Synthesis of monofluoroalkenes via Julia-Kocienski reaction

Article abstract of DOI:10.1016/j.jfluchem.2010.06.009

Monofluoromethyl 3,5-bis(trifluoromethyl)phenyl sulfone 1 was synthesized and employed in Julia-Kocienski fluoroolefination reaction with various ketones and aldehydes. Optimal reaction conditions were found to be the treatment of substrates with KOH or C

Full text of DOI:10.1016/j.jfluchem.2010.06.009

Journal of Fluorine Chemistry 131 (2010) 1192–1197
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of monofluoroalkenes via Julia–Kocienski reaction
*
G.K. Surya Prakash , Anton Shakhmin, Mikhail Zibinsky, Istvan Ledneczki, Sujith Chacko, George A. Olah
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, 837 Bloom Walk, Los Angeles, CA 90089-1661, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
Monofluoromethyl 3,5-bis(trifluoromethyl)phenyl sulfone 1 was synthesized and employed in Julia–
Kocienski fluoroolefination reaction with various ketones and aldehydes. Optimal reaction conditions
were found to be the treatment of substrates with KOH or CsF in DMSO at room temperature. Mixtures of
(E) and (Z) isomers of monofluoroalkenes 4 were obtained in moderate to excellent yields.
Received 13 April 2010
Received in revised form 10 June 2010
Accepted 11 June 2010
Available online 18 June 2010
ß 2010 Elsevier B.V. All rights reserved.
Dedicated to Professor Russel P. Hughes
on the occasion of receiving the 2010
American Chemical Society Award for
Creative Work in Fluorine Chemistry.
Keywords:
Monofluoroolefination
Monofluoroalkenes
Monofluoromethyl arylsulfone
Julia–Kocienski reaction
1. Introduction
article covers various aspects of Julia–Kocienski reaction for the
synthesis of fluorooelfins [12].
Only few versatile methods for the preparation of terminal
monofluoroalkenes are known. These methods include Wittig type
fluoroolefination [1], reduction of terminal difluoroalkenes [2],
alkylation/hydroxyalkylation of fluoromethyl sulfones/sulfoxi-
mines/sulfoxides with subsequent elimination of sulfenate/sulfi-
namide/sulfinate moities [3], electrophilic fluorination of olefins
[4] and phosphonate based fluoroolefination [5]. The latter can also
Herein, we report a synthesis of previously unknown mono-
fluoromethyl arylsulfone 1 as a convenient reagent for the direct
monofluoroolefination of carbonyl compounds. Reaction of 1 with
various aldehydes and ketones gave access to a simple and efficient
way for the preparation of monofluoroalkenes in one step [13].
2. Results and discussion
be considered as
a variation of a Wittig type olefination.
Fluoroalkenes are often viewed as biomimetics of a peptide bond
[6] and have recently been extensively studied for this purpose.
Very recently, difluoromethyl-2-pyridyl sulfone was employed as
an efficient reagent for gem-difluoroolefination of carbonyl
compounds [7]. In addition, a general fluoroalkene synthesis
protocol has been reported using fluorinated 1-phenyl-1-H-
tetrazol-5-sulfonyl derivatives [8].
Synthesis of sulfone 1 was performed in 3 steps starting from
3,5-bis(trifluoromethyl)benzenethiol 2 as depicted in Scheme 1.
Oxidation of intermediate monofluoromethyl 3,5-bis(trifluoro-
methyl)phenyl sulfide was carried out in glacial acetic acid with
30% hydrogen peroxide solution at 80 8C. The overall yield of
compound 1 was 61%.
Taking into account the acidity and reactivity of monofluor-
omethyl 3,5-bis(trifluoromethyl)phenyl sulfone 1 compared to the
recently reported analogs [14], we tested several solvents and
bases in order to find appropriate conditions for this particular
reagent system. After brief screening of conditions (Table 1), we
found that DMSO is the most suitable solvent, and KOH or CsF is the
most efficient base for the protocol.
Also, fluoroolefination of nitrones via the reaction with
a-
fluorosulfoximines [9] and synthesis of -fluoro- -unsaturated
a
a,b
esters employing Julia–Kocienski-type reaction [10] have been
disclosed in the recent literature. In addition synthesis of fluoro
enynes can be accomplished by using a novel
a-fluoro-1,3-
benzothiazol-2-yl propargyl sulfone [11]. A recent comprehensive
When KOH/DMSO system is used, the reaction proceeds
smoothly. However, the conditions did not work very well for
aromatic carbonyl compounds with electron-withdrawing sub-
stituents on the aryl ring. On the other hand, CsF reacts
* Corresponding author. Tel.: +1 213 740 5984.
E-mail address: gprakash@usc.edu (G.K. Surya Prakash).
0022-1139/$ – see front matter ß 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2010.06.009

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1192–1197
1193
Table 1
As was recently proposed by Najera and co-workers [14], the
plausible intermediates for similar type of olefination would be
structures A–D (Scheme 2). Due to the small Van-der-Waals radius
of the fluorine atom and no significant energy difference between
Newman projection structures A, B and C, D for R = Ar, a mixture of
E/Z isomers close to 1:1 is anticipated. As mentioned above, this
was experimentally found for all ketones 3k–t.
Screening of solvents and bases and reaction optimizationa.
[TD$INLE]
On the other hand, aldehydes can give different ratios of
isomers, with R = H, intermediates A and C become somewhat
more energetically advantageous. Surprising selectivites towards
(E)-alkenes for entries 4–7 in Table 2 (15:1, 10:1, 6:1, and 3:1,
respectively) could be due to the electronic effect of the fluorine
atom in the transition state. Another explanation for the observed
selectivities could be a change in the mechanism, which would also
explain significantly lower yields (entries 4–6).
.
