The stereoselective synthesis of (Z)-HFC=CFZnI and stereospecific preparation of (E)-1,2-difluorostyrenes from (Z)-HFC=CFZnI via an unusual Pd(PPh3)4-Cu(I)Br co-catalysis approach or (Z)-HFC=CFSnBu3

Article abstract of DOI:10.1016/j.jfluchem.2010.11.008

(Z)-HFCCFZnI was stereoselectively synthesized from activated zinc dust and (Z)-HFCCFI that was synthesized from chlorotrifluoroethene in a sequential manner. Compared to (E)-HFCCFZnI, (Z)-HFCCFZnI was more challenging to prepare in terms of sluggish metallation and formation of by-products, and underwent slower and incomplete Negishi coupling with aryl iodides. In a modification of Negishi coupling, (E)-α,β-difluorostyrenes were stereospecifically prepared in good to excellent yields under mild conditions from aryl iodides and (Z)-HFCCFZnI with the co-catalysis of Pd(PPh₃)₄/Cu(I)Br. Experimental investigation and mechanistic rationalization suggested that Cu(I)Br would be a scavenger of free ligands for the facilitation of Pd(PPh ₃)₂ formation, and a supplier of ligand for the metathesis process. Alternatively, (Z)-HFCCFSnBu₃ and aryl iodides with an electron-withdrawing group underwent Stille-Liebiskind coupling to afford (E)-α,β-difluorostyrenes.

Full text of DOI:10.1016/j.jfluchem.2010.11.008

Journal of Fluorine Chemistry 132 (2011) 78–87
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
The stereoselective synthesis of (Z)-HFC55CFZnI and stereospecific preparation of
(E)-1,2-difluorostyrenes from (Z)-HFC55CFZnI via an unusual Pd(PPh3)4–Cu(I)Br
co-catalysis approach or (Z)-HFC55CFSnBu3
*
Qibo Liu, Donald J. Burton
Department of Chemistry, The University of Iowa, Iowa City, IA 52242, United States
A R T I C L E I N F O
A B S T R A C T
Article history:
(Z)-HFC55CFZnI was stereoselectively synthesized from activated zinc dust and (Z)-HFC55CFI that was
synthesized from chlorotrifluoroethene in a sequential manner. Compared to (E)-HFC55CFZnI, (Z)-
HFC55CFZnI was more challenging to prepare in terms of sluggish metallation and formation of by-
products, and underwent slower and incomplete Negishi coupling with aryl iodides. In a modification of
Received 19 October 2010
Received in revised form 16 November 2010
Accepted 17 November 2010
Available online 27 November 2010
Negishi coupling, (E)-a,b-difluorostyrenes were stereospecifically prepared in good to excellent yields
under mild conditions from aryl iodides and (Z)-HFC55CFZnI with the co-catalysis of Pd(PPh3)4/Cu(I)Br.
Experimental investigation and mechanistic rationalization suggested that Cu(I)Br would be a scavenger
of free ligands for the facilitation of Pd(PPh3)2 formation, and a supplier of ligand for the metathesis
process. Alternatively, (Z)-HFC55CFSnBu3 and aryl iodides with an electron-withdrawing group
Keywords:
Cuprous bromide
Cuprous complex
Palladium catalysis
underwent Stille–Liebiskind coupling to afford (E)-
a
,b
-difluorostyrenes.
ß 2010 Elsevier B.V. All rights reserved.
(Z)-1,2-Difluoroethenyl zinc iodide
(Z)-1,2-Difluoroethenyltributylstannane
Zinc iodide
(E)-1,2-Difluorostyrenes
1. Introduction
Cuprous halide is well known as a co-catalyst in Stille–
Liebiskind coupling with stannanes [10–12]. However, in the
chemical literature, only one paper has been found that employs a
cuprous salt to assist sluggish Negishi coupling with an organozinc
reagent [13].
Fluorinated styrenes are useful building blocks in organo-
fluorine chemistry and have found application as monomers [1], as
precursors for anti-inflammatory [2] and antifertility [3] com-
pounds, and as precursors for 1,4-diaryl-perfluoro-1,3-butadienes
Previous reports from our laboratories have described a facile
[4]. Several strategies have been utilized in the preparation of
a
,
b
-
preparation of (Z)-a,b-difluorostyrenes via a Pd(PPh3)4 catalyzed
difluorostyrenes. -Difluorostyrene has been prepared in low
a
,
b
cross-coupling of (E)-1,2-difluoroethenylzinc iodide with aryl
iodides [14]. We now report in detail the stereoselective
preparation of (Z)-HFC55CFZnI and the stereospecific synthesis of
yield by dehalogenation of 1-chloro-1-phenyl-1,2,2-trifluor-
oethane [5]. The stereochemistry of the resultant styrene was
not reported. Dehydrofluorination of 1-phenyl-1,1,2-trifluor-
(E)-a,b-difluorostyrenes with (Z)-HFC55CFZnI under the co-catal-
oethane resulted in a low yield of
dehydrofluorination was not extended to other 1-aryl-1,1,2-
trifluoroethanes [6]. Low temperature metallation of several
a
,
b
-difluorostyrene; this
ysis of Pd(PPh3)4/Cu(I)Br in dry DMAC [15], and with (Z)-
HFC55CFSnBu3 under the co-catalysis of Pd(PPh3)4/Cu(I)I in DMF.
isomeric
reagent, followed by hydrolysis, has been reported to give
predominantly (E)- -difluorostyrenes [7]. Protodesilylation of
(Z)-1,2-difluoro-2-arylvinylsilanes by potassium fluoride in aque-
ous DMSO gave (E)- -difluorostyrenes [8,9]. However, a general,
a,b-difluoro-b-chlorostyrenes with an alkyllithium
2. Results and discussion
a,b
2.1. Synthesis of isomerically pure (Z)-HFC55CFZnI (2(Z)) and a
mixture of 94:6 (Z)/(E)-HFC55CFZnI (2(Z) and 2(E))
a,b
stereoselective preparation of (E)-a,b-difluorostyrenes has not
been reported.
Isomerically pure (Z)-HFC55CFZnI (2(Z)) can be prepared by
metallation of (Z)-HFC55CFI (1(Z)) with activated zinc dust in
anhydrous dry DMAC (76% NMR yield) or DMF (<50% NMR yield),
as illustrated in Fig. 1. Likewise, a 94:6 mixture of 2(Z)/2(E) can be
prepared from a 95:5 mixture of 1(Z)/1(E). Noticeably, the Z/E ratio
of 2(Z)/2(E) can decrease to as low as 85/15 when the solution was
stored for extended time periods at ambient temperature.
* Corresponding author. Tel.: +1 319 335 1363; fax: +1 319 335 1270.
E-mail address: donald-burton@uiowa.edu (D.J. Burton).
0022-1139/$ – see front matter ß 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2010.11.008

[
Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
79
sumably via LiF elimination. 5 Was converted to the vinyl iodide
1(Z) via protodesilylation in DMF at ambient temperature.
In a shorter route, a 95:5 isomeric mixture of 1(Z)/1(E) was
prepared from 4, KF and iodine in DMF (Scheme 1).
In an exploratory reaction, as outlined in Fig. 2, we demon-
strated that 2(Z) was capable of undergoing an SN2 reaction with
allyl chloride in DMF to form the pentadiene, 7. The reaction could
be effectively accelerated by the mediation of Cu(I)Br.
H
F
F
I
H
F
F
Zn
RT
ZnI
1(Z)
2(Z)
in DMAC, 76 %
in DMF, < 50 %
Fig. 1.
2.2. Attempted preparation of (E)-1,2-difluorostyrenes (8(E)) from a
94:6 isomeric mixture of 2(Z)/2(E)
Unlike the facile conversion of 1(E) to 2(E) [14], the zinc
metallation of 1(Z) requires effectively activated zinc dust to
secure initiation of the reaction and avoid incomplete reaction,
suggesting the C–I bond in 1(Z) is stronger than in 1(E). When DMF
was employed as solvent, the zinc metallation of 1(Z) afforded no
more than 50% NMR yield of 2(Z), in addition to an unidentified by-
product and the reduction product, (E)-HFC55CFH. A higher yield
was obtained in dry DMAC (N,N-dimethylacetamide) solvent;
however an unidentified by-product and the reduction product
also accompanied the metallation. Although the by-product was
not isolated and identified, it was believed to be generated from
the addition reaction of a (Z)-1,2-difluoroethenyl intermediate and
DMF or dry DMAC based on a report of a related case carried out in
DMF solvent [16]. A lower amount of the by-product was
generated in dry DMAC, presumably because the carbonyl carbon
is less susceptible to nucleophilic attack in DMAC than in DMF.
