Stereospecific preparation of symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes from 1-bromo-1-fluoroalkenes

Article abstract of DOI:10.1016/j.jfluchem.2006.10.002

A straightforward method to prepare symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes is described. High E/Z ratio 1-bromo-1-fluoroalkenes, prepared by isomerization from the E/Z ≈ 1:1 isomeric mixtures, reacted with Bu

Full text of DOI:10.1016/j.jfluchem.2006.10.002

Journal of Fluorine Chemistry 128 (2007) 71–77
www.elsevier.com/locate/fluor
Stereospecific preparation of symmetrical (1Z, 3Z)- and (1E, 3E)-2,
-difluoro-1,4-disubstituted-buta-1,3-dienes from 1-bromo-1-fluoroalkenes
3
*
Jianjun Xu, Donald J. Burton
Department of Chemistry, University of Iowa, Iowa City, IA 52242, United States
Received 16 August 2006; accepted 3 October 2006
Available online 10 October 2006
Abstract
A straightforward method to prepare symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes is described. High E/Z
ratio 1-bromo-1-fluoroalkenes, prepared by isomerization from the E/Z ꢀ 1:1 isomeric mixtures, reacted with Bu SnSnBu and Pd(PPh to
afford (1Z, 3Z)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes in good yield. (Z)-1-Bromo-1-fluoroalkenes, which were prepared by kinetic
3
3
3 4
)
reduction from 1-bromo-1-fluoroalkenes (E/Z ꢀ 1:1), can undergo similar reaction with Bu
3 3 3 4
SnSnBu and Pd(PPh ) /CuI to prepare (1E, 3E)-2,3-
difluoro-1,4-disubstituted-buta-1,3-dienes.
#
2006 Elsevier B.V. All rights reserved.
Keywords: Fluorodiene; Palladium-catalyzed cross-coupling; Stereospecific; Bromofluoroalkenes; Bis(tributyltin)
1
. Introduction
preparation of symmetrical fluorinated dienes: McCarthy and
co-workers have reported symmetrical fluorinated dienes from
palladium-catalyzed coupling reactions between (a-fluoro)
vinyl stannanes and phenyl triflate, oxalyl chloride, and ethyl
chloroformate [21,22]. Wnuk and co-workers also obtained
symmetrical fluorinated dienes in the palladium-catalyzed
coupling reactions between (a-fluoro) vinyl tris(trimethylsi-
lyl)germanes and aryl or alkenyl halides [23]; recently Rolando
and co-workers reported the synthesis of (1E, 3E)-2,3-difluoro-
1,4-disubstituted-buta-1,3-dienes from (Z)-1-bromo-1-fluor-
oalkenes in the presence of bis(pinacolato)diborane and
Cl Pd(PPh ) [24]. Herein, we detail the preparation of both
Fluoroorganic compounds continue to be of strong interest
in polymer chemistry, medicinal chemistry and agrochemistry
because of the unique properties these compounds exhibited
when fluorine atoms are strategically placed in the molecule [1–
3
]. As conjugated dienes and polyenes widely exist as the
essential feature of many natural products, such as pheromones
and juvenile hormones [4], there is increased research interest
in the synthesis and biological activity of their fluorinated
analogues [5–11]. The reaction between Wittig reagents and a-
fluoro-a,b-unsaturated aldehydes has been used to prepare
fluorinated dienes, however the starting materials are difficult to
prepare and the stereoselectivity is poor [5]. Popular
methodologies for the preparation of fluorinated dienes include:
palladium/copper(I) halide catalyzed coupling reactions
between vinylstannanes and vinyl halides [12–14]; the coupling
reaction between fluorinated vinyl zinc reagent and vinyl
halides [15–18]; the coupling reaction between fluorinated
vinyl copper reagent with vinyl halides [19] and copper(II)
salts-mediated homo-coupling of 1,2-difluorovinylstannanes
2
3 2
(1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,
3-dienes via the Pd(PPh ) /Bu SnSnBu -mediated homo-
3
4
3
3
coupling of 1-bromo-1-fluoroalkenes. A portion of this work
has appeared in a preliminary communication [25].
2. Results and discussion
2.1. Preparation of symmetrical (1Z, 3Z)-2,3-difluoro-1,4-
disubstituted-buta-1,3-dienes
[
20]. However few synthetic methods are available for the
1
-Bromo-1-fluoroalkenes 1 (E/Z ꢀ 1:1) can be readily
prepared by established methods [26–28], and are useful
synthons for the preparation of a variety of fluorinated organic
compounds [29–31]. Recently we reported that 1 can isomerize
*
Corresponding author.
E-mail address: donald-burton@uiowa.edu (D.J. Burton).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.10.002

72
J. Xu, D.J. Burton / Journal of Fluorine Chemistry 128 (2007) 71–77
Table 1
Preparation of symmetrical dienes 3 from 2
a
Entry
R of 2
E/Z of 2
Time (h)
Isolated yield (%)
b
1
2
3
4
5
6
7
Ph, 2a
85:15
82:18
81:19
88:12
87:13
81:19
68
45
64 (75) 3a
Scheme 1.
o-ClC
p-MeOC
p-ClC
p-FC
m-NO
6
H
4
6
4
, 2b
, 2c
, 2d
71 (86) 3b
43 (53) 3c
72 (82) 3d
72 (83) 3e
54 (66) 3f
67 (81) 3g
H
4
40
6
H
41
6
H
4
, 2e
, 2f
)H, 2g
53
2
C
6
H
4
130
46
c
PhC(CH
3
83:17
a
19
1
13
All products gave satisfactory F, H, C, GC–MS and HRMS data; the
number in the parenthesis is the conversion that was calculated based on the
amount of the starting (E) isomer in 2.
