Chemoselective and efficient oxidation of sulfides to sulfoxides mediated by trimethylsilyl chloride and superoxide via a trimethylsilylperoxy radical

Article abstract of DOI:10.1016/S0040-4039(00)00828-5

Chemoselective and efficient oxidation of various sulfides were mediated by Me₃SiCl and KO₂ in dry acetonitrile at -15°C to afford corresponding sulfoxides in excellent yields without any interference in the presence of ketone, olefin, ether and hydroxyl functionalities and without further oxidation to the sulfones. A trimethylsilylperoxy radical generated in situ from this new process is proposed. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00828-5

Tetrahedron Letters 41 (2000) 5233±5236
Chemoselective and ecient oxidation of sul®des to sulfoxides
mediated by trimethylsilyl chloride and superoxide via a
trimethylsilylperoxy radical
Yao-Jung Chen* and Yu-Ping Huang
Department of Chemistry, National Chung-Hsing University, Taichung, Taiwan 402, ROC
Received 12 April 2000; revised 15 May 2000; accepted 19 May 2000
Abstract
Chemoselective and ecient oxidation of various sul®des were mediated by Me SiCl and KO in dry
2
3
ꢀ
acetonitrile at ^15 C to a€ord corresponding sulfoxides in excellent yields without any interference in the
presence of ketone, ole®n, ether and hydroxyl functionalities and without further oxidation to the sulfones.
A trimethylsilylperoxy radical generated in situ from this new process is proposed. # 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: superoxide; trimethylsilyl chloride; trimethylsilylperoxy radical; oxidation.
^.
Superoxide anion radical (O ) is a reactive species easily generated in the body which can
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1
cause serious damage to living organisms. Recently, much e€ort has been made not only on its
2
biological toxicity but also on its application in organic synthesis. In general, the four basic types of
reactivities of superoxide have been documented as a base, an anion, a radical, and an electron-
3
transfer reagent. It also has been known that superoxide acts as a moderate reducing agent but a
4
very weak oxidizing agent. In the activation of oxidizing ability of superoxide, numerous studies
have been reported to activate superoxide through the reaction of various organic substrates with
superoxide to form a new peroxy intermediate that can act as a stronger oxidizing agent.5
Although some sul®nyl, sulfonyl and phosphorous peroxy intermediates have been generated
from the reaction of superoxide with each of the corresponding chlorides to testify their oxidizing
5
abilities towards various organic substrates, it is still of great interest to ®nd out more strong-
oxidizing agents, activated from superoxide, for use in organic synthesis. For instance, trialkyl-
silylperoxy radicals are likely to be good candidates for this purpose.
Trialkylsilylperoxy radicals have been prepared and studied by ESR spectroscopy by Howard's
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group. Their results indicate that the structure of these silylperoxy radicals resembles the structure
of alkylperoxy radicals and they exist in equilibrium with a tetroxide at temperature below
*
Corresponding author. Fax: +886-4-286-2547; e-mail: yjchen@dragon.nchu.edu.tw
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00828-5

