Synthesis of 2,3-disubstituted benzo[b]thiophenes via palladium-catalyzed coupling anphilic cyclization of terminal acetylenes

Article abstract of DOI:10.1021/jo011016q

2,3-Disubstituted benzo[b]thiophenes have been prepared in excellent yields via coupling of terminal acetylenes with commercially available o-iodothioanisole in the presence of a palladium catalyst and subsequent electrophilic cyclization of the resulting

Full text of DOI:10.1021/jo011016q

J . Org. Chem. 2002, 67, 1905-1909
1905
Syn th esis of 2,3-Disu bstitu ted Ben zo[b]th iop h en es via
P a lla d iu m -Ca ta lyzed Cou p lin g a n d Electr op h ilic Cycliza tion of
Ter m in a l Acetylen es
Dawei Yue and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
Received October 22, 2001
2,3-Disubstituted benzo[b]thiophenes have been prepared in excellent yields via coupling of terminal
acetylenes with commercially available o-iodothioanisole in the presence of a palladium catalyst
and subsequent electrophilic cyclization of the resulting o-(1-alkynyl)thioanisole derivatives. I2,
Br2, NBS, p-O2NC6H4SCl, and PhSeCl have been utilized as electrophiles. Aryl-, vinyl-, and alkyl-
substituted terminal acetylenes undergo this coupling and cyclization to produce excellent yields
of benzo[b]thiophenes. (Trimethylsilyl)acetylene also undergoes this coupling/cyclization process
with I2, NBS, and the sulfur and selenium electrophiles to afford the corresponding 2-(trimethylsilyl)-
benzo[b]thiophenes. However, cyclization of the silyl-containing thioanisole using Br2 affords 2,3-
dibromobenzo[b]thiophene.
In tr od u ction
The transition-metal-catalyzed cyclization of disubsti-
tuted alkynes possessing a nucleophile in proximity to
the triple bond by either copper or palladium reagents
has been shown to be extremely effective for the synthesis
of a wide variety of carbo- and heterocycles (eq 1).1
F igu r e 1. Diaminobenzothiophene.
such as 1 have been identified as active site directed
thrombin inhibitors.5 Thus, research directed toward
concise, new syntheses of 2,3-disubstituted benzo[b]-
thiophenes has been actively pursued in recent years.1,6
The electrophilic cyclization of unsaturated compounds
has proven to be an efficient method for constructing
heterocycles.7 These reactions are generally viewed as
proceeding through an intramolecular, stepwise electro-
philic addition and dealkylation mechanism involving a
Generally, this methodology requires a good leaving
group on the nucleophile. However, due to sulfur’s affinity
for transition metals, sulfur-containing heterocycles, such
as benzo[b]thiophenes, have never been synthesized
using this strategy.
Benzo[b]thiophenes are of interest, because of their
frequent occurrence in nature and their wide range of
biological and physiological effects.2 Benzo[b]thiophene
derivatives, which are antimitotic agents,3 estrogen
receptor antagonists, and antitumor, antiinflammation,
and antifungal agents,4 are currently in pharmaceutical
use or development. Diaminobenzothiophene derivatives
(4) (a) Magarian, R. A.; Overacre, L. B.; Singh, S.; Meyer, K. L. Curr.
Med. Chem. 1994, 1, 61. (b) Bryant, H. U.; Dere, W. H. Proc. Soc. Exp.
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E. Org. Lett. 2001, 5, 651.
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J .; Sall, D. J .; Scarborough, R. M. J . Med. Chem. 1997, 40, 4308. (b)
Takeuchi, K.; Kohn, T. J .; Bastian, J . A.; Chirgadze, N. Y.; Denney,
M. L.; Harper, R. W.; Lin, H.; Mccowan, J . R.; Gifford-Moore, D. S.;
Richett, M. E.; Sall, D. J .; Smith, G. F.; Zhang, M. Bioorg. Med. Chem.
