Stereoselective synthesis of (Z)-α-organothiovinyltosylates and their application in the synthesis of highly functionalized vinylic sulfides

Article abstract of DOI:10.1055/s-2001-11406

Thioacetylenes 1 afford, upon treatment with p-toluenesulfonic acid in dichloromethane, (O,S)-ketene acetals 2 which can act as useful α-(organothio)vinyl carbocation equivalents, opening a novel route to functionalized vinylic sulfides.

Full text of DOI:10.1055/s-2001-11406

LETTER
371
Stereoselective Synthesis of (Z)- -Organothiovinyltosylates and their
Application in the Synthesis of Highly Functionalized Vinylic Sulfides
Antonio L. Braga,* Daniel J. Emmerich, Claudio C. Silveira, Tales L. C. Martins, Oscar E. D. Rodrigues
a Departamento de Química, Universidade Federal de Santa Maria, Br-97105-900, Santa Maria, RS, Brazil
Received 6 January 2001
Table Preparation of -(organothio)vinyl p-toluenesulfonates 2
Abstract: Thioacetylenes 1 afford, upon treatment with p-toluene-
sulfonic acid in dichloromethane, (O,S)-ketene acetals 2 which can
act as useful -(organothio)vinyl carbocation equivalents, opening
a novel route to functionalized vinylic sulfides.
Key words: (O,S)-ketene acetals, carbocation equivalents, regiose-
lective, addition, vinylsulfides
Thioacetylenes are useful synthetic intermediates having
been applied, for example, as precursors of vinylic sulfide
by a reduction reaction,1 to generate (S,Si)-ketene acetals
on reaction with triethylsilane,2 as building block for , -
unsaturated thioimidates,3 or for functionalized -thiolac-
tams.4 Recently, we found that thiol esters 4 are conve-
niently prepared by reacting thioaceylenes 1 with p-
toluenesulfonic acid in the presence of silica (Scheme 1).5
In that work we postulated that this reaction should in-
volve -(organothio)vinyl p-toluenesulfonates 2 or triflu-
oracetate 3 as intermediates.
Scheme 1
aAll products gave correct elemental analyses C 0.29; H 0.28 and
exhibit spectral properties (1H and 13C NMR and IR) according with
the assigned structures.
We felt that this reaction could be exploited in the synthe-
sis of stereodefined trisubstituted [O,S]-ketene acetals,
which may also be considered as alkenes. As part of our
continuing interest in the preparation and synthetic appli-
cations of thioacetylenes5,6 and functionalized vinylic
chalcogenides,7 we present here a convenient method for
the stereoselective synthesis of trisubstituted vinylic sul-
fides via (1-organothiovinyl) p-toluenesulfonates 2 (thio-
vinyl tosylates).
bDeterminated by 1H NMR
In all cases studied, the only regioisomer obtained was
that shown in Scheme 1. This result can be rationalized
through the stabilization of the intermediate carbocation
by the -sulfur atom.
The assignment of the stereochemistry of the trisubstitut-
ed vinylic sulfides by 1H NMR was not trivial. NOE ex-
periments with mixtures of isomers were attempted, but
the vinylic signals were not sufficiently separated to give
conclusive results. Thus, initially a reasonable assumption
was made that the reaction proceeds with a similar stereo-
selectivity as the corresponding ones of organoselenium
compounds.9 Finally, however, the structure of 2b was
clearly established by a X-ray diffraction study.10 These
results confirm that the reaction of p-TsOH with thio-
acetylenes is both regiospecific and stereoselective in the
The thiovinyl tosylates 2 are obtained by addition of p-tol-
uenesulfonic acid to a dichloromethane solution of thio-
acetylenes 1.
The reaction described above is performed by simply mix-
ing all reagents at 0 °C to give the expected thiovinyl to-
sylates in good yields and high stereoselectivity (Table).8
The only or major diastereoisomers were the (Z)-thiovinyl
tosylates 2, sometimes slightly contaminated with the cor-
responding thiol ester 4.
Synlett 2001 No. 3, 371–373 ISSN 0936-5214 © Thieme Stuttgart · New York