Entry
Solvent
THF
Base
Yield of 4e (%)
Time
1
2
3
4
5
KOH/n-Bu4N+Br
CsOH/n-Bu4N+Br
30
36
–
12 h
12 h
5 h
LDA
CsF
Py
3
12 h
12 h
–
6
7
DMF
NaH (2 equiv.)
CsF
_
12 h
12 h
Analysis of the 19F NMR spectra of the fluoroalkenes 4 showed
that the fluorine atoms appear as a dd at À115 to À130 ppm with
geminal JHF values from 82 to 86 Hz. Vicinal JHF values for Z isomers
were in the 18–23 Hz range, and vicinal JHF values for E-isomers
–
8
9
DMSO
NaH (2 equiv.)
15
5
12 h
12 h
12 h
2 h
NaH (5 equiv.)
NaOH
KOH
10
11
12
13
14
15
16
17
18
–
were in the 40–48 Hz range. Values of 1JCF were obtained from 13
C
26b
25
–
CsOH
Py
2 h
NMR data and they usually lay in the range of 240–290 Hz, which is
consistent with the literature data [5].
12 h
12 h
72 h
5 min
12 h
48 h
Et3N
–
To confirm the molecular weight of all compounds 4 GC–MS
analysis was performed after all the necessary work up and
purification operations. Unfortunately, due to low stability and
propensity of fluoroalkenes to polymerize [15,16], most of them
(4a–4e, 4h, 4n, 4o, 4q–4t) were not analyzed by HRMS. All
compounds were characterized by 1H, 13C and 19F NMR. For
compounds 4m, 4r–t (Table 2) (E)- and (Z)-isomers were separated
and fully characterized. However, we were unable to distinguish
between two isomers for entry 13 due to the similarity of their
NMR spectra.
DBU
31
–
n-Bu4N+OH’’
KF
–
CsF
95
19
20
21
MeCN
NaH
5
20
2
12 h
12 h
12 h
KOH/n-Bu4N+Br
CsF
a
All reactions were carried out at ambient temperature except entry 3 where the
temperature was gradually raised from À78 8C to ambient within 5 h.
b
These reaction conditions showed much better performance compared to other
base/solvent pairs in reaction with electron-rich carbonyl compounds.
In conclusion, an efficient method of synthesis of terminal
fluoroalkenes was developed. Mixtures of E/Z isomers can be
obtained by this method in good yields. Mild conditions and
reasonable reaction time makes this protocol advantageous
compared to few other known methods of fluoroolefination.
significantly slower but provides products in good to excellent
yields in case of both electron-rich and electron-deficient carbonyl
compounds. Enolizable ketones and aldehydes gave poor yields in
this reaction (5–20%) mainly due to side condensation processes
and also due to their significant volatility.
3. Experimental
A variety of aromatic ketones and aldehydes 3a–t were
explored in the fluoroolefination reaction with 1 (Table 2). Yields
of fluoroolefins 4 were in the range of 8–96%. Most of the alkenes
obtained by this method were a mixture of (E) and (Z) isomers in
various ratios.
Ratios of E/Z isomers were determined by integration of the
appropriate peaks in the 19F and 1H NMR spectra of fluoroolefins.
Majority of the ketones gave close to 1:1 mixture of E/Z isomers,
and for a number of the cases, we were unable to assign NMR peaks
for individual isomers. On the contrary, aldehydes gave a wide
range of E/Z ratios (from 1:1 up to 15:1 for compound 3d) and
assignment of the isomers was carried out based on the NMR data.
3.1. General
Unless otherwise mentioned, all reagents were purchased from
commercial sources. 1H, 13C and 19F NMR spectra were recorded on a
Varian Inova 400 MHz NMR spectrometer. 1H NMR chemical shifts
were determined relative to internal (CH3)4Si (TMS) standard at
0.00 ppm. 13C NMR chemical shifts were determined relative to the
13C signal of the solvent: CDCl3 (77.16 ppm). CFCl3 was used as
internal standard for 19F NMR. High resolution mass spectra were
recordedinEI+orFAB+modeonahighresolutionmassspectrometer
at the Mass Spectrometry facility, University of Arizona.
[(Scheme_1)TD$FIG]
Scheme 1. Synthesis of sulfone 1.

1194
G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1192–1197
Table 2 (Continued )
Table 2
Fluoroolefination of carbonyl compounds with 1.
[TD$INLE]
Entry
Carbonyl compound
Base
CsF
Yield of 4 (%)
52 (4s)
E/Z
19
[
1:1
20
[
CsF
67 (4t)
1:1
.
Entry
1
Carbonyl compound
Base
Yield of 4 (%)
E/Z
[
KOH
CsF
35 (4a)
78 (4a)
1.8:1
1.7:1
3.2. Preparation of 3,5-bis(trifluoromethyl)phenyl
monofluoromethyl sulfone
2
3
L
KOH
CsF
82 (4b)
73 (4b)
2.0:1
1.6:1
1.0 g of sodium metal (43.48 mmol) and 40 mL diethyl ether
were placed in a three-necked flask equipped with a dropping
funnel, reflux condenser, and a stir bar. The solution of 10 g
(40.62 mmol) of 3,5-bis(trifluoromethyl)benzenethiol in 50 mL of
Et2O was added to sodium in Et2O dropwise; the stirred mixture
was heated to reflux and was kept under reflux overnight.
Subsequently, the remaining sodium was filtered off, most of
the Et2O was removed under reduced pressure, and large amount
of hexane (ꢀ100 mL) was added to the remaining concentrated
ethereal solution. Precipitated white solid was filtered off and air
dried. 10.02 g (92%) of sodium salt of 3,5-bis(trifluoromethyl)thio-
phenol was obtained and used for the next step without additional
purification.
