An efficient room temperature preparation of bromo difluorovinylzinc reagent (CF2 = CBrZnCl) and a high yield one-pot synthesis of α-bromo-β, β-difluorostyrenes

Article abstract of DOI:10.1016/j.jfluchem.2003.11.029

A high yield room temperature preparation of the1-bromo-2, 2-difluorovinylzinc reagent [CF₂=CBrZnCl] (>89%) was achieved via insitu metallation of CF₃CH₂Br or CF₂=CHBr with LDA in presence of ZnCl₂. P

Full text of DOI:10.1016/j.jfluchem.2003.11.029

Journal of Fluorine Chemistry 125 (2004) 561–566
An efficient room temperature preparation of bromo difluorovinylzinc
reagent (CF2¼CBrZnCl) and a high yield one-pot synthesis
of a-bromo-b,b-difluorostyrenes
R. Anilkumar, Donald J. Burton*
Department of Chemistry, The University of Iowa, Iowa City, IA-52242, USA
Received 15 October 2003; accepted 17 November 2003
Abstract
A high yield room temperature preparation of the1-bromo-2,2-difluorovinylzinc reagent [CF2¼CBrZnCl] (>89%) was achieved via insitu
metallation of CF3CH2Br or CF2¼CHBr with LDA in presence of ZnCl2. Palladium catalyzed cross-coupling of this zinc reagent with aryl
iodides provides a-bromo-b,b-trifluorostyrenes (ArCBr¼CF2) in 64–86% isolated yields, in an essentially ‘one-pot’ procedure.
# 2004 Elsevier B.V. All rights reserved.
Keywords: 2-Bromo-1,1,1-trifluoroethane; 2-Bromo-1,1-difluoroethylene; Bromodifluorovinylzinc; Pd(0) coupling; Bromodifluorovinyllithium; a-Bromo-
b,b-difluorostyrene
1. Introduction
available for the synthesis of a-bromo-b,b-difluorostyrenes
and absolutely nothing for a-iodo-b,b-difluorostyrenes. The
well-known method for a-chloro-b,b-difluorostyrene and a-
bromo-b,b-difluorostyrene is a two-step process—addition
of halogen to RCH¼CF2 [14,15] followed by dehydroha-
logenation [16]. The success of the dehydrohalogenation
process depended on the base employed. A more selective
base like Li2CO3 was used to improve the yield and to avoid
undesired side products (Scheme 1). KOtBu as base pro-
duced a marginal increase in the yield of the styrene.
Recent advancement in the synthesis of a,b,b-trifluoros-
tyrenes via utilization of the trifluorovinylzinc reagent as a
synthon, followed by Pd(0) catalyzed cross coupling with
aryl iodides, included the synthesis a-halo-b,b-difluorostyr-
ene by such strategy [17–20]. One such method was recently
reported from this laboratory for the synthesis of a-bromo-
b,b-difluorostyrenes via the formation of the CF2¼CBrZnX
type zinc reagent followed by subsequent Pd(0) coupling
with aryl iodides (Scheme 2) [21]. Even though it was
possible to obtain a-bromo-b,b-difluorostyrenes in excellent
isolated yield under mild conditions by this method, the
stating materials for this preparation (CF2¼CX2), their cost,
availability and environmentally hazardous nature limited
this procedure.
1,1-Difluoroalkenes (R2C¼CF2) are important fluorine-
containing compounds both from the chemical as well as the
biological point of view. They can be reduced to 1-mono-
fluoroolefins [1,2]; some of them are potential enzyme
inhibitors [3–7] and have exhibited cytotoxic activity
[8,9]. Halogen containing 1,1-difluoroalkenes are useful
building blocks in organofluorine chemistry not only due
to the reactivity of the gem-difluoromethylene unit towards
nucleophilic reagents but also due to the possible functio-
nalization at the halogen (chlorine, bromine, iodine) site.
