Synthesis of chalcogenol esters from chalcogenoacetylenes

Article abstract of DOI:10.1016/S0040-4020(01)00200-9

Thiol and selenol esters were conveniently prepared in good yields by reacting chalcogenoacetylenes with trifluoroacetic acid in dichloromethane in the presence of silica.

Full text of DOI:10.1016/S0040-4020(01)00200-9

TETRAHEDRON
Pergamon
Tetrahedron 57 32001) 3297±3300
Synthesis of chalcogenol esters from chalcogenoacetylenes
Antonio L. Braga,p Tales L. C. Martins, Claudio C. Silveira and Oscar E. D. Rodrigues
Â
Departamento de Quõmica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
Received 5 July 2000; accepted 14 February 2001
AbstractÐThiol and selenol esters were conveniently prepared in good yields by reacting chalcogenoacetylenes with tri¯uoroacetic acid in
dichloromethane in the presence of silica. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
their derivatives or addition to nitriles).8 In this context, we
have shown that chalcogenol esters can be prepared by the
reaction of bis-3organochalcogeno)mercurials with acid
chlorides in the presence of tetrabutylammonium halides
as catalyst in good yields.9 Additionally, we found that
hydrolysis of thioacetylenes with acid in the presence of
silica gel leads to thiol esters in good yields 3Scheme 1).10
Thiol and selenol esters are important intermediates in
organic synthesis. They have been used as precursors of
acyl radicals,1 as mild acyl transfer reagents,2 as inter-
mediates in the synthesis of ketones3 and for asymmetric
aldol reactions.4 Recently, applications of this functional
group have expanded into the synthesis of proteins by
chemical ligation of benzyl thiol esters5 as well as substrates
to undergo facile and ef®cient radical decarbonylation in the
synthesis of 31)-geissoschizine.6
In this paper, we give a full account of our efforts toward the
synthesis of chalcogenol esters by means of the hydrolysis
of chalcogenoacetylenes.
In spite of the growing interest in new organic transfor-
mations of these compounds, preparative methods available
for their synthesis are still limited, with few exceptions,7 to
those based on conventional methodology 3i.e. formal
substitution at the carbonyl carbon of carboxylic acids and
2. Results and discussion
The study of the reaction of 1-3methylthio)-2-phenylethyne
1a and its selenium analog 2a with various acids was
undertaken 3Table 1). To study the ef®ciency of the acid
on the hydrolysis of 1a and 2a, dichloromethane was the
solvent of choice. The ®rst experiments were performed
with several acids 3Table 1). From these, tri¯uoroacetic
acid 3TFA) proved to be the most effective acid for the
hydrolysis of both chalcogenoacetylenes, providing the
Scheme 1.
Table 1. Chalcogenol esters 3a and 4a formation in various acids
Chalcogenoacetylenes
1a and 2a
Chalcogenol esters
3a and 4a
Acid
Time 3h)
YˆS
Yielda 3%)
YˆS
86
YˆSe
48
YˆSe
92
TFA
2
p-TsOH
ClSO3H
HClO4
HCl
107086
6
14096
15
140140 ±
88
56
8070
96
85
48
8040
AcOH
5
a
Refer to isolated yields by column chromatography.
Keywords: selenol esters; selenoacetylenes; thiol esters; thioacetylenes; chalcogenol esters; hydrolysis.
Corresponding author. Tel.: 111-55-55-220-8761; fax: 111-55-55-220-8031; e-mail: albraga@quimica.ufsm.br
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020301)00200-9

3298
A. L. Braga et al. / Tetrahedron 57 ,2001) 3297±3300
Scheme 2.
corresponding chalcogenol ester in very good yields. For
thioacetylenes, both TFA and p-TsOH promoted the
hydrolysis with the same ef®ciency. With other acids,
such as ClSO3H, HClO4, or HCl, 3a and 4a were obtained
in lower yields. In acetic acid, no reaction was observed for
the thioacetylene 3a and very low yields for the seleno-
acetylene 4a.