372
A. L. Braga et al.
LETTER
Scheme 2
References and Notes
(1) Isobe, M.; Nishizawa, S.; Hosokawa, S.; Nishikawa, T. J.
Chem. Soc., Chem. Commun. 1998, 2665.
(2) Isobe, M.; Nishizawa, R; Nishikawa, T.; Yoza, K.
Tetrahedron Lett. 1999, 40, 6927.
(3) Ishitani, H.; Nagayama, S.; Kobayashi, S. J. Org. Chem. 1996,
61, 1902.
(4) Föster, W-R.; Isecke, R.; Spanka, C.; Schaumann, E.
Synthesis 1997, 942.
(5) Braga, A. L.; Rodrigues, O. E. D.; de Avila, E.; Silveira, C. C.
Tetrahedron Lett. 1998, 39, 3395.
(6) (a) Braga, A. L.; Reckziegel, A.; Menezes, P. H.; Silveira, C.
C. Tetrahedron Lett. 1993, 34, 8041. (b) Braga, A. L.;
Reckziegel, A.; Menezes, P. H.; Stefani, H. A. Tetrahedron
Lett. 1993, 34, 393.
(7) Braga, A. L.; Zeni, G.; Andrade, L. H.; Silveira, C. C. Synlett
1997, 595. (b) Braga, A. L.; Zeni, G.; Andrade, L. H.; Silveira,
C. C.; Stefani, H. A. Synthesis 1998, 39.
(8) General Procedure for the reaction of thioacetylenes with
p-TsOH:
Figure The ORTEP view of the (Z)-thiovinyl tosylates 2b
To a solution of thioacetylenes (1.0 mmol) in methylene
chloride (6 mL) was added p-TsOH (1.5 mmol) at 0 °C. The
reaction mixture was stirred for the time and the temperature
indicated in the Table. The reaction mixture was filtered
through an Al2O3 and K2CO3 column and the solvent was
evaporated. The residue was purified by horizontal
destillation.
sense of a cis additon, indicating that the hydrogen and the
tosylate group are added to the same side of the double
bond (Figure).
Selected spectral and analytical data for 2: (1H NMR were
taken at 200 MHz in CDCl3): 2a IR (neat, cm-1) 3015, 2910,
1680, 1590, 1450, 1370, 1185, 1010; 1H NMR 7.87 (d, 2H,
8.6), 7.39-7.26 (m, 7H), 6.52 (s, 1H), 2.42 (s, 3H), 2.21 (s,
3H); 13C NMR (50 MHz) 144.5, 142.9, 132.1, 131.9, 128.8,
128.5, 127.0, 126.3, 125.2, 124.9, 21.2, 14.0.
An attractive feature of the thiovinyl tosylates obtained is
that they contain the easily manipulable and differencia-
ble organothio- and tosyl group at the vinylic position and
both have value as synthetic handles for further transfor-
mations. Thus, reaction of the thiovinyl tosylate 2b with
cyanocuprate in the presence of catalytic amounts of
Pd(PPh3)2Cl2, results in the trisubstituted vinylic sulfide 5
(Scheme 2),11 which may also be considered as alkenes on
reaction with organometallic compounds.12 On the other
hand, reaction of 2a with magnesium bromide afforded
the thiovinyl bromide 6 in good yield.13 In these cases the
substitution takes place with retention of configuration.
2d: IR (neat, cm-1) 3025, 1585, 1470, 1440, 1370, 1165,
1000; 1H NMR Isomer A: 7.60 (d, 2H, 8.3), 7.31-6.94 (m,
7H), 6.03 (t, 1H, 7.9), 2.31 (s, 3H), 2.25-2.07 (m, 2H), 1.52-
1.03 (m, 6H), 0.81 (t, 3H, 6.7); Isomer B: 7.60 (d, 2H, 8.3),
7.31-6.94 (m, 7H), 5.99 (t, 1H, 7.7), 2.31 (s, 3H), 2.25-2.07
(m, 2H), 1.52-1.03 (m, 6H), 0.81 (t, 3H, 6.7); 13C NMR (50
MHz) 143.9, 139.6, 133.0, 132.4, 131.3, 128.4, 128.1, 127.8,
127.3, 125.8, 30.0, 27.6, 27.3, 21.3, 20.5, 12.8.
2e: IR (neat, cm-1) 3462, 2926, 2016, 1633, 1596, 1455,
1372, 1178, 1009; 1H NMR Isomer A: 7.86 (d, 2H, 8.7),