Lett. 1999, 9, 759. (c) Sall, D. J .; Bastian, J . A.; Briggs, S. L.; Buben,
J . A.; Chirgadze, N. Y.; Clawson, D. K.; Denney, M. L.; Giera, D. D.;
Gifford-Moore, D. S.; Harper, R. W.; Hauser, K. L.; Klimkowski, V. J .;
Kohn, T. J .; Lin, H.; McCowan, J . R.; Palkowitz, A. D.; Smith, G. F.;
Takeuchi, K.; Thrasher, K. J .; Tinsley, J . M.; Utterback, B. G.; Yan,
S. B.; Zhang, M. J . Med. Chem. 1997, 40, 3489.
(6) (a) Tony, Y. Z.; O′Toole, J .; Proctor, C. S. Sulfur Rep. 1999, 22,
1. (b) Pelkey, E. T. Prog. Heterocycl. Chem. 1999, 11, 102. (c) Bianchini,
C.; Meli, A. Synlett 1997, 643. (d) Russell, R. K.; Press, J . B. In
Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C.
W., Scriven, E. F. V., Eds.; Elsevier: Amsterdam, 1996, Vol. 2, p 679.
(e) Irie, M.; Uchida, K. Bull. Chem. Soc. J pn. 1998, 71, 985. (f)
Gallagher, T.; Pardoe, D. A.; Porter, R. A. Tetrahedron Lett. 2000, 41,
5415. (g) Arnau, N.; Moreno-Manas, M.; Pleixats, R. Tetrahedron 1993,
49, 11019. (h) McDonald, F. E.; Burova, S. A.; Huffman, L. G. J r.
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(1) (a) Roesch, K. R.; Larock, R. C. Org. Lett. 1999, 4, 553. (b) Nan,
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Fabrizi, G.; Marinelli, F. J . Org. Chem. 1996, 61, 9280. (i) Cacchi, S.;
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10.1021/jo011016q CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/26/2002

1906 J . Org. Chem., Vol. 67, No. 6, 2002
Yue and Larock
Sch em e 1a
Ta ble 1. Son oga sh ir a Cou p lin g of o-Iod oth ioa n isole a n d
Ter m in a l Acetylen es (Sch em e 1)a
a
E+ ) I2, Br2, NBS, p-O2NC6H4SCl, PhSeCl.
cationic intermediate. Taniguchi and co-workers have
explored the cyclization of vinylic cations as a route to
heterocycles but found significant limitations in generat-
ing the vinylic cations.8 Although mechanistic and syn-
thetic work on the preparation of benzofuran and indole
derivatives have been carried out by Cacchi and co-
workers9 and ourselves,10 the synthesis of benzo[b]thio-
phenes by this approach remains relatively unexplored.
Recently, Flynn and co-workers treated o-(1-alkynyl)-
phenyl benzyl sulfides with iodine to obtain 3-iodobenzo-
[b]thiophene derivatives through a 5-endo-dig iodocycliza-
tion.4c The limited availability of the.requisite starting
sulfides, the low yields obtained in their preparation, the
incompatibility of functional groups with this methodol-
ogy, and the failure to demonstrate the scope of this
methodology have encouraged us to report our related
studies.11 Herein, we report the successful application of
this electrophilic cyclization strategy as a convenient and
general synthetic methodology for the synthesis of 2,3-
disubstituted benzo[b]thiophenes.
a
All reactions were run with 5 mmol of o-iodothioanisole, 1.2
equiv of the terminal acetylene, 2 mol % of PdCl2(PPh3)2, 1 mol %
of Cul, and 12.5 mL of Et3N at reaction temperature.
F igu r e 2. Sulfur-stabilized arylpalladium intermediate.
We have found that o-(phenylethynyl)thioanisole (3),
when treated with 12 in CH2Cl2, undergoes smooth
iodocyclization at room temperature and affords a nearly
quantitative yield of the corresponding 2,3-disubstituted
benzo[b]thiophene (10) (Scheme 1; Table 2, entry 1). The
mild reaction conditions, as well as the high yield of this
reaction, encouraged us to extend this methodology to a
range of o-(1-alkynyl)thioanisoles (Table 2; entries 5, 9,
14, 18, 23, and 28). The yields in all cases are essentially
quantitative. It makes little difference if the substituent
on the other end of the alkyne is aryl, vinyl, alkyl,
functionally substituted alkyl, or silyl. Even hindered
trimethylsilyl- (7) or tert-butyl-substituted alkynes (8)
react rapidly and quantitatively.
