Approaches to the preparation of (Z)-1,2-difluorostilbenes

Article abstract of DOI:10.1016/j.jfluchem.2010.07.003

Methodology directed at the preparation of (Z)-1,2-difluorostilbenes has been evaluated. For symmetrical (Z)-1,2-difluorostilbenes, photochemical isomerization of the isomeric (E)-1,2-difluorostilbenes, and HPLC separation of the mixture of stilbene isome

Full text of DOI:10.1016/j.jfluchem.2010.07.003

Journal of Fluorine Chemistry 131 (2010) 989–995
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Approaches to the preparation of (Z)-1,2-difluorostilbenes§
*
Donald J. Burton , C.A. Wesolowski, Qibo Liu, Charles R. Davis
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
Methodology directed at the preparation of (Z)-1,2-difluorostilbenes has been evaluated. For
symmetrical (Z)-1,2-difluorostilbenes, photochemical isomerization of the isomeric (E)-1,2-difluor-
ostilbenes, and HPLC separation of the mixture of stilbene isomers is a reasonable route to a particular
(Z)-stilbene. An alternative approach to both symmetrical and/or unsymmetrical (Z)-1,2-difluoros-
tilbenes has been developed via stereospecific Pd(0) coupling of (E)-1,2-difluoro-aryl-ethenyltributyl-
stannanes under Stille-Liebiskind conditions with aryl idodies. The requisite arylstannanes can be
obtained via the reported route developed by Davis or via (E)-1,2-difluorovinyltributylstannane – a new
route described in this work. The methodology tolerates almost any functionality in the aryl ring, is easily
carried out, is stereospecific and provides the first general route to (Z)-1,2-difluorostilbenes.
ß 2010 Elsevier B.V. All rights reserved.
Received 18 May 2010
Received in revised form 29 June 2010
Accepted 6 July 2010
Available online 15 July 2010
Keywords:
(Z)-1,2-difluorostilbenes
Photochemical isomerization
Pd cross-coupling reactions
(E)-1,2-difluorovinylstannanes
(Z,Z)-1,2,3,4-tetrafluoro-1,3-butadienes
1. Introduction
The yields are modest (ꢁ50%). Russian workers reported this
same compound via the methodology outlined in Eq. (2) [6]. This
1,2-Difluorostilbenes have been of interest to organic chemists
for several decades. These compounds have been tested and/or
utilized in liquid crystal applications [1,2]. Poly(arylenevinylene)s
with fluorinated vinylene units have also recently been investi-
gated for fine-tuning of the electrical and optical properties in
organic light-emitting diodes (OLEDs), and these polymers show
the most bluefield photoluminescence emission in the solid state
reported to date for poly(p-phenylenevinylene)s [3]. More
recently, (E)-1,2-Difluorostilbenes have been demonstrated to be
promising materials for high dielectric biaxiality ferroelectric
mixtures [4].
route avoids the use of C2F4 and low temperatures.
(2)
Unsymmetrical (E)-1,2-difluorostilbenes have been prepared
via the reaction of trifluorostyrenes and aryllithiums, Eq. (3) [1,2].
Most of the reported work with 1,2-difluorostilbenes has been
accomplished with the (E)-isomer. Dixon first reported the
preparation of (E)-1,2-difluorostilbene via the reaction of tetra-
fluoroethene with phenyllithium in ether at ꢀ60 8C [5], Eq. (1).
(3)
Initially, this methodology was somewhat limited due to the
lack of a high yield method for the synthesis of suitable styrene
precursors. However, recent reports have detailed useful routes to
trifluorostyrene and substituted trifluorostyrenes [7–10] and this
route has become a more useful approach to unsymmetrical (E)-
1,2-difluorostilbenes.
(1)
As noted above, the symmetrical (E)-1,2-difluorostilbenes have
been most commonly prepared from C2F4 and aryllithiums. The
yields via this approach are modest, functionality in the
aryllithiums is limited, and generally the stilbene is accompanied
by more highly substituted vinyl derivatives. To circumvent the
multiple substitution problem, the limitation of aryl functionality
§
Preliminary reports of this work were presented at the ACS Winter Fluorine
Conference, St. Petersburg Beach, FL, January 2005; the 19th International
Symposium on Fluorine Chemistry, Jackson Hole, WY, August 2009; and the
44th Midwest ACS Regional Meeting, Iowa City, IA, Abstr. #310, October 2009.
* 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.2010.07.003

990
D.J. Burton et al. / Journal of Fluorine Chemistry 131 (2010) 989–995
in the lithium reagent, and to avoid the use of C2F4 and low
temperatures, we recently reported a highly efficient stereospecific
route to (E)-1,2-difluorostilbenes via the palladium coupling of (E)-
(1,2-difluoro-1,2-ethenediyl)bis [tributylstannane] with aryl
iodides, as illustrated in Eq. (4) [11].
biacetyl(photosensitizer) with a 200 W mercury lamp [13] to give
a 75/25 isomeric mixture of Z/E isomers. Since our recent
methodology provided a high yield, short route to symmetrical
(E)-1,2-difluorostilbenes [11], we were prompted to evaluate this
route as a useful entry to the corresponding symmetrical (Z)-
stilbenes. Recent advances in HPLC separation would immensely
aid this approach. Thus, we prepared (E)-(1,2-difluoro-1,2-
ethenediyl)bis[4-methoxybenzene] via the literature procedure
[11]. Subsequent photochemical isomerization (254 nm, RT,
quartz tube, CDCl3, Rayonet UV Chamber, 1 h) was accompanied
(4)
by a new singlet at
d
ꢀ129 ppm [(Z)-stilbene] in the 19F NMR
spectrum. After 1 h the ratio of (Z/E) stilbenes was 2.9/1. Further
irradiation did not change this ratio, Eq. (8). The two stilbene
isomers could not be effectively separated by column chroma-
tography, pentane eluant, [Rf(Z) = 0.5; Rf(E) = 0.6]. Therefore, the
crude product was separated by HPLC (CH3CN solvent) [16].
