Synthesis of 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans via Sonogashira Cross-Coupling of 3-Iodo-2-(methylsulfanyl)benzo[b]furans with Terminal Alkynes

Article abstract of DOI:10.1055/s-0029-1217041

3-Alkynyl-2-(methylsulfanyl)benzo[b]furans were readily prepared under mild reaction conditions by palladium-catalyzed cross-coupling of 3-iodo-2-(methylsulfanyl)benzo[b]furans with a variety of terminal alkynes. The reaction was performed with propargyl

Full text of DOI:10.1055/s-0029-1217041

PAPER
4001
Synthesis of 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans via Sonogashira
Cross-Coupling of 3-Iodo-2-(methylsulfanyl)benzo[b]furans with Terminal
Alkynes
Synthesis of
3
l
á
yl-2-(methy
v
lsulfanyl)be
i
b
]f
a
urans Manarin, Juliano A. Roehrs, Ricardo Brandão, Cristina W. Nogueira, Gilson Zeni*
Laboratório de Síntese, Reatividade, Avaliação Farmacológica e Toxicológica de Organocalcogênios, CCNE, UFSM, Santa Maria,
Rio Grande do Sul, CEP 97105-900, Brazil
Fax +55(55)32208978; E-mail: gzeni@pq.cnpq.br
Received 27 April 2009; revised 25 July 2009
This reaction is generally cocatalyzed by copper salts, and
Abstract: 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans
were
an amine as base and a phosphine as a ligand for palladi-
um are also typically employed. Recent advances in Sono-
gashira reactions, including the use of metals other than
readily prepared under mild reaction conditions by palladium-cata-
lyzed cross-coupling of 3-iodo-2-(methylsulfanyl)benzo[b]furans
with a variety of terminal alkynes. The reaction was performed with
propargyl alcohols, protected propargyl alcohols, as well as alkyl palladium8 and a copper-free protocol,9 have also been re-
and aryl terminal alkynes. In addition, the 3-alkynylbenzo[b]furans
obtained were readily transformed into more complex products us-
ing the hydrotelluration reaction, which furnished the desired vinyl-
ic tellurides in good yields. Moreover, using a copper-catalyzed
ported.
Our continuing interest in the synthesis10 and
applications11 of organochalcogenides in organic synthe-
sis prompted us to examine and expand the scope of the
Sonogashira reaction of 3-iodo-2-(methylsulfanyl)ben-
zo[b]furans 1a–d with different terminal alkynes 2a–o to
provide 3-alkynylbenzo[b]furans 3a–v (Scheme 1).
homocoupling reaction, we were able to convert a 3-alkynylben-
zo[b]furan into a symmetric diyne in good yield.
Key words: palladium, Sonogashira cross-coupling, furans,
alkynes, catalysis
R3
Heterocycles containing oxygen exhibit a broad range of
biological activities, such as anticancer,1 antiviral,2 anti-
oxidative,3 insecticidal,4 anti-inflammatory,5 and
antifungal6 activity. The synthesis of heterocycles, partic-
ularly the benzo[b]furan nucleus, from a simple synthon
and with a high degree of selectivity has been a major
challenge to organic chemists. The characteristic structure
of these compounds involves the presence of substituent
groups at the C2 and C3 positions of the benzofuran skel-
eton. We were interested in studying the structure–activity
relationship of benzofurans with a chalcogen atom at the
2-position and an alkyne group at the 3-position, in order
to evaluate the pharmacological activity of these com-
pounds. To the best of our knowledge, there are no reports
in the literature dealing with the preparation of these 2,3-
disubstituted benzofurans. In particular, the lack of an ef-
fective method for the introduction of an alkyne substitu-
ent at the C3 position of the skeleton has been an obstacle
to the synthesis of these compounds.
I
R1
R1
R3
2
YR2
YR2
O
PdCl2(PPh3)2 (1 mol%)
CuI (2 mol%), Et3N, r.t.
O
1a–d
3
R1 = H, Me, F
YR2 = SMe, SePh
Scheme 1
The starting materials 1a–d are readily available in 87–
95% yield by electrophilic cyclization12 of (2-chalco-
genoalkynyl)anisoles by treatment with iodine in dichlo-
romethane (Scheme 2).13
YR2
I
R1
R1
I2, CH2Cl2
YR2
30 min., r.t.
