Enantioselective fluoride ring opening of aziridines enabled by cooperative Lewis acid catalysis

Julia A. Kalow, Abigail G. Doyle

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The enantioselective ring opening of aziridines using a latent source of HF is described. A combination of two Lewis acids, (salen)Co and an achiral Ti(IV) cocatalyst, provided optimal reactivity and enantioselectivity for the trans β-fluoroamine product. The use of a chelating aziridine protecting group was crucial. Acyclic and cyclic meso N-picolinamide aziridines underwent fluoride ring opening in up to 84% ee, and the kinetic resolution of a piperidine-derived aziridine was performed with krel=6.6. The picolinamide group may be readily removed without epimerization of the fluoroamine. Preliminary studies revealed a bimetallic mechanism wherein the chiral (salen)Co catalyst delivers the nucleophile and the Ti(IV) cocatalyst activates the aziridine.

Original languageEnglish (US)
Pages (from-to)5702-5709
Number of pages8
JournalTetrahedron
Volume69
Issue number27-28
DOIs
StatePublished - Jul 8 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Keywords

  • Asymmetric catalysis
  • Aziridine opening
  • Cooperative catalysis
  • Fluorination
  • β-Fluoroamine

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