Electrochemical iodofluorination of electron-deficient olefins

Article abstract of DOI:10.1016/j.tet.2009.11.005

Electron-deficient olefins like α,β-unsaturated ester, amide, and phosphonate reacted with iodonium cation species generated by the anodic oxidation of iodide anion in Et₃N-5HF/CH₃NO₂ to form corresponding iodofluorinated

Full text of DOI:10.1016/j.tet.2009.11.005

Tetrahedron 66 (2010) 183–186
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Electrochemical iodofluorination of electron-deficient olefins
*
Hirokatsu Nagura, Shunsuke Kuribayashi, Yutaka Ishiguro, Shinsuke Inagi, Toshio Fuchigami
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 July 2009
Received in revised form 2 November 2009
Accepted 2 November 2009
Available online 6 November 2009
Electron-deficient olefins like
a
,
b
-unsaturated ester, amide, and phosphonate reacted with iodonium
cation species generated by the anodic oxidation of iodide anion in Et3N-5HF/CH3NO2 to form corre-
sponding iodofluorinated compounds in good to moderate yields. The reaction proceeds at room tem-
perature under air atmosphere and constant current conditions. The iodofluorinated products were
shown to be useful fluorine-containing building blocks.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Iodofluorination
Electroorganic chemistry
Electron-deficient olefin
1. Introduction
In this work, we have achieved efficient electrochemical iodo-
fluorination of electron-deficient olefins using Iꢀ/Et3N-5HF/CH3NO2
Organofluorine compounds are a subject of current interest.1 The
addition of cation species and fluoride to olefin is one of the efficient
methods for the preparation of monofluorinated compounds.2
Iodofluorination is particularly attractive since the iodofluorinated
products could be expected to be the versatile fluorine-containing
building blocks. Iodofluorination systems such as I2/F2/CFCl3/
CH2Cl2,3 I2/Et3N-nHF/IF5/CH2Cl2,4 NIS/TBAF/KHF2/HFaq./CH2Cl2,5
IPy2BF4/2HBF4/CH2Cl2,6 have been already demonstrated. However,
these iodonium cation sources and fluoride sources are inaccessible
or not easy to handle. On the other hand, electrochemical iodo-
fluorination using Iꢀ/Et3N-5HF/CH2Cl2/anodic oxidation has also
been reported.7 In this system, reactive intermediate is generated by
anodic oxidation of iodide anion in the presence of fluoride ion.
Therefore, iodide anion sources and HF-amine salt, which are rela-
tively accessible and easy to handle, can be used. However, to our
knowledge, applications of iodofluorination to electron-deficient
olefins are limited,4,6 and no example with electron-deficient olefins
using the electrochemical method have been reported to date.7
Accordingly, development of widely applicable iodofluorination of
system.
2. Results and discussion
Electrochemical iodofluorination of ethyl crotonate (1a) was
carried out using tetrabutylammonium iodide as an iodide anion
source and Et3N-5HF as a fluorine source at room temperature in
a divided cell equipped with Nafion membrane, and other condi-
tions are shown in Table 1. Since 1a is an electron-deficient olefin,
three equivalents of 1a to n-Bu4NI was used. In Entry 1, the reaction
using CH2Cl2 as a solvent was not efficient, and the desired product
2a was formed in 16% yield as a single diastereomer, which is pre-
dicted to be anti-adduct from previous studies on iodo-
fluorination.6,7 On the contrary, the reaction gave 2a in 75% yield by
using CH3NO2 (Entry 2). We assume that CH3NO2 suppresses the
reaction of iodonium cation with water, which interfering with the
iodofluorination. Evenwhen the equimolar amount of n-Bu4NI to 1a
was used, the moderate yield (58%) was obtained (Entry 3). When
the reactionwas conducted in an undivided cell, 2awas notobtained
at all (Entry 4). This suggests that anodically generated iodonium
cation species could be easily reduced at the cathode. In Entry 5, 1a
was added to the anodic solution after the electrolysis of iodide
anion. However, 2a was not formed efficiently in this procedure. It is
known that IF has a tendency to disproportionate to form hyper-
valent iodine species such as IF3 and IF5.9 Therefore, it seems that the
concentration of iodonium cation affects on the state of in-
termediate and varies the reactivity. The reaction using an NIS/Et3N-
5HF/CH3NO2 system was also conducted, and 2a was obtained in
54% yield. However, the reaction was needed to carry out at low
electron-deficient olefins such as a,b-unsaturated esters is of much
importance. Previously, we reported that the electrochemical
fluoro-selenenylation of electron-deficient olefins proceeded
smoothly in (PhSe)2/Et3N-5HF/CH3NO2.8 It was clarified that the
electrochemically generated [PhSeF] equivalent was so stable in
Et3N-5HF/CH3NO2 solution that the reaction becomes very efficient.
