Cyclization of homopropargyl chalcogenides by copper(II) salts: Selective synthesis of 2,3-dihydroselenophenes, 3-arylselenophenes, and 3-haloselenophenes/thiophenes

Article abstract of DOI:10.1002/chem.201302129

Copper(II) halide mediated cyclization of homopropargyl chalcogenides gave three types of chalcogenophene derivatives. Selective product formation was achieved by controlling solvent, temperature, and atmosphere. By using CuBr ₂ and 1,2-dichlor

Full text of DOI:10.1002/chem.201302129

FULL PAPER
DOI: 10.1002/chem.201302129
Cyclization of Homopropargyl Chalcogenides by Copper(II) Salts: Selective
Synthesis of 2,3-Dihydroselenophenes, 3-Arylselenophenes, and
3-Haloselenophenes/thiophenes
Ricardo F. Schumacher, Alisson R. Rosꢀrio, Marlon R. Leite, and Gilson Zeni*[a]
Abstract: Copper(II) halide mediated
cyclization of homopropargyl chalcoge-
nides gave three types of chalcogeno-
phene derivatives. Selective product
formation was achieved by controlling
solvent, temperature, and atmosphere.
By using CuBr2 and 1,2-dichloroethane
at room temperature under ambient
whereas CuBr2 and 1,2-dichloroethane
at reflux gave selectively 2-substituted
selenophenes. When 1,2-dichloroethane
was replaced by dimethylacetamide, 3-
halo-selenophenes were obtained ex-
clusively. The versatility of chalcogeno-
phenes was also studied by reaction of
3-haloselenophenes with terminal al-
kynes under Sonogashira conditions af-
fording the cross-coupled products. In
addition, the reaction of 3-haloseleno-
phenes with boronic acids gave the cor-
responding Suzuki-type products in
good yields.
Keywords: copper
· cyclization ·
heterocycles · selenium heterocy-
cles · synthetic methods
ACHTUNGTRENNUNGatmosphere, 4-bromo dihydroseleno-
phene derivatives were obtained,
Introduction
and O heterocycles.[8] Cyclizations of unsaturated substrate
containing a chalcogen heteroatom, catalyzed by copper
salts, are practically absent from the above cited references,
but some have appeared recently.[9] Among the chalcogen
heterocycles, chalcogenophenes play important roles in sci-
ence and technology, mainly as semiconductors applicable in
high-performance, air-stable thin-film transistors,[10] and re-
cently they have also attracted considerable attention as
pharmacologically active agents.[11] Traditional methods for
the synthesis of chalcogenophenes require harsh reaction
conditions, strong bases, high temperature, and often the use
of toxic polar solvents such as hexamethylphosphoramide
(HMPA), and thus their large-scale applications in industry
are limited.[12] Consequently, the preparation of chalcogeno-
phenes by protocols that are more attractive to both aca-
demia and industry is a subject of great interest. Further-
more, we envisioned examining the versatility of the homo-
propargyl selenides 1 in the preparation of 4-halo-2,3-dihy-
droselenophenes 2, selenophenes 3 and 3-haloselenophenes
4 by using CuX2 as halogenating/cycling agent (Figure 1).
The interest in organochalcogen compounds has increased
considerably in the last decade, because incorporation of a
chalcogen atom in a carbon chain modifies characteristics
such as reactivity, physical properties, and pharmacological
and toxicological profiles.[1] Besides the pharmacological
properties, the presence of chalcogen atom in a potentially
bioactive molecule can dramatically increase the native bio-
logical activity of the substrate.[2] This is mainly attributed to
the fact that the chalcogen atom can serve as hydrogen-
bond acceptor or electron donor that alters the chemical
characteristics of an enzyme active site.[3] From the synthetic
point of view, organochalcogen compounds are often chosen
as ideal substrates in organic synthesis because they have an
adequately polarized carbon–chalcogen bond which is sus-
ceptible to both nucleophilic and electrophilic attack with
high chemo- and regioselectivity.[4] This property leads to
broad applications in organic synthesis, since it allows the in-
troduction of new functionalities. Among these applications,
a major advance is the use of organochalcogen compounds
as substrates in transition metal catalyzed cross-coupling re-
actions,[5] in transmetalation reactions,[6] and more recently
in cyclization reactions.[7] Metal-catalyzed cyclization of un-
saturated substrates containing heteroatoms such as nitrogen
and oxygen is a widely used method for the synthesis of N
Figure 1. Alkynyl selenide 1 and selenophene derivatives 2, 3, and 4.
