Palladium-Catalysed Desulfitative Heck Reaction Tolerant to Aryl Carbon-Halogen Bonds for Access to (Poly)halo-Substituted Stilbene or Cinnamate Derivatives

Article abstract of DOI:10.1055/s-0035-1560449

The palladium-catalysed desulfitative Heck type reaction of (poly)halo-substituted benzenesulfonyl chlorides with alkenes was investigated. Styrene or acrylates in the presence of bromo- or iodobenzenesulfonyl chlorides and a phosphine-free palladium catalyst were found to afford the expected β-arylated Heck type products with complete regio- and stereoselectivities. The reaction tolerates a variety of substituents on the halobenzenesulfonyl chloride. Moreover, no cleavage of the C-Br and C-I bonds was observed in the course of these reactions, allowing further transformations. Using 4-bromobenzenesulfonyl chloride as the central unit, consecutive desulfitative Heck type reaction followed by palladium-catalysed direct arylation allowed to prepare heteroarylated stilbene derivatives in only two steps.

Full text of DOI:10.1055/s-0035-1560449

SYNTHESIS
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1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–J
paper
A
A. Skhiri et al.
Paper
Synthesis
Palladium-Catalysed Desulfitative Heck Reaction Tolerant to Aryl
Carbon–Halogen Bonds for Access to (Poly)halo-Substituted
Stilbene or Cinnamate Derivatives
Aymen Skhiria,b
Ridha Ben Salem*b
Jean-Francois Souléa
Henri Doucet*a
a Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-
Université de Rennes ‘Organométalliques: Matériaux et
Catalyse’, Campus de Beaulieu, 35042 Rennes, France
henri.doucet@univ-rennes1.fr
b Laboratoire de Chimie Organique Physique (UR 11ES74)
Université de Sfax, Faculté des Sciences de Sfax, Route de
la Soukra km 4, 3038 Sfax, Tunisie
ridhabensalem@yahoo.fr
Received: 03.02.2016
Accepted after revision: 29.03.2016
Published online: 11.05.2016
[Pd]
R
+
X
Ar
R
Ar
base
DOI: 10.1055/s-0035-1560449; Art ID: ss-2016-z0085-op
X = Br, I, OTf, SO2Cl...
Abstract The palladium-catalysed desulfitative Heck type reaction of
(poly)halo-substituted benzenesulfonyl chlorides with alkenes was in-
vestigated. Styrene or acrylates in the presence of bromo- or iodoben-
zenesulfonyl chlorides and a phosphine-free palladium catalyst were
found to afford the expected β-arylated Heck type products with com-
plete regio- and stereoselectivities. The reaction tolerates a variety of
substituents on the halobenzenesulfonyl chloride. Moreover, no cleav-
age of the C–Br and C–I bonds was observed in the course of these re-
actions, allowing further transformations. Using 4-bromobenzenesulfo-
nyl chloride as the central unit, consecutive desulfitative Heck type
reaction followed by palladium-catalysed direct arylation allowed to
prepare heteroarylated stilbene derivatives in only two steps.
Scheme 1
The synthesis of halo-substituted stilbene or cinnamate
derivatives is an important field of research in organic
chemistry as they give access to important building blocks
for biochemists. Therefore, reaction conditions promoting
Heck type reaction tolerant to C–halogen bonds would pro-
vide a straightforward access to halo-substituted arenes.
However, although desulfitative couplings are known to tol-
erate both bromo and iodo substituents on benzenesulfonyl
chlorides,4 surprisingly to our knowledge, only one exam-
ple of desulfitative Pd-catalysed Heck-type reaction em-
ploying a bromobenzenesulfonyl chloride has been report-
ed (Scheme 2, top).5a Rare examples of such Pd-catalysed
reactions using a 4-bromobenzenesulfinate or bromoben-
zenesulfonyl hydrazide have been described (Scheme 2,
middle).5b,d A few examples of Rh- or Ru-catalysed Heck
type reactions in the presence of halo-substituted arylation
agents, but without cleavage of the C–halogen bond, have
also been reported.6,7
The use of (poly)halobenzenesulfonyl chlorides as reac-
tants in Pd-catalysed reactions presents several attractive
features: 1) many of them are commercially available at an
affordable cost, 2) they can be easily prepared from sulfonic
acids or sulfur substrates by chlorination, and 3) there are
generally no cleavage of the C–halogen bonds in Pd-cata-
lysed reactions. Therefore, the reaction outcome using such
benzenesulfonyl chlorides in Heck-type reaction needed to
be investigated in more details (Scheme 2, bottom).
Key words palladium, catalysis, desulfitative Heck reaction, haloben-
zenesulfonyl chlorides, alkenes
Mizoroki–Heck reaction is certainly one of the most
powerful methods for the preparation of stilbene or cin-
namate derivatives.1,2 For such reactions, in most cases, aryl
halides were employed as the aryl source (Scheme 1); how-
ever, the reactivity of benzenesulfonyl derivatives was also
studied. For example, Miura and co-workers reported in
1989 the Heck type Pd-catalysed desulfitative reaction of
acrylates with benzenesulfonyl chlorides for the synthesis
of 3-aryl-2-propenoates.3a A few years later, Vogel et al. ex-
tended these Pd-catalysed desulfitative Heck reactions to
styrene and substituted acrylates.3b Jafarpour et al. recently
reported that the reaction of methyl acrylate with benzene-
sulfonyl chloride in the presence of PdCl2 and Cu(OAc)2 as
catalytic system also affords the Heck type products.3c The
arylation of glycals under Pd-catalysed desulfitative Heck
conditions has also been reported.3d
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

B
A. Skhiri et al.
Paper
Synthesis
Based on our previous results on the Pd-catalysed de-
sulfitative8 coupling with heteroarene derivatives,9,10 the
influence of several reaction conditions, using 5 mol%
PdCl2(CH3CN)2 catalyst and Li2CO3 as the base, on the prod-
ucts formation was first examined (Table 1). From 1 equiva-
lent of 4-bromobenzenesulfonyl chloride and 1.5 equiva-
lents of styrene at 100 °C during 24 hours, the desired Heck
type product 1 was obtained in 62% yield with complete re-
gio- and stereoselectivity in favour of the formation of the
E-isomer and without cleavage of the C–Br bond (Table 1,
entry 1). A lower reaction temperature of 80 °C also gave
selectively 1, but in very low yield due to poor conversion
(entry 2). We also investigated the influence of the nature
of the solvent. DMF and CPME were ineffective, as with
these two solvents, 1 could not be isolated (entries 3 and 4).
The reaction performed in ethylbenzene and diethyl car-
bonate gave 1 in poor 22% and 12% yield, respectively (en-
tries 5 and 6). The use of 5 mol% Pd(OAc)2 afforded 1 in a
slightly higher yield of 65%; whereas, a reaction performed
with PdCl2 gave 1 in 41% yield (entries 7 and 8). When
K2CO3 or Cs2CO3 were used as bases instead of Li2CO3, 1 was
obtained in quite low yields (entries 10 and 11). This differ-
ence between carbonated bases might be due to the higher
solubility of Cs2CO3 compared with Li2CO3 or K2CO3 in 1,4-
dioxane. A similar trend had been previously observed in
Pd-catalysed desulfitative Heck reaction or direct aryla-
tion.3d,9a,11
O
PdCl2(PhCN)2
(2.5 mol%)
Miura5a
BuO
BuO
Br
Br
O
K2CO3, R4NCl
xylene
+
44%
78%
ClO2S
BuO
Br
PdCl2 (5 mol%)
DPEphos (5 mol%)
O
Deng5b
O
BuO
O2, anisole
+
NaO2S
Br
Tian5d
Pd(OAc)2 (10 mol%)
O2, DMSO/MeNO2
Ph
Ph
Br
+
73%
R
H2NHNO2S
Br
+
X
X
[Pd]
base
This work
R
ClO2S
X = Br or I
Scheme 2
Herein, we report on the influence of the position of the
halo-substituent on the benzenesulfonyl chlorides in the
Pd-catalysed desulfitative Heck reaction. The influence of
other additional substituents and the reactivity of some di-
and tribromobenzenesulfonyl chlorides were also investi-
gated.
