Lewis acid mediated selective chalcogenalkylation of silyl enol ethers with [O,S]-acetals

Article abstract of DOI:10.1055/s-1999-3429

Silyl enol ethers of ketones were selectively alkylated with [O,S]- acetals mediated by Lewis acid in a Mukaiyama type Aldol reaction. The products were β-alkoxy- and/or β-sulfanyl carbonyl compounds depending on the catalyst employed.

Full text of DOI:10.1055/s-1999-3429

562
SHORT PAPER
Lewis Acid Mediated Selective Chalcogenalkylation of Silyl Enol Ethers with
[O,S]-Acetals
Antonio L. Braga,*a Luciano Dornelles,a Claudio C. Silveira,a Ludger A. Wessjohannb§
a Departamento de Química, Universidade Federal de Santa Maria, Br97105–900, Santa Maria, RS, Brazil
Fax +55(55)2208031; E-mail: albraga@quimica.ufsm.br
b Institut für Organische Chemie, Ludwig-Maximilians-Universität München, Karlstr. 23, D-80333 München, Germany
Received 13 July 1998; revised 22 October 1998
pounds were purified by column chromatography. The
Abstract: Silyl enol ethers of ketones were selectively alkylated
products and yields from the reaction of various acetals
with [O,S]-acetals mediated by Lewis acid in a Mukaiyama type Al-
with three silyl enol ethers are reported in Table 1.
dol reaction. The products were b-alkoxy- and/ or b-sulfanyl carbo-
nyl compounds depending on the catalyst employed.
Key words: Lewis acid, monothioacetal, silyl enol ether, b-chalco-
geno ketone
[O,S]-acetals are compounds which are synthetically
useful1 when applied, for example, to electrooxidative
carbon–carbon bond formation,2 as precursors of free rad-
icals in alkylation reactions,3 to generate a-chalcoge-
nalkyllithiums on reaction with butyllithiums,4 and as
precursors of a-sulfanyl or a-oxocarbenium ions which
react with allyl and allenyltin compounds.5 They can be
hydrolysed to carbonyl compounds under mild condi-
tions.4 Recently we described a general and efficient
methodology for the preparation of these compounds by
addition of thiols to enol ethers.6 In view of our continued
interest in the organochalcogen stabilized carbocations
applied to the stereoespecific formation of new carbon–
carbon bonds, we undertook a systematic investigation of
the reaction between [O,S] acetals and silyl enol ethers,7
i.e. a Mukaiyama type crossed aldol reaction,8 in order to
obtain either the b-alkoxy- or the b-sulfanylalkyl ketones.
A recent report by Hu on the reaction of a-acetoxy
sulfides9 prompted us to disclose our results.
Scheme 1
Initially, a comparative study on the reaction of silyl enol
ethers 1 with [O,S]-acetals 2 in dichloromethane in the
presence of Lewis acids was undertaken (Scheme 1). The
Substitution of the SnCl4 or TiCl4 by other Lewis acids
such as AlCl3, BF3◊Et2O, ZnBr2 and ZnCl2 leads to the for-
formation of b-alkoxy ketones 3 and b-sulfanyl ketones 4
proceeded as expected and it was observed that either
mation of a complex mixture of products containing only
product can be formed depending on the Lewis acid em-
a small amount of the expected b-chalcageno ketones
without selectivity.
ployed. SnCl4 leads preferentially to b-alkoxy carbonyl
compounds whereas b-sulfanyl carbonyl compounds are
We observed that the reaction of silyl enol ether of ke-
tones with higher substituted [O,S]-acetals 2a–b give b-
chalcogeno ketones in good yields and that the reaction of
the same silyl enol ethers with unsubstituted [O,S]-acetal
2c, gives poor yields of the desired products. The good
yields obtained in the reaction with secondary and tertiary
alkylating agents can be attributed to the additional stabi-
lization of the intermediate cation exerted by the methyl
groups.
preferentially produced by the use of TiCl4. This result
can be rationalized in terms of a preferential complexation
of the Lewis acid towards either chalcogen atom in the
mixed acetals,5, 10 based on the difference in the hardness
(softness) of these atoms.