Scheme 2.
b
Reaction was carried out in THF instead of DMF.
c
This E/Z ratio was achieved after partial separation of E/Z ꢁ 1:1 mixture via
column chromatography.
to high E/Z ratios [29,32]; for 1 (R = aryl groups), high E/Z
ratios (E/Z > 75:25) were obtained after storage in a freezer
(
À20 8C) for 1 week (Scheme 1). Alternatively, the isomeriza-
materials of high E/Z ratio 2 (R = substituted aryl groups),
various functional groups can be tolerated. For those 2
(R = alkyl groups), the coupling reactions still worked well
and the corresponding (1Z, 3Z)-diene was isolated in good yield
(Table 1, entry 7).
tion readily occurs when 1 undergoes photolysis at 254 nm for
approximately 1 h. The isomerization is very clean and is most
likely due to a trace amount of bromine in the mixture.
However, for those 1 (R = 1-naphthyl or alkyl groups), no
obvious isomerization was detected (Scheme 2).
For one of the substrates (R = p-MeOC H ), the yield of 3c
6
4
Recently we reported that the (E) isomer of 1 reacts faster
than the corresponding (Z) isomer at room temperature in
palladium-catalyzed coupling reaction [33,34]. It has also been
demonstrated that the reactivity difference occurred in the first
step of oxidative addition between Pd(0) catalyst and 1 [33]. In
an effort to prepare (E)-1-fluoro-2-phenylvinyl tributyltin,
which is a useful synthon [21,22], we tested the coupling
reaction between high E/Z ratio 1-bromo-1-fluoroalkenes 2 and
Bu SnSnBu with Pd(PPh ) as the catalyst [35,36]. Thus 1-
is obviously lower than the other reported examples. This lower
yield is due to the formation of a considerable amount of the
1
9
(1Z, 3E) isomeric diene, as observed by F NMR analysis of
the reaction mixture. There are two possibilities for the
formation of this (1Z, 3E)-diene: it could be formed in the
coupling reaction, or alternatively, the desired (1Z, 3Z)-diene
that was formed by the coupling reaction could isomerize to the
corresponding (1Z, 3E)-diene. An exploratory experiment was
designed to test these two possibilities. A small amount of pure
3
3
3 4
1
9
bromo-1-fluoro-2-phenylethene (E/Z = 85:15), 2a, was reacted
with Bu SnSnBu and Pd(PPh ) (4 mol%) in THF at room
(1Z, 3Z)-diene 3c was dissolved in DMF in a NMR tube.
F
NMR analysis showed no isomerization in two days. When two
drops of Bu SnSnBu were added to the solution in the NMR
3
3
3 4
temperature. Surprisingly, rather than formation of (Z)-1-
fluoro-2-phenylvinyltributyltin, the major product obtained was
3
3
tube, we noticed that approximately 20% of the (1Z, 3Z)-diene
isomerized to the (1Z, 3E)-diene in 12 h. More (1Z, 3E)-diene
was observed after a longer time before the mixture reached
equilibrium. It is likely that this particular (1Z, 3E)-diene was
formed by isomerization from the corresponding (1Z, 3Z)-
diene. This isomerization could be initiated by trace amount of
tributyltin radical, which is formed when bis(tributyltin) is
exposed to UV light in a typical laboratory environment. It
seems that dienes or ethenes that bear the p-MeOC H – group
(
amount of the (1Z, 3E) isomeric diene was also detected in the
1Z, 3Z)-2,3-difluoro-1,4-diphenyl-buta-1,3-diene 3a. A trace
1
9
reaction mixture by F NMR analysis. The desired (1Z, 3Z)-
diene was successfully isolated from the reaction mixture by
silica gel column chromatography, followed by recrystalliza-
1
9
1
13
tion, and was characterized by F, H, C NMR, GC–MS, and
HRMS analysis. The yield was 64% (75% conversion based on
the amount of the starting (E)-1-bromo-1-fluoroalkene).
McCarthy and co-workers had also observed similar
symmetrical 2,3-difluoro-1,4-disubstituted-butadienes as a side
product in the palladium-catalyzed coupling reaction between
6
4
have an obvious tendency to readily isomerize. For example,
the similar diene (1E, 3E)-p-MeOC H CF CFCF CF-
6
4
CFC H OMe-p easily isomerized at room temperature [20];
6
4
1
-fluorovinyltin and phenyl triflate, oxalyl chloride and ethyl
(E)-p-MeOC H CF CFC H OMe-p was also readily isomer-
6 4 6 4
chloroformate [21,22]. Although symmetrical biaryls have
been occasionally reported in some palladium-catalyzed
coupling reactions between aryl halides and Bu SnSnBu
ized to an (E), (Z) isomeric mixture when irradiated with UV
light [41].
3
3
[
37–40], to the best of our knowledge, this type of homo-
2.2. Preparation of (1E, 3E)-2,3-difluoro-1,4-disubstituted-
buta-1,3-dienes
coupling reaction has not been previously reported as an
effective method to prepare symmetrical fluorinated dienes.