* Corresponding author. Tel./fax: þ81 45 924 5406.
E-mail address: fuchi@echem.titech.ac.jp (T. Fuchigami).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.005

184
H. Nagura et al. / Tetrahedron 66 (2010) 183–186
temperature (0 ꢁC) for 12 h, and costly NIS was required. Therefore,
this method does not seem to be suitable for a large scale synthesis.
yields, respectively. Regioselectivity of the reaction was dependent
on the substituent of -unsaturated esters. In the case of 1b, an
iodonium cation was mainly introduced into the -position of the
ester group since -iodination generates less stable cationic in-
termediate due to the electron-withdrawing effect of the ester
group. Substitution of a methyl group at the -position like 1a
should stabilize the cationic intermediate generated by -iodin-
ation, which resulted in exclusive -iodination. On the other hand,
it is reasonable that the substitution of a methyl group at the
-position like 1d enhanced -iodination due to its electron-
a,b
a
Table 1
b
Electrochemical Iodofluorination of Ethyl Crotonate (1a) under Various Conditions
b
a
a
a
b
donating and steric effects. The reaction with p-methoxybenzyl
crotonate (1e), which is easily oxidized (Eopx¼ca. 1.4 V vs Fc/Fcþ),10
did not provide the desired iodofluorinated products (2e). On the
contrary, the reaction with p-trifluoromethylbenzyl crotonate (1f),
which is hardly oxidized (Eopx¼>2.0 V vs Fc/Fcþ),10 gave 2f in 80%
yield. These facts suggest that oxidation of the aromatic moiety of
the ester group of 1e may take place to interfere with the iodo-
fluorination of the olefin moiethy.11 In all cases, the reaction gave
the single diastereomer in a manner similar to 2a. Isolated yields
decreased considerably in all cases because of the instability of the
products during the separation with a silica gel column chroma-
tography, and the corresponding alcohols were detected by GC–MS.
Next, this anodic iodofluorination was extended to other elec-
Entry
Cella
Solvent
Yield of 2ab (%)
1
D
D
D
UD
D
CH2Cl2
16
75(44)
58
2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
3c
4
0
5
7d
a
D: Divided cell equipped with a Nafion membrane. UD: undivided cell.
Determined by 19F NMR. Isolated yield is shown in parentheses.
1.1 equiv. of n-Bu4NI to 1a was used and 2.4 F/mol of electricity was passed.
Ethyl crotonate was added after the electrolysis of n-Bu4NI.
b
c
d
Electrochemical iodofluorination of various
a,b-unsaturated
esters was carried out in the Iꢀ/Et3N-5HF/CH3NO2/anodic oxidation
system, and the results are summarized in Table 2. When ethyl
acrylate (1b) and cyclohexyl acrylate (1c) were employed, regioi-
someric iodofluorinated products were formed in moderate total
yields. The reaction of ethyl methacrylate (1d) also provided
regioisomeric iodofluorinated products 2d and 3d in 20% and 66%
tron-deficient olefins.
a,b-Unsaturated amides and phosphonate
were subjected to the iodofluorination in the Iꢀ/Et3N-5HF/CH3NO2/
anodic oxidation system (Scheme 1). The expected products 5 and 6
were obtained in good to reasonable yields.
b-Substituted acryl-
amide like crotonamide 4c gave 5c exclusively in a similar manner
Table 2
Electrochemical Iodofluorination of various a,b-Unsaturated Esters in I-/Et3N-5HF/CH3NO2/anodic oxidation system
Entry
Olefin
R1
R2
R3
Yielda (%)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
Me
H
H
H
Me
Me
H
H
H
Me
H
Et
Et
2a 75(44)
2b 39(28)
2c 43(21)
2d 20(13)
2e 0
3a 0
3b 9(4)
3c 10(6)
3d 66(40)
3e 0
cyclo-Hex
Et
p-MeOC6H4CH2
p-CF3C6H4CH2
H
2f 80(44)
3f 0
a
Determined by 19F NMR. Isolated yields are shown in parentheses.
