Synthesis and reactivity of 3-alkynyldihydroselenophene derivatives

Article abstract of DOI:10.1002/ejoc.201000588

We present herein our results on the synthesis of 3- alkynyldihydroselenophenes by palladium-catalyzed Sonogashira cross-coupling of 3-iododihydroselenophenes with different alkynes under mild conditions in good to excellent yields. The developed protocol tolerated a wide range of functional groups in the dihydroselenophenes and alkynes. These 3- alkynyldihydroselenophenes, bearing the chalcogen group, underwent highly selective intramolecular cyclizations when treated with I₂ to afford fused dihydroselenophene[2,3,b]selenophene rings. In addition, 3-alkynyldihydroselenophene obtained by this methodology was also submitted to an oxidative reaction by using DDQ to give the aromatic selenophene in moderated yields. The synthesis of a variety 3-alkynyldihydroselenophenes by palladium-catalyzed Sonogashira cross-coupling of 3-iododihydroselenophenes under mild conditions in good to excellent yields is reported.These 3-alkynyldihydroselenophenes, bearing the chalcogen group, underwent highly selective intramolecular cyclizations when treated with I₂ to afford fused dihydroselenophene[2,3,b]selenophene rings.

Full text of DOI:10.1002/ejoc.201000588

FULL PAPER
DOI: 10.1002/ejoc.201000588
Synthesis and Reactivity of 3-Alkynyldihydroselenophene Derivatives
Alisson R. Rosário,[a] Ricardo F. Schumacher,[a] Bibiana M. Gay,[a] Paulo H. Menezes,[b] and
Gilson Zeni*[a]
Keywords: Heterocycles / Cross-coupling / Selenium / Cyclization / Alkynes
We present herein our results on the synthesis of 3-alkynyl-
dihydroselenophenes by palladium-catalyzed Sonogashira
cross-coupling of 3-iododihydroselenophenes with different
alkynes under mild conditions in good to excellent yields.
The developed protocol tolerated a wide range of functional
groups in the dihydroselenophenes and alkynes. These 3-al-
kynyldihydroselenophenes, bearing the chalcogen group,
underwent highly selective intramolecular cyclizations when
treated with I2 to afford fused dihydroselenophene[2,3,b]-
selenophene rings. In addition, 3-alkynyldihydroseleno-
phene obtained by this methodology was also submitted to
an oxidative reaction by using DDQ to give the aromatic se-
lenophene in moderated yields.
metals used,[10] although it sometimes displays intolerance
to some functionalities or proceeds with a lack of regio-
selectivity. On the other hand, the electrophilic cyclization
appears as an alternative route to generate highly function-
alized heterocycles. This methodology takes advantage, in
most cases, by the presence of a halogen atom suitable to
suffer further transformations. This cyclization has been
used as an efficient tool in the synthesis of highly substi-
tuted indoles,[11] furans,[12] thiophenes,[13] selenophenes,[14]
benzo[b]furans,[15] benzo[b]thiophenes,[16] benzo[b]seleno-
phenes,[17] lactones,[18] and pyrroles[19] by employing elec-
trophiles like I2, ICl, or chalcogen derivatives.[20]
These and especially the knowledge that 3-alkynyldihyd-
roselenophenes are promising candidates for electrophilic
cyclization reactions to form fused selenophenes prompted
us to develop a complete investigation on the synthesis of
3-alkynyldihydroselenophenes from 3-iododihydroselen-
ophenes as the sequence showed in Scheme 1.
Introduction
Organoselenium chemistry is a very broad and exciting
field with many opportunities for research and development
of applications. Organoselenium compounds have become
attractive synthetic targets because of their chemo-, regio-,
and stereoselective reactions and their useful biological ac-
tivities.[1] Furthermore, organoselenium compounds can
usually be used in the presence of a wide variety of func-
tional groups, thus avoiding protecting group chemistry.[2]
Among organoselenium compounds, selenophene deriva-
tives are widely studied agents with a diverse array of bio-
logical effects, including antioxidant,[3] antinociceptive,[4]
and anti-inflammatory properties,[5] as well as efficacy as
maturation inducing agents.[6] A great number of these het-
erocycles have been synthesized and their chemistry has at-
tracted a good deal of interest and activity from a variety
of standpoints such as structure, stereochemistry, reactivity,
and applications to organic synthesis.[7] However, the syn-
thetic study of a partially saturated version, 2,3-dihydrosele-
nophene derivatives of selenophenes, has been surprisingly
limited.[8] In the context of heterocycles, the transition-
metal-catalyzed cyclization reaction of simple acyclic pre-
cursors is one of the most attractive ways to directly con-
struct complicated molecules under mild conditions.[9] In
this way, palladium is one of the most common transition
Scheme 1. General scheme for the cross-coupling of 3-iododihydro-
selenophene derivatives with terminal alkynes.