Table 1 Influence of the Conditions on the Pd-Catalysed Desulfitative Reaction of Styrene with 4-Bromobenzenesulfonyl Chloridea
Br
[Pd]
+
ClO2S
Br
base
1
Entry
Catalyst
Solvent
Base
Li2CO3
Temp (°C)
Yield (%)b of 1
1
2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
Pd(OAc)2
1,4-dioxane
1,4-dioxane
DMF
100
80
67 (62)
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
K2CO3
Cs2CO3
5
3
150
120
100
150
100
100
100
100
100
trace
0
4
CPMEc
5
ethylbenzene
diethyl carbonate
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
22
6
12
7
69 (65)
41
8
PdCl2
9
–
0
10
11
PdCl2(CH3CN)2
PdCl2(CH3CN)2
33
8
a Reaction conditions: [Pd] (5 mol%), 4-bromobenzenesulfonyl chloride (1 equiv), styrene (1.5 equiv), Li2CO3 (3 equiv), 24 h.
b Yield determined by GC and 1H NMR of the crude; isolated yields are given in parentheses
c CPME: Cyclopentyl methyl ether.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

C
A. Skhiri et al.
Paper
Synthesis
Then, the scope of the Pd-catalysed desulfitative Heck
reaction of styrene with a variety of halo-substituted ben-
zenesulfonyl chlorides was investigated (Scheme 3). A high
yield of 80% in 2 was obtained for the reaction of 4-iodo-
benzenesulfonyl chloride with styrene. Moreover, no cleav-
age of the C–I bond was observed. ortho-Substituents often
exhibit an important influence on Pd-catalysed reactions
due to their coordination and/or steric properties. There-
fore, the reactivity of 2-bromobenzenesulfonyl chloride and
of a set of 2-substituted 4-bromobenzenesulfonyl chlorides
was investigated. 2-Bromobenzenesulfonyl chloride afford-
ed the desired product 3 in 82% yield. Lower yields of 33%
and 32% in 4 and 5 were obtained in the presence of
2-methoxy- or 2-ethyl-substituted 4-bromobenzenesulfo-
nyl chlorides. These poor yields are probably due to the for-
mation of quite large amounts of oligomers or polymers of
styrene as side-products. However, with these two sub-
strates, the use of a larger excess of styrene (3 equiv) using
Pd(OAc)2 as catalyst allowed to increase the yield in 4 and 5
to 56% and 51%, respectively. On the other hand, 4-bromo-
2-fluorobenzenesulfonyl chloride and more congested 4-
bromo-2-(trifluoromethyl)benzenesulfonyl chloride afford-
ed 6 and 7 in 71% and 79% yield, respectively. From 2-bro-
mo-4-(trifluoro)benzenesulfonyl chloride, the desired
product 8 was also obtained in good yield. It should be
mentioned that for all these reactions, no cleavage of the C–
halogen bonds was observed allowing further transforma-
tions. As both 2,5- and 3,4-dibromobenzene-1-sulfonyl
chlorides can be easily prepared by reaction of 1,4- and 1,2-
dibromobenzenes with chlorosulfonic acid,12a their reactiv-
ity for desulfitative Heck reaction was also evaluated. In
both cases, the expected products 9 and 10 were obtained
in high yields without cleavage of both C–Br bonds. More-
over, the reaction of 2,4,6-tribromobenzene-1-sulfonyl
chloride with styrene was found to afford 11 with the three
C–Br bonds untouched, but in only 12% yield. Currently,
such polyhalo-substituted styrenes are generally prepared
using multi-steps syntheses via Wittig reaction as the key
step.12b,c
R
PdCl2(CH3CN)2
(5 mol%)
1.5 equiv
+
Li2CO3 (3 equiv)
1,4-dioxane
100 °C, 24 h
2–11
R
SO2Cl
1 equiv
I
Br
2 80%
3 82%
MeO
Br
Br
Br
4 33% 56%a
5 32% 51%a
F
Br
F3C
6 71%
7 79%
Br
Br
CF3
Br
Br
8 60%
9 63%
Br
Br
Br
Br
10 76%
11 12% 10%a
a styrene derivative (3 equiv), 40 h, Pd(OAc)2 (5 mol%)
Scheme 3
nyl chloride affording 16 and 17 in good yields. Again, the
use of 3 equivalents of alkene with 5 mol% Pd(OAc)2 catalyst
gave the highest yields. A moderate yield in 18 was ob-
tained using 2-vinylpyridine and 4-bromobenzenesulfonyl
chloride as reaction partners. Then, the reactivity of 4-bro-
mobenzenesulfonyl chloride and 4-iodobenzenesulfonyl
chloride was compared in the presence of three styrene de-
rivatives. Similar yields than with 4-bromobenzenesulfonyl
chloride were obtained in all cases. Moreover, no cleavage
of the C–I bond was observed. For example, 4-fluorostyrene
and 2,3,4,5,6-pentafluorostyrene reacted with 4-iodoben-
zenesulfonyl chloride to give 20 and 21 in 73% and 72%
yields, respectively. Again, in the presence of 4-bromosty-
rene, a low yield in desired product 19 was obtained.
The reactivity of a few other alkenes for such reactions
was also investigated (Scheme 5). The reaction of n-butyl
acrylate with 4-bromobenzenesulfonyl chloride gave the
cinnamate derivative 22 in 70% yield. Again a complete re-
gio- and stereoselectivity in favour of the formation of the
E-isomer was observed. A set of substituents at C2 of 4-bro-
mobenzenesulfonyl chloride, for reaction with n-butyl ac-
rylate, was also tolerated affording the bromo-substituted
cinnamates 23–25 in 78–85% yields. A high yield of 93% in
The influence of some styrene substituents on their re-
activity for this reaction was then examined (Scheme 4).
Lower yields than with styrene were obtained with both 4-
methoxy- and 4-cyanostyrenes, as 12 and 13 were isolated
in only 26% and 51% yield, respectively. However, a bromo
substituent on styrene was tolerated allowing the synthesis
of dibromostilbenes. From 4- and 3-bromostyrenes and 4-
bromobenzenesulfonyl chloride as reaction partner, the de-
sired dibromostilbenes 14 and 15 were obtained in low to
moderate yields, due to the low conversions of these two
bromobenzenesulfonyl chlorides. It should be mentioned
that the use of a larger excess of 3-bromostyrene and
Pd(OAc)2 as catalyst allowed to increase the yield in 15 to
54%. Both 4-fluorostyrene and 2,3,4,5,6-pentafluorostyrene
were also successfully reacted with 4-bromobenzenesulfo-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

D
A. Skhiri et al.
Paper
Synthesis
reoselectively obtained, but in low yield (31%) due to the
partial in situ desilylation of 33 affording 4-iodostyrene as a
side product.