Scheme 1.

H. Nagura et al. / Tetrahedron 66 (2010) 183–186
185
to the case of 1a. In these cases, the single diastereomeric iodo-
4.2. General procedure for electrochemical iodofluorination
fluorinated products were also obtained.
In order to demonstrate the synthetic utility of the electro-
chemically prepared iodofluorinated products, we carried out their
molecular conversion as follows. First, we conducted radical initiated
deiodination followed by allylation of 2b. This reaction proceeded
smoothly and desired product 7 was formed in good yield (73%) as
shown in Scheme 2. The reaction of 2c with sodium azide provided
the corresponding azido derivative 8, which is expected to be a pre-
A solution of n-Bu4NI (1 mmol) and olefins (3 mmol) in Et3N-
5HF/CH3NO2 (2 ml/8 ml) was introduced into a divided cell equip-
ped with a Nafion membrane. Constant current (40 mA) electrolysis
of the solution was carried out with two Pt electrodes (2ꢂ2 cm2)
under an air atmosphere at room temperature. Other conditions are
shown in Tables. After 2 F/mol of electricity was charged, the
electrolysis solution was passed through a short column of silica gel
(CHCl3). The solvent was then removed by evaporation and the
residue was purified by column chromatography on silica gel
(hexane/ethyl acetate¼20/1–5/1), PTLC (hexane/ethyl acetate¼20/
1–5/1), or HPLC (Develosil ODS-5, MeCN as eluent) to provide the
desired fluorinated products. The known product 2b was identified
by comparison to the spectral data of authentic sample.6
cursor to an a
-fluoro aminoacid derivative, in 69%yield (Scheme 3).12
The treatment of 3c with a base like triethylamine provided the de-
sired fluoroalkene 9 in good yield (83%) as shown in Scheme 4.
4.2.1. Ethyl 3-fluoro-2-iodobutanoate (2a). 1H NMR (270 MHz,
CDCl3):
d
¼5.09–4.12 (m, 1H), 4.35 (dd, J¼8.9, 7.4 Hz, 1H), 4.24 (q,
J¼7.1 Hz, 2H), 1.64 (dd, J¼23.9, 6.1 Hz, 3H), 1.30 (t, J¼7.1 Hz, 3H). 13C
NMR (68 MHz, CDCl3):
d¼168.95 (d, J¼5.6 Hz), 89.98 (d,
J¼172.7 Hz), 62.12, 22.94 (d, J¼25.7 Hz), 19.65 (d, J¼22.4 Hz), 13.80.
19F NMR (254 MHz, CDCl3):
d
¼ꢀ84.65–85.14 (m). HRMS(EI): m/z
Scheme 2.
[Mþ] calcd for C6H10FO2I: 259.9710; Found: 259.9711.
4.2.2. Ethyl 2-fluoro-3-iodopropionate (3b). 1H NMR (270 MHz,
CDCl3):
d
¼5.00 (dt, J¼47.5, 4.8 Hz, 1H), 4.31 (q, J¼7.3 Hz, 2H), 3.53 (dd,
J¼23.9, 4.8 Hz, 2H), 1.34 (t, J¼7.3 Hz, 3H). 13C NMR (68 MHz, CDCl3):
d
¼166.86 (d J¼23.5 Hz), 87.21 (d, J¼189.5 Hz), 62.36, 14.25, 1.17 (d,
J¼4.5 Hz).19F NMR (254 MHz, CDCl3):
¼ꢀ106.21 (dt, J¼47.5, 23.9 Hz).
d
HRMS(EI): m/z [Mþ] calcd for C5H8FO2I: 245.9553; Found: 245.9552.
4.2.3. Cyclohexyl 3-fluoro-2-iodopropionate (2c). 1H NMR (270 MHz,
Scheme 3.