Removal of the solvent provided a 41% isolated yield of a colorless
oil, identified via 19F NMR, 1H NMR, 13C NMR and HRMS as (Z)-1,2-
difluoro-1,2-ethenediyl)bis[4-methoxybenzene], 3 (cf. Experi-
mental). The facile preparation of the (E)-stilbene makes this
route practical for the preparation of an individual (Z)-1,2-
difluorostilbene, but is somewhat tedious for the preparation of a
series of (Z)-1,2-difluorostilbenes. However, we can recommend
this route for any researcher interested in a particular symmetri-
cal (Z)-1,2-difluorostilbene. Subsequently, we investigated alter-
native methodology that would employ a common precursor to a
series of (Z)-1,2-difluorostilbenes.
The bis[stannane] precursor is readily prepared in two steps from
chlorotrifluoroethene [12]. The isolated yields are high and the
methodology avoids the use of C2F4, tolerates a wider variety of
functional groups than the organolithium approach and employs a
cheap, safe olefin precursor.
In contrast to the extensive work on the preparation of (E)-1,2-
difluorostilbenes, little progress has been made on synthetic routes
to the isomeric (Z)-1,2-difluorostilbenes. The only route to this
isomeric analog has been via the photochemical isomerization of
the (E)-1,2-difluorostilbene [13], Eq. (5). This methodology
generally produces a mixture of (E)- and (Z)-isomers, which were
separated chromatographically.
(5)
2. Results and discussion
In the initial approach to a more general route to (Z)-1,2-
difluorostilbenes we focused on several synthetic methods to
evaluate routes that would accomplish our overall objective –
namely, the successful preparation of (Z)-1,2-difluorostilbenes (both
symmetricaland unsymmetricalanalogues). We have not attempted
to prepare an extensive list of the (Z)-stilbenes; instead we have
attempted to develop a proof of principle to this class of compounds
that would allow others to prepare the (Z)-stilbene of their choice.
(8)
2.1. (Z)-(1,2-Difluoro-1,2-ethenediyl)bis[tributylstannane], 2
2.3. Preparation of (E)-1,2-difluoro-2-aryl-tributylstannylethenes
The successful preparation of (E)-1,2-difluorostilbenes via Pd(0)
coupling of aryl iodides with (E)-Bu3SnCF = CFSnBu3 [11]
prompted us to investigate the viability of this approach for the
synthesis of the corresponding (Z)-stilbenes. Thus, we prepared the
requisite (Z)-(1,2-difluoro-1,2-ethenediyl)bis[tributylstannane] in
modest yield as outlined below in Eqs. (6) and (7) [14,15].
Recently, we reported a stereospecific route to (E)-1,2-difluoro-
2-aryl-tributylstannylethenes from (Z)-1,2-difluorostyrenes [17],
Eq. (9).
(6)
(9)
Since McCarthy had reported the successful preparation of (Z)-
1-fluoro-1,2-diphenylpropene via Stille coupling of (E)-1-fluoro-2-
phenyl-propenyltributylstannane, Eq. (10) [18,19], and we had
observed successful Stille-Liebeskind cross-coupling reactions of
(Z)-1,2-difluoro-1-tributylstannyl-1-propene with (Z)-1-bromo-1-
fluorostyrene, Eq. (11) [20], arylation of [(E)-1,2-difluoro-2-aryl-
tributylstannylethenes] seemed a potentially useful route to (Z)-
1,2-difluorostilbenes [21]. The co-catalysis (Liebeskind conditions)
[22] of Cu(I)I and Pd(PPh3)4 enhanced the overall yield of the
reaction and minimized side product(s) formation [18,19].
(7)
Attempted coupling of 2 with aryl iodides, such as 1-iodo-4-
nitrobenzene and 4-iodoanisole, under conditions similar to the
successful preparation of the (E)-stilbenes. Pd(PPh3)4/Cu(I)I/DMF
failed to yield any (Z)-stilbene and extensive decomposition of 2
was noted. Thus, this synthetic route was not investigated further.
2.2. Photochemical isomerization
(10)
As noted above, Chinese workers had reported the photo-
chemical isomerization of (E)-1,2-difluorostilbene in benzene and

D.J. Burton et al. / Journal of Fluorine Chemistry 131 (2010) 989–995
991
Two representative examples of 4 were selected to test the
proof of principle of our overall approach. The m-CF3 and the p-
OMe analogs [25] were converted to the corresponding vinyl-
stannanes as illustrated below, Eq. (15).
(11)
To test this idea, Davis [21] reacted (E)-1,2-difluoro-2-(4-
carboethoxyphenyl)tributylstannylethene with iodobenzene with
Pd(0) catalysis, Eq. (12) [21]. A 70% yield (19F NMR) of the (Z)-1,2-
difluorostilbene was obtained, along with 15% p-EtO2CC6H4CF =
CFH and 15% others. Wesolowski subsequently investigated this
reaction further employing Cu(I)I co-catalysis to improve the
overall yield and selectivity [23].
