Intramolecular Mizoroki-Heck Reaction of 2-Thiosubstituted Acrylates for the Synthesis of 3-Substituted Benzo[ b ]thiophene-2-carboxylates

Article abstract of DOI:10.1055/s-0035-1562613

3-Substituted 2-(phenylthio)acrylates prepared from aldol condensation using titanium tetrachloride were employed to synthesize benzo[b]thiophenes. The acrylates containing aryls and alkyls generated the desired benzo[b]thiophenes in reasonable yields und

Full text of DOI:10.1055/s-0035-1562613

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–L
paper
A
S. H. Kwak et al.
Paper
Synthesis
Intramolecular Mizoroki–Heck Reaction of 2-Thiosubstituted
Acrylates for the Synthesis of 3-Substituted Benzo[b]thiophene-
2-carboxylates
Se Hun Kwak
Su-Jeong Lim
Hyun-Jeong Yoo
Ji-Eun Ha
O
EtO2C
R
R
PdBr2 (10 mol%)
TBAB (1 equiv)
NaOAc (2 equiv)
S
S
CO2Et TiCl4 (1.3 equiv)
Et3N (4 equiv)
S
CO2Et
Young-Dae Gong*
Br
Br
CH2Cl2, rt, 10 min !
DMF, 120 °C, 12 h
R
Aldol condensation
R = aryl, alkyl
Mizoroki–Heck
Center for Innovative Drug Library Research, Department
of Chemistry, College of Science, Dongguk University, 26,
3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea
ydgong@dongguk.edu
Received: 16.06.2016
Accepted after revision: 11.07.2016
Published online: 23.08.2016
R
R
Pd(Ph3P)4, Et3N
MeCN, reflux
X
DOI: 10.1055/s-0035-1562613; Art ID: ss-2016-f0436-op
S
S
Abstract 3-Substituted 2-(phenylthio)acrylates prepared from aldol
condensation using titanium tetrachloride were employed to synthe-
size benzo[b]thiophenes. The acrylates containing aryls and alkyls gen-
erated the desired benzo[b]thiophenes in reasonable yields under the
optimized Heck condition, but acrylates having heteroaryls gave the
desired products in poor yields or no products under the condition.
O
O
N
N
Pd(Ph3P)4, Et3N
MeCN, reflux
Br
S
S
O
O
Ph
Ph
Key words Heck reaction, acrylate, benzo[b]thiophene, heterocycles,
TiCl4
Scheme 1 Examples of fused thiophene synthesis via intramolecular
Heck reaction
Mizoroki–Heck reaction is a valuable tool for the forma-
tion of C–C bond between organohalides (or triflates) and
olefins. Along with application of the intermolecular Heck
reaction, the transformation have been widely used intra-
molecularly to construct rings, providing access to a num-
ber of natural products and heterocycles.1 Although a range
of synthetic routes using this protocol for the target mole-
cules have been developed, an unexplored route involving
the Heck protocol with efficient and convenient means re-
mains to be studied. In this regard, our interest was to find
a new way to heterocycles, especially benzo[b]thiophenes,
via intramolecular Heck reaction.
At first, Knoevenagel condensation with piperidine at
refluxing temperature was attempted in order to obtain the
desired acrylate 2a from ethyl (2-bromophenyl)thioacetate
(1a) (Table 1, entry 1). However, we failed to obtain the ac-
rylate 2a. Addition of acetic acid under the same condition
above was also not effective for the condensation (entry 2).
When the ester 1a was treated with ethanolic sodium
ethoxide at room temperature, the acrylate 2a was ob-
tained in poor yield (29%) (entry 3). The acrylate could be
produced via condensation of aldol adduct generated using
LDA at –78 °C, but this procedure was not preferred as it re-
quires inconvenient two steps.7 After scrutinizing condi-
tions for the condensation, we found that TiCl4 with tri-
ethylamine in dichloromethane could be applied to our
substrate and eventually acquired the acrylate 2a in a good
yield (80%) within a short reaction time (10 min).8
Benzo[b]thiophenes2 are biologically prominent hetero-
cycles like other similar skeletons such as benzofurans3 and
indoles.4 A few study for the approach to benzo[b]thio-
phenes5 or fused thiophenes6 via Heck cyclization have
been reported (Scheme 1); however, intermediates for the
synthesis of 2,3-disubstituted benzo[b]thiophenes via in-
tramolecular Heck cyclization have not previously been ex-
plored. Herein, we report the preparation of 2-thiosubsti-
tuted acrylates and the corresponding benzo[b]thiophenes
via intramolecular Heck reaction.
Aryl aldehydes bearing various functional groups, het-
eroaryl, and alkyl aldehydes were reacted in the titanium-
mediated aldol condensation with the acetate 1a, which
readily gave acrylates 2a–p (Table 2, entries 1–16). 2-(Pyri-
dinethio)acetate 1b, 2-(phenylsulfonyl)acetate 1c, 2-(ben-
zylthio)acetate 1d, and 2-(phenylthio)acetonitrile 1e were
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–L

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S. H. Kwak et al.
Paper
Synthesis
Table 1 Aldol Condensation of Ethyl 2-Phenylthioacetate (1a)a
the corresponding 2-(phenylamino)acrylate, which could
be used for the synthesis of indole (entry 21).9 Finally, 2-
(phenyloxy)acrylates 1g and 1h were prepared to investi-
gate whether they could be employed for the synthesis of
benzofuran (entries 22 and 23).3 The geometry of acrylates
2 were assumed to be Z by comparing β-vinyl proton signals
of 2 with those of E- and Z-isomers in the literature.10
We initiated the optimization of Heck reaction with the
acrylate 2a under the conditions either with a phosphine li-
gand or with no ligand (Jeffery conditions) (Table 3, entries
1 and 2).11 Both gave unsatisfactory results. However, in
these experiments, we observed that the Jeffery conditions
gave a cleaner product 3a,12 either without purification or
after short column chromatography, than the conditions
using triphenylphospine. Therefore, optimization studies
were carried out under Jeffery conditions by changing bas-
es, solvents, reaction temperature, additives and palladium
catalysts. Control experiments showed that the suitable
base is sodium acetate (entries 2, 3 and 6), reaction tem-
perature below 120 °C is not enough for complete con-
sumption of the acrylate 2a (entries 5 and 6), DMF as sol-
vent was better than MeCN and NMP (entries 4–6 and 15),
palladium(II) bromide as catalyst was the best (entries 6, 8,
9, 17, and 18), and TBAB (tetrabutylammonium bromide) is
the most appropriate additive among others (entries 6 and
10–14).
