Selective anodic fluorination of electrophilic alkenes

Article abstract of DOI:10.1016/j.jfluchem.2005.02.021

Anodic fluorination of some electrophilic alkenes (conjugated with electron-withdrawn groups), ethyl cinnamates, RC₆H ₄CHCHCO₂Et (R = H, CH₃, CH₃O, F and CF₃), cinnamonitrile, C₆H₄CHCHCN, phenyl stryryl ketone, and t-butyl styryl ketone using ammonium fluorides as the fluorine source and supporting electrolyte, in CH₂Cl₂ as electrolytic solvent yields the expected vicinal difluoro compounds, as mixture of erythro and threo isomers. The anodic fluorination of phenyl 3,5-di-t-butyl-4-hydroxystyryl ketone yields two monofluoro compounds. A possible reaction mechanism is discussed.

Full text of DOI:10.1016/j.jfluchem.2005.02.021

Journal of Fluorine Chemistry 126 (2005) 753–758
www.elsevier.com/locate/fluor
Selective anodic fluorination of electrophilic alkenes
*
Vasile Dinoiu , Kazuako Kanno, Tsuyoshi Fukuhara, Norihiko Yoneda
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 26 August 2004; received in revised form 15 November 2004; accepted 11 February 2005
Abstract
Anodic fluorination of some electrophilic alkenes (conjugated with electron-withdrawn groups), ethyl cinnamates, R–C6H4–CH CH–
CO2Et (R = H, CH3, CH3O, F and CF3), cinnamonitrile, C6H4–CH CH–CN, phenyl stryryl ketone, and t-butyl styryl ketone using
ammonium fluorides as the fluorine source and supporting electrolyte, in CH2Cl2 as electrolytic solvent yields the expected vicinal difluoro
compounds, as mixture of erythro and threo isomers. The anodic fluorination of phenyl 3,5-di-t-butyl-4-hydroxystyryl ketone yields two
monofluoro compounds. A possible reaction mechanism is discussed.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Electrochemical partial fluorination; Electrophilic alkenes; Amine–HF complexes
1. Introduction
ketone, t-butyl styryl ketone, and phenyl 3,5-di-t-butyl-4-
hydroxystyryl ketone) using Et3NꢀnHF (n = 3 and 5) and
Et4NFꢀnHF (n = 2 and 4) as supporting electrolytes and
fluorine sources in CH2Cl2 as electrolytic solvent. The
influence of the nature of the fluorine sources and of the
electrolytic temperature on the anodic fluorination was
investigated.
The selective fluorination of organic molecules has
attracted much interest because a number of partially
fluorinated organic molecules are reported to show
interesting chemical and physical properties and, in some
cases, biological activities [1,2].
The electrochemical partial fluorination (ECPF) of
organic compounds using Et3NꢀnHF (n = 2–4) as a fluorine
source and supporting electrolyte has been developed in the
last few years [3–5]. Recently, a new electrolyte, Et3Nꢀ5HF,
has been found to be electrochemically highly stable and an
excellent fluorinating agent for the electrochemical fluor-
ination of aldehydes and ketones to produce the correspond-
ing acylfluorides and alkylfluorides in good yields [6].
Continuing our efforts on the regioselective anodic
fluorination of unsaturated compounds [7,8], we report in
this paper the anodic fluorination of some electrophilic
alkenes (alkenes conjugated with electron-withdrawing
groups), such as a,b-unsaturated esters (ethyl cinnamates),
cinnamonitrile, and a,b-unsaturated ketones (phenyl stryryl
2. Results and discussion
We first investigate the anodic fluorination of ethyl
cinnamates 1A (a–e), cinnamonitrile 1Ba, phenyl stryryl
ketone 1Ca, and t-butyl styryl ketone 1Da using various
fluorine sources in CH2Cl2 (Scheme 1).