CDCl3):
d
¼4.92–4.44 (m, 4H), 1.82–1.74 (m, 4H), 1.52–1.34 (m, 6H).
13C NMR (68 MHz, CDCl3):
d
¼168.25 (d, J¼3.4 Hz), 83.22 (d,
J¼177.7 Hz), 74.55, 31.11, 25.31, 23.38, 15.89 (d, J¼23.5 Hz). 19F NMR
(254 MHz, CDCl3):
d¼ꢀ118.34 (td, J¼46.2, 9.2 Hz). HRMS(EI): m/z
[Mþ] calcd for C9H14FO2I: 300.0023; Found: 300.0026.
4.2.4. Cyclohexyl 2-fluoro-3-iodopropionate (3c). 1H NMR (270 MHz,
CDCl3):
d
¼5.08–4.87 (m, 2H), 3.59–3.57 (m, 1H), 3.51–3.48 (m, 1H),
1.87–1.73 (m, 4H), 1.56–1.26 (m, 6H). 13C NMR (68 MHz, CDCl3):
d
¼166.25 (d, J¼23.4 Hz), 87.02 (d, J¼189.5 Hz), 74.98, 31.40, 25.19,
23.58, 1.39 (d, J¼23.5 Hz). 19F NMR (254 MHz, CDCl3):
¼ꢀ106.31
d
(dt, J¼48.1, 24.0 Hz). HRMS(EI): m/z [Mþ] calcd for C9H14FO2I:
Scheme 4.
300.0023; Found: 300.0026.
3. Conclusions
4.2.5. Ethyl 3-fluoro-2-iodo-2-methylpropionate (2d). 1H NMR (270
We successfullycarried out iodofluorination of electron-deficient
olefins like a,b-unsaturated esters, amides, and phosponate by using
MHz, CDCl3):
9.1 Hz, 1H), 4.26 (q, J¼7.1 Hz, 2H), 2.14 (s, 3H), 1.31 (t, J¼7.1 Hz, 3H).
13C NMR (68 MHz, CDCl3):
¼170.55 (d, J¼2.8 Hz), 88.02 (d,
J¼181.7 Hz), 62.33, 34.32 (d, J¼20.7 Hz), 26.63 (d, J¼2.8 Hz), 13.71.
d
¼4.92 (dd, J¼46.8, 9.1 Hz, 1H), 4.51 (dd, J¼46.8,
electrochemical oxidation of iodide anion in a Et3N-5HF/CH3NO2
solution. This electrochemical method can be readily conducted
under an air atmosphere at room temperature without any haz-
ardous reagents. In addition, we illustrated that the iodofluorinated
products were useful fluorine-containing building blocks.
d
19F NMR (254 MHz, CDCl3):
d
¼ꢀ120.06 (t, J¼46.8 Hz). HRMS(EI):
m/z [Mþ] calcd for C6H10FO2I: 259.9710; Found: 259.9712.
4.2.6. Ethyl 2-fluoro-3-iodo-2-methylpropionate (3d). 1H NMR (270
4. Experimental
MHz, CDCl3):
d
¼4.30 (q, J¼7.1 Hz, 2H), 3.61 (dd, J¼24.2, 13.2 Hz, 1H),
3.45 (dd, J¼15.2, 11.0 Hz, 1H), 1.71 (d, J¼20.61 Hz, 3H), 1.34 (t,
4.1. General procedure
J¼7.1 Hz, 3H). 13C NMR (68 MHz, CDCl3):
¼168.93 (d, J¼25.2 Hz),
d
92.52 (d, J¼189.5 Hz), 62.36, 23.71 (d, J¼24.0 Hz), 14.26, 8.24
1H, 13C, and 19F NMR spectra were recorded at 270, 68, and
254 MHz, respectively, on a JEOL-NM-EX 270 with tetramethylsi-
lane (0.00 ppm) as an internal standard. The chemical shifts for 19F
(d, J¼25.7 Hz). 19F NMR (254 MHz, CDCl3):
¼ꢀ72.18–72.58 (m).
d
HRMS(EI): m/z [Mþ] calcd for C6H10FO2I: 259.9710; Found: 259.9706.
are given in d ppm downfield from internal trifluoroacetic acid. The
4.2.7. p-Trifluoromethylbenzyl 3-fluoro-2-iodobutanoate (2f). 1H NMR
following abbreviations are used: s, singlet; d, doublet; t, triplet; q,
quartet and m, multiplet. High-resolution mass spectra (HRMS)
were taken on a JEOL MStation JMS-700 mass spectrometer.