The sulfur moiety in this approach to benzo[b]-
thiophenes comes from commercially available o-iodo-
thioanisole. The approach used by Flynn and co-workers4c
introduces the sulfur through a series of steps starting
with 2-iodoaniline or 2-bromo-1-iodobenzene and is thus
less practical. We were pleased to find that the methyl
group on the sulfur is easily removed during the cycliza-
tion step, which makes introduction of the benzyl sulfide
group of Flynn and co-workers unnecessary.4c This
represents the first general route to 2,3-disubstituted
benzo[b]thiophenes by an electrophilic cyclization strat-
egy.
Resu lts a n d Discu ssion
A two-step approach to benzo[b]thiophenes has been
examined involving (i) the Sonagashira coupling of com-
mercially available o-iodothioanisole with terminal alkynes
and (ii) electrophilic cyclization (Scheme 1).
To assess the generality of this approach, the scope of
the Sonagashira coupling of o-iodothioanisole has been
studied. Treatment of o-iodothioanisole with a variety of
terminal alkynes under standard Sonagashira coupling
conditions (5 mmol of o-iodothioanisole, 1.2 equiv of
terminal alkyne, 2 mol % of PdCl2(PPh3)2, 1 mol % of CuI,
and 12.5 mL of Et3N at room temperature for 3-5 h)
affords almost quantitative yields of the coupling prod-
ucts (Table 1).
o-Iodothioanisole shows high reactivity toward the
Sonagashira coupling, and this allows the preparation
of a wide variety of functionally substituted o-(1-alkynyl)-
thioanisoles. This high reactivity may be attributed to
the coordination of sulfur to palladium in the presumed
intermediate (2) (Figure 2), which stabilizes the arylpal-
ladium intermediate and reduces its tendency to undergo
homocoupling. Alkynes with all sorts of substituents,
including phenyl, trimethylsilyl, vinyl, bulky alkyl, and
alkyl groups bearing functional groups, such as hydroxy
and cyano groups, have been successfully employed in
the Sonagashira coupling of o-iodothioanisole. Almost
quantitative yields were obtained in all cases (Table 1).
To explore the scope of this electrophilic cyclization
strategy, four other electrophiles, Br2, NBS, p-O2NC6H4-
SCl, and PhSeCl, have been employed. The reactions
have all been monitored by thin-layer chromatography,
1
and most of the reactions were complete within /2 h. In
virtually all cases examined, excellent yields of benzo-
[b]thiophene of around 90% have been obtained. The
results are summarized in Table 2.
The nature of the electrophile plays an important role
in these cyclization reactions. The iodocyclization reac-
tions are most efficient and general. All functional groups
that we have studied tolerate the reaction conditions, and
yields above 97% were obtained in all cases (Table 2,
entries 1, 5, 9, 14, 18, 23, and 28). Aryl- (entry 1) and
long-chain-alkyl-substituted alkynes (entry 5) are readily
accommodated, and the presence of an olefin (entry 9), a
nitrile (entry 14), or an alcohol (entry 28) group presents
(8) (a) Sonada, T.; Kawakami, M.; Ikeda, T.; Kobayashi, S.; Tan-
iguchi, H. J . Chem. Soc., Chem. Commun. 1976, 612. (b) Kitamura,
T.; Kobayashi, S.; Taniguchi, H.; Hori, K. J . Am. Chem. Soc. 1991,
113, 6240. (c) Kitamura, T.; Takachi, T.; Kawasato, H.; Taniguchi, H.
J . Chem. Soc., Perkin Trans. 1 1992, 1969.
(9) Arcadi, A.; Cacchi, S.; Giancarlo, F.; Marinelli, F.; Moro, L.
Synlett 1999, 1432.
(10) Larock, R. C.; Harrison, L. W. J . Am. Chem. Soc. 1984, 106,
4218.
(11) For a previous communication, see: Larock, R. C.; Yue, D.
Tetrahedron Lett. 2001, 42, 6011-6013.