Similar reactions between other high E/Z ratio 1-bromo-1-
fluoroalkenes and Bu SnSnBu catalyzed by Pd(PPh ) in DMF
It has been demonstrated that at higher temperature [33] or
over a longer reaction time [34] (Z)-1-bromo-1-fluoroalkenes 4
can undergo similar coupling reactions as the (E) isomers at
room temperature. Following the preparation of (1Z, 3Z)-2,
3
3
3 4
were also carried out. (1Z, 3Z)-Dienes were successfully
formed and isolated in good yields (Table 1). For the starting

J. Xu, D.J. Burton / Journal of Fluorine Chemistry 128 (2007) 71–77
73
Table 2
Preparation of symmetrical (1E, 3E)-2,3-difluoro-buta-1,3-dienes from (Z)-1-
bromo-1-fluoroalkenes
Entry
R of 4
E/Z of 4
Temp (8C)
Time (h)
Isolated
yield (%)
a
1
2
3
Ph, 4a
o-ClC
0:100
0:100
0:100
RT
RT
RT
39
44
20
93 6a
Scheme 3.
b
6
H
4
, 4b
, 4c
88 6b
c
p-MeOC
6
H
4
53 6c
3
-difluoro-1,4-disubstituted-buta-1,3-dienes, the synthesis of
a
symmetrical (1E, 3E) isomeric dienes from 4 was investigated
by the same method. Recently, we reported the preparation of
10 mol% Pd(PPh
3
)
4
, 1.0 equiv. CuI were used.
mol% Pd(PPh , 0.5 equiv. CuI were used.
3 4
0 mol% Pd(PPh ) , 1.25 equiv. CuI were used; the product contains 6%
b
c
4
1
3 4
)
(
Z)-1-bromo-1-fluoroalkenes by kinetic reduction of 1 (Scheme
) [32]. (Z)-1-Bromo-1-fluoroalkenes 4 can be obtained in pure
impurity which could not be separated.
3
form, however most of them were utilized with the
corresponding reduced products 5 in a mixture to avoid tedious
isolation and to improve the overall yield [29–32]. Therefore
NMR analysis of the reaction mixture showed that the desired
(1E, 3E)-diene was formed as the only product. However, this
product could not be isolated pure due to its obvious
isomerization tendency in the course of separation. When
R = PhCHCH and n-C H , (Z)-1-bromo-1-fluoroalkenes 4 (in
(
Z)-1-bromo-1-fluoro-2-phenylethene 4a was reacted with
Bu SnSnBu (1.2 equiv.), Pd(PPh ) (4 mol%) at 70 8C and
3
3
3 4
1
9
the reaction progress was monitored by F NMR. (1E, 3E)-2,3-
Difluoro-1,4-diphenyl-buta-1,3-diene 6a was formed as the
major product but considerable amount of (1Z, 3E) and (1Z, 3Z)
isomeric dienes 7, 3a were also detected (Scheme 4). The
desired (1E, 3E)-diene 6a could not be separated from 7 and 3a
by silica gel column chromatography.
3
7 15
a mixture with the corresponding reduced products 5) and
Bu SnSnBu /CuI/DMF did not react at room temperature; at
3
3
higher temperatures the reactions were still sluggish even at
longer reaction times; the separation of pure products from
these reactions mixtures failed.
However, we discovered that the (1E, 3E)-dienes could be
formed as the only product at room temperature with the
addition of 0.5 equiv. of CuI as co-catalyst to the mixture
2.3. Mechanism
(
Scheme 5). For example, when the mixture of (Z)-1-bromo-1-
It was found that in the absence of Pd(PPh ) the reaction
3
4
fluoro-2-(2-chlorophenyl)-ethene 4b and the reduced products
was reacted with Bu SnSnBu (1.2 equiv.), Pd(PPh )
between high E/Z-1-bromo-1-fluoroalkenes 2 and Bu SnSnBu
3 3
failed. In the reaction between 2 and Bu SnSnBu /Pd(PPh ) in
3 3 3 4
3
3
3 4
1
9
(
4 mol%), CuI (0.5 equiv.) in DMF at room temperature,
NMR analysis of the reaction mixture showed that only the (1E,
E)-diene 6b was formed and the reduced products did not
F
DMF, trace amount of 1-fluorovinyltributyltin had been
1
9
detected by F NMR analysis when the reactions were in
progress. Therefore it is reasonable to propose that 1-
fluorovinytin serves as an intermediate. In the coupling
reactions between aryl halides and Pd(0)/Bu SnSnBu aryl
3
participate in the reaction. Pure product (6b) was successfully
isolated by silica gel column chromatography followed by
recrystallization. The yield was 88% (Table 2). Similar
methodology also worked for other (Z)-1-bromo-1-fluoroalk-
enes, such as 4a and 4c. In certain cases, the preparation of
similar symmetrical (1E, 3E)-dienes was unsuccessful how-
ever. For example, when R = 1-naphthyl, the reaction between
3
3
stannanes had been similarly proposed to be the key
intermediate [39].
The proposed mechanism is shown in Scheme 6: L Pd
4
(L = PPh ) first loses two ligands to generate L Pd(0), the
2
3
active catalyst; the oxidative addition between L Pd(0) and (E)-
2
(
ing reduced products) and bistributyltin was carried out at
Z)-1-bromo-1-fluoroalkene (in a mixture with the correspond-
1-bromo-1-fluoroalkene leads to the vinyl palladium(II)
bromide complex; this complex undergoes transmetallation
with Bu SnSnBu to form the vinyl palladium(II) tin
1
9
4
0 8C (the reaction was very slow at room temperature).
