The first preparation of the α-iodo-β,β-difluorovinylzinc reagent (CF2=CIZnCl) and a high-yield one-pot synthesis of α-iodo-β,β-difluorostyrenes

Article abstract of DOI:10.1016/j.jfluchem.2004.10.006

The α-iodo-β,β-difluorovinylzinc reagent (CF ₂=CIZnCl) was synthesized in >87% yield via room-temperature metallation of the commercially available CF₃CH₂I with LDA in the presence of ZnCl₂. This novel zinc reag

Full text of DOI:10.1016/j.jfluchem.2004.10.006

Journal of Fluorine Chemistry 126 (2005) 457–463
www.elsevier.com/locate/fluor
The first preparation of the a-iodo-b,b-difluorovinylzinc
reagent (CF =CIZnCl) and a high-yield one-pot
synthesis of a-iodo-b,b-difluorostyrenes
2
*
R. Anilkumar, Donald J. Burton
Department of Chemistry, The University of Iowa, Iowa City, IA 52242, USA
Received 14 September 2004; received in revised form 11 October 2004; accepted 18 October 2004
Available online 26 November 2004
Dedicated to Professor Richard D. Chambers on the occasion of his 70th birthday.
Abstract
The a-iodo-b,b-difluorovinylzinc reagent (CF =CIZnCl) was synthesized in >87% yield via room-temperature metallation of the
2
commercially available CF
aryl iodides produced a-iodo-b,b-trifluorostyrenes (ArCI=CF
2004 Elsevier B.V. All rights reserved.
3
CH
2
I with LDA in the presence of ZnCl
2
. This novel zinc reagent upon palladium-catalyzed cross-coupling with
2
) in 62–80% isolated yield.
#
Keywords: 2-Iodo-1,1,1-trifluoroethane; Iododifluorovinylzinc; Pd(0) coupling; Trifluorovinyllithium; Iododifluorovinyllithium; a-Iodo-b,b-difluorostyrene
1
. Introduction
approach is not adaptable to the synthesis of RCX=CF2
X = Cl, Br or I), due to acylation of the Wittig reagent.
(
Fluoroolefins containing the terminal difluoromethylene
R C=CF ) group are useful building blocks due to their
2 2
Organometallic routes for the 1,1-difluoroolefin involves
incorporation of a two carbon difluoroolefinic unit
(–CX=CF ) into a precursor either by addition of stabilized
(
unique reactivities in ionic as well as radical reactions [1–5]
and their ability to form monovinylfluorides upon reduction
2
difluorovinyl anions to suitable electrophiles [16–21] or by
metal-catalyzed cross-coupling of difluorovinyl synthons
with aryl or alkenyl iodides [22–26].
[
6,7]. They have also been shown to exhibit unique
biological properties especially for certain mechanism-
based enzyme inhibitors [8–12]. 1,1-Difluoroolefins, bear-
ing a halogen (chlorine, bromine or iodine) at the a-position,
are interesting compounds as they have significant synthetic
potential due to the possible functionalization both at the
terminal olefinic site as well as at the halogen site. Various
methods have been developed for the preparation of 1,1-
difluoroolefins and most of these methods utilize introduc-
tion of either a =CF or a –CX=CF group into the organic
Traditionally a-halo-b,b-difluorostyrenes were prepared
by a two-step process: addition of halogen to RCH=CF2
[27,28] followed by dehydrohalogenation [29]. Though this
method is not general, use of a more selective base like
t
Li CO or KO Bu improved the yield of the a-halo-b,b-
2
3
difluorostyrene significantly (Scheme 1).
A more general route for fluorinated styrenes employs
Pd(0)-catalyzed coupling of fluorovinyl synthons with aryl
iodides under mild reaction conditions [22–26,30–34]. This
approach was initially utilized in this laboratory for the
synthesis of a,b,b-trifluorostyrenes, where Pd(0)-catalyzed
coupling reaction of trifluorovinyl zinc or tin reagents with
aryl iodides produced the corresponding styrenes [30–33].
By a similar approach, various a-bromo-b,b-difluoro-
styrenes were also synthesized in excellent isolated yields
2
2
molecule, though there are exceptions. The most versatile
method to introduce a =CF group is via Wittig olefination
2
chemistry, where olefins of the type R C=CF , where
2
2
R = alkyl, aryl, perfluoroalkyl or hydrogen, have been
synthesized in moderate to good yields [13–15]. But this
*
Corresponding author. Tel.: +1 319 335 1368; fax: +1 319 335 1270.