R
PdCl2(CH3CN)2
X
1.5 equiv
5 mol%
+
Li2CO3 (3 equiv)
1,4-dioxane
100 °C, 24 h
R
R'
12–21
X
SO2Cl
R
PdCl2(CH3CN)2
(5 mol%)
1.5 equiv
+
1 equiv
Br
Br
Br
X = Br or I
Li2CO3 (3 equiv)
1,4-dioxane
100 °C, 24 h
R'
R
22–33
SO2Cl
1 equiv
MeO
NC
12 26% 31%a
13 51%
Br
F
Br
Br
n-BuO2C
n-BuO2C
Br
22 70%
23 83%
F3C
Br
MeO
Br
14 21% 22%a
15 37% 54%a
Br
Br
n-BuO2C
n-BuO2C
n-BuO2C
n-BuO2C
Br
F
24 85%
25 78%
F
F
Br
CF3
Br
F
F
16 24% 61%a
17 22%, 74%a
F
Br
I
26 93%
27 91%
29 82%
I
Br
Br
Br
N
n-BuO2C
n-BuO2C
Br
18 31% 33%a
19 20%a
28 59%
I
I
F
I
Br
F
F
n-BuO2C
NO2
EtO2C
F
F
30 28%
31 20%
20 73%a
21 72%a
F
Br
I
a styrene derivative (3 equiv), 40 h, Pd(OAc)2 (5 mol%)
t-Bu
Si
33 31%
Scheme 4
32 36%a
a 5 equiv of alkene
26 was also obtained for the reaction of n-butyl acrylate
with 2-bromo-4-(trifluoromethyl)benzenesulfonyl chlo-
ride. Both 2,5- and 3,4-dibromobenzene-1-sulfonyl chlo-
rides were also successfully coupled with n-butyl acrylate
affording 27 and 28 in 91% and 59% yield, respectively. The
reaction of n-butyl acrylate with 4-iodobenzenesulfonyl
chloride gave Heck type product 29 in 82% yield, without
C–I bond cleavage. Even the electron-deficient 2-iodo-5-ni-
trobenzenesulfonyl chloride gave the target product 30
without cleavage of the very reactive C–I bond. If terminal
alkenes are reactive under these conditions in Pd-catalysed
desulfitative Heck reaction, on the other hand, ethyl trans-
but-2-enoate13 exhibits a poor reactivity affording 31 in
only 20% yield. However, the reaction was found to be fully
regio- and stereoselective. The reaction of 3,3-dimethylbut-
1-ene with 4-bromobenzenesulfonyl chloride gave 32 in
only 36% yield. Due to the low boiling point of 3,3-dimeth-
ylbut-1-ene, 5 equivalents of this alkene were employed for
this reaction. From dimethyl(phenyl)(vinyl)silane and 4-io-
dobenzenesulfonyl chloride, the E-isomer 33 was also ste-
Scheme 5
Although the mechanism is not yet elucidated, we as-
sume that in the first step an oxidative addition of ArSO2Cl
to Pd(II) affords a Pd(IV) species. Such an oxidative addition
on Pd(II) has been reported to proceed even at room tem-
perature.14 Then, after elimination of SO2, the coordination
of the alkene followed by insertion in the Pd–Ar bond might
afford a Pd–CHRCH2Ar intermediate. Then, β-H elimination
followed by reductive elimination assisted by the base
would produce the β-arylated alkene derivative with regen-
eration of a Pd(II) species.
Since one decade, Pd-catalysed direct arylation of het-
eroaromatics with aryl halides via a C–H bond activation
has become a popular method for generating carbon–car-
bon bonds.15 In order to further demonstrate the synthetic
potential of the halo-substituted stilbenes prepared by our
method, Pd-catalysed direct arylations using 1 as aryl
source was also studied (Scheme 6). Using 2 mol%
PdCl(C3H5)2(dppb)16 catalyst in the presence of KOAc in
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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A. Skhiri et al.
Paper
Synthesis
DMA, 1 was coupled with 2-ethyl-4-methylthiazole and 2-
pentylthiophene to afford 34 and 35 in 53% and 51% yield,
respectively. In both cases, a regioselective C5-arylation of
the heteroarene, without isomerisation of the stilbene dou-
ble bond, was observed.
added and the solution was stirred at r.t. for 20 min. The solvent was
removed in vacuum. The yellow powder was used without purifica-
tion.
31P NMR (81 MHz, CDCl3): δ = 19.3 (s).
Desulfitative Reactions; General Procedure
Br
In a typical experiment, the alkene derivative (1.5 mmol), haloben-
zenesulfonyl chloride derivative (1 mmol), Li2CO3 (0.222 g, 3 mmol),
and PdCl2(CH3CN)2 (12.9 mg, 0.05 mmol) were dissolved in 1,4-diox-
ane (2 mL) under an argon atmosphere. The reaction mixture was
stirred at 100 °C for 24 h. After evaporation of the solvent, the prod-
uct was purified by silica gel column chromatography.
Y
R
PdCl(C3H5)(dppb)
(2 mol%)
S
1
+
KOAc, DMA
130 °C, 24 h
Y
R
N
S
(E)-1-Bromo-4-styrylbenzene (1)17
S
S
From styrene (0.156 g, 1.5 mmol) and 4-bromobenzenesulfonyl chlo-
ride (0.255 g, 1 mmol), product 1 was obtained in 62% (0.160 g) yield
as a white solid; mp 141–143 °C.
34 53%
35 51%
1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J = 8.5 Hz, 2 H), 7.48 (d, J = 8.5
Hz, 2 H), 7.40–7.33 (m, 4 H), 7.28 (t, J = 7.4 Hz, 1 H), 7.10 (d, J = 16.4
Hz, 1 H), 7.03 (d, J = 16.4 Hz, 1 H).
Scheme 6
13C NMR (100 MHz, CDCl3): δ = 137.0, 136.3, 131.8, 129.4, 128.7,
128.0, 127.9, 127.4, 126.6, 121.3.
In summary, we have reported phosphine-ligand free,
ammonium-salt free and oxidant-free conditions allowing
desulfitative palladium-catalysed Heck type reactions us-
ing both bromo- and iodo-substituted benzenesulfonyl
chlorides, in the presence of styrenes or acrylates, as the re-
action partners. In the course of these reactions, no cleav-
age of the benzenesulfonyl chlorides C–Br or C–I bonds was
observed allowing further transformations. The reaction
was found to proceed with easily accessible Pd(CH3CN)2Cl2
catalyst and Li2CO3 as inexpensive base. Moreover, this pro-
cedure tolerates a variety of substituents on the haloben-
zenesulfonyl chlorides. Due to the wide availability of di-
versely functionalised (poly)halo-substituted benzenesul-
fonyl chlorides at an affordable cost, such simple reaction
conditions (no expensive base and ligand) should be very
attractive to synthetic chemists for access to (poly)halo-
substituted stilbene or cinnamate derivatives, compared to
more classical methods, such as Wittig reaction, which re-
quires several steps and, in some cases, affords mixtures of
stereoisomers.
(E)-1-Iodo-4-styrylbenzene (2)18
From styrene (0.156 g, 1.5 mmol) and 4-iodobenzenesulfonyl chlo-
ride (0.303 g, 1 mmol), product 2 was obtained in 80% (0.244 g) yield
as a white solid; mp 156–159 °C.
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.5 Hz, 2 H), 7.55 (d, J = 8.5
Hz, 2 H), 7.43–7.25 (m, 5 H), 7.14 (d, J = 16.4 Hz, 1 H), 7.04 7.14 (d,
J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.8, 137.0, 136.9, 129.6, 128.9,
128.3, 128.0, 127.6, 126.7, 91.9.
(E)-1-Bromo-2-styrylbenzene (3)19
From styrene (0.156 g, 1.5 mmol) and 2-bromobenzenesulfonyl chlo-
ride (0.255 g, 1 mmol), product 3 was obtained in 82% (0.212 g) yield
as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 8.5 Hz, 1 H), 7.65–7.58 (m, 3
H), 7.55 (d, J = 16.4 Hz, 1 H), 7.46–7.32 (m, 4 H), 7.16 (t, J = 7.8 Hz, 1
H), 7.09 (d, J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.3, 137.2, 133.2, 131.6, 128.9,
128.8, 128.2, 127.7, 127.6, 127.0, 126.8, 124.3.