The experimental data are shown in Table 1. It was found
that the anodic fluorination of these activated alkenes yields
vicinal difluoro ester derivatives 2A (a–e), 2Ba and vicinal
difluoro ketones 2Ca and 2Da as mixtures of two diastereo-
isomers, erythro and threo. Low yields were obtained when
the electrochemical reaction occurs without using an electro-
lytic solvent (Entry 1) and in the presence of Et3Nꢀ3HF as
fluorine source (Entries 1 and 2), CH2Cl2 was a suitable
electrolytic solvent (Entries 3–16 and 19–20). High yields
were obtained when the anodic fluorination occurs in the
presence of Et3Nꢀ5HF, Et4NFꢀ2HF, and Et4NFꢀ4HF as
fluorine sources and supporting electrolytes (Entries 3–12
* Corresponding author. Present address: Romanian Academy, ‘‘C.D.
Nenitzescu’’ Institute of Organic Chemistry, Spl. Independentei 202B,
Bucharest 77141, Romania
E-mail address: vdinoiu@yahoo.com (V. Dinoiu).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.02.021

754
V. Dinoiu et al. / Journal of Fluorine Chemistry 126 (2005) 753–758
Scheme 1.
and 19–20). The electrolytic temperature generally was found
not to be a great influence on the anodic fluorination of
substrate1Aa. Roomtemperature(r.t.)seemstobe a sufficient
electrolytic temperature for these reactions (yield = 70%,
Entries 5 and 8).
stabilized C+ formed (higher reactivity for these systems),
and the yields of the difluoro esters are lower (Table 1,
Entries 9–10). Side products, like saturated trifluoro
derivatives or unsaturated monofluoro derivatives, can be
formed, as is shown in literature data [9], for these kind of
reactions.
19F NMR spectra show that the anodic fluorination of
cinamonitrile 1B yields the desired vicinal difluoro
derivative 2Ba as a mixture of two diastereoisomers,
together with the trifluoro derivative 3Ba. The trifluoro
The substituent R influences the yields of reaction, better
yields being obtained when substituent groups are electron
withdrawing, F and CF3 (Table 1, Entries 11 and 12); when
substituent groups are electron donating ones, CH3 and
CH3O, the substrates have lower anodic potentials due to the
Table 1
Electrochemical partial fluorination of functionalized alkenes 1A–D
Entry
Compounds
R
Electrolyte
Solvent
Potential (V) vs. Ag/Ag+
Charge passed (F/mol)
Temperature (8C)
Yielda (%)
3Ba
2
1
2
1Aa
1Aa
1Aa
1Aa
1Aa
1Aa
1Aa
1Aa
1Ab
1Ac
1Ad
1Ae
1Ba
1Ba
1Ba
1Ba
1Ba
1Ba
1Ca
1Da
H
Et3Nꢀ3HF
Et3Nꢀ3HF
Et3Nꢀ5HF
Et4NFꢀ4HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et4NFꢀ2HF
Et3Nꢀ3HF
Et3Nꢀ4HF
Et3Nꢀ5HF
Et3Nꢀ5HF
Et3Nꢀ5HF
Et4NFꢀ2HF
Et4NFꢀ2HF
None
1.9
3.0
2.5
2.5
3.5
3.5
3.5
3.5
3.5
3.5
3.0
4.0
4.0
3.0
3.0
2.5
3.5
3.5
3.5
4.0
5.0
r.t.
r.t.
r.t.
r.t.
r.t.
0
1.5
H
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
AcOEt
MeCNb
CH2Cl2
CH2Cl2
1.95
1.9
16
58
66
70
66
57
70
57
27
63
58
33
27.5
12
27
23
21
48
41
3
H
4
H
1.95
1.95
1.95
1.95
1.95
1.7
5
H
6
H
7
H
ꢁ46
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
8
H
9
CH3
CH3O
F
10
11
12
13
14
15
16
17
18
19
20
1.4
1.9
CF3
H
2.3
1.85
1.9
17
5
H
H
1.8
6
H
1.9
23
18
29
H
1.9
H
1.8
H
1.9
r.t.
r.t.
H
1.9
Unfortunately, we were not able to isolate the pure fluoroacetamide derivative, which was not further investigated.
a
Isolated yield.
b
A fluoroacetamide derivative was obtained, 8% GC yield.