like 6, were observed to react by a similar path upon the
addition of p-TsOH to selenoacetylenes.12
The reactions described here are performed very easily by
simply mixing all reagents at 408C. The chalcogenol esters
are obtained in good yields 3Table 2). The most evident
difference between sulfur and selenium analogs was their
hydrolysis reaction time. We have observed that the rate of
hydrolysis to prepare selenol esters is very slow compared to
the sulfur counterparts. In fact, we observe by NMR experi-
ments that the ®rst step 3addition of the acid to the chalco-
genoacetylenes) have comparable rates. But the rate of the
second step 3hydrolysis to the chalcogenol esters) is slower
in the case of the selenium analogs. At present, we do not
have an explanation for this difference.
We also examined the behavior of other solvent systems
3DMF, chloroform, benzene, ether, THF, 1,2-dichloro-
ethane) under the same experimental conditions. Dichloro-
methane was the only one to promote the hydrolysis
ef®ciently. Also, the reaction did not proceed satisfactorily
in the absence of silica with its natural water content. The
use of additional amounts of water neither improve the
yields nor increase the rates of the reactions.
In this way, several types of chalcogenol esters were
obtained and a good chemoselectivity was observed in
some cases. For example, in the case of compounds 1h
and 2h, it was not necessary to protect the hydroxyl
group. In all cases studied, only the regioisomer shown in
Scheme 2 was obtained. This result can be rationalized in
terms of a carbocation stabilization by the chalcogen atom.13
This procedure is especially useful since the starting
chalcogenoacetylenes are readily available by various
ef®cient methods.14
The reactions can be monitored by NMR and the two stages
of the process 3Scheme 2) can be observed. For example, for
1-3methylthio)-2-phenylethyne 1a,11 within 10min of the
addition of p-TsOH, no methyl signal attributable by
NMR to the starting alkynyl sul®de was observed [expected
signal at d 3CDCl3) 2.33], but a new signal appeared at d
6.49 as a singlet and a weak signal at d 3.79 as a singlet. We
assign the former to the vinylic sul®de 5 and the latter to
thiol ester 3a. The signal due to 3a gradually increases in
intensity at the expense of the signals representing the
vinylic sul®de 5. Analogous compounds with selenium,
3. Conclusions
Table 2. Synthesis of chalcogenol esters by reaction of chalcogeno-
acetylenes with TFA 3according to Scheme 1)
The present procedure nicely complements other methods,
offering several advantages such as the greater availability
of the starting materials, compatibility with various func-
tional groups, and avoiding the use of the very toxic
reagents such as heavy metal thiolates and selenolates or
phenyl dichlorophosphate. Most importantly, the isolation
of pure material is easily achieved.
Chalcogenol ester
YR
Time 3h)
Yielda 3%)
3a
4a
3b
4b
3c
4c
3d
SCH3
2
48
15
64
2086
72
96
86
92
80
88
SeCH3
SPh
SePh
SCH2Cl
SeCH2Cl
SBu-t
82
81
4. Experimental
3e
3f
4d
SCH3
SPh
SeCH3
52
49
54
90
80
86
4.1. General information
3g
4g
SPh
SeCH3
25
48
85
86
IR spectra of neat compounds were obtained using a
Perkin±Elmer 1310IR spectrophotometer and Bruker IFS
28; peaks are reported as nmax in cm21. Microanalyses were
1
performed on Vario EL and Perkin±Elmer CHN 2400. H
3h
4h
SCH3
SeCH3
2060
12
and 13C NMR spectra were recorded with Bruker DPX-200
3200 MHz) or DPX-400 3400 MHz) spectrometers; chemi-
cal shifts are reported in ppm using tetramethylsilane as an
internal standard and CDCl3 as solvent. Mass spectra were
obtained using CG-MS HP 5090±5890 and INCOS-50
Finigan 3IQ-USP). Melting points were determined on a
Reichert Thermovar apparatus. Boiling points are uncor-
rected, determined on a BuÈchi GKR-503Kugelrohrofen).