2,3-Disubstituted Benzo[b]thiophenes
J . Org. Chem., Vol. 67, No. 6, 2002 1907
Ta ble 2. Electr op h ilic Cycliza tion of o-(1-Alk yn yl)th ioa n isoles to 2,3-Disu bstitu ted Ben zo[b]th iop h en es (Sch em e 1)a
entry
o-(1-alkynyl)thioanisole
electrophile
I2
time
E (product)
I (10)
isolated yield (%)
1
2
3
4
5
6
7
8
3
10 min
10 min
10 min
10 min
10 min
10 min
10 min
10 min
10 min
10 min
2 days
10 min
10 min
10 min
10 min
10 min
10 min
10 min
60 min
2 days
10 min
10 min
20 min
30 min
6 h
100
92
97
100
100
91
70
91
97
Br2
Br (11)
p-O2NC6H4SCl
PhSeCl
I2
Br2
p-O2NC6H4SCl
PhSeCl
I2
Br2
NBS
p-O2NC6H4SCl
PhSeCl
I2
p-O2NC6H4S (12)
PhSe (13)
I (14)
4
5
Br (15)
p-O2NC6H4S (16)
PhSe (17)
I (18)
Br (19)
Br (19)
p-O2NC6H4S (20)
PhSe (21)
I (22)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
-
74b
95
97
98
6
7
Br2
Br (23)
79
p-O2NC6H4SCl
PhSeCl
I2
Br2
NBS
p-O2NC6H4SCl
p-O2NC6H4S (24)
PhSe (25)
I (26)
Br (27)
Br (28)
p-O2NC6H4S (29)
PhSe (30)
I (31)
Br (32)
Br (32)
p-O2C6H4S (33)
PhSe (34)
I (35)
Br (36)
p-O2NC6H4S (37)
PhSe (38)
25c
78
100
95d
65
100
100
98
67
52
80
82
PhSeCl
8
9
I2
Br2
NBS
p-O2NC6H4SCl
PhSeCl
I2
20 min
20 min
30 min
30 min
30 min
30 min
98
70
60
95
Br2
p-O2NC6H4SCl
PhSeCl
a
All reactions were run with 0.25 mmol of the o-(1-alkynyl)thioanisole and 1.5 equiv of electrophile in 5 mL of CH2Cl2 at 25 °C unless
otherwise indicated. All NBS reactions were run using 1.2 equiv of NBS in 10 mL of CH2Cl2. 1.2 equiv of NBS at 25 °C for 2 days. c The
b
desired benzo[b]thiophene 24 was obtained as an inseparable 1:3 mixture of 24 and the product of addition of the (p-nitrophenyl)sulfenyl
d
chloride to the alkyne triple bond. The yield was determined by 1H NMR spectroscopy. 1 equiv of Br2 gave the product of bromine
addition to the triple bond; 1.5 equiv of NBS gave a mixture of the simple alkyne addition product and 2,3-dibromobenzo[b]thiophene,
and 2 equiv of Br2 gave 2,3-dibromobenzo[b]thiophene. The yield here is of 2,3-dibromobenzo[b]thiophene.
Sch em e 2
no difficulties. o-((Trimethylsilyl)ethynyl)thioanisole
(entry 18) undergoes iodocyclization smoothly without
desilylation, which provides an efficient method for the
preparation of 3-iodo-2-silylbenzo[b]thiophenes. Even an
alkyne with a bulky tert-butyl group (entry 23) gave
almost a quantitative isolated yield (98%) of the cycliza-
tion product in only 10 min reaction time. The success of
this reaction is presumably due to the highly nucleophilic
nature of the iodide ion formed after the cyclization,
which facilitates methyl group removal from the sulfo-
nium intermediate presumably generated upon cycliza-
tion.
The reactions with Br2 gave results somewhat different
from those of I2. While most alkynes reacted fairly cleanly
with Br2 to afford good to excellent yields of 3-bromoben-
zo[b]thiophenes (entries 2, 6, 15, 24, and 29), there were
also complications not encountered previously using I2.
The carbon-carbon double bond present in alkyne 5 was
found to be more reactive toward Br2 than the triple bond,
and only a trace of the desired bromobenzo[b]thiophene
product was detected (entry 10). However, when the
electrophile was changed from Br2 to NBS, the desired
cyclization product 19 was obtained in 74% yield (entry
11). The reaction of silyl alkyne 7 with Br2 led to a
mixture of 2,3-dibromobenzo[b]thiophene (27) and prod-
ucts of simple addition of the Br2 to the carbon-carbon
triple bond. The formation of 27 can be explained by
either bromocyclization in the desired manner, followed
by more rapid bromodesilylation, or by the mechanism
described in Scheme 2, where the bromine first adds to
the triple bond to form the simple addition product.