As illustrated in Scheme 1, the fluorinated vinyl iodide, 1(Z) can
be stereoselectively prepared from chlorotrifluoroethene via the
silyliodoethene, 5, using Normant’s method [17]. Treatment of a
mixture of chlorotrifluoroethene and triethylsilyl chloride with
butyllithium reagent and in situ trapping of trifluorovinyl lithium
with triethylsilyl chloride gave the trifluorovinylsilane, 3. Reduc-
tion of 3 with lithium aluminum hydride gave predominantly the
Z-isomer of the 1,2-difluoroethenylsilane, 4. Further deprotona-
tion/iodination of 4 at À100 8C gave the silyliodoethene, 5 in an
excellent isolated yield. 4(E) decomposed upon lithiation, pre-
Previous work from our laboratory had established a facile
approach to the stereoselective synthesis of (Z)-1,2-difluorostyr-
enes, 8(Z), using a 95:5 isomeric mixture of 2(E) and 2(Z) (Fig. 3)
[14]. When we attempted to employ a 94:6 mixture of 2(Z)/2(E) in
a similar fashion to prepare an 8(E)/8(Z) mixture, we discovered an
interesting difference.
Unlike the facile preparation of 8(Z) from a 95:5 mixture of 2(E)/
2(Z) (Fig. 3), the coupling reaction of 94:6 2(Z)/2(E) with aryl iodides
(Fig. 4) resulted in a dilemma of incomplete reaction and shift of
stereochemistry to a lower (E)/(Z) ratio in the coupling product even
at elevated temperatures and after prolonged reaction time.
Technically, the synthesis was challenging because 8(E) could not
be separated from the unreacted aryl iodide due to their similarity in
affinity to chromatographic silica gel, and boiling points.
It is not clear why the (E)-isomer isomerizes so rapidly to the
(Z)-isomer in this case. When we attempted to equilibrate the (E)/
(Z) styrenes with Ph2S2 [18], we only obtained polymerization of
the styrenes [19]; thus we could not determine the relative
stabilities of the styrene isomers. Leroy obtained similar results [6].
2.3. Stereospecific preparation of 8(E) from 2(Z)
Concerning the isomerization of 8(E) to 8(Z), we attempted a
stereospecific preparation 8(E) using Negishi cross-coupling of
[()TD$FIG]
1(Z) + 1(E)
Z:E = 95:5
KF, I2
DMF
F
F
F
F
F
F
H
F
F
1. Et3
ºC
LiAlH4
THF
2. BuLi, THF, -78 ºC
Cl
SiEt3
SiEt3
3
4
Z:E = 95:5
79%
84%
1. BuLi, THF / Et2O,
-95 to -100 ºC
I
F
KF, H2O
1(Z)
2. I2
ºC
DMF
F
SiEt3
100% (Z)
5
79%
89%
Scheme 1. Preparation of 1(Z) and 95:5 1(Z)/1(E) mixture from CF25CFC1.

[
Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
[()TD$FIG]
Cu(I)Br, DMF, RT/2 h
PdL4
PdL2
RfAr
CuBr
ArI
H
F
CuBrLn
2 L
H
H
H
H
F
F
DMF
H
+
F
RT/1 week
Cl
ZnI
H
2(Z)
7
6
H
quantitative NMR yield
CuBr
Fig. 2.
Rf
I
[()TD$FIG]
L2Pd
L2Pd
Ar
F
F
H
F
F
F
Ar
ArI, Pd(PPh3)4, DMF
ºC
+
S
Pd
S
H
ZnI
F
ZnI
H
Ar
ZnI2 + S
L
I
2(Z)
8(Z)
2(E)
95
L
RfZnI + L
S = solvent
55 - 93%
:
5
Ar
Fig. 3.
Scheme 2. Proposed mechanism of Pd–Cu(I)Br co-catalyzed coupling of 2(Z)
with ArI.
2(Z) with aryl iodides under the catalysis of Pd(PPh3)4 in DMF;
however, an incomplete reaction mixture was obtained. To
overcome the sluggish metathesis process as mentioned in the
mechanism discussion (Scheme 2), we introduced Cu(I)Br to the
reaction system. We were delighted with the results: a series of
8(E) compounds were readily synthesized in excellent isolated
yields in less than 6 h, at ambient temperature to 40 8C, under
Pd(PPh3)4 catalysis and Cu(I)Br mediation (Table 1) in DMAC as the
solvent.
Table 1
Preparation of (E)-l,2-difluorostyrenes (8(E)).
[TD$INLE]
H
F
F
H
F
Pd(PPh3)4, Cu(I)Br, DMAC
.
+
ArI
F
ZnI
Ar
The rate of the Cu(I)Br-mediated Negishi coupling depends on
the type and position of the substituent on the aromatic ring. In
general, an aryl iodide with an electron-withdrawing group
underwent faster reaction than an aryl iodide with an electron-
releasing group.
Entry
ArI
Product
Yielda (%)
1
2
p-FC6H4–I
p-FC6H4CF5CFH (8(E)-1)
p-ClC6H4CF5CFH (8(E)-2)
p-BrC6H4CF5CFH (8(E)-3)
89
95
94
92
74b
94
84
87
93
87
73
p-ClC6H4–I
p-BrC6H4–I
p-IC6H4–I
3
4
p-C6H4(CF5CFH)2 (8(E)-4)
C6H5CF5CFH (8(E)-5)
5
C6H5–I
6
p-MeOC6H4–I
m-CF3C6H4–I
1-C10H7–I
p-MeOC6H4CF5CFH (8(E)-6)
m-CF3C6H4CF5CFH (8(E)-7)
l-NaphthylCF5CFH (8(E)-8)
m-NO2C6H4CF5CFH (8(E)-9)
p-NO2C6H4CF5CFH (8(E)-10
2-ThiopheneCF5CFH (8(E)-11)
2.4. Analysis of the role of Cu(I)Br in the formation of 8(E)
7
8
To determine if Cu(I)Br would convert 2(Z) to (Z)-HFC55CFCu
and thus accelerate the sluggish coupling reaction with a more
nucleophilic organocopper(I) reagent, we attempted to perform
the cross-coupling reaction stepwise, (1) react 2(Z) with Cu(I)Br in
solventand (2) conduct the reaction using the mixture, aryl iodide
and Pd(PPh3)4. Unfortunately, the reaction mixture for the first
step showed faint 19F NMR signals, suggesting decomposition or
side reactions from the fluorinated organometallic upon treatment
with Cu(I)Br.
As outlined in Fig. 5, the role of Cu(I)Br in Negishi coupling was
alternatively investigated with a similar organozinc reagent,
CF255CFZnBr, 9; CF255CFCu is known to be stable. Surprisingly, in
the presence of Cu(I)Br, the Pd-catalyzed cross-coupling of 9 with
PhI yielded a reaction mixture containing the styrene 10 in only
33% NMR yield along with 30% NMR yield of the vinylcopper
reagent, 11. After an elongated reaction time of 10 h, the
vinylcopper reagent, 11, showed no reaction with the unreacted
9
m-NO2C6H4–I
p-NO2C6H4–I
2-Thiophenyl-I
10
11
a
Isolated yield of (E)-isomer only.
b
Without Cu(I)Br, the reaction took 6 h at 50 8C, the product was isolated in a
yield of 41%, GLPC purity = 95%.
iodobenzene in the presence of Pd(PPh3)4 to give 10 in an
excellent isolated yield (Fig. 6). These observations encouraged us
to look into an alternative mechanistic possibility for the Cu(I)Br
effect.
The role of the cuprous salt is suggested to be a scavenger of free
ligands, similar to the proposal by Farina et al. [10]. Scheme 2
illustrates the suggested mechanistic proposal for this rare cuprous
salt modified Negishi coupling. Pd(PPh3)4 undergoes ligand
dissociation to give the active Pd(0) complex, Pd(PPh3)2. This step
may be accelerated with the removal of free ligands from the
PhI. On the other hand, without Cu(I)Br,
9 coupled with
[()TD$FIG]
H
F
F
H
F
F
F
F
F
F
ArI, Pd(PPh3)4, DMF
ArI
+
+
:
+
:
RT to 60 ºC
> 12 h
Ar
ZnI
H
ZnI
H
Ar
2(E)
8(Z)
2(Z)
8(E)
85
15
94
6
Fig. 4.

[
Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
81
F
F
F
F
F
F
F
F
F
Pd(PPh3)4, Cu(I)Br
DMF, RT/10 h
+
+
PhI
ZnBr
Ph
Cu
9
10
33% nmr yield
11
30% nmr yield
Fig. 5.
[()TD$FIG]
temperature. The vinylsilane 13 was isolated with THF by flash
distillation, and used in the next step without further purification.
Reduction of 13 in THF with LiAlH4 afforded the vinylsilanes
14(Z) and 14(E) in the ratio of 91:9, hence sets a foundation for
further introduction of the trans-1,2-difluoroethenyl unit into
organic molecules.
