Synthesis of functionalized benzothiophenes and dibenzothiophenes by twofold Heck and subsequent 6π-electrocyclization reactions of 2,3-dibromothiophenes and 2,3-dibromobenzothiophenes

Article abstract of DOI:10.1016/j.tet.2012.10.050

Benzothiophenes and dibenzothiophenes were prepared by twofold Heck reactions of 2,3-dibromothiophene and 2,3-dibromobenzothiophene, respectively, and subsequent thermal 6π-electrocyclization. The Heck reaction of 2,3-dibromothiophene and 2,3-dibromobenzo

Full text of DOI:10.1016/j.tet.2012.10.050

Tetrahedron 69 (2013) 160e173
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of functionalized benzothiophenes and dibenzothiophenes
by twofold Heck and subsequent 6
p-electrocyclization reactions
of 2,3-dibromothiophenes and 2,3-dibromobenzothiophenes
a
a,
Serge-Mitherand Tengho Toguem , Imran Malik b, Munawar Hussain a, Jamshed Iqbal c,
ꢀ
Alexander Villinger a, Peter Langer a
,d,
*
a
€
€
Institut fur Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan
c Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan
d
€
€
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 August 2012
Received in revised form 11 October 2012
Accepted 16 October 2012
Available online 23 October 2012
Benzothiophenes and dibenzothiophenes were prepared by twofold Heck reactions of 2,3-dibromothiophene
and 2,3-dibromobenzothiophene, respectively, and subsequent thermal 6p-electrocyclization. The Heck
reaction of 2,3-dibromothiophene and 2,3-dibromobenzothiophene with 1 equiv of alkenes proceeded with
different regioselectivities and afforded 2-alkenylthiophenes and 3-alkenylbenzothiophenes.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Catalysis
Heck reaction
Palladium
Cyclization
Heterocycles
N
O
1. Introduction
OH
The benzothiophene skeleton occurs in the structure of many
natural, synthetic, and biologically active molecules, including
bryoanthrathiophene,1 mobam (4-(N-methyl carbamoyl)benzo[b]-
thiophene)2 and 3-(2-aminoethyl) benzo[b]thiophene.3 Parent
benzothiophene has been found in the coal tar.4 Raloxifene, zileu-
ton, and sertaconazole represent important drugs containing
a benzothiophene unit.5 Benzothiophene derivatives have been
reported as antiangiogenics,1 anti-inflammatories,6 analgesics,7
enzyme inhibitors,6 antiestrogen,8 antitumor,9 and pesticides.10
Due to their significant pharmacological properties, many meth-
odologies for the synthesis of benzothiophenes have been reported
in recent years (Fig. 1).11
O
O
OH
Me
OH
S
S
HO
Bryoanthrathiophene
Raloxifene
N
N
Cl
HO
O
We have reported preliminary results related to the synthesis of
benzothiophenes and dibenzothiophenes by twofold Heckreactions
of 2,3-dibromothiophene12 and 2,3-dibromobenzothiophene,13 re-
N
O
NH2
Cl
S
Me
spectively, and subsequent 6p-electrocyclization/dehydrogenation
reactions. Herein, we report full details of these studies and
S
Zileuton
Sertaconazole
Cl
* Corresponding author. Tel.: þ49 (381)4986410; fax: þ49 (381)4986412; e-mail
address: peter.langer@uni-rostock.de (P. Langer).
Fig. 1. Structure of raloxifene, bryoanthrathiophene, zileuton and sertaconazole.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.050

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
161
extension of the scope to 4,5-dibromothiophene-2-carbaldehyde
and 5-aryl-2,3-dibromothiophenes, which are readily available by
SuzukieMiyaura reactions of 2,3,5-tribromothiophene.
PCy2
iPr
PCy2
OMe
iPr
MeO
2. Results and discussion
2.1. 2,3-Dibromothiophene
Cy = Cyclohexyl
iPr
SPhos
XPhos
The Heck reaction of 2,3-dibromothiophene (1) with alkenes 2
(2.5 equiv) afforded the 2,3-di(alkenyl)benzothiophenes 3aek in
good yields (Scheme 1, Table 1). The best yields were obtained
when the reactions were carried out using Pd(OAc)2 (5 mol %) using
SPhos or XPhos (10 mol %). These biaryl monophosphine ligands
were recently developed by Buchwald and co-workers (Fig. 2).14
The reactions were carried out in DMF at 120 ꢀC for 48 h. The
employment of Pd(PPh3)4 resulted in lower yields. Heating of
a xylene solution of 3aee and 3gek in the presence of Pd/C resulted
in the formation of benzothiophenes 4aee and 4gek in quantita-
Fig. 2. Biaryl monophosphine ligands developed by Buchwald and co-workers.
tive yields. The products are formed by thermal 6p-electro-
cyclization and subsequent dehydrogenation. The reaction had to
be carried out at 200 ꢀC as no conversion was observed at lower
temperatures.
R
R
Br
Br
2
R
i
S
1
S
3a-k
ii
R
R
iii
R
R
S
Fig. 3. Crystal structure of 3i.
S
4a-e, g-k
A
Scheme 1. Synthesis of 3aek and 4aee,gek. Conditions: (i), 2 (2.5 equiv), Pd(OAc)2
(5 mol %), SPhos or XPhos (10 mol %), NEt3, DMF, 120 ꢀC, 48 h; (ii), xylene, 200 ꢀC, 24 h;
(iii), Pd/C (10 mol %), xylene, 200 ꢀC, 48 h.
Table 1
Synthesis of 3aek and 4aee,gek
Scheme 2. Synthesis of 5aee. Conditions: (i), 2 (1.0 equiv), Pd(OAc)2 (2.5e5 mol %),
SPhos or XPhos (5e10 mol %), NEt3, DMF, 120 ꢀC, 24 h.
2, 3, 4
R
% (3)a
% (4)a
a
b
c
d
e
f
g
h
i
CO2Me
81b
90c
86b
93c
92c
89b
85c
94c
83c
88b
82c
98
99
98
98
97
dd
97
98
97
95
dd
Table 2
Synthesis of 5aee
CO2Et
COi2Bu
COn2Bu
2
5
R
% (5)a
COn2Hex
a
b
c
f
a
b
c
d
e
CO2Me
CO2Et
75b
78c
74b
87b
76c
COt2Bu
CO2[CH2CH(Et)(CH2)3CH3]
4-tBuC6H4
4-(MeO)C6H4
4-MeC6H4
4-ClC6H4
COi2Bu
COt2Bu
COn2Hex
e
j
k
a
b
c
Yields of isolated products.
XPhos was used.
SPhos was used.
a
Yields of isolated products.
XPhos was used.
SPhos was used.
b
c
d
Experiment was not carried out.
2.2. 4,5-Dibromothiophene-2-carbaldhyde
The structure of 3i was independently confirmed by X-ray
crystal structure analysis (Fig. 3). In both structures, the two alkenyl
groups are in the same plane and almost in the plane of the thio-
phene ring (torsion angle 0.8 (2)ꢀ).
The Heck reaction of 1 with only 1 equiv of alkenes 2 resulted in
the formation of 2-alkenylthiophenes 5aee by regioselective cou-
pling and subsequent Pd(0)-catalyzed reduction (Scheme 2, Table 2).
The Heck reaction of commercially available 4,5-
dibromothiophene-2-carbaldehyde (6) with 2.5 equiv of alkenes 2
did not give the expected products 9, but 5-alkenylthiophene-2-
carbaldehyde. The formation of these products can be explained by
regioselective coupling of carbon atom C-5 of 6 with the alkenes 2 and
subsequent Pd(0)-catalyzed reduction of one CeBr bond. The

162
S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
reduction can be due to the presence of the aldehyde, an electron
withdrawing group, which makes the molecule more prone to re-
duction. To solve the problem, we have protected the aldehyde as
a Schiff base. The reaction of 6 with 1.5 equiv of 4-methoxyaniline in
glacial acetic acid gave the (E)-4-aryl-N-((4,5-dibromothiophen-2-yl)
methylene) 7 (Scheme 3). The Heck reaction of 7 with alkenes 2
(2.5 equiv) afforded the desired compounds 8aed in 55e76% yield
(Scheme 3, Table 3). The reactions were carried out using Pd(OAc)2
(5 mol %) as the catalyst in the presence of SPhos or P(Cy)3 (10 mol %).
The 1-formyl-4,5-dialkenylthiophenes 9aed were obtained by hy-
drolysis of the imino groupof 8aed(deprotection) (Scheme 3, Table 4).
11aed with alkenes 2 afforded the 2-aryl-4,5-di(alkenyl) thio-
phenes 12aed in 75e89% yield (Scheme 4, Table 5). The reactions
were carried out using P(Cy)3 (10 mol %) as ligand. Products 12aed
were transformed to benzothiophenes 13aed in 82e93% yield.
The structure of 13d was independently confirmed by X-ray
crystal structure analysis (Fig. 5). The phenyl ring located at carbon
C1a and the benzothiophene moiety are in plane. The torsion angles
between the benzothiophene and alkenyl groups are 19.7 (8) and
66.1 (3)ꢀ for O5aeC21aeC7aeC8 and O3aeC16aeC6aeC7a, re-
spectively.
R
R
Br
2
R
H
R
Pd/C
v, vi
S
H
Br
R
O
-CO
i
S
6
9a-d
S
O
4a,c,d,e
ii
Ar-NH2
iv
H2SO4
R
R
2
Br
Br
iii
S
Ar
N
R
S
N
Ar
7
8a-d
Ar = (MeO)C6H4 ( 98%)
Scheme 3. Synthesis of 7, 8aed, 9aed and 4a,c,d,e. Conditions: (i), 2 (2.5 equiv), Pd(OAc)2 (5 mol %), SPhos, XPhos or P(Cy)3 (10 mol %), NEt3 (8.0 equiv), DMF, 90 ꢀC, 12 h; (ii), 30
(1.0 equiv), 4-methoxyaniline (1.5 equiv), glacial acetic acid, 20 ꢀC, 15 min; (iii), 2 (2.5 equiv), Pd(OAc)2 (5 mol %), SPhos or P(Cy)3 (10 mol %), NEt3 (8.0 equiv), DMF, 90 ꢀC, 12 h; (iv),
8aed, dichloromethane, (H2SO4, 2.5 M), 20 ꢀC, 20 h; (v), 9aed, xylene, 200 ꢀC, 24 h; (vi), Pd/C (10 mol %), xylene, 200 ꢀC, 48 h.
Table 3
Synthesis of 8aed
2
8
R
% (8)a
a
c
d
e
a
b
c
CO2Me
COi2Bu
COn2Bu
COn2Hex
62b
76c
55c
67c
d
a
b
c
Yields of isolated products.
SPhos was used.
P(Cy)3 was used.
Table 4
Synthesis of 9aed
8, 9
R
% (9)a
Fig. 4. Molecular structure of 7.
a
b
c
CO2Me
COi2Bu
COn2Bu
COn2Hex
98
95
92
96
The reaction of benzothiophene (14) with bromine (2.0 equiv)
and KOAc (2.0 equiv) in CH2Cl2 (reflux, 18 h) resulted in formation
of (commercially available) 2,3-dibromobenzothiophene (15a) in
84% yield (Scheme 5).17,18 During our experiments related to the
scale-up of this reaction we have found that more vigorous con-
ditions (reflux, 18 h) were required to avoid the formation of
monobrominated byproducts. We have also prepared known19
2,3,6-tribromobenzothiophene (15b) in 70% yield by using an ex-
cess of bromine.
The Heck reaction of 15a with acrylates 2d,l (2.5 equiv) afforded
the 2,3-di(alkenyl)benzothiophenes 16b,e in good yields (Scheme 6,
Table 6). The best yields were obtained when the reactions were
carried out using Pd(OAc)2 (5 mol %) and the biaryl monophosphine
ligand SPhos (10 mol %). The reactions were carried out in DMF at
100 ꢀC for 12 h. Heating of a xylene solution of 16b,e in the presence
of Pd/C resulted in the formation of dibenzothiophene 18b,e in
79e81% yield. The employment of Pd(PPh3)4 and other catalysts and
ligands proved to be less successful in terms of yield.
d
a
Yields of isolated products.
Compounds 4a,c,d,e were formed after thermal 6
p
-electro-
cyclization and aromatization of 9aed. The formation of 4a,c,d,e
can be explained by thermal extrusion of CO. The structures of 7
were independently confirmed by X-ray crystal structure analysis
(Fig. 4). The phenyl ring at C6 is twisted from the plane of the
thiophene by ꢁ2.9 (9)ꢀ. The NeC5eC4 bond angle is 121.5 (3)ꢀ.
2.3. 5-Aryl-2,3-dibromothiophenes
2,3,5-Tribromothiophene (10) was prepared by reaction of thio-
phene with bromine (3.1 equiv) in 81% yield.15 The SuzukieMiyaura
reaction of 10 with aryl boronic acids (1.1 equiv) afforded the 5-aryl-
2,3-dibromothiophenes 11aed16 (Scheme 4). The Heck reaction of

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
163
was established by X-ray crystal structure analysis.13 The best yield
(81%) was obtained when 15a was treated with ethyl acrylate (2b)
using Pd(OAc)2 (5 mol %) in combination with biaryl mono-
phosphine ligand SPhos (10 mol %). The yields dropped when
Pd(PPh3)4 was used. The formation of products 19 can be explained
by Heck reaction, which occurs at carbon atom C-3, and reduction
of the bromide function located at carbon C-2. This result is sur-
prising because the Heck reaction of 2,3-dibromothiophene with
1 equiv of alkenes results in the formation of 2-alkenylthiophenes 5
(vide supra).
The Heck reaction of styrene (2l) with 2,3,6-tribromobenzo-
thiophene (15b) gave the 2,3,6-tri(alkenyl)benzothiophenes 20
(Scheme 8). The reaction was carried out in DMF at 100 ꢀC for 12 h;
Pd(OAc)2 in the presence of SPhos was used asthe catalyst. Product 21
was isolated (mixture of two isomers) when the reaction was carried
out at 130 ꢀC. Reflux of a xylene solution of crude 20 or 21, in the
presence of Pd/C, afforded the 2,3-diphenyl-7-styryldibenzo-
thiophene 22.
Scheme 4. Synthesis of 12aed and 13aed. Conditions: (i), 1 (1.0 equiv), ArB(OH)2
(1.1 equiv), Pd(PPh3)4 (5 mol %), K2CO3 (2 M), 1,4-dioxane/toluene¼1:1, 100 ꢀC, 12 h;
(ii), 11aed(1 equiv),
2 (2.5 equiv), Pd(OAc)2 (5 mol %), P(Cy)3 (10 mol %), NEt3
(8.0 equiv), DMF, 100 ꢀC, 24 h; (iii), 12aed, diphenylether, 200 ꢀC, 24 h; (iv), Pd/C
(10 mol %), diphenylether, 200 ꢀC, 48 h.
3. Conclusion
Table 5
2,3-Dialkenylthiophenes, 4,5-dialkenylthiophene-2-carbaldehyd-
es, 2,3-dialkenyl-5-aryl thiophenes, and 2,3-dialkenylbenzothiop-
henes were prepared by the first Heck reactions of 2,3-dibromo
thiophenes, 4,5-dibromothiophene-2-carbaldehydes, 5-aryl-2,3-
dibromothiophenes, and 2,3-dibromobenzothiophene, respectively.
Functionalized benzothiophenes and dibenzothiophenes were
Synthesis of 12aed and 13aed
2
11, 12, 13
Ar
R
% (12)a
% (13)a
c
d
c
c
a
b
c
4-EtC6H4
COi2Bu
COn2Bu
COi2Bu
COi2Bu
89
75
78
76
93
82
85
88
4-tBuC6H4
3,5-Me2C6H3
2-(MeO)C6H4
d
prepared by Pd/C-catalyzed domino ‘6p-electrocyclization/de-
a
Yields of isolated products.
hydrogenation’ reactions of the 2,3-dialkenylthiophenes and 2,3-
Fig. 5. Crystal structure of 13d.
The Pd(OAc)2-catalyzed reaction of 15a with acrylates 2b,c,e
dialkenylbenzothiophenes. The reaction of 2,3-dibromothiophene
with 1 equiv of alkenes resulted in the formation of 2-alkenylthio-
phenes, while the corresponding reaction of 2,3-dibromobenz-
othiophene proceeded with different regioselectivity and gave
3-alkenylbenzothiophenes.
carried out at 130 ꢀC and using biaryl monophosphine ligand SPhos,
afforded the 1,2-dihydrodibenzothiophenes 17a,c,d as a mixture of
two isomers. Their formation can be explained by a domino ‘two-
fold Heck/thermal
6p-electrocyclization’ cyclization and sub-
sequent double bond migration. Heating of a xylene solution of
crude 17a,c,d in the presence of Pd/C resulted in the formation of
dibenzothiophenes 18a,c,d in 74e77% overall yields. The reaction of
15a with styrene 2k directly afforded dibenzothiophene 18f (83%)
in only one step.
4. Experimental section
4.1. General
SuzukieMiyaura and Stille reactions of 15a regioselectively oc-
cur at carbon atom C-2. Therefore, it was surprising that the Heck
reaction of 15a with 1 equiv of alkenes 2b,d,j,m,l afforded the 3-
(alkenyl)benzothiophenes 19aee (Scheme 7, Table 7). The structure
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR
spectra the deuterated solvents indicated were used. Mass spec-
trometric data (MS) were obtained by electron ionization (EI,