The alkylation reaction was carried out by adding a slight
excess of Lewis acid to equimolar amounts of the silyl
enol ether and the [O,S]-acetal dissolved in dichlo-
romethane at low temperature under argon. After stirring
for 1.5 h at low temperature, the reaction was worked up
in the usual way and the b-chalcogeno carbonyl com-
Some of the b-chalcogeno ketones 3 and 4 are not very
stable compounds and were identified by infrared and 1H
Synthesis 1999, No. 4, 562–564 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Lewis Acid Mediated Selective Chalcogenalkylation
563
(9:1) as eluent. Yields and physical data are shown in Tables 1 and
2.
NMR spectroscopy immediately after the isolation and
purification (Table 2).11
In conclusion, [O,S]-acetals 2 have proved to be syntheti-
cally useful precursors of a-sulfanyl or a-oxycarbenium
ions, which can be generated selectively by the appropri-
ate choice of the Lewis acid.
Acknowledgement
The authors thank the following agencies for support: FAPERGS,
FAPESP, CNPq, PADCT (BR) and GTZ (Germany). L.D. thanks
CAPES for a Doctoral fellowship. Travel support through CAPES/
DAAD-Probal project is acknowledged.
1H NMR and 13C NMR spectra were recorded using a Bruker AC 80
or Bruker AC 200 spectrometer; chemical shifts are reported in ppm
using CDCl3 as solvent and TMS as internal standard. IR spectra
were obtained on a Perkin-Elmer 599-B and Bomem MB-Series
spectrophotometer, microanalyses were performed on Heraeus Var-
io EL and Perkin Elmer CHN 2400. Bps were uncorrected, deter-
mined on a Büchi GKR-50 apparatus. Mps were determined on
Reichert Thermovar apparatus. Analytical TLC was performed on
0.25 mm precoated silica gel plates. Flash chromatography was car-
ried out with 230–400 mesh silica gel (E. Merck).
References
§
new address: Vrije Universiteit Amsterdam, De Boelelaan
1083, NL-1081 HV, Amsterdam, The Netherlands
(1) Wessjohann, L. A.; Sinks U. J. Prakt. Chem. 1998, 340, 189
(2) Yoshida, J.; Sugawara, M.; Kise, N. Tetrahedron Lett. 1996,
37, 3157.
(3) Keck, G. E.; Kordik, C. P. Tetrahedron Lett. 1993, 34, 6875.
(4) Otera, J. Synthesis 1988, 95.
Mukaiyama type Aldol Reaction of Silyl Enol Ethers with [O,S]-
Acetals; General Procedure:
Trost, B. M.; Miller, C. H. J. Am. Chem. Soc. 1975, 97, 7182.
Coldham, I.; Warren, S. J. Chem. Soc., Perkin Trans. 1 1992,
2303.
To a mixture of [O,S]-acetals (1.0 mmol) and the silyl enol ether
(2.0 mmol) in CH2Cl2 (2 mL) at the temperature indicated in Table
1 was added dropwise TiCl4 (2.0 mmol). The mixture was stirred for
1.5 h at the same temperature and then allowed to reach r.t. A sat.
NaHCO3 was added and the mixture was extracted with CH2Cl2 (3
x 10 mL) and the organic layer was worked up in the usual way. The
residue was chromatographed on silica gel using hexane/EtOAc
(5) Sato, T.; Okura, S.; Otera, J.; Nozaki, H. Tetrahedron Lett.
1987, 50, 6299.