N
KOH
KOH
93 (4c)
24 (4d)
1.3:1
4
5
I
15.0:1
CsF
92 (4d)
8 (4e)
1.3:1
L
KOH
10.0:1
CsF
CsF
68 (4e)
25 (4f)
1.5:1
6.0:1
6
7
[TD$INLINE]
Sodium 3,5-bis(trifluoromethyl)thiophenolate (18.65 mmol),
5 g, was placed in a pressure tube, dissolved in 60 mL acetonitrile,
and the solution was rapidly cooled down to À78 8C. 6 mL
(68.94 mmol) of condensed CH2ClF was added to the thiophenolate
solution at À78 8C. The reaction mixture was allowed to warm up
to 40 8C and was stirred overnight. Subsequently, the reaction
mixture was cooled down to room temperature and all the
remaining volatile products were vented. 100 mL water was added
to the residual solution. The mixture was extracted with
chloroform (4 Â 25 mL) and the combined organic phase was
dried over anhydrous magnesium sulfate. Solvents were
evaporated under reduced pressure, the residue (crude 3,5-
bis(trifluoromethyl)phenyl monofluoromethyl sulfide) was dis-
solved in 60 mL glacial acetic acid, and 8.46 g of 30% hydrogen
peroxide was added to the solution. The reaction mixture was
heated to 80 8C and stirred overnight at this temperature. The
resulting solution was poured onto the ice and precipitated
white crystals of 3,5-bis(trifluoromethyl)phenyl monofluoro-
methyl sulfone were collected by suction filtration, washed with
water and air dried. The yield of 3,5-bis(trifluoromethyl)phenyl
monofluoromethyl sulfone was 3.7 g (64%). 1H NMR (400 MHz,
CDCl3): 5.23 (d, JHF = 47 Hz), 8.24 (s), 8.43 (s) ppm. 19F NMR
(376 MHz, CDCl3): À63.4 (s), À210.9 (t, JHF = 47 Hz) ppm. 13C
NMR (100 MHz, CDCl3): 91.8 (d, JCF = 220 Hz), 122.3 (q,
JCF = 272 Hz), 128.7 (t, JCF = 4 Hz), 129.6, 133.7 (q, JCF = 34 Hz),
138.8 ppm.
I
CsF
55 (4g)
3.0:1
8
9
N
KOH
KOH
96 (4h)
75 (4i)
1.3:1
n/a
10
KOH
67 (4j)
1:1
11
12
KOH
KOH
70 (4k)
62 (4l)
1:1
1:1
13
14
15
16
CsF
CsF
CsF
KOH
58 (4m)
62 (4n)
68 (4o)
96 (4p)
1:1
1:1
n/a
n/a
3.3. Typical procedure for the monofluoroolefination of carbonyl
compounds with 3,5-bis(trifluoromethyl)phenyl monofluoromethyl
sulfone in the presence of KOH and TBAF
1.5 mmol of aldehyde or ketone and 1.5 mmol (1 equiv.) of
3,5-bis(trifluoromethyl)phenyl monofluoromethyl sulfone are
placed in a 50 mL round bottom flask and 15 mL of DMSO was
added. A solution of 9 equiv. of KOH in 10 mL DMSO is added
dropwise to the reaction mixture over a period of 2 h. The
reaction mixture was left at room temperature and monitored
by 19F NMR until completion (1–12 h). After completion of the
reaction, the solution is poured into cold saturated solution of
17
18
E
CsF
CsF
17 (4q)
83 (4r)
2.9:1
1.9:1

[
G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1192–1197
1195
Scheme 2. Mechanism of the reaction and plausible reaction intermediates.
ammonium chloride, extracted ethyl acetate (4 Â 25 mL), and
the organic layer dried over anhydrous sodium sulfate. The
solvent was evaporated in a rotavap and the resulting crude
product was purified by column chromatography (EtOAc/
Hex = 1/10). 1 M solution of TBAF in THF can also be used for
this procedure.
1H), 6.64 (dd, JHF = 84 Hz, JHH = 5.2 Hz, 0.8H), 6.88–6.94 (m, 3.6H),
7.15 (dd, JHF = 84 Hz, JHH = 11.2 Hz, 1H), 7.22 (d, JHH = 9.2 Hz, 2H),
7.51 (d, JHH = 8.4 Hz, 1.6H) ppm. 19F NMR (376 MHz, CDCl3)
d
À125.8 (dd, JHF = 84 Hz, JHF = 46 Hz), À133.15 (dd, JHF = 84 Hz,
JHF = 20 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
55.27, 55.31,
110.30, 113.37 (d, JCF = 16 Hz), 113.98, 114.32 125.10 (d,
JCF = 11 Hz), 125.44 (d, JCF = 2 Hz), 127.37 (d, JCF = 3 Hz), 130.22
(d, JCF = 7 Hz), 148.09 (d, JCF = 266 Hz), 149.08 (d, JCF = 256 Hz),
158.94 (d, JCF = 3 Hz), 159.16 (d, JCF = 1 Hz) ppm.
3.4. Typical procedure of monofluoroolefination of carbonyl
compounds with 3,5-bis(trifluoromethyl)phenyl monofluoromethyl
sulfone in the presence of CsF
3.5.3. 4-(2-Fluorovinyl)-N,N-dimethylbenzenamine (4c)
9 equiv. of CsF under inert atmosphere was placed in a 50 mL
round bottom flask and 20 mL of DMSO was introduced.
Subsequently, the mixture of 1.5 mmol of aldehyde or ketone
and 1.5 mmol of 3,5-bis(trifluoromethyl)phenylmonofluoro-
methyl sulfone was dissolved in 10 mL of DMSO, and were added
simultaneously to the solution of CsF. The reaction mixture was
stirred overnight, poured into the cold saturated solution of
ammonium chloride, extracted with ethyl acetate (4 Â 15 mL), and
the organic layer was dried over anhydrous sodium sulfate. The
solvent was evaporated under reduced pressure and the resulting
crude product was purified by column chromatography (EtOAc/
Hex = 1/10).