V. Dinoiu et al. / Journal of Fluorine Chemistry 126 (2005) 753–758
755
Scheme 2.
derivative 3Ba was probably formed by dehydrofluorina-
tion–fluorination of 2. Unfortunately, we were not able to
isolate the pure trifluoro derivative 3Ba, which was not
further investigated.
nucleophilic attack of the fluoride ion takes place on the
benzylic beta-carbon atom. It is known that the most
positive charge in the radical-cation is always located on
the carbonyl carbon atom, but nucleophilic attack on this
atom is fully reversible and does not lead to any products
[7,9]. The second high value of positive charge is located at
beta-carbon atom, so the first fluorination occurs at the
benzylic carbon atom.
The anodic fluorination of cinnamonitrile 1B was
performed in dichloromethane, ethylacetate, and acetonitrile
as electrolytic solvents; no significant influence on the
yields of electrolysis was found, as is shown in Table 1
(Entries 13–18). 19F NMR shows that a fluoroacetamide
derivative was obtained as a minor product (8% yield) when
anodic fluorination occurred in acetonitrile as electrolytic
solvent (Table 1, Entry 18); this compound was not further
investigated.
An interesting fluorination occurs when phenyl 3,5-di-t-
butyl-4-hydroxystyryl ketone 4 (a hindered phenol contain-
ing chalcone), synthesized from 3,5-di-t-butyl-4-hydroxy-
benzaldehyde and acetophenone in acidic conditions, was
anodically fluorinated in the presence of Et4NFꢀ2HF as
fluorine source and supporting electrolyte, and in CH2Cl2 as
electrolytic solvent (Scheme 3). To our pleasant surprise,
unlike our previous finding that fluorination occurs to yield
An ECNECN (electrochemical–chemical–electrochemi-
cal–chemical) mechanism is widely accepted for electro-
chemical partial fluorination reactions [9,10], and most
likely the reactions under our study follow the same pathway
(Scheme 2).
1
vic-difluoro ketones, in this case H and 19F NMR spectra
show that this reaction yields a mixture of two monofluoro
derivatives 5 and 6 in ratio 1:1 (yields are 30% for each).
Compounds 5 and 6 have the C O stretching bands at 1630–
1640 cmꢁ1, and do not have phenolic OH stretching bands.
We believe that the electron-donating hindered phenolic
group changed the reaction mechanism of anodic fluorina-
tion of this ketone derivative and two monofluoro derivatives
were obtained.
The one-electron oxidation of the substrate 1 gave the
radical cation species (RC), which was fluorinated by a
nucleophilic attack of the fluoride ion to afford a fluorinated
radical (FR). The subsequent oxidation of (FR) yielded the
fluorocarbocation (FC). Finally, the vicinal fluorinated
product 2 was formed by the nucleophilic attack of the
fluoride ion toward (FC).
Calculations of the atomic orbital spin population in
primary radical-cations formed by oxidation of cinnamic
esters revealed that the highest spin density appears on the
alpha-carbon atom, adjacent to the ester group, indepen-
dently of the nature of para-substituents R in the benzene
ring [9]. Therefore, the single electron in the radical
cation is always located at this atom and consequently,
We assume that this unexpected fluorination can be
explained by the reaction mechanism shown in Scheme 4, in
which the one-electron oxidation of chalcone 4 generates the
(4-radical-cation) that exists in two tautomers structures in
which the positive charge is located at carbon or oxygen
atom. The nucleophilic fluoride attacks the proton from
hydroxy group and the (4-radical) is formed; this radical has
Scheme 3.

756
V. Dinoiu et al. / Journal of Fluorine Chemistry 126 (2005) 753–758
Scheme 4.
a resonant structure, (4-aroxyl) that is a stable free radical
(aroxyl) due to the presence of the bulky t-butyl groups in
ortho, ortho0-positions. The hyperfine coupling constants
(hfcs), determined by the EPR spectra are the highest
(0.64 mT) on the styryl proton Ha, adjacent to the carbonyl
group, indicating a higher contribution of hyperconjugative
limiting structures placing high spin densities on these
protons [11], and carbon radical is formed. The subsequent
oxidation yields the corresponding (4-carbon cation), which
exist in the tautomeric forms. The nucleophilic attack of
fluoride ion on these cations yields the monofluoro
derivatives 5 and 6 in same ratio.