[a] Laboratório de Síntese, Reatividade, Avaliação Farmacológica
e Toxicológica de Organocalcogênios, CCNE, Universidade
Federal de Santa Maria,
Santa Maria, Rio Grande do Sul, 97105-900, Brazil
[b] Universidade Federal de Pernambuco, Departamento Química
Fundamental,
Results and Discussion
We initially focused on experiments to find a route that
would gave the required starting materials, 3-alkynyldihyd-
roselenophenes, in good yields. We envisioned that this
route could start with the introduction of an iodine group
View this journal online at
Recife, Pernambuco, 50670-901, Brazil
Fax: +55-55-3220-8998
E-mail: gzeni@pq.cnpq.br
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000588.
wileyonlinelibrary.com
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A. R. Rosário, R. F. Schumacher, B. M. Gay, P. H. Menezes, G. Zeni
FULL PAPER
in the C-3 position of the dihydroselenophenes and subse- Table 2. Cross-coupling reaction of 3-iododihydroselenophenes 1a–
e and alkynes 2a–y.
quent functionalization by using palladium-catalyzed Sono-
gashira cross-coupling[21] with terminal alkynes. For the in-
troduction of the iodine group, we chose the electrophilic
cyclization of homopropargyl selenides by using iodine as
the electrophilic source.[22]
Thus, the reaction of homopropargyl selenides
(0.5 mmol) and I2 (1.1 equiv.) in CH2Cl2 (10 mL) at room
temperature gave 3-iododihydroselenophenes in high yields.
By this method, we prepared a number of 3-iododihydro-
selenophenes 1a–e and applied these compounds as starting
materials in palladium-catalyzed Sonogashira cross-cou-
plings.
Our initial studies on the preparation of 3-alkynyldihyd-
roselenophenes focused on the development of an optimum
set of reaction conditions. For this purpose, 2-phenyl-3-
iododihydroselenophene (1a) and 2-methyl-3-butyn-2-ol
(2a) were used as standard substrates. Thus, a mixture of 3-
iododihydroselenophene 1a (0.25 mmol) and alkyne 2a
(0.375 mmol) was treated with a variety of palladium cata-
lysts and various solvents by using NEt3 as a base in the
presence of CuI (Table 1). Careful analysis of the optimized
reaction revealed that the optimum condition for this cou-
pling involved the use of PdCl2(PPh3)2 (5 mol-%), NEt3
(2 mL), 3-iododihydroselenophene 1a (0.25 mmol), propar-
gyl alcohol 2a (0.375 mmol), and CuI (7 mol-%) at room
temperature for 12 h.
Table 1. Optimization of reaction conditions.
Entry
Catalyst (mol-%)
Solvent
Yield [%][a]
1
2
3
4
5
6
7
8
PdCl2 (5)
Pd(OAc)2 (5)
Pd(PPh3)4 (5)
Pd(PhCN)2Cl2 (5)
Pd(acac)2 (5)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NEt3
MeOH
dioxane
THF
toluene
NEt3
46
26
37
18
25
–
93
95
78
65
31
50
67
24
54
traces
Pd(dppe)2 (5)
Pd(PPh3)2Cl2 (5)
Pd(PPh3)2Cl2 (5)
Pd(PPh3)2Cl2(5)
Pd(PPh3)2Cl2 (5)
Pd(PPh3)2Cl2 (5)
Pd(PPh3)2Cl2 (5)
Pd(PPh3)2Cl2 (1)
Pd(PPh3)2Cl2 (10)
Pd(PPh3)2Cl2 (5)[b]
Pd(PPh3)2Cl2 (5)[c]
9
10
11
12
13
14
15
16
NEt3
NEt3
NEt3
[a] Yields were calculated by GC analysis. [b] Reaction was per-
formed in the presence of 5 mol-% of CuI. [c] Reaction was per-
formed in the absence of CuI.