O
OMe
In an attempt to develop an easy, versatile, and efficient
methodology for such compounds, we chose a palladium
cross-coupling reaction between 3-iodo-2-chalcogeno-
benzo[b]furans and terminal alkynes. The palladium-cat-
alyzed cross-coupling reaction of hetaryl halides with
terminal alkynes, commonly referred to as the Sonoga-
shira reaction, is a powerful, versatile, and popular tool for
the selective construction of new carbon–carbon bonds.7
1a R1 = H, YR2 = SMe 93%
1b R1 = Me, YR2 = SMe 95%
1c R1 = F, YR2 = SMe 87%
1d R1 = H, YR2 = SePh 90%
Scheme 2
For a preliminary optimization of the reaction conditions,
we chose 3-iodo-2-(methylsulfanyl)benzo[b]furan (1a)
and phenylacetylene (2a) as the substrates. Thus, a mix-
ture of 1a (0.5 mmol), alkyne 2a (1.25 mmol), triethyl-
amine (2 mL) as solvent, and copper(I) iodide (2 mol%)
SYNTHESIS 2009, No. 23, pp 4001–4009
x
x.
x
x
.
2
0
0
9
Advanced online publication: 12.10.2009
DOI: 10.1055/s-0029-1217041; Art ID: M02209SS
© Georg Thieme Verlag Stuttgart · New York

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F. Manarin et al.
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were employed with a variety of palladium salts, at room Table 2 Optimization of Reaction Conditionsa
temperature (Table 1).
Ph
According to Table 1, both palladium(0) and palladi-
um(II) with the different ligands tested exhibited catalytic
I
activity and PdCl2(PPh3)2 (5 mol%) gave the desired prod-
uct in excellent yield (entry 1). However, it is important to
Ph
SMe
SMe
PdCl2(PPh3)2 (1 mol%)
O
O
note that when the amount of catalyst was reduced from
five to two or one mol%, an increase in the yield was ob-
served (cf. entries 1, 2, and 8). The other palladium salts
were less effective (entries 3, 5–7). When the reactions
were carried out in the absence of palladium or copper, the
desired coupling product was not obtained (entry 9).
CuI (2 mol%), solvent
base, r.t.
1a
3a
Entry
Solvent
Base
Yield (%)b
1
2
DMF
Et3N
60
45
37
92
56
54
67
50
87
trace
99
MeOH
DME
Et3N
Table 1 Study of Catalyst Effect on the Coupling Reactiona
3
Et3N
Ph
4
dioxane
toluene
THF
Et3N
5
Et3N
I
Ph
6
Et3N
SMe
SMe
Pd, CuI, Et3N
O
O
r.t.
7
dioxane
dioxane
dioxane
dioxane
Et3N
K3PO4
K2CO3
pyrrolidine
NaOH
Et3N
3a
1a
8
Entry
Catalyst (mol%)
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (2)
Pd(OAc)2 (2)
Pd(PPh3)4 (2)
PdCl2(NCPh)2 (2)
PdCl2 (2)
Yield 3a (%)b
9
1
2
3
4
5
6
7
8
9
90
10
11
97
trace
85
a CuI (2 mol%) was used in all the reactions.
b Yields were determined by GC analysis.
38
2-(methylsulfanyl)benzo[b]furan (1a; 0.5 mmol), cop-
per(I) iodide (2 mol%), and phenylacetylene (2a; 1.25
mmol), at room temperature for three hours.
34
Pd(acac)2 (2)
PdCl2(PPh3)2 (1)
–
40
To expand the applicability of our method, we applied
these conditions to other halobenzo[b]furans 1a–d and
other terminal alkynes 2a–o. The results, summarized in
Table 3, show that the reaction worked well for a variety
of propargyl alcohols, protected propargyl alcohols, and
aryl- and alkyl-substituted alkynes. A detailed analysis re-
vealed that the reaction was effective with alkynes con-
taining both no substituted and substituted aryl groups
(entries 1–4). Both hindered and nonhindered propargyl
alcohols provided the coupling products in excellent
yields (entries 5–8). We also tested a protected propargyl
alcohol, and, although the reaction gave the product 3k in
84% yield, it required a long reaction time, 24 hours (entry
11). We also found that the coupling reaction was not sen-
sitive to steric effects on the terminal alkynes. For exam-
ple, terminal alkynes containing a tert-butyl or n-butyl
group gave the desired product in comparable yields (en-
tries 12 and 13). The effect of the hydroxy position in the
alkyne chain was also examined. Alkynols 2i and 2j (en-
tries 9 and 10), with four and twelve carbons between the
hydroxy group and the triple bond, respectively, produced
the corresponding product in yields similar to those ob-
tained with alkynes containing the hydroxy group at the
propargyl position.