164
S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
Table 7
Synthesis of 19aee
Br
Br
2
19
R
% (19)a
S
b
d
m
l
a
b
c
d
e
CO2Et
COn2Bu
CN
Ph
4-MeC6H4
81
65
51
74
76
i
15a (84%)
j
S
Br
S
a
Yields of isolated products.
14
ii
Br
Br
4.2. General procedure A for the synthesis of di(alkenyl)
thiophenes (3), (8), (9) and (12)
15b (70%)
Scheme 5. Bromination of benzothiophene (14). Reagents and conditions: (i) Br2
(2.0 equiv), KOAc (2.0 equiv), CH2Cl2, reflux, 18 h; (ii) Br2 (4.5 equiv), KOAc (4.5 equiv),
CH2Cl2, reflux, 24 h.
In a pressure tube (glass bomb) a suspension of Pd(OAc)2 (12 mg,
0.05 mmol, 5 mol %) and L [XPhos, SPhos or P(Cy)3] (10 mol %) in DMF
(5 mL) was purged with argon and stirred at 20 ꢀC to give a yellowish
or brownish clear solution. To the stirred solution were added 2,3-
dibromothiophene (1), 7a,b or 11aed (1.0 mmol), NEt3 (1.1 mL,
8.0 mmol) and analkene(1.25 equiv per Br). The reaction mixturewas
stirred at 100e120 ꢀC for 24e48 h. The solution was cooled to 20 ꢀC,
poured into H2O and CH2Cl2 (25 mL each), and the organic and the
aqueous layer were separated. The latter was extracted with CH2Cl2
(3ꢂ25 mL). The combined organic layers were washed with H2O
(3ꢂ20 mL), dried (Na2SO4), and concentrated in vacuo. The residue
was purified by chromatography (flash silica gel, heptanes/EtOAc).
R
R
R
Br
R
S
+
Br
2b,c,e
R
S
ii
15a
S
R
17a,c,d
i
4.2.1. (2E,20E)-Dimethyl 3,30-(thiophene-2,3-diyl)diacrylate (3a).
Product 3a was prepared starting with 1 (242 mg, 1.0 mmol), methyl
acrylate (0.23 mL, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), XPhos
(10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h
following general procedure A, as a brown oil (204 mg, 81%). 1H NMR
2d,l
iii
R
R
R
R
iii
(300 MHz, CDCl3):
d
¼3.74 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 6.22 (d,
1H, J¼15.5 Hz, CH), 6.24 (d, 1H, J¼15.8 Hz, CH), 7.18 (d, 1H, J¼5.5 Hz,
ArH), 7.25 (d, 1H, J¼5.3 Hz, ArH), 7.79 (d, 1H, J¼15.8 Hz, CH), 7.94 (d,
S
18a-f
S
1H, J¼15.6 Hz, CH). 13C NMR (62 MHz, CDCl3):
¼51.8, 51.9 (OCH3),
d
16b,e
118.8, 120.0, 126.4, 127.8, 133.7, 134.7 (CH), 138.2, 139.8 (C), 166.7,
Scheme 6. Synthesis of 16b,e and 18aef. Reagents and conditions: (i) Pd(OAc)2
(5 mol %), XPhos (10 mol %), 2 (2.5 equiv), Et3N (8.0 equiv), DMF, 100 ꢀC, 12 h; (ii)
Pd(OAc)2 (5 mol %), SPhos (10 mol %), 2 (2.5 equiv), Et3N, DMF, 130 ꢀC, 48 h; (iii) Pd/C
(10 mol %), xylene, reflux, 48 h.
167.1 (CO). IR (KBr, cmꢁ1):
n¼3110, 2950, 2923 (w),1705 (s),1631 (m),
1513 (w), 1427, 1308, 1270 (m), 1190, 1170, 1159 (s), 1110, 1009 (m),
972, 805 (s), 724, 709, 612, 575, 535 (m). GCeMS (EI, 70 eV): m/z (%)¼
252 (30) [M]þ, 221 (13), 193 (45), 192 (22), 177 (22), 161 (58), 149
(26), 135 (13), 134 (100), 133 (18), 89 (19), 67 (13). HRMS (EI, 70 eV):
calcd for C12H12O4S [M]þ: 252.04508; found: 252.04533.
Table 6
Synthesis of 16b,e and 18aef
2
16, 18
R
% (16)a
% (18)a
4.2.2. (2E,20E)-Diethyl 3,30-(thiophene-2,3-diyl)diacrylate (3b).
Product 3b was prepared starting with 1 (242 mg, 1.0 mmol), ethyl
acrylate (0.27 mL, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), SPhos
(10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h
following general procedure A, as a brown semisolid (252 mg, 90%).
b
d
c
e
l
a
b
c
d
e
f
CO2Et
COn2Bu
COi2Bu
COn2Hex
Ph
db
76
81
74
71
db
db
85
77
79
k
4-ClC6H4
db
83c
1H NMR (300 MHz, CDCl3):
d
¼1.26 (t, 3H, J¼7.1 Hz, CH3), 1.27 (t, 3H,
a
b
c
Yields of isolated products based on 15a.
Experiment was not carried out.
Product was directly formed from 15a in one step.
J¼7.1 Hz, CH3), 4.20 (q, 2H, J¼7.1 Hz, CH2O), 4.21 (q, 2H, J¼7.1 Hz,
CH2O), 6.23 (d, 1H, J¼15.5 Hz, CH), 6.24 (d, 1H, J¼15.8 Hz, CH), 7.18
(d, 1H, J¼5.6 Hz, ArH), 7.24 (d, 1H, J¼5.3 Hz, ArH), 7.79 (d, 1H,
J¼15.8 Hz, CH), 7.93 (d, 1H, J¼15.5 Hz, CH). 13C NMR (62 MHz,
70 eV), chemical ionization (CI, isobutane) or electrospray ioniza-
tion (ESI). For preparative scale chromatography silica gel 60
(0.063e0.200 mm, 70e230 mesh) was used. Details of the crystal
structure analyses are given in Ref. 20.
CDCl3):
d
¼14.3 (2CH3), 60.6, 60.7 (CH2O), 119.2, 120.4, 126.4, 127.7,
133.5, 134.5 (CH), 138.2, 139.8 (C), 166.3, 166.7 (CO). IR (KBr, cmꢁ1):
n
¼3095, 2985, 2939, 2872 (w), 1697 (s), 1621 (m), 1505, 1471, 1443,
1394 (w),1369,1315,1298, 1278, 1254, 1212 (m), 1176 (s), 1110,1028,
976, 956, 868, 851 (m), 831, 808 (w), 771, 764, 718, 701, 664, 627,
582 (m). GCeMS (EI, 70 eV): m/z (%)¼280 (24) [M]þ, 235 (11), 207
(31), 206 (15), 179 (21), 178 (08), 163 (45), 162 (07), 161 (34), 136
(12), 135 (100), 134 (44), 91 (16), 89 (13), 29 (19). HRMS (EI, 70 eV):
calcd for C14H16O4S [M]þ: 280.07638; found: 280.07680.
Scheme 7. Synthesis of 19aee. Reagents and conditions: (i), Pd(OAc)2 (2.5e5 mol %),
SPhos (for 19a,b,d) or XPhos (for 19c,e) 5e10 mol %, 2 (1.25 equiv), Et3N, DMF, 130 ꢀC,
24 h.
4.2.3. (2E,20E)-Diisobutyl 3,30-(thiophene-2,3-diyl)diacrylate (3c).
Product 3cwaspreparedstartingwith1 (242mg,1.0mmol), iso-butyl

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
165
Ph
Ph
Ph
Ph
Br
S
+
Ph
Ph
Ph
Br
S
Br
ii
15b
S
21
Ph
Ph
i
iii
Ph
Ph
iii
Ph
S
Ph
S
Ph
22
20
(73% based on 15b)
Scheme 8. Synthesis of 22. Conditions: (i) Pd(OAc)2 (5 mol %), SPhos (10 mol %), 2 (3.75 equiv), NEt3 (8.0 equiv), DMF, 100 ꢀC, 12 h; (ii) Pd(OAc)2 (5 mol %), SPhos (10 mol %), 2
(3.75 equiv), NEt3, DMF, 130 ꢀC, 48 h; (iii) Pd/C (10 mol %), xylene, reflux, 48 h.
acrylate (0.36 mL, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), XPhos
(10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h
following general procedure A, as a brown oil (288 mg, 86%).1H NMR
NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h following
general procedure A, as a brown oil (360 mg, 92%). 1H NMR
(300 MHz, CDCl3):
d
¼0.83 (t, 6H, J¼6.9 Hz, 2CH3), 1.22e1.37 (m,
(250 MHz, CDCl3):
d
¼0.92 (d,12H, J¼6.7 Hz, 4CH3),1.89e1.98 (m, 2H,
12H, 6CH2), 1.58e1.68 (m, 4H, 2CH2), 4.13 (t, 2H, J¼6.8 Hz, CH2O),
4.14 (t, 2H, J¼6.8 Hz, CH2O), 6.22 (d, 1H, J¼15.5 Hz, CH), 6.24 (d, 1H,
J¼15.8 Hz, CH), 7.18 (d, 1H, J¼5.3 Hz, ArH), 7.24 (d, 1H, J¼5.4 Hz,
ArH), 7.78 (d, 1H, J¼15.8 Hz, CH), 7.93 (d, 1H, J¼15.5 Hz, CH). 13C
CH), 3.92 (d, 2H, J¼6.7 Hz, CH2O), 3.93 (d, 2H, J¼6.7 Hz, CH2O), 6.23 (d,
1H, J¼15.5 Hz, CH), 6.25 (d, 1H, J¼15.7 Hz, CH), 7.19 (d, 1H, J¼5.4 Hz,
ArH), 7.25 (d, 1H, J¼5.4 Hz, ArH), 7.79 (d, 1H, J¼15.8 Hz, CH), 7.93 (d,
1H, J¼15.6 Hz, CH). 13C NMR (75 MHz, CDCl3):
d¼19.1 (4CH3), 27.8
NMR (62 MHz, CDCl3):
d¼14.0 (2CH3), 22.5 (2CH2), 25.6 (2CH2),
(2CH), 70.8, 70.9 (CH2O), 119.2, 120.4, 126.4, 127.7, 133.5, 134.5 (CH),
28.7 (2CH2), 31.4 (2CH2), 64.9, 65.0 (CH2O),119.3,120.4, 126.4, 127.6,
138.2,139.8 (C),166.4,166.8 (CO). IR (KBr, cmꢁ1):
n¼3106, 2959, 2873
133.5, 134.4 (CH), 138.2, 139.8 (C), 166.4, 166.8 (CO). IR (KBr, cmꢁ1):
(w), 1704, 1619 (s), 1508, 1468, 1393, 1375, 1342 (w), 1311, 1266, 1237,
1201 (m),1154 (s),1018, 967, 852 (m), 832, 750 (w), 709 (m), 665, 620,
586, 533 (w). GCeMS(EI, 70eV):m/z (%)¼336 (25) [M]þ, 263 (19),180
(15),179 (100),178 (36),163 (82),162 (12),161 (42),135 (83),134 (59),
91 (13), 57 (80), 41 (34). HRMS (EI, 70 eV): calcd for C18H24O4S [M]þ:
336.13898; found: 336.13894.
n
¼2954, 2927, 2857 (w), 1707 (s), 1620 (m), 1510, 1465, 1434, 1379
(w), 1309, 1267, 1240, 1201 (m), 1160 (s), 1058, 1013, 970 (m), 906
(w), 854 (m), 834, 750 (w), 710 (m), 665, 620, 586 (w). GCeMS (EI,
70 eV): m/z (%)¼392 (07) [M]þ, 263 (32), 262 (18), 205 (16), 180
(14), 179 (100), 178 (29), 161 (44), 135 (35),134 (16), 91 (07), 57 (07),
41 (46). HRMS (EI, 70 eV): calcd for C22H32O4S [M]þ: 392.20158;
found: 392.20182.
4.2.4. (2E,20E)-Dibutyl 3,30-(thiophene-2,3-diyl)diacrylate (3d).
Product 3d was prepared starting with 1 (242 mg, 1.0 mmol), n-
butyl acrylate (0.36 mL, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %),
SPhos (10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for
48 h following general procedure A, as a brown oil (312 mg, 93%).
4.2.6. (2E,20E)-Bis(tert-butyl) 3,30-(thiophene-2,3-diyl) diacrylate
(3f). Product 3f was prepared starting with 1 (242 mg, 1.0 mmol),
tert-butyl acrylate (0.36 mL, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %),
XPhos (10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀ
C
1H NMR (300 MHz, CDCl3):
d¼0.90 (t, 6H, J¼7.4 Hz, 2CH3), 1.32e1.40
for 48 h following general procedure A, as yellowish solid (299 mg,
(m, 4H, 2CH2), 1.59e1.64 (m, 4H, 2CH2), 4.14 (t, 2H, J¼6.7 Hz, CH2O),
4.15 (t, 2H, J¼6.7 Hz, CH2O), 6.21 (d, 1H, J¼15.5 Hz, CH), 6.24 (d, 1H,
J¼15.8 Hz, CH), 7.18 (d, 1H, J¼5.3 Hz, ArH), 7.24 (d, 1H, J¼5.4 Hz,
ArH), 7.78 (d, 1H, J¼15.8 Hz, CH), 7.93 (d, 1H, J¼15.6 Hz, CH). 13C
89%), mp¼85e87 ꢀC. 1H NMR (300 MHz, CDCl3):
¼1.45 (s, 9H,
d
3CH3), 1.46 (s, 9H, 3CH3), 6.13 (d, 1H, J¼15.5 Hz, CH), 6.16 (d, 1H,
J¼15.7 Hz, CH), 7.15 (d, 1H, J¼5.3 Hz, ArH), 7.20 (d, 1H, J¼5.4 Hz,
ArH), 7.68 (d, 1H, J¼15.7 Hz, CH), 7.84 (d, 1H, J¼15.6 Hz, CH). 13C
NMR (62 MHz, CDCl3):
d
¼13.7 (2CH3), 19.2 (2CH2), 30.7 (2CH2),
NMR (75 MHz, CDCl3):
d
¼28.2 (6CH3), 80.1, 80.7 (CeO), 121.1, 122.2,
64.5, 64.6 (CH2O), 119.3, 120.4, 126.4, 127.7, 133.5, 134.4 (CH), 138.2,
126.4, 127.3, 132.7, 133.6 (CH), 138.0, 139.6 (C), 165.6, 166.1 (CO). IR
(KBr, cmꢁ1):
¼2976, 2932, 2872 (w), 1700 (s), 1617 (m), 1506, 1474,
139.8 (C), 166.4, 166.8 (CO). IR (KBr, cmꢁ1):
n
¼2957, 2931, 2872 (w),
n
1704 (s), 1619 (m), 1509, 1463, 1433, 1383, 1354 (w), 1309, 1276,
1238,1202 (m),1159 (s), 1061,1024, 968, 853, 751, 710 (m), 665, 619,
584 (w). GCeMS (EI, 70 eV): m/z (%)¼336 (26) [M]þ, 263 (11), 235
(15), 234 (10), 180 (12), 179 (94), 178 (32), 163 (62), 162 (11), 161
(45), 135 (100), 134 (50), 91 (14), 57 (56), 41 (33), 29 (21). HRMS (EI,
70 eV): calcd for C18H24O4S [M]þ: 336.13898; found: 336.13896.
1456, 1432,1390 (w), 1364, 1313, 1275, 1249,1199 (m), 1137 (s), 1039
(m), 999 (w), 971, 960, 911, 849 (m), 787 (w), 754, 727, 712, 694,
662, 621, 582 (m). GCeMS (EI, 70 eV): m/z (%)¼336 (05) [M]þ, 263
(04), 224 (41), 180 (14), 179 (50), 178 (30), 163 (19), 162 (10), 161
(34), 136 (10), 135 (100), 134 (42), 91 (23), 57 (64), 41 (72), 29 (21).
HRMS (ESI): calcd for C18H24NaO4S [MþNa]þ: 359.12875; found:
359.12877.
4.2.5. (2E,20E)-Dihexyl 3,30-(thiophene-2,3-diyl)diacrylate (3e).
Product 3e was prepared starting with 1 (242 mg, 1.0 mmol), hexyl
acrylate (2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), SPhos (10 mol %),
4.2.7. (2E,20E)-Bis(2-ethylhexyl) 3,30-(thiophene-2,3-diyl)diacrylate
(3g). Product 3g was prepared starting with 1 (242 mg, 1.0 mmol),