Generally, olefins of the type R2C¼CF2, where R ¼ alkyl,
aryl, perfluoroalkyl or hydrogen have been synthesized by
Wittig type reactions [10,11], but this approach is not
adaptable to the synthesis of RCX¼CF2, where X ¼ Cl,
Br or I due to the acylation of Wittig reagents. Alternatively,
this type of olefin can be prepared by the reaction of the
Grignard reagent with CF2¼CFX; but such a reaction
provides an undesired isomeric olefin or an exchange reac-
tion occurs to give the trifluorovinyl organometallic com-
pound [12]. In the early 1950s Cohen developed a
preparative method for a-chloro-b,b-difluorostyrene by a
multi step procedure [13]. But there are not many routes
Recently HFC-134a and HCFC-133a have been identified
as excellent synthetic precursors for the generation of tri-
fluorovinyllithium and a-chloro-b,b-difluorovinyllithium
* Corresponding author. Tel.: þ1-319-335-1363; fax: þ1-319-335-1270.
E-mail address: donald-burton@uiowa.edu (D.J. Burton).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2003.11.029

562
R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 125 (2004) 561–566
X2
Li2CO3/DMF
ZnCl2
15-20 oC/THF
i
PhCX=CF2
PhCH=CF2
PhCHX-CF2X
.
2 LDA
[CF2=CBrZnCl]
Pr2NH/THF
+
CF3CH2Br
∆
89%
X = Cl 50%
X = Br 55%
X = Cl 81%
X = Br 91%
Scheme 5. Preparation of a-bromo-b,b-difluorovinylzinc reagent from
CF3CH2Br.
Scheme 1. Preparation of a-halo-b,b-difluorostyrenes by dehydrohalo-
genation.
the selectivity of the metallation under our reaction condi-
tions; where the metallation–transmetallation process was
performed in situ in the presence of zinc chloride using
LDA as a base. Thus, when a THF solution of CF3CH2Br
and anhydrous zinc chloride was treated with two equivalents
of LDA at 15–20 8C, an 89% yield of CF2¼CBrZnCl
(Scheme 5) was formed (as detected by 19F NMR analysis
of the reaction mixture).
I
Br
F
Zn
R
F2C=CBrX
X = Br, I
[CF2=CBrZnX]
F
DMF, rt
Pd(PPh3)4
R
DMF, 60 o
C
77-96%
Scheme 2. Preparation of a-bromo-b,b-difluorostyrenes by zinc insertion
followed by Pd(0) catalyzed coupling.
The 19F NMR spectrum showed both the mono and bis
zinc reagents complexed to diisopropylamine and THF.
Addition of stoichiometric amount of TMEDA to the zinc
reagent medium simplified the NMR spectrum as the zinc
reagent complexes preferentially to TMEDA and thus makes
the mono and bis clearly distinguishable. The 19F NMR
showed chemical shifts at À69.8 (d, J ¼ 54:4 Hz), À83.9 (d,
J ¼ 54:3 Hz) corresponding to the mono zinc reagent and
peaks at À69.3 (d, J ¼ 56:9 Hz), À85.3 (d, J ¼ 57:5 Hz)
corresponding to the bis zinc reagent (mono/bis: 70:30). The
values were also in agreement with the reported values for
the zinc reagent (CF2¼CBrZnBr) generated by zinc inser-
tion to CF2¼CBr2 [21]. The zinc reagent formation was
further confirmed by addition of glacial acetic acid to the
reaction mixture to give CF2¼CHBr (19F NMR: d: À83.9,
dd, J ¼ 37:9, 19.7 Hz, 1F, À84.6, d, J ¼ 37:8 Hz, 1F)
quantitatively.
reagents at low temperature (Scheme 3) [22–24]. Various
groups have demonstrated the synthetic potential of the
trifluorovinyl or chlorodifluorovinyl anions thus generated,
making them excellent alternatives for CF2¼CFX or
CF2¼CX2 [25–28].
2. Results and discussion
We have recently developed an excellent room tempera-
ture preparation of the trifluorovinylzinc reagent from HFC-
134a and the chlorodifluorovinyl zinc reagent from HCFC
133a by using an insitu metallation strategy in the presence
of an amine medium [29,30]. Pd(0) catalyzed coupling of
these zinc reagents with aryl iodides produced a cost-effec-
tive synthetic route for a,b,b-trifluorostyrenes and a-chloro-
b,b-difluorostyrenes (Scheme 4).