(270 MHz, CDCl3):
d
¼7.63 (d, J¼8.1 Hz, 2H), 7.49 (d, J¼8.1 Hz, 2H),
5.27 (s, 2H), 5.15–4.87 (m, 1H), 4.41 (dd, J¼9.2, 7.1 Hz, 1H), 1.65 (dd,
J¼24.1, 6.3 Hz, 3H). 13C NMR (68 MHz, CDCl3):
¼168.72 (d, J¼4.5 Hz),
d

186
H. Nagura et al. / Tetrahedron 66 (2010) 183–186
138.83, 130.27 (q, J¼33.0 Hz), 127.94, 125.48 (q, J¼3.4 Hz), 123.84 (q,
J¼271.6 Hz), 90.12 (d, J¼173.3 Hz), 66.60, 22.03 (d, J¼25.7 Hz), 19.56
reaction mixture was stirred for 1 h. Then water (10 ml) was added
to the mixture and the organic phase was extracted with EtOAc. The
organic phase was dried over Na2SO4 and the solvent was removed
in the reduced pressure. The crude product was purified by a thin-
layered chromatography (Hexane/EtOAc¼9/1) to give 8 (11 mg, 60%
yield).
(d, J¼21.8 Hz). 19F NMR (254 MHz, CDCl3):
¼14.11 (s, 3F), ꢀ84.32
d
(dqd, J¼46.0, 24.1, 7.1 Hz, 1F). HRMS(FAB): m/z [MþNaþ] calcd for
C12H11F4O2NaI: 412.9638; Found: 412.9632.
4.2.8. Diethyl 2-fluoro-1-iodoethyl-1-phosphonate (5a). 1H NMR
1H NMR (270 MHz, CDCl3):
J¼46.5, 3.8 Hz, 2H), 4.05 (dt, J¼25.6, 3.8 Hz, 1H), 1.91–1.72 (m, 4H),
1.58–1.25 (m, 6H). 13C NMR (68 MHz, CDCl3):
¼166.36 (d,
J¼7.3 Hz), 82.98 (d, J¼175.5 Hz), 75.37, 61.70 (d, J¼20.1 Hz), 31.36,
d¼4.98–4.89 (m, 1H), 4.75 (dd,
(270 MHz, CDCl3):
d
¼4.90–4.55 (m, 2H), 4.29–4.18 (m, 4H), 4.17–
3.98 (m, 1H), 1.40–1.33 (m, 6H). 13C NMR (68 MHz, CDCl3):
d¼83.00
d
(d, J¼179.4 Hz), 63.92 (dd, J¼6.7, 2.2 Hz), 16.36 (dd, J¼6.1, 1.1 Hz),
12.62 (dd, J¼150.4, 20.1 Hz). 19F NMR (254 MHz, CDCl3):
25.23, 23.50. 19F NMR (254 MHz, CDCl3):
d
¼ꢀ150.88 (td, J¼46.5,
d
¼ꢀ126.83–127.36 (m). HRMS(FAB): m/z [MþHþ] calcd for
25.6 Hz). HRMS(EI): m/z [Mþ] calcd for C9H14FN3O2: 215.1070;
C6H14FO3IP: 310.9709; Found: 310.9713.
Found: 215.1068.