166
S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
2-ethylhexyl acrylate (0.52 mL, 2.5 mmol), Pd(OAc)2 (11 mg,
5 mol %), SPhos (10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at
120 ꢀC for 48 h following general procedure A, as a brown oil
2853, 1609, 1511, 1440, 1377, 1259, 1180, 1091, 1017 (w), 957 (s), 938,
905, 850, 829 (m), 800, 729 (s), 707, 637 (m). GCeMS (EI, 70 eV): m/
z (%)¼316 (100) [M]þ, 315 (11), 301 (22), 225 (17), 224 (12), 212 (10),
211 (62), 209 (12). HRMS (EI, 70 eV): calcd for C22H20S [M]þ:
316.12802; found: 316.12823.
(380 mg, 85%). 1H NMR (300 MHz, CDCl3):
d¼0.85 (t, 12H, J¼7.1 Hz,
4CH3), 1.17e1.38 (m, 16H, CH-Aliphatic), 1.55e1.61 (m, 2H, CH),
4.02e4.07 (m, 4H, 2CH2O), 6.22 (d, 1H, J¼15.5 Hz, CH), 6.24 (d, 1H,
J¼15.8 Hz, CH), 7.19 (d, 1H, J¼5.4 Hz, ArH), 7.24 (d, 1H, J¼5.3 Hz,
ArH), 7.78 (d, 1H, J¼15.8 Hz, CH), 7.93 (d, 1H, J¼15.5 Hz, CH). 13C
4.2.11. 2,3-Bis(4-chlorostyryl)thiophene (3k). Product 3k was pre-
pared starting with 1 (242 mg,1.0 mmol), 4-chloro styrene (0.32 mL,
2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), SPhos (10 mol %), NEt3
(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h following general
procedure A, as a brown solid (292 mg, 82%), mp¼106e108 ꢀC. 1H
NMR (75 MHz, CDCl3):
d
¼11.0 (2CH3),14.0 (2CH3), 23.0 (2CH2), 23.8,
23.9 (CH2), 28.9 (2CH2), 30.4, 30.5 (CH2), 38.8 (2CH), 67.2 (2CH2O),
119.3, 120.5, 126.4, 127.6, 133.5, 134.4 (CH), 138.2, 139.8 (C), 166.5,
166.9 (CO). IR (KBr, cmꢁ1):
n
¼2957, 2927, 2858 (w), 1708 (s), 1621
NMR (300 MHz, CDCl3):
d
¼6.80 (d, 1H, J¼15.7 Hz, CH), 6.81 (d, 1H,
(m), 1510, 1461, 1379 (w), 1308, 1267, 1241 (m), 1161 (s), 1028, 970
(m), 854, 833, 750, 710, 665, 620, 586 (w). GCeMS (EI, 70 eV): m/z
(%)¼448 (04) [M]þ, 207 (24), 180 (17), 179 (100), 178 (31), 161 (30),
135 (19), 134 (11), 71 (23), 57 (31), 43 (20). HRMS (EI, 70 eV): calcd
for C26H40O4S [M]þ: 448.26418; found: 448.26485.
J¼16.1 Hz, CH), 7.07 (d, 1H, J¼5.2 Hz, ArH), 7.14e7.29 (m, 7H, 5ArH
and 2CH), 7.33e7.36 (dd, 4H, J¼3.2, 8.3 Hz, ArH). 13C NMR (75 MHz,
CDCl3):
d
¼119.9, 121.1, 124.3, 125.9 (CH), 127.6 (4CH), 128.0, 128.6
(CH),128.9 (2CH),129.0 (2CH),133.3,133.4, 135.5,135.9,136.8, 138.5
(C). IR (KBr, cmꢁ1):
n
¼3093, 3037, 2990, 2851, 1622, 1613, 1565, 1510
(w), 1488 (m), 1439, 1401, 1328, 1255, 1245, 1178, 1103 (w), 1087,
1009, 957, 939, 852, 829 (m), 806 (s), 729, 705, 690, 636 (m), 592 (w).
4.2.8. 2,3-Bis(4-tert-butylstyryl)thiophene (3h). Product 3h was
prepared starting with 1 (242 mg, 1.0 mmol), 4-tert-butylstyrene
(0.45 mL, 2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), SPhos (10 mol %),
NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h following
GCeMS (EI, 70 eV): m/z (%)¼356 (70) [Mþ
(
37Cl, 37Cl)], 356 (100) [Mþ
(
35Cl, 37Cl)], 321 (15), 320 (13), 286 (12), 252 (13), 245 (24), 231 (99),
210 (27), 142 (14), 125 (19). HRMS (EI, 70 eV): calcd for C20H14Cl2S
general procedure A, as
a brown solid (376 mg, 94%),
[Mþ (Cl, 37Cl)]: 354.00313; found: 354.00225.
mp¼171e174 ꢀC. 1H NMR (300 MHz, CDCl3):
¼1.25 (s, 9H, 3CH3),
d
1.26 (s, 9H, 3CH3), 6.83 (d, 1H, J¼15.9 Hz, CH), 6.88 (d, 1H, J¼16.1 Hz,
CH), 7.04 (d, 1H, J¼5.3 Hz, ArH), 7.15e7.22 (m, 3H, ArH), 7.28e7.32
(m, 4H, ArH), 7.35e7.39 (m, 4H, ArH). 13C NMR (62 MHz, CDCl3):
4.3. General procedure B for the synthesis of benzothio-
phenes (4) and (13)
d
¼31.3 (6CH3), 34.6, 34.7 (C), 119.0, 120.3, 123.6 (CH), 125.7 (4CH),
126.0 (CH), 126.2 (4CH), 129.0, 129.5 (CH), 134.4, 134.8, 136.8, 138.4,
150.8, 150.9 (C). IR (KBr, cmꢁ1):
A xylene or diphenylether solution (3 mL) of 3aee, hel or 12aed
(0.5 mmol) was stirred at 200 ꢀC for 24 h in a pressure tube. The
solution was allowed to cool to 20 ꢀC and Pd/C (30 mg, 10 mol %)
was added. The solution was stirred at 200 ꢀC for 48 h under argon
atmosphere. The reaction mixture was filtered and the filtrate was
concentrated in vacuo. The residue was purified by chromatogra-
phy (flash silica gel, heptanes/EtOAc).
n
¼3028 (w), 2957 (m), 2864, 1903,
1605, 1515, 1504, 1462, 1409, 1391 (w), 1361, 1268 (m), 1246, 1199,
1107, 1015 (w), 953, 940, 852, 827, 809 (m), 741 (w), 714 (m), 665
(w), 635 (m), 610 (w), 558 (s). GCeMS (EI, 70 eV): m/z (%)¼400
(100) [M]þ, 385 (27), 343 (15), 287 (10), 254 (11), 253 (42), 209 (14),
185 (36), 157 (20), 147 (20), 91 (12), 57 (47). HRMS (EI, 70 eV): calcd
for C28H32S [M]þ: 400.22192; found: 400.22190.
4.3.1. Dimethyl benzo[b]thiophene-5,6-dicarboxylate (4a). Compound
4a was prepared starting with 3a (100 mg, 0.39 mmol), following
general procedure B, as a brown highly viscous oil (99 mg, 98%). 1H
4.2.9. 2,3-Bis(4-methoxystyryl)thiophene (3i). Product 3i was pre-
pared starting with 1 (242 mg, 1.0 mmol), 4-methoxystyrene
NMR (300 MHz, CDCl3):
d
¼3.86 (s, 6H, OCH3), 7.34 (d, 1H, J¼5.4 Hz,
(0.33 mL, 2.5 mmol), Pd(OAc)2 (11 mg,
5
mol %), SPhos
ArH), 7.59 (d,1H, J¼5.5 Hz, ArH), 8.10 (s,1H, ArH), 8.20 (s,1H, ArH).13C
(10 mol %), NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h
NMR (75 MHz, CDCl3):
d
¼51.7, 51.7 (OCH3), 122.9, 124.1, 123.5 (CH),
following general procedure A, as a brown oil (289 mg, 83%). 1H
126.2, 127.4 (C), 129.8 (CH), 139.9, 140.6 (C), 167.0, 167.4 (CO). IR (KBr,
NMR (300 MHz, CDCl3):
d
¼3.69 (s, 6H, 2OCH3), 6.74e6.80 (m, 6H,
cmꢁ1):
n
¼2950, 2925, 2852, 1840,1780 (w), 1716 (s),1601, 1545,1491
4ArH and 2CH), 6.97 (d, 1H, J¼5.3 Hz, ArH), 7.06 (d, 1H, J¼16.1 Hz,
CH), 7.12 (d, 1H, J¼5.4 Hz, ArH), 7.21 (d, 1H, J¼15.9 Hz, CH), 7.33 (dd,
(w),1433 (m),1400,1356 (w),1316,1277,1263,1246,1220,1198,1124,
1099, 1075 (m), 1009, 968, 893, 836, 787, 777, 759, 736, 703, 651, 628,
604, 530 (w). GCeMS(EI, 70 eV): m/z (%)¼250 (40) [M]þ, 220 (13), 219
(100), 133 (12). HRMS (EI, 70 eV): calcd for C12H10O4S [M]þ:
250.02943; found: 250.02983.
4H, J¼2.8, 8.8 Hz, ArH). 13C NMR (62 MHz, CDCl3):
¼55.3 (2OCH3),
d
114.2 (2CH), 114.3 (2CH), 117.7, 119.0, 123.3, 125.9 (CH), 127.6 (2CH),
127.7 (2CH), 128.6, 129.0 (CH), 130.0, 130.3, 136.5, 138.2, 159.3, 159.4
(C). IR (KBr, cmꢁ1):
n
¼3030, 2963, 2834 (w), 1597 (m), 1573 (w),
1510, 1505 (m), 1462, 1455, 1440, 1435, 1410, 1303, 1283 (w), 1246,
1172 (s), 1107, 1093 (w), 1024, 967, 957, 946, 931, 849, 812, 804, 778,
765, 726, 704, 631 (m). GCeMS (EI, 70 eV): m/z (%)¼348 (100) [M]þ,
347 (10), 240 (10), 227 (39), 225 (10), 121 (51). HRMS (EI, 70 eV):
calcd for C22H20O2S [M]þ: 348.11785; found: 348.11778.
4.3.2. Diethyl benzo[b]thiophene-5,6-dicarboxylate (4b). Compound
4b was prepared starting with 3b (100 mg, 0.36 mmol), following
general procedure B, as a brown highly viscous oil (99 mg, 99%). 1H
NMR (300 MHz, CDCl3):
d
¼1.32 (t, 6H, J¼7.1 Hz, 2CH3), 1.32 (q, 4H,
J¼7.1 Hz, 2OCH2), 7.34 (d, 1H, J¼5.4 Hz, ArH), 7.58 (d, 1H, J¼5.4 Hz,
ArH), 8.10 (s, 1H, ArH), 8.20 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
4.2.10. 2,3-Bis(4-methylstyryl)thiophene (3j). Product 3j was pre-
pared starting with 1 (242 mg, 1.0 mmol), 4-methyl styrene
(2.5 mmol), Pd(OAc)2 (11 mg, 5 mol %), XPhos (10 mol %), NEt3
(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 48 h following
general procedure A, as a brown oil (278 mg, 88%). 1H NMR
d
¼14.1 (2CH3), 61.6, 61.7 (OCH2),123.8,124.1,124.5 (CH),127.7,128.8
(C), 130.6 (CH), 140.8, 141.5 (C), 167.5, 168.0 (CO). IR (KBr, cmꢁ1):
n
¼2979, 2933, 2903, 2871 (w),1714 (s),1622,1600,1544,1490,1463,
1449, 1388 (w), 1365, 1313 (m), 1273, 1241 (s), 1191, 1173, 1120, 1095,
1073, 1018 (m), 972, 907, 854, 804 (w), 774, 755, 701 (m), 649, 607,
545 (w). GCeMS (EI, 70 eV): m/z (%)¼278 (30) [M]þ, 233 (20), 206
(15), 205 (100),121 (12). HRMS (EI, 70 eV): calcd for C14H14O4S [M]þ:
278.06073; found: 278.06090.
(250 MHz, CDCl3):
d
¼2.28 (s, 6H, 2CH3), 6.83 (d, 1H, J¼15.9 Hz, CH),
6.85 (d, 1H, J¼16.1 Hz, CH), 7.03 (d, 1H, J¼5.4 Hz, ArH), 7.09 (d, 4H,
J¼7.8 Hz, ArH), 7.16e7.22 (m, 2H, ArH), 7.30e7.37 (m, 5H, 3ArH and
2CH). 13C NMR (62 MHz, CDCl3):
d¼21.2 (2CH3), 118.8, 119.9, 123.6,
125.9 (CH), 126.4 (4CH), 129.1 (CH), 129.4 (4CH), 129.6 (CH), 134.4,
134.7, 136.7, 137.6, 137.7, 138.4 (C). IR (KBr, cmꢁ1):
¼3123, 2916,
4.3.3. Diisobutyl benzo[b]thiophene-5,6-dicarboxylate (4c). Compo-
und 4c was prepared starting with 3c (100 mg, 0.30 mmol), following
n