Puri®cation of products by column chromatography and
54
3i
4i
SCH3
SeCH3
16
54
85
65
4j
16
65
a
Refer to isolated yields by column chromatography.

A. L. Braga et al. / Tetrahedron 57 ,2001) 3297±3300
3299
the hydrolysis reactions were performed using Merck Silica
Gel-603230±400mesh).
0.3 mmHg; IR 3neat) 3062, 3029, 2924, 1711, 1495, 1453,
1206, 1175, 1032, 968, 700, 560 cm21 1H NMR d
;
3200 MHz, CDCl3): 7.37±7.25 3m, 5H), 4.87 3s, 2H), 3.89
3s, 2H); 13C NMR d 350MHz, CDCl 3): 197.3, 131.7, 130.2,
128.8, 128.2, 53.6, 35.9. Anal. calcd for C9H9OSeCl: C,
43.66; H, 3.66. Found: C, 43.11; H, 3.36.
4.2. Synthesis of the chalcogenol esters 3 and 4: general
procedure
Typical procedure for thiol ester 3a: To a round ¯ask was
added 1-3methylthio)-2-phenylethyne 1a 30.148 g; 1 mmol),
5 mL of dichloromethane, p-TsOH 30.19 g; 1.1 mmol) and
1 g of silica. The resulting suspension was heated at 408C.
After 10h, 5.0mL of dichoromethane was added and the
silica removed by ®ltration. The solvent was removed and
the residue was puri®ed by column chromatography over
silica eluting with hexane.
4.2.7. S-Methyl thiohexanoate 3d. Bp 40±458C/
0.5 mmHg; IR 3neat) 2954, 2927, 2858, 1693, 1465 cm21
;
1H NMR d 3200 MHz, CDCl3): 2.55 3t, Jˆ7.0Hz, 2H), 2.29
3s, 3H), 1.66 3qui, Jˆ7.0Hz, 2H), 1.34±1.303m, 4H), 0.89
3t, Jˆ7.0Hz, 3H); 13C NMR d 350MHz, CDCl 3): 199.9,
43.8, 31.0, 25.3, 22.2, 13.7, 11.4. Anal. calcd for
C7H14OS: C, 57.49; H, 9.65. Found: C, 57.11; H, 9.69.
4.2.8. S-Phenyl thiohexanoate 3e. Bp 95±1008C/
Typical procedure for selenol ester 4a: To a round ¯ask
was added 1-3methylseleno)-2-phenylethyne 2a 30.195 g;
1.0mmol), 5 mL of dichloromethane, TFA 30.171 g; 1.5
mmol) and 1 g of silica. The resulting suspension was
heated at 408C. After 48 h, dichloromethane was added
and the silica removed by ®ltration. The solvent was
removed and the residue was puri®ed by column chroma-
tography over silica eluting with hexane.
1.1 mmHg; IR 3neat) 2956, 2929, 2859, 1708, 1477 cm21
;
1H NMR d 3200 MHz, CDCl3): 7.39±7.34 3m, 5H), 2.63 3t,
Jˆ7.0Hz, 2H), 1.69 3qui, Jˆ7.0Hz, 2H), 1.35±1.32 3m,
4H), 0.89 3t, Jˆ7.0Hz, 3H); 13C NMR d 350MHz,
CDCl3): 197.3, 134.3, 129.2, 129.1, 127.8, 43.5, 30.8,
24.9, 22.0, 13.7. Anal. calcd for C12H16OS: C, 69.19; H,
7.74. Found: C, 68.81; H, 7.54.
4.2.9. Se-Methyl hexaneselenoate 4d. Bp 858C/0.5 mmHg;
4.2.1. S-Methyl phenylthioacetate 3a. Bp 508C/
1
IR 3neat) 2937, 2926, 2870, 1710, 1458 cm21; H NMR d
1
0.9 mmHg; IR 3neat) 3010, 2910, 1670 cm21; H NMR d
3200 MHz, CDCl3): 2.62 3t, Jˆ7.2 Hz, 2H), 2.21 3s, 2H),
1.66 3m, 2H), 1.37±1.29 3m, 4H), 0.91 3t, Jˆ6.4 Hz, 3H);
13C NMR d 350MHz, CDCl 3): 201.9, 47.9, 30.9, 25.2, 22.3,
13.8, 4.7; MS m/z 194 312%), 123, 99, 71, 57 3100%). Anal.
calcd for C7H14OSe: C, 43.53; H, 7.31. Found: C, 43.18; H,
6.98.
