The first synthesis of β-phenylchalcogeno-α,β-unsaturated esters via hydrochalcogenation of acetylenes using microwave and solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2005.01.060

A simple, clean, and efficient solvent-free protocol was developed for hydrochalcogenation of methyl propiolate derivatives with phenylchalcogenolate anion generated in situ from the respective diphenyl dichalcogenide (S, Se, Te) using alumina supported s

Full text of DOI:10.1016/j.tetlet.2005.01.060

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1679–1682
The first synthesis of b-phenylchalcogeno-a,b-unsaturated esters
via hydrochalcogenation of acetylenes using microwave and
solvent-free conditions
Gelson Perin,a,* Raquel G. Jacob,b Francisco de Azambuja,a Giancarlo V. Botteselle,a
a
Geonir M. Siqueira, Rogerio A. Freitag and Eder J. Lenarda˜o
a
c,
*
´
a
´
ˆ
Departamento de Quımica Organica, Universidade Federal de Pelotas, UFPel, PO Box 354, 96010-900 Pelotas, RS, Brazil
b
´
Departamento de Quımica, Universidade Federal de Santa Maria, UFSM, Santa Maria, RS, Brazil
ˆ
c
´ ´
Departamento de Quımica Analıtica e Inorganica, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil
Received 3 December 2004; revised 12 January 2005; accepted 13 January 2005
Available online 29 January 2005
Abstract—A simple, clean, and efficient solvent-free protocol was developed for hydrochalcogenation of methyl propiolate deriva-
tives with phenylchalcogenolate anion generated in situ from the respective diphenyl dichalcogenide (S, Se, Te) using alumina
supported sodium borohydride. This efficient and improved method is general and furnishes the (Z)-b-phenylchalcogeno-a,b-
unsaturated esters in yields and with selectivity comparable to those using organic solvent and inert atmosphere. The use of
MW irradiation facilitates the procedure and accelerates the reaction.
Ó 2005 Elsevier Ltd. All rights reserved.
Functionalized vinyl chalcogenides (S, Se, and Te) have
been found to be a potential tool in organic synthesis,
since they are very versatile intermediates for the selec-
tive construction of isolated or conjugated olefins.1
Among the functionalized vinyl chalcogenides, those
containing a Michael acceptor, like an ester group at
the adjacent sp2 carbon (a b-organylchalcogeno-a,b-
unsaturated ester), are of greatest interest since they
combine the chemical reactivity of the vinyl chalcoge-
nides and the vinyl ester.2
anions2c,e,5,6 has solved the unpleasant smell problem.
Unfortunately, these improvements were not extended
to alkynes bearing electron-withdrawing groups, like es-
ters, and have not eliminated the use of organic solvents
and inert atmosphere. Due to the increasing interest on
functionalized vinyl chalcogenides, the development of
new and efficient methods for the preparation of these
compounds with defined regio- and stereochemistry is
of general interest in organic synthesis.
Looking for cleaner approaches to classical syntheses,
we have developed several protocols involving solid sup-
ported catalyst under solvent-free conditions7 and MW
irradiation.8,9 As a continuation of our studies toward
the development of new methods for the synthesis of
vinyl sulfides, selenides, and tellurides, we report herein
the synthesis of b-phenylchalcogeno esters 2 and 3 by
The method of choice to prepare (Z)-1,2-disubstituted
vinyl chalcogenides is the addition of organo chalcoge-
nols, or the respective chalcogenolate anions, to acetyl-
enes.1,3 Despite the practicality of experimental
procedure and high regio- and stereoselectivity, this
method shows some disadvantages, such as, the use of
stinking, volatile, and toxic thiophenol, unstable and
air sensitive tellurolate and selenolate anions, use of long
heating time and inert atmosphere. The in situ genera-
tion of organyl thiolate,4 selenolate,2c,4,5 and tellurolate
Al2O3/NaBH4 (30%)
R
CO2Me
C6H5YYC6H5
+
R
r.t., 65oC or MW (662 W)
1
CO2Me
R
Keywords: Microwave irradiation; Solvent-free reaction; b-Phenyl-
chalcogeno esters.
+
R = Ph, C5H11
Y = S, Se, Te
C6H5Y
CO2Me
C6H5Y 3a-f
2a-f
*
Corresponding authors. Tel./fax: +55 532757354; e-mail: gelson_
perin@ufpel.edu.br
Scheme 1.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.060

1680
G. Perin et al. / Tetrahedron Letters 46 (2005) 1679–1682
hydrochalcogenation of acetylenes using Al2O3/NaBH4
without any solvent10,11 (Scheme 1, Table 1).
the (Z)-stereoisomer 2a in a Z:E ratio = 79:21 (Table
1, entry 1, Method A). The use of 0.127 g of the catalytic
system has not significantly increased the yield.