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
167
general procedure B, as a brown oil (99 mg, 98%). 1H NMR (300 MHz,
CDCl3):
J¼8.3 Hz, ArH), 7.13 (d, 4H, J¼8.1 Hz, ArH), 7.26 (d,1H, J¼5.3 Hz, ArH),
7.36 (d,1H, J¼5.4 Hz, ArH), 7.77 (s,1H, ArH), 7.83 (s,1H, ArH).13C NMR
d¼0.93 (d, 6H, J¼6.7 Hz, 2CH3), 0.94 (d, 6H, J¼6.7 Hz, 2CH3),
1.91e2.06 (m, 2H, CH), 4.05 (d, 4H, J¼6.8 Hz, 2CH2O), 7.35 (dd, 1H,
J¼0.7, 5.6 Hz, ArH), 7.58 (d, 1H, J¼5.5 Hz, ArH), 8.10 (s, 1H, ArH), 8.20
(62 MHz, CDCl3):
d¼31.4 (6CH3), 34.4 (2C), 123.7, 123.9 (CH), 124.6
(4CH), 125.1, 126.9 (CH), 129.6 (2CH), 129.7 (2CH), 137.6, 137.7, 138.6,
(s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼19.1 (2CH3), 19.2 (2CH3),
138.7, 138.8, 138.9 (C), 149.2, 149.3 (C). IR (KBr, cmꢁ1):
n¼3026, 2958,
27.7, 27.8 (CH), 71.8, 71.9 (CH2O), 123.8, 124.0, 124.4 (CH), 127.8, 128.9
2902, 2864, 2245, 1906, 1602, 1514, 1449, 1408, 1390 (w), 1361 (m),
1320, 1307 (w), 1267 (m), 1200, 1181, 1111, 1085, 1085, 1058, 1038,
1014, 960, 907, 894, 876 (w), 834 (s), 776, 762 (w), 731, 719 (m), 683,
661, 646, 633 (w), 602, 562 (m). GCeMS (EI, 70 eV): m/z (%)¼398
(100) [M]þ, 384 (25), 383 (84), 184 (12), 156 (16), 57 (29). HRMS (EI,
70 eV): calcd for C28H30S [M]þ: 398.20627; found: 398.20642.
(C), 130.6 (CH), 140.8, 141.5 (C), 167.6, 168.3 (CO). IR (KBr, cmꢁ1):
n
¼3106, 2958, 2873 (w), 1716 (s), 1626, 1601, 1545, 1490, 1468 (w),
1448, 1452, 1405, 1392, 1392, 1375, 1341 (m), 1314, 1271, 1239, 1190,
1167, 1119, 1097, 1073 (s), 1005, 982, 945, 904, 785, 775, 754, 702 (m),
682, 653, 626 (w). GCeMS (EI, 70 eV): m/z (%)¼334 (8) [M]þ, 222
(57), 206 (17), 205 (100), 178 (15), 160 (06). HRMS (EI, 70 eV): calcd
for C18H22O4S [M]þ: 334.12388; found: 334.12360.
4.3.8. 5,6-Bis(4-methoxyphenyl)benzo[b]thiophene (4i). Compound
4i was prepared starting with 3i (100 mg, 0.29 mmol), following
general procedure B, as a brown highly viscous oil (99 mg, 97%). 1H
4.3.4. Dibutyl benzo[b]thiophene-5,6-dicarboxylate (4d). Compound
4d was prepared starting with 3d (100 mg, 0.30 mmol), following
general procedure B, as a brown oil (99 mg, 98%). 1H NMR
NMR (300 MHz, CDCl3):
d
¼3.69 (s, 6H, 2OCH3), 6.7 (dd, 4H, J¼1.3,
8.6 Hz, ArH), 7.01 (dd, 4H, J¼1.9, 8.7 Hz, ArH), 7.25 (d, 1H, J¼5.4 Hz,
ArH), 7.35 (d, 1H, J¼5.4 Hz, ArH), 7.72 (s, 1H, ArH), 7.78 (s, 1H, ArH).
(300 MHz, CDCl3):
d
¼0.90 (t, 6H, J¼7.4 Hz, 2CH3), 1.32e1.42 (m, 4H,
2CH2), 1.62e1.71 (m, 4H, 2CH2), 4.26 (t, 4H, J¼6.7 Hz, 2CH2O), 7.35
(dd, 1H, J¼0.6, 5.4 Hz, ArH), 7.57 (d, 1H, J¼5.4 Hz, ArH), 8.09 (s, 1H,
13C NMR (75 MHz, CDCl3):
d¼55.2 (2OCH3), 113.4 (4CH), 123.7,
123.9, 125.1, 126.9 (CH), 131.0 (2CH), 131.1 (2CH), 134.1, 134.3, 137.2,
ArH), 8.19 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼13.7 (2CH3),
137.3, 138.8, 138.9 (C), 158.2, 158.3 (CeO). IR (KBr, cmꢁ1):
n
¼3132,
19.2 (2CH2), 30.6 (2CH2), 65.5, 65.6 (CH2O), 123.8, 124.1, 124.4 (CH),
127.8,128.8 (C),130.6 (CH),140.8,141.5 (C),167.6,168.1 (CO). IR (KBr,
2952, 2929, 2833, 2540, 1712 (w), 1607 (m), 1574 (w), 1484, 1449,
1439 (m), 1415, 1390, 1319 (w), 1286 (m), 1240, 1173 (s), 1107 (m),
1087, 1085 (w), 1044, 1025 (m), 958 (w), 905 (m), 830 (s), 801, 759,
730, 716 (m), 683, 670, 657, 628, 603 (w), 585, 546, 534 (m). GCeMS
(EI, 70 eV): m/z (%)¼346 (100) [M]þ, 271 (12). HRMS (EI, 70 eV):
calcd for C22H18O2S [M]þ: 346.10220; found: 346.10260.
cmꢁ1):
n
¼2957, 2930, 2871 (w), 1717 (s), 1625, 1600, 1543, 1490,
1452, 1405, 1381 (w), 1314 (m), 1273 (s), 1241, 1190, 1119, 1096, 1074
(m), 1018, 961, 942, 903, 840 (w), 775, 754, 736, 700 (m), 651, 545
(w). GCeMS (EI, 70 eV): m/z (%)¼334 (11) [M]þ, 222 (27), 206 (13),
205 (100), 178 (11). HRMS (EI, 70 eV): calcd for C18H22O4S [M]þ:
334.12333; found: 334.12338.
4.3.9. 5,6-Di-p-tolylbenzo[b]thiophene (4j). Compound 4j was pre-
pared starting with 3j (100 mg, 0.32 mmol), following general pro-
cedure B, as a brown highly viscous oil (99 mg, 95%). 1H NMR
4.3.5. Dihexyl benzo[b]thiophene-5,6-dicarboxylate (4e). Compound
4e was prepared starting with 3e (100 mg, 0.26 mmol), following
general procedure B, as a brown oil (99 mg, 97%). 1H NMR
(250 MHz, CDCl3):
d
¼2.23 (s, 6H, 2CH3), 6.94 (d, 4H, J¼7.3 Hz, ArH),
6.99 (d, 4H, J¼8.2 Hz, ArH), 7.25 (d, 1H, J¼5.4 Hz, ArH), 7.35 (d, 1H,
(300 MHz, CDCl3):
d
¼0.80e0.85 (m, 6H, 2CH3), 1.18e1.40 (m, 12H,
J¼5.5 Hz, ArH), 7.74 (s, 1H, ArH), 7.79 (s, 1H, ArH). 13C NMR (62 MHz,
6CH2), 1.63e1.72 (m, 4H, 2CH2), 4.25 (q, 4H, J¼6.8 Hz, 2OCH2), 7.35
CDCl3):
d
¼21.2 (2CH3), 123.7, 124.0, 125.3, 127.0 (CH), 128.6 (4CH),
(dd, 1H, J¼0.5, 5.5 Hz, ArH), 7.58 (d, 1H, J¼5.5 Hz, ArH), 8.10 (s, 1H,
129.9 (2CH), 130.0 (2CH), 135.9, 136.0, 137.5, 137.6, 138.7 (C), 138.8
ArH), 8.20 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼14.0 (2CH3),
(2C), 138.9 (C). IR (KBr, cmꢁ1.):
n
¼3020, 2916, 2848 (w), 1512 (m),
22.5 (2CH2), 25.6 (2CH2), 28.5 (2CH2), 31.5 (2CH2), 65.8, 65.9
(OCH2), 123.8, 124.1, 124.4 (CH), 127.8, 128.8 (C), 130.5 (CH), 140.8,
1484 (w),1448 (m),1409,1319,1181,1110,1087,1057,1036,1018, 943,
894, 875 (m), 814 (s), 758, 724, 657, 583, 526 (w). GCeMS (EI, 70 eV):
m/z (%)¼314 (100) [M]þ, 299 (42), 298 (19), 285 (10), 284 (28). HRMS
(EI, 70 eV): calcd for C22H18S [M]þ: 314.11237; found: 314.11245.
141.5 (C), 167.6, 168.0 (CO). IR (KBr, cmꢁ1):
n
¼2953, 2926, 2856 (w),
1720 (s), 1624, 1601, 1544, 1490, 1465, 1455, 1378, 1314 (w), 1272,
1241, 1189, 1167, 1120, 1097, 1074 (m), 993, 904, 837, 776, 755, 724,
701, 652 (w). GCeMS (EI, 70 eV): m/z (%)¼390 (7) [M]þ, 222 (23),
206 (13), 205 (100). HRMS (EI, 70 eV): calcd for C22H30O4S [M]þ:
390.18593; found: 390.18607.
4.4. Synthesis of 2-alknylthiophenes (5)
4.4.1. (E)-Methyl-3-(thiophen-2-yl)acrylate (5a). Product 5a was
prepared starting with 1 (242 mg, 1.0 mmol), methyl acrylate
(0.09 mL, 1.0 mmol), Pd(OAc)2 (11 mg, 5 mol %), XPhos (10 mol %),
NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 24 h following
general procedure A, as a brown oil (126 mg, 75%). 1H NMR
4.3.6. Bis(2-ethylhexyl) benzo[b]thiophene-5,6-dicarboxylate
(4g). Compound 4g was prepared starting with 3g (100 mg,
0.26 mmol), following general procedure B, as a brown oil (99 mg,
97%). 1H NMR (300 MHz, CDCl3):
1.25e1.41 (m, 16H, CH-Aliphatic), 1.59e1.65 (m, 2H, CH), 4.15e4.18
(m, 4H, 2CH2O), 7.33 (d, 1H, J¼5.4 Hz, ArH), 7.56 (d, 1H, J¼5.4 Hz,
ArH), 8.07 (s, 1H, ArH), 8.17 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼0.77e0.88 (m, 12H, 4CH3),
(230 MHz, CDCl3):
d
¼3.71 (s, 3H, OCH3), 6.18 (d, 1H, J¼15.9 Hz, CH),
7.18e7.27 (m, 2H, ArH), 7.40e7.42 (m, 1H, ArH), 7.60 (d, 1H,
J¼15.9 Hz, CH). 13C NMR (62 MHz, CDCl3):
¼51.6 (OCH3), 117.4,
d
125.1, 126.9, 128.1 (CH), 137.5 (C), 138.3 (CH), 167.6 (CO). IR (KBr,
d
¼11.0 (2CH3), 14.1 (2CH3), 23.0 (2CH2), 23.8 (2CH2), 29.0 (2CH2),
cmꢁ1):
n
¼3098, 29,993, 2946, 2841 (w), 1703, 1699, 1632 (s), 1515
30.4 (2CH2), 38.7, 38.8 (CH), 68.1, 68.2 (CH2O), 123.7, 124.1, 124.4
(CH), 127.9, 129.0 (C), 130.5 (CH), 140.8, 141.5 (C), 167.7, 168.1 (CO). IR
(w), 1435 (m), 1392, 1370 (w), 1306, 1275, 1247, 1197 (m), 1168 (s),
1054, 1043, 1012, 979, 922, 865, 842, 828 (m), 793 (s), 754, 736, 725,
666, 608, 590 (m). GCeMS (EI, 70 eV): m/z (%)¼168 (62) [M]þ, 138
(10), 137 (100), 110 (08), 109 (42), 65 (16). HRMS (EI, 70 eV): calcd
for C8H8O2S [M]þ: 168.02395; found: 168.02367.
(KBr):
n
¼2956, 2927 (m), 2858 (w), 1720 (s), 1625, 1459, 1379, 1313
(w), 1270 (s), 1240, 1190, 1167, 1120, 1097, 1073, 774, 701 (m), 654,
544 (w) cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼446 (02) [M]þ, 223 (27),
222 (41), 205 (100), 57 (10). HRMS (EI, 70 eV): calcd for C26H38O4S
[M]þ: 446.24853; found: 446.24915.
4.4.2. (E)-Ethyl-3-(thiophen-2-yl)acrylate (5b). Product 5b was
prepared starting with 1 (242 mg, 1.0 mmol), ethyl acrylate
(0.11 mL, 1.0 mmol), Pd(OAc)2 (11 mg, 5 mol %), SPhos (10 mol %),
NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 24 h following
general procedure A, as a brown oil (141 mg, 78%). 1H NMR
4.3.7. 5,6-Bis(4-tert-butylphenyl)benzo[b]thiophene (4h). Compo-
und 4h was prepared starting with 3h (100 mg, 0.25 mmol), fol-
lowing general procedure B, as a brown highly viscous oil (99 mg,
98%). 1H NMR (300 MHz, CDCl3):
d¼1.21 (s, 18H, 6CH3), 7.01 (d, 4H,
(300 MHz, CDCl3):
d
¼1.26 (t, 3H, J¼7.1 Hz, CH3), 4.18 (q, 2H,