(15)
Subsequent Stille cross-coupling of our model substrates under
Liebeskind conditions stereospecifically afforded the (Z)-1,2-
difluorostilbenes in excellent yields, Eqs. (16) and (17).
(12)
(16)
The requisite (E)-1,2-difluoro-2-aryl-tributylstannylethenes
can be readily prepared by the method reported by Davis and
Burton [17], as outlined in Eq. (13). This method works well and
stereospecifically permits preparation of a variety of (E)-stannanes.
The limiting step in this route is the synthesis of the (E)-CFH = CFI.
Thus, we investigated an alternative precursor to the same (Z)-1,2-
difluorostyrenes, 4. Since we have demonstrated that fluorinated
vinylsilanes can be easily converted (stereospecifically) to
fluorinated vinylstannanes [14], we studied the use of (E)-(1,2-
difluorovinyl)tributylstannane as an alternative to (E)-CFH=CFI.
(17)
(13)
(E)-(1,2-difluorovinyl)tributylstannane, 1, is readily prepared in
high yield as outlined in Eq. (14). The vinylsilane, 5, is readily
prepared via our published methodology [24].
Thus, as illustrated above, arylation of (E)-1,2-difluoro-2-aryl-
tributylstannylethenes provides
a useful synthetic route to
functionalized (Z)-1,2-difluorostilbenes [26].
(14)
Table 1
Stille cross-coupling reactions of 1 with aryl iodides.
[DT$INLE]
Retrosynthetic analysis for the preparation of (Z)-1,2-difluor-
ostilbenes is outlined in Scheme 1.
To evaluate the utility of 1 for the preparation of (Z)-1,2-
difluorostyrenes, 1 was cross-coupled with several aryl iodides
under Stille-Liebeskind conditions. These results are summarized
in Table 1.
Entry
X
Yield (%)a
1
2
3
4
p-C(O)CH3
p-OMe
m-CF3
75
92
74
66
p-CH3
a
Scheme 1. Retrosynthetic analysis for the preparation of (Z)-1,2-difluorostilbenes.
Isolated yields.

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D.J. Burton et al. / Journal of Fluorine Chemistry 131 (2010) 989–995
2.4. (Z,Z)-1,2,3,4-tetrafluoro-1,3-butadienes
the electron impact mode using a DB-1 column (0.25 mm
ID ꢂ 15 m). High resolution mass spectra were obtained by the
University of Iowa High Resolution Mass Spectrometry Facility.
Analytical GLPC were performed on a Hewlett–Packard Model
5890 equipped with a thermal conductivity detector and 3393A
integrator. The column was packed with 5% OV-101 on chromo-
sorb P. Flash column chromatography was carried out as described
by Still et al. [28]. All melting points were determined in a 1.2 mm
capillary tube in a Thomas–Hoover Unimelt apparatus and are
uncorrected. DMF was dried overnight over CaH2, then distilled at
reduced pressure. Aryl iodides, stannane precursors, and routine
commercial chemicals were used as received. Pd(PPh3)4 was
prepared by Coulson’s procedure [29]. Cu(I)I iodide (Aldrich) was
purified by continuous extraction with anhydrous THF in a Soxhlet
extraction apparatus as described by Posner [30]. Potassium
fluoride and copper (II) acetate were dried by azeotropic
distillation with benzene solvent and a Dean-Stark apparatus.
Residual benzene was removed under reduced pressure.
In earlier work with fluorinated vinylstannanes, we had
developed
a useful procedure for the copper (II) mediated
homocoupling of 1,2-difluorovinylstannanes [27]. Unfortunately,
at that time, only one (Z,Z)-1,2-difluorovinylstannane was
available to us. Since the (Z,Z)-1,2-difluorovinylstannanes, 6 and
8 were available to us in this work, we also reacted these
vinylstannanes with Cu(II)(OAc)2 and isolated modest yields of the
respective, (Z,Z)-1,2,3,4-tetrafluoro-1,3-butadienes, as illustrated
in Eq. (18).
(18)
4.2. Preparation of (E)-(1,2-difluorovinyl)tributylstannane, 1
3. Conclusions
A
250 ml two-neck flask, equipped with a stir bar, a
Symmetrical (E)-1,2-difluorostilbenes can be photoisomerized
at 254 nm in ꢁ1 h to provide a mixture of (E)- and (Z)-1,2-
difluorostilbenes significantly enriched in the (Z)-isomer. HPLC
separation of these isomers provides a modest yield of pure
symmetrical (Z)-1,2-difluorostilbenes. Since the (E)-1,2-difluoros-
tilbenes can be readily prepared in high yield and wide tolerance of
functionality in one step from (E)-Bu3SnCF = CFSnBu3, this route is
a convenient route to an individual (Z)-1,2-difluorostilbene of the
researcher’s choice. An alternative approach to both symmetrical
and/or unsymmetrical (Z)-1,2-difluorostilbenes has been devel-
oped via stereospecific Pd(0) coupling of (E)-1,2-difluoro-aryl-
ethenyltributylstannanes under Stille-Liebeskind conditions with
aryliodides. The requisite stannanes can be easily accessed from
substituted (Z)-1,2-difluorostyrenes either via the reported route
starting from (E)-HCF = CFI or via (E)-(1,2-difluorovinyl)tributyl-
stannane – an alternative method developed in this work. Thus,
any type of (E)- or (Z)-1,2-difluorostilbene can now be readily
accessed.