F
3
3
Scheme 4.
Scheme 5.

74
J. Xu, D.J. Burton / Journal of Fluorine Chemistry 128 (2007) 71–77
were prepared by kinetic reduction of the E/Z ꢀ 1:1 isomeric
mixtures, can undergo similar coupling reaction with
Pd(PPh ) , CuI and Bu SnSnBu to provide the symmetrical
3
4
3
3
(1E, 3E)-dienes.
3
. Experimental
.1. General experimental procedures
All reaction mixtures were monitored by F NMR analysis
3
1
9
1
19 13
using a Bruker AC-300. The H, F, C spectra of the final
products were obtained on a Bruker AC-300 (CDCl , CFCl or
3
3
TMS were used as the internal references, respectively). Low
resolution mass spectra analyses were performed at 70 eVin the
electron-impact mode on a single-quardrapole instrument
interfaced to a gas chromatograph. High-resolution mass
spectra (HRMS) were obtained in the University of Iowa High
Resolution Mass Spectrometry Facility. Melting points were
obtained in a Thomas-Hoover Unimelt apparatus and are
uncorrected.
Scheme 6. Proposed mechanism for the formation of symmetrical (1Z, 3Z)-
dienes.
intermediate; reductive elimination of this vinyl palladium(II)
tin intermediate generates1-fluorovinyltin; transmetallation
between the newly formed 1-fluorovinyltin and the vinyl
palladium(II) bromide complex gives bis(vinyl) palladium(II)
complex; finally symmetrical diene is formed by reductive
3.2. General procedures for the preparation of (1Z, 3Z)-
dienes (3)
A 25 ml dry round-bottom flask equipped with a stirring bar
and a N tee, was charged with Pd(PPh ) (0.16 g, 0.14 mmol)
2
3 4
elimination, and the active L Pd(0) catalyst is recycled.
2
and dry DMF (5 ml). High E/Z ratio 1-bromo-1-fluoroalkene
(4.0 mmol, includes (E) isomer 3.4 mmol) was added and the
solution was stirred at room temperature for 15 min. After the
addition of Bu SnSnBu (2.37 g, 4.08 mmol), the reaction
It has been shown that (Z)-1-bromo-1-fluoroalkenes can
undergo oxidative addition at 70 8C or higher temperature [33].
The mechanism for the room temperature formation of (1E,
3
3
3
E)-2,3-difluoro-buta-1,3-dienes from (Z)-1-bromo-1-fluor-
mixture was allowed to stir at room temperature. When the
oalkenes in the presence of 0.5 equiv. of CuI is not very clear
at this moment. CuI has been demonstrated to be a good
cocatalyst in a variety of palladium-involved coupling reactions
reaction was completed, Co(OAc) Á4H O (1.25 g, 5.0 mmol)
2
2
was added to remove tributyltin halides from the reaction
mixture [44]. Silica gel column chromatography followed by
recrystallization provided pure products.
[
12,21,42,43], it even makes the Sonogashira coupling reaction
between (Z)-1-bromo-1-fluoroalkenes and terminal alkynes
possible at room temperature [34]. In this Sonogashira coupling
reaction, it is likely that CuI greatly accelerates the
transmetallation step, which makes the first step of oxidative
addition possible at room temperature. Similarly, in the room
temperature formation of (1E, 3E)-2,3-difluoro-buta-1,3-dienes
from (Z)-1-bromo-1-fluoroalkenes in the presence of CuI, it can
be argued that CuI also accelerates the two transmetallation
steps (from vinyl palladium(II) bromide to vinyl palladium tin,
and from 1-flurovinytin to bis(vinyl)palladium(II) complex,
respectively), therefore the oxidative addition between (Z)-1-
3.2.1. (1Z, 3Z)-2,3-Difluoro-1,4-diphenyl-butadiene (3a)
Similarly, a mixture of 1-bromo-1-fluoro-2-phenylethene
(0.80 g, 4.0 mmol, E/Z = 85:15), bis(tributyltin) (2.37 g,
4.1 mmol), Pd(PPh ) (0.16 g, 0.14 mmol) in THF (8 ml) at
3
4
room temperature for 68 h gave 0.31 g white crystals after a
silica gel column (hexanes, R = 0.27) followed by recrystalli-
f
zation from hexanes. The 64% yield (75% conversion based on
1
9
the consumed (E) 1-bromo-1-fluoroalkene). (1Z, 3Z) 100%.
3
F
NMR (CDCl ) (ppm): d À128.4 (dd, JFH(trans) = 28.1 Hz,
3
4
1
J
J = 7.4 Hz, 4H), 7.38 (tm, J = 7.6 Hz, 4H), 7.29 (tm, J = 7.4 Hz,
= 14.7 Hz, 2F); H NMR (CDCl ) (ppm): d 7.60 (d,
3
FH
bromo-1-fluoroalkene and L Pd(0) becomes feasible at room
2
3
2H), 6.24 (dd, J
4
= 28.7 Hz, J = 14.3 Hz, 2H);
13
temperature.