Our initial efforts were made toward the determination
of the optimum conditions to perform the protocol.
Thus, we chose methyl phenylpropiolate (1 equiv) and
diphenyl diselenide (0.5 equiv) to establish the best con-
ditions for the hydrochalcogenation reaction.
Aiming to reduce the reaction time, the mixture of ester,
diphenyl diselenide, and Al2O3/NaBH4 (0.080 g) was
irradiated with MW (662 W, Method B). Complete con-
version was observed after 3 min and the product was
obtained in comparable yield and higher selectivity (Ta-
ble 1, entry 2). When the same protocol was performed
at reduced MW power (353 W), it was observed, after
20 min, incomplete conversion and the product could
be isolated in 57% yield.
We examined the reaction time, amount of Al2O3/
NaBH4 (30%), temperature and use of microwave.11 It
was found that using 0.050 g of Al2O3/NaBH4, at room
temperature, the reaction proceeded slowly in 60% yield
after 6 h. However, by using 0.080 g of sodium borohy-
dride supported on alumina, the desired product was
obtained in very good yield (83%). The appearance of
two different signals in the olefinic region of the 1H
NMR (6.32 and 5.64 ppm) indicated the formation of
two isomers, which were identified as being 2a and 3a.
The reaction was stereoselective, giving predominantly
When the reaction was performed in the presence of alu-
mina alone, without NaBH4 no reaction took place in all
the conditions tested and the starting materials were
recovered. By using only NaBH4, the desired products
2a and 3a were obtained only in 50% yield, together with
several other byproducts (detected by GC).
Table 1. Synthesis of b-phenylchalcogeno-a,b-unsaturated esters under solvent-free conditions
Entry
R
Y
Products
Methoda
Time
(min)
Yield (%)
2+3b
Ratioc
Z:E
dH (vinyl)
Z
E
C6H5
CO2Me
C6H5
C6H5Se
+
1
C6H5
Se
A
360
83
79:21
6.32
5.64
C6H5Se
CO2Me
3a
2a
2
3
4
C6H5
C6H5
C6H5
Se
Se
Se
2a + 3a
2a + 3a
2a + 3a
B
C
C
3
3
82
50
69
85:15
—
73:27
30
C5H11
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
C5H11
C6H5Se
+
5
C5H11
C5H11
C6H5
C6H5
C5H11
C5H11
C6H5
C6H5
C5H11
C5H11
Se
Se
Te
Te
Te
Te
S
A
B
A
B
A
B
A
B
C
B
240
6
69
62
73
73
50
52
74
61
50
55
87:13
84:16
98:2
6.17
6.72
6.61
6.09
5.85
5.48
5.90
5.89
5.39
5.14
C6H5Se
CO2Me
3b
2b
6
2b + 3b
C6H5
C6H5
+
7
300
3
C6H5Te
CO2Me
C6H5Te
3c
2c
8
2c + 3c
92:8
C5H11
C5H11
C6H5Te
+
9
600
10
90:10
83:17
88:12
76:24
83:17
83:17
C6H5Te
CO2Me
3d
2d
10
11
12
13
14
2d + 3d
C6H5
C6H5
+
360
10
C6H5S
CO2Me
C6H5S
3e
2e
S
2e + 3e
C5H11
C6H5S
2f + 3f
C5H11
C6H5S
+
S
240
CO2Me
3f
2f
S
11
a Method A: the experiments were performed at room temperature. Method B: the experiments were performed at 662 W. Method C: the reaction
mixture was heated at 65 °C using an oil bath.11
b Yields of pure products isolated by column chromatography (AcOEt/hexanes) and identified by mass spectrometry, 1H, 13C NMR.2
c Determined by GC of the crude reaction mixture and confirmed after isolation of the individual isomers.

G. Perin et al. / Tetrahedron Letters 46 (2005) 1679–1682
1681
In order to check the possibility of intervention of spe-
cific (non-purely thermal) microwave effects, the reac-
tion with Al2O3/NaBH4 (30%) was also examined
using a pre-heated oil bath for the same time (3 min)
and final temperature (65 °C), as measured at the end
of exposure during the MW-assisted synthesis. How-
ever, the products were obtained only in poor yield (Ta-
ble 1, entry 3, Method C). It was observed that 30 min
were required to completely consume the starting mate-
rials, but the yield and selectivity of Z-2a decreased
(Table 1, entry 4). Although the energy transfer and
distribution in a domestic microwave oven is not con-
trolled as in professional chemistry oven, we found that
the microwave-assisted reactions are more efficient,
more convenient and cleaner.