thermometer, and a cold-water condenser attached to a nitrogen
inlet adapter was charged with 1.10 g (19.0 mmol) of anhydrous
potassium fluoride, 34.0 g (57 mmol) of bis(tributyltin)oxide and
60 ml of dry DMF. The flask was immersed in a 5-10 8C water bath,
and 15.0 g (110 mmol) of (E)-(1,2-difluorovinyl)trimethylsilane
was added via a syringe over 10 min. The cold bath was removed
and the mixture was stirred for 2 h at room temperature, then for
12 h at 50 8C. Then, the reaction mixture was transferred to a
500 ml separatory funnel and partitioned between 150 ml of
hexanes and 40 ml H2O. The aqueous layer was extracted with
40 ml of hexanes, the hexanes layer combined and washed with
40 ml H2O; the organic layer dried over MgSO4 and concentrated
by rotary evaporation. The crude vinylstannane was purified by
distillation under reduced pressure through a jacketed short-path
Vigreux column to give 36.5 g (94%) of 1, bp. 96–97 8C/0.3 mm Hg,
2
3
GLPC = 100%. 19F NMR:
d
ꢀ143.0 (dd, JHF = 77.3 Hz, JFF = 9.2 Hz),
3
3
ꢀ147.1 (dd, JHF = 25.6 Hz, JFF = 9.5 Hz); 19F {1H} NMR:
d
ꢀ143.0
(d, JFF = 8.4 Hz), ꢀ147.1 (d, JFF = 9.0 Hz); 1H NMR =
d 5.96 (dd,
3
3
3
2
In addition to the development of approaches to (Z)-1,2-
difluorostilbenes, the (Z)-1,2-difluoro-aryl-ethenyltributylstan-
nanes used herein can be readily stereospecifically converted to
(Z,Z)-1,2,3,4-tetrafluoro-1,3-butadienes.
2JHF = 77.2 Hz, JHF = 25.7 Hz, 1H) 5.96 (ddd, JHF = 77.3 Hz,
3JHF = 25.6 Hz). JHSn = 4.2 Hz, 1.48–1.60 (m, 6H), 1.32 (sextet,
3
3JHH = 7.4 Hz, 6H), 1.00–1.08 (m, 6H), 0.90 (t, 3JHH = 7.3 Hz, 9H); 13
C
1
2
NMR:
d 154.9 (dd, JCF = 313.2 Hz, JCF = 7.3 Hz), 141.7 (dd,
2
3
1JCF = 282.4 Hz, JCF = 7.1 Hz), 28.9 (s), 28.9 (d, JCSn = 22.0 Hz).
27.2 (s), 27.2 (d, 2JCSn = 28.9 Hz), 13.7 (s), 10.0 (d, 1JCSn = 347.2 Hz).
GC-MS, m/z (relative intensity): 297 (71), 296 (M+-C4H9, 23), 295
(54), 241 (100).
4. Experimental
4.1. General experimental procedures
Routine 19F NMR spectra were recorded on a JEOL FX90Q
Spectrometer (83.81 MHz) and high resolution data was obtained
on a Bruker AC-300 Spectrometer (282.41 MHz). Chemical shifts
have been reported in ppm relative to internal CFCl3. Spectra of
reaction mixtures were obtained in the 7Li external lock mode.
Quantitative determinations were carried out by integration
relative to internal benzotrifluoride. Unless noted otherwise,
CDCl3 was used as the NMR lock solvent. Routine 1H NMR
(300.17 MHz) spectra and high resolution data were generally
obtained on a Bruker AC-300 Spectrometer. Chemical shifts have
been reported in ppm relative to internal TMS. Unless otherwise
noted, CDCl3 was used as the NMR lock solvent. High resolution
4.3. Photochemical isomerization of (E)-(1,2-difluoro-1,2-
ethenediyl)bis[40-methoxybenzene]
A quartz NMR tube was charged with 13.7 mg (0.050 mmol) of
(E)-(1,2-difluoro-1,2-ethenediyl)bis[40-methoxybenzene]
in
0.6 ml CDCl3. The reaction solution was shaken manually until it
became homogeneous. Then, the reaction solution was irradiated
at 254 nm in a Rayonet UV chamber at ambient temperature for
1 h. 19F NMR analysis of the reaction mixture indicated the
formation of a new singlet at ꢀ129 ppm, which was later identified
as (Z)-(1,2-difluoro-1,2-ethenediyl)bis[4’methoxybenzene] 3. The
ratio of the two isomers (Z/E) was 2.9/1. Further irradiation did not
change the ratio. The reaction mixture was poured onto a silica gel
column and eluted with a mixture of pentane and ether, Rf(Z) = 0.5,
Rf(E) = 0.6. However, efficient separation of the two isomers could
not be achieved. After recovery of the crude product mixture, the
two isomers were separated by HPLC (elution with CH3CN) [16].