4.2.9. 3-Fluoro-2-iodo-2-methylpropionamide (5b). 1H NMR (270
4.5. Synthesis of cyclohexyl 2-fluoro-2-propenate (9)
MHz, CDCl3):
d
¼6.12 (br s,1H), 5.62 (br s,1H), 4.61 (td, J¼46.8, 9.7 Hz,
2H), 2.14 (s, 3H). 13C NMR (68 MHz, CDCl3):
d
¼172.26 (d, J¼1.7 Hz),
To a stirred solution of 3c (28 mg) in CH2Cl2 (3.0 ml) was added
triethylamine (17 mg) at 0 ꢁC under nitrogen atmosphere and the
reaction mixture was stirred for 0.5 h. Then the reaction mixture
was further stirred for 3.5 h at room temperature. The reaction was
quenched by the addition of 1 M HCl (5.0 ml) and the organic phase
was extracted with CH2Cl2. The organic phase was dried over
Na2SO4 and the solvent was removed in the reduced pressure. The
crude product was purified by a thin-layered chromatography
(Hexane/EtOAc¼9/1) to give 9 (12 mg, 74% yield).
88.72 (d, J¼181.1 Hz), 37.66 (d, J¼17.9 Hz), 27.68 (d, J¼3.4 Hz). 19F
NMR (254 MHz, CDCl3):
d¼ꢀ121.73 (t, J¼46.8 Hz). HRMS(EI): m/z
[Mþ] calcd for C4H7FNOI: 230.9556; Found: 230.9554.
4.2.10. 2-Fluoro-3-iodo-2-methylpropionamide (6b). 1H NMR (270
MHz, CDCl3):
d
¼6.36 (br s, 1H), 5.82 (br s, 1H), 3.69 (dd, J¼27.9,
11.2 Hz,1H), 3.44 (dd, J¼15.1,11.2 Hz,1H),1.72 (d, J¼21.4 Hz, 3H). 13C
NMR (68 MHz, CDCl3):
d¼172.4 (d, J¼21.8 Hz), 95.19 (d, J¼191.6 Hz),
23.66 (d, J¼24.0 Hz), 8.48 (d, J¼24.6 Hz). 19F NMR (254 MHz,
1H NMR (270 MHz, CDCl3):
d
¼5.65 (dd, J¼43.5, 3.1 Hz, 1H), 5.30
(dd, J¼13.0, 3.1 Hz, 1H), 4.96–4.86 (m, 1H), 1.94–1.74 (m, 4H), 1.53–
1.26 (m, 6H). 13C NMR (68 MHz, CDCl3):
¼159.72 (d, J¼30.7 Hz),
153.57 (d, J¼261.6 Hz), 102.19 (d, J¼15.7 Hz), 74.57, 31.44, 25.31,
CDCl3):
d
¼ꢀ71.21–71.64 (m). HRMS(FAB): m/z [MþHþ] calcd for
C4H8FNOI: 231.9635; Found: 231.9637.
d
4.2.11. 3-Fluoro-2-iodobutyramide (5c). 1H NMR (270 MHz, CDCl3):
23.66. 19F NMR (254 MHz, CDCl3):
d
¼ꢀ40.10 (dd, J¼43.5, 13.0 Hz).
d
¼5.93 (br s, 1H), 5.76 (br s, 1H), 4.89 (dqd, J¼46.4, 6.2, 5.9 Hz, 1H),
HRMS(EI): m/z [Mþ] calcd for C9H13FO2: 172.0900; Found:
4.39 (dd, J¼16.5, 5.9 Hz, 1H), 1.58 (dd, J¼23.8, 6.2 Hz, 3H). 13C NMR
172.0941.
(68 MHz, CDCl3):
d¼169.55 (d, J¼3.3 Hz), 90.28 (d, J¼174.8 Hz),
26.45 (d, J¼22.4 Hz), 19.51 (d, J¼22.4 Hz). 19F NMR (254 MHz,
CDCl3):
d
¼ꢀ90.24–90.77 (m). HRMS(EI): m/z [Mþ] calcd for
Acknowledgements
C4H7FNOI: 230.9556; Found: 230.9556.
This work was supported by The Society of Iodine Science. The
authors thank Ms. M. Ishikawa of Center for Advanced Materials
Analysis (Suzukakedai), Technical Department, Tokyo Institute of
Technology, for HRMS analysis and Morita Chemical Industries Co.
Ltd. for generous gifts of Et3N-5H.F.