[a] Dr. R. F. Schumacher, A. R. Rosꢀrio, M. R. Leite, Prof. Dr. G. Zeni
Laboratꢁrio de Sꢂntese, Reatividade
Avaliażo Farmacolꢁgica e Toxicolꢁgica de OrganocalcogÞnios
Universidade Federal de Santa Maria
Results and Discussion
Santa Maria, Rio Grande do Sul, 97105-900 (Brazil)
E-mail: gzeni@ufsm.br
We first turned our attention to cyclization of homoproparg-
yl selenides 1[13] to synthesize 4-halo-2,3-dihydroseleno-
phenes 2. For this purpose, we systematically evaluated the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302129.
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Table 1. Influence of reaction conditions on the formation of 4-bromo-
that certain soluble halide salts play an important roles in
taking copper halides into solution.[15] These halide salts are
thought to increase metal solubility and stability and to pre-
vent aggregation of the metal. We thus screened additives
using CuBr2 (2 equiv) as copper source and 1,2-dichloro-
ethane as solvent at room temperature. However, under
these experimental conditions with LiBr, NaBr, or Bu4NBr
as additive, the yield of the target product was not improved
(Table 1, entries 14–16). Finally, the optimal reaction condi-
tions were determined as follows: substrate 1a (0.5 mmol)
and CuBr2 (2 equiv) were stirred in 1,2-dichloroethane
(2 mL) at room temperature under air for 8 h (Table 1,
entry 9). On the basis of these results, we performed a sys-
tematic study by applying these conditions to several substi-
tuted homopropargyl selenides 1 to test the tolerance of
functional groups and their effects on the conversion
(Table 2).
2,3-dihydroselenophene (2a).[a]
Copper [equiv]
Solvent
Additive
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
2
2
2
2
2
2
2
2
2
1
0.1
3
4
2
2
2
MeCN
acetone
toluene
DMF
THF
EtOH
DMA
CH2Cl2
DCE
DCE
DCE
DCE
DCE
–
–
–
–
–
–
–
–
–
–
–
–
40
8
–
20
25
32
50
50
72
38
7
70
50
42
50
65
–
DCE
DCE
DCE
LiBr[b]
NaBr[b]
Bu4NBr[b]
Table 2. Cyclization reactions of homopropargyl selenides 1a–h mediat-
ed by CuBr2.[a]
[a] Reactions were performed with 1a (0.5 mmol), CuBr2, and solvent
(4 mL) at room temperature under air for 8 h. [b] Two equivalents of ad-
ditive were used.
role of solvents, temperature, additives, and the amount of
copper by subjecting homopropargyl selenide 1a to a cop-
per(II)-catalyzed cyclization process (Table 1). In a prelimi-
nary experiment we treated homopropargyl selenide 1a
(0.5 mmol) with CuBr2 (2 equiv) in MeCN at room tempera-
ture under air. After 8 h, the cyclization reaction provided
only 40% yield of isolated 4-bromo-2,3-dihydroselenophene
2a (Table 1, entry 1). Replacing the solvent MeCN by ace-
tone resulted in a lower yield, and in the case of toluene the
cyclized product was not obtained (Table 1, entries 2 and 3).