C
150.2 (dd, JCF = 257.6 Hz,
HF(trans)
HF
1
In conclusion, the readily available starting materials 1-
bromo-1-fluoroalkenes were used as precursors for the
preparation of symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-
difluoro-1,4-disubstituted-buta-1,3-dienes. Isomerization of
NMR (CDCl3) (ppm):
2
d
JCF = 43.9 Hz), 132.7, 129.6, 129.52, 129.48, 128.9, 128.3,
107.4 (m); mp: 115–116 8C; GC–MS, product isomerized on
the column, m/z (relative intensity) of one isomer: 243 (M + 1,
+
+
18), 242 (M , 100), 241 (18), 227 (25), 222 (25), 221 (44), 220
1
-bromo-1-fluoroalkenes (E/Z ꢀ 1:1) can lead to high E/Z
ratios (E/Z > 75:25) by storage at À20 8C or by photolysis at
54 nm. These high E/Z ratio 1-bromo-1-fluoroalkenes react
with Pd(PPh ) and Bu SnSnBu to afford symmetrical (1Z,
(41), 202 (11), 201 (16), 191 (7), 165 (53), 164 (73), 146 (7),
145 (20), 127 (28), 110(13), 109 (22), 91 (18); the other isomer:
2
+
243 (M + 1, 24), 242 (M , 100), 241 (22), 227 (31), 222 (31),
+
3
4
3
3
3
Z)-dienes in good yields. (Z)-1-Bromo-1-fluoroalkenes, which
221 (50), 220 (46), 202 (12), 201 (18), 191 (8), 165 (60), 164

J. Xu, D.J. Burton / Journal of Fluorine Chemistry 128 (2007) 71–77
75
(77), 145 (22), 127 (34), 121 (13), 110 (16), 109 (25), 91 (19);
HRMS calculated 242.0907 for C H F , observed 242.0897.
chromatography (hexanes 100%, R = 0.33) followed by
f
recrystallization from hexanes, 0.09 g white crystals was
obtained, yield 72% (82% conversion based on the amount of
1
6 12 2
1
9
the consumed (E)-1-bromo-1-fluoroalkene). (1Z, 3Z) 100%. F
3.2.2. (1Z, 3Z)-1,3-Di(2-chlorophenyl)-2,3-difluoro-
butadiene (3b)
Similarly, a mixture of 1-bromo-1-fluoro-2-(2-chlorophe-
nyl)ethene (0.47 g, 2.0 mmol, E/Z = 82:18), bis(tributyltin)
3
NMR (CDCl ) (ppm): d À128.1 (dd, JFH(trans) = 28.7 Hz,
FH 3
3
4
1
= 14.9 Hz, 2F); H NMR (CDCl ) (ppm): d 7.52 (dm,
J
J = 8.4 Hz, 4H), 7.35 (dm, J = 8.6 Hz, 4H), 6.20 (dd,
3
4
13
(
(
1.14 g, 1.97 mmol), Pd(PPh ) (0.08 g, 0.07 mmol) in DMF
3
JHF(trans) = 28.1 Hz, J = 14.2 Hz, 2H); C NMR (CDCl3)
HF
4
1
(ppm): d 132.4 (d, J = 237.3 Hz), 130.55, 130.50, 128.9,
5 ml) was reacted at room temperature for 45 h to give 0.22 g
CF
+
106.5; GC–MS, m/z (relative intensity): 314 (M + 4, 11), 313
white crystals after a silica gel column (hexanes 100%,
Rf = 0.33) followed by recrystallization from hexanes. The 71%
yield (86% conversion based on the consumed (E)-1-bromo-1-
+
(10), 312 (M + 2, 64), 311 (15), 310 (M , 97), 277 (23), 275
+
(68), 240 (96), 239 (70), 238 (53), 221 (20), 220 (100), 200 (9),
199 (13), 198 (16), 164 (30), 163 (16), 119 (52), 110 (15), 109
1
9
fluoroalkene). (1Z, 3Z) 100%. F NMR (CDCl ) (ppm): d
3
3
4
1
35
10 2 2
À127.7 (dd, JFH(trans) = 26.5 Hz, JFH = 14.0 Hz, 2F);
H
NMR (CDCl ) (ppm): d 7.90 (dd, J = 7.7 Hz, J = 1.5 Hz, 2H),
(14); HRMS calculated 310.0128 for C H
16
C1 F , observed
310.0117.
3
7
.42 (dd, J = 7.8 Hz, J = 1.2 Hz, 2H), 7.29 (t, J = 7.2 Hz, 2H),
.22 (td, J = 7.8 Hz, J = 1.3 Hz, 2H), 6.73 (dd,
7
3.2.5. (1Z, 3Z)-2,3-Difluoro-1,4-di(4-fluorophenyl)-
butadiene (3e)
3
4
JHF(trans) = 27.8 Hz, J = 13.9 Hz, 2H); C NMR (CDCl3)
13
FH
1
ppm): d 150.9 (dd, JCF = 260.0 Hz, J = 43.3 Hz), 133.8,
2
(
Similarly, a mixture of 1-bromo-1-fluoro-2-(4-fluorophe-
nyl)-ethylene (0.175 g, 0.8 mmol, E/Z = 87:13, the amount of
(E) isomer is 0.696 mmol), bis(tributyltin) (0.484 g,
0.835 mmol), Pd(PPh3)4 (0.032 g, 0.028 mmol) in DMF
(4 ml) was reacted at room temperature for 53 h. After silica
CF
1
30.8 (t, J = 6.5 Hz), 130.5, 129.9, 129.4, 127.2, 104.0 (t,
J = 3.0 Hz); mp: 144–145 8C; GC–MS, m/z (relative intensity):
+
+
+
3
14 (M + 4, 7), 312 (M + 2, 40), 310 (M , 61), 277 (22), 275
63), 155 (14), 240 (66), 239 (77), 238 (100), 221 (18), 220 (88),
19 (17), 218 (14), 199 (13), 198 (10), 164 (34), 163 (14), 119
94), 109 (26), 97 (20); HRMS calculated 310.0128 for
(
2
gel column chromatography (hexanes 100%, R = 0.35)
f
(
followed by recrystallization from hexanes, 0.08 g white
crystals was obtained, yield 72% (83% conversion based on the
amount of the consumed (E)-1-bromo-1-fluoroalkene). (1Z, 3Z)
3
5
C H
1
Cl F , observed 310.0138.