4.2.12. 4-Isopropyl-3-(3-fluoro-2-iodobutanoyl)oxazolidin-2-one
(5d). Diastereomer a (major): 1H NMR (270 MHz, CDCl3):
d¼5.86
(dd, J¼9.4, 7.3 Hz, 1H), 5.35–5.07 (m, 1H), 4.55–4.49 (m, 1H), 4.36–
4.22 (m, 2H), 2.48–2.36 (m, 1H), 1.71 (dd, J¼24.2, 6.3 Hz. 3H), 0.97
(d, J¼6.9 Hz, 3H), 0.95 (d, J¼6.9 Hz, 3H). 13C NMR (68 MHz,
CDCl3):
d
¼168.49 (d, J¼2.8 Hz), 152.86, 89.54 (d, J¼171.6 Hz),
References and notes
63.47, 58.33, 27.89, 21.38 (d, J¼25.2 Hz), 19.64 (d, J¼22.4 Hz),
17.97, 15.06. 19F NMR (254 MHz, CDCl3):
d
¼ꢀ84.13–84.72 (m).
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Rozen, S. J. Org. Chem. 1998, 63, 4632.
3. Rozen, S.; Brand, M. J. Org. Chem. 1986, 51, 222.
4. Yoneda, N. J. Fluorine Chem. 2004, 125, 7.
5. Kuroboshi, M.; Hiyama, T. Bull. Chem. Soc. Jpn. 1995, 68, 1799.
6. Barluenga, J.; Campos, P. J.; Gonzalez, J. M.; Suarez, J. L. J. Org. Chem. 1991, 56,
2234.
HRMS(FAB): m/z [MþHþ] calcd for C10H16FNO3I: 344.0159; Found:
344.0164.
Diastereomer b (miner): 1H NMR (270 MHz, CDCl3):
d¼5.92 (dd,
J¼10.6, 7.6 Hz, 1H), 5.00–4.74 (m, 1H), 4.48–4.23 (m, 3H), 2.43–2.32
(m, 1H), 1.47 (dd, J¼23.2, 6.1 Hz, 3H), 0.94 (d, J¼7.0 Hz, 3H), 0.89 (d,
J¼7.0 Hz, 3H). 13C NMR (68 MHz, CDCl3):
¼168.42 (d, J¼8.9 Hz),
d
153.04, 89.28 (d, J¼174.9 Hz), 63.63, 59.08, 28.70, 24.10 (d,
J¼24.6 Hz), 19.35 (d, J¼22.9 Hz), 17.99, 14.76. 19F NMR (254 MHz,
CDCl3):
d
¼–92.11–93.26 (m). HRMS(FAB): m/z [MþHþ] calcd for
C10H16FNO3I: 344.0159; Found: 344.0158.
4.3. Synthesis of ethyl 2-fluoromethyl-4-pentenoate (7)
7. Kobayashi, S.; Sawaguchi, M.; Ayuba, S.; Fukuhara, T.; Hara, S. Synlett 2001, 1938.
8. Nagura, H.; Inagi, S.; Fuchigami, T. Tetrahedron 2009, 65, 1559.
9. Schmeisser, M.; Sartori, P.; Naumann, D. Chem. Ber. 1970, 103, 880.
10. Cyclic voltammetry measurement was carried out with 5 mM of olefin and
5 mM of ferrocene (Fc) as a reference in Et3N-5HF (2 ml)/CH3NO2 (8 ml) at a Pt
plate electrode (0.5ꢂ0.5 cm2) using a Hokutodenko HA-501 Potentiostat/Gal-
vanostat. Sweep late was 100 mV/s and Ag wire was used as a pseudo-reference
electrode.
The reaction was carried out according to the literature8 using
2b. The products 7 was identified by comparison to the spectral
data of authentic sample.8
4.4. Synthesis of cyclohexyl 2-azido-3-fluoropropionate (8)
11. (a) Miller, L. L.; Kujawa, E. P.; Campbell, C. B. J. Am. Chem. Soc. 1970, 92, 2821;
(b) Kataoka, K.; Hagiwara, Y.; Midorikawa, K.; Suga, S.; Yoshida, J. Org. Process
Res. Dev. 2008, 12, 1130.
To a stirred solution of 2c (26 mg) in DMF (4.0 ml) was added
sodium azide (12 mg) at 0 ꢁC under nitrogen atmosphere and the
12. Sasson, R.; Rozen, S. J. Fluorine Chem. 2006, 127, 962.