3200 MHz, CDCl3): 7.32±7.24 3m, 5H), 3.803s, 2H), 2.25
3s, 3H); 13C NMR d 350MHz, CDCl 3): 197.7, 133.6, 129.5,
128.6, 127.3, 50.3, 11.8; MS m/z 166 313%), 138, 119, 91
3100%). Anal. calcd for C9H10OS: C, 65.03; H, 6.06. Found:
C, 64.91; H, 6.12.
4.2.2. Se-Methyl phenylselenoacetate 4a. Bp 658C/
0.5 mmHg; IR 3neat) 3027, 2931, 1699, 1599, 1493 cm21
;
4.2.10. S-Phenyl 2--1-cyclohexenyl)thioacetate 3f. IR
1
3neat) 3058, 2929, 1710, 1581, 1476 cm21; H NMR d
1H NMR d 3200 MHz, CDCl3): 7.28±7.17 3m, 5H), 3.76 3s,
2H), 2.103s, 3H); 13C NMR d 350MHz, CDCl 3): 200.2,
133.1, 129.9, 128.6, 127.6, 53.9, 5.2; MS m/z 214 325%),
119, 91 3100%).
3200 MHz, CDCl3): 7.41±7.33 3m, 5H), 5.45 3m, 1H),
3.23 3s, 2H), 1.83±1.79 3m, 4H), 1.48±1.33 3m, 4H); 13C
NMR d 350MHz, CDCl 3): 195.7, 134.3, 130.6, 129.0,
128.9, 128.1, 127.6, 52.4, 28.6, 25.3, 22.6, 21.7. Anal.
calcd for C14H16OS: C, 72.37; H, 6.94. Found: C, 72.02;
H, 6.71.
4.2.3. S-Phenyl phenylthioacetate 3b. Mp 628C; IR 3neat)
3023, 1685, 1493, 1453 cm21 1H NMR d 3200 MHz,
;
CDCl3): 7.46±7.26 3m, 10H), 3.88 3s, 2H); 13C NMR d
350MHz, CDCl 3): 195.1, 134.3, 133.2, 129.5, 129.3,
129.0, 128.4, 128.0, 127.4, 50.0. Anal. calcd for
C14H12OS: C, 73.65; H, 5.30. Found: C, 73.91; H, 5.39.
4.2.11. Se-Methyl 2--1-cyclohexenyl)selenoacetate 4g. Bp
558C/0.5 mmHg; IR 3neat) 3391, 2931, 1704, 1435,
1
1268 cm21; H NMR d 3200 MHz, CDCl3): 5.69 3m, 1H),
3.16 3s, 2H), 2.17 3s, 3H), 2.06±1.90 3m, 4H), 1.66±1.56 3m,
4H); 13C NMR d 350MHz, CDCl 3): 201.3, 130.6, 128.6,
56.3, 28.5, 25.5, 22.7, 21.7, 4.7; MS m/z 218 35%), 123,
95, 67, 55 3100%). Anal. calcd for C9H14OSe: C, 49.78;
H, 6.50. Found: C, 49.25; H, 6.41.
4.2.4. Se-Phenyl phenylselenoacetate 4b. Mp 42.5±
42.78C; IR 3KBr) 3059, 3029, 2875, 1709, 1579, 1494,
1
1476, 1438 cm21; H NMR d 3200 MHz, CDCl3): 7.40±
7.15 3m, 10H), 3.83 3s, 2H); 13C NMR d 350MHz,
CDCl3): 198.6, 135.7, 132.6, 130.0, 129.2, 128.8, 128.7,
127.8, 126.6, 53.6; MS m/z 276 310%), 157, 118, 91
3100%). Anal. calcd for C14H12OSe: C, 61.10; H, 4.39.