(6) Braga, A. L.; Silveira, C. C.; Dornelles, L., Zeni, G.; Galarza,
F. A. D.; Wessjohann, L. A. Synth. Commun. 1995, 25, 3155.
(7) Similar reactions using others chalcogen-stabilized carbenium
ions have been described: [oxygen] Murata, S.; Suzuki, M.;
Noyori, R. Tetrahedron 1988, 44, 4259.*
Table 1 b-Chalcogeno Ketones 3 and 4 Prepared According to Scheme 1
Silyl Enol Ethers
1
[O, S] acetals
2
Lewis
Acid
Products
[yields (%)]
SnCl4
TiCl4
SnCl4
3a
3a
3b
3b
3c
(62)
(4)
(73)
(3)
–
4a
4a
4b
4b
4c
(2)
(86)
(9)
a
TiCl4
(70)
(35)
TiCl4
SnCl4
TiCl4
SnCl4
3d
3d
3e
3e
(71)
(12)
(70)
(3)
4d
4d
4e
4e
(3)
(68)
(13)
(58)
2a
2b
a
TiCl4
2c
2a
TiCl4
SnCl4
3f
–
4f
(30)
(3)
3g
(60)
4g
TiCl4
SnCl4
3g
3h
3h
3i
(4)
(80)
(4)
–
4g
4h
4h
4i
(65)
(2)
2b
2c
a
TiCl4
(82)
(27)
TiCl4
a The reaction was performed at –23oC
Synthesis 1999, No. 4, 562–564 ISSN 0039-7881 © Thieme Stuttgart · New York

564
A. L. Braga et al.
SHORT PAPER
Table 2 Characteristic Spectroscopic Data of Products 3 and 4
Prod-
uct
IR (Neat)
1H NMR (CDCl3)
d, J (Hz)
13C NMR (CDCl3)
d
u (cm-1)
3a
2941,1716,
1101, 754
3.18 ( s, 3H), 2.83 (q, 1H, J = 7.0), 2.48 (q, 1H, J = 7.0), 1.17 (s, 3H),
1.13 (s, 3H), 1.04 (d, 3H, J = 6.8), 0.99 (t, 3H, J = 7.0)
214.6, 53.7, 48.9, 37.8, 22.8,
21.0, 12.6, 7.7
4a
2972, 1710,
1436, 757
7.22-7.71 (m, 5H), 2.70 (q, 2H, J = 7.1), 2.43 (q, 1H, J = 7.1), 1.47
(s, 3H), 1.27 (s, 3H), 1.24 (d, 3H, J = 7.0), 0.97 (t, 3H, J = 7.1)
213.8, 137.4, 131.5, 128.8,
128.4, 52.6, 37.9, 27.4, 24.6,
13.4, 7.4
3b
4b
2974, 1713,
1099, 974
3.12-3.72 (m, 3H), 2.23-2.82 (m, 3H), 1.19 (t, 3H, J = 7.0), 1.10
(d, 3H, J = 6.4), 1.08 (t, 3H, J = 7.2), 1.04 (d, 3H, J = 7.0)
212.1, 63.4, 61.2, 53.3, 35.9,
19.9, 14.7, 12.5, 7.5
2973, 1712,
1438, 746
7.14-7.62 (m, 5H), 3.22-3.71 (m, 1H), 2.22-2.91 (m, 3H), 1.24
(t, 3H, J = 6.9), 1.07 (d, 3H, J = 6.7), 0.96 (d, 3H, J = 6.6)
213.2, 132.8, 132.2, 128.8,
127.0, 50.9, 46.3, 35.9, 20.2,
12.5, 7.5
4c
3d
4d
2973, 1712,
1457, 740
7.13-7.54 (m, 5H), 3.24 (d, 2H, J = 6.8), 2.21-2.92 (m, 3H), 1.15
(d, 3H, J = 6.7), 1.01 (t, 3H, J = 7.4)
213.2, 130.7, 129.5, 128.9,
126.5, 45.4, 36.4, 35.1, 16.7, 7.5
2943, 1717,
1184, 753
3.16 (s, 3H), 1.71-2.41 (m, 7H), 1.32 (s, 3H), 1.18 (s, 3H)
217.1, 56.1, 49.1, 40.1, 25.6,
23.9, 22.0, 20.1
2933, 1716,
1476, 691
7.22-7.63 (m, 5H), 1.62-2.45 (m, 7H), 1.48 (s, 3H), 1.22 (s, 3H)