{1H} 13C NMR spectra were recorded on
a Bruker AC-300
Spectrometer (75.48 MHz). Chemical shifts have been reported
in ppm relative to internal TMS. Unless otherwise noted, CDCl3 was
used as the NMR lock solvent. Low resolution mass spectra were
obtained using a TRIO-1 GC–MS instrument operated at 70 ev in

D.J. Burton et al. / Journal of Fluorine Chemistry 131 (2010) 989–995
993
Removal of the solvent at RT/1 mm Hg gave 4.8 mg (41%) of a
46–47 8C. The spectroscopic data (19F, 1H, 13C NMR, GC–MS) were
in good agreement with the data reported by Davis and Burton
[17].
colorless oil [(Z)-stilbene] 3. 19F NMR:
d
ꢀ129.4 (s, 2F); 1H NMR:
d
7.26 (dm, 3JHH = 9 Hz, 4H), 6.81 (dm, 3JHH = 9 Hz, 4H), 3.80 (s, 6H);
13C NMR:
d
160.2 (s), 144.6 (dd, 1JCF = 246.2 Hz, 2JCF = 22 Hz), 129.5
(overlapping dd, 2JCFꢁ JCF = 3.6 Hz), 122.6 (2nd order spectrum due
to virtual coupling), 113.9 (s), 55.3 (s). FTIR (CCl4, cmꢀ1): 1609 (m),
1515 (s), 1298 (m), 1252 (vs), 1176 (m), 1029 (s). GC–MS, m/z
(relative intensity): 276 (M+, 100), 261 (80), 201 (24.7), 189 (13.9):
4.7. Preparation of (Z)-1-(1,2-difluorovinyl)-4-(methyl)benzene
3
Similar to 4.4, 35 ml dry DMF, 0.5 g (0.4 mmol) of Pd(PPh3)4,
4.36 g (20.0 mmol) of 4-iodotoluene, 1.90 g (20.0 mmol) of Cu(I)I
and 8.47 g (24.0 mmol) of 1 gave a crude residue which was
distilled at partial pressure through a jacketed short-path Vigreux
column to give 2.17 g (70%) of (Z)-1-(1,2-difluorovinyl)-4-
(methyl)benzene as a clear, colorless, liquid (containing ꢁ5%
DMF impurity). This material was further purified by silica gel
chromatography (pentane, Rf = 0.37) to yield 2.02 g (66%) of the
titled compound as a clear, colorless liquid, bp 65 8C/4 mm Hg. The
spectroscopic data (19F, 1H, 13C NMR, GC–MS) were in good
agreement with the data reported by Davis and Burton [17].
UV (CHCl3): 299 nm (
ꢀ1); HRMS: calc’d for C16H14F2O2: 276.0962; found: 276.0960.
e e
= 6150 cmꢀ1 Mꢀ1), 248 ( = 5525 cmꢀ1
M
4.4. Preparation of (Z)-1-(1,2-difluorovinyl)-(4-(methoxy)benzene)
A 100 ml two neck flask equipped with a stir bar, water
condenser, rubber septum, and nitrogen inlet adapter was charged
sequentially with 3.24 g (13.9 mmol) of p-iodoanisole, 1.32 g
(6.93 mmol) of Cu(I)I, 0.32 g (0.28 mmol) of Pd(PPh3)4 and 20 ml of
dry DMF. After stirring the mixture for 5 min, the flask was
immersed in a 10 8C water bath and 6.35 g (18.0 mmol) of 1 was
added via syringe over 10 min. The black mixture was stirred for
24 h at 35–40 8C. Then, the reaction mixture was diluted with
20 ml of Et2O, treated with 2.0 g (34 mmol) of KF and dissolved in
15 ml of H2O. The mixture was stirred for 15 min, the white
precipitate (Bu3SnF) was removed by filtration through a coarse-
fritted funnel. The filtrate was transferred to a 250 ml separatory
funnel containing 100 ml H2O and 50 ml Et2O. The aqueous layer
was extracted with 2 ꢂ 30 ml Et2O and the combined ether
extracts were washed with 20 ml brine, dried over MgSO4, and
concentrated by rotary evaporation. Purification by silica gel
chromatography (5% ethyl acetate in hexane, Rf = 0.23) afforded
2.16 g (92%) of the titled compound, GLPC = 100% as a clear,
yellowish oil. The spectroscopic data obtained (19F, 1H, 13C, GC–
MS) were in good agreement with the data reported by Davis and
Burton [17].
4.8. Preparation of (E)-1,2-difluoro-2-(4-
methoxyphenyl)tributylstannylethene, 6
A 100 ml three-neck flask equipped with a stir bar, low
temperature thermometer, rubber septum and nitrogen inlet
adapter was charged with 1.50 g (8.82 mmol) of (Z)-1-(1,2-
difluorovinyl)-4-methoxylbenzene, 10 ml THF and 10 ml Et2O.
The mixture was cooled to ꢀ105 8C in a pentane-liquid nitrogen
bath, then n-BuLi (4.23 ml, 10.6 mmol, 2.5 M in hexanes) was
added via a syringe maintaining the internal temperature at ꢀ100
to ꢀ105 8C throughout the addition. After complete addition of the
n-BuLi, the resultant milky-yellow mixture was stirred at ꢀ100 to
ꢀ105 8C for 1 h, then 4.13 g (12.7 mmol) of Bu3SnCl (dissolved in
5 ml Et2O) was slowly added via a syringe at ꢀ105 8C. After
warming to room temperature overnight, volatile materials were
removed in vacuo, and the crude residue was loaded directly onto a
silica gel column (10%) ethyl acetate in hexanes, (Rf = 0.53) to give
2.41 g (60%) of, (E)-1,2-difluoro-2-(4-methoxyphenyl)tributyl-
stannylethene, 6, as a clear, colorless liquid. The spectroscopic
data (19F, 1H, 13C NMR, GC–MS) were in good agreement with the
data reported by Davis and Burton [17].