EtO2C
Ph
conditions
O
S
CO2Et
S
+
Ph
Br
Br
1a
2a
Entry
Conditions
Yield (%)
1b
piperidine, toluene, 120 °C, 24 h
piperidine, AcOH, toluene, 120 °C, 24 h
NaOEt, EtOH, r.t., 3 h
–
2b,c
3d
–
29
80
4e
TiCl4, Et3N, CH2Cl2, r.t., 10 min
a Ester 1a (0.4 mmol), benzaldehyde (1.05 equiv).
b Piperidine (0.5 equiv).
c AcOH (0.5 equiv).
d NaOEt (1.5 equiv).
e TiCl4 (1.3 equiv), Et3N (4 equiv).
also investigated with benzaldehyde, which gave acrylates
2q–s and acrylonitrile 2t (entries 17–20). Unlike the ester
1a, the acetonitrile 1e provided E- and Z-isomers, separable
via flash column chromatography (entry 20). This is proba-
bly because nitrile group has smaller steric interactions
than ethyl ester. In case of the ethyl aryl glycinate 1f, an al-
dol product 2u was isolated as a major product rather than
Table 2 Preparation of Acrylates 2a
A
EWG
TiCl4, Et3N
CH2Cl2, rt
O
R1
A
EWG
+
R1
R2
R2
1
2
A = S, O, NH, NMe
EWG = CO2Et, CN
X
EWG
Entry
1
R2
Product
Yield (%)
80
R1
EtO2C
S
CO2Et
S
1a
2a
2b
Br
Br
EtO2C
EtO2C
EtO2C
S
2
3
4
88
76
81
CF3
F3C
Br
S
2c
CN
NC
Br
S
2d
NO2
O2N
Br
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–L

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S. H. Kwak et al.
Paper
Synthesis
Table 2 (continued)
X
EWG
Entry
R2
Product
Yield (%)
86
R1
EtO2C
S
5
2e
2f
F
F
Br
Cl
EtO2C
EtO2C
EtO2C
EtO2C
6
85
S
Cl
Br
S
7
8
2g
2h
2i
88
85
53
46b
93
54
73
61
50
CO2Me
MeO2C
MeO
Br
S
OMe
Br
O
O
S
9
O
O
Br
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
S
10
11
12
13
14
15
2j
Me
Br
S
2k
2l
Br
S
Br
S
S
S
S
2m
2n
2oa
Br
S
S
Br
H
N
S
HN
Br
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S. H. Kwak et al.
Paper
Synthesis
Table 2 (continued)
R2
Product
Yield (%)
58
X
EWG
Entry
R1
EtO2C
N
S
16
2p
2q
2r
N
Br
EtO2C
N
N
S
CO2Et
S
17
1b
1c
61
63
Br
Br
EtO2C
O
O
S
CO2Et
S
O
18
19
20
21
O
Br
Br
CO2Et
S
CO2Et
S
1d
1e
1f
2s
2t
2u
87
91
36
Br
Br
NC
S
CN
S
Br
Br
OH
H
N
EtO2C
EtO2C
EtO2C
CO2Et
NH
Br
Br
O
CO2Et
CO2Et
O
22
23
1g
1h
2v
62
59
Br
Br
O
I
O
I
2w
a Ester 1 (2 mmol), aldehyde (1.05 equiv), TiCl4 (1.3 equiv), and Et3N (4 equiv).
b Slightly impure product, which slowly decomposed.
With the optimal conditions in hand, the substrate
scope and limitations of the conditions were next explored
(Table 4). The reactions proceeded well whether acrylates 2
have an electron-donating or electron-withdrawing group
on the phenyl ring (R2) to afford 3a–i. Furthermore, acry-
lates 2 having alkyl groups (R2) under the conditions gave
the corresponding benzo[b]thiophenes 3k and 3l except for
ethyl (2-arylthio)crotonate 2j. The instability of 2j could ex-
plain this failure. Unfortunately, acrylates 2m–p involving
heterocycles (R2) gave poor yields (3ma, 3n, 3ob) or no
products (2oa and 2p). 3-(5-Methylthiophen-2-yl)acrylate
2m also underwent cyclization to yield both the tricycle
3mb and a thiol detached by-product 3mc. Attempts to
synthesize the thieno[2,3-b]pyridine from 2q failed. The
sulfonyl acrylate 2r gave only the vinyl sulfone 3r.13 2-(Ben-
zylthio)acrylate 2s under the optimized condition gave a
complex mixture. Acrylonitrile 2t was not a suitable sub-
strate for the construction of benzo[b]thiophene under the
Heck condition. This result was unexpected because re-
placement of ethyl ester with nitrile would not be a signifi-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–L

E
S. H. Kwak et al.
Paper
Synthesis
cant change. Also, attempts to synthesize the benzofuran
from 2-(phenyloxy)acrylate 2v failed even though the more
reactive iodide 2w than the bromide 2v was used.
aryls at the 3-position, and benzofuran. Further studies in
order to achieve intramolecular Heck reaction for the unre-
active substrates are in progress.
Table 3 Optimization of Intramolecular Heck Reaction of 2aa
All commercial reagents and solvents were used as received without
further purification. The reactions were monitored by TLC. Column
chromatography was performed with silica gel (230–400 mesh). 1H
and 13C NMR spectra were recorded on a 500 MHz spectrometer ref-
erenced to TMS at δ = 0.00 as an internal standard. HRMS were ob-
tained using a TOF LC/MS system.
EtO2C
Ph
CO2Et
S
conditions
S
Ph
Br
2a
3a
Acrylates 2; General Procedure
Entry
[Pd]
Additive
Base
Temp (°C)
Time (h)
Yield
(%)b
To a solution of the respective aldehyde (1.05 mmol) and the appro-
priate 2-(arylthio)acetate 1 (1 mmol) in CH2Cl2 (4 mL) was added
dropwise TiCl4 (1.3 mmol, 1.0 M in CH2Cl2). The mixture was stirred
for 5 min, then Et3N (4 mmol) was added dropwise. After 10 min, H2O
was added to the mixture and extracted with CH2Cl2. The combined
organic layers were dried (MgSO4) and filtered. After removal of the
solvent under vacuum, the residue was purified by column chroma-
tography to afford the desired product 2 (Table 2).
d
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Ph3Pc
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAOAc
TBACl
TBAF
TBAI
K2CO3
120/12
120/12
120/12
100/24
100/24
120/3
–
K2CO3
Et3N
13
34
15f
30g
75
64
74
60
62
65
25
50i
69
56
15k
3
4e
5
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
–
6
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-phenylacrylate (2a)
Pale yellow solid; yield: 581 mg (80%); mp 79–81 °C.
7h
8
120/24
120/16
120/24
120/3
IR (ATR): 3053, 2981, 2901, 1712, 1487, 1271, 1226, 1174, 841, 754
cm–1
.
9
Pd2dba3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdBr2
1H NMR (500 MHz, CDCl3): δ = 8.23 (s, 1 H), 7.87–7.79 (m, 2 H), 7.54
(dd, J = 7.9, 1.2 Hz, 1 H), 7.43–7.34 (m, 3 H), 7.20–7.13 (m, 1 H), 7.11
(dd, J = 7.9, 1.7 Hz, 1 H), 7.04–6.97 (m, 1 H), 4.14 (q, J = 7.1 Hz, 2 H),
1.09 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 165.83, 147.13, 137.29, 134.06,
132.99, 130.83, 130.21, 128.76, 128.42, 127.74, 127.22, 124.54,
122.71, 61.95, 13.86.
10
11
12
13
14
15j
16
17
120/3
120/24
120/24
120/24
120/24
120/24
120/12
LiBr
TBAB
TBAB
TBAB
HRMS (APCI): m/z [M + H]+ calcd for C17H16BrO2S: 363.0049; found:
363.0049.
NaOAc
78
(75)l
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-[4-(trifluoromethyl)phe-
nyl]acrylate (2b)
18
Pd(TFA)2
TBAB
NaOAc
120/12
78
a Acrylate 2a (0.2 mmol), Pd cat. (10 mol%), additive (1 equiv), base (2
equiv), and DMF (1 mL).