In summary, we have reported a selective electrochemical
fluorination of some electrophilic alkenes, i.e. ethyl
cinnamates, cinnamonitrile, phenyl stryryl ketone, t-butyl
styryl ketone, and phenyl 3,5-di-t-butyl-4-hydroxystyryl
ketone using Et3NꢀnHF (n = 3 and 5) and Et4NFꢀnHF (n = 2
and 4) as supporting electrolytes and fluorine sources.
Anodic fluorination of ethyl cinnamates, cinnamonitrile,
phenyl stryryl ketone, and t-butyl styryl ketone yield vicinal
difluoro esters or difluoro ketones, as mixtures of two
diastereoisomers, erythro and threo. In the anodic fluorina-
tion of cinnamonitrile, the trifluoro derivative 3B was also
formed. The highest yields were obtained when Et4NFꢀ2HF,
Et4NFꢀ4HF, and Et3Nꢀ5HF were used as fluorine sources in
the ECF of ethyl cinnamates 1A (a–e) and when Et4NFꢀ2HF,
Et3Nꢀ3HF, and Et3Nꢀ5HF were used in ECF of ethyl
cinnamonitrile 1Ba.
The anodic fluorination of phenyl 3,5-di-t-butyl-4-
hydroxystyryl ketone yielded two monofluoro derivatives.
Room temperature was found to be a sufficient electrolytic
temperature for these reactions.
3. Experimental
The electrolytes, Et3NꢀnHF and Et4NFꢀnHF, were kind
gifts of Morita Chemical Industries Co. Ltd. (Japan) and
were used without purification.
Caution: They are toxic and contact with skin causes
serious burns. Therefore, it is recommended that rubber
gloves be used.
3.1. Anodic fluorination of unsaturated esters
and ketones
Typical anodic difluorination conditions were as follows.
Anodic oxidation of 1A (1 mmol) and 1B (1 mmol) was
carried out with an undivided cell with a platinum anode and
cathode (2 cm ꢂ 2 cm) in 15 mL fluorine source or in 8 mL
fluorine source and 8 mL CH2Cl2 or MeCN. Anodic
potentials were determined by cyclic voltammertry. The
reference electrode was Ag/AgNO3 (0.01 M) in MeCN
containing Et4NꢀBF4 (0.1 M).
Since positive oxidative potentials were involved, careful
handling of the solvent supporting electrolyte system was

V. Dinoiu et al. / Journal of Fluorine Chemistry 126 (2005) 753–758
757
needed, moisture avoided, to ensure polymerization-free
electrolysis.
erythro: 1H NMR: 1.31 (t, J = 7 Hz, 3H); 4.26 (q,
J = 7 Hz, 2H); 5.30 (ddd, J = 49.3 Hz, J = 12.9 Hz,
J = 3.4 Hz, 1H); 5.83 (ddd, J = 44.1 Hz, J = 20.7 Hz,
J = 3.4 Hz, 1H); 7.1–7.4 (m, 5H). 19F NMR: ꢁ29.7 (m,
1F); ꢁ43.2 (m, 1F). IR (neat, cmꢁ1) 1766 (nC O). HRMS:
calcd. for C11H12F2O2 m/e 214.0805, found 214.0795.
Ethyl 2,3-difluoro-3-[4-methylphenyl] propionate (2Ab)
was purified by flash chromatography on silica gel, eluting
with 5:1 mixture of hexane and ethyl acetate to give a
colorless oil.
The electrolytic mixture was diluted with water and
extracted with three portions of CH2Cl2. The organic phase
was washed with brine and dried over MgSO4. After the
removal of MgSO4 by filtration, the products were isolated
by column chromatography on silica gel and identified by
1H- and 19F NMR spectra, IR spectra, MS spectra and
HMRS. Melting points were obtained on a Mel-Temp
melting point apparatus and are uncorrected. IR spectra were
obtained on FT/IR-410 Jasco spectometer. 1H NMR and 19
F
threo: 1H NMR: 1.22 (t, J = 7 Hz, 3H); 2.32 (s, 3H); 4.28
(q, J = 7 Hz, 2H); 5.28 (ddd, J = 47.3 Hz, J = 22.8 Hz,
J = 3.4 Hz, 1H); 5.78 (ddd, J = 48.2 Hz, J = 23.2 Hz,
J = 3.4 Hz, 1H); 7.1–7.4 (m, 4H). 19F NMR: ꢁ23.7 (m,
1F); ꢁ40.8 (m, 1F). IR (neat, cmꢁ1) 1767 (nC O). HRMS:
calcd. for C12H14F2O2 m/e 228.0962, found 228.0949.