F
F
F
F
F
F
Pd(PPh3)4, DMF
RT/12 h
PhI
+
ZnBr
Ph
9
10
100% nmr yield
The mono-stannane 12 was synthesized from 14 and bis(-
tributyltin) oxide under the catalysis of TBAF in nearly quantitative
isolated yield. A flash chromatographic purification increased the
ratio of Z/E isomers possibly due to decomposition of 12(E).
The mono-stannane 12(Z) could be alternatively prepared
using tributyltin chloride (Fig. 7).
92% isolated yield
Fig. 6.
reaction mixture via the formation of Cu(I)BrLn complex. Oxidative
addition of ArI to Pd(PPh3)2 gives ArIPd(PPh3)2. One of the two PPh3
ligands in ArIPd(PPh3)2 may be replaced by a solvent molecule to
create a susceptible site for a nucleophilic displacement with the
presumably weaker nucleophile, 2(Z). The free ligand generated
here may again be scavenged by Cu(I)Br. Further transmetallation
of ArIPd(S)(PPh3) (note: S = solvent) with 2(Z) followed by ligand
displacement gives ArRfPd(PPh3)2. Eventual reductive elimination
in ArRfPd(PPh3)2 affords the cross-coupling product, 8(E), and
regenerates the active Pd(0) complex, Pd(PPh3)2 for the next
catalytic coupling cycle.
2.6. Pd-catalyzed couplings of (Z)-HFC55CFSnBu3 (12(Z)) with aryl
iodides
As summarized in Table 2, 12(Z) has also been utilized for the
preparation of 8(E). In general, the cross-coupling of aryl iodides
with 12(Z) are slower than those with 2(Z); 12(Z) behaved as a less
nucleophilic reagent for transmetallation than 2(Z). For example,
para-bromoiodobenzene underwent cross-coupling at RT with
2(Z) in 1 h, whereas 12(Z) required 3 h at 70 8C for cross-coupling
of the same aryl iodide. In the Stille–Liebeskind coupling reaction
between 12(Z) and aryl iodides, those aryl iodides with electron-
releasing groups (e.g., methyl or methoxy) were not completely
consumed, even under forced conditions. As a consequence, the
cross-coupling product could not be obtained pure due to the lack
of inefficient separation from the un-reacted aryl iodide. On the
other hand, aryl iodides containing electron-withdrawing groups
coupled readily with 12(Z).
2.5. Stereoselective synthesis of (Z)-HFC55CFSnBu3 (12(Z)) from
CF255CFCl
(Z)-HFC55CFSnBu3 (12(Z)) has been stereoselectively synthe-
sized sequentially from CF255CFCl [20]. As illustrated in Scheme 3,
butyl lithium underwent chlorine–lithium exchange to generate
[CF255CFLi] at low temperature, which was in situ trapped with
Me3SiCl to give 13. Me3SiCl was used as the limiting reagent to
avoid contaminants with close boiling points in the product, while
CF255CFCl and the by-product CF255CFH are gases at room
The advantages of 12(Z) over 2(Z) are two-fold. (1) 12(Z) is
far more stable due to its greater moisture stability than 2(Z).
Thus, 12(Z) does not need to be used in excess; whereas 2(Z)
[()TD$FIG]
H
F
F
F
F
F
F
F
F
LiAlH4
THF
1. n-BuLi, THF, -78 to -82 ºC
2. Me3SiCl
SiMe3
SiMe3
Cl
14
13
90% NMR yield
Z : E = 91 : 9
90% NMR yield
Bu3SnOSnBu3
TBAF (cat.), THF
F
H
F
SnBu3
12
98% based on Bu3SnOSnBu3
Z : E = 93 : 7
Z : E = 97 : 3 after further
seperation by column
chromatography.
Scheme 3. Stereoselective synthesis of 12(Z) from CF25CFC1.

[
Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
H
F
F
F
2.7. NMR characteristics of 8(E)
H
F
KF, ClSnBu3,
ºC/1 h
Selective 19F NMR chemical shifts and coupling constants data
of 8(E) are summarized in Table 3. Generally, the chemical shift of
the vinyl fluorine varies in a narrow range, with the exception of
the naphthyl (entry 8), 4-nitrophenyl (entry 10), 2-thiophenyl
(entry 11), 4-cyanophenyl (entry 13), and 2-pyridyl derivatives
(entry 14). The variation in chemical shift is affected by the
anisotropic effect from the aromatic ring.
67%
SiMe3
SnBu3
14
Z : E = 91 : 9
12
Z : E = 93 : 7
Fig. 7.
In general, Fa shifts downfield relative to the CFCl3 internal
reference when an electron-withdrawing group is attached to the
aromatic ring; upfield when the aromatic ring is substituted with
an electron-releasing group. Interestingly, except for 8(E)-8, 8(E)-
10, 8(E)-11, 8(E)-13, 8(E)-14, the chemical shift of Fb is nearly
independent of the substituent group. On the other hand, coupling
constants between the vinyl fluorines or between the vinyl proton
and the vinyl fluorine showed almost no variation with the
exception of 8(E)-8, 8(E)-10, 8(E)-11, 8(E)-13, 8(E)-14.
Table 2
Pd(PPh3)4-catalyzed cross-couplings of (Z)-l,2-difluoroethenyltributylstannane
with aryl iodides.
[
.
The 19F NMR of 8(E)-10 (entry 10) and 8(E)-13 (entry 13)
appeared as second-order spectra. The {1H}19F NMR of 8(E)-10
revealed a singlet peak at À167.1 ppm, indicating the two fluorines
occurred to have identical chemical shift owing to the electron-
withdrawing effect from the para-nitro group. The {1H}19F NMR of
8(E)-13 showed two adjacent singlet peaks at À167.8 ppm and
À168.2 ppm. Thus, instead of AXY spin systems like the other
examples (entries 1–9, 11, and 12), 8(E)-10 and 8(E)-13 behaved
like an AXX’ spin system.
Entry
ArI
Conditions
Products
Isolated yield
1
2
3
4
5
6
3-ClC6H4I
RT/1 h
8(E)-12
8(E)-13
8(E)-3
82%
83%
4-CNC6H4I
4-BrC6H4I
2-Pyridyl-I
3-MeC6H4I
4-MeOC6H4I
RT/1 h
70 8C/3 h
RT/1 h
92%
8(E)-14
8(E)-15
8(E)-6
21%a
N.Ab
N.Ab
RT/3 days
60 8C/18 h
a
Unstable product quickly decomposed at room temperature.
b
Incomplete reaction (NMR yield was less than 60%), product was isolated
Table 4 summarizes the carbon/fluorine coupling constants
on the vinyl carbons and the most adjacent aromatic carbon.
Generally, the magnitude of 1JFC are consistent with slight variation
among the benzene-based derivatives, between 248 Hz and
together with the unreacted aryl iodide.
1
1
254 Hz for JFCa; 228 Hz and 229 Hz for JFCb. Except for 8(E)-8
and 8(E)-11 of different aromatic systems, and 8(E)-9 and 8(E)-10
with nitro substituents, the 2JFC fall into a narrow range, 2JFCa = 71–
74 Hz; 2JFCb = 30–32 Hz. The values of 3JFCc and 2JFCc are stabilized
in a narrow range. Both 8(E)-10 and 8(E)-13 have second-
order spectrum coupling patterns in the vinyl carbon. 8(E)-14,
was used in excess. (2) 12(Z) is easier to prepare in terms of a
shorter synthetic route, and easier to store, due to its moisture
stability than 2(Z).
Except for the relatively low reactivity, the most awkward
drawback of the tin reagent, 12(Z) is the toxicity of both 12(Z) and
its by-product, Bu3SnI. It can be difficult to remove Bu3SnI from the
coupling product. On the other hand, the zinc reagent, 2(Z) is not
toxic, and its by-product, ZnI2 is easy to separate from the styrene
product.
a
2-pyridyl system showed substantial differences in both
1
chemical shift and coupling constant. In general, JFCa ꢀ 250 Hz,
2JFCa ꢀ 70 Hz,
2JFCc ꢀ 25 Hz.
2JFCb ꢀ 31 Hz,
1JFCb ꢀ 230 Hz,
3JFCc ꢀ 6 Hz,
Table 3
19F NMR data of (E)-l,2-difluorostyrenes (8(E)).
[TD$INLE]
c
a
b
H
F
.