Yellow oil; yield: 759 mg (88%).
1H NMR (500 MHz, CDCl3): δ = 8.16 (s, 1 H), 7.87 (d, J = 8.1 Hz, 2 H),
7.65 (d, J = 8.2 Hz, 2 H), 7.55 (dd, J = 7.9, 1.1 Hz, 1 H), 7.22–7.16 (m, 1
H), 7.13 (dd, J = 7.9, 1.5 Hz, 1 H), 7.09–7.01 (m, 1 H), 4.14 (q, J = 7.1 Hz,
2 H), 1.09 (t, J = 7.2 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 165.33, 144.17, 137.48, 136.44,
133.16, 131.35 (q, J = 32.7 Hz), 130.67, 129.43, 127.92, 127.84, 127.79,
125.30 (q, J = 3.6 Hz), 123.79 (q, J = 272.5 Hz), 123.31, 62.20, 13.82.
b Yield determined by 1H NMR spectroscopy.
c Ph3P: 20 mol%.
d Intractable mixtures and 3a.
e MeCN as solvent instead of DMF.
f Unreacted 2a: 67%.
g Unreacted 2a: 20%.
h Pd(OAc)2: 5 mol%.
i Unreacted 2a: 15%.
j NMP as solvent instead of DMF.
k Unreacted 2a: 66%.
HRMS (APCI): m/z [M + H]+ calcd for C18H15BrF3O2S: 430.9923; found:
430.9909.
l Isolated yield.
In conclusion, we have reported on the new route for
the 1,2-disubstituted benzo[b]thiophenes. The advantages
of this route are that the preparation of acrylates is easy and
a number of them can be prepared. However, the optimized
Heck condition was not effective to the substrates for the
synthesis of thieno[2,3-b]pyridine, isothiochromene, 2-cya-
nobenzo[b]thiophene, benzo[b]thiophenes having hetero-
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(4-cyanophenyl)acrylate (2c)
Pale yellow solid; yield: 590 mg (76%); mp 98–100 °C.
IR (ATR): 3053, 2903, 2217, 1711, 1272, 1228, 1176, 755 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.08 (s, 1 H), 7.85 (d, J = 8.2 Hz, 2 H),
7.67 (d, J = 8.4 Hz, 2 H), 7.55 (dd, J = 8.0, 1.1 Hz, 1 H), 7.22–7.16 (m, 1
H), 7.14 (dd, J = 7.9, 1.5 Hz, 1 H), 7.06 (td, J = 8.0, 1.7 Hz, 1 H), 4.14 (q,
J = 7.1 Hz, 2 H), 1.08 (t, J = 7.2 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–L

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S. H. Kwak et al.
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Synthesis
Table 4 Intramolecular Heck Reaction of Acrylates and Acrylonitrilea
A
A
EWG
PdBr2, NaOAc
EWG
TBAB, DMF, 120 °C
X
2
R2
R2
A = S, O, NH, NMe
EWG = CO2Et, CN
X = Br or I
3
Precursor 2
Product 3
Yield (%)
Precursor 2
Product 3
Yield (%)
CO2Et
CO2Et
S
S
2a
3a (75)
2b
3b (53)
CF3
CO2Et
CO2Et
S
S
2c
2e
2g
3c (58)
3e (62)
3g (73)
2d
2f
3d (53)
3f (70)
3h (56)
NO2
CN
CO2Et
S
CO2Et
S
Cl
S
F
CO2Et
CO2Et
S
2h
CO2Me
OMe
CO2Et
S
CO2Et
CO2Et
S
S
d
2i
3i (68)
3k (51)
2j
2l
–
O
O
CO2Et
S
S
2k
3l (46)
CO2Et
S
CO2Et
S
S
S
2mb
3ma (11)c
3mb (6)c
2nb
3n (12)c
CO2Et
CO2Et
S
d
H
N
2oa
–
S
CO2Et
CO2Et
N
S
3mc (6)c
2obb
3ob (4)
S
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–L

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S. H. Kwak et al.
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Synthesis
Table 4 (continued)
Precursor 2
Product 3
Yield (%)
Precursor 2
Product 3
Yield (%)
CO2Et
CO2Et
S
S
N
d
e
2p
2r
–
2q
–
N
O
O
S
CO2Et
S
3r (27%)f
2s
2v
–
d
Br
CN
CO2Et
S
O
d
d
2t
–
–
CO2Et
O
d
2w
–
a Acrylate 2 (0.5 mmol), PdBr2 (10 mol%), TBAB (1 equiv), NaOAc (2 equiv), and DMF (2.5 mL) at 120 °C for 12 h.
b Toluene was used as the solvent instead of DMF.
c The product was isolated by preparative TLC.
d Not detected.
e No reaction.
f Unreacted 2r: 8%.
13C NMR (126 MHz, CDCl3): δ = 165.10, 142.93, 138.46, 136.05,
133.23, 132.05, 130.81, 129.77, 129.25, 128.05, 127.88, 123.60,
118.39, 112.96, 62.30, 13.79.
HRMS (APCI): m/z [M + H]+ calcd for C18H14BrNO2S: 388.0001; found:
387.9978.
13C NMR (126 MHz, CDCl3): δ = 165.71, 162.58 (d, J = 246.4 Hz),
138.63 (d, J = 2.3 Hz), 136.94 (d, J = 7.9 Hz), 134.74, 133.34, 132.04,
129.94 (d, J = 8.4 Hz), 128.83, 128.40, 127.93, 124.99, 124.42 (d, J = 2.9
Hz), 115.87 (d, J = 21.2 Hz), 115.21 (d, J = 22.4 Hz), 61.83, 13.66.
HRMS (APCI): m/z [M + H]+ calcd for C17H15BrFO2S: 380.9955; found:
380.9943.
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(4-nitrophenyl)acrylate (2d)
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(2-chlorophenyl)acrylate
(2f)
Yellow solid; yield: 661 mg (81%); mp 102–103 °C.
IR (ATR): 2991, 1702, 1513, 1340, 1251, 1199, 1012, 846 cm–1
.
Pale yellow oil; yield: 676 mg (85%).
1H NMR (500 MHz, CDCl3): δ = 8.24 (d, J = 8.9 Hz, 2 H), 8.11 (s, 1 H),
7.91 (d, J = 8.7 Hz, 2 H), 7.56 (dd, J = 8.0, 1.1 Hz, 1 H), 7.23–7.14 (m, 2
H), 7.07 (td, J = 7.9, 1.8 Hz, 1 H), 4.14 (q, J = 7.2 Hz, 2 H), 1.09 (t, J = 7.2
Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 165.02, 147.85, 142.24, 140.33,
135.87, 133.27, 131.09, 129.99, 129.93, 128.18, 127.91, 123.74,
123.54, 62.36, 13.79.
1H NMR (500 MHz, CDCl3): δ = 8.36 (s, 1 H), 7.72 (dd, J = 7.2, 2.1 Hz, 1
H), 7.51 (dd, J = 7.9, 1.1 Hz, 1 H), 7.40 (dd, J = 7.7, 1.6 Hz, 1 H), 7.34–
7.24 (m, 2 H), 7.22–7.11 (m, 2 H), 7.02 (td, J = 7.9, 1.8 Hz, 1 H), 4.17 (q,
J = 7.1 Hz, 2 H), 1.11 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 165.16, 143.27, 136.78, 134.55,
133.02, 132.87, 130.83, 130.64, 129.43, 129.31, 128.17, 127.77,
127.51, 126.41, 123.13, 62.08, 13.85.