2 2
6
10
1
9
3.2.3. (1Z, 3Z)-2,3-Difluoro-1,3-di(4-methoxyphenyl)-
butadiene (3c)
100%. F NMR (CDCl ) (ppm): d À122.8 (m, 2F), À129.8 (dd,
3
3
4
1
JFH(trans) = 28.9 Hz, J = 14.8 Hz, 2F); H NMR (CDCl )
3
Similarly, a mixture of 1-bromo-1-fluoro-2-(4-methoxyphe-
nyl)-ethene (0.46 g, 2.0 mmol, E/Z = 81:19), bis(tributyltin)
(ppm): d 7.57 (ddm, J = 8.9 Hz, J = 5.5 Hz, 4H), 7.07 (tt,
3
J = 8.7 Hz, J = 5.0 Hz, 4H), 6.19 (dd, JHF(trans) = 28.3 Hz,
4
13
J = 14.2 Hz, 2H); C NMR (CDCl ) (ppm): d 162.3 (d,
3
(
1.13 g, 1.94 mmol), Pd(PPh ) (0.07 g, 0.06 mmol) in DMF
3
4
19
1
1
2
(
5 ml) was reacted at room temperature for 40 h. F NMR
JCF = 248.7 Hz), 149.6 (dd, J = 256.2 Hz, J = 43.6 Hz),
CF
showed that the (1Z, 3E)-diene was also formed in the mixture
as a side product; 0.13 g white crystal was obtained after silica
gel column chromatography (ethyl acetate:hexanes = 5:95,
Rf = 0.19) followed by recrystallization from hexanes/ether.
The 43% yield (53% conversion based on the consumed (E)-1-
131.0 (pentet, J = 4.1 Hz), 128.6 (d, J = 2.0 Hz), 115.8 (d,
J = 20.7 Hz), 106.1; mp: 154–156 8C; GC–MS, m/z (relative
+
+
intensity): 279 (M + 1, 22), 278 (M , 100), 277 (13), 258 (36),
257 (46), 256 (47), 245 (14), 238 (22), 183 (38), 182 (47), 163
(14), 145 (23), 139 (16), 127 (19), 119 (14), 109 (13); HRMS
calculated 278.0719 for C H F , observed 278.0704.
1
9
bromo-1-fluoroalkene). (1Z, 3Z) 100%. F NMR (CDCl3)
3
16
10 4
4
(
ppm): d À131.2 (dd, J
= 29.2 Hz, J = 13.6 Hz, 2F);
FH(trans) FH
1
H NMR (CDCl ) (ppm): d 7.53 (dm, J = 8.7 Hz, 4H), 6.90
3
3.2.6. (1Z, 3Z)-2,3-Difluoro-1,4-di(3-nitrophenyl)-
butadiene (3f)
3
dm, J = 8.4 Hz, 4H), 6.13 (dd, J
4
= 29.0 Hz, J
(
=
HF
HF(trans)
1
4.5 Hz, 2H), 3.83 (d, J = 0.8 Hz, 6H); C NMR (CDCl )
3
1
Similarly, a mixture of 1-bromo-1-fluoro-2-(3-nitrophenyl)-
ethene (0.302 g, 1.23 mmol, E/Z = 81:19, the amount of (E)
isomer is 1.0 mmol), bis(tributyltin) (0.696 g, 1.20 mmol),
Pd(PPh ) (0.046 g, 0.04 mmol) in DMF (5 ml) was reacted at
3
1
2
(
ppm): d 159.5, 149.3 (dd, JCF = 255.0 Hz, J = 45.1 Hz),
CF
1
1
1
30.8 (t, J = 2.9 Hz), 125.7, 114.4, 106.2 (t, J = 3.8 Hz); mp:
+
75–177 8C; GC–MS, m/z (relative intensity): 303 (M + 1,
9), 302 (M , 100), 282 (13), 271 (16), 195 (23), 151 (46);
3
4
+
room temperature (use aluminum foil to cover the reaction
container) for 130 h. After silica gel column chromatography
(ethyl acetate:hexanes = 20:80, R = 0.33) followed by recrys-
HRMS calculated 302.1118 for C H O F , observed
1
8 16 2 2
3
02.1118.
f
tallization from ether, 0.11 g yellow solid was obtained, yield
54% (66% conversion based on the amount of the consumed
3.2.4. (1Z, 3Z)-1,3-Di(4-chlorophenyl)-2,3-difluoro-
butadiene (3d)
1
9
(E)-1-bromo-1-fluoroalkene). (1Z, 3Z) 100%.