99
n.r.c
a CuI (2 mol%) was used in all the reactions.
b Yields were determined by GC analysis.
c Reaction carried out in the absence of CuI (n.r. = no reaction).
An analysis of the influence of the solvent showed that the
best results were obtained when dioxane was used
(Table 2, entry 4). N,N-Dimethylformamide, methanol,
1,2-dimethoxyethane, toluene, and tetrahydrofuran gave
moderate yields (entries 1–3, 5, and 6). However, when
triethylamine was used as solvent and base, the Sonoga-
shira product was obtained in 99% yield (entry 11). We
also investigated other bases, and found that optimal re-
sults were achieved when organic bases such as pyrroli-
dine and triethylamine were used (entries 4, 9, and 11),
while inorganic bases, such as potassium phosphate and
potassium carbonate, gave the desired product in moder-
ate yields (entries 7 and 8). When sodium hydroxide was
used as the base, only traces of the desired product were
detected (entry 10). Thus, a careful analysis revealed that
the optimum conditions for this coupling involved the use
of PdCl2(PPh3)2 (1 mol%), triethylamine (2 mL), 3-iodo-
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Synthesis of 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans
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Table 3 Cross-Coupling Reactions between 3-Iodobenzo[b]furans 1a–c and Alkynes 2a–o
R3
I
R1
PdCl2(PPh3)2
(1 mol%)
R1
YR2
R3
YR2
+
O
CuI (2 mol%)
Et3N, r.t.
O
2a–o
3a–v
1a–c
R1 = H, Me, F
YR2 = SMe, SePh
Entry
Substrate
Alkyne
Product
Yield (%)a,b
I
1
99
SMe
O
2a
1a
1a
SMe
O
3a
2
96
2b
SMe
OMe
O
3b
OMe
3
1a
95
2c
SMe
O
3c
OMe
4
1a
85
MeO
2d
SMe
OH
O
3d
3e
5
1a
93
OH
SMe
2e
O
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F. Manarin et al.
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Table 3 Cross-Coupling Reactions between 3-Iodobenzo[b]furans 1a–c and Alkynes 2a–o (continued)
R3
I
R1
PdCl2(PPh3)2
(1 mol%)
R1
YR2
R3
YR2
+
O
CuI (2 mol%)
Et3N, r.t.
O
2a–o
3a–v
1a–c
R1 = H, Me, F
YR2 = SMe, SePh
Entry
Substrate
Alkyne
Product
Yield (%)a,b
OH
HO
6
1a
80
88
2f
SMe
OH
O
3f
7
8
1a
1a
OH
2g
SMe
O
3g
OH
86
OH
2h
SMe
O
3h
OH
9
1a
80
OH
2i
SMe
O
3i
3j
C12H24OH
10
1a
78
C12H24OH
2j
SMe
O
O
84c
O
11
1a
2k
SMe
O
3k
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Synthesis of 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans
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Table 3 Cross-Coupling Reactions between 3-Iodobenzo[b]furans 1a–c and Alkynes 2a–o (continued)
R3
I
R1
PdCl2(PPh3)2
(1 mol%)
R1
YR2
R3
YR2
+
O
CuI (2 mol%)
Et3N, r.t.