HRMS (APCI): m/z [M + H]+ calcd for C17H15BrNO4S: 407.9900; found:
407.9872.
HRMS (APCI): m/z [M + H]+ calcd for C17H15BrClO2S: 396.9659; found:
396.9658.
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(3-fluorophenyl)acrylate
(2e)
Methyl (Z)-4-{2-[(2-Bromophenyl)thio]-3-ethoxy-3-oxoprop-1-
en-1-yl}benzoate (2g)
Pale yellow oil; yield: 656 mg (86%).
Pale yellow solid; yield: 741 mg (88%); mp 85–87 °C.
1H NMR (500 MHz, CDCl3): δ = 7.58 (dd, J = 8.0, 1.2 Hz, 1 H), 7.46 (dd,
J = 7.9, 1.5 Hz, 1 H), 7.32–7.23 (m, 3 H), 7.14–7.08 (m, 3 H), 7.06–6.99
(m, 2 H), 4.07 (q, J = 7.1 Hz, 2 H), 1.03 (t, J = 7.1 Hz, 3 H).
IR (ATR): 3003, 2980, 2955, 1705, 1590, 1428, 1279, 1241, 1193, 1107,
1016, 770 cm–1
.
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1H NMR (500 MHz, CDCl3): δ = 8.16 (s, 1 H), 8.04 (d, J = 8.4 Hz, 2 H),
7.83 (d, J = 8.3 Hz, 2 H), 7.53 (dd, J = 8.0, 1.2 Hz, 1 H), 7.17 (td, J = 7.7,
1.3 Hz, 1 H), 7.12 (dd, J = 7.9, 1.6 Hz, 1 H), 7.03 (td, J = 7.9, 1.7 Hz, 1 H),
4.13 (q, J = 7.1 Hz, 2 H), 3.91 (s, 3 H), 1.07 (t, J = 7.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C14H16BrO2S: 327.0049; found:
327.0045.
Ethyl (Z)-2-[(2-Bromophenyl)thio]-5-methylhex-2-enoate (2l)
13C NMR (126 MHz, CDCl3): δ = 166.44, 165.45, 144.75, 138.35,
136.64, 133.13, 130.96, 130.47, 129.54, 129.39, 127.83, 127.70,
127.56, 123.25, 62.16, 52.31, 13.84.
HRMS (APCI): m/z [M + H]+ calcd for C19H18BrO4S: 421.0104; found:
421.0093.
Pale yellow oil; yield: 371 mg (54%).
IR (ATR): 2956, 2869, 1711, 1446, 1243, 1041, 1019, 745 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.60–7.48 (m, 2 H), 7.17 (td, J = 7.8, 1.4
Hz, 1 H), 7.03–6.95 (m, 2 H), 4.13 (q, J = 7.1 Hz, 2 H), 2.43 (t, J = 7.2 Hz,
2 H), 1.85 (dq, J = 13.4, 6.7 Hz, 1 H), 1.10 (t, J = 7.2 Hz, 3 H), 0.96 (d, J =
6.6 Hz, 6 H).
13C NMR (126 MHz, CDCl3): δ = 165.04, 154.20, 137.64, 132.90,
127.89, 127.58, 126.69, 126.45, 122.05, 61.60, 39.78, 28.32, 22.55,
13.92.
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(4-methoxyphenyl)acrylate
(2h)
Pale yellow oil; yield: 668 mg (85%).
IR (ATR): 2976, 1709, 1603, 1509, 1249, 1173, 1020, 829, 749 cm–1
.
HRMS (APCI): m/z [M + H]+ calcd for C15H20BrO2S: 343.0362; found:
1H NMR (500 MHz, CDCl3): δ = 8.24 (s, 1 H), 7.89 (d, J = 8.7 Hz, 2 H),
7.53 (d, J = 7.9 Hz, 1 H), 7.15 (t, J = 7.6 Hz, 1 H), 7.07 (d, J = 7.8 Hz, 1 H),
7.00 (t, J = 7.6 Hz, 1 H), 6.91 (d, J = 8.9 Hz, 2 H), 4.16 (q, J = 7.1 Hz, 2 H),
1.11 (t, J = 7.1 Hz, 3 H).
343.0365.
Ethyl (Z)-2-[(2-Bromophenyl)thio)-3-(5-methylthiophen-2-yl)ac-
rylate (2m)
13C NMR (126 MHz, CDCl3): δ = 166.24, 161.43, 147.84, 137.59,
133.20, 132.94, 128.08, 127.72, 126.88, 126.70, 122.25, 120.62,
113.96, 61.80, 55.37, 13.95.
HRMS (APCI): m/z [M + H]+ calcd for C18H18BrO3S: 393.0155; found:
393.0156.
Brown oil; yield: 560 mg (73%).
1H NMR (500 MHz, CDCl3): δ = 8.46 (s, 1 H), 7.52 (d, J = 7.8 Hz, 1 H),
7.33 (d, J = 3.7 Hz, 1 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.98 (t, J = 8.1 Hz, 2 H),
6.77 (d, J = 3.7 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H), 2.48 (s, 3 H), 1.15 (t, J =
7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 166.02, 149.41, 143.57, 137.30,
137.28, 135.93, 132.94, 127.74, 126.96, 126.76, 125.64, 122.14,
116.35, 61.77, 15.92, 14.11.
Ethyl (Z)-3-(Benzo[d][1,3]dioxol-5-yl)-2-[(2-bromophenyl)thio]ac-
rylate (2i)
Pale yellow solid; yield: 432 mg (53%); mp 90–91 °C.
HRMS (APCI): m/z [M + H]+ calcd for C16H16BrO2S2: 382.9770; found:
IR (ATR): 2994, 2906, 1678, 1573, 1485, 1372, 1235, 1195, 1099, 1016,
382.9772.
928, 809 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.65 (d, J = 1.3 Hz, 1 H),
7.53 (d, J = 7.9 Hz, 1 H), 7.28 (dd, J = 8.1, 1.2 Hz, 1 H), 7.15 (d, J = 7.6,
Hz, 1 H), 7.06 (dd, J = 7.8, 1.1 Hz, 1 H), 7.00 (td, J = 7.6, 1.1 Hz, 1 H),
6.83 (d, J = 8.1 Hz, 1 H), 5.99 (s, 2 H), 4.13 (q, J = 7.1 Hz, 2 H), 1.09 (t, J =
7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 166.10, 149.60, 147.79, 147.58,
137.36, 132.97, 128.19, 127.85, 127.74, 127.02, 122.36, 121.22,
110.03, 108.31, 101.62, 61.88, 13.92.
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(thiophen-2-yl)acrylate (2n)
Pale yellow solid; yield: 451 mg (61%); mp 97–98 °C.