Attack of another 1 equiv of Br2 on the simple addition
product might then lead to cyclization and formation of
a 2,3-dihydrobenzo[b]thiophene bearing bromine atoms
and a silyl group. Elimination of trimethylsilyl bromide
would afford 27. When the electrophile was changed from
Br2 to NBS, the desired cyclization product 3-bromo-2-
silylbenzo[b]thiophene (28) was obtained in 65% yield.
The bromocyclization reaction times of NBS and o-(l-
alkynyl)thioanisoles (entries 11, 200, and 25) are gener-
ally longer than the bromocyclization reaction times
employing Br2, and the yields are generally lower.
The commercially available reagents p-O2NC6H4SCl
and PhSeCl are generally good electrophiles in this
cyclization reaction, when there is no nucleophilic func-
tionality present in the o-(1-alkynyl)thioanisoles. o-(1-
Alkynyl)thioanisoles 3-5, 7, and 8 all give decent yields
of the desired disubstituted benzo[b]thiophene products.
However, the yields from p-O2NC6H4SCl cyclizations are
generally lower than those of the PhSeCl cyclizations,

1908 J . Org. Chem., Vol. 67, No. 6, 2002
Yue and Larock
Sch em e 3a
has been successfully employed by Flynn and co-workers
in the synthesis of tubulin binding agents.4c We have
found that 2,3-diphenylbenzo[b]thiophene can be ob-
tained in a 92% overall yield from o-iodothioanisole and
phenylacetylene by our two-step coupling/cyclization
process, followed by Suzuki cross-coupling of the inter-
mediate 3-iodo-2-phenylbenzo[b]thiophene with NaBPh4
(Scheme 3). One should be able to prepare many other
2,3-disubstituted benzo[b]thiophenes using these iodo
substrates and known palladium methodology.
Con clu sion s
a
Reagents and reaction conditions: (i) 2 mol % PdCl2(PPh3)2,
1 mol % CuI, Et3N, 25 °C for 6 h; (ii) I2, CH2Cl2, 25 °C for 10 min;
(iii) 5 mol % Pd(OAc)2, NaBPh4, 1:1 DMF/H2O, 1 equiv of Na2CO3,
100 °C for 12 h.
A very efficient synthesis of 2,3-disubstituted benzo-
[b]thiophenes has been developed by a two-step approach
involving the Sonagashira cross-coupling of terminal
alkynes and commercially available o-iodothioanisole,
followed by electrophilic cyclization using 12, Br2, NBS,
and sulfur and selenium electrophiles. All electrophiles
give benzo[b]thiophenes in good to excellent yields. A
wide variety of thioanisole-containing acetylenes with
various functional groups undergo this overall process
in good to excellent yields. The steric and electronic
effects of the substituents on the carbon-carbon triple
bond of the alkynylthioanisole intermediates have been
studied.
which are in turn lower than those of the iodocyclization
reactions. The reason for this is not clear at this time,
but factors to be considered include the electrophilicity
and hardness of the electrophiles.
Substituents on the triple bond of the o-(1-alkynyl)-
thioanisoles also affect the yields of the cyclization
reactions. Substrates with substituents which are in
conjugation with the triple bond, such as the phenyl
group in alkyne 3 and the vinylic group in alkyne 5,
appear to cyclize more rapidly and generally produce
higher yields of products. Bulky substrates, such as the
tert-butyl group in alkyne 6, tend to hinder cyclization.
Longer reaction times are often needed, and lower yields
often result. However, no products involving simple
addition of the electrophile to the alkyne triple bond are
observed with this alkyne.
Long alkyl chains also play a role in the cyclization.
The presence of an n-octyl group on the triple bond, as
in alkyne 2, lowered the yields of the (p-nitrophenyl)-
sulfenyl and phenylselenyl cyclization reactions (entries
7 and 8), relative to the halocyclization processes (entries
5 and 6). Some product of the simple addition of p-O2N-
C6H4SCl to the carbon-carbon triple bond of the o-(1-
alkynyl)thioanisole 2 was observed (entry 7).