O
2a–o
3a–v
1a–c
R1 = H, Me, F
YR2 = SMe, SePh
Entry
Substrate
Alkyne
Product
Yield (%)a,b
12
1a
89
2l
SMe
O
3l
13
1a
75
2m
SMe
O
3m
14
1a
45
2n
SMe
O
3n
I
15
75
SMe
O
2a
SMe
1b
O
3o
I
F
16
72
SMe
F
O
2a
1c
SMe
OH
O
3p
17
1c
80
OH
F
2e
SMe
O
3q
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Table 3 Cross-Coupling Reactions between 3-Iodobenzo[b]furans 1a–c and Alkynes 2a–o (continued)
R3
I
R1
PdCl2(PPh3)2
(1 mol%)
R1
YR2
R3
YR2
+
O
CuI (2 mol%)
Et3N, r.t.
O
2a–o
3a–v
1a–c
R1 = H, Me, F
YR2 = SMe, SePh
Entry
Substrate
Alkyne
Product
Yield (%)a,b
OH
18
1c
91
OH
F
2h
SMe
O
3r
I
19
50d
SePh
O
2a
2g
2o
1d
1d
SePh
O
3s
3t
OH
20
21
40d
OH
SePh
OH
O
1d
55d
OH
SePh
OH
O
3u
22
1d
45d
OH
2e
SePh
O
3v
a Isolated yields.
b The reactions were carried out for 2–6 h at r.t.
c The reaction was carried out for 24 h at r.t.
d The reactions were carried out for 16 h at 60 °C.
Finally, we explored the possibility of expanding our the reaction worked well, affording the 3-alkynylben-
methodology to other 3-iodobenzo[b]furans 1b,c with a zo[b]furan derivatives 3o–r in good to excellent yields,
methyl and fluorine in the aromatic ring. It was found that
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Synthesis of 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans
4007
under the same reaction conditions (Table 3, entries 15–
18).
H
In an attempt to broaden the scope of our methodology,
the possibility of performing the reaction with an orga-
noselenium group on the 3-iodobenzofurans was also in-
vestigated. Substrate 1d, which has a phenylselanyl group
on the 2-position, was cross-coupled efficiently with
alkynes (Table 3, entries 19–22).
CuCl, TMEDA
SMe
O
O
acetone
O
[O], 45 °C
SMe
MeS
4a 71%
5b 75%
Scheme 4
In addition, the 3-alkynylbenzo[b]furans obtained by this
method appear to be promising intermediates for the prep-
aration of more highly substituted benzo[b]furans. We
therefore investigated the synthesis of vinylic telluride 5a
using compound 4a as starting material. For this purpose,
3-alkynylbenzo[b]furan 3e was subjected to a retro-
Favorskii reaction,14 in which a propargylic monoacetyl-
enic alcohol reacted with sodium hydroxide in toluene un-
der reflux for twelve hours, affording the terminal alkyne
4a in 71% yield (Scheme 3). Then, compound 4a reacted
with dibutyl ditelluride and sodium borohydride in etha-
nol under reflux for six hours, by the hydrotelluration re-
action,15 affording the corresponding vinylic telluride 5a,
in 60% yield. Many classes of organotellurium com-
pounds have been prepared and studied to date, and vinyl-
ic tellurides are certainly the most useful and promising of
these compounds in view of their usefulness in organic
syntheses, including in the synthesis of natural products.16
In summary, we have described the Sonogashira cross-
coupling reaction of 3-iodo-2-(methylsulfanyl)ben-
zo[b]furan with a variety of terminal alkynes in the pres-
ence of a catalytic amount of PdCl2(PPh3)2, copper(I)
iodide as cocatalyst, and triethylamine as solvent and
base, under mild reaction conditions. In addition, the 3-
alkynylbenzo[b]furans obtained were readily transformed
into more complex products by the hydrotelluration reac-
tion, furnishing the desired vinylic telluride in good
yields. Similarly, using copper-catalyzed homocoupling
reactions, we were able to convert 3-alkynylbenzo[b]fu-
ran into symmetric diynes in good yields. The studies of
the structure–activity relationship and pharmacological
activity of these compounds are in progress and will ap-
pear in a specialized journal soon.
1H NMR were obtained at 400 MHz of samples dissolved in CDCl3.
Chemical shifts are reported in ppm, referenced to the solvent peak
of CDCl3 or tetramethylsilane (TMS) as the external reference. 13
C
OH
H
NMR were obtained at 100 MHz of samples dissolved in CDCl3.