3
F NMR
JFH(trans) = 27.1 Hz,
Similarly, a mixture of 1-bromo-1-fluoro-2-(4-chlorophe-
nyl)-ethene (0.188 g, 0.8 mmol, E/Z = 88:12, the amount of (E)
isomer is 0.704 mmol), bis(tributyltin) (0.490 g, 0.845 mmol),
Pd(PPh ) (0.033 g, 0.028 mmol) in DMF (4 ml) was reacted
(CDCl ) (ppm):
4
d
JFH = 14.0 Hz, 2F); H NMR (CDCl ) (ppm): d 8.49 (m,
À125.8 (dd,
3
1
3
2H), 8.18 (dd, J = 7.9 Hz, J = 1.9 Hz, 2H), 7.91 (d, J = 7.9 Hz,
= 27.1 Hz,
3
2H), 7.59 (t, J = 8.0 Hz, 2H), 6.41 ( J
3
4
HF(trans)
4
13
JHF = 14.0 Hz, 2H); C NMR (CDCl ) (ppm): d 134.9,
3
at room temperature for 41 h. After silica gel column

76
J. Xu, D.J. Burton / Journal of Fluorine Chemistry 128 (2007) 71–77
1
(ppm): d 148.6 (dd, J = 251.4 Hz, J = 39.4 Hz), 130.4 (t,
2
1
33.6, 129.7, 124.0 (m), 123.0, 106.7; mp: 213–215 8C; GC–
CF
CF
+
+
MS, m/z (relative intensity): 333 (M + 1, 3), 332 (M , 100),
15 (15), 272 (13), 239 (28), 238 (68), 227 (25), 207 (22), 163
18), 151 (18), 97 (15), 57 (22). HRMS calculated 332.0609 for
C H N O F , observed 332.0610.
J = 3.5 Hz), 127.3, 127.2 (d, J = 2.5 Hz), 126.9, 115.4 (dd,
2
3
3
JCF = 18.1 Hz, J = 12.9 Hz); GC–MS, m/z (relative inten-
CF
+
sity): 243 (M + 1, 33), 242 (M , 89), 241 (40), 227 (52), 222
+
(
(46), 221 (63), 220 (71), 202 (19), 201 (35), 165 (48), 164 (100),
145 (36), 127 (39), 109 (31), 91 (25); HRMS calculated
242.0907 for C H F , observed 242.0915.
1
6 10 2 4 2
3
.2.7. (3Z, 5Z)-4,5-Difluoro-2,7-diphenyl-octa-3,5-diene
3g)
Similarly, a mixture of 1-bromo-1-fluoro-3-pheny-1-butene
0.229 g, 1.0 mmol, E/Z = 83:17, the amount of (E) isomer
1
6 12 2
(
3.3.2. (1E, 3E)-1,4-Di(2-chlorophenyl)-2,3-difluoro-
butadiene (6b)
(
is 0.830 mmol), bis(tributyltin) (0.578 g, 0.996 mmol),
Pd(PPh ) (0.038 g, 0.033 mmol) in DMF (3 ml) was reacted
at room temperature for 46 h. After silica gel column
Similarly, a mixture of 1-bromo-1-fluoro-2-(2-chlorophe-
nyl)-ethene (includes (Z)-1-bromo-1-fluoroalkene 0.188 g,
0.8 mmol, E/Z = 0:100), bis(tributyltin) (0.557 g, 0.96 mmol),
3
4
chromatography (ethyl acetate:hexanes = 3:97, R = 0.13),
f
CuI (0.076 g, 0.40 mmol), Pd(PPh ) (0.037 g, 0.032 mmol) in
3 4
waxy colorless liquid was obtained, 0.10 g, 67% yield (81%
conversion based on the consumed (E)-1-bromo-1-fluoroalk-
DMF (4 ml) reacted at room temperature for 44 h. After silica
gel column chromatography (hexanes 100%, R = 0.39)
followed by recrystallization from hexanes, the desired product
f
1
9
ene). (1Z, 3Z) 100%. F NMR (CDCl ) (ppm): d À133.0 (dd,
3
3
4
1
= 12.8 Hz); H NMR (CDCl )
19
was obtained as white crystals, 0.11 g, 88% yield. F NMR
JFH(trans) = 26.7 Hz,
ppm): d 7.16–7.34 (m, 10H), 5.36 (ddd, J
J
FH
3
3
3
4
(
4
= 26.5 Hz,
JHF = 13.3 Hz, JHH = 9.9 Hz, 2H), 3.98 (dq, J = 9.9 Hz,
(CDCl ) (ppm): d À111.2 (dd, JFH(cis) = 11.9 Hz, JFH
=
7.6 Hz, 2F); H NMR (CDCl ) (ppm): d 7.25 (m, 2H), 7.07–
HF(trans)
3
3
1
3
1
J = 7.1 Hz, 2H), 0.87 (d, J = 7.4 Hz, 6H); C NMR (CDCl3)
3
3
7.12 (m, 6H), 6.59 (dd, J
13
4
= 10.8 Hz, J = 7.2 Hz, 2H);
1
C NMR (CDCl ) (ppm): d 150.1 (dd, JCF = 253.3 Hz,
HF(cis)
HF
1
ppm): d 148.5 (dd, J = 245.6 Hz, J = 46.9 Hz), 145.0 (d,
2
(
J = 7.3 Hz), 128.6, 126.8, 126.4, 112.2 (dd, J = 6.3 Hz,
CF
CF
3
2
JCF = 36.0 Hz), 133.3 (m), 130.1 (t, J = 5.0 Hz), 129.6, 129.2,
128.9, 126.8, 113.6 (dd, J = 19.3 Hz, J = 14.6 Hz); mp: 84–
+
J = 2.5 Hz); GC–MS, m/z (relative intensity): 298 (M , 5),
+
2
83 (5), 263 (3), 220 (20), 193 (22), 165 (31), 149 (18), 134
15), 133 (23), 129 (28), 115 (22), 105 (100), 103 (22), 91 (64),
86 8C; GC–MS, m/z (relative intensity): 314 (M + 4, 7), 313
+
+
(
(7), 312 (M + 2, 41), 311 (9), 310 (M , 63), 277 (25), 275 (69),
257 (6), 255 (17), 240 (72), 239 (81), 238 (100), 221 (20), 220
(92), 218 (20), 200 (9), 199 (16), 198 (13), 164 (38), 163 (15),
7
2
7 (32). HRMS calculated 298.1533 for C H F , observed
20 20 2
98.1530.