IR (ATR): 3103, 2990, 1703, 1582, 1253, 1200, 1036, 1019, 748, 719
cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.54 (s, 1 H), 7.57–7.51 (m, 3 H), 7.15–
7.08 (m, 2 H), 7.02–6.96 (m, 2 H), 4.19 (q, J = 7.1 Hz, 2 H), 1.16 (t, J =
7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 165.78, 142.75, 137.85, 136.92,
136.34, 133.37, 132.97, 127.75, 127.14, 126.92, 126.90, 122.32,
118.64, 61.89, 14.05.
HRMS (APCI): m/z [M + H]+ calcd for C18H16BrO4S: 406.9947; found:
406.9937.
HRMS (APCI): m/z [M + H]+ calcd for C15H14BrO2S2: 368.9613; found:
368.9610.
Ethyl 2-[(2-Bromophenyl)thio]but-2-enoate (2j)
Brown oil; yield: 277 mg (46%).
1H NMR (500 MHz, CDCl3): δ (major isomer) = 7.63 (q, J = 7.0 Hz, 1 H),
7.52 (dd, J = 7.9, 1.2 Hz, 1 H), 7.20–7.14 (m, 1 H), 7.02–6.94 (m, 2 H),
4.14 (q, J = 7.1 Hz, 2 H), 2.10 (d, J = 7.0 Hz, 3 H), 1.13 (t, J = 7.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C12H14BrO2S: 300.9892; found:
300.9897.
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(1H-pyrrol-2-yl)acrylate
(2oa)
Yellow solid; yield: 352 mg (50%); mp 71–72 °C.
1H NMR (500 MHz, CDCl3): δ = 12.10 (s, 1 H), 7.51 (d, J = 5.9 Hz, 2 H),
7.18 (t, J = 7.5 Hz, 1 H), 7.10 (d, J = 7.3 Hz, 2 H), 6.99 (t, J = 7.5 Hz, 1 H),
6.63 (s, 1 H), 6.33 (s, 1 H), 4.15 (q, J = 7.1 Hz, 2 H), 1.08 (t, J = 7.1 Hz, 3
H).
Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-cyclopropylacrylate (2k)
Pale yellow oil; yield: 609 mg (93%).
13C NMR (126 MHz, CDCl3): δ = 167.74, 143.32, 139.75, 132.79,
128.25, 127.56, 127.09, 126.47, 124.92, 122.11, 121.14, 111.15,
109.46, 61.78, 13.83.
HRMS (APCI): m/z [M + H]+ calcd for C15H15BrNO2S: 352.0001; found:
351.9999.
1H NMR (500 MHz, CDCl3): δ = 7.49 (dd, J = 7.9, 1.2 Hz, 1 H), 7.20–7.15
(m, 1 H), 7.01–6.95 (m, 2 H), 6.94 (d, J = 10.7 Hz, 1 H), 4.13 (q, J = 7.1
Hz, 2 H), 2.25–2.16 (m, 1 H), 1.12 (t, J = 7.1 Hz, 3 H), 1.08–1.04 (m, 2
H), 0.83–0.78 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 165.22, 161.51, 137.92, 132.85,
127.59, 127.26, 126.39, 121.47, 121.36, 61.52, 14.59, 14.07, 9.83.
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Ethyl (Z)-2-[(2-Bromophenyl)thio]-3-(pyridin-3-yl)acrylate (2p)
Yellow solid; yield: 423 mg (58%); mp 58–59 °C.
13C NMR (126 MHz, CDCl3): δ = 151.25, 133.61, 133.55, 132.87,
131.63, 131.55, 129.42, 129.25, 129.13, 128.33, 125.08, 116.16,
102.62.
HRMS (APCI): m/z [M + H]+ calcd for C15H11BrNS: 315.9790; found:
315.9760.
IR (ATR): 3056, 2990, 1699, 1413, 1239, 1220, 1036, 1016, 808, 758
cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.53 (s, 1 H), 7.56–7.50 (m, 3 H), 7.15–
7.08 (m, 2 H), 7.01–6.94 (m, 2 H), 4.19 (q, J = 7.1 Hz, 2 H), 1.16 (t, J =
7.1 Hz, 3 H).
Minor Isomer 2t
White solid; yield: 228 mg (36%); mp 46–47 °C.
13C NMR (126 MHz, CDCl3): δ = 165.80, 142.73, 137.89, 136.96,
136.33, 133.36, 133.00, 127.77, 127.20, 126.94, 126.92, 122.37,
118.72, 61.90, 14.07 (one carbon is missing due to overlapping).
HRMS (APCI): m/z [M + H]+ calcd for C16H15BrNO2S: 364.0001; found:
364.0024.
1H NMR (500 MHz, CDCl3): δ = 7.77–7.70 (m, 2 H), 7.67 (dd, J = 7.9, 1.4
Hz, 1 H), 7.56 (dd, J = 7.8, 1.5 Hz, 1 H), 7.53 (s, 1 H), 7.49–7.40 (m, 3 H),
7.36 (td, J = 7.6, 1.2 Hz, 1 H), 7.24 (td, J = 7.8, 1.7 Hz, 1 H).
13C NMR (126 MHz, CDCl3): δ = 146.81, 133.70, 133.62, 133.34,
132.28, 130.69, 130.49, 130.30, 128.75, 128.37, 126.94, 116.79,
107.30.
Ethyl (Z)-2-[(3-Bromopyridin-2-yl)thio]-3-phenylacrylate (2q)
Pale brown solid; yield: 444 mg (61%); mp 97–98 °C.
Ethyl 2-[(2-Bromophenyl)amino]-3-hydroxy-3-phenylpropanoate
(2u)
1H NMR (500 MHz, CDCl3): δ = 8.31 (dd, J = 4.7, 1.4 Hz, 1 H), 8.19 (s, 1
H), 7.72 (td, J = 6.0, 1.4 Hz, 6 H), 7.41–7.35 (m, 3 H), 6.89 (dd, J = 7.9,
4.7 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 1.14 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 166.12, 158.08, 147.67, 145.70,
139.57, 134.25, 130.64, 129.77, 128.32, 124.12, 120.84, 118.40, 61.74,
14.01.
Colorless oil; yield: 262 mg (36%).
1H NMR (500 MHz, CDCl3): δ = 7.41 (td, J = 7.0, 1.4 Hz, 3 H), 7.39–7.26
(m, 4 H), 7.05 (td, J = 7.8, 1.2 Hz, 1 H), 6.59 (td, J = 7.8, 1.4 Hz, 1 H),
6.43 (dd, J = 8.2, 1.0 Hz, 1 H), 5.22 (d, J = 8.7 Hz, 1 H), 5.12 (t, J = 4.3 Hz,
1 H), 4.24 (dd, J = 8.7, 4.6 Hz, 1 H), 4.12 (q, J = 7.1 Hz, 2 H), 3.00 (d, J =
4.1 Hz, 1 H), 1.13 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 171.54, 143.78, 139.53, 132.66,
128.50, 128.37, 128.36, 126.34, 119.40, 112.52, 111.04, 74.34, 63.49,
61.72, 14.02.
HRMS (APCI): m/z [M + H]+ calcd for C16H15BrNO2S: 364.0001; found:
364.0011.
Ethyl (Z)-2-[(2-Bromophenyl)sulfonyl]-3-phenylacrylate (2r)
White solid; yield: 498 mg (63%); mp 101–102 °C.
IR (ATR): 2989, 1716, 1615, 1320, 1216, 1152, 1035, 855, 749 cm–1
HRMS (APCI): m/z [M + H]+ calcd for C17H19BrNO3: 364.0543; found:
364.0534.