F
Ar
Entry
8(E)
dF (ppm)
dF (ppm)
3JF
2JHcF
3JF
Hc
b
F
a
b
a
b
b
1
2
p7FC6H4CF5CFH (8(E)-1)
p-ClC6H4CF5CFH 8(E)-2)
pBrC6H4CF5CFH 8(E)-3)
pC6H4(CF5CFH)2 (8(E)-4)
C6H5CF5CFH (8(E)-5)
À175.0
À172.7
À172.46
À172.0
À174.1
À177.3
À171.6
À174.2
À169.6
ND
À166.3
À167.0
À167.1
À167.8
À166.9
À166.3
À167.6
À147.8
À167.1
ND
125
126
125
125
125
125
125
137
126
ND
75
75
75
75
76
76
75
76
74
ND
75
75
NDa
67
5
5
3
5
4
5
5
5
6
p-MeOC6H4CF5CFH (8(E)-6)
mCF3C6H4CF5CFH (8(E)-7)
1-NaphthylCF5CFH (8(E)-8)
m-NO2C6H4CF5CFH (8(E)-9)
p-NO2C6H4CF5CFH (8(E)-10)
2-ThiophenylCF5CFH (8(E)-11)
m-C1C6H4CF5CFH (8(E)-12)
p-CNC6H4CF5CFH (8(E)-13)
2-PyridylCF5CFH (8(E)-14)
5
7
5
8
0
9
5
10
11
12
13
14
ND
0
À172.3
À171.9
À168.2 or À167.8
À169.2
À161.1
À167.2
125
125
125
127
5
À168.2 or À167.8
NDa
13
À169.9
a
ND, not determined, because the spectrum is second-order.

Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
83
Table 4
JCF (Hz) in the {1H}13C NMR spectra of (E)-l,2-difluorostyrenes (8(E)).
[DT$INLE]
2
H
a
F
b
.
1
F
c
Entry
8(E)
1JCaF1
2JCaF2
2JCbF1
1JCbF2
3JCcF1
2JCcF2
1
2
p-FC6H4CF5CFH (8(E)-1)
p-ClC6H4CF5CFH (8(E)-2)
p-BrC6H4CF5CFH (8(E-2)
p-C6H4(CF5CFH)2 (8(E)-4)
C6H5CF5CFH (8(E)-5)
250
73
32
229
6
6
25
25
25
25
24
25
25
22
26
11
29
25
ND
20
252
72
31
228
3
252
72
31
229
6
4
253
72
30
229
7
5
251
73
31
229
6
6
p-MeOC6H4CF5CFH (8(E)-6)
m-CF3C6H4CF5CFH (8(E)-7)
1-NaphthaleneCF5CFH (8(E)-8)
m-NO2C6H4CF5CFH (8(E)-9)
p-NO2C6H4CF5CFH (8(E)-10)
2-ThiopheneCF5CFH (8(E)-11)
m-ClC6H4CF5CFH (8(E)-12)
p-CNC4H4CF5CFH (8(E)-13)
2-PyridylCF5CFH (8(E)-14)
248
74
32
228
6
7
253
71
30
229
6
8
246
71
37
237
4
9
254
69
29
228
6
10
11
12
13
14
ND
ND
68
ND
37
ND
6
250
228
8
253
72
31
228
6
ND
ND
5 or ND
ND
5 or ND
ND
ND
3
196 or ND
196 or ND
ND: not determined, because the spectrum is second-order (a novel virtual coupling pattern). This unique virtual coupling will be presented elsewhere.
3. Conclusion
and then dried in vacuo at room temperature. Cu(I)Br was treated
with aqueous HBr (48%), precipitated with excess cold water,
washed with water, acetone, and ether, and then dried in vacuo.
Cu(I)I was purified by dissolution–precipitation process in water
using NaI or KI [21]. Pd(PPh3)4 was prepared by Coulson’s
procedure [22]. CF255CFSiEt3 [23] was prepared by a modification
of the literature procedure from CF255CFCl, BuLi, Et3SiCl in THF.
CHF55CFSiEt3 (Z:E = 95:5) [18] and (E)-IFC55CFSiEt3 [17] were
prepared by the literature procedures. All reagents were obtained
from common commercial sources.
(Z)-HFC55CFZnI was sequentially synthesized from CF255CFCl
via (Z)-HFC55CFI. (Z)-HFC55CFZnI showed substantially lower
reactivity than (E)-HFC55CFZnI in cross-coupling reactions with
aryl iodides under catalysis of Pd(PPh3)4; and the slow cross-
coupling resulted in isomerization in the styrene product.
Consequently, we required Cu(I)Br co-catalysis to facilitate the
reaction and avoid E/Z isomerization of the difluorostyrene. The
role of Cu(I)Br in the unusual Cu(I)Br/Pd(0) co-catalysis in
organozinc cross-coupling reaction was suggested as a ligand
scavenger to accelerate ligand dissociation, as well as
to compensate free ligands in metathesis where free ligands
4.2. Preparation of (Z)-HFC55CFI (1(Z))
were needed. A series of (E)-
a
,
b
-difluorostyrenes were stereospe-
A two-neck 1-l round bottom flask equipped with a Teflon-
coated stir bar, dry ice/isopropanol condenser and rubber septum,
was charged with dry DMF (300 ml), (E)-1,2-difluoro-2-iodo-1-
triethylsilylethene (92.1 g, purity 95%, 288 mmol), and KF (18.2 g,
314 mmol). Water (5.2 g, 289 mmol) was then gradually intro-
duced into the solution via a syringe over 5 min. A mild exothermic
reaction was observed. The reaction mixture was stirred at room
temperature for 0.5 h, then subjected to flash distillation at RT/
1 mmHg, and the distillate was trapped in a liquid nitrogen cooled
flask. The resultant colorless distillate was dried over 5 g of P2O5
and distilled by flash distillation RT/1 mmHg. Further fractional
distillation of the distillate through a 10 cm Vigreux column
cifically prepared in excellent isolated yields from isomerically
pure (Z)-HFC55CFZnI under the co-catalysis of Pd(PPh3)4/Cu(I)Br.
(Z)-HFC55CFSnBu3 also coupled with aryl iodides containing an
electron-withdrawing group under the co-catalysis of Pd(PPh3)4/
Cu(I)I to afford (E)-a,b-difluorostyrenes in good yields.
4. Experimental
4.1. General experimental procedures
All glassware was oven-dried prior to use. 19F NMR
(282.44 MHz), 1H NMR (300.17 MHz) and {1H}13
C
NMR
yielded 42.7 g (79%) of a colorless liquid, GLPC purity = 100%,
3
(75.48 MHz) spectra were recorded on an AC-300 spectrometer
in CDCl3 solvent. The chemical shifts are reported in parts per
million downfield to the TMS internal standard for 1H NMR and
{1H}13C NMR. The chemical shifts are reported in parts per million
upfield to the CFCl3 internal standard for 19F NMR. FTIR spectra
were recorded as CCl4 solutions and reported in wavenumbers
(cmÀ1). Low resolution GC–MS spectra were obtained at 70 eV in
the electron-impact mode on a TRIO-1-GC–MS instrument. GLPC
analysis were performed on a 5% OV-101 on Chromosorb P column
bp = 44–45 8C. 19F NMR:
d
À132.1 (d, JFF = 145 Hz), À158.8 (dd,
2
2
3JFF = 145 Hz, JHF = 76 Hz). 1H NMR:
d 7.5 (dd, JHF = 76 Hz, 1 Hz).
146.3 (dd, JCF = 248 Hz, JCF = 56 Hz), 104.2 (dd,
13C NMR:
d
1
2
1JCF = 315 Hz, JCF = 57 Hz). GC–MS, m/z (relative intensity): 190
(M+, 100), 127 (49), 63 (76). HRMS calcd for C2HF2I 189.9090, obsd.
189.9106.
2
Literature data [17]: 19F NMR (d, CDCl3 as solvent, C6H5CF3 as
internal standard):
76.3 Hz); 1H NMR:
d
d
À68.9 (d, J = 145 Hz), À95.7 (dd, J = 145,
7.45 (dd, J = 76.4, 0.9 Hz); 13C NMR:
d
104.1
with
a
thermal conductivity detector. High-resolution mass
(dd, J = 314.9, 56.4 Hz), 146.3 (dd, J = 247, 56.4 Hz).
spectral determinations were made at the University of Iowa
High Resolution Mass Spectrometry Facility. All reactions were
carried out under an atmosphere of nitrogen. DMAC (CaH2) and
DMF (CaH2) were distilled at reduced pressure. THF was dried by
distillation from sodium benzophenone ketyl at ambient pressure.
Zinc (325 mesh, Aldrich) was activated by washing with dilute HCl
4.3. Preparation of (Z)-HFC55CFZnI (2(Z))
A two-neck 500-ml round bottom flask equipped with a Teflon-
coated stir bar, a dry ice/isopropanol condenser attached to a
nitrogen source and a rubber septum, was charged with 190 ml of

84
Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
dry DMAC, 30 g (461 mmol) of acid-washed zinc dust and 39.9 g
(209.8 mmol) of (Z)-1,2-difluoroiodoethene (1(Z)). After the
reaction mixture had been stirred for 0.5 h, a strong exothermic
reaction was observed. The solution was then stirred for an
additional 1.5 h. Analysis of the 19F NMR spectrum of the reaction
mixture indicated complete consumption of 1(Z). The 19F NMR
yield (C6H5CF3 as the internal standard) of 2(Z) was 76%. 19F NMR:
GC–MS, m/z (relative intensity): 174 (M+, 100), 139 (27), 119 (40).