(E)-4-Bromo-1-methoxy-2-styrylbenzene (4)20
All reactions were run under argon in Schlenk tubes using vacuum
lines. Analytical grade 1,4-dioxane was not distilled before use. Li2CO3
(>99%) was used. Commercial alkene derivatives and halobenzenesul-
fonyl chlorides were used without purification. The reactions were
followed by GC and NMR. 1H and 13C spectra were recorded on a
Bruker 400 MHz spectrometer in CDCl3 solutions. Chemical shifts are
reported in ppm relative to CDCl3(7.26 for 1H NMR and 77.0 for 13C
NMR). Flash chromatography was performed on silica gel (230–400
mesh).
From styrene (0.156 g, 1.5 mmol) and 2-methoxy-5-bromobenzene-
sulfonyl chloride (0.285 g, 1 mmol), product 4 was obtained in 33%
(0.095 g) yield as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 2.5 Hz, 1 H), 7.53 (d, J = 8.3
Hz, 2 H), 7.42–7.25 (m, 5 H), 7.09 (d, J = 16.4 Hz, 1 H), 6.77 (d, J = 8.7
Hz, 1 H), 3.87 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.0, 137.5, 131.1, 130.4, 129.0,
128.8, 128.7, 127.9, 126.8, 122.2, 113.4, 112.7, 55.9.
PdCl(C3H5)(dppb)16
(E)-1-Bromo-3-ethyl-4-styrylbenzene (5)
An oven-dried 40 mL Schlenk tube equipped with a magnetic stirring
bar under argon atmosphere was charged with [Pd(C3H5)Cl]2(182 mg,
0.5 mmol) and dppb (426 mg, 1 mmol). Anhyd CH2Cl2 (10 mL) was
From styrene (0.156 g, 1.5 mmol) and 2-ethyl-4-bromobenzenesulfo-
nyl chloride (0.284 g, 1 mmol), product 5 was obtained in 32% (0.092
g) yield as a yellow oil.
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A. Skhiri et al.
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 8.5 Hz, 2 H), 7.49 (d, J = 8.5
Hz, 1 H), 7.43–7.25 (m, 6 H), 6.99 (d, J = 16.4 Hz, 1 H), 2.77 (q, J = 7.6
Hz, 2 H), 1.24 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 138.3, 136.6, 133.8, 131.4, 130.8,
128.9, 128.4, 126.8, 126.5, 126.1, 125.2, 123.3.
Anal. Calcd for C14H10Br2 (338.04): C, 49.74; H, 2.98. Found: C, 49.89;
H, 3.12.
13C NMR (100 MHz, CDCl3): δ = 144.0, 137.5, 134.9, 131.7, 130.8,
129.3, 128.9, 128.0, 127.4, 126.7, 125.2, 121.6, 26.4, 15.2.
(E)-1,4-Dibromo-2-styrylbenzene (10)
Anal. Calcd for C16H15Br (287.19): C, 66.91; H, 5.26. Found: C, 67.12; H,
5.15.
From styrene (0.156 g, 1.5 mmol) and 2,5-dibromobenzene-1-sulfo-
nyl chloride (0.334 g, 1 mmol), product 10 was obtained in 76% (0.257
g) yield as a yellow solid; mp 62–64 °C.
(E)-4-Bromo-2-fluoro-1-styrylbenzene (6)
From styrene (0.156 g, 1.5 mmol) and 2-fluoro-4-bromobenzenesul-
fonyl chloride (0.273 g, 1 mmol), product 6 was obtained in 71%
(0.197 g) yield as a white solid; mp 78–80 °C.
1H NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 8.3 Hz, 2 H), 7.47 (t, J = 8.1
Hz, 1 H), 7.38 (t, J = 8.0 Hz, 2 H), 7.35–7.25 (m, 3 H), 7.17 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 160.1 (d, J = 254.1 Hz), 137.0, 131.6 (d,
J = 4.8 Hz), 128.9, 128.3, 128.1 (d, J = 4.3 Hz), 127.7 (d, J = 3.6 Hz),
126.8, 124.5 (d, J = 12.0 Hz), 121.1 (d, J = 9.9 Hz), 120.0 (d, J = 3.4 Hz),
119.5 (d, J = 25.4 Hz).
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 2.3 Hz, 1 H), 7.55 (d, J = 8.3
Hz, 1 H), 7.46–7.20 (m, 7 H), 7.04 (d, J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.2, 136.7, 134.5, 132.8, 131.6,
129.6, 128.9, 128.6, 127.1, 126.3, 122.7, 121.6.
Anal. Calcd for C14H10Br2 (338.04): C, 49.74; H, 2.98. Found: C, 49.47,
H, 3.18.
(E)-1,3,5-Tribromo-2-styrylbenzene (11)
From styrene (0.156 g, 1.5 mmol) and 2,4,6-tribromobenzene-1-sul-
fonyl chloride (0.620 g, 1 mmol), product 11 was obtained in 12%
(0.050 g) yield as a white solid; mp 80–82 °C.
Anal. Calcd for C14H10BrF (277.13): C, 60.68; H, 3.64. Found: C, 60.47;
H, 3.80.
1H NMR (400 MHz, CDCl3): δ = 7.76 (s, 2 H), 7.54 (d, J = 8.0 Hz, 2 H),
7.39 (t, J = 8.0 Hz, 2 H), 7.35 (t, J = 8.0 Hz, 1 H), 6.97 (d, J = 16.4 Hz, 1
H), 6.92 (d, J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.5, 137.4, 136.3, 134.9, 128.9,
128.7, 126.9, 126.1, 124.5, 121.0.
(E)-4-Bromo-1-styryl-2-(trifluoromethyl)benzene (7)
From styrene (0.156 g, 1.5 mmol) and 2-trifluoromethyl-4-bromo-
benzenesulfonyl chloride (0.323 g, 1 mmol), product 7 was obtained
in 79% (0.258 g) yield as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 7.81 (s, 1 H), 7.66 (s, 2 H), 7.53 (d,
J = 8.3 Hz, 2 H), 7.45–7.35 (m, 3 H), 7.33 (t, J = 8.0 Hz, 1 H), 7.09 (d,
J = 16.4 Hz, 1 H).
Anal. Calcd for C14H9Br3 (416.93): C, 40.33; H, 2.18. Found: C, 40.54; H,
2.01.
13C NMR (100 MHz, CDCl3): δ = 136.6, 135.5 (q, J = 1.7 Hz), 135.1,
133.4, 129.3 (q, J = 6.0 Hz), 129.1 (q, J = 31.0 Hz), 128.9, 128.7, 128.6,
127.1, 123.4 (q, J = 274.4 Hz), 123.3 (q, J = 2.0 Hz), 120.9.
(E)-1-Bromo-4-(4-methoxystyryl)benzene (12)21
From 4-methoxystyrene (0.201 g, 1.5 mmol) and 4-bromobenzene-
sulfonyl chloride (0.255 g, 1 mmol), product 12 was obtained in 26%
(0.075 g) yield as a white solid; mp 207–209 °C.
1H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 8.0 Hz, 2 H), 7.43 (d, J = 8.0
Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.05 (d, J = 16.4 Hz, 1 H), 6.93–6.87
(m, 3 H), 3.83 (s, 3 H).
Anal. Calcd for C15H10BrF3 (327.14): C, 55.07; H, 3.08. Found: C, 55.00;
H, 3.22.