The cyclization reaction was then carried out in DMF, THF,
and ethanol as solvents, and the yields of isolated products
were not better than 32% (Table 1, entries 4–6). The yields
are rather low and could not significantly be improved by
changing the solvent to dimethylacetamide (DMA) and di-
chloromethane (Table 1, entries 7 and 8). Among the sol-
vents tested, 1,2-dichloroethane (DCE) provided the best
yield, and product 2a was obtained in 72% yield (Table 1,
entry 9). Assuming that CuBr2 acts not only as a triple-bond
activator, but also as a bromine source and as oxidizing
agent for Cu0,[9a] use of less than 2.0 equiv of CuBr2 would
hamper the cyclization reaction. To test our hypothesis the
reaction was carried out with 1.0 and 0.1 equivalents of
CuBr2. As predicted, under these conditions the cyclized
product was obtained in poor yields (Table 1, entries 10 and
11). These results are in agreement with other studies[14] sug-
gesting that Cu0, formed in the reaction medium, can be oxi-
dized by CuII to produce CuI, which justifies the need for
two equivalents of CuBr2 for this reaction (for mechanistic
proposal, see Supporting Information). Moreover, we found
that more than 2 equiv of CuBr2 had no positive effect on
the yield (Table 1, entries 12 and 13). It was demonstrated
Alkynyl
selenide 1
Product 2
Yield
[%]
1
2
1a
1b
2a 72
2b 60
2c 55
2d 56
3
4
1c
1d
5
6
1e
1 f
2e 62
2 f 60
7
8
1g
1h
2g 57
2h 51
[a] Reactions were performed with 1 (0.5 mmol), CuBr2 (2 equiv), and
1,2-dichloroethane (2 mL) at room temperature under air for 8 h.
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Cyclization of Homopropargyl Chalcogenides
FULL PAPER
Table 3. Influence of reaction conditions on the preparation of seleno-
On the one hand, these conditions were applicable to
both electron-donating (Table 2, entries 2–5) and electron-
withdrawing substituents (Table 2, entries 6 and 7) on the
aryl ring of homopropargyl selenides 1b–g. Besides, the re-
action yield does not seem to be strongly influenced by the
steric effect of the substituent, since ortho-substituted aro-
matic rings were compatible with the reaction conditions,
and the corresponding 2,3-dihydroselenophenes 2b,c were
obtained in very similar yields (Table 2, entries 2 and 3). On
the other hand, only 51% yield of product 2h was obtained
for the cyclization between homopropargyl selenide 1h
having an alkyl group directly attached to the triple bond,
where it may exert negative effects (Table 2, entry 8). o-Al-
kynylanisoles could undergo cyclization reaction in the pres-
ence of transition metal to afford benzofuran derivatives.[16]
Regarding selenium versus oxygen cyclization, we did not
obtain any amount of benzo[b]furan derivative, and the
unique product obtained during the course of this cycliza-
tion was selenophene derivative 2c (Table 2, entry 3). This
high selectivity can be attributed to the electronic effect
(the relative nucleophilicity of the selenium atom, the cati-
onic nature of the intermediate) and the resistance of the
methoxyl group to demethylation and ring closure.[17]
Aromatic halo heterocycles are versatile reagents in or-
ganic synthesis.[18] In particular, heterocycles such as halo-
chalcogenophenes are useful precursors for the synthesis of
a variety of more highly functionalized heterocyclic sys-
tems.[12] The most promising application of halochalcogeno-
phenes is copper/palladium-catalyzed cross-coupling reac-
tions.[11] For example, palladium-catalyzed cross-coupling of
halo-chalcogenophenes with terminal alkynes has been
widely used in the synthesis of chalcogenophenes with phar-
macological activity, such as furans, thiophenes, seleno-
phenes, and tellurophenes.[19] Other applications of halo-
chalcogenophenes include palladium-catalyzed coupling re-
actions with organoboron compounds to give alkyl, aryl and
heteroaryl substituents at different positions of the chalcoge-
nophene.[20] Although a variety of reagents are effective in
performing the oxidation/aromatization of dihydroheterocy-
cles, some methods suffer from low chemical yields, strongly