1H NMR (400 MHz, CDCl3)
d 2.94 (s, 6H), 3.00 (s, 5.4H), 5.54 (dd,
JHF = 46 Hz, JHH = 5.2 Hz, 0.9H), 6.37 (dd, JHF = 20 Hz, JHH = 11.2 Hz,
1H), 6.59 (dd, JHF = 84 Hz, JHH = 5.2 Hz, 0.9H), 6.69–6.74 (m, 3.8H),
7.11 (dd, JHF = 84 Hz, JHH = 11.2 Hz, 1H), 7.17 (d, JHH = 9.8 Hz, 2H),
7.46 (d, JHH = 10 Hz, 1.8H) ppm. 19F NMR (376 MHz, CDCl3)
d
À127.7 (dd, JHF = 84 Hz, JHF = 46 Hz), À135.9 (dd, JHF = 84 Hz,
JHF = 20 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
40.47, 40.57,
110.69, 112.28, 112.74, 113.68 (d, JCF = 16 Hz), 120.59 (d,
JCF = 12 Hz), 121.1, 127.9 (d, JCF = 3 Hz), 129.93 (d, JCF = 7 Hz),
146.15 (d, JCF = 264 Hz), 148.13 (d, JCF = 252 Hz), 149.77 (d,
JCF = 3 Hz), 150.05 (d, JCF = 1 Hz) ppm.
3.5.4. 1-Chloro-4-(2-fluorovinyl)benzene (4d)
3.5. Spectral data of products
1H NMR (400 MHz, CDCl3)
d 5.58 (dd, JHF = 44 Hz, JHH = 5.4 Hz,
1H), 6.36 (dd, JHF = 18.8 Hz, JHH = 11.2 Hz, 1H), 6.66 (dd, JHF = 82 Hz,
JHH = 5.4 Hz, 1H), 7.14 (dd, JHF = 82 Hz, JHH = 11.2 Hz, 1H), 7.17 (d,
JHH = 11.2 Hz, 2H), 7.26–7.33 (m, 4H), 7.44 (d, JHH = 8.4 Hz,
3.5.1. 1-(2-Fluorovinyl)benzene (4a)
1H NMR (400 MHz, CDCl3)
d 5.63(dd, JHF = 45 Hz, JHH = 5.2 Hz,
0.9H), 6.42 (dd, JHF = 19 Hz, JHH = 12 Hz, 1H), 6.67 (dd, JHF = 83 Hz,
JHH = 5.2 Hz, 0.9H), 7,19 (dd, JHF = 83 Hz, JHH = 12 Hz, 1H), 7.25–
7.38 (m, 5.7), 7.17 (d, JHH = 9.8 Hz, 2H), 7.54 (d, JHH = 9.2 Hz,
2H) ppm. 19F NMR (376 MHz, CDCl3)
d
À121.9 (dd, JHF = 82 Hz,
JHF = 44 Hz), À129 (dd, JHF = 82 Hz, JHF = 18.8 Hz) ppm. 13C NMR
(100 MHz, CDCl3)
d 109.90, 113.6 (d, JCF = 17 Hz), 127.45 (d,
1.8H) ppm. 19F NMR (376 MHz, CDCl3)
d
À122.7 (dd, JHF = 83 Hz,
JCF = 3 Hz), 128.77 129.05, 130.16 (d, JCF = 7 Hz), 131.08 (d,
JCF = 13 Hz), 131.24 (d, JCF = 12 Hz), 133.25, 133.27, 148.68 (d,
JCF = 270 Hz), 150.5 (d, JCF = 259 Hz) ppm.
JHF = 45 Hz), À130.5 (dd, JHF = 83 Hz, JHF = 19 Hz) ppm. 13C NMR
(100 MHz, CDCl3) d 40.47, 40.57, 110.69, 112.28, 112.74, 113.68 (d,
JCF = 16 Hz), 120.59 (d, JCF = 12 Hz), 121.1, 127.9 (d, JCF = 3 Hz),
129.93 (d, JCF = 7 Hz), 146.15 (d, JCF = 264 Hz), 148.13 (d,
JCF = 252 Hz), 149.77 (d, JCF = 3 Hz), 150.05 (d, JCF = 1 Hz) ppm.
3.5.5. 1-Fluoro-4-(2-fluorovinyl)benzene (4e)
1H NMR (400 MHz, CDCl3)
d 5.58 (dd, JHF = 44 Hz, JHH = 5.4 Hz,
0.9H), 6.36 (dd, JHF = 19.2 Hz, JHH = 11.6 Hz, 1H), 6.63 (dd,
JHF = 83 Hz, JHH = 5.4 Hz, 0.9H), 6.98–7.05 (m, 4.8H), 7.19–7.26
3.5.2. 1-(2-Fluorovinyl)-4-methoxybenzene (4b)
1H NMR (400 MHz, CDCl3)
d
3.84 (s, 3H), 3.85 (s, 2.5), 5.6 (dd,
(m, 4.8H) ppm. 19F NMR (376 MHz, CDCl3)
d
À114.2 (m), À114.9
JHF = 46 Hz, JHH = 5.2 Hz, 0.8H), 6.4 (dd, JHF = 20 Hz, JHH = 11.2 Hz,
(m), À124 (dd, JHF = 83 Hz, JHF = 44 Hz), À130.6 (dd, JHF = 83 Hz,

1196
G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1192–1197
JHF = 19.2 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
109.88, 113.5
128.67 (d, JCF = 3 Hz), 128.80 (d, JCF = 3 Hz), 129.05, 129.34,
129.76 (d, JCF = 4 Hz), 129.87 (d, JCF = 4 Hz), 134.13, 134.21,
137.25, 137.33, 137.68, 137.73, 145.55 (d, JCF = 266 Hz), 145.66
(d, JCF = 266 Hz) ppm. HRMS: calculated: 196.0888, found:
196.0896.