E-mail address: donald-burton@uiowa.edu (D.J. Burton).
by the Pd(0)-catalyzed coupling reaction of CF =CBrZnX
2
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.10.006

458
R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 126 (2005) 457–463
Scheme 1. Preparation of a-halo-b,b-difluorostyrenes by dehydrohalogenation.
Scheme 2. Preparation of a-bromo-b,b-difluorostyrenes by zinc insertion followed by Pd(0)-catalyzed coupling.
of a-chloro-b,b-difluorovinyllithium at low temperature
36–38].
[
Utilizing the synthetic potential of these environmentally
friendly halocarbons, we have recently developed an
excellent synthetic route for a,b,b-trifluorostyrenes and
a-chloro-b,b-difluorostyrenes [39–41]. Here, the trifluoro-
vinylzinc reagent (CF =CFZnCl) and the a-chloro-b,b-
2
difluorovinyl zinc reagent (CF =CXZnCl, X = Cl, Br) were
2
generated by LDA metallation of a THF solution of ZnCl2
and HFC-134a or HCFC-133a at room temperature. The
vinyl zinc reagents thus generated were coupled with aryl
iodides to produce a,b,b-trifluorostyrenes and a-chloro-
b,b-difluorostyrenes in excellent isolated yields (Scheme 4).
An extension of this methodology was later applied for the
synthesis of a-bromo-b,b-difluorostyrenes [42]. Here the
Scheme 3. Generation of trifluorovinyllithium from HFC-134a and its
reaction with various electrophiles.
(generated by the zinc insertion into CF =CBr ) with aryl
2 2
iodides (Scheme 2) [34].
Recent work of Coe and co-workers demonstrated the
halocarbon HFC-134a as an excellent synthetic precursor for
the preparation of trifluorovinyllithium at low temperature
a-bromo-b,b-difluorovinylzinc reagent (CF =CBrZnCl),
2
generated by metallation of CF CH Br or CF =CHBr,
2
3
2
was coupled with aryl iodides to produce a-bromo-b,b-
difluorostyrenes (Scheme 5).
(Scheme 3) [35–38]. The trifluorovinyllithium thus pro-
duced reacted with various electrophiles to produce the
corresponding substituted products (Scheme 3). They have
also identified HCFC-133a as a precursor for the generation
Herein, we report a further extension of this methodology
for the synthesis of a-iodo-b,b-difluorostyrenes via the
a-iodo-b,b-difluorovinylzinc reagent.
Scheme 4. Preparation of a,b,b-trifluorostyrenes, a-chloro-b,b-difluorostyrenes via the corresponding fluorovinylzinc reagents generated from HFC-134a or
HCFC-133a.
2
Scheme 5. Preparation of a-bromo-b,b-difluorostyrenes via CF =CBrZnCl.

R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 126 (2005) 457–463
459
2
. Results and discussion
After the successful synthesis of a-bromo-b,b-difluor-
ostyrenes by our metallation-coupling methodology, we
investigated whether a-iodo-b,b-difluorostyrenes could be
prepared by this route, as they would potentially be useful
for further functionalization at the iodine site. Also the a-
iodo-b,b-difluorovinylzinc reagent and the a-iodo-b,b-
difluorostyrenes were hitherto unknown in the literature,
and the method could essentially yield a useful route for
the synthesis of these compounds. Commercially available
Scheme 6. Preparation of a-iodo-b,b-difluorovinylzinc reagents.
preferential complexation of the zinc reagents to TMEDA,
which makes the mono and bis zinc reagents clearly
1
9
distinguishable. The F NMR spectra of the zinc reagent
showed peaks at ꢀ58.0 (d, J = 53 Hz, 1F), ꢀ71.8 (d,
J = 53 Hz, 1F) corresponding to the mono zinc reagent and
peaks at ꢀ57.0 (d, J = 56 Hz, 2F), ꢀ73.2 (d, J = 56 Hz, 2F)
corresponding to the bis zinc reagent (mono/bis: 85:15).
Hydrolysis of the zinc reagent with glacial acetic acid
1
-iodo-2,2,2-trifluoroethane (CF CH I) was chosen as a
3 2
precursor for the a-iodo-b,b-difluorovinylzinc reagent. It
was of interest to examine whether there are competing
reactions resulting in two different zinc reagents during
the metallation of CF CH I. Metallation at the hydrogen
produced CF =CHI quantitatively (ꢀ73.2, d, J = 31 Hz, 1F;
2
ꢀ77.6, dd, J = 31, 25 Hz, 1F) and thus confirmed the
formation of CF =CIZnCl.