FTIR (CCl4, cmÀ1): 1598 (m), 1494 (s), 1399 (m), 1354 (m), 1151
(vs), 1121 (m), 1107 (s), 1098 (m). HRMS calcd for C8H535ClF2
174.0048, obsd. 174.0049.
4.4.3. (E)-p-BrC6H4CF55CFH (8(E)-3)
Similarly,
a
mixture of 4-bromoiodobenzene (1.72 g,
d
(DMAC) À172.3 (dd, 3JFF = 104 Hz, 3JHF = 12 Hz, 1 F), À184.5 (dd,
5.96 mmol, 98%), Pd(PPhh3)4 (0.3 g, 0.3 mmol, 4 mol%), 2(Z)
(60 ml, 9 mmol, 0.15 M, 1.5 eq.) in dry DMAC, and Cu(I)Br (1 g,
7 mmol) was stirred at room temperature for 1 h. After silica gel
column chromatography (pentane, Rf = 0.56), removal of the
solvent gave 1.22 g (94%) of a colorless liquid, GLPC purity > 99%.
2
3JFF = 104 Hz, JHF = 87 Hz, 1 F).
If the reaction could not be initiated after stirring the reaction
mixture for a number of hours, it is our experience that the
initiation may be accomplished by following the next two steps:
(1) Stop stirring until a brown material appears on the surface of
the zinc metal, and then (2) restart stirring. This process can
normally help initiate the metallation.
19F NMR:
d
À167.1 (dd, 3JFF = 125 Hz, 3JHF = 5 Hz, 1 F), À172.4 (dd,
2
3JFF = 125 Hz, JHF = 75 Hz, 1 F). 1H NMR:
d 7.5 (d, distorted,
3JHH = 9 Hz, 2 H), 7.4 (d, distorted, partially overlapping with peak
3
at 7.3 ppm, JHH = 9 Hz, 2 H), 7.3 (dd, partially overlapping with
4.4. General procedure for the preparation of (E)-
a
,
b
-
peak at
(dd, 1JCF = 229 Hz, 2JCF = 31 Hz), 141.2 (dd, 1JCF = 252 Hz,
d d 151.0
= 7.4 ppm, 2JHF = 75 Hz, 3JHF = 5 Hz, 1 H). 13C NMR:
difluorostyrenes (8(E)) from (Z)-HFC55CFZnI (2(Z))
2JCF = 72 Hz), 131.8 (d, JCF = 2 Hz), 127.9 (dd, JCF = 25 Hz,
3JCF = 6 Hz), 126.7 (dd, 3JCF = 9 Hz, 4JCF = 7 Hz), 123.6 (d, 5JCF = 3 Hz).
GC–MS, m/z (relative intensity): 220 (M+, 97), 218 (M+, 100), 139
(33), 119 (98). FTIR (CCl4, cmÀ1): 1489 (m), 1151 (s), 1118 (m),
1106 (m), 1083 (m), 1010 (m). HRMS calcd for C8H5F279Br
217.9543, obsd. 217.9557.
4
2
A two-neck 50-ml round bottom flask equipped with a Teflon-
coated stir bar, a cold water condenser attached to a nitrogen
source and a septum, was charged with the aryl iodide (7.4 mmol,
99% purity), Pd(PPh3)4 (0.5 g, 0.4 mmol, 6 mol%), Cu(I)Br (1 g,
7 mmol) and 2(Z) (19 ml, 11.4 mmol, 0.60 M) in dry DMAC. The
reaction mixture was stirred at room temperature for 1 h. 19F NMR
analysis of the reaction mixture showed the formation of 8(E); GC–
MS of a pre-chromatographed reaction mixture showed the
complete disappearance of the aryl iodide. The dark reaction
mixture was poured directly onto a silica gel column and eluted
with pentane. Eluents with similar UV-active TLC spots were
combined and the majority of the pentane was removed by simple
distillation. Removal of the remaining trace amount of solvent at
À35 8C/1 mmHg yielded 8(E).
4.4.4. (E,E)-p-(HFC55CF)C6H4(CF55CFH) (8(E)-4)
Similarly, a mixture of 1,4-diiodobenzene (2.02 g, 6.06 mmol,
99%), Pd(PPh3)4 (0.65 g, 0.6 mmol, 5 mol%), 2(Z) (30 ml, 18 mmol,
0.60 M, 1.48 eq.) in dry DMAC, and Cu(I)Br (1.8 g, 13 mmol) was
stirred at room temperature for 2 h. After silica gel column
chromatography (pentane, Rf = 0.56), removal of the solvent gave
1.12 g (92%) of a white crystalline solid, mp 49.5–50.5 8C. 19F NMR:
3
3
d
À167.8 (dd, JFF = 125 Hz, JHF = 5 Hz,
2
F), À172.0 (dd,
7.7 (s, 4 H), 7.4 (dd,
151.1 (dd, 1JCF = 229 Hz,
3JFF = 125 Hz, JHF = 75 Hz, 2 F). 1H NMR:
d
2
4.4.1. (E)-p-FC6H4CF55CFH (8(E)-1)
2JHF = 75 Hz, 3JHF = 5 Hz, 2 H). 13C NMR:
d
1
2
Similarly,
a
mixture of 4-fluoroiodobenzene (2.12 g,
2JCF = 30 Hz), 141.6 (dd, JCF = 253 Hz, JCF = 72 Hz), 129.6 (ddd,
3
5
3
9.54 mmol), 10 ml of dry DMAC, Pd(PPh3)4 (0.5 g, 0.4 mmol,
5 mol%), 2(Z) (6.25 ml, 15 mmol, 2.4 M, 1.5 eq.) in dry DMAC,
and Cu(I)Br (1.4 g, 9.8 mmol) was stirred at 45 8C for 3 h. After silica
gel column chromatography (pentane, Rf = 0.46), removal of the
2JCF = 25 Hz, JCF = 7 Hz, JCF = 3 Hz), 125.3 (ddd, JCF = 9 Hz,
4JCF = 7 Hz, JCF = 2 Hz). GC–MS, m/z (relative intensity): 202 (M+,
4
100), 151 (31). FTIR (CCl4, cmÀ1): 1685 (m), 1410 (m), 1361 (m),
1227 (m), 1158 (vs), 1120 (s), 1089 (m). HRMS calcd for C10H6F4
202.0406, obsd. 202.0406.
solvent gave 1.39 g (89%) of a colorless liquid, GLPC purity: 96%. 19
F
3
3
NMR:
d
À111.1 (t, JHF = 5 Hz, 1 F), À166.3 (dd, JFF = 125 Hz,
3JHF = 5 Hz, 1 F), À175.0 (dd, JFF = 125 Hz, JHF = 75 Hz, 1 F). 1H
3 2
4.4.5. (E)-C6H5CF55CFH (8(E)-5)
NMR:
d
7.6 (ddm, 3JHH = 9 Hz, 3JHF = 5 Hz, 2 H), 7.3 (dd, 2JHF = 75 Hz,
Similarly, a mixture of iodobenzene (1.94 g, 9.51 mmol),
3JHF = 5 Hz, 1 H), 7.0 (dm, JHH = 9 Hz, 2 H). 13C NMR:
d
163.3 (dd,
Pd(PPh3)4 (0.34 g, 0.29 mmol, 5 mol%), 2(Z) (16 ml, 10.4 mmol,
0.65 M, 1.1 eq.) in dry DMAC, and Cu(I)Br (1.4 g, 9.8 mmol) was
stirred at 40 8C for 4 h. After silica gel column chromatography
3
1JCF = 250 Hz, JCF = 3 Hz), 151.4 (ddd, JCF = 229 Hz, JCF = 32 Hz,
5
1
2
5JCF = 1 Hz), 140.8 (ddd, JCF = 250 Hz, JCF = 73 Hz, JCF = 2 Hz),
1
2
6
3
3
2
127.6 (dd, JCF = 16 Hz, JCF = 8 Hz), 125.5 (ddd, JCF = 25 Hz,
(pentane), removal of the solvent gave 0.98 g (74%) of a colorless
4
2
4
3
3JCF = 6 Hz, JCF = 3 Hz), 115.9 (dd, JCF = 22 Hz, JCF = 2 Hz). GC–
MS, m/z (relative intensity): 158 (M+, 93), 157 (100), 138 (28), 127
(25), 107 (47). FTIR (CCl4, cmÀ1): 1607 (m), 1512 (s), 1370 (m),
1352 (m), 1240 (s), 1160 (m), 1148 (vs), 1102 (m). HRMS calcd for
C8H5F3 158.0343, obsd. 158.0345.
liquid, GLPC purity > 99%. 19F NMR:
d
À166.9 (dd, JFF = 125 Hz,
3JHF = 5 Hz, 1 F), À174.1 (dd, JFF = 125 Hz, JHF = 76 Hz, 1 F). 1H
3
2
3
NMR:
d
7.6 (d, JHH = 8 Hz, 2 H), 7.3–7.2 (m, partially overlapping
with peak at 7.19 ppm, 3 H), 7.2 (dd, 2JHF = 76 Hz, 3JHF = 5 Hz, 1 H).