(d, JCF = 17 Hz), 115.7, 116.0, 127.8 (d, JCF = 3 Hz), 127.9 (d,
JCF = 3 Hz), 130.6 (d, JCF = 7 Hz), 130.7 (d, JCF = 7 Hz), 131.24 (d,
JCF = 12 Hz), 148.0 (d, JCF = 267 Hz), 150.0 (d, JCF = 258 Hz), 161.1,
163.53 ppm.
3.5.6. 4-(2-Fluorovinyl)benzonitrile (4f)
3.5.12. 1-(2-Fluoro-1-phenylvinyl)-4-methoxybenzene (4k)
1H NMR (400 MHz, CDCl3)
d
5.66 (dd, JHF = 43 Hz, JHH = 5.4 Hz,
1H NMR (400 MHz, CDCl3)
d 3.84 (s, 2.7H), 3.85 (s, 3H),
1H), 6.4 (dd, JHF = 18.4 Hz, JHH = 11.2 Hz, 1H), 6.75 (dd, JHF = 82 Hz,
JHH = 5.4 Hz, 1H), 7.25 (dd, JHF = 82 Hz, JHH = 11.2 Hz, 1H), 7.32–
6.9–6.95 (m, 3.8H), 6.94 (d, JHF = 84 Hz, 1H), 6.96 (d, JHF = 84 Hz,
0.9H), 7.19–7.22 (m), 7.26–7.30 (m, 1.8H), 7.33–7.4 (m,
7.35 (m, 2H), 7.57–763 (m, 6H) ppm. 19F NMR (376 MHz, CDCl3)
d
11.5H) ppm. 19F NMR (376 MHz, CDCl3)
d
d
À129.6 (d, JHF = 84 Hz),
À117.2 (dd, JHF = 82 Hz, JHF = 44 Hz), À124.0 (dd, JHF = 82 Hz,
À129.9 (d, JHF = 84 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
JHF = 18.4 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
109.8, 110.9,
55.35, 55.30, 113.71, 114.03, 125.79 (d, JCF = 5 Hz), 125.80 (d,
JCF = 5 Hz), 127.80, 127.85, 128.28, 128.57, 128.86 (d, JCF = 3 Hz),
129.83 (d, JCF = 5 Hz), 129.90 (d, JCF = 3 Hz), 131.58 (d, JCF = 5 Hz),
137.31, 137.39, 145.19 (d, JCF = 266 Hz), 145.33 (d, JCF = 265 Hz),
159.13, 159.48 ppm. HRMS: calculated: 228.0950, found:
228.0953.
111.05, 113.1 (d, JCF = 17 Hz), 118.8, 118.9, 126.7 (d, JCF = 3 Hz),
128.7 (d, JCF = 4 Hz), 132.4, 132.7, 137.2, 137.7 (d, JCF = 13 Hz),
150.5 (d, JCF = 275 Hz), 152.3 (d, JCF = 264 Hz) ppm. HRMS:
calculated: 147.0484, found: 147.0490.
3.5.7. Methyl 4-(2-fluorovinyl)benzoate (4g)
1H NMR (400 MHz, CDCl3)
d
3.87 (s, 3H), 3.88 (s,), 5.64
3.5.13. 4-(2-Fluoro-1-phenylvinyl)-N,N-dimethylbenzenamine (4l)
(dd, JHF = 44 Hz, JHH = 5.4 Hz, 0.8H), 6.38 (dd, JHF = 18.8 Hz,
JHH = 11.2 Hz, 1H), 6.68 (dd, JHF = 82 Hz, JHH = 5.4 Hz, 0.8H),
7.22 (dd, JHF = 82 Hz, JHH = 11.2 Hz, 1H), 7.13–7.28 (d,
JHH = 8.4 Hz, 2H), 7.53 (d, JHH = 8.8 Hz, 1.6H), 7.93–798 (m,
1H NMR (400 MHz, CDCl3)
d
3.01 (s, 4.8H), 3.02 (s, 6H), 6.72–
6.77(m, 3.6H), 6.91 (d, JHF = 84 Hz, 1H), 6.98 (d, JHF = 84 Hz, 0.8H)
7.14–7.18 (m, 1.6H), 7.3–7.35 (m, 4H), 7.36–7.45 (m, 6H) ppm. 19
NMR (376 MHz, CDCl3) À131.9 (d,
À130.8 (d, JHF = 84 Hz),
JHF = 84 Hz) ppm. 13C NMR (100 MHz, CDCl3)
40.46, 40.55,
F
d
d
4H) ppm. 19F NMR (376 MHz, CDCl3)
d
À118.8 (dd, JHF = 82 Hz,
d
JHF = 44 Hz), À126.2 (dd, JHF = 82 Hz, JHF = 18.8 Hz) ppm. 13C NMR
111.91, 112.38, 124.73, 124.80, 126.23 (d, JCF = 5 Hz), 126.08 (d,
JCF = 5 Hz), 127.60, 127.67, 128.19, 128.44, 129.09 (d, JCF = 3 Hz),
129.45 (d, JCF = 3 Hz), 129.92 (d, JCF = 4 Hz), 130.68 (d, JCF = 3 Hz),
137.71, 137.80, 144.60 (d, JCF = 264 Hz), 144.74 (d, JCF = 265 Hz),
149.92, 150.26 ppm. HRMS: calculated: 241.1267, found:
241.1265.