2
3
2
site was expected to produce the iodozinc reagent
CF =CIZnCl), whereas metallation at the iodine site would
result in the hydrozinc reagent (CF =CHZnCl) [43]. Though
The zinc reagent was then reacted with iodobenzene and
catalytic Pd(0) at r.t. for 24 h to produce a-iodo-b,b-
difluorostyrene in 79% isolated yield (Table 1, entry 1). It
was noticed that the coupling reaction of the iodobenzene
(
2
2
metallation at the halogen sites was not observed in the LDA
metallation of CF CH Cl and CF CH Br [41,42], metalla-
tion of the iodine site might be expected for CF CH I due to
with CF =CIZnCl at r.t. was not as facile as that of other
2
3
2
3
2
halozinc reagents. The difference in reactivity could be
explained by a closer examination at the transmetallation
process in the palladium cycle. A few literature reports,
available on the mechanistic studies on the transmetallation
step of palladium cycle, enlighten the major role played
by the steric effects during the transmetallation process
[44–47]. Though iodine at the a-carbon is expected to
increase the reactivity of the zinc reagent electronically
towards the transmetallation process, its bulkiness could
create considerable steric crowding in the transition state
resulting in a slower transmetallation process and thus a less
facile coupling process. In order to facilitate faster reaction,
the coupling reaction of the iododifluorovinylzinc reagent
and 1-fluoro-4-iodobenzene was attempted under heating
conditions (60 8C, 12 h) and resulted in a mixture of products
with partial decomposition of the iododifluorovinylzinc
3
2
the more labile C–I bond. Thus, via the conditions
standardized for the metallation of HFC-134a, a THF
solution of CF CH I and anhydrous zinc chloride was
3
2
treated with 2.0 equiv. of LDA at 15–20 8C (Scheme 6). The
yellow-colored reaction mixture was subjected to F NMR
1
9
analysis using PhCF as the internal standard and showed the
3
exclusive formation of the a-iodo-b,b-difluorovinylzinc
reagent in 87% yield. No product resulting from the
metallation at the iodine site (CF =CHZnCl) was detected
2
1
by F NMR [43].
9
1
The F NMR spectrum also revealed the presence of
9
both mono (CF =CIZnCl) and bis zinc reagents
2
[
Addition of a stoichiometric amount of TMEDA to the
(CF =CI) Zn] complexed to diisopropylamine and THF.
2 2
1
reaction medium simplified the F NMR spectrum with
9
Table 1
b
Entry
1
Iodide (Arl)
Temp/time
a-Iodo-b,b-difluorostyrenes
a
NMR yield
Yield (%)
C
6
H
5
I
r.t., 12 h then 60 8C, 2 h
r.t., 12 h then 65 8C, 2 h
r.t., 18 h then 60 8C, 2 h
r.t., 14 h then 65 8C, 3 h
r.t., 18 h then 60 8C, 5 h
r.t., 15 h then 65 8C, 4 h
r.t., 5 h then 65 8C, 2 h
r.t., 24 h then 60 8C, 1 h
65 8C, 48 h
C
6
H
5
CI=CF
CI=CF
CI=CF
CI=CF
2
2
92
92
88
89
85
86
90
85
48
–
79
71
73
78
72
78
80
67
–
c
2
p-FC
m-FC
p-ClC
o-MeC
m-NO
m-MeOC
m-F CC
o-F CC
p-IC
6
H
4
I
p-FC
6
H
4
2
3
6
H
4
I
m-FC
p-ClC
6
H
4
2
d
4
6
H
4
I
6
H
4
5
6
7
8
6
H
4
I
o-MeC
m-O NC
m-MeOC
m-F CC
CC
6
H
4
CI=CF
2
2
C
6
H
4
I
2
6
H
4
CI=CF
CI=CF
CI=CF
CI=CF
=CIC CI=CF
2
6
H
4
I
6
H
4
2
3
6
H
4
I
3
6
H
4
2
9
3
6
H
4
I
o-F
3
6
H
4
2
e
10
6
H
4
I
r.t., 24 h then 65 8C, 4 h
p-CF
2
6
H
4
2
62
LDA; ZnCl2
Arl; PdðPPh3Þ4
ꢁ
r:t: to65 C
CF3CH2Iꢀ!1
5ꢀ20 ꢁ
½CF2¼ClZnClŠꢀ!