oxidative conditions, unwieldy workup, or side-product for-
mation. Despite the disadvantages to this approach, recently
Chen and co-workers reported a powerful strategy for the
oxidation of 2,5-dihydroheterocycles using a bromine source
and obtained good results in aromatization.[21] In this ap-
proach, dihydroheterocycles were used as starting materials
for aromatization. To avoid multistep reactions, we envi-
sioned that the 3 and 4 (Figure 1) could be obtained by a
one-pot cyclization/aromatization sequence of homopro-
pargyl selenides, under similar conditions to those used for
the preparation of 2a in Table 1, entry 9. For this purpose,
we treated, under ambient atmosphere, homopropargyl sele-
nide 1a (0.25 mmol) with CuBr2 (2 equiv) in refluxing 1,2-di-
chloroethane (2 mL). The 3-bromo-2-phenylselenophene 4a
(7% yield) was obtained besides dehalogenated seleno-
phene 3a, derived from cyclization/aromatization without
incorporation of the bromine atom (Table 3, entry 1). This
phenes 3a and 4a.[a]
CuBr2 [equiv]
Solvent
Yield of 3a:4a [%]
1
2
3
4
5
6
7
2
2
4
4
2
4
4
DCE
45:7
20:42
–:60
–:58
–:50
–:65
–:86
toluene[b]
DCE
toluene[b]
DMF[b]
DMF[b]
DMA[b]
[a] Reactions were performed with 1a (0.5 mmol) and solvent (4 mL) at
reflux temperature under air. [b] A temperature of 1008C was used.
result is significant since we obtained a further class of chal-
cogenophenes by using similar reaction conditions. With this
result in hand, we studied the behavior of the cyclization/ox-
idation reaction by varying solvents, temperature, and
amount of copper(II) bromide (Table 3, entries 2–7). When
the reaction was carried out in toluene, 4a was obtained in
42% yield, along with 20% yield of 3a (Table 3, entry 2).
When the reaction was performed with 4 equiv of CuBr2 in
1,2-dichloroethane the desired selenophene 4a was obtained
in 60% yield with complete absence of 3a (Table 3, entry 3).
No remarkable increase in the yield of the product was ob-
served on keeping 4 equiv of CuBr2 and changing the sol-
vent from 1,2-dichloroethane to toluene or DMF (Table 3,
entries 4–6). The use of dimethylacetamide as solvent with
4 equiv of CuBr2 at 1008C was superior to other conditions
tested (Table 3, entry 7) that either promoted the formation
of 3-bromoselenophene 4a in the best yield or avoided the
formation of 3a. Under the reaction conditions shown in
Table 3, homopropargyl selenides 1a and 2 equiv of CuBr2
under ambient atmosphere in 1,2-dichloroethane at reflux
gave preferably selenophene 3a, whereas using 4 equiv of
CuBr2 in dimethylacetamide at 1008C gave exclusively the
3-bromoselenophene 4a.
We systematically applied the conditions of entries 1 and
7 in Table 3 to other substituted homopropargyl selenides 1
to test the tolerance for functional groups and their effects
on the conversion. For preparation of selenophenes 3, aryl
groups having neutral and electron-donating substituents
gave the worst yields of 45 and 65% compared to the sub-
stituent having electron-withdrawing groups which afforded
the cyclized products in 75 and 70% yield (Scheme 1).
Beside the synthesis of 2-substituted selenophenes 3, a
series of 3-halo 2-substituted selenophenes 4 and 5 was also
prepared (Table 4). For the preparation of 3-bromo-seleno-
phene 4, we observed that the reaction yield does not seem
to be strongly influenced by the electronic effect of the sub-
stituent, since different aryl groups having neutral, electron-
withdrawing, and electron-donating groups in the aromatic
rings were compatible with the reaction conditions, and
yielded the corresponding selenophenes 4a–g without any
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G. Zeni et al.
tained for cyclization with homopropargyl selenide 1b
having a methyl group at the ortho position, that is, the
steric hindrance of the o-methyl group appears to exert a
significant negative effect (Table 4, entry 2). When the reac-
tion was carried out with homopropargyl selenide 1h having
an alkyl group directly bonded to the alkyne, a decrease in
the yield was observed, and cyclized 3-bromo-4-butyl-sele-
nophene 4h was obtained in 63% yield (Table 3, entry 8).