Herein, we report an extension of this methodology for the
synthesis of a-bromo-b,b-difluorostyrenes via the a-bromo-
b,b-difluorovinylzinc reagent. The only previous report of
the a-bromo-b,b-difluorovinylzinc reagent was from this
laboratory where the zinc reagent was generated by zinc
insertion reaction into CF2¼CBr2 [21]. The success of
generating the zinc reagent form CF3CH2Br or CF2¼CHBr
depends on the selective metallation at the proton site rather
than metal halogen exchange. It was of interest to determine
The zinc reagent CF2¼CBrZnCl was also generated in
95% yield from CF2¼CHBr by insitu treatment with 1.0 eq
of LDA and zinc chloride at 15 8C (Scheme 6).
The increase in the yield of the bromodifluorovinylzinc
reagent (>89% by the metallation of CF3CH2Br or
CF2¼CHBr) compared to that of trifluorovinylzinc reagent
(73% by the metallation of HFC-134a) under similar reac-
tion conditions is attributed to the increased stability of the
intermediate bromodifluorovinyllithium (CF2¼CBrLi)
compared to trifluorovinyllithium (CF2¼CFLi) [29]. Since
-F-
Base
Base
E+
[CF2=CX]-
[CF3CXH]-
CF3CH2X
[CF2=CXH]
CF2=CXE
-80 oC
X = F, Cl
Scheme 3. Generation of trifluorovinyl and chlorodifluorovinyllithium by metallation of HFC-134a and HCFC-133a.
I
R
CX=CF2
ZnCl2
15-20 oC/THF
2 LDA
[CF2=CXZnCl]
R
+
CF3CH2X
Pd(PPh3)4
X = F, 73%
X = Cl, 91%
X = F, 61-86%
X = Cl, 65-85%
Scheme 4. Preparation of a,b,b-trifluorostyrenes and a-chloro-b,b-difluorostyrenes via trifluorovinyl/chorodifluorovinylzinc reagents.

R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 125 (2004) 561–566
563
corresponding a-bromo-b,b-difluorostyrene in 76% isolated
yield (Scheme 7).
1.0 LDA, ZnCl2
15-20 oC/THF
i
.
CF=CHBr
[CF2=CBrZnCl]
Pr2NH/THF
95%
After the successful synthesis of a-bromo-b,b-difluoros-
tyrene, this methodology was successfully applied for the
synthesis of a variety of substituted a-bromo-b,b-difluor-
ostyrenes. Thus, the zinc reagent was generated from
CF3CH2Br or CF2¼CHBr, and was treated with various
aromatic iodides with electron donating and electron with-
drawing groups in the ring using Pd(0) as catalyst at RT or
heating at 65 8C to produce the styrenes in good isolated
yields (Table 1). Reaction was smooth even with iodides
having a bulky CF3 ortho substituent (entry 7). Reaction
with the heterocyclic iodide 2-iodothiophene was sluggish
producing a mixture of styrene and traces of unreacted
iodide (entry 9).
In conclusion, we have developed a high yield synthesis of
a-bromo-b,b-difluorovinyl zinc reagent starting from the
commercially available halocarbons CF3CH2Br or CF2¼
CHBr by a metallation/insitu transmetallation process using
LDA/ZnCl2. Pd(0) catalyzed coupling reaction of this zinc
reagent with various aryl iodides produced a-bromo-b,b-
difluorostyrenes in excellent isolated yields. The metalla-
tion–coupling process could be performed either ‘one-pot’
or a stock solution of the zinc reagent prepared could be used
for separate coupling reactions. Future reports will detail
functionalization of these styrene derivatives.
Scheme 6. Preparation of a-bromo-b,b-difluorovinylzinc reagent from
CF2¼CHBr.
I
Br
F
Pd(PPh3)4
THF
i
.
[CF2=CBrZnCl]
+
Pr2NH/THF
F
76%
Scheme 7. Pd(0) catalyzed coupling of bromodifluorovinylzinc reagent
with iodobenzene.