1
2
13C NMR:
d 152.1 (dd, JCF = 229 Hz, JCF = 31 Hz), 141.1 (dd,
1JCF = 251 Hz, JCF = 73 Hz), 129.5 (d, JCF = 2 Hz), 129.4 (dd,
2
5
3
4
4.4.2. (E)-p-ClC6H4CF55CFH (8(E)-2)
2JCF = 24 Hz, JCF = 6 Hz), 128.8 (d, JCF = 2 Hz), 125.5 (dd,
4
Similarly,
a
mixture of 4-chloroiodobenzene (1.79 g,
3JCF = 8 Hz, JCF = 7 Hz). GC–MS, m/z (relative intensity): 140 (M+,
7.43 mmol, 99%), Pd(PPh3)4 (0.5 g, 0.5 mmol, 6 mol%), 2(Z)
(19 ml, 11.4 mmol, 0.60 M, 1.5 eq.) in dry DMAC, and Cu(I)Br
(1 g, 7 mmol) was stirred at room temperature for 1 h. After silica
gel column chromatography (pentane, Rf = 0.57), removal of the
solvent gave 1.23 g (95%) of a colorless liquid, GLPC purity > 99%.
100), 139 (35), 114 (27). FTIR (CCl4, cmÀ1): 3109 (m), 3064 (m),
1688 (m), 1497 (m), 1447 (m), 1358 (s), 1226 (m), 1149 (vs), 1101
(s). The spectroscopic data is in agreement with the reported
literature data [7].
19F NMR:
d
À167.0 (dd, 3JFF = 126 Hz, 3JHF = 5 Hz, 1 F), À172.7 (dd,
4.4.6. (E)-p-CH3OC6H4CF55CFH (8(E)-6)
2
3JFF = 126 Hz, JHF = 75 Hz, 1 F). 1H NMR:
d
7.5–7.1 (m, 5 H). 13C
Similarly, a mixture of 4-iodoanisole (1.17 g, 7.23 mmol, 99%),
Pd(PPh3)4 (0.6 g, 0.5 mmol, 7 mol%), 2(Z) (18 ml, 10.8 mmol,
0.60 M, 1.5 eq.) in dry DMAC, and Cu(I)Br (1.1 g, 7.7 mmol) was
stirred at 40 8C for 6 h. After silica gel column chromatography
1
2
NMR:
d 151.4 (dd, JCF = 228 Hz, JCF = 31 Hz), 141.3 (dd,
1JCF = 252 Hz, JCF = 72 Hz), 135.6 (d, JCF = 3 Hz), 129.1 (s), 127.7
2
5
2
3
3
4
(dd, JCF = 25 Hz, JCF = 6 Hz), 126.7 (dd as t, JCF and JCF = 8 Hz).

Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
85
(pentane/CH2Cl2 (9:2, v/v), Rf = 0.48), removal of the solvent gave
185 (M+, 100), 139 (44), 119 (80). FTIR (CCl4, cmÀ1): 1537 (s), 1351
(s), 1155 (vs). HRMS calcd for C8H5F2NO2 185.0288, obsd.
185.0274.
1.16 g (94%) of a slightly yellow liquid, GLPC purity: 100%. 19F
3
3
NMR:
3JFF = 125 Hz, 2JHF = 76 Hz, 1 F). 1H NMR:
7.2 (dd, 2JHF = 76 Hz, 3JHF = 5 Hz, 1 H), 6.8 (dm, 3JHH = 9 Hz, 2 H), 3.7
d
À166.2 (dd, JFF = 125 Hz, JHF = 5 Hz, 1 F), À177.3 (dd,
d
7.5 (dm, 3JHH = 9 Hz, 2 H),
4.4.10. (E)-p-NO2C6H4CF55CFH (8(E)-10)
5
1
(s, 3H). 13C NMR:
d
160.5 (d, JCF = 2 Hz), 152.1 (dd, JCF = 228 Hz,
Similarly, a mixture of 4-nitroiodobenzene (1.28 g, 5.04 mmol,
98%), Pd(PPh3)4 (0.15 g, 0.13 mmol, 3 mol%), 2(Z) (50 ml, 7.5 mmol,
0.15 M, 1.5 eq.) in dry DMAC, and Cu(I)Br (0.7 g, 4.9 mmol) was
stirred at room temperature for 20 min. After silica gel column
chromatography (pentane/CH2Cl2 (4:1, v/v)), removal of the
solvent gave 0.81 g (87%) of a white solid, mp 83–84 8C. 19F
2JCF = 32 Hz), 139.9 (dd, JCF = 248 Hz, JCF = 74 Hz), 127.0 (dd as t,
1
2
3JCF and JCF = 8 Hz), 121.8 (dd, JCF = 25 Hz, JCF = 6 Hz), 114.1 (d,
4JCF = 2 Hz), 55.1 (s). GC–MS, m/z (relative intensity): 170 (M+, 100),
155 (34). FTIR (CCl4, cmÀ1): 3007 (m), 2959 (m), 2936 (m), 2911
(m), 2838 (m), 1610 (s), 1577 (m), 1515 (s), 1464 (m), 1364 (m),
1303 (m), 1255 (s), 1225 (m), 1181 (s), 1145(vs), 1114 (s), 1036 (s).
HRMS calcd for C9H8F2O 170.0543, obsd. 170.0527.
4
2
3
NMR:
d
d
À166.9to À167.1 (2nd order NMR spectrum, 2F). {1H}19
F
3
NMR (
) À167.1 (s, 2F). 1H NMR:
d
8.3 (dm, JHH = 9 Hz, 2 H), 7.8
3
2
3
(dm, JHH = 9 Hz, 2 H), 7.5 (dd, JHF = 44 Hz, JHF = 35 Hz, 1 H). 13C
4.4.7. (E)-m-CF3C6H4CF55CFH (8(E)-7)
NMR:
d 150.0 (2nd order NMR spectrum), 147.9 (s), 143.1 (2nd
2
3
Similarly,
a
mixture of 3-iodobenzotrifluoride (1.94 g,
order NMR spectrum), 134.8 (dd, JCF = 11 Hz, JCF = 6 Hz), 126.0
3
4
7.13 mmol), Pd(PPh3)4 (0.4 g, 0.34 mmol, 5 mol%), 2(Z) (17 ml,
10.4 mmol, 0.61 M, 1.45 eq.) in dry DMAC, and Cu(I)Br (1 g, 7 mmol)
was stirred at 40 8C for 2 h. After silica gel column chromatography
(pentane), removal of the solvent gave 1.24 g (84%) of a colorless
(dd as t, JCF and JCF = 9 Hz), 123.9 (s). GC–MS, m/z (relative
intensity): 185 (M+, 100), 127 (47), 119 (95). FTIR (CCl4, cmÀ1):
1683 (m), 1602 (m), 1528 (s), 1347 (vs), 1320 (m), 1156 (s), 1114
(m). HRMS calcd for C8H5F2NO2 185.0288, obsd. 185.0287.
liquid, GLPC purity: 100%. 19F NMR:
d
À63.4 (s, 3 F), À167.6 (dd,
3JFF = 125 Hz, 3JHF = 5 Hz, 1 F), À171.6 (dd, 3JFF = 125 Hz, 2JHF = 75 Hz,
4.4.11. (E)-2-C4H3SCF55CFH (8(E)-11)
1 F). 1H NMR:
d
7.9 (s, 1 H), 7.7 (d, JHH = 8 Hz, 1 H), 7.5 (d,
Similarly, a mixture of 2-iodothiophene (1.80 g, 8.48 mmol,
99%), Pd(PPh3)4 (0.3 g, 0.3 mmol, 3 mol%), 2(Z) (20 ml, 12 mmol,
0.60 M, 1.4 eq.) in dry DMAC, and Cu(I)Br (0.7 g, 4.9 mmol) was
stirred at room temperature for 1 h. After silica gel column
chromatography (pentane), removal of the solvent gave 0.90 g
(73%) of a colorless liquid, GLPC purity > 99%. The product quickly
3
3JHH = 7.8 Hz, 1 H), 7.4 (dd as t, partially overlapping with peak at
7.3 ppm, 3JHH = 8 Hz, 1 H), 7.3 (dd, partially overlapping with peak at
2
3
7.4 ppm, JHF = 75 Hz, JHF = 5 Hz, 1 H). 13C NMR:
d 151.1 (dd,
2
1
2
1JCF = 229 Hz, JCF = 30 Hz), 142.3 (dd, JCF = 253 Hz, JCF = 71 Hz),
2
4
2
131.9 (qd, JCF = 33 Hz, JCF = 2 Hz), 130.5 (dd, JCF = 25 Hz,
3JCF = 6 Hz), 129.6 (d, JCF = 2 Hz), 128.8 (m), 126.3 (m), 124.6 (q,
decomposed to a dark residue at room temperature. 19F NMR:
d
3
1JCF = 272 Hz), 122.5 (qd, JCF = 8 Hz, JCF = 4 Hz). GC–MS, m/z
(relative intensity): 208 (M+, 100), 189 (21), 158 (16). FTIR (CCl4,
cmÀ1): 1316 (s), 1173 (s), 1153 (s), 1140 (s), 1075 (m). HRMS calcd
for C9H5F5 208.0311, obsd. 208.0294.