4.5. Preparation of (Z)-1-(1,2-difluorovinyl)-3-
(trifluoromethyl)benzene
Similar to 4.4, 35 ml DMF, 0.5 g (0.4 mmol) Pd(PPh3)4, 5.44 g
(20.1 mmol) of 3-iodobenzotrifluoride, 1.90 g (10.0 mmol) of
Cu(I)I, and 8.47 g (24.0 mmol) of 1 gave the crude product, which
was distilled at partial pressure through a jacketed short-path
Vigreux column to give 3.28 g (79%) of (Z)-1-(1,2-difluorovinyl)-3-
(trifluoromethyl)benzene (containing ꢁ9% DMF impurity). This
material was further purified by silica gel chromatography
(pentane, Rf = 0.29) to give 3.06 g (74%) of the titled compound
4.9. Preparation of (E)-1,2-difluoro-2-(3-
trifluoromethylphenyl)tributylstannylethene, 8
A 100 ml three-neck flask equipped with a stir bar, low
temperature thermometer, rubber septum and nitrogen inlet
adapter was charged with 2.88 g (13.8 mmol) of (Z)-1-(1,2-
difluorovinyl)-3-(trifluoromethyl)benzene, 20 ml THF and 15 ml
Et2O. The mixture was cooled to ꢀ110 8C in a pentane-liquid
nitrogen bath then n-BuLi (6.64 ml, 16.6 mmol, 2.5 M in hexanes)
was added via syringe, maintaining the internal temperature at
ꢀ105 to ꢀ110 8C throughout the addition. During the addition of
the n-BuLi, the solution turned bright orange to blood red. After the
addition was complete, the solution remained a brownish-red
color. After the addition of n-BuLi was completed, the reaction
mixture was stirred at ꢀ105 to ꢀ110 8C for 1 h; then 5.4 g
(16.6 mmol) of Bu3SnCl (dissolved in 5 ml of Et2O) was slowly
added via a syringe at ꢀ110 8C. The reaction mixture was then
slowly warmed to room temperature overnight and the volatiles
removed in vacuo. The crude stannane was loaded directly onto a
silica gel column (hexanes, Rf = 0.34) to afford an 81:19 mixture of
the titled compound and the starting material (as determined by
19F NMR analysis). The starting material was removed by stirring
the mixture for 12 h at 0.2 mm Hg to yield 3.40 g (50%) of the titled
as a clear, colorless liquid, bp 64 8C/7 mm Hg. 19F NMR:
d
ꢀ63.5 (s,
3
3
3F), ꢀ143.1 (dd, JHF = 16.7 Hz, JFF = 10.8 Hz, 1F), ꢀ161.9 (dd,
3
2JHF = 72.0 Hz, JFF = 10.9 Hz, 1F); 19F {1H} NMR:
d
ꢀ63.5 (s, 3F),
ꢀ143.1 (d, JFF = 10.9 Hz, 1F), ꢀ161.9 (d, JFF = 10.7 Hz, 1F); 1H
3
3
2
3
NMR:
d 7.49–7.65 (m, 4H), 7.05 (dd, JHF = 71.9 Hz, JHF = 16.9 Hz,
1H); 13C NMR:
d 147.9 (dd, JCF = 247.5 Hz, JCF = 11.7 Hz), 135.3
1
2
1
2
2
(dd, JCF = 259.8 Hz, JCF = 15.2 Hz), 131.9 (q, JCF = 32.9 Hz) 130.3
(d, JCF = 24.8 Hz), 129.8 (s), 126–127.1 (m), 126.2–126.5 (m),
2
1
124.2 (q, JCF = 272.5 Hz), 120.6–120.9 (m). GC–MS, m/z (relative
intensity): 209 (M+, 100). HRMS: calc’d for C9HF5, 208.0311, found,
208.0311.
4.6. Preparation of (Z)-1-(1,2-difluorovinyl)-4-(acetyl)benzene
Similar to 4.4, 3.44 g (14.0 mmol) of 4-iodoacetophenone,
1.52 g (8.0 mmol) Cu(I)I, 0.32 g (0.28 mmol) Pd(PPh3)4, 20 ml of
dry DMF, and 6.0 g (17 mmol) of
1 gave, after silica gel
chromatography (20% ethyl acetate in hexanes, Rf = 0.26), a
yellow-brown solid, which after recrystallization from pentane,
gave 1.9 g (75%) of the titled compound as off-white needles, mp
compound as a clear, colorless liquid: 19F NMR:
d
ꢀ63.3 (s, 3F),
3
3
ꢀ114.9 (d, JFF = 5.3 Hz, 1F), ꢀ135.9 (d, JFF = 6.3 Hz, 1F), ꢀ135.9
2
3
(dd, JFSn = 174.5 Hz, JFF = 4.6 Hz), satellites due to natural

994
D.J. Burton et al. / Journal of Fluorine Chemistry 131 (2010) 989–995
2
2
abundances of 7.68% 117Sn and 8.58% 119Sn isotopomers. 1H NMR:
d
131.5 (q, JCF = 32.7 Hz), 130.7 (d, JCF = 24.5 Hz), 129.4 (s) 128.6
3
7.50–7.67 (m, 4H), 1.30–1.47 (m, 6H), 1.24 (sextet, JHH = 7.3 Hz,
(s), 128.2 (dd, 3JCF = 4JCF = 3.9 Hz), 126.8 (d, 3JCF = 3.9 Hz), 125.1 (m)
1
6H), 0.90–0.95 (m, 6H), 0.84 (t, 3JHH = 7.2 Hz, 9H); 13C NMR:
(d, 1JCF = 312.7 Hz), 154.6 (dd, 1JCF = 269.8 Hz, 2JCF = 12.4 Hz), 154.6
d
156.1
123.7 (q, JCF = 272.4 Hz), 26.6 (s). HRMS: calc’d for C17H11OF5
326.0730, found 326.0718.