.
1H NMR (500 MHz, CDCl3): δ = 8.27 (dd, J = 7.9, 1.7 Hz, 1 H), 7.73 (dd,
J = 7.9, 1.2 Hz, 1 H), 7.55–7.49 (m, 3 H), 7.48–7.44 (m, 2 H), 7.42–7.38
(m, 2 H), 4.12 (q, J = 7.1 Hz, 2 H), 1.03 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.51, 148.27, 138.38, 135.45,
134.66, 132.84, 131.96, 131.63, 131.55, 130.12, 128.80, 127.69,
121.07, 62.24, 13.50.
Ethyl (Z)-2-(2-Bromophenoxy)-3-phenylacrylate (2v)
White solid; yield: 431 mg (62%); mp 80–81 °C.
IR (ATR): 2994, 2903, 1712, 1471, 1224, 1096, 1096, 924, 767, 753 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.74–7.71 (m, 2 H), 7.61 (d, J = 7.9 Hz, 1
H), 7.37–7.31 (m, 3 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.91 (t, J = 7.6 Hz, 1 H),
6.79 (d, J = 8.2 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 1.18 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 163.18, 153.11, 139.90, 133.72,
132.27, 130.46, 129.83, 128.80, 128.34, 127.37, 123.79, 114.91,
111.99, 61.59, 14.03.
HRMS (APCI): m/z [M + H]+ calcd for C17H16BrO4S: 394.9947; found:
394.9941.
Ethyl (Z)-2-[(2-Bromobenzyl)thio]-3-phenylacrylate (2s)
Pale yellow oil; yield: 656 mg (87%).
HRMS (APCI): m/z [M + H]+ calcd for C17H16BrO3: 347.0277; found:
347.0282.
1H NMR (500 MHz, CDCl3): δ = 7.68–7.64 (m, 2 H), 7.45 (d, J = 7.7 Hz, 1
H), 7.32–7.28 (m, 3 H), 7.16–7.11 (m, 2 H), 7.03–6.98 (m, 1 H), 4.34 (q,
J = 7.1 Hz, 2 H), 4.13 (s, 2 H), 1.39 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 166.32, 146.12, 136.85, 134.46,
132.94, 130.98, 130.82, 129.57, 128.79, 128.08, 127.31, 125.60,
124.59, 61.95, 39.05, 14.40.
Ethyl (Z)-2-(2-Iodophenoxy)-3-phenylacrylate (2w)
White solid; yield: 465 mg (59%); mp 92–93 °C.
1H NMR (500 MHz, CDCl3): δ = 7.84 (dd, J = 7.8, 1.4 Hz, 1 H), 7.72 (dd,
J = 7.5, 1.9 Hz, 2 H), 7.37–7.31 (m, 3 H), 7.18 (td, J = 8.2, 1.4 Hz, 1 H),
6.78 (td, J = 7.7, 1.2 Hz, 1 H), 6.73 (dd, J = 8.2, 1.1 Hz, 1 H), 4.18 (q, J =
7.1 Hz, 2 H), 1.17 (t, J = 7.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C18H18BrO2S: 377.0205; found:
377.0193.
13C NMR (126 MHz, CDCl3): δ = 163.18, 155.50, 140.08, 139.78,
132.29, 130.50, 129.81, 129.35, 128.79, 127.27, 124.35, 113.95, 85.77,
61.57, 14.06.
HRMS (APCI): m/z [M + H]+ calcd for C17H16IO3: 395.0139; found:
395.0129.
2-[(2-Bromophenyl)thio]-3-phenylacrylonitrile (2t)
Major Isomer 2t
White solid; yield: 348 mg (55%); mp 48–49 °C.
1H NMR (500 MHz, CDCl3): δ = 7.83 (dd, J = 7.3, 2.0 Hz, 2 H), 7.63 (dd,
J = 7.9, 1.2 Hz, 1 H), 7.57 (s, 1 H), 7.51–7.43 (m, 4 H), 7.35 (td, J = 7.7,
1.2 Hz, 1 H), 7.19 (td, J = 7.8, 1.5 Hz, 1 H).
Benzo[b]thiphenes 3; General Procedure
To a solution of acrylate 2 (0.5 mmol) in DMF (2.5 mL) in an 8 mL
screw-capped vial were added PdBr2 (10 mol %), NaOAc (2 equiv), and
TBAB (1 equiv). The mixture was heated at 120 °C for 12 h. After cool-
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ing to r.t., H2O was added to the mixture and extracted with Et2O. The
combined organic layers were dried (MgSO4) and filtered. After re-
moval of the solvent under vacuum, the residue was purified by col-
umn chromatography to afford the desired product 3 (Table 4).
Ethyl 3-(3-Fluorophenyl)benzo[b]thiophene-2-carboxylate (3e)
Yellow solid; yield: 93 mg (62%); mp 58–59 °C.
IR (ATR): 3071, 2989, 2902, 1711, 1278, 1216 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 8.1 Hz, 1 H), 7.51 (d, J = 8.2
Hz, 1 H), 7.48 (td, J = 7.6, 1.4 Hz, 2 H), 7.46–7.40 (m, 1 H), 7.36 (td, J =
7.6, 1.0 Hz, 2 H), 7.20–7.14 (m, 2 H), 7.13–7.08 (m, 1 H), 4.23 (q, J = 7.1
Hz, 2 H), 1.20 (t, J = 7.1 Hz, 3 H).
Ethyl 3-Phenylbenzo[b]thiophene-2-carboxylate (3a)
Pale yellow solid; yield: 106 mg (75%); mp 48–49 °C.
IR (ATR): 3054, 2983, 2903, 1713, 1503, 1488, 1272, 1227, 1175, 1060,
13C NMR (126 MHz, CDCl3): δ = 162.47 (d, J = 246.0 Hz), 162.44,
142.06, 142.04, 140.11 (d, J = 72.3 Hz), 136.88, 136.81, 129.53 (d, J =
8.4 Hz), 129.24, 127.28, 125.55 (d, J = 2.9 Hz), 125.00 (d, J = 4.8 Hz),
122.56, 116.89 (d, J = 22.1 Hz), 114.95 (d, J = 21.0 Hz), 61.41, 13.96.
HRMS (APCI): m/z [M + H]+ calcd for C17H14FO2S: 301.0693; found:
301.0684.
1026, 754 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 8.1 Hz, 1 H), 7.53 (d, J = 8.2
Hz, 1 H), 7.51–7.42 (m, 4 H), 7.41–7.37 (m, 2 H), 7.34 (t, J = 7.6 Hz, 1
H), 4.22 (q, J = 7.1 Hz, 2 H), 1.19 (t, J = 7.2 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.64, 143.77, 140.40, 140.17,
134.72, 129.68, 128.68, 127.98, 127.10, 125.27, 124.75, 122.46, 61.23,
13.96 (one carbon is missing due to overlapping).
Ethyl 3-(2-Chlorophenyl)benzo[b]thiophene-2-carboxylate (3f)
Yellow oil; yield: 111 mg (70%).
HRMS (APCI): m/z [M + H]+ calcd for C17H15O2S: 283.0787; found:
283.0781.
IR (ATR): 2905, 1706, 1537, 1469, 1273, 1243, 1185, 1053, 841, 755
cm–1
.