NMR spectra were recorded, in CDCl3 as a solvent, on a
JEOL Datum (400 MHz) spectrometer. The chemical shifts
for 1H NMR are reported in d ppm downfield from internal
TMS, and those for 19F NMR are given in d ppm downfield
from internal C6F6, d(CFCl3) of the C6F6 reference being
ꢁ162.2 ppm. All reactions with air-sensitive compounds
were carried out under a nitrogen atmosphere. Column
chromatography was conducted with silica gel. GC analyses
were performed using a Hitachi G-5000 instrument (flame
ionization detector, FID) with a 30 m column Neutra Bond.
The mass spectra of compounds 2A (a–e), and 2Ba
contained the M+ or (M–HF)+ ions of low intensity and a
number of strong, characteristic fragmentation ions
(Table 2) allowed assignment of the structures.
1
erythro: H NMR: 1.23 (t, J = 7 Hz, 3H); 2.32 (s, 3H);
4.31 (q, J = 7 Hz, 2H); 4.98 (ddd, J = 49.3 Hz, J = 12.2 Hz,
J = 3.2 Hz, 1H); 5.76 (ddd, J = 44.2 Hz, J = 20.7 Hz,
J = 3.2 Hz, 1H); 7.1–7.4 (m, 4H). 19F NMR: ꢁ28.3 (m,
1F); ꢁ42.1 (m, 1F). IR (neat, cmꢁ1) 1767 (nC O). HRMS:
calcd. for C12H14F2O2 m/e 228.0962, found 228.0949.
Ethyl 2,3-difluoro-3-[4-methoxyphenyl]propionate (2Ac)
was purified by flash chromatography on silica gel, eluting
with 5:1 mixture of hexane and ethyl acetate to give a
colorless oils. Only the threo isomer was isolated.
threo: 1H NMR: 1.31 (t, J = 7 Hz, 3H); 3.82 (s, 3H); 4.28
(q, J = 7 Hz, 2H); 5.03 (ddd, J = 47.3 Hz, J = 24.7 Hz,
J = 3.2 Hz, 1H); 5.77 (ddd, J = 44.4 Hz, J = 22.7 Hz,
J = 3.2 Hz, 1H); 7.1–7.4 (m, 4H). 19F NMR: ꢁ25 (m,
1F); ꢁ42.1 (m, 1F). IR (neat, cmꢁ1) 1767 (nC O). HRMS:
calcd. for C12H14F2O3 m/e 244.0911, found 244.0886.
Ethyl 2,3-difluoro-3-[4-fluorophenyl]propionate (2Ad)
was purified by flash chromatography on silica gel, eluting
with 5:1 mixture of hexane and ethyl acetate to give a
colorless oil.
1
All compounds were characterized by H and 19F NMR
spectra, which confirmed their structure. The threo and
erythro configurations of difluoro-compounds were unam-
bigously demonstrated by the magnitude of vicinal H–F
coupling constants (ca. 23–26 and 12–13 Hz, respectively)
in their 1H and 19F NMR spectra. These values are
characteristic for such structures as is shown in literature
data [9].
Ethyl 2,3-difluoro-3-phenylpropionate (2Aa) was pur-
ified by flash chromatography on silica gel, eluting with 5:1
mixture of hexane and ethyl acetate to give a colorless oil.
threo: 1H NMR: 1.31 (t, J = 7 Hz, 3H); 4.23 (q, J = 7 Hz,
2H); 5.06 (ddd, J = 47.1 Hz, J = 25.6 Hz, J = 2.9 Hz, 1H);
5.85 (ddd, J = 44.6 Hz, J = 23.2 Hz, J = 2.9 Hz, 1H); 7.1–
7.4 (m, 5H). 19F NMR: ꢁ15.2 (m, 1F); ꢁ41.7 (m, 1F). IR
(neat, cmꢁ1) 1766 (nC O). HRMS: calcd. for C11H12F2O2 m/
e 214.0805, found 214.0795.