1
2
2
(ddd, JCF = 269.3 Hz, JCSn = 74.4 Hz, JCF = 12.3 Hz), 132.4 (dd,
2JCF = 26.8 Hz, JCF = 4.0 Hz), 131.3 (q, JCF = 32.9 Hz), 131.0 (s),
129.3 (s), 126.3 (d, JCF = 3.8 Hz), 124.5 (m), 124.0 (q,
1JCF = 272.3 Hz), 28.9 (s), 28.9 (d, JCSn = 20.4 Hz), 27.3 (s), 27.3
4.12. Preparation of (Z,Z)-1,2,3,4-tetrafluoro-1,4-bis(3-
trifluoromethylphenyl)-1,3-butadiene
3
2
3
3
(d, 2JCSn = 62.3 Hz), 13.6 (s), 10.9 (s), 10.9 (d, 1JCSn = 352.5 Hz). GS–
MS, m/z (relative intensity): 441 (M+-C4H9, 27), 177 (HSnBu+, 20),
169 (M+-F2SnBu3, 100). HRMS: calc’d for C17H22F2120Sn (M+-C4H9)
441.0657, found 441.0664.
A 100 ml three-neck flask equipped with a stir bar, rubber
septum and nitrogen inlet adapter was charged with 0.37 g
(4.0 mmol) of copper (II) acetate, 10 ml dry DMF, 1.00 g
(2.01 mmol) (E)-1,2-difluoro-2-(3-trifluoromethylphenyl)tributyl-
stannylethene. After stirring for 24 h at RT, the reaction mixture
was loaded directly onto a silica gel column (hexanes, Rf = 0.21) to
yield 0.42 g (50%) of (Z,Z)-1,2,3,4-tetrafluoro-1,4-bis(3-trifluoro-
4.10. Preparation of (Z)-1,2-difluoro-4-carboethoxy-40-
methoxystilbene, 7
methylphenyl)-1,3-butadiene as a white solid: mp 60–63 8C. 19F
3
A 100 ml three-neck flask equipped with a stir bar, rubber
septum, and a nitrogen inlet adapter was charged sequentially
with 10 ml of dry DMF, 0.11 g (0.09 mmol, 5 mol%) of tetrakis(-
triphenylphosphine) palladium (0) and 0.51 g (1.8 mmol) of
ethyl-4-iodobenzoate. The mixture was stirred for 10 min, then
0.18 g (0.92 mmol, 50 mol%) of copper (I) iodide was added to the
mixture. The flask was immersed in a cold-water bath (ꢁ10 8C),
and l.10 g, (2.40 mmol) of 6 was added via a syringe over 5 min.
After 10 min the cold-water bath was removed, and the dark
solution was stirred for 24 h at room temperature. Then, the flask
was charged with 0.5 g, (9 mmol) of KF and the reaction mixture
was stirred an additional 24 h at RT. The reaction mixture was
then loaded directly onto a silica gel column, eluted with 10% ethyl
acetate in hexanes (Rf = 0.34) to give 0.54 g (92%) of the titled
NMR:
3JFF = 8.9 Hz, 2F); 1H NMR:
(m, 4H), 7.25 (bs, 2H); 13C NMR:
d
ꢀ63.8 (s, 6F), ꢀ119.1 (d, JFF = 8.0 Hz, 2F), ꢀ139.4 (d,
3
d
7.57 (d, JHH = 7.5 Hz, 2H), 7.32–7.42
150.3 (dm, 1JCF = 260.9 Hz), 137.6
d
1
2
3
4
(dddd, JCF = 256.3 Hz, JCF = 32.4 Hz, JCF = 23.7 Hz, JCF = 6.0 Hz,),
2
131.6 (q, JCF = 33.3 Hz), 13.3 (bs), 129.3 (s), 129.0 (d,
2JCF = 23.2 Hz), 127.4 (d, JCF = 3.0 Hz), 123.8 (bs), 123.4 (q,
3
1JCF = 272.7 Hz). GC-MS, m/z (relative intensity): 414 (M+, 100),
69 (45). HRMS: calc’d for C18H8F10 414.0466, found 414.0440.