was found that the hydrosulfurylation of methyl phenyl-
propiolate using 0.080 or 0.127 g of Al2O3/NaBH4 fur-
nished 2e, respectively, in 40% and 44% yield, after
stirring for 6 h at room temperature. However, the yield
could be increased to 74% by using 0.253 g of Al2O3/
NaBH4 (Table 1, entry 11, Method A). However, for
the hydrosulfurylation of the methyl pentylpropiolate,
it was observed that the reaction occurs only under heat-
ing or microwave and the respective b-phenylthio esters
2f and 3f were obtained only in modest yields (Table 1,
entries 13 and 14). In all the studied cases, the Z and E
isomers can be easily separated by column chromatogra-
phy (hexane/AcOEt as eluent).
In conclusion, several b-phenylchalcogeno esters could
be prepared from moderate to good yields by hydro-
chalcogenation of acetylenes under solid supported
(Al2O3/NaBH4) and solvent-free conditions at room
temperature, gently heating or under MW irradiation.
This improved, simple, fast, and clean protocol elimi-
nates the use of inert atmosphere and minimizes the
organic solvent and energy demands. Besides these
advantages, the reaction time could be reduced from
several hours to few minutes (when MW was employed),
under milder conditions and with non-aqueous work-
up.
Once the best conditions were established, the protocols
were extended to other methyl propiolate derivatives
and diphenyl chalcogenides. In all the studied cases,
the b-organylchalcogeno-a,b-unsaturated esters 2 and
3 were obtained from reasonable to good yields by using
the optimized conditions described above for the prepa-
ration of 2a (Table 1, entries 1 and 2). However, for the
synthesis of b-organyltelluro- and thio-a,b-unsaturated
esters (entries 7–14) a larger amount of the Al2O3/
NaBH4 system was necessary.
It was found that using 0.080 g of Al2O3/NaBH4, the
reaction of methyl phenylpropiolate with diphenyl ditel-
luride at room temperature (Method A), occurred
slowly (7 h), in 62% yield. However, the yield could be
increased (73%) and the time reduced (5 h) by using
0.127 g of the supported hydride (Table 1, entry 7).
The product was obtained almost exclusively with the
Z-configuration (Z:E ratio = 98:2), as detected by GC
Acknowledgements
The authors thank SCT-RS, FAPERGS, and CNPq for
financial support.
1
References and notes
and H NMR. Otherwise, the use of argon atmosphere
has displayed no significant increase in yield and selec-
tivity of the product. When the same reaction was per-
formed under MW irradiation (Method B), complete
conversion after irradiation for 3 min was observed
(Table 1, entry 8).
1. (a) Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani,
H. A. Synthesis 1997, 373; (b) Comasseto, J. V.; Barrien-
tos-Astigarraga, R. E. Aldrichim. Acta 2000, 33, 66; (c)
Harmata, M.; Jones, D. Tetrahedron Lett. 1996, 37, 783;
(d) Trost, B. M.; Ornstein, P. L. Tetrahedron Lett. 1981,
22, 3463; (e) Wenkert, E.; Ferreira, T. W. J. Chem. Soc.,
Chem. Commun. 1982, 840; (f) Bohlmann, F.; Bresinsky,
E. Chem. Ber. 1964, 97, 2109.
2. (a) Wadsworth, D. H.; Detty, M. R. J. Org. Chem. 1980,
45, 4611; (b) Detty, M. R.; Murray, B. J.; Smith, D. L.;
Zumbulyadis, N. J. Am. Chem. Soc. 1983, 105, 875; (c)
Detty, M. R.; Murray, B. J. J. Am. Chem. Soc. 1983, 105,
883; (d) Huang, X.; Zhao, C.-Q. Synth. Commun. 1997, 27,
3491; (e) Uemura, S.; Fukuzawa, S. Tetrahedron Lett.
1982, 23, 1181.
3. Truce, W. E.; Goldhamer, D. L. J. Am. Chem. Soc. 1959,
81, 5795.
4. Braga, A. L.; Alves, E. F.; Silveira, C. C.; Andrade, L. H.
Tetrahedron Lett. 2000, 41, 161.
5. Dabdoub, M. J.; Baroni, A. C. M.; Lenarda˜o, E. J.;
Gianeti, T. R.; Hurtado, G. R. Tetrahedron 2001, 57,
4271.
6. Zeni, G.; Formiga, H. B.; Comasseto, J. V. Tetrahedron
Lett. 2000, 41, 1311.
