New entries toward 3,3-difluoropiperidines

J Org Chem. 2008 Jul 18;73(14):5458-61. doi: 10.1021/jo800768q. Epub 2008 Jun 12.

Abstract

Difluoropiperidines attract considerable interest from organic and medicinal chemists, but their synthesis is often problematic. This paper describes a new synthetic pathway toward valuable 3,3-difluoropiperidines starting from suitable delta-chloro-alpha,alpha-difluoroimines. The latter imines can be synthesized via electrophilic fluorination of the corresponding delta-chloroimines using NFSI (N-fluorodibenzenesulfonimide) in acetonitrile. After hydride reduction of the imino bond and subsequent intramolecular substitution of the chloride atom, new 3,3-difluoropiperidines were obtained in good yields. In addition, this methodology was applied to establish the first synthesis of N-protected 3,3-difluoropipecolic acid, a new fluorinated amino acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorine Compounds / chemical synthesis*
  • Fluorine Compounds / chemistry
  • Molecular Structure
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry

Substances

  • Fluorine Compounds
  • Piperidines