Found: C, 61.17; H, 4.01.
4.2.12. S-Methyl 3-hydroxythiopropanoate 3h. Bp 458C/
0.2 mmHg; IR 3neat) 3380, 2930, 1681, 1412, 1049 cm21
;
1H NMR d 3200 MHz, CDCl3): 3.83 3t, Jˆ5.6 Hz, 2H),
2.84 3t, Jˆ5.6 Hz, 2H), 2.54 3s, 1H), 2.35 3s, 3H); 13C
NMR d 350MHz, CDCl 3): 199.5, 58.7, 45.9, 11.5. Anal.
calcd for C4H8O2S: C, 39.98; H, 6.71. Found: C, 39.55; H,
6.33.
4.2.5. S-Chloromethyl phenylthioacetate 3c. IR 3neat)
1
3028, 1702, 1495, 1454, 1235, 1180, 1016 cm21; H NMR
d 3200 MHz, CDCl3): 7.34±7.23 3m, 5H), 4.83 3s, 2H), 3.86
3s, 2H); 13C NMR d 350MHz, CDCl 3): 193.8, 132.24,
129.7, 128.7, 127.8, 50.2, 41.8. Anal. calcd for C9H9OSCl:
C, 53.87; H, 4.52. Found: C, 54.12; H, 4.66.
4.2.13. Se-Methyl 3-hydroxypropaneselenoate 4h. Bp
558C/0.3 mmHg; IR 3neat) 3400, 2930, 1697 cm21 1H
;
NMR d 3200 MHz, CDCl3): 3.83 3t, Jˆ5.6 Hz, 2H), 2.84
3t, Jˆ5.6 Hz, 2H), 2.18 3s, 3H), 2.14 3s, 1H); 13C NMR d
4.2.6. Se-Chloromethyl phenylselenoacetate 4c. Bp 688C/

3300
A. L. Braga et al. / Tetrahedron 57 ,2001) 3297±3300
3. 3a) McGarvey, G. J.; Williams, J. M.; Hiner, R. N.; Matsubara,
Y.; Oh, T. J. Am. Chem. Soc. 1986, 108, 4943. 3b) Conrow, R.;
Portoghese, P. J. Org. Chem. 1986, 51, 938. 3c) Back, T. G.;
Kerr, R. G. Tetrahedron 1982, 38, 3241. 3d) Back, T. G.; Kerr,
R. G. Tetrahedron 1985, 41, 4759.
350MHz, CDCl 3): 201.6, 58.5, 50.2, 5.0; MS m/z 168 35%),
93, 73 3100%). Anal. calcd for C4H8O2Se: C, 28.76; H, 4.83.
Found: C, 28.40; H, 4.51.
4.2.14. S-Methyl 3,3-dimethylthiobutanoate 3i. Bp 25±
308C/0.5 mmHg; IR 3neat) 2957, 2927, 2869, 1690, 1464,
4. 3a) Mukaiyama, T.; Uchiro, H.; Shiina, I.; Kobayashi, S.
Chem. Lett. 1990, 1019. 3b) Kobayashi, S.; Uchiro, H.;
Fujishita, Y.; Shiina, I.; Mukaiyama, T. J. Am. Chem. Soc.
1991, 113, 4247. 3c) Suh, K.-H.; Choo, D.-J. Tetrahedron
Lett. 1995, 36, 6109.
1
1366 cm21; H NMR d 3200 MHz, CDCl3): 2.403s, 2H),
2.24 3s, 3H), 1.03s, 9H); 13C NMR d 350MHz, CDCl 3):
197.4, 56.0, 30.8, 29.0, 11.0. Anal. calcd for C7H14OS: C,
57.49; H, 9.65. Found: C, 57.07; H, 9.45.
5. Baca, M.; Muir, T.; Schnolzer, M.; Kent, S. J. Am. Chem. Soc.
1995, 117, 1881.