To demonstrate the efficiency of this reaction, we ex-
plored the generality of our method by extending the best
conditions to other terminal alkynes and different 3-iodo-
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Synthesis and Reactivity of 3-Alkynyl-dihydroselenophene Derivatives
Table 2. (Continued).
Table 2. (Continued).
[a] Yields of 3a–y are given for isolated products.
dihydroselenophenes; the results are summarized in Table 2.
First, to determine the real influence of the terminal al-
kynes, we used 2-phenyl-3-iododihydroselenophene (1a) for
all experiments. The results demonstrated that the reaction
worked well for both hindered and nonhindered propargyl
alcohols (Table 2, Entries 1–3). We observed that the reac-
tion also worked well with long-chain and protected pro-
pargyl alcohols (Table 2, Entries 4 and 5). In addition to
propargyl alcohols, the reaction with aliphatic alkynes also
led to the formation of the desired products in good yields
(Table 2, Entries 6–9). We observed that the reaction is not
sensitive to electronic effects of the aromatic ring directly
bonded to the alkyne. For example, alkynes having an aryl-
or an aryl-substituted group gave similar yields (Table 2,
Entries 10 and 11). By contrast, when the reaction was car-
ried out with 1,3-diyne a decrease in the yield was observed
and the Sonogashira product was obtained in 40% yield
(Table 2, Entries 12). Finally, we then explored the possibil-
ity of expanding our methodology to 3-iododihydroseleno-
phenes 1b–e having a hydrogen, alcohol chain, sulfur, and
selenium groups in the C-2 position. It was found that the
reaction worked well, affording 3-alkynyldihydroseleno-
phenes derivatives 3m–y in moderate to excellent yields under
the same reaction conditions (Table 2, Entries 13–25). The
limitation in our method was observed when compound 1c
(Table 2, Entry 16), which has a hindered alcohol in the C-2
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A. R. Rosário, R. F. Schumacher, B. M. Gay, P. H. Menezes, G. Zeni
FULL PAPER
Table 3. Electrophilic cyclization with iodine.[a]
tuted benzo[b]selenophenes were obtained in good yields by
the electrophilic cyclization of 2-(1-alkynyl)selenoanisoles
by using I2 as an electrophilic source.[17]
Inspired by Larock’s reaction, we extended this method
to access new fused chalcogenophenes 4a–e. Gratifyingly,
we found that the electrophilic cyclization of 3-alkynyldihy-
droselenophenes with I2 in CH2Cl2 as the solvent at room
temperature afforded the desired fused chalcogenophenes
4a–e in moderated to good yields (Table 3).
Recently, it was reported that 2,3-dichloro-5,6-dicya-
nobenzoquinone (DDQ) is a useful promoter for the oxi-
dation of 2,3-dihydrothiophene[23] or 2,3-dihydrofuran[24] to
aromatic thiophene or furan. As demonstrated in Scheme 2,
the reaction of DDQ with 3-alkynyldihydrochalcogeno-
phene 3j also proceeded smoothly to give the corresponding
2,3-disubstituted selenophene 5a in moderate yield.
Conclusions
We described herein an efficient methodology for the
synthesis of 3-alkynyldihydroselenophene derivatives
through Sonogashira cross-coupling of 3-iododihydroselen-
ophenes with different alkynes. This cross-coupling reaction
proceeded cleanly under mild conditions and was per-
formed with propargylic alcohols, propargylic ethers, as
well as aliphatic and aryl alkynes. The products obtained
were effective for subsequent electrophilic cyclization reac-
tions by using iodine as the electrophilic source, giving the
fused chalcogenophenes in moderate yields. A 3-alkynyldi-
hydroselenophene obtained by this methodology was also
submitted to an oxidative reaction by using DDQ to give
the aromatic selenophene in moderate yield.
Experimental Section
General Procedure for the Formation of 3-Alkynyldihydroselenoph-
enes: To a Schlenk tube, under an argon atmosphere, containing
the appropriate 3-iododihydroselenophene (0.25 mmol) in Et3N
(1.5 mL) was added Pd(PPh3)2Cl2 (0.0087 g, 0.0124 mmol). After
that, the appropriate terminal alkyne (0.3 mmol) dissolved in Et3N
(0.5 mL) was then added. The resulting solution was stirred for
5 min at room temperature. After this time, CuI (0.0033 g,
0.0017 mmol) was added, and the reaction mixture was stirred at
room temperature for the required time. The mixture was then di-
luted with ethyl acetate (20 mL) and washed with brine
(3ϫ10 mL). The organic phase was separated, dried with MgSO4,
and concentrated under vacuum. The residue was purified by flash
chromatography (silica gel, ethyl acetate/hexane).