Due apparently to the electron-withdrawing effect of
the cyano group on the alkyl chain, the reactions of 5-(2-
(methylmercapto)phenyl)-5-hexynenitrile (6) with the
sulfur and selenium electrophiles (entries 16 and 17) gave
lower yields than the simple alkyl-substituted alkyne 2.
In fact, p-O2NC6H4SCl gave mainly the product of simple
addition of the electrophile to the carbon-carbon triple
bond and only a 25% yield of the desired product was
obtained (entry 16). The cyano group here could serve
as a nucleophile, which possibly interacts with the sulfur
and selenium electrophiles and lowers the yields of the
cyclization reactions.
An alcohol group can also interfere in the cyclization
process. While the yield for the iodocyclization of the o-(1-
alkynyl)thioanisole 9 with a hydroxyl group on the end
of the long alkyl chain of the alkyne is still high, the Br2
and p-O2NC6H4SCl cyclizations give much lower yields
(entries 29 and 30). The hydroxyl group of alkyne 7 may
be reacting directly with the p-O2NC6H4SCl, generating
HCl and a ((p-nitrophenyl)sulfenyl)oxy group on the end
of the alkyl chain. The 3-substituted benzo[b]thiophenes
produced by this new chemistry should be very useful
for the synthesis of additional benzo[b]thiophenes. For
example, the 3-iodobenzo[b]thiophenes produced by this
strategy can be further functionalized by applying pal-
ladium-mediated coupling techniques. This methodology
Exp er im en ta l Section
Gen er a l Con sid er a tion s. All 1H and 13C NMR spectra
were recorded at 300 and 75.5 MHz or 400 and 100 MHz. Thin-
layer chromatography was performed using commercially
prepared 60 mesh silica gel plates (Whatman K6F), and
visualization was effected with short-wavelength UV light (254
nm). All melting points are uncorrected. High-resolution mass
spectra were recorded on a Kratos MS50TC double-focusing
magnetic sector mass spectrometer using El at a voltage of 70
eV. All reagents were used directly as obtained commercially,
unless otherwise noted. Anhydrous forms of ethyl ether,
hexanes, ethyl acetate, methylene chloride, and DMF were
purchased from Fisher Scientific Co. 2-Iodothioanisole, phe-
nylacetylene, 1-decyne, 1-cyclohexenylacetylene, 11-undecyn-
1-ol, tert-butylacetylene, (trimethylsilyl)acetylene, 5-hexyne-
nitrile, and Et3N were purchased from Aldrich Chemical Co.,
Inc. The palladium salts were donated by J ohnson Matthey
Inc. and Kawaken Fine Chemicals Co. Ltd.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed F or -
m a tion of o-(1-Alk yn yl)th ioa n isoles. To a solution of Et3N
(12.5 mL), PdCl2(PPh3)2 (0.070 g, 2 mol %), 5 mmol of
o-iodothioanisole, and 6 mmol of terminal acetylene (stirring
for 5 min beforehand) was added CuI (0.010 g, 1 mol %), and
stirring was continued for another 2 min before flushing with
Ar; the flask was then sealed. The mixture was stirred at room
temperature for 3-6 h, and the resulting solution was filtered,
washed with a satuated aqueous NaCl solution, and extracted
with diethyl ether (2 × 10 mL). The combined ether fractions
were dried over Na2SO4 and concentrated under vacuum to
yield the crude product. The crude product was purified by
flash chromatography on silica gel using ethyl acetate/hexane
as the eluent.
o-(P h en yleth yn yl)th ioa n isole (3). The product was ob-
tained as a yellow oil. The 1H and 13C NMR spectral data were
in good agreement with the literature data.12
(12) Campo, M. A.; Larock, R. C. Org. Lett. 2000, 2, 3675.
(13) (a) Pinto, D. J . P.; Copeland, R. A.; Covington, M. B.; Pitts, W.
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2,3-Disubstituted Benzo[b]thiophenes
J . Org. Chem., Vol. 67, No. 6, 2002 1909
Characterization data for all other o-(1-alkynyl)thioanisoles
prepared in this study can be found in the Supporting
Information.