Ethyl 3-[4-(Trifluoromethyl)phenyl]benzo[b]thiophene-2-carboxy-
late (3b)
1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 8.2 Hz, 1 H), 7.52 (dd, J = 7.6,
1.5 Hz, 1 H), 7.48–7.43 (m, 1 H), 7.41–7.26 (m, 5 H), 4.26–4.15 (m, 2
H), 1.14 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.28, 140.37, 140.17, 139.43,
134.15, 133.75, 131.02, 130.28, 129.40, 129.36, 127.16, 126.42,
124.88, 124.81, 122.56, 61.29, 13.84.
Yellow solid; yield: 93 mg (53%); mp 57–58 °C.
IR (ATR): 2939, 1706, 1321, 1272, 1236, 1157, 1106, 1058, 850 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.90 (d, J = 8.2 Hz, 1 H), 7.75 (d, J = 8.1
Hz, 2 H), 7.52 (d, J = 8.0 Hz, 2 H), 7.50–7.45 (m, 2 H), 7.37 (td, J = 7.6,
0.7 Hz, 2 H), 4.23 (q, J = 7.1 Hz, 2 H), 1.20 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.36, 142.00, 140.48, 139.69,
138.63, 130.19 130.16 (q, J = 32.5 Hz), 129.36, 127.41, 125.10, 125.01
(q, J = 3.7 Hz), 124.85, 124.21 (q, J = 272.1 Hz), 122.63, 61.50, 13.94.
HRMS (APCI): m/z [M + H]+ calcd for C17H14ClO2S: 317.0398; found:
317.0397.
Ethyl 3-[4-(Methoxycarbonyl)phenyl]benzo[b]thiophene-2-car-
boxylate (3g)
HRMS (APCI): m/z [M + H]+ calcd for C18H14F3O2S: 351.0661; found:
351.0658.
Pale yellow solid; yield: 124 mg (73%); mp 108–109 °C.
1H NMR (500 MHz, CDCl3): δ = 8.16 (d, J = 8.2 Hz, 2 H), 7.89 (d, J = 8.1
Hz, 1 H), 7.50–7.45 (m, 4 H), 7.35 (t, J = 7.6 Hz, 1 H), 4.22 (q, J = 7.1 Hz,
2 H), 3.96 (s, 3 H), 1.18 (t, J = 7.1 Hz, 3 H).
Ethyl 3-(4-Cyanophenyl)benzo[b]thiophene-2-carboxylate (3c)
White solid; yield: 89 mg (58%); mp 134–135 °C.
IR (ATR): 2994, 2228, 1709, 1272, 1236, 1175, 831, 757 cm–1
.
13C NMR (126 MHz, DMSO-d6): δ = 166.11, 161.63, 141.76, 139.59,
139.12, 138.98, 130.19, 129.19, 128.87, 128.79, 127.74, 125.61,
124.54, 123.13, 61.29, 52.31, 13.73.
1H NMR (500 MHz, CDCl3): δ = 7.91 (d, J = 8.2 Hz, 1 H), 7.83–7.76 (m, 2
H), 7.56–7.49 (m, 3 H), 7.44 (d, J = 7.9 Hz, 1 H), 7.42–7.35 (m, 1 H),
4.25 (q, J = 7.2 Hz, 2 H), 1.23 (t, J = 7.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C19H17O4S: 341.0842; found:
13C NMR (126 MHz, CDCl3): δ = 162.17, 141.32, 140.51, 139.82,
139.31, 131.83, 130.66, 129.54, 127.51, 125.23, 124.57, 122.71,
118.78, 111.91, 61.60, 14.00.
341.0867.
Ethyl 3-(4-Methoxyphenyl)benzo[b]thiophene-2-carboxylate (3h)
HRMS (APCI): m/z [M + H]+ calcd for C18H14NO2S: 308.0740; found:
Pale yellow solid; yield: 87 mg (56%); mp 142–143 °C.
IR (ATR): 3059, 3004, 2840, 1709, 1234, 1171, 1026, 848, 756 cm–1
.
308.0712.
1H NMR (500 MHz,CDCl3): δ = 7.87 (d, J = 8.1 Hz, 1 H), 7.58 (d, J = 8.2
Hz, 1 H), 7.51–7.43 (m, 1 H), 7.39–7.32 (m, 3 H), 7.06–6.99 (m, 2 H),
4.25 (q, J = 7.1 Hz, 2 H), 3.89 (s, 3 H), 1.24 (t, J = 7.2 Hz, 3 H).
Ethyl 3-(4-Nitrophenyl)benzo[b]thiophene-2-carboxylate (3d)
Yellow solid; yield: 86 mg (53%); mp 119–120 °C.
13C NMR (126 MHz, CDCl3): δ = 162.68, 159.44, 143.69, 140.36,
140.29, 131.01, 128.16, 127.08, 126.70, 125.32, 124.68, 122.46,
113.47, 61.20, 55.29, 14.09.
HRMS (APCI): m/z [M + H]+ calcd for C18H17O3S: 313.0893; found:
313.0896.
IR (ATR): 3106, 2981, 1683, 1506, 1343, 1288, 1250, 1086, 854, 838
762 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.35 (td, J = 8.7, 2.0 Hz, 3 H), 7.91 (d, J =
8.2 Hz, 1 H), 7.58 (td, J = 8.8, 2.2 Hz, 3 H), 7.52 (td, J = 7.6, 1.1 Hz, 2 H),
7.44 (d, J = 7.9 Hz, 1 H), 7.38 (td, J = 7.5, 0.8 Hz, 2 H), 4.24 (q, J = 7.1 Hz,
2 H), 1.23 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.15, 147.61, 141.82, 140.98,
140.55, 139.27, 130.89, 129.69, 127.59, 125.33, 124.54, 123.32,
122.76, 61.69, 14.05.
HRMS (APCI): m/z [M + H]+ calcd for C17H14NO4S: 328.0638; found:
328.0613.
Ethyl 3-[Benzo[d][1,3]dioxol-5-yl]benzo[b]thiophene-2-carboxyl-
ate (3i)
Pale yellow solid; yield: 111 mg (68%); mp 98–99 °C.
IR (ATR): 2986, 2899, 2796, 1715, 1483, 1229, 1032, 758 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–L

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1H NMR (500 MHz, CDCl3): δ = 7.86 (d, J = 8.1 Hz, 1 H), 7.58 (d, J = 8.2
Hz, 1 H), 7.46 (t, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 6.93 (d, J = 7.9
Hz, 1 H), 6.89–6.84 (m, 2 H), 6.04 (s, 2 H), 4.26 (q, J = 7.1 Hz, 2 H), 1.26
(t, J = 7.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C16H15O2S2: 303.0508; found:
303.0467.
Ethyl (E)-3-(5-Methylthiophen-2-yl)acrylate (3mc)14
13C NMR (126 MHz, CDCl3): δ = 162.56, 147.46, 147.36, 143.38,
140.31, 140.18, 128.48, 128.07, 127.17, 125.25, 124.78, 123.37,
122.49, 110.43, 108.10, 101.20, 61.29, 14.11.
Yellow oil; yield: 6 mg (6%).