threo: 1H NMR: 1.27 (t, J = 7 Hz, 3H); 4.26 (q, J = 7 Hz,
2H); 5.02 (ddd, J = 47.1 Hz, J = 25.4 Hz, J = 3 Hz, 1H);
5.83 (ddd, J = 44.4 Hz, J = 23.2 Hz, J = 3 Hz, 1H); 7.1–7.4
(m, 4H). 19F NMR: ꢁ28.2 (m, 1F); ꢁ43.3 (m, 1F); 50.1 (s,
1F). IR (neat, cmꢁ1) 1767 (nC O). HRMS: calcd. for
C11H11F3O2 m/e 232.0711, found 232.0694.
erythro: 1H NMR: 1.28 (t, J = 7 Hz, 3H); 4.28 (q,
J = 7 Hz, 2H); 5.24 (ddd, J = 49.3 Hz, J = 12 Hz,
J = 3.4 Hz, 1H); 5.87 (ddd, J = 43.7 Hz, J = 21.5 Hz,
J = 3.4 Hz, 1H); 7.1–7.4 (m, 4H). 19F NMR: ꢁ22.9 (m,
1F); ꢁ42.2 (m, 1F); 50.1 (s, 1F). IR (neat, cmꢁ1) 1767
(nC O). HRMS: calcd. for C11H11F3O2 m/e 232.0711, found
232.0694.
Table 2
The most characteristic ions in the mass spectra of compounds 2A and B
Compound Ion; m/z (relative intensity)
M+
(M–HF)+ (R–Ph–CHF–CHF)+ (R–Ph–CHF)+
2Aa
2Ab
2Ad
2Ae
214 (5)
194 (23) 141 (10)
109 (100)
123 (100)
127 (100)
177 (100)
Ethyl
2,3-difluoro-3-[4-tri-fluoromethylpheny]propio-
228 (10) 208 (25) 155 (9)
232 (4) 212 (22) 159 (10)
282 (10) 262 (20) 209 (14)
nate (2Ae) was purified by flash chromatography on silica
gel, eluting with 5:1 mixture of hexane and ethyl acetate to
give a colorless oil.
threo: 1H NMR: 1.30 (t, J = 7 Hz, 3H); 4.29 (q, J = 7 Hz,
2H); 5.06 (ddd, J = 46.8 Hz, J = 26.8 Hz, J = 2.7 Hz, 1H);
5.83 (ddd, J = 44.4 Hz, J = 23.6 Hz, J = 2.7 Hz, 1H); 7.1–
Compound
M+
(M–HF)+
(Ph–CHF)+
109 (100)
2Ba
167 (28)
147 (17)
Compound 2Ac could not be isolated and it was not further investigated.

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V. Dinoiu et al. / Journal of Fluorine Chemistry 126 (2005) 753–758
7.4 (m, 4H). 19F NMR: ꢁ98.6 (s, 3F); ꢁ131.3 (m, 1F);
ꢁ142.9 (m, 1F). IR (neat, cmꢁ1) 1767 (nC O). HRMS:
calcd. for C12H11F5O2 m/e 282.0679, found 282.0693.
erythro: 1H NMR: 1.26 (t, J = 7 Hz, 3H); 4.30 (q,
J = 7 Hz, 2H); 5.33 (ddd, J = 49.0 Hz, J = 13.4 Hz,
J = 3.2 Hz, 1H); 5.94 (ddd, J = 44.2 Hz, J = 21.2 Hz,
J = 3.2 Hz, 1H); 7.1–7.4 (m, 4H). 19F NMR: ꢁ98.6 (s,
3F); ꢁ125.7 (m, 1F); ꢁ139.7 (m, 1F). IR (neat, cmꢁ1) 1767
(nC O). HRMS: calcd. for C12H11F5O2 m/e 282.0679, found
282.0693.
(m, 1F); ꢁ196.9 (m, 1F). IR (neat, cmꢁ1) 1698 (nC O). MS
m/z 244 (M+), 105 (Ph–CO)+, 77 (Ph). HRMS: calcd. for
C15H10F2O m/e 244.0700, found 244.0692.