(E)-2-Bromo-1-styryl-4-(trifluoromethyl)benzene (8)
From styrene (0.156 g, 1.5 mmol) and 2-bromo-4-trifluoromethyl-
benzenesulfonyl chloride (0.323 g, 1 mmol), product 8 was obtained
in 60% (0.196 g) yield as a colourless oil.
13C NMR (100 MHz, CDCl3): δ = 159.7, 136.8, 131.9, 129.9, 129.1,
127.9, 127.8, 125.4, 120.9, 114.3, 55.5.
1H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 1.7 Hz, 1 H), 7.76 (d, J = 8.2
Hz, 1 H), 7.60–7.55 (m, 3 H), 7.47 (d, J = 16.4 Hz, 1 H), 7.39 (t, J = 8.0
Hz, 2 H), 7.35 (t, J = 8.0 Hz, 1 H), 7.13 (d, J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.8, 136.5, 133.9, 130.5 (q, J = 33.1
Hz), 130.2 (q, J = 3.0 Hz), 128.9, 128.8, 127.2, 126.9, 126.2, 124.5 (q,
J = 3.7 Hz), 124.0, 123.2 (q, J = 272.4 Hz).
(E)-4-(4-Bromostyryl)benzonitrile (13)22
From 4-cyanostyrene (0.194 g, 1.5 mmol) and 4-bromobenzenesulfo-
nyl chloride (0.255 g, 1 mmol), product 13 was obtained in 51% (0.145
g) yield as a yellow solid; mp 192–194 °C.
1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 8.0 Hz, 2 H), 7.57 (d, J = 8.0
Hz, 2 H), 7.51 (d, J = 8.0 Hz, 2 H),7.39 (d, J = 8.0 Hz, 2 H), 7.15 (d,
J = 16.4 Hz, 1 H), 7.07 (d, J = 16.4 Hz, 1 H).
Anal. Calcd for C15H10BrF3 (327.14): C, 55.07; H, 3.08. Found: C, 55.30;
H, 3.07.
13C NMR (100 MHz, CDCl3): δ = 141.6, 135.4, 132.7, 132.1, 131.2,
128.5, 127.6, 127.1, 122.7, 119.1, 111.0.
(E)-1,2-Dibromo-4-styrylbenzene (9)
(E)-1,2-Bis(4-bromophenyl)ethene (14)23
From styrene (0.156 g, 1.5 mmol) and 3,4-dibromobenzene-1-sulfo-
nyl chloride (0.334 g, 1 mmol), product 9 was obtained in 63% (0.213
g) yield as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.76 (d, J = 2.1 Hz, 1 H), 7.57 (d, J = 8.3
Hz, 1 H), 7.50 (d, J = 8.5 Hz, 2 H), 7.37 (t, J = 7.8 Hz, 2 H), 7.35–7.25 (m,
2 H), 7.11 (d, J = 16.4 Hz, 1 H), 6.97 (d, J = 16.4 Hz, 1 H).
From 4-bromostyrene (0.183 g, 1.5 mmol) and 4-bromobenzenesul-
fonyl chloride (0.255 g, 1 mmol), product 14 was obtained in 21%
(0.071 g) yield as a white solid; mp 216–219 °C.
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 8.4 Hz, 4 H), 7.36 (d, J = 8.4
Hz, 4 H), 7.02 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.1, 132.0, 128.3, 128.2, 121.8.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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A. Skhiri et al.
Paper
Synthesis
(E)-1-Bromo-3-(4-bromostyryl)benzene (15)24
(E)-1,2,3,4,5-Pentafluoro-6-(4-iodostyryl)benzene (21)
From 3-bromostyrene (0.366 g, 3 mmol) and 4-bromobenzenesulfo-
nyl chloride (0.255 g, 1 mmol), product 15 was obtained in 54% (0.182
g) yield as a white solid; mp 97–100 °C.
From 2,3,4,5,6-pentafluorostyrene (0.582 g, 3 mmol) and 4-iodoben-
zenesulfonyl chloride (0.303 g, 1 mmol), product 21 was obtained in
72% (0.285 g) yield as a white solid; mp 107110 °C.
1H NMR (400 MHz, CDCl3): δ = 7.65 (s, 1 H), 7.49 (d, J = 8.4 Hz, 2 H),
7.43–7.38 (m, 2 H), 7.36 (d, J = 8.4 Hz, 2 H), 7.22 (t, J = 8.0 Hz, 1 H),
7.03 (d, J = 16.4 Hz, 1 H), 6.99 (d, J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.3, 135.9, 132.0, 130.8, 130.3,
129.4, 129.0, 128.2, 127.9, 125.4, 123.1, 121.9.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.34 (d, J = 16.8
Hz, 1 H), 7.25 (d, J = 8.2 Hz, 2 H), 6.97 (d, J = 16.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 144.9 (dm, J = 250.0 Hz), 140.1 (dm,
J = 250.0 Hz), 138.2, 137.8 (dm, J = 250.0 Hz), 136.1 (m), 128.6, 113.5,
112.3 (t, J = 13.6 Hz), 94.8.
Anal. Calcd for C14H6F5I (396.09): C, 42.45; H, 1.53. Found: C, 42.55, H,
1.41.
(E)-1-Bromo-4-(4-fluorostyryl)benzene (16)25
From 4-fluorostyrene (0.244 g, 3 mmol) and 4-bromobenzenesulfo-
nyl chloride (0.255 g, 1 mmol), product 16 was obtained in 61% (0.169
g) yield as a white solid; mp 138–140 °C.
1H NMR (400 MHz, CDCl3): δ = 7.53–7.45 (m, 4 H), 7.35 (d, J = 8.4 Hz, 2
H), 7.09–7.02 (m, 3 H), 6.92 (d, J = 16.4 Hz, 1 H).
Butyl (E)-3-(4-Bromophenyl)acrylate (22)7
From n-butyl acrylate (0.192 g, 1.5 mmol) and 4-bromobenzenesulfo-
nyl chloride (0.255 g, 1 mmol), product 22 was obtained in 70% (0.198
g) yield as a white solid; mp 37–39 °C.
13C NMR (100 MHz, CDCl3): δ = 162.6 (d, J = 257.5 Hz), 136.3, 133.3,
132.0, 128.4, 128.2 (d, J = 8.0 Hz), 128.0, 127.4 (d, J = 2.4 Hz), 121.5,
115.8 (d, J = 21.9 Hz).
1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 16.0 Hz, 1 H), 7.50 (d, J = 8.3
Hz, 2 H), 7.37 (d, J = 8.3 Hz, 2 H), 6.42 (d, J = 16.0 Hz, 1 H), 4.20 (t,
J = 7.6 Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2 H), 1.41 (sext, J = 7.6 Hz, 2 H),
0.95 (t, J = 7.6 Hz, 3 H).
(E)-1-(4-Bromostyryl)-2,3,4,5,6-pentafluorobenzene (17)23
13C NMR (100 MHz, CDCl3): δ = 166.9, 143.2, 133.5, 132.2, 129.5,
124.5, 119.1, 64.7, 30.9, 19.3, 13.9.
From 2,3,4,5,6-pentafluorostyrene (0.582 g, 3 mmol) and 4-bromo-
benzenesulfonyl chloride (0.255 g, 1 mmol), product 17 was obtained
in 74% (0.258 g) yield as a white solid; mp 104–106 °C.