4.2.15. Se-Methyl 3,3-dimethylbutaneselenoate 4i. Bp
458C/0.5 mmHg; IR 3neat) 2956, 2907, 1710, 1465, 1366,
6. Martin, S. F.; Chen, K. X.; Eary, C. T. Org. Lett. 1999, 1, 79.
7. 3a) Barrett, A. G. M.; Graboski, G. G.; Russell, M. A. J. Org.
Chem. 1986, 51, 1012. 3b) Uemura, S.; Takahashi, H.; Ohe,
K.; Sugita, N. J. Organomet. Chem. 1989, 361, 63.
3c) Khumtaveeporn, K.; Alper, H. J. Org. Chem. 1994, 59,
1414. 3d) Inoue, T.; Takanobu, T.; Kambe, A.; Ogawa, A.;
Ryu, I.; Sonoda, N. J. Org. Chem. 1994, 59, 5824.
3e) Maeda, H.; Fujiwara, S.; Nishiyama, A.; Shin-Ike, T.;
Kambe, N.; Sonoda, N. Synthesis 1997, 342.
1
1003 cm21; H NMR d 3400 MHz, CDCl3): 2.53 3s, 2H),
2.203s, 3H), 1.04 3s, 9H); 13C NMR d 3100 MHz, CDCl3):
200.4, 60.6, 31.5, 29.6, 5.3. Anal. calcd for C7H14OSe: C,
43.53; H, 7.31. Found: C, 43.11; H, 6.91.
4.2.16. Se-Methyl 3-methoxypropaneselenoate 4j. IR
3neat) 2930, 2885, 2815, 1701, 1450, 1385, 1115 cm21
;
1H NMR d 3200 MHz, CDCl3): 3.68 3t, Jˆ6.2 Hz, 2H),
3.35 3s, 3H), 2.88 3t, Jˆ6.2 Hz, 2H), 2.23 3s, 3H); 13C
NMR d 350MHz, CDCl 3): 199.7, 67.7, 58.7, 47.8, 4.8;
MS m/z 182 35%), 94, 87, 59 3100%). Anal. calcd for
C5H10O2Se: C, 33.16; H, 5.57. Found: C, 32.79; H, 5.12.
8. 3a) Spessard, G. O.; Masamune, S.; Chan, W. K. Org. Synth.
Coll. Vol. VII 1990, 81 3see also page 87). 3b) Adamczyk, M.;
Fishpaugh, J. R. Tetrahedron Lett. 1996, 37, 4305. 3c) Kanda,
T.; Nakaida, S.; Murai, T. Chem. Lett. 1995, 87.
9. Silveira, C. C.; Braga, A. L.; Larghi, E. L. Organometallics
1999, 18, 5183.
Acknowledgements
10. Braga, A. L.; Rodrigues, O. E. D.; de Avila, E.; Silveira, C. C.
Tetrahedron Lett. 1998, 39, 3395.
The authors thank the following agencies for support:
CAPES, GTZ 3Germany) and Professor Ludger Wessjohann
for revision of the manuscript. T. L. C. Martins thanks
CAPES for a Master Fellowship.
11. In this speci®c case only one vinylic isomer was observed.
See: Braga, A. L.; Emerich, D. J.; Silveira, C. C.; Martins, T.
C.; Rodrigues, O. E. D. Synlett, in press.
12. Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A.
Tetrahedron 1995, 51, 4691.
13. 3a) Hermans, B.; Hevesi, L. Reactions of selenium-
stabilized carbocations. In Organoselenium Chemistry;
Back, T. G., Ed.; Elsevier: New York, 1999; pp. 153±172.
3b) Comasseto, J. V.; Menezes, P. H.; Stefani, H. A.; Zeni,
G.; Braga, A. L. Tetrahedron 1996, 52, 9687. 3c) Braga, A. L.;
Marchi, M. I.; Andrade, L. H.; Silveira, C. C. Synth. Commun.
2000, 30, 407.
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