4-(2-Fluoro-3-oxo-3-phenylpropylidene)-2,6-di-t-butyl-
cyclohexa-2,5-dien-1-one (5) was purified by flash chro-
matography on silica gel, eluting with 20:1 mixture of
hexane and ethyl acetate to give a yellowish-brown oil that
crystallizes as yellowish-brown crystals (EtOH), mp 145 8C.
1H NMR (400 MHz, CDCl3): 1.24 (s, 9H); 6.33 (t,
J = 15 Hz, 1H); 6.79 (s, 1H); 7.37 (dd, J = 15 Hz, 1H); 7.50
2,3-Difluoro-3-phenylpropionitril (2Ba) was purified by
flash chromatography on silica gel, eluting with 10:1
mixture of hexane and ethyl acetate to give a colorless oil.
threo: 1H NMR: 1.22 (t, J = 7 Hz, 3H); 4.26 (q, J = 7 Hz,
2H); 5.22 (ddd, J = 46.1 Hz, J = 17.8 Hz, J = 3.4 Hz, 1H);
5.82 (ddd, J = 45.6 Hz, J = 17.1 Hz, J = 3.4 Hz, 1H); 7.1–
7.4 (m, 4H). 19F NMR: ꢁ27.9 (m, 1F); ꢁ30.4 (m, 1F). IR
(neat, cmꢁ1) 1767 (nC O). HRMS: calcd. for C9H7F2N m/e
167.0546, found 167.0561.
(t, J = 8Hz); 7.66 (t, J = 8Hz, 1H); 8.02 (d, J = 8Hz, 1H). 19
F
NMR (400 MHz, CDCl3): 71.6 (s, 1F). IR (neat, cmꢁ1) 1630
(nC O). HRMS: calcd. for C23H27FO2 m/e 354.1995, found
354.1972.
4-Fluoro-2,6-di-t-butyl-4-[(1E)-3-oxo-3-phenylprop-1-
enyl]cyclohexa-2,5-dien-1-one (6) was purified by flash
chromatography on silica gel, eluting with 20:1 mixture of
hexane and ethyl acetate to give a yellowish oil that
1
crystallizes as yellow crystals (EtOH), mp 137–139 8C. H
erythro: 1H NMR: 1.26 (t, J = 7 Hz, 3H); 4.23 (q,
J = 7 Hz, 2H); 5.34 (ddd, J = 46.8 Hz, J = 12.2 Hz,
J = 5.7 Hz, 1H); 5.70 (ddd, J = 46.9 Hz, J = 12.2 Hz,
J = 5.7 Hz, 1H); 7.1–7.4 (m, 4H). 19F NMR: ꢁ23.7 (m,
1F); ꢁ31.94 (m, 1F). IR (neat, cmꢁ1) 1767 (nC O). HRMS:
calcd. for C9H7F2N m/e 167.0546, found 167.0561.
t-Butyl, 1,2-difluoro-2-phenyl-ethyl ketone (2Ca) was
purified by flash chromatography on silica gel, eluting with
20:1 mixture of hexane and ethyl acetate to give a colorless
oil.
NMR: 1.25 (s, 9H); 6.48 (s, 1H); 6.63 (dd, J = 15.2 Hz,
J = 19 Hz, 1H); 7.31 (d, J = 15.2 Hz, 1H); 7.49 (t, J = 8 Hz,
1H); 7.58 (t, J = 8 Hz); 7.66 (t, J = 8 Hz, 1H); 7.96 (d,
J = 8 Hz, 1H). 19F NMR: 9.2 (s, 1F). IR (neat, cmꢁ1) 1640
(nC O). HRMS: calcd. for C23H27FO2 m/e 354.1995, found
354.1962.
Acknowledgment
1
threo: H NMR: 1.48 (s, 9H); 5.14 (ddd, J = 47.3 Hz,
J = 27.1 Hz, J = 2.9 Hz, 1H); 5.96 (ddd, J = 44.6 Hz,
J = 23.9 Hz, J = 2.9 Hz, 1H); 7.30–7.90 (m, 5H). 19F
One of the authors, V. Dinoiu, is deeply indebted to the
Japan Society for the Promotion of Science (JSPS) for
granting him a research fellowship.