168
S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
J¼7.1 Hz, CH2O), 6.18 (d, 1H, J¼15.9 Hz, CH), 7.19e7.26 (m, 2H, ArH),
7.40e7.42 (m, 1H, ArH), 7.59 (d, 1H, J¼15.9 Hz, CH). 13C NMR
acetic acid (5 mL) was stirred at room temperature for 15 min to
give a greenish precipitate. Then it was filtered and washed with
ethanol to give the pure imine 7 (365 mg, 98%), mp¼136e137 ꢀC. 1H
(62 MHz, CDCl3):
d
¼14.3 (CH3), 60.4 (CH2O), 117.9, 125.1, 126.9,
127.9,138.0 (CH),137.6 (C),167.2 (CO). IR (KBr, cmꢁ1):
n
¼3098, 2978,
NMR (300 MHz, CDCl3):
d
¼3.75 (s, 3H, OCH3), 6.83 (dd, 2H, J¼2.1,
2927, 2853 (w), 1703 (s), 1632 (m), 1518, 1463, 1444, 1392, 1365 (w),
1302, 1276, 1244, 1204 (m), 1152 (s), 1094, 1033, 975, 863, 828, 783,
700, 666, 605, 592 (m). GCeMS (EI, 70 eV): m/z (%)¼182 (46) [M]þ,
154 (11), 138 (12), 137 (100), 110 (20), 109 (37), 65 (16). HRMS (EI,
70 eV): calcd for C9H10O2S [M]þ: 182.03960; found: 182.03963.
6.8 Hz, ArH), 7.12 (s, 1H, ArH), 7.14 (dd, 2H, J¼2.1, 6.8 Hz, ArH), 8.33
(s, 1H, N]CH). 13C NMR (62 MHz, CDCl3):
¼55.5 (OCH3), 114.5
(2CH),122.5 (2CH),132.8 (CH), 143.1 (2CeBr), 144.0 (2C),148.2 (CH),
158.9 (CeO). IR (KBr, cmꢁ1):
d
n
¼2932, 2834 (w), 1614, 1579, 1519,
1502, 1463, 1427, 1417, 1287 (m), 1239 (s), 1200, 1183, 1159, 1118 (m),
1030 (s), 991, 950 (m), 827 (s), 770, 665, 636, 582 (m), 546 (w).
4.4.3. (E)-Isobutyl-3-(thiophen-2-yl)acrylate (5c). Product 5c was
prepared starting with 1 (242 mg, 1.0 mmol), iso-butyl acrylate
(0.14 mL, 1.0 mmol), Pd(OAc)2 (11 mg, 5 mol %), XPhos (10 mol %),
NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 24 h following
general procedure A, as a brown highly viscous oil (155 mg, 74%). 1H
GCeMS (EI, 70 eV): m/z (%)¼377 (53) [Mþ
(
81Br, 81Br)], 375 (100)
[Mþ (Br, 81Br)], 373 (52) [Mþ (Br, Br)], 360 (93), 358 (47), 172 (19), 92
(12), 77 (12), 64 (11). HRMS (EI, 70 eV): calcd for C12H9Br2NOS [Mþ
(Br, 81Br)]þ: 374.87456; found: 374.87422.
NMR (250 MHz, CDCl3):
d
¼0.90 (d, 6H, J¼6.7 Hz, 2CH3), 1.85e2.01
4.6. Synthesis of 2,3-di(alkenyl)thiophenes (8)
(m,1H, CH), 3.91 (d, 2H, J¼6.7 Hz, CH2O), 6.20 (d,1H, J¼15.9 Hz, CH),
7.18e7.25 (m, 2H, ArH), 7.40e7.42 (m, 1H, ArH), 7.59 (d, 1H,
4.6.1. (2E,20E)-Dimethyl 3,30-{5-[(E)-(4-methoxyphenylimino)methyl]
thiophene-2,3-diyl}diacrylate (8a). Product 8a was prepared start-
ing with 7 (186 mg, 0.5 mmol), methyl acrylate (0.12 mL,
1.25 mmol), Pd(OAc)2 (6 mg, 5 mol %), SPhos (10 mol %), NEt3
(0.55 mL, 4.0 mmol), DMF (5 mL) at 90 ꢀC for 12 h following general
procedure A, as a brown oil (119 mg, 62%). 1H NMR (300 MHz,
J¼15.9 Hz, CH). 13C NMR (75 MHz, CDCl3):
¼19.2 (2CH3), 27.9 (CH),
d
70.6 (CH2O),117.9,125.2,126.9,127.9 (CH),137.6 (C),138.0 (CH),167.3
(CO). IR (KBr):
n
¼3098, 2958, 2931, 2872 (w),1704 (s),1632 (m),1518,
1468,1426,1394,1375,1342 (w),1305,1276,1203 (m),1151 (s),1084
(w),1013, 974 (m), 867, 859, 828 (w), 783 (m), 699, 667 (w), 605 (m),
569, 537 (w) cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼210 ([M]þ, 12), 154
(71),138 (10),137 (100),112 (12),109 (31), 65 (13), 39 (08). HRMS (EI,
70 eV): calcd for C11H14O2S [M]þ: 210.07090; found: 210.07110.
CDCl3):
d
¼3.75 (s, 9H, 3OCH3), 6.25 (d, 1H, J¼16.4 Hz, CH), 6.31 (d,
1H, J¼16.4 Hz, CH), 6.85 (d, 2H, J¼9.0 Hz, ArH), 7.15 (d, 2H, J¼9.0 Hz,
ArH), 7.46 (s, 1H, ArH), 7.76 (d, 1H, J¼15.7 Hz, CH), 7.92 (d, 1H,
J¼15.3 Hz, CH), 8.44 (s, 1H, N]CH). 13C NMR (75 MHz, CDCl3):
4.4.4. (E)-tert-Butyl-3-(thiophen-2-yl)acrylate (5d). Product 5d was
prepared starting with 1 (242 mg, 1.0 mmol), tert-butyl acrylate
(0.14 mL, 1.0 mmol), Pd(OAc)2 (11 mg, 5 mol %), XPhos (10 mol %),
NEt3 (1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 24 h following
general procedure A, as a brown oil (182 mg, 87%). 1H NMR
d
¼51.9, 52.0, 55.5 (OCH3), 114.5 (2CH), 120.2, 120.3 (CH), 122.6
(2CH), 129.1, 133.4, 134.3 (CH), 138.5 (C), 142.2 (CeN), 143.2, 144.4
(C), 149.0 (CH), 159.1 (CeO), 166.6, 167.0 (CO). IR (KBr, cmꢁ1):
n
¼2957, 2935, 2830 (w), 1709, 1637 (m), 1614 (s), 1574, 1508, 1453,
1440, 1386, 1367, 1304, 1291 (m), 1243,1171,1162 (s), 1120, 1108 (m),
1022, 970 (s), 864 (m), 832 (s), 795, 780, 732, 705, 678, 599, 554,
537 (m). GCeMS (EI, 70 eV): m/z (%)¼385 (60) [Mþ], 383 (19), 326
(79), 327 (100), 310 (35), 294 (60), 267 (16), 252 (27), 162 (12), 147
(20), 134 (35). HRMS (EI, 70 eV): calcd for C20H19NO5S [M]þ:
385.09784; found: 385.09850.
(300 MHz, CDCl3):
d
¼1.45 (s, 9H, 3CH3), 6.12 (d, 1H, J¼15.9 Hz, CH),
7.18e7.25 (m, 2H, ArH), 7.36e7.39 (m, 1H, ArH), 7.59 (d, 1H,
J¼16.0 Hz, CH). 13C NMR (75 MHz, CDCl3):
¼28.2 (3CH3), 80.4
d
(CeO), 119.9, 125.2, 126.8, 127.4, 137.1 (CH), 137.8 (C), 166.6 (CO). IR
(KBr, cmꢁ1):
n
¼3098, 2976, 2927, 2855 (w), 1705 (s), 1633 (m), 1518,
1455, 1392 (w), 1366, 1309, 1281 (m), 1248, 1219 (w), 1148 (s), 1085,
1041, 978, 855, 829, 787, 702, 665, 606, 529 (w). GCeMS (EI, 70 eV):
m/z (%)¼210 (16) [M]þ, 154 (100), 137 (57), 126 (10), 112 (30), 109
(21), 65 (12), 57 (20), 41 (14). HRMS (EI, 70 eV): calcd for C11H14O2S
[M]þ: 210.07090; found: 210.07071.
4.6.2. (2E,20E)-Diisobutyl3,30-{5-[(E)-(4-methoxyphenylimino)methyl]
thiophene-2,3-diyl}diacrylate (8b). Product 8b was prepared starting
with 7 (186 mg, 0.5 mmol), iso-butyl acrylate (0.18 mL, 1.25 mmol),
Pd(OAc)2 (6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3 (0.55 mL,
4.0 mmol), DMF (5 mL) at 90 ꢀC for 12 h following general procedure
4.4.5. (E)-Hexyl-3-(thiophen-2-yl)acrylate (5e). Product 5e was
prepared starting with 1 (242 mg, 1.0 mmol), hexyl acrylate
(1.0 mmol), Pd(OAc)2 (11 mg, 5 mol %), SPhos (10 mol %), NEt3
(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ꢀC for 24 h following
general procedure A, as a brown oil (180 mg, 76%). 1H NMR
A, as a brown oil (178 mg, 76%). 1H NMR (300 MHz, CDCl3):
d¼0.92
(dd, 12H, J¼0.8, 6.7 Hz, 4CH3), 1.92e1.98 (m, 2H, CH), 3.76 (s, 3H,
OCH3), 3.92 (dd, 4H, J¼1.9, 6.7 Hz, 2CH2O), 6.31 (t, 2H, J¼15.8 Hz, CH),
6.85 (dd, 2H, J¼2.1, 6.8 Hz, ArH), 7.18 (dd, 2H, J¼2.2, 6.8 Hz, ArH), 7.49
(s, 1H, ArH), 7.76 (d, 1H, J¼15.8 Hz, CH), 7.92 (d, 1H, J¼15.5 Hz, CH),
(300 MHz, CDCl3):
d
¼0.83 (t, 3H, J¼6.8 Hz, CH3), 1.21e1.29 (m, 6H,
8.45 (s, 1H, N]CH). 13C NMR (75 MHz, CDCl3):
(2CH), 54.5 (OCH3), 69.9, 70.0 (CH2O), 113.5 (2CH), 119.7, 119.8 (CH),
121.6 (2CH), 128.2, 132.2, 133.1 (CH), 137.4 (C), 141.2 (CeN), 142.2,
143.3 (C), 148.0 (CH), 158.0 (CeO), 165.2, 165.6 (CO). IR (KBr, cmꢁ1):
d
¼18.1 (4CH3), 26.8
3CH2), 1.54e1.64 (m, 2H, CH2), 4.11 (t, 2H, J¼6.8 Hz, CH2O), 6.19 (d,
1H, J¼15.9 Hz, CH), 7.18e7.25 (m, 2H, ArH), 7.40e7.42 (m, 1H, ArH),
7.59 (d, 1H, J¼15.9 Hz, CH). 13C NMR (62 MHz, CDCl3):
¼14.0 (CH3),
d
22.5, 25.6, 28.7, 31.4 (CH2), 64.7 (CH2O), 118.0, 125.1, 126.9, 127.9
n¼2960, 2873, 2835 (w), 1692 (s), 1608, 1574, 1501, 1465, 1393, 1377,
(CH), 137.6 (C), 138.0 (CH), 167.3 (CO). IR (KBr, cmꢁ1):
n
¼3098, 2953,
1367 (m), 1343, 1305 (w), 1282, 1268 (m), 1246, 1234 (s), 1199,
1178 (m), 1166, 1156 (s), 1109 (m), 1024, 1014 (s), 967, 951, 930, 908,
856, 843 (m), 827 (s), 779, 735, 712, 664, 636, 617, 599, 553, 535 (m).
MS (EI, 70 eV): m/z (%)¼469 (100) [Mþ], 343 (15), 312 (21), 296
(16), 294 (10), 268 (26), 252 (10), 134 (17), 78 (12), 63 (14), 57 (32).
HRMS (EI, 70 eV): calcd for C26H31NO5S [M]þ: 469.19175; found:
469.19242.
2927, 2856 (w), 1707 (s), 1632 (m), 1518, 1465, 1391, 1379 (w), 1302,
1276, 1245, 1203 (m), 1162 (s), 1112, 1082, 976 (m), 908, 867, 860,
829 (w), 784, 711 (m), 668 (w), 605 (m). GCeMS (EI, 70 eV): m/z
(%)¼238 (12) [M]þ, 155 (16), 154 (100), 138 (10), 137 (81), 112 (13),
110 (12), 109 (32), 65 (14). HRMS (EI, 70 eV): calcd for C13H18O2S
[M]þ: 238.10220; found: 238.10245.
4.5. Synthesis of (E)-N-[(4,5-dibromothiophen-2-yl)methy-
lene]-4-methoxyaniline (7)
4.6.3. (2E,20E)-Dibutyl 3,30-{5-[(E)-(4-methoxyphenylimino)methyl]
thiophene-2,3-diyl}diacrylate (8c). Product 8c was prepared start-
ing with 7 (186 mg, 0.5 mmol), n-butyl acrylate (0.18 mL,
1.25 mmol), Pd(OAc)2 (6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3
(0.55 mL, 4.0 mmol), DMF (5 mL) at 90 ꢀC for 12 h following general
A
mixture of 4,5-dibromothiophene-2-carbaldehyde (6)
(269 mg, 1.0 mmol), 4-methoxyaniline (184 mg, 1.5 mmol) in glacial

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
169
procedure A, as a brown oil (128 mg, 55%). 1H NMR (300 MHz,
CDCl3):
(75), 149 (23), 134 (64), 89 (39), 67 (17), 59 (41). HRMS (EI, 70 eV):
calcd for C13H12O5S [M]þ: 280.04000; found: 280.04067.
d
¼0.90 (t, 6H, J¼7.4 Hz, 2CH3), 1.30e1.43 (m, 4H, 2CH2),
1.57e1.68 (m, 4H, 2CH2), 3.76 (s, 3H, OCH3), 4.15 (t, 2H, J¼6.7 Hz,
CH2O), 4.16 (t, 2H, J¼6.7 Hz, CH2O), 6.27 (d, 1H, J¼15.9 Hz, CH), 6.32
(d, 1H, J¼15.6 Hz, CH), 6.85 (dd, 2H, J¼2.8, 9.0 Hz, ArH), 7.14e7.20
(m, 2H, ArH), 7.51 (s, 1H, ArH), 7.76 (d, 1H, J¼15.8 Hz, CH), 7.92
(d, 1H, J¼15.5 Hz, CH), 8.45 (s, 1H, N]CH). 13C NMR (75 MHz,
4.7.2. (2E,20E)-Diisobutyl 3,30-(5-formylthiophene-2,3-diyl)diacrylate
(9b). Compound 9c was prepared starting with 8b (234 mg,
0.50 mmol), following general procedures C, as a brown oil (172 mg,
95%). 1H NMR (300 MHz, CDCl3):
d
¼0.92 (d, 12H, J¼6.7 Hz, 4CH3),
CDCl3):
d
¼13.7 (2CH3), 19.2 (2CH2), 30.7 (2CH2), 55.5 (OCH3), 64.7,
1.88e2.02 (m, 2H, CH), 3.95 (d, 4H, J¼6.7 Hz, 2CH2O), 6.33 (d, 1H,
J¼15.8 Hz, CH), 6.41 (d, 1H, J¼15.6 Hz, CH), 7.74 (d, 1H, J¼15.8 Hz,
CH), 7.84 (s, 1H, ArH), 7.92 (d, 1H, J¼15.6 Hz, CH), 9.85 (s, 1H, O]
64.8 (CH2O), 114.4 (2CH), 120.8, 122.4 (CH), 122.6 (2CH), 129.2,
133.2, 134.1 (CH), 138.4 (C), 142.3 (CeN), 143.3, 144.3 (C), 149.1
(CH), 159.1 (CeO), 166.3, 166.7 (CO). IR (KBr, cmꢁ1):
n
¼2956, 2869,
CH). 13C NMR (75 MHz, CDCl3):
d
¼19.1 (4CH3), 27.8 (2CH), 71.1, 71.3
2835 (w), 1698, 1613 (s), 1557, 1529 (w), 1503, 1455, 1392 (m), 1281,
1242 (s), 1202 (m), 1164 (s), 1108, 1064, 1031 (m), 963 (s), 933, 858
(m), 833 (s), 800, 780, 739, 713, 666, 601, 555, 531 (m). MS
(EI, 70 eV): m/z (%)¼469 (100) [Mþ], 343 (15), 312 (20), 296 (15),
294 (10), 268 (27), 252 (10), 134 (19), 78 (14), 63 (15), 57 (15). HRMS
(EI, 70 eV): calcd for C26H31NO5S [M]þ: 469.19175; found:
469.19256.
(CH2O), 121.9, 122.9, 132.7, 133.6, 134.3 (CH), 138.3, 143.3, 146.3 (C),
165.6, 166.2 (CO), 182.6 (O]CH). IR (KBr, cmꢁ1):
n
¼2978, 2926,
2848 (w),1708,1671 (s),1625,1449,1375,1279,1240 (m),1176,1157,
1031 (s), 968, 954, 854, 677 (m). GCeMS (EI, 70 eV): m/z (%)¼364
(20) [Mþ], 291 (18), 208 (22), 207 (100), 191 (72), 163 (61), 135 (33),
91 (11), 89 (15), 57 (75), 41 (37), 29 (18). HRMS (EI, 70 eV): calcd for
C19H24O5S [M]þ: 364.13390; found: 364.13470.
4.6.4. (2E,20E)-Dihexyl 3,30-{5-[(E)-(4-methoxyphenylimino)methyl]
thiophene-2,3-diyl}diacrylate (8d). Product 8d was prepared start-
ing with 7 (186 mg, 0.5 mmol), n-hexyl acrylate (0.22 mL,
1.25 mmol), Pd(OAc)2 (6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3
(0.55 mL, 4.0 mmol), DMF (5 mL) at 90 ꢀC for 12 h following general
procedure A, as a brown oil (176 mg, 67%). 1H NMR (300 MHz,
4.7.3. (2E,20E)-Dibutyl 3,30-(5-formylthiophene-2,3-diyl)diacrylate
(9c). Compound 9c was prepared starting with 8c (234 mg,
0.50 mmol), following general procedures C, as a brown oil (167 mg,
92%). 1H NMR (300 MHz, CDCl3):
d¼0.90 (t, 6H, J¼7.4 Hz, 2CH3),
1.33e1.40 (m, 4H, 2CH2), 1.59e1.66 (m, 4H, 2CH2), 4.15 (t, 2H,
J¼6.8 Hz, CH2O), 4.17 (t, 2H, J¼6.7 Hz, CH2O), 6.32 (d, 1H, J¼15.8 Hz,
CH), 6.39 (d, 1H, J¼15.6 Hz, CH), 7.74 (d, 1H, J¼15.9 Hz, CH), 7.82 (s,
1H, ArH), 7.90 (d, 1H, J¼15.6 Hz, CH), 9.84 (s, 1H, O]CH). 13C NMR
CDCl3):
d
¼0.83 (t, 6H, J¼6.7 Hz, 2CH3), 1.23e1.35 (m, 12H, 6CH2),
1.59e1.67 (m, 4H, 2CH2), 3.76 (s, 3H, OCH3), 4.14 (t, 2H, J¼6.8 Hz,
CH2O), 4.15 (t, 2H, J¼6.8 Hz, CH2O), 6.27 (d, 1H, J¼16.4 Hz, CH), 6.33
(d, 1H, J¼15.7 Hz, CH), 6.85 (d, 2H, J¼8.9 Hz, ArH), 7.17e7.20 (m, 2H,
ArH), 7.48 (s, 1H, ArH), 7.75 (d, 1H, J¼15.8 Hz, CH), 7.92 (d, 1H,
J¼15.5 Hz, CH), 8.45 (s, 1H, N]CH). 13C NMR (75 MHz, CDCl3):
(62 MHz, CDCl3):
d
¼13.7 (2CH3), 19.0, 19.1 (CH2), 30.6, 30.7 (CH2),
64.9, 65.1 (CH2O), 121.9, 123.0, 132.7, 133.6, 134.2 (CH), 138.3, 143.2,
146.3 (C), 165.7, 166.3 (CO), 182.5 (O]CH). IR (KBr, cmꢁ1):
n
¼2957,
2930, 2871 (w),1705,1671 (s),1621,1443,1308,1274,1242 (m),1162
(s), 1061, 1025, 967, 856, 661, 600 (m). GCeMS (EI, 70 eV): m/z (%)¼
364 (06) [Mþ], 263 (35), 262 (19), 207 (100), 189 (40), 163 (15), 161
(15), 135 (28), 91 (11), 57 (23), 41 (25), 29 (21). HRMS (EI, 70 eV):
calcd for C19H24O5S [M]þ: 364.13390; found: 364.13398.
d¼14.0 (2CH3), 22.5 (2CH2), 25.6 (2CH2), 28.6, 28.7 (CH2), 31.4
(2CH2), 55.5 (OCH3), 65.0, 65.1 (CH2O), 114.5 (2CH), 120.8 (2CH),
122.6 (2CH), 129.2, 133.2, 134.1 (CH), 138.4 (C), 142.3 (CeN), 143.3,
144.3 (C), 149.1 (CH), 159.0 (CeO), 166.3, 166.7 (CO). IR (KBr, cmꢁ1):
n
¼2954, 2927, 2857 (w), 1695, 1612 (s), 1575, 1529 (w), 1502, 1454
(m), 1268, 1237, 1165, 1158 (s), 1015, 969, 827, 779 (m), 711, 662, 601
(w), 553, 533 (m). MS (EI, 70 eV): m/z (%)¼525 (100) [Mþ], 312 (22),
296 (19), 294 (10), 268 (29), 252 (10), 134 (22), 43 (44), 41 (12).
HRMS (EI, 70 eV): calcd for C30H39NO5S [M]þ: 525.25435; found:
525.25419.
4.7.4. (2E,20E)-Dihexyl 3,30-(5-formylthiophene-2,3-diyl)diacrylate
(9d). Compound 9d was prepared starting with 8d (262 mg,
0.50 mmol), following general procedures C, as a brown oil
(201 mg, 96%). 1H NMR (300 MHz, CDCl3):
d
¼0.29 (t, 6H, J¼6.8 Hz,
2CH3), 0.69e0.81 (m, 12H, 6CH2), 1.07e1.12 (m, 4H, 2CH2), 3.61 (t,
4H, J¼6.8 Hz, 2CH2O), 5.78 (d, 1H, J¼15.8 Hz, CH), 5.85 (d, 1H,
J¼15.6 Hz, CH), 7.20 (d, 1H, J¼15.8 Hz, CH), 7.29 (s, 1H, ArH), 7.37 (d,
1H, J¼15.6 Hz, CH), 9.30 (s, 1H, O]CH). 13C NMR (62 MHz, CDCl3):
4.7. General procedure C for the synthesis of 2,3-di(alkenyl)-
5-formylthiophenes (9)
d
¼14.0 (2CH3), 22.5 (2CH2), 25.5 (2CH2), 28.5, 28.6 (CH2), 31 (2CH2),
In a pressure tube (glass bomb), to a solution of compounds
8aee (0.5 mmol) in dichloromethane (1 mL) was added H2SO4
(4 mL, 2.5 M). The reaction mixture was stirred at room tempera-
ture for 20 h. The solution was poured into H2O and CH2Cl2 (25 mL
each) and the organic and the aqueous layer were separated. The
latter was extracted with CH2Cl2 (3ꢂ25 mL), the organic phases
were combined, dried (Na2SO4), filtered, and concentrated in vacuo.
65.2, 65.4 (CH2O), 121.9, 123.0, 132.7, 133.6, 134.2 (CH), 138.3, 143.2,
146.3 (C), 165.6, 166.2 (CO), 182.5 (O]CH). IR (KBr, cmꢁ1):
n
¼2953,
2926, 2855 (w), 1707, 1670 (s), 1622, 1443, 1305, 1271, 1243 (m),
1163 (s), 966, 857 (m), 725, 684 (w), 661 (m), 601 (w). GCeMS (EI,
70 eV): m/z (%)¼420 (04) [Mþ], 291 (32), 233 (20), 207 (100), 189
(37), 163 (11), 135 (18), 43 (49), 41 (16). HRMS (EI, 70 eV): calcd for
C23H32O5S [M]þ: 420.19650; found: 420.19703.
4.7.1. (2E,20E)-Dimethyl 3,30-(5-formylthiophene-2,3-diyl)diacrylate
(9a). Compound 9a was prepared starting with 8a (192 mg,
0.50 mmol), following general procedures C, as a brown solid
4.8. Synthesis of 2,3-di(alkenyl)-5-arylthiophenes (12)
4.8.1. (2E,20E)-Isobutyl 3,30-(5-(4-ethylphenyl)thiophene-2,3-diyl)di-
acrylate (12a). Product 12a was prepared starting with 11a
(173 mg, 0.5 mmol), iso-butyl acrylate (0.18 mL, 1.25 mmol),
Pd(OAc)2 (6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3 (0.55 mL,
4.0 mmol), DMF (5 mL) at 100 ꢀC for 24 h following general pro-
cedure A, as a brown oil (196 mg, 89%). 1H NMR (300 MHz, CDCl3):
(137 mg, 98%), mp¼142e145 ꢀC. 1H NMR (300 MHz, CDCl3):
¼3.77
d
(s, 6H, 2CH3O), 6.32 (d, 1H, J¼15.8 Hz, CH), 6.40 (d, 1H, J¼15.6 Hz,
CH), 7.75 (d, 1H, J¼15.9 Hz, CH), 7.82 (s, 1H, ArH), 7.92 (d, 1H,
J¼15.7 Hz, CH), 9.85 (s, 1H, O]CH). 13C NMR (62 MHz, CDCl3):
d
¼51.1, 51.2 (CH3O),120.4,121.5,131.9,132.8,133.1 (CH),137.3,142.4,
145.3 (C), 165.0, 165.6 (CO), 181.6 (O]CH). IR (KBr, cmꢁ1):
n
¼3084,
d
¼0.90 (d, 6H, J¼6.7 Hz, 2CH3), 0.91 (d, 6H, J¼6.7 Hz, 2CH3), 1.17 (t,
2958, 2922, 2850 (w), 1708, 1668, 1620 (s), 1442, 1472, 1302, 1276,
1242, 1212 (m), 1191, 1160 (s), 1031, 1015 (m), 966 (s), 915, 863, 853,
730, 685, 663, 607, 538 (m). GCeMS (EI, 70 eV): m/z (%)¼280 (47)
[Mþ], 249 (23), 221 (100), 220 (47), 205 (47), 189 (80), 177 (46), 161
3H, J¼7.6 Hz, CH3), 1.87e2.01 (m, 2H, 2CH), 2.58 (q, 2H, J¼7.6 Hz,
CH2), 3.92 (d, 2H, J¼6.7 Hz, CH2O), 3.93 (d, 2H, J¼6.7 Hz, CH2O), 6.20
(d, 1H, J¼15.4 Hz, CH), 6.29 (d, 1H, J¼15.7 Hz, CH), 7.15 (d, 2H,
J¼8.2 Hz, ArH), 7.37 (s, 1H, ArH), 7.42 (d, 2H, J¼8.2 Hz, ArH), 7.76 (d,

