Stereoselective synthesis of α-phenylchalcogeno-α,β-unsaturated esters

Article abstract of DOI:10.1016/S0040-4039(02)00477-X

Ethyl α-phenylchalcogeno α,β-unsaturated esters were prepared in a stereoselective manner by the reaction of ethyl propiolates with organocuprates, followed by the reaction with the appropriate electrophilic organosulfur, organoselenium or organotellurium source.

Full text of DOI:10.1016/S0040-4039(02)00477-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3395–3397
Stereoselective synthesis of a-phenylchalcogeno-a,b-unsaturated
esters†
Claudio C. Silveira,* Antonio L. Braga and Robson B. Guerra
Departamento de Qu´ımica, Universidade Federal de Santa Maria, Caixa Postal 5001-97105-900, Santa Maria, RS, Brazil
Received 12 February 2002; revised 7 March 2002; accepted 8 March 2002
Abstract—Ethyl a-phenylchalcogeno a,b-unsaturated esters were prepared in a stereoselective manner by the reaction of ethyl
propiolates with organocuprates, followed by the reaction with the appropriate electrophilic organosulfur, organoselenium or
organotellurium source. © 2002 Elsevier Science Ltd. All rights reserved.
Considerable effort has been devoted to the develop-
ment of new synthetic methods to access vinylic chalco-
genides, specially the functionalized ones. These
methods have been the subject of several review articles
published in recent years.1 Recently we described con-
venient methods for the synthesis of a-phenylseleno-
a,b-unsaturated esters,2 a potentially very useful class
of vinylic selenides,3,4 scarcely described in the litera-
ture.4,5 Most of these methods furnishes the desired
compounds as a mixture of E/Z isomers. Due to our
interest in new methodologies for the synthesis of
vinylic chalcogenides,6 we intend to develop a stereose-
lective method to access a-phenylseleno-a,b-unsatu-
rated esters. Our attention was focused to use the
known regio- and stereospecific conjugated addition of
organocuprates to a,b-acetylenic esters to generate cis
1,4 adduct,7 which could be trapped by a convenient
organoselenium source. By this method, along with the
(Scheme 1). The reaction mixture was then slowly
warmed to room temperature, followed by a normal
work-up and column chromatography purification.11
1H NMR analysis of the crude and the purified material
indicated that the reaction occurred with total retention
of configuration, the Z-isomer being detected as the
only product in 73% yield (entry 2, Table 1).
The method was then extended to other ethyl propio-
late derivatives, such as pentyl 1b and phenyl propiolate
1c, reacting with sulfur, selenium and tellurium elec-
trophiles. From our study, a very easy and general
entry to the tetrasubstituted vinylic derivatives, not
accessible by most of the other methods described, can
now be disponible.2,4,5
On the reaction of n-BuCu(CN)Li with ethyl pentylpro-
piolate 1b and phenylpropiolate 1c, the same behavior
as for ethyl propiolate was observed, and the reaction
followed the same pattern, furnishing the desired prod-
ucts 2e–j in moderate to good yields (entries 5–10,
Table 1). Otherwise, on the addition of MeCu(CN)Li to
pentylpropiolate, it was necessary to increase the tem-
perature from –78 to –25°C for 1 h to observe the
addition of the cuprate to the triple bond. A strict
control of reaction temperature was necessary to avoid
the formation of isomers. After cooling back to –78°C,
followed by the addition of the electrophile, the reac-
tion was slowly warmed to rt, and the desired products
were isolated in moderate yields (entries 11–13). Again,
organoselenium
derivatives,
the
corresponding
organosulfur8 and organotellurium9 could be accessible
equally, by the employment of the adequate elec-
trophilic organochalcogen source.
We started our experiments by reacting ethyl propiolate
1a with lithium butylcyano cuprate in THF, at −78°C,
following a procedure that we had described some years
ago.10 After 1 h at this temperature, HMPA and a THF
solution of benzeneselenenyl bromide were added
Keywords: selenium and compounds; sulfur compounds; tellurium
and componds; esters; copper and compounds; vinylic chalcogenides.
* Corresponding author. Tel./fax: +55 55 220 8754; e-mail:
silveira@quimica.ufsm.br
†
Preliminary results were presented at the 8th International Confer-
ence on the Selenium and Tellurium Compounds, Sa˜o Pedro, SP,
Brasil, 6–11, August 2000.
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00477-X