À161.1 (d, JFF = 125 Hz,
1
d
F), À172.3 (dd, JFF = 125 Hz,
3
3
3
3
2JHF = 75 Hz, 1 F). 1H NMR:
7.3 (m, 2 H), 7.2 (dd, JHF = 75 Hz,
2
3JHF = 3 Hz, 1 H), 7.0–6.9 (m, 1 H). 13C NMR:
d 149.8 (dd,
1JCF = 228 Hz, JCF = 37 Hz), 139.1 (dd, JCF = 250 Hz, JCF = 68 Hz),
2
1
2
2
3
130.5 (dd, JCF = 29 Hz, JCF = 8 Hz), 127.5–127.4 (m), 125.9 (dd,
3JCF = 6 Hz, JCF = 4 Hz). GC–MS, m/z (relative intensity): 146 (M+,
4
4.4.8. (E)-1-C10H7CF55CFH (8(E)-8)
Similarly, a mixture of 1-iodonaphthalene (1.27 g, 5.00 mmol),
Pd(PPh3)4 (0.15 g, 0.13 mmol, 3 mol%), 2(Z) (15 ml, 8 mmol,
0.53 M, 1.6 eq.) in dry DMAC, and Cu(I)Br (0.7 g, 4.9 mmol) was
stirred at 40 8C for 2.5 h. After silica gel column chromatography
(pentane/CH2Cl2 (4:1, v/v), Rf = 0.49), removal of the solvent gave
0.83 g (87%) of a slightly yellow liquid, GLPC purity > 99%. 19F
100). HRMS calcd for C6H4F2S 146.0002, obsd. 146.0004.
4.5. (E)-C6H4CF55CFH (8(E)-5) from a 94:6 isomeric mixture of (Z)-
and (E)-HFC55CFZnI (2(Z) and 2(E)) in the absence of Cu(I)Br
A two-neck 25-ml round bottom flask equipped with a Teflon-
coated stir bar, a cold water condenser attached to a nitrogen
source and a septum, was charged with (Z)- and (E)-1,2-
3
3
NMR:
d
À147.8 (d, JFF = 137 Hz, 1 F), À174.2 (dd, JFF = 137 Hz,
2JHF = 76 Hz, 1 F). 1H NMR:
d
7.2–8.0 (m). 13C NMR:
d
153.0 (dd,
1JCF = 237 Hz, JCF = 37 Hz), 140.8 (dd, JCF = 246 Hz, JCF = 71 Hz),
133.8 (d, 3JCF = 1 Hz), 131.1 (s), 130.9 (s), 128.6 (s), 128.5 (s), 127.1
(s), 126.4 (s), 125.7 (dd, JCF = 22 Hz, JCF = 4 Hz), 125.3 (d,
3JCF = 2 Hz), 125.0 (s). GC–MS, m/z (relative intensity): 190 (M+,
93), 189 (53), 188 (56), 170 (100). FTIR (CCl4, cmÀ1): 3053 (m),
1509 (m), 1348 (m), 1185 (m), 1165 (m), 1140 (vs). HRMS calcd for
difluoroethenylzinc iodide (Z:E = 94:6, 28.5 mmol, 15 ml, 1.9 M,
2.9 eq.) in dry DMAC, iodobenzene (2.00 g, 9.61 mmol), and
Pd(PPh3)4 (0.3 g, 0.26 mmol, 3 mol%). The reaction mixture was
stirred at 50 8C for 6 h. Only 60–65% 19F NMR yield of the product
was estimated. Additional reaction time (50 8C/2 h) did not
improve the conversion. Then the dark mixture was poured onto
a silica gel column and washed with pentane. Eluents with similar
UV-active TLC spots were combined and the majority of the
pentane was removed by simple distillation. Removal of the
remaining trace amount of solvent at À30 8C/1 mmHg yielded
0.59 g (41%) of a colorless liquid, GLPC purity = 95%. This product
exhibited 19F, 1H and 13C NMR spectra similar to the previously
prepared sample (4.4.5).
2
1
2
2
3
C12H8F2 190.0594, obsd. 190.0585.
4.4.9. (E)-m-NO2C6H4CF55CFH (8(E)-9)
Similarly, a mixture of 3-nitroiodobenzene (1.83 g, 7.27 mmol,
99%), Pd(PPh3)4 (0.3 g, 0.3 mmol, 4 mol%), 2(Z) (18 ml, 10.8 mmol,
0.60 M, 1.5 eq.) in dry DMAC, and Cu(I)Br (1 g, 7 mmol) was stirred
at room temperature for 1 h. After silica gel column chromatogra-
phy (CH2Cl2, Rf = 0.76), removal of the solvent gave 1.24 g (93%) of a
3
slightly yellow semi-solid. 19F NMR:
d
À167.1 (dd, JFF = 126 Hz,
4.6. Preparation of (Z)-1,2-difluoroethenyltributylstannane (12(Z))
3JHF = 5 Hz, 1 F), À169.6 (dd, JFF = 126 Hz, JHF = 74 Hz, 1 F). 1H
3
2
NMR:
d
8.4 (s, 1 H), 8.2 (d, 3JHH = 8 Hz, 1 H), 7.9 (d, 3JHH = 8 Hz, 1 H),
A one-neck 1-l round bottom flask equipped with a Teflon-
coated stir bar, cold-water condenser and nitrogen tee, was
charged with a 91:9 isomeric mixture of (Z) and (E)-1,2-
difluorotrimethylsilylethylenes (404 mmol, in hexanes), tributyl-
tin chloride (144 g, 424 mmol, 96%, 1.05 eq.), KF (27.0 g, 465 mmol,
1.15 eq.) and 700 ml of DMF. The solution was stirred at 80 8C for
1 h. Most of the low boiling point materials in the reaction mixture
7.6 (dd as t, partially overlapping with 7.5 ppm peak, 3JHH = 8 Hz, 1
2
3
H), 7.5 (dd, JHF = 74 Hz, JHF = 5 Hz, 1 H). 13C NMR:
d
149.9 (dd,
2
1
1JCF = 228 Hz, JCF = 29 Hz), 148.5 (s), 142.5 (dd, JCF = 254 Hz,
2JCF = 69 Hz), 130.9 (dd, JCF = 10 Hz, JCF = 7 Hz), 130.6 (dd,
2JCF = 26 Hz, 3JCF = 6 Hz), 129.9 (d, 4JCF = 2 Hz), 124.0 (d, 5JCF = 1 Hz),
120.2 (dd as t, 3JCF and 4JCF = 9 Hz). GC–MS, m/z (relative intensity):
3
4

86
Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
was removed by rotary evaporation. The resultant residue was
extracted with ether (5 Â 150 ml) and washed with 1 l
(5 Â 200 ml) of cold water. The organic layer was separated with
a separatory funnel and dried over anhydrous MgSO4. Most of the
solvent was removed by rotary evaporation. The resultant residue
was eluted with hexanes through a silica gel column. Fractions
with similar Rf values were combined. The solvent was removed at
RT/1 mmHg. Vacuum distillation of the residue yielded 94.68 g
(67%) of a colorless liquid, GLPC purity = 99% (Z:E = 93:7), bp 76–
78 8C/0.1 mmHg. The colorless liquid was further eluted with
hexanes through a silica gel column. Fractions with similar Rf
values were collected. Most of the solvent was removed by rotary
evaporation. Removal of the remaining solvent at 20 8C/0.1 mmHg
yielded a colorless liquid, GLPC purity > 99% (Z: 97%, E: 3%). This
product has 19F, 1H and {1H}13C NMR spectra similar to the
alternatively prepared sample [20].
(0.70 g, 1.9 mmol, 96%, 1.1 eq.), Pd(PPh3)4 (0.05 g, 0.04 mmol,
2 mol%), and Cu(I)I (0.12 g, 0.63 mmol) was stirred at room
temperature for 1 h. The reaction mixture was washed with
aqueous KF (4 Â 50 ml) and water (5 Â 25 ml), then was extracted
with ether (4 Â 30 ml). The combined ether layers were dried over
anhydrous MgSO4. MgSO4 was then filtered via gravity filtration.