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234
ꢀ
6a
2
33 K. Surprisingly, no further works dealing with their applications in organic synthesis were
reported. The reasons might be partly because the generation of silylperoxy radicals by photolysis
of trialkylsilane in an oxygen-saturated solvent containing di-tert-butyl peroxide must produce a
stronger oxidant of tert-butoxyl radical which might be expected to interfere the process of reac-
tion studied before the formations of peroxy radicals in the course of reaction.6a For practical
purposes, it is desirable to develop a new and ecient process for the preparation of these silyl-
peroxy radicals. In this report, we demonstrate that chemoselective and ecient oxidation of
various sul®des, bearing ketone, ole®n, ether and hydroxyl functionalities, were mediated by tri-
ꢀ
methylsilyl chloride 1 and superoxide in dry acetonitrile at ^15 C to give the corresponding sulfoxides
exclusively in excellent yields. The reaction pathway is proposed to undergo through trimethylsilyl-
peroxy radical 2 generated in situ from this new process.
The new process for the oxidation of sul®des is represented in Scheme 1 with the results sum-
marized in Table 1. In a general procedure (entry 1), a solution of Me SiCl (0.06 mL, 0.473
3
mmol) in dry acetonitrile (1 mL) was added slowly within 15 min to a heterogeneous solution of
KO (65 mg, 0.914 mmol) and methyl phenyl sul®de (0.05 mL, 0.426 mmol) in dry acetonitrile (3 mL)
2
ꢀ
at ^15 C with vigorous stirring under nitrogen. After stirring for 5 h at the same temperature, the
reaction mixture was quenched by addition of 1N HCl (3 mL) and ice (2 g), and then extracted
with ethyl acetate (3Â15 mL) at room temperature. The combined organic portions were washed
with water (15 mL) and brine (15 mL), dried over MgSO and evaporated under reduced pressure.
4
The crude product was puri®ed by preparative TLC or column chromatography using ethyl
acetate:hexane (2:1) as eluent to give methyl phenyl sulfoxide (55.3 mg, 93%). For a blank test,
the oxidation of methyl phenyl sul®de to the corresponding sulfoxide underwent extremely slowly
(98% of sul®de recovered) while the reaction was only treated with KO without Me SiCl under
the same reaction condition described above.
2 3
Scheme 1. The reaction pathway proposed for oxidation of sul®des mediated by trimethylsilyl chloride and superoxide
ꢀ
in acetonitrile at ^15 C
1
In all cases, only traceable amount of the sulfones were isolated or detected by H NMR
spectroscopy. Interestingly, the results indicate that silylperoxy radical 2, rapidly generated in situ
form Me SiCl and KO , is mild enough to allow the selective and high-yield oxidation of sul®des
3
2

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235
Table 1
Oxidation of sul®des to the corresponding sulfoxidesa
to sulfoxides at lower temperature without any interference in the presence of ketone, ole®n, ether
and hydroxyl functionalities and with no further oxidation to sulfones. It has been known that
oxidants commonly used for these reactions, such as m-chloroperoxybenzoic acid, hydrogen
7
peroxide, iodosyl benzene, sodium periodate, oxone et al., require higher reaction temperatures
than that needed by silylperoxy radical 2. It is also remarkable that silylperoxy radical 2 oxidized
sul®des to corresponding sulfoxides selectively in excellent yields as it has been known that a
major diculty encountered in the preparation of sulfoxides through oxidation of sul®des is the
overoxidation to sulfones.7
It has also been rationalized that the oxidation of sul®des to sulfoxides is found to be electro-
8
philic in contrast to the nucleophilic oxidation of sulfoxides to sulfones. Besides the selective
oxidation of sul®des to sulfoxides without further oxidation to sulfones, a competition oxidation
of methyl 4-acetyl-, 4-methoxy- and nonsubstituted-phenyl sul®des was carried out under the
same reaction condition described above for 1 h to give 4, 32 and 10% yields of the corresponding
sulfoxides, respectively. The results indicate that the sulfur atom of these sul®des bearing an
electron-donating group of 4-methoxy is oxidized more rapidly than that bearing an electron-
withdrawing group of 4-acetyl due to its more nucleophilic character. Based on results mentioned
above, silylperoxy radical 2 generated in situ from Me SiCl and KO performs more likely to be
3
2
electrophilic. It is noteworthy that the electrophilic oxidation of methyl phenyl sul®de to the corre-
sponding sulfoxide mediated by Me SiCl and KO was inhibited in the presence of 1,4-diaza-
3
2
9
bicyclo[2.2.2]octane (DBACO) which is known to be a radical scavenger agent. Certainly, the
result shows that a radical species must exist and play an important role in the course of the

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236
oxidation reaction. Although trimethylsilylperoxy radical 2 formed from Me SiCl and KO has
3
2
not yet been con®rmed in this study, it seems reasonable to propose that the strongly electrophilic
oxidant generated from this new process is most likely to be silylperoxy radical 2 owing to its
6
radical character as in the case of Howard's studies. However, an alternative mechanism involving
anion character 3 and silyl tetroxide 4 still cannot be ruled out.
In conclusion, we have demonstrated that silylperoxy radical 2, rapidly generated in situ from
Me SiCl and KO , performs a strongly electrophilic oxidizing ability to undergo the chemo-
3
2
selective and ecient oxidation of sul®des to corresponding sulfoxides in excellent yields without
any interference in the presence of ketone, ole®n, ether and hydroxyl functionalities and without
further oxidation to the sulfones under mild conditions. The con®rmation of 2 formed from this new
process and its applications used more widely in organic synthesis have been under investigations.
Acknowledgements
We gratefully acknowledge generous support from the National Science Council of the
Republic of China.
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