ArCl¼CF2.
C=THF
a
1
All the styrenes gave satisfactory H, C, F NMR, HRMS data.
13
19
b
c
d
e
Isolated yield.
Product styrene contaminated with 4% iodide.
Product styrene contaminated with 2% iodide.
Reaction was sluggish product styrene contaminated with traces of monostyrene and 1,4-diiodobenzene.

460
R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 126 (2005) 457–463
1
reagent. F NMR analysis of this reaction mixture showed a
9
shifts have been reported in ppm relative to an internal
reference (CDCl , CFCl or TMS). Unless noted otherwise,
CDCl was used as the NMR lock solvent. Low-resolution
considerable amount of reduced product (CF =CHI) along
2
3
3
with coupled product and unreacted 1-fluoro-4-iodobenzene.
In order to check the thermal stability of the iododifluor-
ovinylzinc reagent under Pd(0) catalysis, a blank coupling
reaction experiment with no aromatic iodide was performed.
Thus, a THF solution of the iododifluorovinylzinc reagent,
heated at 60 8C with a catalytic amount of Pd(0) for 12 h,
3
mass spectra were obtained using a Voyeger GC–MS
instrument operated at 70 eV in the electron impact mode,
using a 15 m CB-5 column. The reported fragment peaks
correspond to the most abundant ions, in addition to the
parent ion(s). High-resolution mass spectra (HRMS) were
obtained by the University of Iowa high-resolution mass
spectrometry facility. Column chromatography was carried
out using silica gel purchased from Em Science (Silica Gel
60, particle size 63–200 mm). Tetrahydrofuran (THF) was
dried by distillation from sodium benzophenone/ketyl at
atmospheric pressure immediately prior to use. Pd(PPh3)4
produced 40% of the reduced product (CF =CHI) and no
2
unreacted zinc reagent was detected. Thus, heating of the
reaction mixture for long time to facilitate faster reaction
destroyed the zinc reagent to a great extent. So a balance was
struck, where slightly fewer equivalents of iodide
(
presence of Pd(0) catalyst, and the reaction was monitored
0.7 equiv.) and the zinc reagent were stirred at r.t. in the
was prepared by Coulson’s procedure [48]. N was used
2
1
9
via F NMR. After significant amount of conversion
without further purification. All other reagents and
chemicals were obtained from commercial sources and
used directly. All boiling points were measured during
distillation and are uncorrected.
(
ꢂ80%) of the zinc reagent to styrene, the mixture was
heated at 60 8C for a shorter period to effect complete
conversion.
After the successful coupling reaction of the iododi-
fluorovinylzinc reagent with iodobenzene and 1-fluoro-4-
iodobenzene under these modified conditions (Table 1,
entries 1 and 2), the same sequence was performed with
other aromatic iodides to test the generality of this method.
Reactions were successful with both electron-donating and
electron-withdrawing aromatic iodides to produce the
corresponding substituted a-iodo-b,b-difluorostyrenes in
excellent isolated yields (Table 1, entries 2–10).
3.1. General procedure for the synthesis of a-iodo-b,b-
difluorovinylzinc reagent (CF =CIZnCl)
2
A 100 mL 2-necked RB flask fitted with a nitrogen tee
and a septum was charged with diisopropylamine (7.0 mL,
50.0 mmol) and THF (20.0 mL). This solution was cooled to
0 8C and 2.5 M n-BuLi (25.0 mL, 50.0 mmol) was added
slowly over 20 min. The resulting solution was allowed to
stir for an additional 10 min.
For some aromatic iodides, the coupling reaction was
very sluggish especially with o-iodobenzotrifluoride, where
no coupled product was detected when the reaction mixture
was stirred at r.t. for 5 h. However, heating the reaction
A 250 mL three-necked RB flask fitted with a condenser,
septum and a low-temperature thermometer was assembled
while hot and flushed with nitrogen. The flask was charged
1
9
mixture at 65 8C for 2 days produced 48% (by F NMR) of
with ZnCl (3.4 g, 25.0 mmol) and THF (15.0 mL). The
2
1
9
the coupled product (entry 9). F NMR analysis of this
reaction mixture also showed a large amount of unreacted
iodide along with a significant amount of reduced product.
