Alpha- vs ortho-lithiation of N-alkylarylaziridines: probing the role of the nitrogen inversion process

J Org Chem. 2008 Dec 5;73(23):9214-20. doi: 10.1021/jo8016549.

Abstract

The lithiation reaction of monophenyl- and diphenylaziridines has been investigated in detail in an effort to understand why the former undergo exclusively or mainly ortho-lithiation while the latter are lithiated exclusively at the alpha-position. Evidence is reported that ruled out the possibility that the alpha-lithiation, observed for the diphenylaziridines, is the result of an ortho- to alpha-translocation phenomenon, thus substantiating a direct alpha-deprotonation process. The role of the aziridine nitrogen lone-pair has been considered: dynamics at the aziridine nitrogen as well as complex-induced proximity effects seem to be responsible for the observed regioselectivity in both monophenyl and diphenylaziridines. It turns out that, by tuning the reaction conditions for the lithiation of trans-1-alkyl-2-methyl-3-phenylaziridines, it is possible to generate with high regioselectivity alpha- and/or ortho-lithiated aziridines, which can be stereoselectively functionalized by electrophilic trapping. A regioselective ortho-functionalization of diphenylaziridines is made possible by halogen- or tin-lithium exchange and by deprotonation of bis-deuterated aziridines.

MeSH terms

  • Aziridines / chemistry*
  • Chemistry, Organic / methods*
  • Electrochemistry / methods
  • Gas Chromatography-Mass Spectrometry / methods
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Nitrogen / chemistry*
  • Temperature

Substances

  • Aziridines
  • Nitrogen