[a] Yields of 4a–e are given for isolated products.
Scheme 2. Oxidation of 3-alkynyldihydroselenophene 3j with DDQ.
position of the selenophene ring, was treated with propargyl
alcohol 2a. Unfortunately, in this case the reaction condi-
tions failed to give the desired product. The starting mate-
rial was recovered in its entirety, even under forcing condi-
tions.
Because chalcogenophene derivatives exhibit a broad
range of biological activities and applications as intermedi-
ates in organic synthesis, we wondered if it would be pos-
sible to prepare fused chalcogenophenes directly from 3-
alkynyldihydrochalcogenophenes previously prepared. Re-
2-Methyl-4-(2-phenyl-4,5-dihydroselenophen-3-yl)but-3-yn-2-ol (3a):
1
Yield: 0.069 g (95%). H NMR (400 MHz, CDCl3): δ = 7.74–7.71
(m, 2 H, CH-Ar), 7.35–7.25 (m, 3 H, CH-Ar), 3.30 (t, JH,H
=
7.6 Hz, 2 H, CH2CH2), 3.16 (t, JH,H = 7.3 Hz, 2 H, CH2CH2), 2.18
(s, 1 H, OH), 1.51 (s, 6 H, CH) ppm. 13C NMR (100 MHz, CDCl3):
δ = 135.58, 128.48, 128.75, 127.98, 114.50, 99.94, 96.83, 79.98,
65.76, 44.06, 32.21, 24.01 ppm. MS: m/z (%) = 291 (100), 276 (56),
211 (30), 181 (21), 167 (40), 153 (51), 141 (31), 115 (37), 77 (22).
C15H16OSe (292.04): calcd. C 61.86, H 5.54; found C 62.10, H 5.56.
3-(2-Phenyl-4,5-dihydroselenophen-3-yl)prop-2-yn-1-ol (3b): Yield:
1
cently, Larock and co-workers reported that 2,3-disubsti- 0.046 g (70%). H NMR (400 MHz, CDCl3): δ = 7.73–7.68 (m, 2
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Synthesis and Reactivity of 3-Alkynyl-dihydroselenophene Derivatives
H, CH-Ar), 7.39–7.28 (m, 3 H, CH-Ar), 4.37 (s, 2 H, CH), 3.37–
3.14 (m, 4 H, CH2CH2), 1.84 (s, 1 H, OH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 145.53, 135.49, 128.54, 128.31, 128.13,
114.37, 90.33, 83.22, 51.69, 44.09, 24.04 ppm. MS: m/z (%) = 261
(65), 163 (59), 151 (100), 139 (25), 126 (52), 114 (31).
3-Iodo-2-phenyl-4,5-dihydroselenopheno[2,3-b]thiophene (4a) Yield:
0.069 g (70%). H NMR (400 MHz, CDCl3): δ = 7.57–7.35 (m, 5
1
H), 3.84 (t, JH,H = 7.8 Hz, 2 H, CH2CH2), 3.22 (t, JH,H = 7.8 Hz,
2 H, CH2CH2) ppm. 13C NMR (50 MHz, CDCl3): δ = 149.32,
144.02, 137.73, 129.06, 128.44, 128.36, 128.15, 128.85, 35.41,
31.31 ppm. MS (%): m/z (%) = 391 (54), 281 (31), 207 (62), 184
(48), 115 (13), 73 (43), 44 (100).
3-Methyl-1-(2-phenyl-4,5-dihydroselenophen-3-yl)pent-1-yn-3-ol (3c):
1
Yield: 0.073 g (95%). H NMR (CDCl3, 200 MHz): δ = 7.74–7.70
(m, 2 H, CH-Ar), 7.38–7.26 (m, 3 H, CH-Ar), 3.37–3.28 (m, 2 H, General Procedure for Aromatization: To a Schlenk tube, under an
CH2CH2), 3.22–3.13 (m, 2 H, CH2CH2), 1.97 (s, 1 H, OH), 1.75–
1.64 (q, JH,H = 6.1 Hz, 2 H, CH2CH3), 1.47 (s, 3 H, CH), 1.02–
0.95 (t, JH,H = 7.5 Hz, 3 H, CH2CH3) ppm. 13C NMR (100 MHz,
argon atmosphere, containing the appropriate 3-alkynyldihydrose-
lenophene (0.25 mmol) in toluene (2 mL) was added DDQ
(0.5 mmol), and the reaction mixture was heated at 90 °C for 12 h.