Removal of the solvent via rotary evaporation yielded a solid,
which was eluted with CH2Cl2 through a silica gel column; Rf = 0.6.
Most of the solvent was removed via rotary evaporation. Removal
of the remaining solvent at À10 8C/1 mmHg yielded 0.25 g (83%) of
a light yellow solid. 19F NMR:
NMR spectrum); {1H}19
NMR:
d
À167.5 to À168.5 ppm (2nd order
F
d
À167.8 (d, AB pattern,
3
3JFF = 125 Hz, 1 F), À168.2 (d, AB pattern, JFF = 125 Hz, 1 F); 1H
4
5
4
NMR:
d 7.8 (distorted d, JHF or JHF = 9 Hz, 2 H), 7.7 (d, JHF or
5JHF = 9 Hz, 2 H), 7.4 (dd, 2JHF = 50 Hz, 3JHF = 30 Hz, 1 H); 13C NMR:
d
150.0 (2nd order NMR spectrum), 142.7 (2nd order NMR
spectrum), 133.1 (dd, 2JCF = 16 Hz, 3JCF = 2 Hz), 132.6 (d,
3
4
4.7. General procedure for the preparation of (E)-
a
,
b
-
4JCF = 2 Hz), 125.6 (dd as t, JCF = 9 Hz, JCF = 9 Hz), 118.3 (s),
112.8 (d, 5JCF = 1 Hz); GC–MS, m/z (relative intensity): 166 (8), 165
(M+, 100); FTIR (CCl4, cmÀ1): 2232 (m), 1683 (m), 1509 (m), 1407
(m), 1361 (m), 1156 (vs); HRMS calcd for C9H5F2N 165.0390, obsd
165.0394.
difluorostyrenes 8(E) from (Z)-HFC55CFSn(CH2CH2CH2CH3)3 (12(Z))
A one-neck 25-ml round bottom flask equipped with a Teflon-
coated stir bar and a nitrogen tee, was charged with 15 ml of dry
DMF, aryl iodide (7.07 mmol, 99% purity), 12(Z) (3.97 g,
11.3 mmol, 1.5 eq.), Pd(PPh3)4 (0.3 g, 0.3 mmol, 5 mol%), and Cu(I)I
(1.0 g, 5.2 mmol). The reaction mixture was stirred at room
temperature to 70 8C for 1–3 h. 19F NMR analysis of the reaction
4.7.4. (E)-2-C5H4NCF55CFH (8(E)-14)
Similarly, a mixture of dry DMF (10 ml), 2-iodopyridine (1.58 g,
99%, 7.6 mmol), (Z)-1,2-difluoroethenyltributylstannane (3.10 g,
8.4 mmol, 96.5%, 1.1 eq.), Pd(PPh3)4 (0.44 g, 0.38 mmol, 5 mol%),
and Cu(I)I (1.5 g, 7.9 mmol, 1 eq.) was stirred at room temperature
for 1 h. The reaction mixture was poured directly onto a silica gel
column and eluted with CH2Cl2; Rf = 0.2. Most of the solvent was
removed via rotary evaporation. Removal of the remaining solvent
at À10 8C/1 mmHg yielded 0.23 g (21%) of a colorless liquid. The
product quickly decomposed to a dark residue at room tempera-
mixture showed the formation of 8(E); GC–MS of
a pre-
chromatographed reaction mixture showed the complete disap-
pearance of the aryl iodide. The dark reaction mixture was poured
directly onto a silica gel column and eluted with pentane. Eluents
with similar UV-active TLC spots were combined and the majority
of the pentane was removed by simple distillation. Removal of the
remaining trace amount of solvent at À35 8C/1 mmHg yielded 8(E).
ture. 19F NMR:
d
À169.2 (dd, 3JFF = 127 Hz, 2JHF = 67 Hz, 1 F), À169.9
4.7.1. (E)-p-BrC6H4CF55CFH (8(E)-3)
(dd, 3JFF = 127 Hz, 3JHF = 13 Hz, 1 F); 1H NMR: 8.7 (d, 3JHH = 5 Hz, 1
d
Similarly, a mixture of DMF (15 ml), 4-bromoiodobenzene
(2.05 g, 7.1 mmol, 99%), (Z)-1,2-difluoroethenyltributylstannane
(3.97 g, 11.3 mmol, 1.5 eq.), Pd(PPh3)4 (0.3 g, 0.3 mmol, 5 mol%),
and Cu(I)I (1.0 g, 5.2 mmol) was stirred at 70 8C for 3 h. After silica
gel column chromatography (pentane, Rf = 0.6), removal of the
solvent at À10 8C/1 mmHg gave 1.41 g (92%) of a colorless liquid,
GLPC purity = 100%. The product exhibited 19F, 1H and 13C NMR
spectra similar to the previously prepared sample (Section 4.4.3).
H), 7.7 (ddd as dt, 3JHH = 8 Hz, 5JHF = 1 Hz, 1 H), 7.6 (d, 3JHH = 8 Hz, 1
H), 7.5 (dd, partially overlapping with the peak at 7.6 ppm,
3
3
3
2JHF = 67 Hz, JHF = 13 Hz, 1 H), 7.2 (ddd, JHH = 8 Hz, JHH = 5 Hz,
6JHF = 1 Hz, 1 H); 13C NMR:
149.8(d, 4JCF = 1 Hz), 148.3 (dd, 2JCF = 20 Hz, 3JCF = 3 Hz), 142.9 (2nd
order NMR spectrum), 136.6 (d, JCF = 2 Hz), 123.8 (d, JCF = 1 Hz),
121.7 (dd, 3JCF = 9 Hz, 4JCF = 4 Hz); GC–MS, m/z (relative intensity):
142(8), 141 (M+, 100), 140 (16), 122 (30), 114(14).
d 150.6 (dd, JCF = 196 Hz, JCF = 5 Hz),
1
2
4
5
4.7.2. (E)-m-ClC6H4CF55CFH (8(E)-12)
4.8. Attempted preparation of 8(E)-6 from 12(Z)
Similarly, a mixture of DMF (10 ml), 3-chloroiodobenzene
(1.38 g, 5.7 mmol, 98%), (Z)-1,2-difluoroethenyltributylstannane
(2.17 g, 5.95 mmol, 96.5%, 1.05 eq.), Pd(PPh3)4 (0.3 g, 0.26 mmol,
5 mol%), and Cu(I)I (1.0 g, 5.2 mmol) was stirred at room
temperature for 1 h. After silica gel column chromatography
(pentane), removal of the solvent at À10 8C/1 mmHg gave 0.83 g
A one-neck 25-ml round bottom flask equipped with a Teflon-
coated stir bar and a nitrogen tee, was charged with 10 ml of dry
DMF, 4-iodoanisole (1.70 g, 7.3 mmol), 12(Z) (2.93 g, 8 mmol,
1.1 eq.), Pd(PPh3)4 (0.4 g, 0.3 mmol, 5 mol%) and Cu(I)I (1.5 g,
7.9 mmol, 1 eq.). The reaction mixture was stirred at 60 8C for 6 h.
19F NMR analysis of the reaction mixture showed the formation of
the 8(E)-6 (60% NMR yield) and about 30% of unreacted 12(Z); GC–
MS analysis of a pre-chromatographed reaction mixture also
showed a significant amount of unreacted 4-iodoanisole.
(82%) of a colorless liquid, GLPC purity = 97%. 19F NMR:
d
À167.2
3
3
3
(dd, JFF = 125 Hz, JHF = 5 Hz, 1 F), À171.9 (dd, JFF = 125 Hz,
2JHF = 75 Hz, 1 F); 1H NMR:
d
7.6 (s, broad, 1 H), 7.5 (m, 1 H), 7.3
2
3
(dd, partially overlapping, JHF = 75 Hz, JHF = 5 Hz, 1 H), 7.3 (m, 2
H); 13C NMR:
d 150.5 (dd, JCF = 229 Hz, JCF = 31 Hz), 141.5 (dd,
1
2
1JCF = 253 Hz, JCF = 72 Hz), 134.6 (d, JCF = 2 Hz), 130. 7 (dd,
2
4
Acknowledgment
2JCF = 25 Hz, JCF = 6 Hz), 129.9 (d, JCF or JCF = 2 Hz), 129.4 (d,
3
4
5
4JCF or 5JCF = 2 Hz), 125.3 (dd as t, 3JCF = 9 Hz, 4JCF = 8 Hz), 123.3 (dd
We would like to thank the National Science Foundation for
financial support of this work.
3
4
as t, JCF = 9 Hz, JCF = 8 Hz); GC–MS, m/z (relative intensity):
176(27), 174 (M+, 100), 139 (65); HRMS calcd for C8H535ClF2
174.0048, obsd 174.0060.
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(0.42 g,
1.8 mmol),
(Z)-1,2-difluoroethenyltributylstannane

Q. Liu, D.J. Burton / Journal of Fluorine Chemistry 132 (2011) 78–87
87
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