The use of propargyl alcohol 1j or alkyl selenide substituted
1i as substrate was also tested, and cyclization gave the de-
sired cyclized 3-bromoselenophenes in moderate yields
(Table 4, entries 9 and 10). Our methodology could be readi-
ly adapted to the preparation of 3-chloroselenophenes 5
simply by replacing CuBr2 with CuCl2 (Table 4). This result
is significant, particularly when the different reactivity of
the halogens for further functionalization is considered.
Thiophenes are useful substrates found in numerous natu-
ral products and biologically active molecules.[21] In this con-
text, we also investigated the behavior of homopropargyl
sulfides 6 containing differently substituted aromatic rings.
The synthesis of 3-bromo- and 3-chlorothiophenes 7 and 8
was also feasible employing CuBr2 and CuCl2, respectively,
in dimethylacetamide at 1008C under air (Scheme 2). The
Scheme 1. Synthesis of 2-arylselenophenes 3.
Table 4. Synthesis of 3-bromoselenophenes 4a–j[a] and 3-chlorochalcoge-
nophenes 5a–j.[b]
Alkynyl
Product
Yield
[%]
selenide 1
4 or 5
1a
4a
5a
86
67
1
2
1b
4b
5b
30
41
1c
4c
5c
53
52
3
1d
1e
1 f
1g
4d
5d
78
68
4
5
6
4e
5e
60
48
Scheme 2. Synthesis of 3-halothiophenes 7 and 8.
4 f
5 f
85
77
cyclization reaction tolerated neutral, electron-donating, and
electron-withdrawing groups and gave the expected prod-
ucts in moderate yields. Although the yields are lower than
those of selenophenes under the same conditions, this may
be acceptable considering the higher nucleophilicity of sele-
nium compared to sulfur and that a halogenated aromatic
heterocycle is generated from an acyclic substrate in a
simple and easily handled protocol.
To complete our investigation and to show the versatility
and the synthetic value of our methodology, we tested the
reactivity of 3-bromoselenophene 4a toward Sonogashira-
and Suzuki-type cross-coupling reactions. Thus, the reaction
of 4a with terminal alkynes in the presence of a cooperative
Pd/Cu system as catalyst in Et3N afforded the 3-alkynylsele-
nophenes 9a (from phenylacetylene) and 9b (from 2-
methyl-3-butyn-2-ol) in 60 and 57% yield of isolated prod-
uct, respectively. In addition, the reaction of 4a with m-ace-
tylphenyl boronic acid and p-methylphenyl boronic acid
gave the corresponding Suzuki-type products 10a and 10b
in 50 and 70% yield, respectively (Scheme 3).
4g
5g
69
66
7
1h
1i
4h
5h
63
56
8
9
4i
5i
42
35
1j
4j
5j
53
60
10
[a] Conditions for synthesis of 4a–j: alkyne 1 (0.5 mmol) and CuBr2
(4 equiv) in dimethylacetamide (4 mL) at 1008C for 12 h.
major byproducts and in very similar yields (Table 4, en-
tries 1–7). However, a moderate yield of product 4b was ob-
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Chem. Eur. J. 2013, 19, 13059 – 13064

Cyclization of Homopropargyl Chalcogenides
FULL PAPER
Scheme 4d and e were conducted with homopropargyl sele-
nide 1a and dihydroselenophene 2a under our optimized
conditions to obtain 3-bromoselenophenes 3, but argon at-
mosphere was used instead of air. Under these conditions,
propargyl selenide 1a in the presence of CuBr2 gave a mix-
ture of 2,3-dihydroselenophene 2a as major product and the
expected product 3a in 36% yield (Scheme 4d). In the ab-
sence of CuBr2 no product 3a was obtained and dihydrose-
lenophene 2a was completely recovered. These reactions
show that 1) room temperature is essential to formation of
4-halo-2,3-dihydroselenophenes; 2) the formation of seleno-
phenes 3 depends on the solvent and temperature; 3) tem-
perature and air are crucial to the formation of 3-halo-sele-
nophenes 4; and 4) 4-halo-2,3-dihydroselenophene 2 seems
to be a common intermediate to the formation of both sele-
nophenes 3 and 3-haloselenophenes 4.