Chemical shifts are reported in ppm, referenced to the solvent peak
of CDCl3. High-resolution mass spectra were recorded on a double
focusing magnetic sector mass spectrometer using EI at 70 eV. GC-
MS analyses were performed using Shimadzu QP2010PLUS GC/
MS combination. Column chromatography was performed using
silica gel (230–400 mesh) following the methods described by Still.
Thin-layer chromatography (TLC) was performed using silica gel
GF254, 0.25 mm thickness. For visualization, TLC plates were ei-
ther placed under ultraviolet light, or stained with iodine vapor or
acidic vanillin. The following solvents were dried and purified by
distillation from the reagents indicated: tetrahydrofuran from sodi-
um with a benzophenone ketyl indicator. All other solvents were
ACS or HPLC grade unless otherwise noted. Air- and moisture-sen-
sitive reactions were conducted in flame-dried or oven-dried glass-
ware equipped with tightly fitted rubber septa and under a positive
atmosphere of dry nitrogen or argon. Reagents and solvents were
handled using standard syringe techniques. Temperatures above
room temperature were maintained by use of a mineral oil bath with
an electrically heated coil connected to a controller.
NaOH, toluene
SMe
SMe
reflux, 12 h
O
O
4a 71%
3e
(BuTe)2, NaBH4
EtOH, reflux, 6 h
TeBu
SMe
O
5a 60%
Scheme 3
The terminal alkyne 4a thus obtained was readily trans-
formed into a diyne system via an oxidative homocou-
pling reaction catalyzed by a copper salt (Scheme 4).
Diynes are important structural units for biologically ac-
tive organic compounds, including anticancer antibiot-
ics,17 and other natural products,18 as well as for new
functional materials.19 In view of this, we carried out the
reaction of the terminal alkyne 4a with copper(I) chloride
(5 mol%) and N,N,N¢,N¢-tetramethylethylenediamine (5
mol%) in acetone under heating and an oxygen atmo-
sphere for four hours; this gave the symmetric diyne 5b in
75% yield (Scheme 4).20
Cross-Coupling Reaction; General Procedure
The appropriate benzofuran 1a–c (0.5 mmol) was added to a
Schlenk tube containing PdCl2(PPh3)2 (0.0035 g, 1 mol%) and Et3N
(2 mL) under an argon atmosphere. To the resulting soln was added
CuI (0.0019 g, 2 mol%). The reaction mixture was stirred for 15 min
at r.t. Then a soln of the appropriate terminal alkyne 2 (1.25 mmol)
in Et3N (1 mL) was added dropwise, and the reaction mixture was
stirred at r.t. Subsequently, the mixture was diluted with CH2Cl2 (20
mL) and washed with brine (3 × 20 mL). The organic phase was
separated, dried (MgSO4), and concentrated under vacuum. The res-
idue was purified by flash chromatography (silica gel, EtOAc–
hexane). Selected spectral and analytical data are given below.
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F. Manarin et al.
PAPER
2-(Methylsulfanyl)-3-(phenylethynyl)benzofuran (3a)
Yield: 0.130 g (99%).
MS (EI, 70 eV): m/z (%) = 244 (2), 241 (100), 226 (89), 211 (26),
179 (20), 151 (20).
1H NMR (400 MHz, CDCl3): d = 7.63–7.56 (m, 3 H), 7.43–7.32 (m,
5-Methyl-2-(methylsulfanyl)-3-(phenylethynyl)benzofuran (3o)
Yield: 0.104 g (75%).
1H NMR (400 MHz, CDCl3): d = 7.59–7.57 (m, 2 H), 7.40–7.27 (m,
5 H), 7.09–7.06 (m, 1 H), 2.65 (s, 3 H), 2.45 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 154.8, 153.5, 133.0, 131.4, 128.9,
128.3, 128.2, 125.9, 119.4, 110.3, 96.9, 79.2, 21.2, 16.1.
4 H), 7.28–7.26 (m, 2 H), 2.67 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 154.9, 131.5, 128.9, 128.3, 124.7,
123.4, 123.2, 119.6, 110.8, 104.8, 97.1, 79.0, 16.1.
MS (EI, 70 eV): m/z (%) = 264 (3), 261 (100), 246 (56), 218 (20),
202 (22), 149 (14).