170
S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
1H, J¼16.0 Hz, CH), 7.91 (d, 1H, J¼15.4 Hz, CH). 13C NMR (62 MHz,
(d,1H, J¼15.7 Hz, CH), 7.93 (d, 1H, J¼15.6 Hz, CH). 13C NMR (75 MHz,
CDCl3):
d
¼14.3 (CH3), 18.1 (4CH3), 26.8 (2CH), 27.6 (CH2), 69.8
CDCl3):
d
¼18.2 (4CH3), 26.8 (2CH), 54.6 (OCH3), 69.7, 69.8 (CH2O),
(2CH2O), 117.4, 119.4, 120.1 (CH), 125.0 (2CH), 127.6 (2CH), 129.2 (C),
132.4, 133.4 (CH), 137.5, 138.2, 144.4, 145.3 (C), 165.5, 165.8 (CO). IR
110.7, 117.0, 118.9, 120.0 (CH), 120.6 (C), 122.8, 127.2, 128.9, 132.7,
133.7 (CH), 136.9, 138.1, 140.6, 154.9 (C), 165.6, 165.9 (CO). IR (KBr,
(KBr, cmꢁ1):
n
¼2960, 2933, 2872 (w), 1702 (s), 1622 (m), 1504, 1468,
cmꢁ1):
n
¼3099, 2957, 2844 (w), 1692 (s), 1605, 1462 (m), 1441, 1393,
1417, 1392, 1375 (w), 1303, 1271, 1246, 1220 (m), 1156 (s), 1019, 969,
823 (m), 774, 713, 680, 614, 550 (w). MS (EI, 70 eV): m/z (%)¼440
(51) [Mþ], 367 (16), 283 (53), 265 (46), 239 (57), 223 (23), 221 (12),
207 (21), 169 (13), 149 (12), 133 (15), 111 (18), 97 (26), 83 (28), 69
(69), 57 (100), 44 (68). HRMS (EI, 70 eV): calcd for C26H32O4S [M]þ:
440.20158; found: 440.20124.
1375, 1342 (w), 1268,1253,1240, 1210 (s), 1179,1162, 1115 (m), 1024,
970 (s), 950, 846 (m), 744 (s), 717, 683, 603 (w). MS (EI, 70 eV): m/z
(%)¼442 (11) [M]þ, 285 (57), 269 (13), 267 (25), 243 (11), 241 (54),
57 (100), 41 (42). HRMS (ESI): calcd for C25H31O5S [MþH]þ:
443.1887; found: 443.1876.
4.9. Synthesis of benzothiophenes (13)
4.8.2. (2E,20E)-Dibutyl 3,30-[5-(4-tert-butylphenyl)thiophene-2,3-
diyl]diacrylate (12b). Product 12b was prepared starting with 11b
(187 mg, 0.5 mmol), n-butyl acrylate (0.18 mL,1.25 mmol), Pd(OAc)2
(6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3 (0.55 mL, 4.0 mmol), DMF
(5 mL) at 100 ꢀC for 24 h following general procedure A, as a brown
4.9.1. Diisobutyl 2-(4-ethylphenyl)benzo[b]thiophene-5,6-dicarboxylate
(13a). Compound 13a was prepared starting with 12a (100 mg,
0.23 mmol), following the general procedure B, as a brown semisolid
1
(92 mg, 93%). H NMR (300 MHz, CDCl3):
d
¼0.92 (d, 6H, J¼6.8 Hz,
oil (176 mg, 75%). 1H NMR (300 MHz, CDCl3):
d¼0.89 (t, 6H,
2CH3), 0.93 (d, 6H, J¼6.7 Hz, 2CH3), 1.18 (t, 3H, J¼7.6 Hz, CH3),
1.92e2.05 (m, 2H, 2CH), 2.60 (q, 2H, J¼7.6 Hz, CH2), 4.03 (d, 2H,
J¼6.7 Hz, CH2O), 4.04 (d, 2H, J¼6.7 Hz, CH2O), 7.18 (d, 2H, J¼8.8 Hz,
ArH), 7.47 (s, 1H, ArH), 7.54 (dd, 2H, J¼1.7, 6.6 Hz, ArH), 7.98 (s, 1H,
J¼6.8 Hz, 2CH3), 1.26 (s, 9H, 3CH3), 1.32e1.40 (m, 4H, 2CH2),
1.57e1.67 (m, 4H, 2CH2), 4.14 (t, 2H, J¼6.8 Hz, CH2O), 4.16 (t, 2H,
J¼6.7 Hz, CH2O), 6.20 (d, 1H, J¼15.6 Hz, CH), 6.29 (d, 1H, J¼15.8 Hz,
CH), 7.33e7.36 (m, 3H, ArH), 7.45 (d, 2H, J¼8.4 Hz, ArH), 7.77 (d, 1H,
J¼15.9 Hz, CH), 7.92 (d, 1H, J¼15.3 Hz, CH). 13C NMR (75 MHz,
ArH), 8.13 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d¼15.4 (CH3), 19.2
(4CH3), 27.7, 27.8 (CH), 28.7 (CH2), 71.8 (2CH2O), 118.7, 123.5, 123.9
(CH), 126.6 (2CH), 127.3 (C), 128.6 (2CH), 129.4, 130.8, 140.9, 142.2,
CDCl3):
d
¼13.8 (2CH3), 19.2 (2CH2), 30.8 (2CH2), 31.2 (3CH3), 34.8
(C), 64.6, 64.7 (CH2O), 118.5, 120.5, 121.2 (CH), 125.8 (2CH), 126.1
(2CH), 130.0 (C), 133.5, 134.5 (CH), 138.6, 139.3, 146.2, 152.4 (C),
145.6, 149.0 (C), 167.5, 168.2 (CO). IR (KBr, cmꢁ1):
n¼2958, 2873 (m),
1721, 1708 (s), 1593, 1552, 1526 (w), 1495, 1469 (m), 1419, 1403, 1392
(w), 1371, 1303 (m), 1281, 1254, 1229, 1179, 1119, 1090 (s), 1013, 982,
945, 898, 888, 832 (m), 818 (s), 780, 719, 691 (m), 657, 634, 590, 549
(w). GCeMS (EI, 70 eV): m/z (%)¼438 (69) [M]þ, 382 (16), 326 (24),
310 (22), 309 (100), 221 (13). HRMS (EI, 70 eV): calcd for C26H30O4S
[M]þ: 438.18593; found: 438.18532.
166.6, 166.9 (CO). IR (KBr, cmꢁ1):
n¼2957, 2932, 2871 (w), 1714 (m),
1695 (s), 1613 (m), 1504, 1456, 1391, 1361 (w), 1271, 1251, 1228 (m),
1163 (s), 1113, 1064, 1026, 968, 823 (m), 739, 607, 529 (w). MS (EI,
70 eV): m/z (%)¼468 (26) [M]þ, 367 (10), 366 (18), 351 (16), 322
(12), 311 (36), 293 (23), 267 (47), 251 (22), 237 (15), 223 (12), 211
(13), 91 (27), 69 (15), 66 (12), 57 (100), 44 (48), 41 (68). HRMS (ESI):
calcd for C28H37O4S [MþH]þ: 469.2407; found: 469.2405.
4.9.2. Dibutyl 2-(4-tert-butylphenyl)benzo[b]thiophene-5,6-dicar-
boxylate (13b). Compound 13b was prepared starting with 12b
(100 mg, 0.21 mmol), following general procedure B, as a yellowish
4.8.3. (2E,20E)-Diisobutyl
3,30-[5-(3,5-dimethylphenyl)thiophene-
2,3-diyl]diacrylate (12c). Product 12c was prepared starting with
11c (173 mg, 0.5 mmol), iso-butyl acrylate (0.18 mL, 1.25 mmol),
Pd(OAc)2 (6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3 (0.55 mL,
4.0 mmol), DMF (5 mL) at 100 ꢀC for 24 h following general pro-
cedure A, as a brown oil (171 mg, 78%). 1H NMR (300 MHz, CDCl3):
solid (81 mg, 82%), mp¼56e58 ꢀC.1H NMR (250 MHz, CDCl3):
¼0.89
d
(t, 6H, J¼7.3 Hz, 2CH3), 1.28 (s, 9H, 3CH3), 1.34e1.43 (m, 4H, 2CH2),
1.61e1.72 (m, 4H, 2CH2), 4.25 (t, 2H, J¼6.7 Hz, CH2O), 4.26 (t, 2H,
J¼6.7 Hz, CH2O), 7.39 (dd, 2H, J¼1.9, 6.6 Hz ArH), 7.48 (s, 1H, ArH),
7.58 (dd, 2H, J¼1.9, 6.6 Hz, ArH), 7.99 (s,1H, ArH), 8.13 (s,1H, ArH). 13C
d
¼0.91 (d, 6H, J¼6.7 Hz, 2CH3), 0.92 (d, 6H, J¼6.7 Hz, 2CH3),
NMR (62 MHz, CDCl3):
d
¼13.7 (2CH3), 19.2 (2CH2), 30.6, 30.7 (CH2),
1.88e2.02 (m, 2H, 2CH), 2.28 (s, 6H, 2CH3), 3.93 (d, 2H, J¼6.7 Hz,
CH2O), 3.94 (d, 2H, J¼6.7 Hz, CH2O), 6.22 (d, 1H, J¼15.5 Hz, CH), 6.32
(d, 1H, J¼15.8 Hz, CH), 6.92 (s, 1H, ArH), 7.15 (s, 2H, ArH), 7.37 (s, 1H,
ArH), 7.78 (d, 1H, J¼15.8 Hz, CH), 7.93 (d, 1H, J¼15.5 Hz, CH). 13C
31.2 (3CH3), 34.8 (C), 65.6 (2CH2O), 118.7, 123.6, 123.9 (CH), 126.1
(2CH), 126.4 (2CH), 127.2, 129.3, 130.6, 140.9, 142.2, 148.9, 152.5 (C),
167.5, 168.2 (CO). IR (KBr, cmꢁ1):
n¼2955, 2927, 2869 (m), 1709 (s),
1650, 1625, 1595, 1497, 1460, 1390, 1359 (w), 1330 (m), 1306, 1284,
1258, 1239 (s), 1189, 1122 (m), 1094 (s), 1060, 1017, 834, 819, 778 (m),
729, 719, 578 (w), 532 (m). GCeMS (EI, 70 eV): m/z (%)¼466 (100)
[M]þ, 452 (20), 451 (67), 410 (11), 395 (23), 337 (62), 321 (14), 250
(13). HRMS (ESI): calcd for C28H35O4S [MþH]þ: 467.2251; found:
467.2256. Anal. Calcd for C28H34O4S: C, 72.07; H, 7.34; S, 6.87. Found:
C, 72.08; H, 7.52; S, 6.88.
NMR (75 MHz, CDCl3):
d¼19.2 (4CH3), 21.3 (2CH3), 27.9 (2CH), 70.8
(CH2O), 70.9 (CH2O), 118.5, 120.4, 121.5 (CH), 123.9 (2CH), 130.7
(CH), 132.6 (C), 133.5, 134.5 (CH), 138.7 (C), 138.8 (2C), 139.2, 146.5
(C), 166.5, 166.8 (CO). IR (KBr, cmꢁ1):
n¼2958 (m), 2872 (w), 1705
(s), 1615, 1602 (m), 1530 (w), 1467, 1375, 1309, 1265, 1240, 1213 (m),
1155 (s), 1021, 967, 829, 687 (m), 598, 541 (w). GCeMS (EI, 70 eV):
m/z (%)¼440 (34) [M]þ, 339 (14), 338 (16), 309 (11), 283 (65), 265
(51), 240 (18), 239 (100), 238 (30), 224 (18), 91 (16), 57 (94), 44 (63),
41 (51). HRMS (ESI): calcd for C26H33O4S [MþH]þ: 441.2094; found:
441.2090.
4.9.3. Diisobutyl 2-(3,5-dimethylphenyl)benzo[b]thiophene-5,6-
dicarboxylate (13c). Compound 13c was prepared starting with
12c (100 mg, 0.23 mmol), following general procedure B, as a white
solid (84 mg, 85%), mp¼66e68 ꢀC. 1H NMR (300 MHz, CDCl3):
4.8.4. (2E,20E)-Diisobutyl 3,30-[5-(2-methoxyphenyl)thiophene-2,3-
diyl]diacrylate (12d). Product 12d was prepared starting with 11d
(174 mg, 0.5 mmol), iso-butyl acrylate (0.18 mL, 1.25 mmol),
Pd(OAc)2 (6 mg, 5 mol %), P(Cy)3 (10 mol %), NEt3 (0.55 mL,
4.0 mmol), DMF (5 mL) at 100 ꢀC for 24 h following general pro-
cedure A, as a brown oil (168 mg, 76%). 1H NMR (300 MHz, CDCl3):
d
¼0.93 (d, 6H, J¼6.7 Hz, 2CH3), 0.94 (d, 6H, J¼6.7 Hz, 2CH3),
1.92e2.08 (m, 2H, 2CH), 2.29 (s, 6H, 2CH3), 4.03 (d, 2H, J¼6.7 Hz,
CH2O), 4.04 (d, 2H, J¼6.7 Hz, CH2O), 6.94 (s, 1H, ArH), 7.17 (s, 2H,
ArH), 7.49 (s, 1H, ArH), 7.99 (s, 1H, ArH), 8.13 (s, 1H, ArH). 13C NMR
(62 MHz, CDCl3):
d
¼18.2 (4CH3), 20.3 (2CH3), 26.7, 26.8 (CH), 70.8
(2CH2O), 118.0, 122.5, 123.0 (CH), 123.5 (2CH), 126.3, 128.3 (C), 129.8
(CH), 132.2 (C), 137.7 (2C), 140.0, 141.0, 148.2 (C), 166.5, 167.1 (CO). IR
d
¼0.91 (d, 12H, J¼6.8 Hz, 4CH3), 1.86e2.01 (m, 2H, 2CH), 3.86 (s, 3H,
OCH3), 3.92 (d, 2H, J¼6.6 Hz, CH2O), 3.93 (d, 2H, J¼6.6 Hz, CH2O),
6.23 (d, 1H, J¼15.3 Hz, CH), 6.28 (d, 1H, J¼15.3 Hz, CH), 6.88e6.94
(m, 2H, ArH), 7.20e7.26 (m, 1H, ArH), 7.52e7.58 (m, 2H, ArH), 7.78
(KBr, cmꢁ1):
n
¼2957, 2924, 2871 (m), 1716 (s), 1600, 1514, 1487 (w),
1468 (m), 1405, 1392, 1376, 1344 (w), 1305, 1273, 1261 (m), 1236 (s),
1180, 1163, 1120, 1091, 1012, 979, 946, 899, 843, 816, 781, 748, 721,