(100 MHz, CDCl3)
d 52.2, 110.3, 113.5 (d, JCF = 16.8 Hz), 126.1 (d,
JCF = 3 Hz), 128.8 (d, JCF = 7 Hz), 129.8, 130.2, 137.2 (d, JCF = 2 Hz),
137.5 (d, JCF = 12 Hz), 149.8 (d, JCF = 273 Hz), 151.6 (d,
JCF = 262 Hz), 166.8, 166.9 ppm. HRMS: calculated: 180.0587,
found: 180.0589.
3.5.8. 1-((E)-2-fluorovinyl)-2,4,5-trimethoxybenzene (4h)
3.5.14. 4-(2-Fluoro-1-phenyl)benzonitrile (4m-a)
1H NMR (400 MHz, CDCl3)
d
3.80 (s, 3H), 3.81 (s, 3H), 3.86 (s,
1H NMR (400 MHz, CDCl3)
d 7.05 (d, JHF = 82 Hz, 1H), 7.35–7.42
3H), 6.4 (dd, JHF = 22 Hz, JHH = 11.2 Hz, 1H), 6.48 (s, 1H), 6.67 (s,
1H), 7.29 (dd, JHF = 86 Hz, JHH = 11.2 Hz, 1H) ppm. 19F NMR
(m, 4H), 7.63–7.65 (m, 5H) ppm. 19F NMR (376 MHz, CDCl3)
d
À127.8 (d, JHF = 82 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d 111.6,
(376 MHz, CDCl3)
d
À128.4 (dd, JHF = 86 Hz, JHF = 22 Hz) ppm.
56.3, 56.5, 56.8, 97.8, 110.2 (d,
118.8, 125.7 (d, JCF = 7.6 Hz), 128.5, 128.6, 129.2 (d, JCF = 3 Hz),
129.8 (d, JCF = 4 Hz), 132.5, 133.9, 142.8 (d, JCF = 8 Hz), 147.1 (d,
JCF = 270 Hz) ppm. HRMS: calculated: 223.0797, found: 223.0789.
13C NMR (100 MHz, CDCl3)
d
JCF = 18 Hz), 112.0, 113.2 (d, JCF = 11 Hz), 143.3, 149.4, 150.4 (d,
JCF = 231 Hz), 151.9.
3.5.15. 4-(2-Fluoro-1-phenyl)benzonitrile (4m–b)
3.5.9. 1-((Z)-2-fluorovinyl)-2,4,5-trimethoxybenzene (4h)
1H NMR (400 MHz, CDCl3)
d
6.975 (d, JHF = 82 Hz, 1H), 7.15–7.18
(m, 2H), 7.33–7.37 (m, 3H), 7.42–7.49 (m, 2H), 7.6–7.64 (m,
2H) ppm. 19F NMR (376 MHz, CDCl3)
À128.1 (d, JHF = 82 Hz) ppm.
13C NMR (100 MHz, CDCl3)
111.5, 118.9, 125.1 (d, JCF = 4 Hz),
1H NMR (400 MHz, CDCl3)
d 3.78 (s, 3H), 3.82 (s, 3H), 3.87 (s,
3H), 5.95 (dd, JHF = 47 Hz, JHH = 5.4 Hz, 1H), 6.58 (dd, JHF = 84 Hz,
JHH = 5.4 Hz, 1H), 7.23 (s, 1H), 7.36 (s, 1H) ppm. 19F NMR (376 MHz,
d
d
CDCl3)
(100 MHz, CDCl3)
d
À126.8 (dd, JHF = 84 Hz, JHF = 47 Hz) ppm. 13C NMR
128.5, 128.9 (d, JCF = 3 Hz), 130.5 (d, JCF = 4 Hz), 120.5, 132.2, 135.7
(d, JCF = 8 Hz), 140.0, 147.2 (d, JCF = 272 Hz) ppm.
d 56.2, 56.6, 56.9, 97.4, 110.1 (d, JCF = 2.3 Hz),
113.6 (d, JCF = 12 Hz), 143.1, 147.2 (d, JCF = 266 Hz), 149.4,
151.1 ppm.
3.5.16. 1-Chloro-4-(2-fluoro-1-phenylvinyl)benzene (4n)
1H NMR (400 MHz, CDCl3)
d
6.96 (d, JHF = 83 Hz, 1H), 6.97
3.5.10. 2-Fluoro-1,1-diphenylethene (4i)
(d, JHF = 83 Hz, 0.8H), 7.17–7.20 (m, 2H), 7.21–7.26 (m, 2H), 7.28–
1H NMR (400 MHz, CDCl3)
d
7.00 (d, JHF = 82.5 Hz, 1H), 7.27–
7.29 (m, 2H), 7.35–7.38 (m, 4H), 7.39–7.41(m, 4H) ppm. 19F NMR
(376 MHz, CDCl3)
–128.5 (d, JHF = 82.5 Hz) ppm. 13C NMR
(100 MHz, CDCl3) 126.35 (d, JCF = 6 Hz), 127.89, 127.92, 128.34,
7.42 (m, 12.2H) ppm. 19F NMR (376 MHz, CDCl3)
d
À127.4 (d,
JHF = 83 Hz),
d
À127.5 (d, JHF = 83 Hz) ppm. 13C NMR (100 MHz,
d
CDCl3) d 125.35 (d, JCF = 5 Hz), 125.50 (d, JCF = 7 Hz), 128.11,
d
128.15, 128.44, 128.56, 128.75, 128.79, 128.85, 129.78
(d, JCF = 4 Hz), 130.03 (t, JCF = 3 Hz), 131.16, 131.21, 135.57,
135.65, 136.54, 136.62, 145.95 (d, JCF = 268 Hz), 146.16
(d, JCF = 268 Hz) ppm.
128.64, 128.79 (d, JCF = 3 Hz), 129.88 (d, JCF = 5 Hz), 137.08, 137.15,
145.90 (d, JCF = 267 Hz) ppm. HRMS: calculated: 198.0845, found:
198.0852.
