Practical and Highly Selective Sulfur Ylide-Mediated Asymmetric Epoxidations and Aziridinations Using a Cheap and Readily Available Chiral Sulfide: Extensive Studies To Map Out Scope, Limitations, and Rationalization of Diastereo- and Enantioselectivities

Ona Illa Soler, Mariam Namutebi, Chandreyee Saha, Mehrnoosh Ostovar, Chia-Chun Chen, Mairi F. Haddow, Sophie Nocquet-Thibault, Matteo Lusi, Eoghan M. McGarrigle*, Varinder K. Aggarwal

*Corresponding author for this work

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

74 Citations (Scopus)
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Abstract

The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, gamma-terpinene, and limonene in 61% yield. A mechanism involving radical intermediates for this reaction is proposed based on experimental evidence. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines is described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and alpha,beta-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. In epoxidations, the degree of reversibility in betaine formation dominates both the diastereoselectivity and the enantioselectivity. Appropriate tuning of reaction conditions based on understanding the reaction mechanism enables high selectivities to be obtained in most cases. In aziridinations, betaine formation is nonreversible with semistabilized ylides and diastereoselectivities are determined in the betaine forming step and are more variable as a result.

Original languageEnglish
Pages (from-to)11951-11966
Number of pages16
JournalJournal of the American Chemical Society
Volume135
Issue number32
Early online date31 Jul 2013
DOIs
Publication statusPublished - 14 Aug 2013

Keywords

  • IN-SITU GENERATION
  • PHASE-TRANSFER CONDITIONS
  • VINYL SULFONIUM SALTS
  • D-ERYTHRO-SPHINGOSINE
  • STEREOSELECTIVE-SYNTHESIS
  • GLYCIDIC AMIDES
  • N-SULFONYLIMINES
  • NITRIDOMANGANESE COMPLEX
  • STYRENE MONOOXYGENASE
  • THERMODYNAMIC CONTROL

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