NMR: ꢁ194.0 (m, 1F); ꢁ200.4 (m, 1F). IR (neat, cmꢁ1
)
1698 (nC O). MS m/z 226 (M+), 141 (Ph–CHF–CHF)+, 109
(Ph–CHF)+, 77 (Ph)+. HRMS: calcd. for C13H16F2O m/e
226.1169, found 226.1167.
References
1
erythro: H NMR: 1.49 (s, 9H); 5.37 (ddd, J = 49.2 Hz,
J = 10.7 Hz, J = 4.1 Hz, 1H); 5.83 (ddd, J = 43.6 Hz,
J = 20.9 Hz, J = 4.1 Hz, 1H); 7.30–7.90 (m, 5H). 19F
[1] R. Filler, Y. Kobayashi, Biomedical Aspects of Fluorine Chemistry,
Kodansha Ltd., Tokyo, 1982;
J.T. Welch, S. Eswarkrishnan, Fluorine in Bioorganic Chemistry, J.
Wiley, New York, 1990.
NMR: ꢁ187.9 (m, 1F); ꢁ198.4 (m, 1F). IR (neat, cmꢁ1
)
1698 (nC O). MS m/z 226 (M+), 141 (Ph–CHF–CHF)+, 109
(Ph–CHF)+, 77 (Ph)+; HRMS: calcd. for C13H16F2O m/e
226.1169, found 226.1167.
[2] B.E. Smart, J. Fluorine Chem. 109 (2001) 3–11.
[3] E. Laurent, B. Marquet, R. Tardivel, Tetrahedron 45 (1989) 4431–
4444.
[4] N. Yoneda, Tetrahedron 47 (1991) 5329–5365.
[5] (a) T. Fuchigami, M. Shimojo, A. Konno, J. Org. Chem. 60 (1995)
7654–7659;
Phenyl, 1,2-difluoro-2-phenyl-ethyl ketone (2Da) was
purified by flash chromatography on silica gel, eluting with
20:1 mixture of hexane and ethyl acetate to give a colorless
oil.
(b) T. Fuchigami, A. Konno, K. Nakagawa, M. Shimojo, J. Org.
Chem. 59 (1994) 5937–5941.
threo: 1H NMR: 5.57 (ddd, J = 47.6 Hz, J = 25.4 Hz,
J = 3.2 Hz, 1H); 6.02 (ddd, J = 44.9 Hz, J = 23.0 Hz,
J = 3.2 Hz, 1H); 7.36–7.90 (m, 10H). 19F NMR: ꢁ192.5
(m, 1F); ꢁ199.3 (m, 1F). IR (neat, cmꢁ1) 1698 (nC O). MS
m/z 244 (M+), 105 (Ph–CO)+, 77 (Ph). HRMS: calcd. for
C15H10F2O m/e 244.0700, found 244.0692.
[6] S.Q. Chen, T. Fukuhara, S. Hara, N. Yoneda, Electrochem. Acta 42
(1997) 1951–1960.
[7] V. Dinoiu, T. Fukuhara, S. Hara, N. Yoneda, J. Fluorine Chem. 103
(2000) 75–80.
[8] V. Dinoiu, T. Fukuhara, K. Miura, N. Yoneda, J. Fluorine Chem. 121
(2003) 227–231.
[9] W. Dmowski, T. Kozlowski, Electrochim. Acta 42 (1997) 513–523.
[10] E. Laurent, B. Marquet, R. Tardivel, H. Thiebault, Bull. Soc. Chim. Fr.
(1986) 955–964.
1
erythro: H NMR: 5.84 (ddd, J = 42.0 Hz, J = 6.3 Hz,
J = 2.2 Hz, 1H); 5.98 (ddd, J = 44.2 Hz, J = 18.8 Hz,
J = 2.2 Hz, 1H); 7.36–7.90 (m, 10H). 19F NMR: ꢁ186.5
[11] J. Herdan, V. Dinoiu, A. Meghea, A. Schiketanz, M. Gheorghiu, A.T.
Balaban, Rev. Roum. Chim. 35 (1990) 1017–1024.