Butyl (E)-3-(4-Bromo-2-fluorophenyl)acrylate (23)
1H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 8.4 Hz, 2 H), 7.40 (d, J = 8.4
Hz, 2 H), 7.37 (d, J = 16.8 Hz, 1 H), 6.97 (d, J = 16.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 146.9 (dm, J = 250.0 Hz), 140.0 (dm,
J = 250.0 Hz), 137.2 (dm, J = 250.0 Hz), 138.6 (m), 137.7, 132.0, 128.3,
123.0, 113.4 (m), 112.0 (t, J = 13.6 Hz).
From n-butyl acrylate (0.192 g, 1.5 mmol) and 2-fluoro-4-bromoben-
zene-1-sulfonyl chloride (0.273 g, 1 mmol), product 23 was obtained
in 83% (0.250 g) yield as a white solid; mp 36–38 °C.
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 16.0 Hz, 1 H), 7.41 (t, J = 9.0
Hz, 1 H), 7.33–7.26 (m, 2 H), 6.52 (d, J = 16.0 Hz, 1H), 4.21 (t, J = 7.6
Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2 H), 1.41 (sext, J = 7.6 Hz, 2 H), 0.95
(t, J = 7.6 Hz, 3 H).
(E)-2-(4-Bromostyryl)pyridine (18)26
13C NMR (100 MHz, CDCl3): δ = 166.8, 160.9 (d, J = 258.4 Hz), 136.1 (d,
J = 2.5 Hz), 130.0 (d, J = 3.6 Hz), 128.0 (d, J = 3.7 Hz), 124.4 (d, J = 9.7
Hz), 121.8 (d, J = 11.8 Hz), 121.5 (d, J = 6.6 Hz), 120.1 (d, J = 25.3 Hz),
64.8, 30.9, 19.3, 13.8.
From 2-vinylpyridine (0.158 g, 1.5 mmol) and 4-bromobenzenesulfo-
nyl chloride (0.255 g, 1 mmol), product 18 was obtained in 31% (0.081
g) yield as a brown solid; mp 106–108 °C.
1H NMR (400 MHz, CDCl3): δ = 8.61 (d, J = 5.1 Hz, 1 H), 7.82 (d, J = 8.1
Hz, 2 H), 7.74 (td, J = 7.7, 1.6 Hz, 1 H), 7.68 (d, J = 8.1 Hz, 2 H), 7.64 (d,
J = 14.9 Hz, 1 H), 7.42 (d, J = 14.9 Hz, 1 H), 7.40 (d, J = 7.7 Hz, 1 H), 7.28
(dd, J = 7.7, 5.1 Hz, 1 H).
Anal. Calcd for C13H14BrFO2 (301.15): C, 51.85; H, 4.69. Found: C,
51.59; H, 4.87.
13C NMR (100 MHz, CDCl3): δ = 150.9, 150.5, 141.2, 139.5, 137.2,
Butyl (E)-3-[4-Bromo-2-(trifluoromethyl)phenyl]acrylate (24)
132.8, 131.5, 129.6, 129.0, 125.7, 125.3.
From n-butyl acrylate (0.192 g, 1.5 mmol) and 2-trifluoromethyl-4-
bromobenzenesulfonyl chloride (0.323 g, 1 mmol), product 24 was
obtained in 85% (0.298 g) yield as a colourless oil.
(E)-1-Bromo-4-(4-iodostyryl)benzene (19)27
1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 16.0 Hz, 1 H), 7.83 (s, 1 H),
7.69 (d, J = 8.4 Hz, 1 H), 7.57 (d, J = 8.4 Hz, 1 H), 6.40 (d, J = 16.0 Hz, 1
H), 4.22 (t, J = 7.6 Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2 H), 1.41 (sext,
J = 7.6 Hz, 2 H), 0.95 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 166.0, 138.9, 135.4, 132.5, 130.4 (q,
J = 31.1 Hz), 129.6 (q, J = 5.8 Hz), 129.5, 123.8, 123.3, 123.0 (q,
J = 274.7 Hz), 65.0, 30.8, 19.3, 13.9.
From 4-bromostyrene (0.366 g, 3 mmol) and 4-iodobenzenesulfonyl
chloride (0.303 g, 1 mmol), product 19 was obtained in 20% (0.077 g)
yield as a white solid; mp 240–242 °C.
1H NMR (400 MHz, CDCl3): δ = 7.67 (d, J = 8.2 Hz, 2 H), 7.47 (d, J = 8.2
Hz, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.23 (d, J = 8.2 Hz, 2 H), 7.03 (d,
J = 16.3 Hz, 1 H), 6.97 (d, J = 16.3 Hz, 1 H).
(E)-1-Fluoro-4-(4-iodostyryl)benzene (20)28
Anal. Calcd for C14H14BrF3O2 (351.16): C, 47.88; H, 4.02. Found: C,
47.79; H, 4.14.
From 4-fluorostyrene (0.244 g, 3 mmol) and 4-iodobenzenesulfonyl
chloride (0.303 g, 1 mmol), product 20 was obtained in 73% (0.236 g)
yield as a white solid; mp 165–167 °C.
Butyl (E)-3-(5-Bromo-2-methoxyphenyl)acrylate (25)
1H NMR (400 MHz, CDCl3): δ = 7.68 (d, J = 8.3 Hz, 2 H), 7.47 (dd,
J = 8.6, 5.5 Hz, 2 H), 7.23 (d, J = 8.3 Hz, 2 H), 7.10–7.03 (m, 3 H), 6.92
(d, J = 16.4 Hz, 1 H).
From n-butyl acrylate (0.192 g, 1.5 mmol) and 5-bromo-2-methoxy-
benzene-1-sulfonyl chloride (0.285 g, 1 mmol), product 25 was ob-
tained in 78% (0.244 g) yield as a white solid; mp 60–62 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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A. Skhiri et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 16.0 Hz, 1 H), 7.60 (d, J = 2.5
Hz, 1 H), 7.41 (dd, J = 8.8, 2.5 Hz, 1 H), 6.78 (d, J = 8.8 Hz, 1 H), 6.48 (d,
J = 16.0 Hz, 1 H), 4.20 (t, J = 7.6 Hz, 2 H), 3.86 (s, 3 H), 1.68 (quint,
J = 7.6 Hz, 2 H), 1.41 (sext, J = 7.6 Hz, 2 H), 0.96 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.2, 157.4, 138.4, 133.8, 131.2,
125.6, 120.2, 113.1, 113.0, 64.5, 55.9, 30.9, 19.3, 13.9.
13C NMR (100 MHz, CDCl3): δ = 166.8, 143.4, 138.2, 134.0, 129.6,
119.2, 96.5, 64.6, 30.8, 19.3, 13.8.
Butyl (E)-3-(2-Iodo-5-nitrophenyl)acrylate (30)
From n-butyl acrylate (0.192 g, 1.5 mmol) and 2-iodo-5-nitroben-
zene-1-sulfonyl chloride (0.347 g, 1 mmol), product 30 was obtained
in 28% (0.105 g) yield as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.30 (d, J = 2.3 Hz, 1 H), 8.14 (dd,
J = 8.7, 2.3 Hz, 1 H), 8.04 (d, J = 16.0 Hz, 1 H), 7.77 (d, J = 8.7 Hz, 1 H),
6.55 (d, J = 16.0 Hz, 1 H).
Anal. Calcd for C14H17BrO3 (313.19): C, 53.69; H, 5.47. Found: C, 53.48;
H, 5.38.