3.5.11. 1-(2-Fluoro-1-phenylvinyl)-4-methyl-4-methylbenzene (4j)
3.5.17. 1,1-Bis(4-chlorophenyl)-2-fluoroethene (4o)
1H NMR (400 MHz, CDCl3)
d
2.44 (s, 3H), 2.45 (s, 2.55H), 7.00
1H NMR (400 MHz, CDCl3)
d 6.9 (d, JHF = 83 Hz, 1H), 7.14–7.16
(d, JHF = 84 Hz, 0.85H), 7.02 (d, JHF = 84 Hz, 1H), 7.25–7.27 (m,
3.65H), 7.31–7.36 (m, 4.5H), 7.38–7.42 (m, 4.5H), 743–7.45 (m,
(m, 2H), 7.24–7.27 (m, 2H), 7.31–7.35(m, 4H) ppm. 19F NMR
(376 MHz, CDCl3)
À126.7 (d, JHF = 83 Hz) ppm. 13C NMR
(100 MHz, CDCl3) d 124.56 (d, JCF = 6 Hz), 128.72, 129.018,
d
4H) ppm. 19F NMR (376 MHz, CDCl3)
d
À128.8 (d, JHF = 84 Hz),
d
À129.25 (d, JHF = 84 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
21.25,
130.04 (d, JCF = 3 Hz), 131.12 (d, JCF = 4 Hz), 134.00, 134.22,
135.08, 135.16, 146.25 (d, JCF = 269 Hz) ppm.
21.36, 126.18 (t, JCF = 5 Hz), 127.80, 127.84, 128.28, 128.57,

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1192–1197
1197
3.5.18. 2-Fluoro-1,1-dip-tolylethene (4p)
1H NMR (400 MHz, CDCl3)
2.43 (s, 3H), 2.44 (s, 3H), 6.98
3.5.24. (Z)-4-fluoro-1,1-diphenylbuta-1,3-diene (4t)
1H NMR (400 MHz, CDCl3)
5.51 (ddd, JHF = 41.8 Hz,
d
d
(d, JHF = 84 Hz, 1H), 7.20–7.25 (m, 4H), 7.32–7.34 (m, 4H) ppm. 19
F
JHH = 4.8 Hz, JHH = 11.2 Hz 1H), 6.45 (ddd, JHF = 88 Hz, JHH = 4.8 Hz,
JHH = 1.2 Hz 1H), 6.94 (d, JHH = 11.2 Hz, 1H), 7.19–7.28(m, 7H),
NMR (376 MHz, CDCl3)
(100 MHz, CDCl3)
d
À129.7 (d, JHF = 84 Hz) ppm. 13C NMR
d
21.26, 21.37, 126.02 (d, JCF = 4 Hz), 128.69 (d,
7.32–7.39(m, 3H) ppm. 19F NMR (376 MHz, CDCl3)
d
À125.6 (dd,
JCF = 3 Hz), 129.02, 129.30, 129.75 (d, JCF = 5 Hz), 134.30, 134.38,
137.60, 137.65, 145.33 (d, JCF = 266 Hz) ppm. HRMS: calculated:
226.1158, found: 226.1160.
JHF = 88.6 Hz, JHF = 41.8 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
109.6, 117.5 (d, JCF = 5 Hz), 127.7, 127.8, 128.3, 128.4, 130.4, 139.4,
141.9, 143.2 (d, JCF = 5 Hz), 149.3 (d, JCF = 268 Hz) ppm.
3.5.19. 1-Fluoroundec-1-ene (4q)
3.5.25. (E)-4-fluoro-1,1-diphenylbuta-1,3-diene (4t)
1H NMR (400 MHz, CDCl3)
d
0.88 (t, JHH = 7.2 Hz, 4.35H), 1.26–
1H NMR (400 MHz, CDCl3)
d 6.11 (ddd, JHF = 17.6 Hz,
1.36 (m, 20.3H), 1.86–1.9(m, 2H), 2.07–2.13 (m, 0.9H), 4.64–4.79
(m, 0.45H), 5.28–5.39 (m, 1H), 6.43(ddt, JHF = 88 Hz, JHH = 4 Hz,
JHH = 1.6 Hz 0.45H), 6.48(ddt, JHF = 88 Hz, JHH = 12 Hz, JHH = 1.2 Hz
JHH = 11.6 Hz, JHH = 11.2 Hz 1H), 6.49 (d, JHH = 11.6 Hz, 1H), 6.95
(dd, JHF = 83.6 Hz, JHH = 10.8 Hz, 1H), 7.17–7.28 (m, 7H), 7.32–7.40
(m, 3H) ppm. 19F NMR (376 MHz, CDCl3)
d
À124.51 (dd,
1H) ppm. 19F NMR (376 MHz, CDCl3)
d
À131.64 (dd, JHF = 86.8 Hz,
JHF = 83.6 Hz, JHF = 17.6 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
JHF = 19 Hz), À132.02 (dd, JHF = 86 Hz, JHF = 43 Hz) ppm. 13C NMR
112.7 (d, JCF = 17 Hz), 119.7 (d, JCF = 11 Hz), 127.5, 127.6, 127.7,
128.3, 128.5, 130.32, 139.3, 142.1, 143.2 (d, JCF = 13 Hz), 153.3 (d,
JCF = 262 Hz) ppm.
(100 MHz, CDCl3) d 14.2, 22.7, 22.8, 25.0, 25.1, 25.2, 29.1, 29.2, 29.3,
29.5, 29.6, 29.7, 29.8, 32.0, 11.3 (d, JCF = 5.3 Hz), 111.8 (d,
JCF = 8.4 Hz), 147.6 (d, JCF = 254 Hz), 148.6 (d, JCF = 252 Hz) ppm.