A search in literature2b showed that the hydrotelluration
of phenylpropiolate esters with methyl phenyltellurolate
anion in presence of EtOH/THF under inert atmosphere
yielded exclusively the methyl (Z)-3-phenyl-3-(phenyl-
telluro)propenoate 2c. On the other hand, by using
our solvent-less protocols (Methods A and B), we have
obtained two isomers (2c and 3c), with a large predom-
inance of the Z isomer 2c. Attempts to explain this
apparent losts of control in selectivity, we repeated the
described procedure using the solvent (THF/ethanol)
and argon atmosphere. Surprisingly and in contrast to
the reported data,2b 2c was obtained in 75% yield as
mixture of isomers (Z:E ratio = 96:4). The Z and E es-
ters were easily separable by column chromatography
(AcOEt/hexanes as eluent), with the more polar isomer
showing the E-configuration (3c), according to analysis
1
13
of GC and their H and C NMR spectra.11
7. Perin, G.; Jacob, R. G.; Botteselle, G. V.; Kublik, E. L.;
Lenarda˜o, E. J.; Cella, R.; Santos, P. C. S. J. Brazil. Chem.
Soc., submitted for publication.
8. Jacob, R. G.; Perin, G.; Loi, L. N.; Pinno, C. S.;
Lenarda˜o, E. J. Tetrahedron Lett. 2003, 44, 3605.
In order to exploit the generality of our method, we have
also carried out few experiments employing phenyl thio-
late anion, generated in situ from diphenyl disulfide. It

1682
G. Perin et al. / Tetrahedron Letters 46 (2005) 1679–1682
9. Jacob, R. G.; Perin, G.; Botteselle, G. V.; Lenarda˜o, E. J.
Tetrahedron Lett. 2003, 44, 6809.
NMR (200 MHz, CDCl3): d 7.38–7.43 (m, 2H); 6.88–7.14
(m, 8H); 6.72 (s, 1H); 3.86 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 168.4, 156.1, 140.9, 140.4 (2C), 133.6, 128.4,
128.0 (2C), 127.8, 127.5, 127.2, 120.9, 118.8, 113.9, 52.0.
(E)-3c (second eluted fraction): MS m/z (rel int.) 368 (M+,
40.0), 205 (100.0), 161 (87.0), 77 (85.0). 1H NMR
(200 MHz, CDCl3): d 7.83–7.88 (m, 2H); 7.25–7.43 (m,
8H); 5.90 (s, 1H); 3.46 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 140.9, 140.5, 140.4, 130.0, 129.5, 128.4, 128.1,
127.9, 127.2, 126.8, 122.6, 114.9, 51.0. Method B: the
aforementioned whole mixture was previously stirred for
1 min and then irradiated with microwave (used a domes-
tic Brastemp model VIP-38 Sensor Crisp operating at
2.45 GHz) at 662 W13 for 3.0–11.0 min (Table 1) and the
product extracted and purified according to described on
Method A. Method C: the procedure described on Method
A was followed and the reaction mixture was stirred under
heating at 65 °C (oil bath) for 3–240 min (Table 1).
12. Varma, R. S.; Saini, R. K. Tetrahedron Lett. 1997, 38,
4337.
10. The solid supported catalysts were prepared by the
following procedure: to a pestle mortar was added
alumina (0.7 g of Al2O3 90, 0.063–0.200 mm, Merck) and
NaBH4 (0.3 g) and the mixture was stirred for 1 min and
immediately used in the reaction.12
11. General procedure for the synthesis of b-phenylchalcogeno
esters 2a–f and 3a–f. Method A: a mixture of methyl
phenylpropiolate (0.160 g; 1 mmol) and diphenyl ditellu-
ride (0.207 g; 0.5 mmol) was added to aluminum oxide
10
impregnated with NaBH4 (0.127 g). The mixture was
stirred at room temperature. The reaction progress was
followed by TLC, and after 300 min (see Table 1) the
reaction vessel was cooled, and the product was filtered off
the aluminum oxide by washing with ethyl acetate
(10 mL). The solvent was evaporated under reduced
pressure and the residue was purified by column chroma-
tography over silica gel (SiO2) eluting with hexane/ethyl
acetate (98:2), yielding the esters 2c and 3c as a mixture of
Z and E isomers (0.269 g, 73%, Z:E ratio = 98:2). The
spectral data are in perfect agreement with those reported
in the literature.2 (Z)-2c (first eluted fraction): MS m/z (rel
13. The oven powers were determined as described by
Kingston, H. M. In Introduction to Microwave Sample
Preparation—Theory and Practice; Jassie, L. B., Ed.;
American Chemical Society: DC, 1988.
1
int.) 368 (M+, 58.0), 205 (45.0), 161 (100.0), 77 (31.0). H