined organic layers were dried (anhyd Na2SO4), filtered,
and concentrated in vacuo. The residue was purified by column
chromatography (silica gel, hexane–EtOAc, 5:1) to give the corre-
sponding alcohol 12t (0.033 g, 0.11 mmol, 37%).
19F NMR (CDCl3): d = –127.64 (ddd, J = 19.55, 80.85, 276.02 Hz,
2 F), –116.93 (dd, J = 56.03, 275.64 Hz, 2 F).
HRMS: m/z [M + Na]+ calcd for C17H16F4NaO2: 351.0984; found:
351.0977.
IR (neat): 3517, 3117, 3002, 2923, 2853, 1649, 1606, 1523, 1459,
1419, 1351, 1296, 1263, 1236, 1186, 1117, 1076, 1014, 980, 920,
856, 807, 754, 737, 704, 477 cm–1.
1H NMR (CDCl3): d = 1.82 (s, 3 H), 2.77 (s, 1 H), 5.57 (d, J = 11.90
Hz, 1 H), 5.70 (dt, J = 17.18, 2.4 Hz, 1 H), 5.93 (ddt, J = 11.90,
17.18, 11.90 Hz, 1 H), 7.76 (d, J = 8.79 Hz, 2 H), 8.20 (dt, J = 9.59,
2.2 Hz, 2 H).
13C NMR (CDCl3): d = 25.18–25.27 (m), 29.65, 75.72 (t, J = 25.65
Hz), 113.14–113.87 (m), 115.68–116.39, 118.18–118.98, 122.82,
122.93 (d, J = 1.61 Hz), 123.01, 127.25 (t, J = 21.89 Hz), 146.89 (d,
J = 2.51 Hz), 147.58.
19F NMR (CDCl3, CFCl3): d = –109.32 (dd, J = 263.61, 11.90 Hz, 1
F), –110.88 (ddd, J = 258.72, 11.90, 4.89 Hz, 1 F), –119.07 (dd,
J = 278.28, 4.89 Hz, 1 F), –120.48 (d, J = 278.28 Hz, 1 F).
2,2,3,3-Tetrafluoro-1-phenylhexane-1,4-diol (18l)
Isolated with dr 11:1.
IR (neat): 3347, 3037, 2979, 2942, 2884, 1496, 1457, 1313, 1237,
1202, 1175, 1114, 1029, 989, 911, 884, 822, 789, 732, 699, 612, 489
cm–1.
1H NMR (CDCl3): d = 1.04 (t, J = 7.59 Hz, 3 H), 1.60–1.88 (m, 2
H), 3.85 (d, J = 6.30 Hz, 1 H), 3.89–3.99 (m, 1 H), 4.43 (d, J = 4.00
Hz, 1 H), 5.04 (d, J = 21.29 Hz, 1 H), 7.26–7.45 (m, 5 H).
13C NMR (CDCl3): d = 10.27, 22.60–22.70 (m), 71.93 (dd,
J = 52.11, 28.11 Hz), 72.88 (t, J = 72.89 Hz), 113.35–120.10 (m, 2
C), 128.48, 128.65, 129.51, 135.06.
19F NMR (CDCl3, CFCl3): d = –127.97 (ddt, J = 278.28, 21.29, 7.33
Hz, 1 F), –127.52 (ddt, J = 275.64, 14.67, 7.33 Hz, 1 F), –119.12
(ddt, J = 275.64, 12.41, 6.30 Hz, 1 F), –117.31 (d, J = 276.02 Hz, 1
F).
HRMS (FAB): m/z [M + H]+ calcd for C12H12F4NO3: 294.0753;
found: 294.0757.
HRMS (EI): m/z [M+] calcd for C12H14F4O2: 266.0930; found:
266.0933.
3,3,4,4-Tetrafluoro-5-phenyltetrahydrofuran-2-ol (17a); Typi-
cal Procedure
The alcohol 12a (4.5 mmol) was dissolved in CH2Cl2 (15 mL) and
cooled to –78 °C. Then the argon in the flask was replaced with O3,
and the mixture was stirred at this temperature for 3 h. The reaction
was quenched with Me2S, and extracted with EtOAc (3 ×). The mix-
ture was filtered, and the thus obtained filtrate was concentrated in
vacuo. The residue was purified by column chromatography (silica
gel, hexane–EtOAc, 2: 1) to give the corresponding tetrahydrofuran
as an isomeric mixture in a ratio of ca. 7:3.
1H NMR (CDCl3): d = 3.31–3.36 (m, 1 H), 5.30–5.46 (m, 1 H),
5.60–5.64 (m, 1 H), 7.39–7.49 (m, 5 H).
19F NMR (CDCl3): d = –137.26 to –120.05 (m, 4 F).
HRMS: m/z [M+] calcd for C10H8F4O2: 236.0460; found: 236.0459.
References
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T. Konno et al.
PAPER
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(7) The absolute stereochemistry was determined on the basis of
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(9) There has been no report on the synthesis of unsymmetric
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which symmetric 2,2,3,3-tetrafluoro-1,4-diol derivatives
were synthesized, have been published thus far.
(a) Fuchigami, T.; Hagiwara, T. JP 6228030, 1994.
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(6) Unpublished results.
Synthesis 2011, No. 1, 33–44 © Thieme Stuttgart · New York