3-[(2-Methoxyphenyl)ethynyl]-2-(methylsulfanyl)benzofuran
(3d)
MS (EI, 70 eV): m/z (%) = 274 (100), 260 (70), 231 (16), 216 (16),
199 (11), 137 (10).
Yield: 0.124 g (85%).
5-Fluoro-2-(methylsulfanyl)-3-(phenylethynyl)benzofuran (3p)
Yield: 0.101 g (72%).
1H NMR (400 MHz, CDCl3): d = 7.57–7.55 (m, 2 H), 7.35–7.33 (m,
3 H), 7.32–7.25 (m, 2 H), 6.97 (td, J = 6.4, 3.0 Hz, 1 H), 2.67 (s, 3
1H NMR (400 MHz, CDCl3): d = 7.66–7.64 (m, 1 H), 7.53 (dd,
J = 5.8, 1.7 Hz, 1 H), 7.41–7.39 (m, 1 H), 7.31–7.24 (m, 3 H), 6.96–
6.86 (m, 2 H), 3.91 (s, 3 H), 2.69 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 159.8, 154.7, 134.0, 133.1, 129.7,
124.6, 123.3, 120.4, 119.7, 112.4, 110.6, 105.2, 93.5, 82.9, 81.0,
55.7, 16.1.
H).
13C NMR (100 MHz, CDCl3): d = 160.8, 158.4, 156.9, 151.1, 131.4,
128.5, 128.3, 122.9, 122.1 (d, J = 26.3 Hz), 111.4 (d, J = 9.5 Hz),
105.3 (d, J = 25.6 Hz), 97.4, 78.3, 15.7.
MS (EI, 70 eV): m/z (%) = 293 (6), 290 (100), 275 (48), 261 (45),
244 (19), 215 (23), 186 (16).
MS (EI, 70 eV): m/z (%) = 280 (26), 278 (100), 264 (84), 236 (28),
2-Methyl-4-[2-(methylsulfanyl)benzofuran-3-yl]but-3-yn-2-ol
220 (39), 191 (23), 139 (9).
(3e)
Yield: 0.114 g (93%).
1H NMR (400 MHz, CDCl3): d = 7.52–7.49 (m, 1 H), 7.38–7.36 (m,
1 H), 7.25–7.20 (m, 2 H), 2.76 (s, 1 H), 2.60 (s, 3 H), 1.68 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 154.8, 154.7, 128.8, 124.5, 123.2,
119.3, 110.6, 104.1, 101.8, 71.8, 65.7, 31.5, 15.9.
3-Ethynyl-2-(methylsulfanyl)benzofuran (4a) by Retro-
Favorskii Reaction
Powdered NaOH (0.120 g, 3 mmol) was added to a two-necked
round-bottomed flask equipped with a reflux condenser, containing
a soln of 3e (0.246 g, 1.0 mmol) in toluene (10 mL) under an argon
atmosphere. The mixture was slowly heated to reach reflux temper-
ature, during which time the reaction mixture became dark brown,
and was refluxed for 12 h. After this, the mixture was diluted with
CH2Cl2 (20 mL), and washed with brine (3 × 20 mL). The organic
phase was separated, dried (MgSO4), and concentrated under vacu-
um. The residue was purified by flash chromatography (silica gel,
EtOAc–hexane).
MS (EI, 70 eV): m/z (%) = 246 (2), 243 (89), 228 (55), 186 (17), 143
(28), 42 (100).
HRMS (EI): m/z calcd for C14H14O2S: 246.0715; found: 246.0717.
1-[2-(Methylsulfanyl)benzofuran-3-yl)ethynyl]cyclohexanol
(3h)
Yield: 0.122 g (86%).
Yield: 0.133 g (71%).
1H NMR (400 MHz, CDCl3): d = 7.57–7.53 (m, 1 H), 7.43–7.38 (m,
1H NMR (400 MHz, CDCl3): d = 7.53–7.50 (m, 1 H), 7.40–7.38 (m,
1 H), 7.28–7.22 (m, 2 H), 2.62 (s, 3 H), 2.33 (s, 1 H), 2.10–2.00 (m,
2 H), 1.70–1.59 (m, 7 H), 1.34–1.25 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 154.9, 153.8, 128.9, 124.6, 123.3,
119.5, 110.7, 104.3, 100.8, 74.1, 69.4, 40.1, 25.2, 23.5, 16.0.