4.13. Preparation of (Z,Z)-1,2,3,4-tetrafluoro-1,4-bis(4-
methoxyphenyl)-1,3-butadiene
Similar to 4.12, 0.79 g (4.4 mmol) copper (II) acetate, 10 ml
DMF, and 1.00 g (2.18 mmol) of (E)-1,2-difluoro-2-(4-methoxy-
phenyl)-tributylstannylethene were stirred at RT for 24 h. The
reaction mixture was loaded directly onto a silica gel column (10%
ethyl acetate in hexanes, Rf = 0.19) to give 0.38 g (52%) of the titled
(Z,Z)-diene as a viscous, yellow-orange oil that solidified on
compound as a white solid, mp 53–55 8C. 19F NMR:
d
ꢀ121.0 (d,
3JFF = 15.0 Hz, 1F), ꢀ134.5 (d, 3JFF = 14 Hz, 1F). 1H NMR:
d
7.93 (d,
3JHH = 8.5 Hz, 2H), 7.37 (d, 3JHH = 8.6 Hz, 2H), 7.29 (d, 3JHH = 8.9 Hz,
2H), 6.84 (d, 3JHH = 8.8 Hz, 2H), 4.36 (q, 3JHH = 7.1 Hz, 2H), 3.81 (s,
3
3H), 1.37 (t, JHH = 7.1 Hz, 3H). 13C NMR:
d
165.7 (s), 161.3 (s),
standing to a yellow solid, mp 38–41 8C. 19F NMR:
d
ꢀ118.6 (d,
7.14 (dt,
147.0
(dd,
1JCF = 251.3 Hz,
2JCF = 20.3 Hz),
144.0
(dd,
3JFF = 10.4 Hz, 2F) ꢀ140.6 (d, 3JFF = 10.9 Hz, 2F); 1H NMR:
d
1JCF = 243.8 Hz, JCF = 22.2 Hz), 134.7 (d, JCF = 24.4 Hz), 130.9
J = 9.3 Hz, J = 2.4 Hz 4H), 6.76 (dt, J = 9.4 Hz, J = 2.3 Hz, 4H), 3.79 (s,
2
2
(s), 130.3 (dd, JCF = 4JCF = 2.6 Hz), 129.6 (s), 127.3 (dd,
6H); 13C NMR: 161.3 (s), 151.4 (dm, 1JCF = 259.2 Hz), 136.1 (dm,
d
3
3JCF = 4JCF = 3.9 Hz), 121.8 (d, JCF = 24.1 Hz), 114.4 (s), 61.2 (s),
1JCF = 250.7 Hz), 128.6 (m), 120.4 (d, 2JCF = 23.6 Hz), 113.9 (s), 55.3
2
55.2 (s), 14.3 (s). GC-MS, m/z (relative intensity) 319 (M+1, 21),
318 (M+, 100). HRMS: calc’d for C18H16F2O3, 318.1068, found
318.1064.
(s). GC-MS, m/z (relative intensity): 338 (M+, 100). HRMS: calc’d for
C18H14F4O2 338.0930, found 338.0904.
References
4.11. Preparation of (Z)-1,2-difluoro-3-(trifluoromethyl)-40-
[1] K. Sato, S. Inoue, J. Ishihara, K. Machida, U.S. Pat. #5,380,461 (1995).
[2] S. Shinya, O. Yokokouji, T. Miyajima, H. Koh, K. Machida, U.S. Pat. 5,914,071
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(acetyl)stilbene, 9
[3] F. Babudri, A. Cardone, G.M. Farinola, C. Martinalli, R. Mendichi, F. Naso, M.
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[13] cf. For a typical example, G. Ji, G. Chen, Z. Wu, X. Jiang, Huazue Xuebao 45 (1987)
904–909.
A 100 ml two-necked flask equipped with a magnetic stir bar,
rubber septum, and nitrogen inlet adapter was charged sequen-
tially with 10 ml of DMF, 0.14 g (0.13 mmol, 5 mol%) of tetra-
kis(triphenylphosphine)palladium(0) and 0.62 g (2.5 mmol) of 4-
iodoacetophenone. After the mixture was stirred for 10 min; 0.25 g
(1.3 mmol, 50 mol%) copper (I) iodide was added to the mixture.
The flask was immersed in a cold-water bath (ꢁ10 8C) and 1.5 g
(3.02 mmol) of 8 was added via a syringe over 5 min. After 10 min
the cold-water bath was removed, and the dark solution was
stirred for 24 h at room temperature. The flask was charged with
0.5 g (9 mmol) of KF, and the reaction mixture was stirred for a few
hours at RT. Then, the reaction mixture was loaded directly onto a
silica gel column and eluted with 10% ethyl acetate in hexanes
(Rf = 0.4) to yield 0.75 g (92%) of (Z)-1,2-difluoro-3-(trifluoro-
methyl)-40(acetyl)stilbene as an orange oil. 19F NMR:
d
ꢀ63.6 (s,
3F), ꢀ126.2 (d, 3JFF = 11.4 Hz, 1F), ꢀ128.1 (d, 3JFF = 11.6 Hz, 1F); 1H
[14] L. Xue, L. Lu, S. Pedersen, Q. Liu, R. Narske, D.J. Burton, J. Org. Chem. 62 (1997)
1064–1071.
[15] R.M. Narske, Ph.D. Thesis, University of Iowa (1997), unpublished results.
[16] We wish to thank Professor James Gloer (Univ. of Iowa) for the use of his HPLC
equipment and assistance with the separation of isomers.
[17] C.R. Davis, D.J. Burton, J. Org. Chem. 62 (1997) 9217–9222.
3
3
NMR:
d 7.90 (d, JHH = 8.5 Hz, 2H), 7.64 (d, JHH = 10.4 Hz, 2H),
7.42–7.51 (m, 4H), 2.60 (s, 3H); 13C NMR:
d 197.1 (s), 145.6 (dd,
1JCF = 249.6 Hz, 2JCF = 20.8 Hz), 145.5 (dd, 1JCF = 250.3 Hz,
2
2JCF = 21.6 Hz), 138.0 (s), 133.9 (d, JCF = 23.7 Hz), 131.6 (s),

D.J. Burton et al. / Journal of Fluorine Chemistry 131 (2010) 989–995
995
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3476–3482.
[25] These two analogs were selected to demonstrate the viability of an aryl with a
strong electron-withdrawing group and a strong electron-donating group to
participate in (Z)-stilbene formation.
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5905–5911, and the references therein.
[26] Although proof of principle was established for unsymmetrical (Z)-1,2-difluor-
ostilbenes, the approach can obviously be employed for the preparation of
symmetrical functionalized (Z)-1,2-difluorostilbenes.
[27] E.J. Blumenthal, D.J. Burton, Israel J. Chem. 39 (1999) 109–115.
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[23] C.A. Wesolowski, Ph.D. Thesis, University of Iowa, 2000.
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