little was known about the nature and stability of the
bromodifluorovinyllithium, we have performed a series of
experiments to test its thermal stability. Bromodifluorovi-
nyllithium, [CF2¼CBrLi] was generated from CF2¼CHBr
at À80 8C using LDA in THF medium containing stoichio-
metric amount of TMEDA and the resulting clear solution
was warmed to À10 8C (turned completely dark) and
quenched with zinc chloride. This reaction produced an
81% yield of the zinc reagent. The reaction under similar
conditions without TMEDA produced a 63% yield of the
zinc reagent. These experiments, even though the solution
turned dark during the warming process, demonstrated that
most of the [CF2¼CBrLi] was intact even at À10 8C in both
experiments. Similar experiments with [CF2¼CFLi] pro-
duced only ꢀ5% yield of the zinc reagent. These experi-
ments illustrate the increased stability of [CF2¼CBrLi]
compared to [CF2¼CFLi] at temperatures near to room
temperature. [CF2¼CBrLi] was also generated using n-BuLi
in the absence of an amine in the medium at À80 8C. The
resulting brown solution was warmed and quenched with
ZnCl2 at À10 8C to produce only a 24% yield of the zinc
reagent. This confirms the increased stability of these
fluorinated lithium reagents in an amine medium especially
in the presence of TMEDA.
3. Experimental
1H, {1H}13C and 19F NMR spectra were recorded on a
Brucker AC-300 or a WM 360 Spectrometer. Chemical
shifts have been reported in ppm relative to an internal
reference (CDCl3, CFCl3 or TMS). Unless noted otherwise,
CDCl3 was used as the NMR lock solvent. Low resolution
mass spectra were obtained using a Voyeger GC–MS instru-
ment operated at 70 eV in the electron impact mode, using a
15 m CB-5 column. The reported fragment peaks corre-
spond to the most abundant ions, in addition to the parent
ion(s). High-resolution mass spectra (HRMS) were obtained
The zinc reagent generated by both routes were coupled
with iodobenzene using Pd(PPh3)4 as catalyst to produce
Table 1
Preparation of various a-bromo-b,b-difluorostyrenes
ð1Þ 15À20 ꢁ
C
CF3CH2Br1:1 eq: þ ZnCl21:0 eq: þ LDA2:0 eq:
!
CArCBr¼CF2
ð2Þ Arl; PdðPPh3Þ4; RT; 65 ꢁ
No.
Iodide (ArI)
Temp/time
a-Bromo-b,b-difluorostyrene
19F NMR yield
Yield (%)a
1
2
3
4
5
6
7
8
C6H5I
p-FC6H4I
RT, 12 h then 60 8C, 1 h
RT, 14 h
C6H5CBr¼CF2
96
99
95
99
89
94
96
88
76
75
82
86
75
82
74
69
p-FC6H4CBr¼CF2
p-ClC6H4I
o-MeC6H4I
m-NO2C6H4I
p-MeOC6H4I
o-F3CC6H4I
p-IC6H4I
RT,14 h then 60 8C, 2 h
60 8C, 12 h
RT, 22 h
p-ClC6H4CBr¼CF2
o-MeC6H4Br¼CF2
m-O2NC6H4CBr¼CF2
p-MeOC6H4CBr¼CF2
o-F3CC6H4CBr¼CF2
p-CF2¼CBrC6H4CBr¼CF2
65 8C, 5 h
65 8C, 15 h
65 8C, 5 h
9b
RT, 24 h then 60 8C, 4 h
84
64
a Isolated yield of pure product.
b This reaction was sluggish and the product styrene was contaminated with 4–5% 2-iodothiophene.

564
R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 125 (2004) 561–566
by the University of Iowa High Resolution Mass Spectro-
metry Facility. Column chromatography was carried out
using silica gel purchased from Em Science (Silica Gel
60, particle size 63–200 ms). Tetrahydrofuran (THF) was
dried by distillation from sodium benzophenone/ketyl at
atmospheric pressure immediately prior to use. Pd(PPh3)4
was prepared by Coulson’s procedure (Inorg. Synth. 13
(1972) 121–124). N2 was used without further purification.
All other reagents and chemicals were obtained from com-
mercial sources and used directly. All boiling points were
measured during distillation and are uncorrected.
several times with pentane or hexane and the combined
extracts evaporated on a rotary evaporator. The residual
liquid was distilled under reduced pressure or purified by
column chromatography over silica gel.
3.3. C6H5CBr¼CF2
Iodobenzene (3.6 g, 18.0 mmol) and Pd(PPh3)4 (0.358 g,
1.5 mol%) were added to the zinc reagent (22.5 mmol). The
reaction mixture was stirred at RT for 12 h and then heated at
60 8C for 1 h, the color of the reaction mixture slowly
changed from yellow to brown to black during this period.