Scheme 3. Suzuki- and Sonogashira-type cross-coupling reactions of 3-
bromo-selenophene 4a. a) [PdACHTNUGTRENNUNG
toluene/dioxane, 908C. b) [PdCl
alkyne, Et3N, 80 8C.
CHTUNGTRENNUNG
Conclusion
We have developed an alternative and selective method for
the synthesis of chalcogenophene derivatives by intramolec-
ular 5-endo-dig cyclization of homopropargyl chalcogenides.
This study introduced copper(II) salts as halogenating/cycliz-
ing agent for the selective preparation of 4-halodihydrosele-
nophenes 2, 2-substituted selenophenes 3, and 3-halochalco-
genophenes 4, 5, 7, and 8. These results are significant since,
using similar reaction conditions, we obtained four classes of
chalcogenophene derivatives. The reactions were carried out
under air, which is considered an economic protocol. Un-
fortunately, under these cyclization reactions alkynyl sulfides
could not be used to generate 2,3-dihydrothiophenes, since
they proved to unreactive under the presented conditions.
The presence of a halogen substituent in the selenophene
structure allowed further structural elaboration through con-
version of the halogen group to other substituents. For ex-
ample, employing compound 4a as substrate under Suzuki
and Sonogashira coupling conditions afforded the corre-
À
sponding products through C C bond formation in moder-
Scheme 4. Experiments on mechanism elucidation.
ate to good yields. Another feature of this protocol is that
the reactions were carried with copper salts, which are
readily available commercially, inexpensive, and relatively
nontoxic.
To demonstrate the influence of air as a non-unique but
essential oxidant in the formation of the selenophene ring,
as well as to obtain evidence for the reaction mechanism,
we carried out the experiments depicted in Scheme 4. 1) As
demonstrated in Table 2 (entry 1), homopropargyl selenide
1a reacted with CuBr2 in 1,2-dichloroethane at room tem-
perature under air to give 2a in 72% yield (Scheme 4a).
2) When dichloromethane was heated to reflux under air in
the presence of substrate 2a and in the absence of CuBr2,
selenophene 3a was obtained in 80% yield (Scheme 4b).
This indicates that substrate 2a is the key intermediate in
the reaction of homopropargyl selenide 1 with CuBr2 to
form product 3. When the solvent was changed to dimethyl-
Experimental Section
General procedure for CuX2-promoted synthesis of 5-substituted-2,3-di-
hydroselenophenes 2: Two equivalents of CuBr2 were added to a solution
of 0.5 mmol of the appropriate alkynyl selenide 1 in 4 mL of DCE. The
reaction mixture was allowed to stir at room temperature for the desired
time. The reaction was quenched with saturated aqueous NH4Cl/NH4OH
(20 mL) and extracted with CH2Cl2 (3ꢄ10 mL). The combined organic
layers were dried over anhydrous Mg2SO4 and concentrated under
vacuum to yield the crude product, which was purified by flash chroma-
tography on silica gel with hexane as the eluent. Representative data for
ACHTUNGTRENNUNG
4-bromo-5-phenyl-2,3-dihydroselenophene ACTHNUTRGENUG(N 2a): Yield: 0.103 g (72%);
1H NMR (CDCl3, 400 MHz): d=7.57–7.48 (m, 2H), 7.40–7.29 (m, 3H),
3.43–3.32 ppm (m, 4H); 13C NMR (CDCl3, 100 MHz): d=135.0, 130.9,
ACHTUNGTRENNUNG
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13063

G. Zeni et al.
128.7, 128.5, 128.2, 105.0, 47.0, 22.2; MS: m/z (%): 287 (33), 128 (100),
115 (31), 102 (12), 89 (16), 208 (12); elemental analysis (%) calcd for
C10H9BrSe: C 41.70, H 3.15; found: C 41.85, H 3.22.