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
171
690, 681, 603 (m). GCeMS (EI, 70 eV): m/z (%)¼438 (57) [M]þ, 382
(12), 326 (26), 310 (22), 309 (100), 236 (14). HRMS (ESI): calcd for
C26H31O4S [MþH]þ: 439.1938; found: 439.1944. Anal. Calcd for
C26H30O4S: C, 71.20; H, 6.89; S, 7.31. Found: C, 71.08; H, 7.13; S, 7.47.
a xylene solution (3 mL) of the crude product was added Pd/C
(30 mg, 10 mol %). The solution was stirred under reflux for 48 h
under argon atmosphere. The reaction mixture was filtered, and the
filtrate was concentrated in vacuo. The residue was purified by
chromatography (flash silica gel, heptaneseEtOAc) to yield the
product.
4.9.4. Diisobutyl 2-(2-methoxyphenyl)benzo[b]thiophene-5,6-
dicarboxylate (13d). Compound 13d was prepared starting with
12d (100 mg, 0.23 mmol), following general procedure B, as yel-
lowish solid (87 mg, 88%), mp¼96e98 ꢀC. 1H NMR (300 MHz,
4.12.1. Diethyl dibenzo[b,d]thiophene-2,3-dicarboxylate (18a). Com-
pound 18a was prepared starting with 15a (292 mg, 1.0 mmol) as an
amorphous white solid (249 mg, 76%); mp 118e119 ꢀC. 1H NMR
CDCl3):
d
¼0.93 (d, 12H, J¼6.7 Hz, 4CH3), 1.92e2.06 (m, 2H, 2CH),
3.89 (s, 3H, OCH3), 4.03 (d, 2H, J¼6.7 Hz, CH2O), 4.04 (d, 2H,
J¼6.7 Hz, CH2O), 6.93e6.99 (m, 2H, ArH), 7.24e7.29 (m, 1H, ArH),
7.63 (dd, 1H, J¼1.5, 7.7 Hz, ArH), 7.73 (s, 1H, ArH), 8.02 (s, 1H, ArH),
(300 MHz, CDCl3):
d
¼1.33 (t, 3H, J¼7.76 Hz, CH3), 1.35 (t, 3H,
J¼7.76 Hz, CH3), 4.31e4.40 (m, 4H, 2CH2O), 7.41e7.48 (m, 2H, ArH),
7.79e7.82 (m,1H, ArH), 8.12 (s,1H, ArH), 8.13e8.15 (m,1H, ArH), 8.43
8.14 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼19.2 (4CH3), 27.8
(s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d¼14.2 (2CH3), 61.7, 61.8
(2CH), 55.6 (OCH3), 71.8 (2CH2O), 111.8, 121.1, 122.0 (CH), 122.3 (C),
123.2, 124.0 (CH), 127.2, 128.9 (C), 129.3, 130.1 (CH), 141.3, 141.5,
(CH2O), 122.3, 122.4, 123.0, 123.6, 125.1, 128.0 (CH), 128.5, 130.4,
~
134.4, 137.1, 140.7, 141.9 (C), 167.5, 167.7 (CO). IR (KBr):
n
¼3053 (w),
144.6, 156.4 (C), 167.7, 168.3 (CO). IR (KBr, cmꢁ1):
n
¼2955, 2928,
2975 (w), 2931 (w), 2896 (w), 2867 (w),1706 (s),1632 (w), 1603 (w),
1540 (w), 1483 (w), 1469 (w), 1440 (m), 1366 (m), 1314 (m), 1247 (s),
1229 (s), 1098 (s), 1021 (s), 913 (w), 885 (w), 873 (w), 853 (w), 765
(s), 757 (s), 708 (s), 642 (w), 583 (w), 552 (w) cmꢁ1. MS (EI, 70 eV):
m/z (%)¼328 (40) [M]þ, 284 (06), 257 (54), 229 (19), 211 (58), 185
(100); HRMS (EI, 70 eV): m/z calcd for C18H16O4S [M]þ: 328.08715;
found: 328.08765.
2872 (w), 1707 (s), 1627, 1594, 1579, 1547, 1509, 1481 (w), 1468, 1458
(m), 1435, 1408, 1376, 1341 (w), 1307, 1283, 1267 (m), 1252, 1242 (s),
1167, 1125, 1101, 1025, 982, 906, 833, 772 (m), 755 (s), 735, 690 (m),
594, 548 (w). GCeMS (EI, 70 eV): m/z (%)¼440 (63) [M]þ, 384 (12),
328 (13), 312 (20), 311 (100). HRMS (ESI): calcd for C25H29O5S
[MþH]þ: 441.1730; found: 441.1738. Anal. Calcd for C25H28O5S: C,
68.16; H, 6.41; S, 7.28. Found: C, 68.15; H, 6.55; S, 7.48.
4.12.2. Dibutyl dibenzo[b,d]thiophene-2,3-dicarboxylate (18b). Comp-
ound 18b was prepared starting with 15a (292 mg, 1.0 mmol) as
4.10. Synthesis of 2,3-dibromobenzothiophene (15a)
a highly viscous oil (311 mg, 81%). 1H NMR (300 MHz, CDCl3):
d¼0.91
To a CH2Cl2 solution (50 mL) of benzo[b]thiophene (14, 5.00 g,
37.3 mmol) and KOAc (7.30 g, 74.6 mmol) was added Br2 (3.8 mL,
74.6 mmol) at 20 ꢀC, and the solution was heated under reflux for
24 h. To the solution was added a satd solution of Na2S2O3 and
NaHCO3. The organic and the aqueous layer were separated, and
the latter was extracted with CH2Cl2 (3ꢂ30 mL). The combined
organic layers were dried (Na2SO4), filtered, and concentrated in
vacuo. The residue was purified by flash silica column chromatog-
raphy (pure heptanes) to yield 15a as a white solid (9.1 g, 84%). The
spectroscopic data were identical with those reported.17,18
(t, 3H, J¼7.3 Hz, CH3), 0.92 (t, 3H, J¼7.4 Hz, CH3), 1.34e1.47 (m, 4H),
1.64e1.74 (m, 4H), 4.28 (t, 2H, J¼6.7 Hz, OCH2), 4.30 (t, 2H, J¼6.6 Hz,
OCH2), 7.44e7.48 (m, 2H, ArH), 7.80e7.83 (m, 1H, ArH), 8.13 (s, 1H,
ArH), 8.15e8.17 (m, 1H, ArH), 8.43 (s, 1H, ArH). 13C NMR (62 MHz,
CDCl3):
d
¼12.7 (2CH3),18.2, 29.6, 64.7 (CH2),121.3,121.4,122.0,122.6,
124.0, 127.0 (CH), 127.5, 129.4, 133.4, 136.1, 139.7, 140.8 (C), 166.5,
~
166.8 (CO). IR (KBr):
n
¼2957 (m), 1717 (s), 1459 (m), 1263 (s), 1119
(m), 1092 (m), 1018 (w), 760 (m), 731 (m) cmꢁ1. MS (EI, 70 eV): m/z
(%)¼384 (20) [M]þ, 328 (06), 311 (04), 272 (31), 255 (100), 228 (10),
211 (05), 171 (12). HRMS (EI, 70 eV): m/z calcd for C22H24O4S [M]þ:
384.13898; found: 384.139182.
4.11. Synthesis of 2,3,6-tribromobenzothiophene (15b)
4.12.3. Diisobutyl dibenzo[b,d]thiophene-2,3-dicarboxylate (18c). Com
pound 18c was prepared starting with 15a (292 mg, 1.0 mmol) as
To a CH2Cl2 solution (50 mL) of benzo[b]thiophene (14, 5.00 g,
37.3 mmol) and KOAc (16.5 g, 167.9 mmol) was added Br2 (8.6 mL,
167.9 mmol) at 20 ꢀC, and the solution was heated under reflux for
24 h. To the solution was added a satd solution of Na2S2O3 and
NaHCO3. The organic and the aqueous layer were separated, and
the latter was extracted with CH2Cl2 (3ꢂ30 mL). The combined
organic layers were dried (Na2SO4), filtered, and concentrated in
vacuo. The residue was purified by flash silica column chromatog-
raphy (pure heptanes) to yield 15b as a white solid (9.7 g, 70%). The
spectroscopic data were identical with those reported.19
highly viscous oil (284 mg, 74%). 1H NMR (300 MHz, CDCl3):
d¼0.94
(d, 6H, J¼1.6 Hz, CH3), 0.96 (d, 6H, J¼1.6 Hz, CH3), 1.94e2.06 (m, 2H),
4.06 (d, 2H, J¼6.5 Hz, OCH2), 4.08 (d, 2H, J¼6.7 Hz, OCH2), 7.44e7.47
(m, 2H), 7.80e7.83 (m, 1H), 8.13 (s, 1H, ArH), 8.15e8.16 (m, 1H), 8.43
(s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
27.7, 122.3, 122.4, 123.0, 123.6, 125.0, 128.0 (CH), 128.6, 130.4, 134.4,
d
¼19.2 (CH3), 71.9 (OCH2),
~
137.1, 140.7, 141.8 (C), 167.5, 167.8 (CO). IR (KBr):
n
¼2959 (m), 2873
(w), 1717 (s), 1604 (w), 1468 (m), 1263 (s), 1120 (m), 1091 (m), 982
(m), 759 (m), 730 (m) cmꢁ1. MS (EI, 70 eV): m/z (%)¼384 (20) [M]þ,
328 (06), 311 (02), 272 (56), 255 (100), 228 (11), 211 (05). 171 (12).
HRMS (EI, 70 eV): m/z calcd for C22H24O4S [M]þ: 384.13898; found:
384.13901.
4.12. General procedure D for the synthesis of (18aef)
In a pressure tube (glass bomb) a suspension of Pd(OAc)2 (12 mg,
0.05 mmol, 2.5 mol % per Br atom) and dicyclohexyl-(20,60-dime-
thoxybiphenyl-2-yl) phosphine (SPhos) (41 mg, 10 mol %) in DMF
(5 mL) was flushed with Ar and stirred at 20 ꢀC to give a yellowish
or brownish transparent solution. To the stirred solution were
added the 2,3-dibromobenzothiophene (15a, 292 mg, 1.0 mmol),
Et3N (1.1 mL, 8.0 mmol), and the acrylate (1.25 equiv per Br). The
reaction mixture was stirred at 100e130 ꢀC for 12e48 h. The so-
lution was cooled to 20 ꢀC, poured into H2O and CH2Cl2 (25 mL
each), and the organic and the aqueous layer were separated. The
latter was extracted with CH2Cl2 (3ꢂ25 mL). The combined organic
layers were washed with H2O (3ꢂ20 mL), dried (Na2SO4), concen-
trated in vacuo, and passed through a column (silica gel). To
4.12.4. Dihexyl dibenzo[b,d]thiophene-2,3-dicarboxylate(18d). Comp-
ound 18d was prepared starting with 15a (292 mg, 1.0 mmol) as
highly viscous oil (338 mg, 77%). 1H NMR (300 MHz, CDCl3):
d¼0.83
(t, 3H, J¼6.1 Hz, CH3), 0.84 (t, 3H, J¼5.4 Hz, CH3), 1.23e1.39 (m, 12H),
1.64e1.74 (m, 4H), 4.27 (t, 2H, J¼6.8 Hz, OCH2), 4.28 (t, 2H, J¼6.9 Hz,
OCH2), 7.43e7.46 (m, 2H), 7.79e7.82 (m, 1H), 8.12 (s, 1H, ArH),
8.13e8.15 (m, 1H), 8.42 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3):
d
¼14.0 (2CH3), 22.5, 25.6, 28.5, 31.5 (CH2), 66.0 (OCH2), 122.3, 122.4,
123.0, 123.6, 125.0, 128.0 (CH), 128.6, 130.4, 134.4, 137.1, 140.7, 141.9
~
(C), 167.6, 167.8 (CO). IR (KBr):
n
¼2953 (m), 2927 (m), 1718 (s), 1459
(w), 1263 (s), 1120 (m), 1092 (m), 760 (m), 729 (m) cmꢁ1. MS (EI,
70 eV): m/z (%)¼440 (14) [M]þ, 356 (06), 272 (33), 255 (100), 228