Acknowledgment
3.5.20. 2-((E)-2-fluorovinyl)pyridine (4r)
1H NMR (400 MHz, CDCl3)
d
6.36(dd, JHF = 17.6 Hz,
JHH = 11.2 Hz, 1H), 7.06–7.1 (m, 2H), 7.53–7.58 (m, 1H), 7.58 (dd,
JHF = 83 Hz, JHH = 11.2 Hz, 1H), 8.43–8.45 (m, 1H) ppm. 19F NMR
Financial support by Loker Hydrocarbon Research Institute is
gratefully acknowledged.
(376 MHz, CDCl3)
d
À127.92 (dd, JHF = 83 Hz, JHF = 17.6 Hz) ppm.
113.9 (d, JCF = 16 Hz), 121.8 (d,
13C NMR (100 MHz, CDCl3)
d
References
JCF = 5 Hz), 122.3 (d, JCF = 3 Hz), 136.8, 149.5, 152.7 (d, JCF = 4 Hz),
154.4 (d, JCF = 264 Hz) ppm.
[1] (a) M. Schlosser, M. Zimmermann, Synthesis (1969) 75;
(b) D.G. Cox, N. Gurusamy, D.J. Burton, J. Am. Chem. Soc. 107 (1985) 2811;
(c) K. Kataoka, S. Tsuboi, Synthesis (1999) 452.
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Commun. (1985) 678;
3.5.21. 2-((Z)-2-fluorovinyl)pyridine (4r)
1H NMR (400 MHz, CDCl3)
d 5.86 (dd, JHF = 44 Hz, JHH = 5.4 Hz,
1H), 6.75 (dd, JHF = 82 Hz, JHH = 5.4 Hz, 1H), 7.07–7.1(m, 1H), 7.59–
7.63 (m, 1H), 7.7 (d, JHH = 8 Hz, 1H), 8.49–8.51 (m, 1H) ppm.
19F NMR (376 MHz, CDCl3)
d
À118.31 (dd, JHF = 82 Hz,
JHF = 44 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
112.3 (d, JCF = 2 Hz),
(c) M.L. Boys, E.W. Collington, H. Finch, S. Swanson, J.F. Whitehead, Tetrahedron
Lett. 29 (1988) 3365;
(d) J.R. McCarthy, D.P. Matthews, M.L. Edwards, D.M. Stemerick, E.T. Jarvi,
Tetrahedron Lett. 31 (1990) 5449.
122.1 (d, JCF = 2 Hz), 124.5 (d, JCF = 2 Hz), 136.5, 149.2, 150.6 (d,
JCF = 262 Hz), 152.2 (d, JCF = 2 Hz) ppm.
[4] (a) S.H. Lee, J. Schwartz, J. Am. Chem. Soc. 108 (1986) 2445;
(b) N.A. Petasis, A.K. Yudin, I.A. Zavialov, G.K.S. Prakash, G.A. Olah, SYNLETT
(1997) 606;
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[6] S. Couve-Bonnaire, D. Chachard, X. Pannecoucke, Org. Biomol. Chem. 5 (2007)
1151, and references therein..
3.5.22. 2-Bromo-5-((E)-2-fluorovinyl)thiophene (4s)
1H NMR (400 MHz, CDCl3)
d 6.44 (dd, JHF = 17.2 Hz,
JHH = 11.6 Hz, 1H), 6.79 (dd, JHF = 88 Hz, JHH = 4 Hz, 1H), 6.96 (d,
JHH = 11.4 Hz, 1H), 7.16 (d, JHH = 11.4 Hz, 1H) ppm. 19F NMR
(376 MHz, CDCl3)
d
À128.3 (dd, JHF = 88 Hz, JHF = 17.2 Hz) ppm.
107.84 (d, JCF = 20.6 Hz), 110.5 (d,
[7] Y. Zhao, W. Huang, L. Zhu, J. Hu, Org. Lett. 12 (7) (2010) 1444.
[8] A.K. Ghosh, B. Zajc, J. Org. Chem. 74 (22) (2009) 8531.
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[10] D.A. Alonso, M. Fuensanta, E. Gomez-Bengoa, C. Najera, Adv. Synth. Catal. 350
(2008) 1823.
13C NMR (100 MHz, CDCl3)
d
JCF = 4 Hz), 126.3 (d, JCF = 6 Hz), 130.3, 136.6 (d, JCF = 12.2 Hz), 149.9
(d, JCF = 262 Hz) ppm.
[11] Preliminary accounts of this work R. Kumar, B. Zajc, ORGN-673, 236th ACS
National Meeting, Philadelphia, PA, United States, August 17–21, 2008.
[12] B. Zajc, R. Kumar, Synthesis (2010) 1822.
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Chacko, I. Ledneczki, G.A. Olah, ORGN-549, 237th ACS National Meeting, Salt Lake
City, UT, United States, March 22–26, 2009.
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(24) (1983).
3.5.23. 2-Bromo-5-((Z)-2-fluorovinyl)thiophene (4s)
1H NMR (400 MHz, CDCl3)
d
5.89 (dd, JHF = 44 Hz, JHH = 4.8 Hz,
1H), 6.64 (dd, JHF = 82 Hz, JHH = 5.2 Hz, 1H), 6.8 (d, JHH = 4 Hz, 1H),
7.16 (d, JHH = 6 Hz, 1H) ppm. 19F NMR (376 MHz, CDCl3)
À120.4
(dd, JHF = 82 Hz, JHF = 44 Hz) ppm. 13C NMR (100 MHz, CDCl3)
d
d
105.2 (d, JCF = 3 Hz), 113.4 (d, JCF = 10 Hz), 127.1 (d, JCF = 3 Hz),
129.5, 136.2 (d, JCF = 2 Hz), 147.2 (d, JCF = 268 Hz) ppm.
[16] F. Bergmann, A. Kalmus, E. Breuer, J. Am. Chem. Soc. 80 (1958) 4540.