Coupling reaction using 1,4-diiodobenzene was also slightly
sluggish at r.t. and produced the corresponding bis styrene in
saturated solution was cooled to 15 8C using a cold-water
bath and CF CH I (2.7 mL, 27.5 mmol) was added via a
3
2
syringe. The pre-generated LDA was then slowly added
(25 min) through a cannula keeping the temperature
between 15 and 20 8C. The reaction mixture was stirred
1
9
6
2% isolated yield (entry 10).
In conclusion, a high-yield room-temperature preparation
for 2 h at 20 8C and then allowed to settle. The F NMR
spectrum of the zinc reagent recorded at this stage showed
the formation of zinc reagents complexed to THF and
diisopropylamine along with traces of unreacted CF CH I.
of the a-iodo-b,b-difluorovinylzinc reagent (CF =CIZnCl)
2
was achieved via reaction of CF CH I with LDA in the
3
2
3
2
presence of ZnCl . The a-iodo-b,b-difluorovinylzinc
2
A small amount of bis zinc reagent was also detected along
1
with the mono zinc reagent (mono/bis: 85:15). The F NMR
9
reagent thus generated was coupled with aryl iodides using
Pd(0) catalysis to produce a-iodo-b,b-trifluorostyrenes in
excellent isolated yields under mild conditions. This method
serves as the first preparation of the a-iodo-b,b-difluoro-
vinylzinc reagent and the first general synthetic route for
a-iodo-b,b-difluorostyrenes. Future reports will describe
the functionalization of these a-iodo-b,b-difluorostyrenes.
yield of the zinc reagent was 87% (versus PhCF as an
3
internal standard).
1
9
F
NMR of (CF =CIZnCl)ꢃTMEDA: ꢀ58.0 (d,
2
1
9
J = 53 Hz, 1F), ꢀ71.8 (d, J = 53 Hz, 1F). F NMR of
(CF =CI) ZnꢃTMEDA: ꢀ57.0 (d, J = 56 Hz, 2F), ꢀ73.2
2
2
(d, J = 56 Hz, 2F).
3.2. General procedure for the coupling reaction of the
a-iodo-b,b-difluorovinylzinc reagent with aromatic iodides
3
. Experimental
1
1
13
19
H, { H} C and F NMR spectra were recorded on a
Brucker AC-300 or a WM 360 Spectrometer. Chemical
To the zinc reagent generated in the previous experiment
(CF =CIZnCl), was added the aromatic iodide (usually
2

R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 126 (2005) 457–463
461
0
.7–0.75 equiv.) and the tetrakistriphenylphosphinepalla-
3.5. Synthesis of p-ClC H CI=CF
6 4 2
dium (usually 2 mol%). The mixture was stirred at r.t.
for a prolonged time (until an ꢂ80% conversion) and
then heated at 60 8C. The reaction progress was monitored
using F NMR by sampling small aliquots of the reaction
mixture. After complete conversion, the reaction mixture
was triturated several times with pentane or hexane
and the combined extracts evaporated on a rotary evaporator.
The crude product was purified by distillation under
reduced pressure or by column chromatography over silica
gel.
Following the general procedure for the coupling
reaction, 1-chloro-4-iodobenzene (4.3 g, 18.0 mmol), zinc
reagent (22.0 mmol) and Pd(PPh ) (0.449 g, 2.0 mol%)
1
9
3
4
were stirred at r.t. for 14 h (>75% conversion) followed by
heating at 65 8C for 3 h to give the corresponding styrene in
1
9
89% yield (by F NMR). The reaction mixture was
triturated several times with hexane. Evaporation of the
solvent followed by distillation under reduced pressure
afforded the p-ClC H CI=CF as a clear liquid in 78%
6
4
2
(
4.23 g, 14.1 mmol) yield.
1
9
3
.3. Synthesis of C H CI=CF
6
b.p.: 96–98 8C at 11 mmHg. F NMR (CDCl ): d ꢀ70.2
5
2
3
1
(
d, J = 24 Hz, 1F), ꢀ77.4 (d, J = 24 Hz, 1F); H NMR
1
(CDCl ): d 7.38–7.35 (m, 2H), 7.32–7.28 (m, 2H); C NMR
3
Iodobenzene (3.6, 17.7 mmol) and Pd(PPh ) (0.423 g,
3
4
3
1
.5 mol%) were added to the zinc reagent (22.0 mmol). The
reaction mixture was stirred at r.t. for 12 h (>80%
(CDCl ): d 153.0 (dd, J = 291, 284 Hz), 134.6 (s), 130.1 (t,
3
J = 3 Hz), 128.8 (s), 47.1 (dd, J = 32, 27 Hz); GC–MS: 302
1
9
+
[M + 2] (32), 300 [M ] (46), 173 (96), 138 (BP, 100), 127
+
conversion) followed by heating at 60 8C for 2 h.