172
S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
(09), 182 (07). HRMS (EI, 70 eV): m/z calcd for C26H32O4S [M]þ:
440.20158; found: 440.20186.
139.4 (C), 166.2 (CO). IR (KBr):
n
¼2956 (m), 1719 (s), 1542 (w), 1459
~
(m),1316 (m),1262 (s),1119 (m),1092 (m),1018 (w), 898 (w), 760 (m),
731 (m) cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼260 (90) [M]þ, 245 (14),
231 (20), 217 (40), 204 (27), 187 (100), 175 (18), 160 (29). HRMS (EI,
70 eV): m/z calcd for C15H16O2S [M]þ: 260.09110; found: 260.09136.
4.12.5. 2,3-Diphenyldibenzo[b,d]thiophene (18e). Compound 18e
was prepared starting with 15a (292 mg, 1.0 mmol) as a brownish
semisolid (265 mg, 79%). 1H NMR (300 MHz, CDCl3):
d
¼7.11e7.34
(m, 10H), 7.44e7.50 (m, 4H), 7.70 (d, 1H, J¼8.3 Hz, ArH), 7.89 (s, 1H,
ArH). 13C NMR (75 MHz, CDCl3):
4.13.3. (E)-3-(Benzo[b]thiophen-3-yl)acrylonitrile (19c). Compound
19c was prepared starting with 15a (292 mg, 1.0 mmol) as light
d¼120.7, 122.7, 123.6, 123.7, 126.5,
126.7, 127.6, 128.6, 128.7, 128.8 (CH), 130.3, 133.8, 137.4, 139.1, 140.4
brown semisolid (94 mg, 51%). 1H NMR (300 MHz, CDCl3):
d¼5.63
~
(C). IR (KBr):
n
¼2926 (w), 2850 (w), 1665 (m), 1594 (m), 1446 (m),
(d, 1H, J¼16.3 Hz), 7.26e7.41 (m, 1H), 7.49 (d, 1H, J¼16.2 Hz),
1246 (m), 1107 (m), 958 (w), 746 (m), 691 (s), 595 (w) cmꢁ1. MS (EI,
70 eV): m/z (%)¼336 (15) [M]þ, 321 (06), 302 (03), 261 (32), 184
(04), 167 (05). HRMS (EI, 70 eV): m/z calcd for C24H16S [M]þ:
336.09672; found: 336.09660.
7.68e7.73 (m, 3H), 7.78e7.84 (m, 1H). 13C NMR (62 MHz, CDCl3):
d
¼96.9 (CH),117.7 (C),122.5, 124.8,125.2,127.0 (CH), 128.5 (C),129.2
~
n
(CH), 138.1, 139.2 (C), 143.3 (CH). IR (KBr).
¼2921 (m), 2213 (w),
1611 (m), 1457 (m), 1365 (w), 1107 (m), 952 (m), 745 (s), 618 (m)
cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼260 (90) [M]þ, 185 (100), 158
(09), 140 (10), 126 (01), 114 (05). HRMS (EI, 70 eV): m/z calcd for
C11H7NS [M]þ: 185.02937; found: 185.02874.
4.12.6. 2,3-Bis(4-chlorophenyl)dibenzo[b,d]thiophene (18f). Compound
18f was prepared starting with 15a (292 mg, 1.0 mmol) as a brown
semisolid (336 mg, 83%). 1H NMR (300 MHz, CDCl3):
d
¼7.24e7.43 (m,
10H), 7.60e7.93 (m, 4H). 13C NMR (75 MHz, CDCl3):
d
¼121.3, 121.9,
4.13.4. (E)-3-Styrylbenzo[b]thiophene (19d). Compound 19d was
prepared starting with 15a (292 mg, 1.0 mmol) as a colorless
crystalline solid (174 mg, 76%); mp 93e95 ꢀC. 1H NMR (300 MHz,
CDCl3): ¼7.12e7.23 (m, 2H), 7.28e7.36 (m, 5H), 7.46 (s, 1H, ArH),
7.46e7.49 (m, 2H, ArH), 7.77e7.83 (m, 1H, ArH), 7.91e7.94 (m, 1H,
ArH). 13C NMR (62 MHz, CDCl3):
122.2, 123.0, 124.4, 124.6, 124.9, 127.6, 127.7, 128.9 (CH), 133.3, 133.6,
~
133.8, 135.1, 135.9, 137.2, 137.7, 140.1, 140.5, 142.5 (C). IR (KBr):
n
¼3058
(w), 1708 (s), 1587 (m), 1489 (m), 1421 (w), 1358 (w), 1219 (m), 1090
(m), 1012 (m), 828 (m), 756 (s) cmꢁ1. MS (EI, 70 eV): m/z (%)¼404 (40)
[M]þ, 384 (67), 368 (08), 351 (08), 334 (07), 307 (12), 266 (12), 224
(15), 202 (07), 161 (34). HRMS (EI, 70 eV): m/z calcd for C24H14Cl2S
[M]þ: 404.01878; found: 404.01880.
d
d
¼120.7, 121.8, 122.0, 123.0, 124.33,
124.6, 126.4, 127.7, 128.8, 130.3 (CH), 134.2, 137.4, 137.8, 140.5 (C). IR
~
n
(KBr):
¼2921 (s), 2851 (s), 1667 (m), 1598 (m), 1492 (m), 1454 (m),
1446 (m), 1434 (m), 1377 (w), 1365 (w), 1346 (w), 1260 (w), 1243
(w), 1204 (w), 1176 (w), 1156 (w), 1029 (w), 1019 (w), 948 (w), 907
(w), 887 (w), 864 (w), 757 (s), 748 (s), 730 (s), 696 (s), 623 (w), 591
(w), 555 (w), 538 (w) cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼236 (100)
[M]þ, 221 (18), 202 (16), 189 (05), 117 (08). HRMS (EI, 70 eV): m/z
calcd for C16H12S [M]þ: 236.06542; found: 236.064490.
4.13. General procedure E for the synthesis of (19aee)
In a pressure tube (glass bomb) a suspension of Pd(OAc)2 (06 mg,
0.025 mmol) and dicyclohexyl-(20,60-dimethoxybiphenyl-2-yl)
phosphine (SPhos, 21 mg, 0.05 mmol) in DMF (5 mL) was flushed
with Ar and stirred at 20 ꢀC to give a yellowish or brownish trans-
parent solution. To the stirred solution were added the 2,3-
dibromobenzothiophene (15a, 292 mg, 1.0 mmol), Et3N (1.1 mL,
8.0 mmol), and the acrylate (1.25 mmol). The reaction mixture was
stirred at 130 ꢀC for 24 h. The solution was cooled to 20 ꢀC, poured
into H2O and CH2Cl2 (25 mL each), and the organic and the aqueous
layer were separated. The latter was extracted with CH2Cl2
(3ꢂ25 mL). The combined organic layers were washed with H2O
(3ꢂ20 mL), dried (Na2SO4), concentrated in vacuo, and passed
through a column (flash silica gel, heptaneseEtOAc) to yield the
product.
4.13.5. (E)-3-(4-Methylstyryl)benzo[b]thiophene (19e). Compound
19e was prepared starting with 15a (292 mg, 1.0 mmol) as a white
crystalline solid (190 mg, 76%); mp 107e109 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼2.29 (s, 3H, CH3), 7.11e7.38 (m, 6H), 6.88 (d,1H, J¼16.0 Hz),
7.79 (d, 2H, J¼7.3 Hz), 7.92 (d, 2H, J¼7.2 Hz). 13C NMR (62 MHz,
CDCl3):
d
¼21.3 (CH3), 119.7, 121.4, 121.9, 123.0, 124.2, 124.5, 126.3,
~
129.4,130.2 (CH),134.3,134.6,137.6,137.8,140.5 (C). IR (KBr):
n
¼2919
(m),1642 (w),1425 (m),1234 (m),1109 (w), 962 (m), 805 (s), 754 (s),
730 (s), 709 (w) cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼250 (75) [M]þ,
235 (100), 221 (06), 202 (11), 189 (04), 158 (02), 139 (02). HRMS (EI,
70 eV): m/z calcd for C17H14S [M]þ: 250.08107; found: 250.08125.
4.13.1. (E)-Ethyl 3-(benzo[b]thiophen-3-yl)acrylate (19a). Compound
19a was prepared starting with 15a (292 mg, 1.0 mmol) as a colorless
4.14. Synthesis of (E)-2,3-diphenyl-7-styryldibenzo[b,d]thio-
phene (22)
viscous oil (188 mg, 81%). 1H NMR (250 MHz, CDCl3):
d¼1.28 (t, 3H,
J¼7.1 Hz, CH3), 4.21 (q, 2H, J¼7.2, 14.3 Hz, OCH2), 6.45 (d, 1H,
J¼16.1 Hz), 7.25e7.40 (m, 2H), 7.66 (s, 1H, ArH), 7.78e7.81 (m, 1H),
7.88 (d, 1H, J¼16.1 Hz), 7.91e7.95 (m, 1H). 13C NMR (62 MHz, CDCl3):
In a pressure tube (glass bomb) a suspension of Pd(OAc)2 (12 mg,
0.05 mmol, 1.7 mol % per Br atom) and dicyclohexyl-(20,60-dime-
thoxybiphenyl-2-yl) phosphine (SPhos, 41 mg, 0.10 mmol) in DMF
(5 mL) was flushed with Ar and stirred at 20 ꢀC to give a yellowish
or brownish transparent solution. To the stirred solution were
added the 2,3,6-tribromobenzothiophene (15b, 371 mg, 1.0 mmol),
Et3N (1.1 mL, 8.0 mmol), and styrene (1.25 equiv per Br). The re-
action mixture was stirred at 130 ꢀC for 48 h. The solution was
cooled to 20 ꢀC, poured into H2O and CH2Cl2 (25 mL each), and the
organic and the aqueous layers were separated. The latter was
extracted with CH2Cl2 (3ꢂ25 mL). The combined organic layers
were washed with H2O (3ꢂ20 mL), dried (Na2SO4), concentrated in
vacuo, and passed through a column (silica gel). To a xylene solu-
tion (3 mL) of the crude product was added Pd/C (30 mg, 10 mol %).
The solution was stirred under reflux for 48 h under argon atmo-
sphere. The reaction mixture was filtered, and the filtrate was
concentrated in vacuo. The residue was purified by chromatogra-
phy (flash silica gel, heptaneseEtOAc) to yield the product.
d
¼14.3 (CH3), 60.5 (OCH2),118.7, 122.1, 123.0, 124.9,125.0, 128.0 (CH),
~
131.6 (C),136.3 (CH),137.1, 140.5 (C),167.1 (CO). IR (KBr):
n
¼2978 (w),
1703 (s), 1627 (s), 1503 (w), 1368 (m), 1257 (m), 1158 (s), 1093 (w),
1043 (m), 971 (m), 731 (s) cmꢁ1. GCeMS (EI, 70 eV): m/z (%)¼232
(92) [M]þ, 217 (02), 204 (09), 187 (100), 175 (04), 160 (29), 147 (07),
115 (67). HRMS (EI, 70 eV): m/z calcd for C13H12O2S [M]þ: 232.05525;
found: 232.05530.
4.13.2. (E)-Butyl 3-(benzo[b]thiophen-3-yl)acrylate (19b). Compound
19b was prepared starting with 15a (292 mg,1.0 mmol) as a colorless
viscous oil (169 mg, 65%). 1H NMR (300 MHz, CDCl3):
d¼0.89 (t, 3H,
J¼7.4 Hz, CH3), 1.30e1.42 (m, 2H), 1.57e1.69 (m, 2H), 4.16 (t, 2H,
J¼6.7 Hz, OCH2), 6.45 (d,1H, J¼15.9 Hz), 7.25e7.41 (m, 2H), 7.66 (s,1H,
ArH), 7.77e7.81 (m,1H), 7.88 (d,1H, J¼16.1 Hz), 7.91e7.95 (m,1H).13C
NMR (75 MHz, CDCl3):
117.7, 121.1, 121.9, 123.9, 124.0, 126.9 (CH), 130.6 (C), 135.2 (CH), 136.1,
d
¼12.7 (CH3), 18.2, 29.7 (CH2), 63.4 (OCH2),

S.-M. Tengho Toguem et al. / Tetrahedron 69 (2013) 160e173
173
6. Mourey, R. J.; Burnette, B. L.; Brustkern, S. J.; Daniels, J. S.; Hirsch, J. L.; Hood,
W. F.; Meyers, M. J.; Mnich, S. J.; Pierce, B. S.; Saabye, M. J.; Schindler, J. F.;
South, S. A.; Webb, E. G.; Zhang, J.; Anderson, D. R. J. Pharmacol. Exp. Ther.
2010, 333, 797.
4.14.1. (E)-2,3-Diphenyl-7-styryldibenzo[b,d]thiophene (22). Comp-
ound 22 was prepared starting with 15b (371 mg, 1.0 mmol) as
a brownish semisolid (319 mg, 73%). 1H NMR (300 MHz, CDCl3):
7. Najer, H.; Giudicelli, R.; Moral, C.; Menin, M. Bull. Soc. Chim. Fr. 1966, 153, 40.
8. Black, L. J.; Jones, C. D.; Falcone, J. F. Life Sci. 1983, 32, 1031.
9. Hellmann, K.; Marshall, P. G.; Stayt, S. Biochem. Pharmacol. 1967, 16, 681.
10. Kennedy, D. A.; Summers, L. A. J. Heterocycl. Chem. 1981, 409, 39.
11. (a) Kuhn, M.; Falk, F. C.; Paradies, J. Org. Lett. 2011, 13, 4100; (b) Nakamura, I.;
Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 4473; (c) Wang, Z.; Geng,
W.; Wang, H.; Zhang, S.; Zhang, W.-X.; Xi, Z. Tetrahedron Lett. 2011, 52, 6997; (d)
Inami, T.; Baba, Y.; Kurahashi, T.; Matsubara, S. Org. Lett. 2011, 13, 1912; (e)
Yamashita, M.; Horiguchi, H.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009,
74, 7481; (f) Zhou, Y.; Liu, W.-J.; Ma, Y.; Wang, H.; Qi, L.; Cao, Y.; Wang, J.; Pei, J. J.
Am. Chem. Soc. 2007, 129, 12386; (g) Bryan, C. S.; Braunger, J. A.; Lautens, M.
Angew. Chem., Int. Ed. 2009, 48, 7064; (h) Yasukawa, T.; Satoh, T.; Miura, M.;
Nomura, M. J. Am. Chem. Soc. 2002, 124, 12680.
d
¼7.01e7.20 (m, 7H), 7.24e7.34 (m, 7H), 7.40e7.47 (m, 6H),
7.75e7.86 (m, 2H, ArH). 13C NMR (62 MHz, CDCl3):
d¼120.7, 121.3,
122.1, 122.3, 122.9, 125.6, 126.5, 126.6, 127.5, 128.6, 128.7, 128.8 (CH),
129.7, 130.3 (C), 130.4 (CH), 137.3, 137.4, 137.4, 137.5, 139.9, 140.5,
141.2, 142.1 (C). IR (KBr):
~
n
¼3054 (w), 3023 (w), 291 (w), 1681 (m),
1596 (m), 1493 (m), 1445 (m), 1178 (w), 1155 (w),1072 (w),1026 (w),
956 (s), 908 (w), 876 (w), 812 (w), 747 (s), 733 (s), 688 (s) cmꢁ1. MS
(EI, 70 eV): m/z (%)¼438 (19) [M]þ, 368 (31), 338 (100), 259 (20), 234
(16), 202 (10), 105 (15). HRMS (EI, 70 eV): m/z calcd for C32H22
S
[M]þ: 438.14422; found: 438.144012.
12. Tengho Toguem, S.-M.; Hussain, M.; Malik, I.; Villinger, A.; Langer, P. Tetrahedron
Lett. 2009, 50, 4962.
13. Hussain, M.; Malik, I.; Langer, P. Synlett 2009, 2691.
References and notes
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A. R.; Falcone, J. F.; Clemens, J. A. J. Med. Chem. 1984, 27, 1057; (b) Raga, M.;
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17. Bussenius, J.; Laber, N.; Muller, T.; Eberbach, W. Chem. Ber. 1994, 127, 247.
18. Heynderickx, A.; Samat, A.; Gugliemetti, R. Synthesis 2002, 213.
19. Cooper, J.; Ewing, D. F.; Scrowston, R. M.; Westwood, R. J. Chem. Soc. C 1970, 14,
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20. CCDC 906013–906015 contains all crystallographic details of this publication
and is available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or
can be ordered from the following address: Cambridge Crystallographic Data
Centre, 12 Union Road, GB-Cambridge CB21EZ; fax: (þ44)1223-336-033; or
deposit@ccdc.cam.ac.uk.