CDCl3): δ = 144.76, 135.53, 128.46, 128.35, 127.97, 114.61, 95.79, After this time, the mixture was diluted with ethyl acetate (20 mL)
80.97, 69.28, 44.14, 36.39, 29.09, 24.00, 8.98 ppm. MS: m/z (%) =
306 (100), 225 (37), 199 (20), 151 (15), 112 (18). C16H18OSe
(306.05): calcd. C 62.95, H 5.94; found C 62.69, H 5.91.
and washed with brine (3ϫ10 mL). The combined organic layer
was dried with anhydrous MgSO4 and concentrated under vacuum.
The residue was purified by flash chromatography (silica gel, ethyl
acetate/hexane).
4-(2-Phenyl-4,5-dihydroselenophen-3-yl)but-3-yn-1-ol (3d): Yield:
1
2-Phenyl-3-(2-phenylethynyl)selenophene (5a): Yield: 0.031 g (40%).
1H NMR (200 MHz, CDCl3): δ = 7.87 (d, JH,H = 5.9 Hz, 2 H, CH-
Ar), 7.48–7.31 (m, 7 H, CH-Ar) ppm. 13C NMR (50 MHz, CDCl3):
δ = 152.73, 135.69, 134.20, 131.36, 128.54, 128.32, 128.30, 128.21,
128.07, 123.40, 119.81, 102.34, 90.41, 86.66 ppm. MS (%): m/z (%)
= 307 (98), 228 (100), 215 (20), 200 (17), 153 (21), 113 (48), 101
(14). C18H12Se (308.01): calcd. C 70.36, H 3.94; found C 70.49, H
4.02.
0.050 g (72%). H NMR (400 MHz, CDCl3): δ = 7.74–7.70 (m, 2
H, CH-Ar), 7.38–7.26 (m, 3 H, CH-Ar), 3.72–3.66 (t, JH,H
=
6.1 Hz, CH2CH2), 3.35–3.12 (m, 4 H, CH2CH2), 2.61–2.45 (t, JH,H
= 6.2 Hz, 2 H, CH2CH2), 1.86 (s, 1 H, OH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 135.81, 128.41, 128.25, 128.11, 115.29,
89.76, 80.25, 60.97, 44.21, 24.15, 23.94 ppm. MS: m/z (%) = 275
(97), 229 (30), 163 (100), 151 (64), 138 (37), 114 (22).
3-(Hex-1-ynyl)-2-phenyl-4,5-dihydroselenophene (3f): Yield: 0.056 g
1
Supporting Information (see footnote on the first page of this arti-
cle) Spectroscopic data for all compounds 3, 4, and 5.
(77%). H NMR (400 MHz, CDCl3): δ = 7.77–7.75 (m, 2 H, CH-
Ar), 7.33–7.24 (m, 3 H, CH-Ar), 3.32–3.25 (m, 2 H, CH2CH2),
3.18–3.14 (t, JH,H = 7.3 Hz, 2 H, CH2CH2), 2.34–2.31 (t, JH,H
=
7.1 Hz, 2 H, CH2CH2), 1.55–1.37 (m, 5 H, CH2CH2), 0.920–0.88
(t, JH,H = 7.3 Hz, 3 H, CH2CH3), 13C NMR (100 MHz, CDCl3): δ
= 135.85, 128.30, 127.91, 120.06, 115.91, 99.92, 94.26, 78.28, 44.63,
30.59, 23.62, 21.89, 19.40, 13.54 ppm. MS: m/z (%) = 288 (91), 270
(44), 231 (24), 208 (15), 176 (29), 151 (100), 139 (22), 115 (25), 88
(13). C16H18Se (290.06): calcd. C 66.43, H 6.27; found C 66.70, H
6.30.
Acknowledgments
We are grateful to Conselho Nacional de Desenvolvimento Ci-
entífico e Tecnológico (INCT-catalise), Coordenação de Aper-
feiçoamento de Pessoal de Nível Superior (SAUX), and Fundação
de Amparo à Pesquisa do Estado do Rio Grande do Sul for fellow-
ship and financial support.