19F NMR of the reaction mixture showed complete conver-
sion with a 96% yield of a-bromo-b,b-difluorostyrene. The
mixture was then triturated with pentane (6 ꢂ 25 ml). The
lower black residue separated from the pentane extracts.
The combined pentane extracts were evaporated under
vacuum on rotary evaporator. The crude mixture was then
carefully distilled under reduced pressure to obtain the pure
a-bromo-b,b-difluorostyrene as a clear liquid in 76% (2.99 g,
13.7 mmol) yield. bp, 51–52 8C at 11 mm.
3.1. General procedure for the synthesis of the a-bromo-
b,b-difluorovinylzinc reagent [CF2¼CBrZnCl]
A 100 ml two-necked RB fitted with a nitrogen tee and a
septum was charged with diisopropylamine (70.0 ml,
50.0 mmol) and THF (20.0 ml). The mixture was cooled
to 0 8C and 2.5 M n-BuLi (25.0 ml, 50.0 mmol) was slowly
added over 20 min; the resulting mixture was allowed to stir
for 10 min.
A 250 ml three-necked RB fitted with a condenser, sep-
tum and a low temperature thermometer were assembled
while hot and flushed with nitrogen gas. It was charged with
ZnCl2 (3.4 g, 25.0 mmol) and THF (15.0 ml). The saturated
solution was cooled to 15 8C using a cold-water bath and
CF3CH2Br (2.5 ml, 27.5 mmol) was added via a syringe.
The pre-generated LDA was slowly added (25 min) through
a cannula keeping the temperature between 15 and 20 8C (1.0
equivalent of LDAwas used in the case of CF2¼CHBr; where
CF2¼CHBr was condensed into the reaction mixture using a
dryice/isopropanol condenser). The reaction mixture was
stirred for 2 h at 20 8C and then allowed to settle. The 19F
NMR of the pale yellow reaction mixture recorded at this
stage showed formation of mono and bis zinc reagents
complexed to THF and diisopropylamine along with traces
of unreacted CF3CH2Br. The 19F NMR yield of the zinc
reagent was 89%. TMEDA (0.1 ml) was added to the NMR
tube and the 19F NMR of this solution showed mono and bis
zinc reagents (mono=bis ¼ 70 : 30) complexed only to
TMEDA. 19F NMR of [CF2¼CBrZnCl]. TMEDA: d À69.8
(d, J ¼ 54:4 Hz, 1F), À83.9 (d, J ¼ 54:3 Hz, 1F); 19F NMR
of (CF2¼CBr)2Zn.TMEDA: d À69.3 (d, J ¼ 56:9 Hz, 2F),
À85.3 (d, J ¼ 57:5 Hz, 2F).
19FNMR (CDCl3): d À78.9 (d, J ¼ 31:1 Hz, 1F), À85.1
(d, J ¼ 31:2 Hz, 1F); 1H NMR(CDCl3):d 7.44–7.48(m, 2H),
7.26–7.37 (m, 3H); 13C NMR (CDCl3): d 153.2 (dd,
J ¼ 294:1, 286.5 Hz), 131.6 (d, J ¼ 3:6 Hz), 128.9 (s),
128.8 (s), 128.5 (s), 79. 9 (dd, J þ¼ 30:5, 26.2 Hz); GC–
MS: 220 (Mþ þ 2) (64), 218 (M ) (65), 139 (94), 119
(BP, 100), 99 (69), 87 (41), 63 (64), 62 (53); HRMS: calcd
for C8H5F279Br 217.9543 found 217.9546, calcd for
C8H5F281Br 219.9522 found 219.9520.
3.4. p-FC6H4CBr¼CF2
Following the general procedure for the coupling reac-
tion,1-fluoro-4-iodobenzene (3.89 g, 17.5 mmol), zinc
reagent (21.4 mmol) and Pd(PPh3)4 (0.348 g, 1.5 mol%)
at RT for 14 h followed by work-up and careful distillation
under reduced pressure afforded the p-fluoro-a-bromo-b,b-
difluorostyrene as a clear liquid in 75% (3.1 g, 13.1 mmol)
yield. bp, 45–48 8C at 11 mm.