3-((p -Nit r op h e n yl)su lfe n yl)-2-p h e n ylb e n zo[b]t h io-
p h en e (12). The product was obtained as a yellow oil. 1
H NMR
(400 MHz, CDCl3): δ 7.10-7.13 (d, J ) 8.8 Hz, 2H), 7.42-
7.46 (m, 5H), 7.65-7.67 (m, 2H), 7.74-7.76 (d, J ) 8.8 Hz,
1H), 7.92-7.94 (d, J ) 8.4 Hz, 1H), 8.01-8.04 (d, J ) 9.2 Hz,
2H). 13C NMR (100 MHz, CDCl3): δ 115.8, 122.6, 123.4, 124.1,
124.2, 125.6, 125.8, 128.8, 129.5, 129.7, 132.9, 138.6, 140.3,
145.3, 147.8, 151.3. IR (neat, cm-1): 3061, 2918, 2849, 1577,
1512, 1337, 753. HRMS: m/z calcd for C20H13NO2S2 363.038 77,
found 363.039 43.
Gen er a l P r oced u r e for th e lod o- a n d Br om ocycliza -
tion s. To a solution of 0.25 mmol of the o-(1-alkynyl)-
thioanisole and 3 mL of CH2Cl2 was added gradually 2 equiv
of I2 or Br2 dissolved in 2 mL of CH2Cl2. The reaction mixture
was flushed with Ar and stirred at room temperature for 30
min. The excess I2 or Br2 was removed by washing with a
saturated aqueous solution of Na2S2O3. The aqueous solution
was then extracted by diethyl ether (2 × 10 mL). The combined
ether layers were dried over anhydrous Na2SO4 and concen-
trated under vacuum to yield the crude product, which was
purified by flash chromatography on silica gel using ethyl
acetate/hexanes as the eluent.
3-Iod o-2-p h en ylben zo[b]th iop h en e (10). Theproduct was
obtained as a yellow oil. The 1H and 13C NMR spectral data
were in good agreement with the literature data.12
Characterization data for all other 3-halobenzo[b]thiophenes
prepared in this study can be found in the Supporting
Information.
Gen er a l P r oced u r e for th e p-O2NC6H4SCl a n d P h SeCl
Cycliza tion s. To a solution of 0.25 mmol of the o-(1-alkynyl)-
thioanisole and CH2Cl2 (3 mL) was added a solution of 0.375
mmol of p-O2NC6H4SCl and PhSeCl and CH2Cl2 (2 mL). The
mixture was stirred for 2 min, the flask was flushed with Ar,
and the mixture was then stirred at the designated temper-
ature for 30 min. The reaction mixture was washed with 20
mL of water and extracted with diethyl ether. The combined
ether layers were dried over anhydrous Na2SO4 and concen-
trated under vacuum to yield the crude product, which was
further purified by flash chromatography on silica gel using
ethyl acetate/hexanes as the eluent.
Characterization data for all other 3-thio- and 3-selenoben-
zo[b]thiophenes prepared in this study can be found in the
Supporting Information.
2,3-Diph en ylben zo[b]th ioph en e (39). Details of the prepa-
ration of 2,3-diphenylbenzo[b]thiophene by the Suzuki cross-
coupling of 3-iodo-2-phenylbenzo[b]thiophene and NaBPh4 can
be found in the Supporting Information.
Ack n ow led gm en t. We gratefully acknowledge par-
tial financial support from the donors of the Petroleum
Research Fund, administered by the American Chemi-
cal Society, and we thank J ohnson Matthey, Inc., and
Kawaken Fine Chemicals Co., Ltd., for providing the
palladium salts.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for o-(1-alkynyl)thioanisoles (3-9), 3-halobenzo[b]-
thiophenes (10, 11, 14, 15, 18, 19, 22, 23, 26-28, 31, 32, 35,
and 36), 3-thio and 3-selenobenzo[b]thiophenes (12, 13, 16, 17,
20, 21, 24, 25, 29, 30, 33, 34, 37, and 38), and 2,3-diphenyl-
benzo[b]thiophenes (39) and figures giving 1H and 13C NMR
spectra for compounds 3-39. This material is available free
of charge via the Internet at http://pubs.acs.org.
(16) (a) Benati, L.; Montevecchi, P. C.; Spagnolo, P. J . Chem. Soc.,
Perkin Trans. 1 1992, 13, 1659. (b) Albertazzi, A.; Leardini, R.; Pedulli,
G. F.; Tundo, A.; Zanrdi, G. J . Org. Chem. 1984, 49, 4482.
J O011016Q