7.32 (d, 2H, 8.7), 5.65 (t, 1H, 7.0), 3.71-3.59 (m, 4H), 3.09 (d,
2H, 6.7), 2.42 (s, 3H), 2.38-2.14 (m, 4H), 2.04 (s, 3H); Isomer
B: 7.86 (d, 2H, 8.7), 7.32 (d, 2H, 8.7), 5.59 (t, 1H, 6.7), 3.71-
3.59 (m, 4H), 3.09 (d, 2H, 6.7), 2.42 (s, 3H), 2.38-2.14 (m,
4H), 2.04 (s, 3H); 13C NMR (50 MHz) 145.8, 144.8, 129.1,
127.8, 123.1, 121.9, 66.2, 54.1, 52.6, 21.0, 15.4.
(9) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A.
Tetrahedron 1995, 51, 4691.
Additionally, reaction of thiovinyl tosylates with terminal
alkynes in the presence of Pd(II), result in a coupling re-
action to produce profitable chalcogenoenynes.14
Acknowledgement
The authors thank the following agencies for support: FAPERGS,
CNPq and GTZ (Germany). Prof. Ludger Wessjohann for discus-
sion and help with the manuscript. D. J. E. thanks CAPES for a Ma-
ster fellowship. Travel support through CAPES/DAAD-Probral
project is acknowledged.
(10) Braga, A. L.; Rodrigues, O. E. D.; Emmerich, D. J. Silveira,
C. C.; Hörner, M.; Vazquez-Lopez, E. J. Chem. Crystallogr.
1999, 29, 677.
Synlett 2001, No. 3, 371–373 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of (Z)- -Organothiovinyltosylates
373
(11) General Procedure for the reaction of compound 2b with
Ph2Cu(CN)Li2:
(12) Babudri, F.; Fiandanese, V.; Mazzone, L.; Naso, F.
Tetrahedron Lett. 1994, 35, 8847.
To a solution of the cyanocuprate, prepared under argon from
PhLi (6.5 mmol) and CuCN (3.5 mmol) in THF (20 mL) at
78 °C, Pd(PPh3)2Cl2 (0.1 mmol) and compound 2b (1 mmol)
were added. The mixture was stirred at 78 °C for a few
minutes and then allowed to slowly warm to 0 °C. Stirring was
continued for 3-5 h. The progress of the reaction was
monitored by TLC. The reaction mixture was poured into
aqueous ammonium chloride solution, extracted with
dichloromethane and the organic layer was dried over MgSO4.
The solvents were evaporated and the residue was purified by
flash silica-gel chromatography eluting with hexane, to give
the product 5. (1H NMR were taken at 200 MHz in CDCl3) 1H
NMR 7.73 7.56 (m, 4H), 7.43 6.91 (m, 12 H); 13C NMR
(50 MHz) 140.9, 136.7, 135.6, 135,2, 134.7, 132.3, 129.5,
129,1, 128.6, 128.1, 128.9, 127.8, 127.8, 125.8;
(13) General Procedure for the reaction of compound 2a with
MgBr2:
A mixture of the compound 2a (2.5 mmol) and magnesium
bromide (4 mmol) in ether (20 mL) was stirred for 1 h at room
temperature. The reaction mixture was poured into water,
extracted with ether and the organic layer was dried over
MgSO4. The solvents were evaporated and the residue was
purified by flash silica gel chromatography eluting with light
petroleum, to give the product 6. (1H NMR were taken at 200
MHz in CDCl3) 1H NMR 7.50 7.25 (m, 5H); 7.21 (s, 1H);
2.38 (s, 3H). Spectroscopic data were in good agreement with
the literature.7
(14) Braga, A. L.; Martins, T. L.; Silveira, C. C.; Rodrigues, O. E.
D.; Emmerich, D. J. Synlett, 2001, 369.
MS m/z (relative intensity): 288 (30), 211 (5), 178 (100), 167
(5), 152 (5), 121 (15), 77 (5).
Article Identifier:
1437-2096,E;2001,0,03,0371,0373,ftx,en;S06600ST.pdf
Synlett 2001, No. 3, 371–373 ISSN 0936-5214 © Thieme Stuttgart · New York