Direct stereospecific synthesis of unprotected N-H and N-Me aziridines from olefins

Science. 2014 Jan 3;343(6166):61-5. doi: 10.1126/science.1245727.

Abstract

Despite the prevalence of the N-H aziridine motif in bioactive natural products and the clear advantages of this unprotected parent structure over N-protected derivatives as a synthetic building block, no practical methods have emerged for direct synthesis of this compound class from unfunctionalized olefins. Here, we present a mild, versatile method for the direct stereospecific conversion of structurally diverse mono-, di-, tri-, and tetrasubstituted olefins to N-H aziridines using O-(2,4-dinitrophenyl)hydroxylamine (DPH) via homogeneous rhodium catalysis with no external oxidants. This method is operationally simple (i.e., one-pot), scalable, and fast at ambient temperature, furnishing N-H aziridines in good-to-excellent yields. Likewise, N-alkyl aziridines are prepared from N-alkylated DPH derivatives. Quantum-mechanical calculations suggest a plausible Rh-nitrene pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Aziridines / chemical synthesis*
  • Biological Products / chemistry*
  • Catalysis
  • Hydrogen / chemistry
  • Hydroxylamines / chemistry*
  • Nitrogen / chemistry

Substances

  • Alkenes
  • Aziridines
  • Biological Products
  • Hydroxylamines
  • Hydrogen
  • O-(2,4-dinitrophenyl)hydroxylamine
  • Nitrogen