1
43 (11), 119 (72), 109 (18); HRMS calculated 310.0128 for
3
5
3.3. General procedures for the preparation of (1E, 3E)-
dienes (6)
C H F Cl , observed 310.0120.
16 10 2 2
3.3.3. (1E, 3E)-2,3-Difluoro-1,4-di(4-methoxyphenyl)-
butadiene (6c)
A 25 ml dry round-bottom flask equipped with a stirring bar
and a N tee, was charged with Pd(PPh ) (0.046 g, 0.04 mmol)
Similarly, a mixture of 1-bromo-1-fluoro-2-(4-methoxy-
pheny)-ethene (includes (Z)-1-bromo-1-fluoroalkene 0.231 g,
1.0 mmol, E/Z = 0:100), bis(tributyltin) (1.044 g, 1.20 mmol),
CuI (0.245 g, 1.25 mmol), Pd(PPh ) (0.115 g, 0.10 mmol) in
2
3 4
and dry DMF (4 ml). A mixture of (Z)-1-bromo-1-fluoroalkene
includes (Z)-1-bromo-1-fluoroalkene 1.0 mmol) and the
(
reduced products was added and the solution was stirred at
room temperature for 15 min. After the addition of
Bu SnSnBu (0.696 g, 1.2 mmol) and CuI (0.095 g, 0.5 mmol),
3
4
DMF (4 ml) reacted at room temperature for 20 h. After silica
gel column chromatography (ethyl acetate:hexanes = 15:85,
Rf = 0.33), the desired product was obtained (contains 6% of
impurity which could not be completely separated) as a slightly
3
3
the reaction mixture was allowed to stir at room temperature.
When the reaction was completed, Co(OAc) Á4H O (1.25 g,
2
2
1
9
5
.0 mmol) was added to remove the tributyltin halides from the
yellow liquid, 0.08 g, 53% yield. F NMR (CDCl ) (ppm): d
3
1
reaction mixture [44]. Silica gel column chromatography
followed by recrystallization (if necessary) gave pure products.
À111.2 (dd, J = 10.7 Hz, J = 5.7 Hz, 2F); H NMR (CDCl )
3
(ppm): d 7.17(d, J = 8.8 Hz, 4H), 6.74 (d, J = 8.5 Hz, 4H), 6.49
(
1
dd, J = 11.2 Hz, J = 6.2 Hz, 2H), 3.75 (d, J = 0.7 Hz, 6H); C
3
1
3
.3.1. (1E, 3E)-2,3-Difluoro-1,4-diphenyl-butadiene (6a)
Similarly, a mixture of 1-bromo-1-fluoro-2-phenyl-ethene
NMR (CDCl ) (ppm): d 159.3, 148.5 (dd, J = 249.7 Hz,
3 CF
2
JCF = 39.1 Hz), 129.5 (d, J = 1.9 Hz), 123.6 (t, J = 4.2 Hz),
115.7 (dd, J = 20.3 Hz, J = 14.8 Hz), 113.7, 55.0; GC–MS, m/z
(include (Z)-1-bromo-1-fluoroalkene 0.161 g, 0.8 mmol, E/
Z = 0:100) and the reduced products, bis(tributyltin) (0.557 g,
+
+
(relative intensity): 303 (M + 1, 18), 302 (M , 100), 301 (9),
287 (11), 282 (17), 271 (19), 239 (14), 214 (10), 207 (13), 201
(16), 195 (31), 194 (20), 180 (14), 157 (14), 151 (35); HRMS
calculated 302.1118 for C H O F , observed 302.1112.
0
0
3
.96 mmol), CuI (0.152 g, 0.80 mmol), Pd(PPh ) (0.092 g,
3 4
.08 mmol) in DMF (4 ml) was reacted at room temperature for
9 h. After silica gel column chromatography (ethyl acetate:-
1
8 16 2 2
hexanes = 3:97, R = 0.38), the desired product was obtained as
f
1
a slight yellow liquid, 0.09 g, 93% yield. F NMR (CDCl )
9
Acknowledgement
3
3
4
1
(
NMR (CDCl ) (ppm): d 7.17–7.19 (m, 10H), 6.53 (dd,
ppm): d À109.7 (dd, J
= 12.1 Hz, J = 6.6 Hz, 2F); H
FH(cis) FH
We gratefully appreciate the financial support from the
National Science Foundation.
3
3
4 13
JHF(cis) = 10.9 Hz, JHF = 6.0 Hz, 2H); C NMR (CDCl3)

J. Xu, D.J. Burton / Journal of Fluorine Chemistry 128 (2007) 71–77
77
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