19F NMR (CDCl3): d À79.0 (d, J ¼ 33:1 Hz, 1F), À85.3
(d, J ¼ 31:0 Hz, 1F), À112.1 (m, 1F); 1H NMR (CDCl3): d
7.45 (m, 2H), 7.05 (m, 2H); 13C NMR (CDCl3): d 162.8
(d, J ¼ 250:2 Hz), 153.3 (dd, J ¼ 293:9, 286.7 Hz), 130.9
(m), 126.8 (s), 115.8 (d, J ¼ 23:2 Hz), 79.0 (dd, J ¼ 34:9,
25.8 Hz); GC–MS: 238 (Mþ2) (53), 236 (Mþ) (55), 157
(BP, 100), 137 (74), 107 (40), 87 (37), 81 (39); HRMS: calcd
for C8H4F379Br 235.9448 found 235.9447, calcd for
C8H4F381Br 237.9428 found 237.9427.
3.2. General procedure for the Pd (0) catalyzed coupling
reaction of the a-bromo-b,b-difluorovinylzinc reagent
with aromatic iodides
To the zinc reagent, generated by the above procedure,
was added the aromatic iodide (usually 0.80 eq) and tetra-
kistriphenylphosphinepalladium (1.5 mol%). The reaction
mixture was either stirred at RT or heated at 60 8C using an
oil bath. The reaction progress was monitored using 19F
NMR by sampling small aliquots of the reaction mixture.
After the reaction was completed, the mixture was triturated
3.5. p-ClC6H4CBr¼CF2
Following the general procedure for the coupling reaction,
1-chloro-4-iodobenzene (4.17 g, 17.5 mmol), zinc reagent
(21.4 mmol) and Pd(PPh3)4 (0.348 g, 1.5 mol%) at RT for
14 h and then at 60 8C for 2 h, followed by work-up and

R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 125 (2004) 561–566
565
distillation under reduced pressure afforded the p-chloro-a-
bromo-b,b-difluorostyrene as a clear liquid in 82% (3.6 g,
14.3 mmol) yield. bp, 75 8C at 11 mm.
and Pd(PPh3)4 (0.334 g, 1.5 mol%) at 65 8C for 5 h, followed
by work-up and distillation under reduced pressure produced
the m-methoxy-a-bromo-b,b-difluorostyrene as a clear liquid
in79% (2.8 g, 13.7 mmol) yield. bp, 93–95 8C at 11 mm.
19FNMR (CDCl3): d À80.4 (d, J ¼ 34:0 Hz, 1F), À86.6
(d, J ¼ 34:6 Hz, 1F); 1H NMR (CDCl3): d 7.40 (dm,
J ¼ 8:9 Hz, 2H), 6.88 (dm, J ¼ 9:0 Hz, 2H), 3.80 (s, 3H);
13C NMR (CDCl3): d 160.0 (s), 153.0 (dd, J ¼ 292:6,
285.6 Hz), 130.3 (t, J ¼ 3:5 Hz), 123.9 (d, J ¼ 4:1 Hz),
114.0 (s), 79.8 (dd, J ¼ 34þ:3, 24.8 Hz), 55.4 (s); GC–MS:
250 (Mþ þ 2) (24), 248 (M ) (24), 169 (BP, 100), 154 (25),
126 (73), 125 (61), 99 (67). HRMS: calcd for C9H7F279BrO
247.9648 found 247.9636, calcd for C9H7F281BrO 249.9628
found 249.9606.
19FNMR (CDCl3): d À77.9 (d, J ¼ 29:4 Hz, 1F), À84.2
(d, J ¼ 29:0 Hz, 1F); 1H NMR (CDCl3): d 7.31–7.35
(m, 2H), 7.39–7.43 (m, 2H); 13C NMR (CDCl3): d 153.3
(dd, J ¼ 294:2, 286.4 Hz), 134.9 (s), 130.1 (t, J ¼ 3:4 Hz),
128.8 (s), 79.0 (dd, J ¼ 34:0, 25.6 Hz); GC–MS: 254
(Mþ þ 2) (61), 252 (Mþ) (48), 173 (86), 138 (BP, 100), 99
(41), 87 (57), 62 (46); HRMS: calcd for C8H479BrBr35ClF2
251.9153 found 251.9151, calcd for C8H481Br35ClF2
253.9132 found 253.9129, calcd for C8H479Br37ClF2
253.9123 found 253.9129, calcd for C8H481Br37ClF2
255.9103 found 255.9107.