NMR analysis of the reaction mixture showed complete
F
3
5
(45), 87 (37), 62 (35); HRMS: Calcd. for C H ClF2I,
8 4
3
299.9014; found 299.9011; Calcd. for C H ClF2I,
7
conversion of the zinc reagent to the corresponding styrene
(
8
4
19
92% yield based on F NMR) along with a trace amount of
301.8989; found 301.8987.
reduced product. The mixture was then triturated with
hexane (6 ꢄ 20 mL). The combined hexane extracts were
subjected to rotary evaporation under vacuum. The crude
mixture was then carefully distilled under reduced pressure
to obtain the pure a-iodo-b,b-difluorostyrene as a clear
liquid in 79% (3.7 g, 13.9 mmol) yield.
3.6. Synthesis of m-O NC H CI=CF
2
2
6
4
Following the general procedure for the coupling
reaction, 1-iodo-3-nitrobenzene (4.1 g, 16.5 mmol), zinc
reagent (22.0 mmol) and Pd(PPh ) (0.410 g, 2.0 mol%)
3
4
1
9
b.p.: 72–75 8C at 12 mmHg. F NMR (CDCl ): d ꢀ71.0
were stirred at r.t. for 15 h (>50% conversion) followed
by heating at 60 8C for 4 h to give the styrene in 86%
yield (by F NMR) along with a trace amount of reduced
3
1
(
d, J = 25 Hz, 1F), ꢀ78.2 (d, J = 26 Hz, 1F); H NMR
1
3
CDCl ): d 7.22–7.43 (m, 5H); C NMR (CDCl ): d
19
(
3
3
1
52.9 (dd, J = 298, 283 Hz), 133.9 (s), 129.7 (s), 128.7
product. The reaction mixture was triturated several times
with hexane. Evaporation of the solvent followed by
distillation under reduced pressure afforded the correspond-
ing styrene as a pale yellow liquid that solidified upon
cooling. Recrystallization from hexane producedm-
O NC H CI=CF as pale yellow needles in 78% (4.0 g,
+
(
s), 128.5 (s), 48.5 (dd, J = 58, 28 Hz); GC–MS: 266 [M ]
14), 139 (42), 127 (BP, 100), 119 (46), 99 (33), 63
33); HRMS: Calcd. for C H F I, 265.9404; found
(
(
8
5 2
2
65.9404.
.4. Synthesis of p-FC H CI=CF
2
2
6
4
2
3
12.9 mmol) yield.
m.p.: 40–42 8C.
6
4
1
9
F NMR (CDCl ): d ꢀ68.3 (d,
3
1
Following the general procedure for the coupling
reaction, 1-fluoro-4-iodobenzene (4.0 g, 18.0 mmol), zinc
J = 20 Hz, 1F), ꢀ75.3 (d, J = 20 Hz, 1F); H NMR (CDCl ):
3
d 8.33 (t, J = 2 Hz, 1H), 8.16 (dm, J = 8 Hz, 1H), 7.78 (dm,
1
3
reagent (22.0 mmol) and Pd(PPh ) (0.358 g, 1.5 mol%)
3
J = 7.6 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H); C NMR (CDCl3):
d 153.7 (dd, J = 300, 285 Hz), 148.2 (s), 135.8 (t, distorted),
136 (t, J = 2 Hz), 128 (s), 124.8 (t, J = 2 Hz), 123.5 (s), 45.7
4
were stirred at r.t. for 12 h (>75% conversion) followed by
heating at 60 8C for 2 h to give the corresponding styrene in
1
9
2% yield (by F NMR) along with a trace amount of
+
9
(dd, J = 31, 26 Hz); GC–MS: 311 [M ] (92), 184 (47), 138
(BP, 100), 126 (24), 88 (30); HRMS: Calcd. for
C H F INO , 310.9255; found 310.9257.
reduced product and unreacted iodide. The reaction mixture
was triturated several times with pentane. Evaporation of the
solvent followed by careful distillation under reduced
pressure afforded the p-FC H CI=CF as a clear liquid in
8
4
2
2
3.7. Synthesis of m-MeOC H CI=CF
2
6
4
2
6
4
7
1% (3.64 g, 12.8 mmol) yield.
