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

VK Aggarwal*, Remy Angelaud, Dominique Bihan, Paul Blackburn, Robin Fieldhouse, Silvia J Fonquerna, Gair D Ford, George Hynd, Elfyn Jones, Ray VH Jones, Philippe Jubault, Matthew J Palmer, Paul D Ratcliffe, Harry Adams

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

38 Citations (Scopus)

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 C-2 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 traps-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 traps-stilbene oxide again in generally good yield (9-92%) and with moderate enantioselectivity (20-77% ee). The range of C-2 symmetric chiral sulfide catalysts based on 5 and 6 membered rings gave traps-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.

Translated title of the contributionSynthesis and Evaluation of a broad range of chiral sulfides for asymmetric sulfur ylide epoxidation of aldehydes
Original languageEnglish
Pages (from-to)2604-2622
Number of pages19
JournalPerkin 1
Issue number20
DOIs
Publication statusPublished - 21 Oct 2001

Keywords

  • OPTICALLY-ACTIVE EPOXIDES
  • CINCHONA ALKALOIDS
  • CARBONYL-COMPOUNDS
  • TERTIARY ALCOHOLS
  • SULFONIUM YLIDES
  • REAGENTS
  • ENONES
  • ACIDS
  • POWERFUL
  • KETONES

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