3.6. o-MeC6H4CBr¼CF2
3.9. o-CF3C6H4CBr¼CF2
Following the general procedure for the coupling reaction,
2-iodotoluene (3.83 g, 17.6 mmol), zinc reagent (22.0 mmol)
and Pd(PPh3)4 (0.348 g, 1.5 mol%) at 60 8C for 12 h, fol-
lowed by work-up and careful distillation under reduced
pressure yielded the o-methyl-a-bromo-b,b-difluorostyrene
as a clear liquid in 86% (3.52 g, 15.2 mmol) yield [21]. bp,
52–53 8C at 11 mm.
Following the general procedure for the coupling reaction,
2-iodobenzotrifluoride (4.56 g, 16.8 mmol), zinc reagent
(21.0 mmol) and Pd(PPh3)4 (0.334 g, 1.5 mol%) at 65 8C
for 15 h, followed by work-up and distillation under reduced
pressure afforded the o-trifluoromethyl-a-bromo-b,b-
difluorostyrene as a colorless liquid in 74% (3.55 g,
12.4 mmol) yield [21].(The 13C NMR values reported for
this compound in [21] is not correct due to an error in
reporting). bp, 51–53 8C at 11 mm.
19FNMR (CDCl3): d À83.1 (d, J ¼ 32:6 Hz, 1F), À84.5
(d, J ¼ 33:5 Hz, 1F); 1H NMR(CDCl3):d 7.20–7.30(m, 4H),
2.33 (s, 3H); 13C NMR (CDCl3): d 152.7 (t, J ¼ 289:1 Hz),
137.8(d, J ¼ 1:4 Hz), 130.9(s), 130.6(s), 130.5(s), 129.9(s),
126.2 (s), 76.8 (dd, J ¼ 41:2, 25.7 Hz), 19.3 (s); GC–MS: 234
(Mþ þ 2) (62), 232 (Mþ) (63), 153 (64), 151 (62), 134 (52),
133 (BP, 100), 75 (51), 63 (50), 51 (57).
19FNMR (CDCl3): d À61.4 (d, J ¼ 5:4 Hz, 3F), À81.2
(m, 2F); 1H NMR (CDCl3): d 7.71 (d, J ¼ 7:6 Hz, 1H), 7.58
(m, 1H), 7.44–7.53 (m, 2H); 13C NMR (CDCl3): d 153.0
(t, J ¼ 288:9 Hz), 133.0 (d, J ¼ 2:4 Hz), 132.4 (s), 130.3 (s),
130.1 (s), 126.7 (q, J ¼ 4:7 Hz), 123.5 (q, J ¼ 273:4 Hz),
73.2 (dd, J ¼ 41:2, 30.8 Hz); GC–MS: 288 (Mþ þ 2) (74),
286 (Mþ) (75), 207 (BP, 100), 187 (88), 157 (66), 138 (71),
99 (36), 87 (47), 69 (66).
3.7. m-O2NC6H4CBr¼CF2
Following the general procedure for the coupling reaction,
1-iodo-3-nitrobenzene (4.38 g, 17.6 mmol), zinc reagent
(22.0 mmol) and Pd(PPh3)4 (0.348 g, 1.5 mol%) at RT for
22 h, followed by work-up and distillation under reduced
pressure afforded the m-nitro-a-bromo-b,b-difluorostyrene
as a pale yellow liquid in 75% (3.5 g, 13.2 mmol) yield. bp,
115–116 8C at 11 mm.
3.10. Synthesis of p-F2C¼BrCC6H4CBr¼CF2
Following the general procedure for the coupling reaction,
1,4-diiodobenzene (2.77 g, 8.4 mmol), zinc reagent
(21.0 mmol) and Pd(PPh3)4 (0.324 g, 1.5 mol%) at 65 8C
for 5 h, followed by work-up and distillation under reduced
pressure yielded the bis-a-bromo-b,b-difluorostyrene as a
colorless solid, which was crystallized from hexane 69%
(2.08 g, 5.81 mmol) [21]. mp, 52–53 8C.