1
9
b.p.: 63–65 8C at 11 mmHg. F NMR (CDCl ): d ꢀ71.0
Following the general procedure for the coupling
reaction, 4-iodoanisole (4.0 g, 17.2 mmol), zinc reagent
(23.0 mmol) and Pd(PPh ) (0.429 g, 2.0 mol%) were stirred
3
(
d, J = 25 Hz, 1F), ꢀ78.2 (d, J = 25 Hz, 1F), ꢀ112.5 (m,
1
F); H NMR (CDCl ): d 7.40 (m, 2H), 7.01 (m, 2H);
13
1
NMR (CDCl ): d 162.5 (d, J = 251 Hz), 153 (dd, J = 298,
C
3
3 4
at r.t. for 5 h (>80% conversion) followed by heating at
65 8C for 2 h to give the corresponding styrene in 90% yield
(by F NMR) along with a small amount of reduced
product. The mixture was triturated several times with
3
2
J = 32, 27 Hz); HRMS: Calcd. for C H F I, 283.9310, found
84 Hz), 131.5 (m), 130.0 (s), 115.6 (d, J = 21 Hz), 46.9 (dd,
1
9
8
4 3
2
83.9306.

462
R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 126 (2005) 457–463
hexane. Evaporation of the solvent followed by distillation
under reduced pressure afforded the m-MeOC H CI=CF as
BP, 100], 315 (11), 207 (84), 187 (83), 138 (57), 127 (56);
HRMS: Calcd. for C H F I, 333.9278; found 333.9280.
6
4
2
9 4 5
a clear liquid in 80% (4.10 g, 13.8 mmol) yield.
1
9
b.p.: 133–136 8C at 12 mmHg. F NMR (CDCl ): d
3
3.10. Synthesis of o-MeC H CI=CF
6 4 2
1
ꢀ
70.8 (d, J = 24 Hz, 1F), ꢀ77.4 (d, J = 26 Hz, 1F); H NMR
(
CDCl ): d 7.23 (t, J = 8 Hz, 1H), 7.01 (d, J = 8 Hz, 1H),
3
Following the general procedure for the coupling
reaction, 2-iodotoluene (3.76 g, 17.2 mmol), zinc reagent
(23.0 mmol) and Pd(PPh ) (0.423 g, 1.5 mol%) were stirred
1
3
6
NMR (CDCl ): d 159.5 (s), 153.0 (dd, J = 298, 284 Hz),
.96 (s, 1H), 6.81 (dd, J = 8, 3 Hz, 1H), 3.78 (s, 3H);
C
3
3
4
1
1
35.2 (s), 129.6 (s), 122.0 (t, J = 2 Hz), 115.5 (d, J = 2 Hz),
14.4 (s), 48.2 (dd, J = 31, 26 Hz), 56.4 (s); GC–MS: 296
at r.t. for 18 h (50% conversion) followed by heating t 60 8C
1
9
for 4 h to give the styrene in 85% yield (by F NMR) along
with a trace amount of reduced product. The reaction
mixture was triturated several times with pentane. Evapora-
tion of the solvent followed by careful distillation under
reduced pressure yielded the o-MeC H CI=CF as a clear
+
[
M ] (89), 169 (78), 154 (BP) (100), 138 (27), 126 (83), 107
33), 99 (59), 87 (38), 75 (53); HRMS: Calcd. for C H F IO,
(
9
7 2
2
95.9510; found 295.9517.
6
4
2
3
.8. Synthesis of m-FC H CI=CF
6
4
2
liquid in 72% (3.49 g, 12.5 mmol) yield.
1
9
b.p.: 65–67 8C at 11 mmHg. F NMR (CDCl ): d ꢀ75.4
3
1
Following the general procedure for the coupling
reaction, 1-fluoro-3-iodobenzene (3.7 g, 16.7 mmol), zinc
(
(
d, J = 26 Hz, 1F), ꢀ77.0 (d, J = 25 Hz, 1F); H NMR
13
CDCl ): d 7.13–7.24 (m, 4H), 2.26 (s, 3H); C NMR
3
reagent (22.2 mmol) and Pd(PPh ) (0.443 g, 2.0 mol%)
3
4
(CDCl ): d 152.3 (dd, J = 294, 285 Hz), 137.2 (d, J = 3 Hz),
3
were stirred at r.t. for 18 h followed by 60 8C for 2 h to give
1
4
1
33.2 (s), 130.6 (s), 130.4 (d, J = 2 Hz), 129.5 (s), 126.3 (s),
1
9
+
4.8 (dd, J = 34, 29 Hz), 19.6 (s); GC–MS: 280 [M ] (63),
53 (71), 133 (100, BP), 127 (36), 51 (38); HRMS: Calcd.
the corresponding styrene in 88% yield (by F NMR) along
with a trace amount of reduced product. The reaction
mixture was triturated several times with pentane. Evapora-
tion of the solvent followed by careful distillation under
reduced pressure afforded the m-FC H CI=CF as a clear
for C H F I, 279.9561; found 279.9570.