217.8, 128.8, 128.3, 127.7,
127.2, 57.0, 40.3, 38.4, 29.2,
25.1, 19.2
3e
4e
4f
2923, 1728,
1148, 744
3.23-4.01(m, 3H), 1.85-2.32 (m, 7H), 1.24 (d, 1.5H, J = 6.1), 1.13
(t, 3H, J = 6.9), 1.05 (d, 1.5H, J = 6.8)
219.3, 66.7, 56.8, 53.3, 41.6,
25.5, 23.5, 19.9, 15.8
2966, 1733,
1477, 740
7.13-7.54 (m, 5H), 3.51-4.01 (m, 1H), 1.66-2.53 (m, 7H), 1.38
(d, 1.5H, J = 6.8), 1.15 (d, 1.5H, J = 6.8)
217.4, 135.3, 131.5, 127.7,
127.5, 59.5, 38.1, 31.2
2962, 1737,
1480, 740
7.13-7.54 (m, 5H), 3.49 (d, 1H, J = 3.1), 3.38 (d, 1H, J = 3.1), 1,65-
2.82 (m, 7H)
216.2, 135.1, 130.7, 128.9,
125.0, 59.5, 38.1, 29.6, 23.3,
14.0
3g
4g
2929, 1720,
1216, 754
3.15 (s, 3H), 1.54-2.66 (m, 9H), 1.29 (s, 3H), 1.20 (s, 3H)
207.1, 56.8, 54.5, 44.1, 35.7,
26.8, 25.9, 23.4, 21.3
2934, 1709,
1442, 761
7.13-7.54 (m, 5H), 1.53-2.45 (m, 9H), 1.37 (s, 3H), 1.34 (s, 3H)
210.4, 136.9, 131.3, 128.3,
126.8, 57.5, 43.6, 41.3, 30.2,
28.5, 27.5, 25.3, 23.3
3h
4h
2932, 1713,
1216, 756
3.23-3.91 (m, 3H), 1.62-2.42 (m, 9H), 1.36 (d, 1.5H, J = 5.4), 1.17
(t, 3H, J = 6.7), 1.16 (d, 1.5H, J = 6.4)
212.1, 73.1, 64.4, 55.3, 42.1,
27.9, 24.4, 18.4, 16.4, 15.2
2935, 1707,
1444, 744
7.22-7.61 (m, 5H), 3.52-4.01 (m, 1H), 1.55-2.61 (m, 9H), 1.31
(d, 1.5H, J = 6.8), 1.24 (d, 1.5H, J = 6.8)
210.8, 132.2, 131.5, 128.8,
126.7, 54.0, 43.5, 41.7, 27.4,
24.8, 16.9, 13.5
4i
2934, 1707,
1438, 740
7.13-7.54 (m, 5H), 3.21-3.71 (m, 2H), 1.43-2.42 (m, 9H)
211.8, 130.4, 129.2, 128.7,
126.2, 50.1, 41.7, 33.0, 27.6,
26.7, 24.7
Saraswathy, V. G.; Sankararaman, N. J. Chem. Soc., Perkin
Trans. 1 1996, 29.;
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Angew. Chem., Int. Ed. 1977, 16, 817.
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Chem. Lett. 1992, 819.
Mukaiyama, T.; Murakami, M. Synthesis 1987, 1043.
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Trans. 1 1998, 279.
[selenium]: Nsunda, K. M.; Hevesi, L. Tetrahedron Lett.
1984, 25, 4441.
Comasseto, J. V.; Silveira, C. C. Synth. Commun. 1986, 16,
1167.
(10) Hermans, B.; Hevesi, L. J. Org. Chem. 1995, 60, 6141.
(11) All compounds showed spectroscopic and analytical data
consistent with the assigned structures and in accordance with
the literature (cf. especially literature 7 marked with asterisk*).
Synthesis 1999, No. 4, 562–564 ISSN 0039-7881 © Thieme Stuttgart · New York