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Issue 20, 2001
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Synthesis and evaluation of a broad range of chiral sulfides for asymmetric sulfur ylide epoxidation of aldehydes

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Abstract

We have recently developed a catalytic, sulfur ylide mediated process for converting aldehydes into epoxides using benzaldehyde tosylhydrazone sodium salt which decomposes to generate phenyldiazomethane in situ. Although chiral 1,3-oxathianes gave good yields and excellent diastereo- and enantio-control when phenyldiazomethane was employed, only low yields were obtained when using the simplified procedure employing benzaldehyde tosylhydrazone sodium salt. Thus, a range of more robust chiral sulfides based on thianes, thiolanes, and 1,4-oxathianes were designed to achieve high yield and high enantioselectivity. The sulfides all possessed the following features: conformationally locked cyclic sulfide in which only one of the two lone pairs was accessible (not relevant for C2 symmetric substrates); ylide conformation and face selectivity was to be controlled through non-bonded steric interactions. Chirality was introduced from chiral pool materials (camphor, amino acids, lactic acid, limonene, carvone, glyceraldehyde), through enzyme mediated reduction/hydrolysis and through the use of chiral reagents (hydroboration). The sulfide catalysts were tested in the reaction between benzaldehyde tosylhydrazone salt and benzaldehyde to give trans-stilbene oxide. The range of chiral sulfide catalysts derived from camphor gave trans-stilbene oxide in generally good yield (23–95%) and with moderate enantioselectivity (40–76% ee). The range of novel chiral thianes and 1,4-oxathianes gave trans-stilbene oxide again in generally good yield (9–92%) and with moderate enantioselectivity (20–77% ee). The range of C2 symmetric chiral sulfide catalysts based on 5 and 6 membered rings gave trans-stilbene oxide in moderate yield (10–78%) and with variable enantioselectivity (8–87% ee). In none of the cases could high enantioselectivity and high yield be achieved simultaneously. Analysis of the results led us to the conclusion that the moderate enantioselectivity was a result of poor control in the ylide conformation and this led to the design of completely rigid [2.2.1] bicyclic sulfides which finally gave high enantioselectivity and high yield in the epoxidation process.

Graphical abstract: Synthesis and evaluation of a broad range of chiral sulfides for asymmetric sulfur ylide epoxidation of aldehydes

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Article information


Submitted
20 Jun 2001
Accepted
06 Aug 2001
First published
24 Sep 2001

J. Chem. Soc., Perkin Trans. 1, 2001, 2604-2622
Article type
Paper

Synthesis and evaluation of a broad range of chiral sulfides for asymmetric sulfur ylide epoxidation of aldehydes

V. K. Aggarwal, R. Angelaud, D. Bihan, P. Blackburn, R. Fieldhouse, S. J. Fonquerna, G. D. Ford, G. Hynd, E. Jones, R. V. H. Jones, P. Jubault, M. J. Palmer, P. D. Ratcliffe and H. Adams, J. Chem. Soc., Perkin Trans. 1, 2001, 2604
DOI: 10.1039/B105416N

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