7 2
9
6
4
2
3.11. Synthesis of p-F C=ICC H CI=CF
2 6 4 2
liquid in 73% (3.45 g, 12.1 mmol) yield.
1
9
b.p.: 64–65 8C at 12 mmHg. F NMR (CDCl ): d ꢀ69.7
3
Following the general procedure for the coupling reaction
,4-diiodobenzene (2.8 g, 8.6 mmol), zinc reagent
23.0 mmol) and Pd(PPh ) (0.457 g, 2.0 mol%) were stirred
(
d, J = 22 Hz, 1F), ꢀ76.6 (d, J = 22 Hz, 1F), ꢀ112.9 (m,
1
1
F); H NMR (CDCl ): d 7.14–7.34 (m, 3H), 6.98 (dt, J = 8,
1
1
1
3
(
1
Hz, 1H); C NMR (CDCl ): d 162.3 (d, J = 247 Hz),
3
3 4
3
at r.t. for 24 h followed by heating at 65 8C for 4 h to give the
corresponding bis styrene along with traces of mono styrene
and reduced product. The reaction mixture was triturated
several times with hexane; evaporation of the solvent
followed by distillation under reduced pressure yielded the
p-F C=ICC H CI=CF as a low melting solid 62% (2.4 g,
53.1 (dd, J = 301, 284 Hz), 135.9 (d, J = 9 Hz), 130.0 (dd,
J = 23, 4 ), 125.4 (q, J = 4 Hz), 116.8 (dt, J = 23, 4 Hz),
15.6 (d, J = 20 Hz), 47.0 (dd, J = 30, 29 Hz); GC–MS: 284
1
+
[
M ] (89), 157 (97), 137 (BP, 100), 127 (71), 107 (76), 87
74), 81 (66), 57 (61); HRMS: Calcd. for C H F I,
(
8
4 3
2
6
4
2
2
83.9310; found 283.9312.
5.3 mmol).
1
9
b.p.: 99–104 8C at 12 mmHg. F NMR (CDCl ): d ꢀ69.6
3
3
.9. Synthesis of m-F CC H CI=CF
2
1
3
6
4
(
(
d, J = 21 Hz, 2F), ꢀ76.9 (d, J = 23 Hz, 2F); H NMR
1
CDCl ): d 7.42 (s, 4H); C NMR (CDCl ): d 153.1 (dd,
3
3
3
Following the general procedure for the coupling
reaction, 3-iodobenzotrifluoride (3.67 g, 13.5 mmol), zinc
J = 299, 285 Hz), 134.1 (bs), 129.7 (dd, J = 3.6, 2.4 Hz),
+
7.6 (dd, J = 31, 27 Hz); GC–MS: 454 [M , 10], 327 (14),
00 (19), 127 (100, BP), 99 (26); HRMS: Calcd. for
4
2
reagent (18.0 mmol) and Pd(PPh ) (0.354 g, 2.0 mol%)
3
4
were stirred at r.t. for 28 h followed by heating at 65 8C for
C H F I , 453.8339; found 453.8344.
10 4 4 2
1
9
1
h to give the corresponding styrene in 85% yield (by
F
NMR) along with a small amount of reduced product. The
reaction mixture was triturated several times with hexane.
Evaporation of the solvent followed by distillation under
reduced pressure afforded the m-F CC H CI=CF as a
Acknowledgements
3
6
4
2
We are grateful to the National Science Foundation for
support of this research work.
colorless liquid in 67% (3.0 g, 9.0 mmol) yield.
1
9
b.p.: 70–71 8C at 12 mmHg. F NMR (CDCl ): d ꢀ63.3
3
(
s, 3F), ꢀ69.4 (d, J = 22 Hz, 1F), ꢀ76.6 (d, J = 21 Hz, 1F);
1
H NMR (CDCl ): d 7.7 (s, 1H), 7.62 (d, J = 8 Hz, 1H), 7.54
3
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31.3 (q, J = 32 Hz), 129.3 (s), 126.7 (m), 125.5 (m), 123.8
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