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phenes 3: Two equivalents of CuBr2 were added to
a solution of
0.5 mmol of the appropriate alkynyl selenide 1 in 4 mL of DCE. The re-
action mixture was allowed to stir at reflux temperature for the desired
time. The reaction was quenched with saturated aqueous NH4Cl/NH4OH
(20 mL) and extracted with CH2Cl2 (3ꢄ10 mL). The combined organic
layers were dried over anhydrous Mg2SO4 and concentrated under
vacuum to yield the crude product, which was purified by flash chroma-
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(3a): Yield: 0.046 g (45%); 1H NMR (CDCl3,
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MS: m/z (%): 208 (64), 128 (100), 115 (23), 102 (21), 51 (12).
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General procedure for CuX2-promoted synthesis of 3-halo 2-substituted
selenophenes 4 and 5: Four equivalents of CuX2 were added to a solution
of 0.5 mmol of the appropriate alkynyl selenide 1 in 4 mL of DMA. The
reaction mixture was allowed to stir at 1008C for the desired time. The
reaction was quenched with saturated aqueous NH4Cl/NH4OH (20 mL)
and extracted with ethyl acetate (3ꢄ10 mL). The combined organic
layers were dried over anhydrous Mg2SO4 and concentrated under
vacuum to yield the crude product, which was purified by flash chroma-
tography on silica gel with hexane as the eluent. Representative data for
3-bromo-2-phenylselenophene ACHTUNGTRNEUNG
(4a): Yield: 0.122 g (86%); 1H NMR
(CDCl3, 200 MHz): d=7.91 (d, J=5.86 Hz, 1H), 7.63–7.57 (m, 2H),
7.46–7.34 ppm (m, 3H), 7.30 (d, J=5.86 Hz, 1H); 13C NMR (CDCl3,
50 MHz): d=142.9, 134.6, 134.3, 129.9, 129.2, 128.4, 128.1, 107.9 ppm;
MS: m/z (%): 285 (77), 206 (26), 126 (34), 115 (100), 103 (11), 89 (10); el-
emental analysis (%) calcd for C10H7BrSe: C 41.99, H 2.47; found: C
42.12, H 2.55.
General procedure for CuX2-promoted synthesis of 3-halo 2-substituted
thiophenes 7 and 8: Four equivalents of CuX2 were added to a solution
of 0.5 mmol of the appropriate alkynyl sulfide 6 in 4 mL of DMA. The
reaction mixture was allowed to stir at 1008C for the desired time. The
reaction was quenched with saturated aqueous NH4Cl/NH4OH (20 mL)
and extracted with ethyl acetate (3ꢄ10 mL). The combined organic
layers were dried over anhydrous Mg2SO4 and concentrated under
vacuum to yield the crude product, which was purified by flash chroma-
tography on silica gel with hexane as eluent. Representative data for 3-
bromo-2-phenylthiophene ACHTNUGRTNEUNG
(7a): Yield: 0.025 g (42%); 1H NMR (CDCl3,
400 MHz): d=7.67–7.62 (m, 2H), 7.47–7.36 (m, 3H), 7.28–7.23 (m, 1H),
7.06–7.03 ppm (d, J=5.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=
138.2, 132.8, 131.6, 129.0, 128.4, 128.2, 124.9, 107.5 ppm; MS: m/z (%):
239 (91), 159 (15), 115 (100), 79 (14); elemental analysis (%) calcd for
C10H7BrS: C 50.23, H 2.95; found: C 50.44, H 3.02.
Acknowledgements
We are grateful to FAPERGS (PRONEX-10/0005-1), CAPES and CNPq
(CNPq/INCT-catalise) for the financial support. CNPq is also acknowl-
edged for the fellowships (G.Z., A.R.R., and R.F.S.).
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Received: June 4, 2013
Published online: September 3, 2013
13064
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