19FNMR (CDCl3): d À75.6 (d, J ¼ 25:3 Hz, 1F), À82.0 (d,
J ¼ 26:4 Hz, 1F); 1H NMR(CDCl3):d 8.40 (s, 1H), 8.21 (dm,
J ¼ 8:2 Hz, 1H), 7.80 (dm, J ¼ 7:9 Hz, 1H), 7.63 (t, J ¼
7:8 Hz, 1H); 13C NMR (CDCl3): d 153.8 (dd, J ¼ 297:5,
289.0 Hz), 148.2 (s), 134.5 (t, J ¼ 3:2 Hz), 133.4 (d,
J ¼ 2:9 Hz), 129.7 (s), 123.8 (t, J ¼ 3:4 Hz), 123.6 (s),
78.1 (dd, J ¼ 33:1, 27.9 Hz); GC–MS: 265 (Mþ þ 2) (10),
263 (Mþ) (10), 138 (BP, 100), 99 (36), 87 (37), 62 (34);
HRMS: calcd for C8H4F279BrNO2 262.9393 found 262.9392,
calcd for C8H4F281BrNO2 264.9373 found 264.9373.
19FNMR (CDCl3): d À77.2 (d, J ¼ 28:4 Hz, 2F), À83.6
(d, J ¼ 28:2 Hz, 2F); 1H NMR (CDCl3): d 7.53 (s, 4H); 13
C
NMR (CDCl3): d 153.5 (dd, J ¼ 294:3, 288.0 Hz), 128.9
(t ¼ not resloved), 79.4 (dd, J ¼ 35:4, 28.1þHz); GC–MS:
362 (Mþ þ 4) (2), 360 (Mþ þ 2) (4), 358 (M ) (2), 281 (3),
279 (4), 200 (34), 150 (30), 149 (34), 123 (35), 99 (BP, 100),
75 (87), 74 (46), 62 (39), 51(58).
3.8. p-MeOC6H4CBr¼CF2
3.11. 2-(2-Bromo-1,1-difluoroethenyl) thiophene
Following the general procedure for the coupling reaction,
4-iodoanisole (3.9 g, 16.8 mmol), zinc reagent (20.5 mmol)
Following the general procedure for the coupling reac-
tion, 2-iodothiophene (3.5 g, 16.8 mmol), zinc reagent

566
R. Anilkumar, D.J. Burton / Journal of Fluorine Chemistry 125 (2004) 561–566
[7] B.A. Madden, D.G. Prestwich, Bioorg. Med. Chem. Lett. 7 (1997)
309–314.
(21.0 mmol) and Pd(PPh3)4 (0.334 g, 1.5 mol%) at RT for
24 h, followed by work-up and distillation under reduced
pressure afforded the 2-(2-bromo-1,1-difluoroethenyl) thio-
phene as a colorless liquid in 64% (2.5 g, 11.2 mmol) yield.
bp, 48–50 8C at 11 mm.
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B.J. Lippert, R.D. Snyder, P.S. Sunkara, J. Am. Chem. Soc. 112
(1991) 7439–7440.
19FNMR (CDCl3): d À80.1 (d, J ¼ 24:3 Hz, 1F), À80.4
(d, J ¼ 25:1 Hz, 1F); 1H NMR (CDCl3): d 7.35 (dd, J ¼ 1:3,
5.3 Hz, 1H), 7.22 (dd, J ¼ 1:2, 3.8 Hz, 1H), 7.02 (ddd,
J ¼ 1:0, 3.8, 4.9 Hz, 1H); 13C NMR (CDCl3): d 153.1
(dd, J ¼ 298:3, 290.6 Hz), 132.9 (d, J ¼ 7:8 Hz), 128.4
(t, J ¼ 5:0 Hz), 127.3 (s), 127.1 (bs), 75.3 (dd, J ¼ 34:4,
29.8 Hz); GC–MS: 226 (M þ 2) (28), 224 (Mþ) (28), 210
(100), 145 (80), 127 (74), 111 (96), 101 (68), 83 (76), 57
(95); HRMS: calcd for C6H379BrF2S 223.9107 found
223.9107, calcd for C6H381BrF2S 225.9086 found 225.9084.
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Acknowledgements
We are grateful to the National Science Foundation for
support of this research work.
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