Butyl (E)-3-[2-Bromo-4-(trifluoromethyl)phenyl]acrylate (26)
From n-butyl acrylate (0.192 g, 1.5 mmol) and 2-bromo-4-trifluoro-
methylbenzenesulfonyl chloride (0.323 g, 1 mmol), product 26 was
obtained in 93% (0.326 g) yield as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 16.0 Hz, 1 H), 7.87 (s, 1 H),
7.69 (d, J = 8.4 Hz, 1 H), 7.54 (d, J = 8.4 Hz, 1 H), 6.45 (d, J = 16.0 Hz, 1
H), 4.24 (t, J = 7.6 Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2 H), 1.41 (sext,
J = 7.6 Hz, 2 H), 0.95 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 166.1, 141.6, 138.3, 132.9 (q, J = 33.5
Hz), 130.5 (q, J = 3.0 Hz), 128.2, 125.2, 124.6 (q, J = 3.7 Hz), 123.6,
123.0 (q, J = 272.7 Hz), 65.0, 30.8, 19.3, 13.9.
13C NMR (100 MHz, CDCl3): δ = 165.8, 148.6, 139.2, 138.2, 135.6,
128.4, 125.5, 125.0, 122.1, 65.2, 30.8, 19.3, 13.9.
Anal. Calcd for C13H14NIO4 (375.16): C, 41.62; H, 3.76. Found: C, 41.66;
H, 3.99.
Ethyl (E)-3-(4-Bromophenyl)but-2-enoate (31)29
From ethyl trans-but-2-enoate (0.171 g, 1.5 mmol) and 4-bromoben-
zenesulfonyl chloride (0.255 g, 1 mmol), product 31 was obtained in
20% (0.054 g) yield as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 6.5 Hz, 2 H), 7.34 (d, J = 6.5
Hz, 2 H), 6.11 (s, 1 H), 4.21 (q, J = 6.7 Hz, 2 H), 2.54 (d, J = 1.3 Hz, 3 H),
1.31 (t, J = 6.7 Hz, 3 H).
Anal. Calcd for C14H14BrF3O2 (351.16): C, 47.88; H, 4.02. Found: C,
47.98; H, 4.19.
13C NMR (100 MHz, CDCl3): δ = 166.8, 154.2, 141.2, 131.8, 128.0,
123.3, 117.8, 60.1, 17.9, 14.5.
Butyl (E)-3-(2,5-Dibromophenyl)acrylate (27)
From n-butyl acrylate (0.192 g, 1.5 mmol) and 1,4-dibromobenzene-
1-sulfonyl chloride (0.334 g, 1 mmol), product 27 was obtained in
91% (0.329 g) yield as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 16.0 Hz, 1 H), 7.72 (d, J = 2.4
Hz, 1 H), 7.46 (d, J = 8.3 Hz, 1 H), 7.29 (dd, J = 8.3, 2.4 Hz, 1 H), 6.39 (d,
J = 16.0 Hz, 1 H), 4.24 (t, J = 7.6 Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2 H),
1.41 (sext, J = 7.6 Hz, 2 H), 0.97 (t, J = 7.6 Hz, 3 H).
(E)-1-Bromo-4-(3,3-dimethylbut-1-enyl)benzene (32)30
From 3,3-dimethylbut-1-ene (0.420 g, 5 mmol) and 4-bromoben-
zenesulfonyl chloride (0.255 g, 1 mmol), product 32 was obtained in
36% (0.086 g) yield as a white solid; mp 62–65 °C.
1H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 6.3 Hz, 2 H), 7.22 (d, J = 6.3
Hz, 2 H), 6.24 (s, 2 H), 1.12 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 142.8, 137.2, 131.6, 127.7, 123.7,
13C NMR (100 MHz, CDCl3): δ = 166.9, 141.5, 136.5, 134.7, 133.9,
130.6, 123.8, 122.4, 121.7, 64.8, 30.8, 19.3, 13.8.
120.5, 33.6, 29.6.
Anal. Calcd for C13H14Br2O2 (362.06): C, 43.13; H, 3.90. Found: C,
43.01; H, 3.87.
(E)-(4-Iodostyryl)dimethyl(phenyl)silane (33)
From dimethyl(phenyl)(vinyl)silane (0.243 g, 1.5 mmol) and 4-iodo-
benzenesulfonyl chloride (0.303 g, 1 mmol), product 33 was obtained
in 31% (0.113 g) yield as a colourless oil.
1H NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 8.3 Hz, 2 H), 7.60–7.53 (m, 2
H), 7.40–7.35 (m, 3 H), 7.18 (d, J = 8.3 Hz, 2 H), 6.85 (d, J = 19.1 Hz, 1
H), 6.59 (d, J = 19.1 Hz, 1 H), 0.44 (s, 6 H).
Butyl (E)-3-(3,4-Dibromophenyl)acrylate (28)
From n-butyl acrylate (0.192 g, 1.5 mmol) and 3,4-dibromobenzene-
1-sulfonyl chloride (0.334 g, 1 mmol), product 28 was obtained in
59% (0.214 g) yield as a yellow solid; mp 38–41 °C.
1H NMR (400 MHz, CDCl3): δ = 7.76 (d, J = 2.1 Hz, 1 H), 7.62 (d, J = 8.3
Hz, 1 H), 7.54 (d, J = 16.0 Hz, 1 H), 7.30 (dd, J = 8.3, 2.1 Hz, 1 H), 6.43
(d, J = 16.0 Hz, 1 H), 4.21 (t, J = 7.6 Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2
H), 1.41 (sext, J = 7.6 Hz, 2 H), 0.95 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 144.2, 138.3, 137.8, 137.7, 134.0,
129.3, 128.6, 128.4, 128.0, 93.8, –2.5.
Anal. Calcd for C16H17ISi (364.30): C, 52.75, H, 4.70. Found: C, 52.64, H,
4.48.
13C NMR (100 MHz, CDCl3): δ = 166.8, 141.8, 135.4, 134.2, 132.9,
127.7, 126.6, 125.6, 120.4, 64.8, 30.9, 19.3, 13.9.
Anal. Calcd for C13H14Br2O2 (362.06): C, 43.13; H, 3.90. Found: C,
43.20; H, 3.99.
(E)-2-Ethyl-4-methyl-5-(4-styrylphenyl)thiazole (34)
(E)-1-Bromo-4-styrylbenzene (1; 0.259 g, 1 mmol), 2-ethyl-4-meth-
ylthiazole (0.191 g, 1.5 mmol), KOAc (0.196 g,
2 mmol), and
Butyl (E)-3-(4-Iodophenyl)acrylate (29)7
PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) were dissolved in DMA (2
mL) under an argon atmosphere. The reaction mixture was stirred at
130 °C for 24 h. After evaporation of the solvent, the product was pu-
rified by silica gel column chromatography affording 34 in 53% (0.162
g) yield as a yellow solid; mp 112–114 °C.
From n-butyl acrylate (0.192 g, 1.5 mmol) and 4-iodobenzenesulfonyl
chloride (0.303 g, 1 mmol), product 29 was obtained in 82% (0.271 g)
yield as a white solid; mp 39–41 °C.
1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 8.3 Hz, 2 H), 7.57 (d, J = 16.0
Hz, 1 H), 7.23 (d, J = 8.3 Hz, 2 H), 6.43 (d, J = 16.0 Hz, 1 H), 4.20 (t,
J = 7.6 Hz, 2 H), 1.68 (quint, J = 7.6 Hz, 2 H), 1.41 (sext, J = 7.6 Hz, 2 H),
0.95 (t, J = 7.6 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.5 Hz, 2 H), 7.56 (d, J = 8.5
Hz, 2 H), 7.47–7.35 (m, 4 H), 7.30 (t, J = 7.4 Hz, 1 H), 7.19 (d, J = 16.4
Hz, 1 H), 7.14 (d, J = 16.4 Hz, 1 H), 3.04 (q, J = 7.6 Hz, 2 H), 2.53 (s, 3 H),
1.44 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 170.4, 147.1, 137.3, 136.8, 131.7,
130.9, 129.5, 129.4, 128.9, 128.0, 127.9, 126.8, 126.7, 27.1, 16.4, 14.5.