3396
C. C. Sil6eira et al. / Tetrahedron Letters 43 (2002) 3395–3397
Table 1. a-Phenylchalcogeno-a,b-unsaturated esters pre-
pared
spectra and by the comparison with authentic samples
prepared by other methods, recently described by us.2
In the case of reactions with ethyl propiolate, only the
Z-isomer could be detected. In the case of reaction with
ethyl pentylpropiolate and ethyl phenylpropiolate, only
1
one isomer could be detected by GC and H and 13C
NMR analysis.
As we discussed above, by our method the correspond-
ing vinylic sulfides could be easily accessible by reaction
of the intermediate vinylic cuprate with S-phenylben-
zenethio sulfonate. The functionalized vinylic sulfides
were isolated in good to fair yields (entries 1, 5, 8, 11,
and 14, Table 1). Worth of mention it is that the use of
other eletrophilic sources of PhS group, such as PhSCl
and PhSSPh, was less effective, furnishing the desired
products in very low yields. By the use of benzenetel-
lurenyl iodide as the electrophile, the corresponding
vinylic tellurides could be prepared in quite good yields
(40–70%; entries 3, 7, 10, 13, 16 and 17; Table 1). To
our knowledge, these a-phenyltellurium a,b-unsatu-
rated esters are very scarcely described; the only
method being the aryltellurenamides addition to
dimethylacetylene dicarboxylate.9 Methods for the
preparation and synthetic applications of b-phenyltel-
lurium a,b-unsaturated esters have been already
described.12
Entry
R
R1
Product
Y
Yield (%)a
1
2
3
4
5
6
7
8
H
H
H
H
n-C4H9
n-C4H9
n-C4H9
s-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
CH3
CH3
CH3
CH3
CH3
CH3
s-C4H9
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
S
44
73
52
60
59
81
58
41
43
40
41
51
Se
Te
Se
S
Se
Te
S
Se
Te
S
Se
Te
S
C6H5
C6H5
C6H5
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C6H5
C6H5
C6H5
C6H5
9
10
11
12
13
14
15
16
17
42 (49)b
40
Se
Te
Te
55 (66)b
70
45
a Isolated yields after column chromatography. All new compounds
were fully characterized.
In conclusion, the reaction of propiolate esters with
organocopper(I) reagents, followed by addition of elec-
trophilic phenylchalcogeno reagents, affords efficiently
a variety of a-phenylchalcogeno a,b-unsaturated esters
with high regio- and stereoselectivity. The products are
tri- or tetrasubstituted alkenes in which two syntheti-
cally versatile groups are linked to the same sp2-
hybridized carbon atom.
b Isolated yield using cuprate:propiolate:electrophile=1.5:1.5:1.0.
the formation of only one isomer, as analyzed by GC,
1H and 13C NMR, was observed.
A similar low reactivity was observed on the addition
of the MeCu(CN)Li to ethyl phenylpropiolate, being
necessary to warm the reaction mixture from –78 to
–25°C or higher temperature, before cooling back to
–78°C to add the electrophile. As a consequence of this
lower reactivity, the formation of the isomers could not
be avoided. All three products 2n–p (entries 14–16,
Table 1) were isolated as E/Z-mixture of isomers, with
ratios from 1:1 (entries 14 and 16) to 2:1 (entry 15). In
the same way, it was experimentally observed that
yields were improved when 1.5 equiv. of propiolate
were used instead of equimolar amounts of propiolate
and electrophile (entries 13 and 15, Table 1).
Acknowledgements
The authors thank the following agencies for financial
support: FAPERGS, CAPES and CNPq.
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We also carried out a few experiments with the cuprate
derived from sec-butyllithium, to verify the generality
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the same conditions as described to n-BuCu(CN)Li. On
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desired product 2d was isolated in 60% yield (entry 4).
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confirmed by the analysis of the 1H and 13C NMR

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1 h. HMPA (2 mL) and ben-
zenechalcogenyl halide (2 mmol) were added and the
reaction mixture was left to reach room temperature in 4
h. The reaction was poured into water and an aqueous
ammonium chloride solution and extracted with ethyl
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was purified by silica gel column chromatography.
Selected spectral data: Ethyl (Z)-2-phenylthio-2-hep-
tenoate (entry 1): IR (film): 1714.2 cm−1 (CꢀO); lH (200
MHz; CDCl3) 0.90 (t, 3H, J=7.0 Hz); 1.07 (t, 3H, J=7.0
Hz); 1.25–1.60 (m, 4H); 2.52 (q, 2H, J=7.1 Hz); 4.09 (q,
2H, J=7.0 Hz); 7.0–7.5 (m, 6H). 13C NMR (50 MHz;
CDCl3) lC 13.73; 13.79; 22.35; 30.41 (2C); 61.32; 125.83;
126.56; 128.01; 128.75; 135.97; 153.13; 165.30; m/z 264
(M+); 218 (48); 189 (42); 147 (51); 81 (65); 29 (100%).
Ethyl (Z)-2-phenylseleno-2-heptenoate (entry 2): IR
(film): 1714.8 cm−1 (CꢀO); lH (200 MHz; CDCl3) 0.89 (t,
3H, J=7.0 Hz); 0.91 (t, 3H, J=7.0 Hz); 1.0–1.6 (m, 4H);
2.48 (q, 2H, J=7.2 Hz); 4.09 (q, 2H, J=7.0 Hz); 7.0–7.5
(m, 6H). 13C NMR (50 MHz; CDCl3) lC 13.70; 13.80;
22.29; 30.36; 32.35; 61.35; 124.65; 126.53; 128.92; 130.06;
131.08; 152.95; 165.72. Ethyl (E)-3-phenyl-2-phenyltel-
luro-2-heptenoate (entry 7): IR (film): 1715.4 cm−1 (CꢀO);
lH (200 MHz; CDCl3) 0.68 (t, 3H, J=7.1 Hz); 0.75–1.00
(m, 3H); 1.10–1.40 (m, 4H); 2.73 (m, 2H); 3.52 (q, 2H,
J=7.1 Hz); 7.00–7.50 (m, 8H); 7.75–7.90 (m, 2H). 13C
NMR (50 MHz; CDCl3) lC 13.25; 13.67; 22.24; 29.92;
41.91; 60.26; 109.85; 113.27; 127.35 (2C); 127.81; 128.05;
128.95; 138.94; 140.71; 153.51; 168.63; m/z 438 (M+2);
436 (10); 205 (10); 184 (10); 128 (9); 115 (24); 77 (33); 28
(100%).
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11. General experimental procedure: To a round bottom
flask under argon was added CuCN (0.268 g; 3.0 mmol)