1H NMR (500 MHz, CDCl3): δ = 7.69 (d, J = 15.6 Hz, 1 H), 7.05 (d, J = 3.6
Hz, 1 H), 6.70 (dd, J = 3.6, 1.2 Hz, 1 H), 6.10 (d, J = 15.6 Hz, 1 H), 4.24 (q,
J = 7.1 Hz, 2 H), 2.49 (s, 3 H), 1.32 (t, J = 7.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C18H15O4S: 326.0686; found:
327.0691.
Ethyl 3-(Thiophen-2-yl)benzo[b]thiophene-2-carboxylate (3n)
Ethyl 3-Cyclopropylbenzo[b]thiophene-2-carboxylate (3k)
Brown solid; yield: 17 mg (12%).
Colorless oil; yield: 63 mg (51%).
IR (ATR): 2981, 1713, 1693, 1226, 1058, 758, 734 cm–1
1H NMR (500 MHz, CDCl3): δ = 8.06 (d, J = 8.0 Hz, 1 H), 7.79 (d, J = 8.0
Hz, 1 H), 7.44–7.35 (m, 2 H), 4.40 (q, J = 7.1 Hz, 2 H), 2.32 (tt, J = 8.7,
5.6 Hz, 1 H), 1.41 (t, J = 7.1 Hz, 3 H), 1.18–1.14 (m, 2 H), 0.89–0.85 (m,
2 H).
1H NMR (500 MHz, CDCl3): δ = 7.87 (d, J = 8.1 Hz, 1 H), 7.74 (d, J = 8.2
Hz, 1 H), 7.53 – 7.45 (m, 2 H), 7.39 (ddd, J = 8.1, 7.1, 1.0 Hz, 1 H), 7.21–
7.14 (m, 2 H), 4.28 (q, J = 7.1 Hz, 2 H), 1.26 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.30, 140.31, 139.90, 135.60,
134.05, 130.54, 128.61, 127.26, 126.80, 126.69, 125.23, 125.01,
122.42, 61.43, 14.01.
.
13C NMR (126 MHz, CDCl3): δ = 163.03, 144.79, 140.27, 140.19,
HRMS (APCI): m/z [M + H]+ calcd for C15H13O2S2: 289.0351; found:
129.88, 126.74, 124.72, 124.24, 122.68, 61.26, 14.36, 9.83, 7.48.
289.0340.
HRMS (APCI): m/z [M + H]+ calcd for C14H15O2S: 247.0787; found:
247.0785.
Ethyl 3-(1-Methyl-1H-pyrrol-2-yl)benzo[b]thiophene-2-carboxyl-
ate (3ob)
Ethyl 3-Isobutylbenzo[b]thiophene-2-carboxylate (3l)
Colorless oil; yield: 60 mg (46%).
Brown oil; yield: 6 mg (4%).
1H NMR (500 MHz, CDCl3): δ = 7.89 (dd, J = 8.1, 1.0 Hz, 1 H), 7.73 (dd,
J = 8.1, 1.1 Hz, 1 H), 7.51 (ddd, J = 8.2, 7.1, 1.2 Hz, 1 H), 7.44–7.38 (m, 1
H), 6.86 (t, J = 2.1 Hz, 1 H), 6.36–6.30 (m, 1 H), 6.26 (dd, J = 3.6, 1.7 Hz,
1 H), 4.38–4.24 (m, 2 H), 3.45 (s, 3 H), 1.30 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 162.31, 140.64, 140.23, 135.01,
130.51, 127.29, 125.72, 125.25, 124.89, 123.08, 122.41, 110.19,
107.72, 61.36, 34.27, 14.15.
IR (ATR): 2957, 2868, 1711, 1525, 1242, 1217, 1098, 1062, 909, 758,
732 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.83 (dd, J = 12.3, 7.9 Hz, 2 H), 7.49–
7.33 (m, 2 H), 4.38 (q, J = 7.2 Hz, 2 H), 3.19 (d, J = 7.3 Hz, 2 H), 2.15–
2.02 (m, 1 H), 1.41 (t, J = 7.2 Hz, 3 H), 0.97 (d, J = 6.6 Hz, 6 H).
13C NMR (126 MHz, CDCl3): δ = 163.35, 145.10, 140.56, 140.13,
127.51, 126.90, 124.21, 124.13, 122.60, 61.12, 35.82, 30.02, 22.76,
14.32.
HRMS (APCI): m/z [M + H]+ calcd for C16H16NO2S: 286.0896; found:
286.0892.
HRMS (APCI): m/z [M + H]+ calcd for C15H19O2S: 263.1100; found:
263.1100.
(E)-1-Bromo-2-(styrylsulfonyl)benzene (3r)13
Yellow solid; yield: 44 mg (27%); mp 115–117 °C.
Ethyl 3-(5-Methylthiophen-2-yl)benzo[b]thiophene-2-carboxylate
(3ma)
1H NMR (500 MHz, CDCl3): δ = 7.81 (d, J = 8.5 Hz, 2 H), 7.70 (d, J = 8.5
Hz, 2 H), 7.67 (d, J = 15.4 Hz, 1 H), 7.48 (d, J = 6.6 Hz, 2 H), 7.40 (q, J =
6.6 Hz, 3 H), 6.83 (d, J = 15.4 Hz, 1 H).
13C NMR (126 MHz, CDCl3): δ = 143.1, 139.8, 132.6, 132.2, 131.4,
129.2, 129.1, 128.6, 126.8.
Pale yellow solid; yield: 17 mg (11%).
1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J = 8.1 Hz, 1 H), 7.81 (d, J = 8.1
Hz, 1 H), 7.50–7.45 (m, 1 H), 7.42–7.35 (m, 1 H), 6.98 (d, J = 3.4 Hz, 1
H), 6.83 (dd, J = 3.4, 1.2 Hz, 1 H), 4.30 (q, J = 7.1 Hz, 2 H), 1.31 (d, J = 7.1
Hz, 2 H).
Acknowledgment
13C NMR (126 MHz, CDCl3): δ = 162.33, 141.37, 140.28, 139.90,
136.21, 131.48, 129.80, 128.74, 127.22, 125.34, 125.11, 124.92,
122.39, 61.39, 15.37, 14.08.
HRMS (APCI): m/z [M + H]+ calcd for C16H15O2S2: 303.0508; found:
303.0493.
This study was supported by the Bio & Medical Technology Develop-
ment Program of the National Research Foundation funded by the
Ministry of Science, ICT & Future Planning (No. 2014M3A9A9073847),
the Ministry of Trade, Industry & Energy, and the Korean Institute for
Advancement of Technology through the industrial infrastructure
program for fundamental technologies (Grant Number M0000338).
Ethyl 2-Methylbenzo[b]thieno[3,2-d]thiophene-5-carboxylate
(3mb)
Light yellow solid; yield: 9 mg (6%).
Supporting Information
1H NMR (500 MHz, CDCl3): δ = 9.10–9.01 (m, 1 H), 8.35–8.23 (m, 1 H),
7.67 (s, 1 H), 7.64–7.57 (m, 2 H), 4.49 (q, J = 7.1 Hz, 2 H), 2.73 (s, 3 H),
1.48 (t, J = 7.2 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 167.56, 145.02, 140.12, 134.86,
129.07, 128.93, 126.70, 126.36, 126.34, 125.44, 123.93, 122.99,
120.52, 61.01, 16.52, 14.46.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562613.
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