(5) For a single example of Pd-catalysed Heck type reaction with a
4-bromobenzenesulfonyl chloride, see: (a) Miura, M.;
Hashimoto, H.; Itoh, K.; Nomura, M. J. Chem. Soc., Perkin Trans. 1
1990, 2207. For an example of Pd-catalysed Heck type reaction
with a 4-bromobenzenesulfinate, see: (b) Zhou, X.; Luo, J.; Liu,
J.; Peng, S.; Deng, G.-J. Org. Lett. 2011, 13, 1432. (c) Hu, S.; Xia,
P.; Cheng, K.; Qi, C. Appl. Organomet. Chem. 2013, 27, 188. For
examples of Pd-catalysed Heck type reaction with a 4-bromo-
benzenesulfonyl hydrazide, see: (d) Yang, F.-L.; Ma, X.-T.; Tian,
S.-K. Chem. Eur. J. 2012, 18, 1582.
Anal. Calcd for C20H19NS (305.44): C, 78.65; H, 6.27. Found: C, 78.79,
H, 6.09.
(E)-2-Pentyl-5-(4-styrylphenyl)thiophene (35)
(6) For a single example of Rh-catalysed Heck type reaction with a
4-bromobenzenesulfonyl chloride, see: Dubbaka, S. R.; Vogel, P.
Chem. Eur. J. 2005, 11, 2633.
(E)-1-Bromo-4-styrylbenzene (1; 0.259 g, 1 mmol), 2-pentylthio-
phene (0.231 g, 1.5 mmol), KOAc (0.196 g,
2 mmol), and
PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) were dissolved in DMA (2
mL) under an argon atmosphere. The reaction mixture was stirred at
130 °C for 24 h. After evaporation of the solvent, the product was pu-
rified by silica gel column chromatography affording 35 in 51% (0.169
g) yield as a brown solid; mp 190–192 °C.
1H NMR (400 MHz, CDCl3): δ = 7.60–7.46 (m, 6 H), 7.37 (t, J = 7.4 Hz, 2
H), 7.26 (t, J = 7.4 Hz, 1 H), 7.15 (d, J = 3.5 Hz, 1 H), 7.11 (s, 2 H), 6.75
(d, J = 3.5 Hz, 1 H), 2.81 (t, J = 7.6 Hz, 2 H), 1.77–1.65 (m, 2 H), 1.44–
1.33 (m, 4 H), 0.92 (t, J = 7.6 Hz, 3 H).
(7) For examples of Ru-catalysed Heck type reaction with halo-
substituted arylboronic acids, see: Farrington, E. J.; Barnard, C. F.
J.; Rowsell, E.; Brown, J. M. Adv. Synth. Catal. 2005, 347, 185.
(8) For a review on transition-metal-mediated C–S bond activation,
see: Wang, L.; He, W.; Yu, Z. Chem. Soc. Rev. 2013, 42, 599.
(9) For selected examples of Pd-catalysed direct arylations via
desulfitative coupling from our laboratory, see: (a) Yuan, K.;
Doucet, H. Chem. Sci. 2014, 5, 392. (b) Loukotova, L.; Yuan, K.;
Doucet, H. ChemCatChem 2014, 6, 1303. (c) Hfaiedh, A.; Yuan,
K.; Ben Ammar, H.; Ben Hassine, B.; Soulé, J.-F.; Doucet, H.
ChemSusChem 2015, 8, 1794.
13C NMR (100 MHz, CDCl3): δ = 146.0, 141.5, 137.5, 136.1, 134.1,
128.8, 128.5, 128.3, 127.7, 127.1, 126.6, 125.7, 125.2, 122.8, 31.5, 31.4,
30.4, 22.6, 14.2.
(10) For Pd-catalysed conjugate addition using benzenesulfonyl
chlorides and enones, see: Yuan, K.; Sang, R.; Soulé, J.-F.;
Doucet, H. Catal. Sci. Technol. 2015, 5, 2904.
Anal. Calcd for C23H24S (332.50): C, 83.08, H, 7.28. Found: C, 82.94; H,
7.30.
(11) Amatore, C.; Jutand, A.; Le Duc, G. Chem. Eur. J. 2012, 18, 6616.
(12) (a) Loeser, R.; Bergmann, R.; Frizler, M.; Mosch, B.;
Dombrowski, L.; Kuchar, M.; Steinbach, J.; Guetschow, M.;
Pietzsch, J. ChemMedChem 2013, 8, 1330. (b) Nielsen, C. B.;
Johnsen, M.; Arnbjerg, J.; Pittelkow, M.; McIlroy, S. P.; Ogilby, P.
R.; Jorgensen, M. J. Org. Chem. 2005, 70, 7065. (c) Biet, T.; Fihey,
A.; Cauchy, T.; Vanthuyne, N.; Roussel, C.; Crassous, J.; Avarvari,
N. Chem. Eur. J. 2013, 19, 13160.
Acknowledgment
We thank the Centre National de la Recherche Scientifique, and
Rennes Metropole and Scientific Ministry of Higher Education and
Research of Tunisia for providing financial support.
(13) For selected examples of Heck type reactions with disubstituted
alkenes, see: (a) Melpolder, J.; Heck, R. J. Org. Chem. 1976, 41,
265. (b) Cortese, N.; Ziegler, C.; Hrnjez, B.; Heck, R. J. Org. Chem.
1978, 43, 2952. (c) Cacchi, S.; Arcadi, A. J. Org. Chem. 1983, 48,
4236. (d) Amorese, A.; Arcadi, A.; Bernocchi, E.; Cacchi, S.;
Cerrini, S.; Fereli, W.; Ortar, G. Tetrahedron 1989, 45, 813.
(e) Beller, M.; Riermeier, T. Tetrahedron Lett. 1996, 37, 6535.
(f) Beller, M.; Riermeier, T. Eur. J. Inorg. Chem. 1998, 1, 29.
(g) Netherton, M.; Fu, G. Org. Lett. 2001, 3, 4295. (h) Berthiol, F.;
Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2003, 1091.
(i) Kondolff, I.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2003,
44, 8487.
(14) Zhao, X.; Dong, V. M. Angew. Chem. Int. Ed. 2011, 50, 932.
(15) For reviews, see: (a) Satoh, T.; Miura, M. Chem. Lett. 2007, 36,
200. (b) Li, B.-J.; Yang, S.-D.; Shi, Z.-J. Synlett 2008, 949.
(c) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269.
(d) Ackermann, L.; Vicente, R.; Kapdi, A. Angew. Chem. Int. Ed.
2009, 48, 9792. (e) Joucla, L.; Djakovitch, L. Adv. Synth. Catal.
2009, 351, 673. (f) Ackermann, L. Chem. Rev. 2011, 111, 1315.
(g) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F.
Angew. Chem. Int. Ed. 2012, 51, 10236. (h) Neufeldt, S. R.;
Sanford, M. S. Acc. Chem. Res. 2012, 45, 936. (i) Wencel-Delord,
J.; Glorius, F. Nat. Chem. 2013, 5, 369. (j) Rossi, R.; Bellina, F.;
Lessi, M.; Manzini, C. Adv. Synth. Catal. 2014, 356, 17. (k) He, M.;
Soulé, J.-F.; Doucet, H. ChemCatChem 2014, 6, 1824. (l) Miura,
M.; Satoh, T.; Hirano, K. Bull. Chem. Soc. Jpn 2014, 87, 751.
(m) Bheeter, C. B.; Chen, L.; Soulé, J.-F.; Doucet, H. Catal. Sci.
Technol. 2016, 6, 2005.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562114.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J