1 H), 7.29–7.24 (m, 2 H), 3.52 (s, 1 H), 2.64 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 156.2, 154.8, 128.9, 124.7, 123.5,
119.5, 110.8, 103.7, 85.0, 73.7, 16.0.
MS (EI, 70 eV): m/z (%) = 188 (2), 185 (100), 171 (84), 143 (62),
127 (15), 100 (17).
MS (EI, 70 eV): m/z (%) = 282 (100), 267 (13), 236 (61), 185 (34),
163 (12), 143 (26).
(Z)-3-[2-(Butyltellanyl)vinyl]-2-(methylsulfanyl)benzofuran
(5a)
2-(Methylsulfanyl)-3-[3-(p-tolyloxy)prop-1-ynyl]benzofuran
NaBH4 (0.095 g, 2.5 mmol) was added in small portions to a soln of
4a (0.188 g, 1 mmol) in THF (5 mL) and the (BuTe)2 (0.184 g, 0.5
mmol) in EtOH (10 mL) at r.t. under argon. Towards the end of the
addition, when the red color of the soln had disappeared, the mix-
ture was refluxed for 12 h. After this, the mixture was diluted with
EtOAc (20 mL) and washed with brine (3 × 20 mL). The organic
phase was separated, dried (MgSO4), and concentrated under vacu-
um. The residue was purified by flash chromatography (silica gel,
EtOAc–hexane).
(3k)
Yield: 0.129 g (84%).
1H NMR (400 MHz, CDCl3): d = 7.47–7.45 (m, 1 H), 7.38–7.36 (m,
1 H), 7.26–7.20 (m, 2 H), 7.10 (d, J = 8.5 Hz, 2 H), 6.97 (d, J = 8.5
Hz, 2 H), 4.96 (s, 2 H), 2.58 (s, 3 H), 2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 155.8, 155.6, 154.8, 130.7, 129.9,
129.8, 124.7, 123.4, 119.6, 115.0, 114.7, 110.7, 103.8, 92.1, 56.9,
20.5, 16.0.
MS (EI, 70 eV): m/z (%) = 304 (16), 230 (14), 198 (100), 166 (16).
Yield: 0.223 g (60%).
1H NMR (400 MHz, CDCl3): d = 7.50–7.47 (m, 1 H), 7.42–7.39 (m,
1 H), 7.34 (d, J = 10 Hz, 1 H), 7.28 (d, J = 10 Hz, 1 H), 7.27–7.19
(m, 2 H), 2.67 (t, J = 7.6 Hz, 2 H), 2.54 (s, 3 H), 1.78 (quin, J = 7.4
Hz, 2 H), 1.37 (sext, J = 7.3 Hz, 2 H), 0.90 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 155.3, 146.9, 127.7, 127.5, 124.5,
122.6, 121.7, 119.9, 110.7, 110.3, 99.9, 33.9, 24.9, 17.2, 13.3, 8.1.
3-(3,3-Dimethylbut-1-ynyl)-2-(methylsulfanyl)benzofuran (3m)
Yield: 0.091 g (75%).
1H NMR (400 MHz, CDCl3): d = 7.52–7.50 (m, 1 H), 7.39–7.34 (m,
1 H), 7.26–7.21 (m, 2 H), 2.62 (s, 3 H), 1.37 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 154.8, 153.6, 129.3, 124.5, 123.0,
119.5, 110.6, 106.7, 105.6, 68.3, 31.0, 28.4, 16.1.
Synthesis 2009, No. 23, 4001–4009 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Alkynyl-2-(methylsulfanyl)benzo[b]furans
4009
MS (EI, 70 eV): m/z (%) = 371 (42), 315 (25), 300 (22), 268 (21),
186 (43), 172 (100), 143 (30), 113 (23).
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
We are grateful to FAPERGS, CAPES (SAUX), and CNPq (CNPq/
INCT-catalise) for the financial support. CNPq is also acknowled-
ged for the fellowships of G.Z. and F.M.
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Synthesis 2009, No. 23, 4001–4009 © Thieme Stuttgart · New York