4-(2-Phenylethynyl)-2,3-dihydroselenophene (3m): Yield: 0.053 g
1
(90%). H NMR (200 MHz, CDCl3): δ = 7.45–7.25 (m, 5 H, CH-
[1] a) C. W. Nogueira, G. Zeni, J. B. T. Rocha, Chem. Rev. 2004,
104, 6255–6286; b) C. W. Nogueira, E. B. Quinhones, E. A. C.
Jung, G. Zeni, J. B. T. Rocha, Inflammation Res. 2003, 52, 56–
63.
Ar), 7.07 (t, JH,H = 1.91 Hz, CH-vin), 3.36 (t, JH,H = 8.31 Hz, 2
H, CH2CH2), 2.98 (t, JH,H = 8.31 Hz, 2 H, CH2CH2) ppm. 13C
NMR (100 MHz, CDCl3): δ = 131.31, 130.02, 128.27, 127.99,
123.29, 121.36, 99.95, 89.21, 86.53, 40.60, 25.52 ppm. MS: m/z (%)
= 304 (55), 246 (52), 231 (17), 181 (21), 165 (100), 152 (50), 141
(24), 115 (19). C12H10Se (233.99): calcd. C 61.80, H 4.32; found C
62.10, H 4.37.
[2] a) K. C. Nicolaou, N. A. Petasis, Selenium in Natural Products
Synthesis, CIS, Philadelphia, 1984; b) C. Paulmier, Selenium
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1986, vol. 1; d) D. Liotta, Organoselenium Chemistry, Wiley,
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Chemistry: A Practical Approach, Oxford University Press, Ox-
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D. Liotta, Acc. Chem. Res. 1984, 17, 28–34; i) T. Wirth, Topics
in Current Chemistry Vol. 208: Organoselenium Chemistry:
Modern Developments in Organic Synthesis, Springer, Heidel-
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Chem. Int. Ed. 2009, 48, 2588–2591.
[3] F. C. Meotti, D. O. Silva, A. R. S. Santos, G. Zeni, J. B. T. Ro-
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[4] C. E. P. Gonçales, D. Araldi, R. B. Panatieri, J. B. T. Rocha, G.
Zeni, C. W. Nogueira, Life Sci. 2005, 76, 2221–2234.
[5] a) G. Zeni, D. S. Lüdtke, C. W. Nogueira, R. B. Panatieri, A. L.
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Panatieri, D. O. Silva, P. H. Menezes, A. L. Braga, C. C. Sil-
4-(3,3-Dimethylbut-1-ynyl)-2,3-dihydroselenophene (3o): Yield:
0.039 g (72%). 1H NMR (400 MHz, CDCl3): δ = 6.80 (t, JH,H
=
1.95 Hz, 1 H, CH-vin), 3.27 (t, JH,H = 8.31 Hz, 2 H, CH2CH2),
2.83 (t, JH,H = 8.31 Hz, 2 H, CH2CH2), 1.23 (s, 9 H, CH) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 127.05, 121.91, 98.40, 75.96, 40.98,
30.95, 30.56, 25.13 ppm. MS (%): m/z (%) = 215 (77), 200 (100),
172 (14), 135 (72), 122 (51), 91 (49), 77 (45). C10H14Se (214.03):
calcd. C 56.34, H 6.62; found C 56.51, H 6.75.
General Procedure for Iodocyclizations: To a Schlenk tube, under
an argon atmosphere, containing the appropriate 3-alkynyldihydro-
selenophene in CH2Cl2 (2 mL) was added gradually I2 (1.1 equiv.)
dissolved in CH2Cl2 (3 mL). The reaction mixture was allowed to
stir at room temperature for the required time. The excess amount
of I2 was removed by washing with saturated aqueous Na2S2O3.
The product was then extracted with CH2Cl2 (3ϫ10 mL). The
combined organic layer was dried with anhydrous MgSO4 and con-
centrated under vacuum to yield the crude product, which was
purified by flash chromatography (silica gel, ethyl acetate/hexane).
Eur. J. Org. Chem. 2010, 5601–5606
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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A. R. Rosário, R. F. Schumacher, B. M. Gay, P. H. Menezes, G. Zeni
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Received: April 28, 2010
Published Online: August 24, 2010
5606
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5601–5606