New Entries toward 3,3-Difluoropiperidines

• DOI: 10.1021/jo800768q
• Publication Date: 2008-06-12T10:02:01Z
• Authors: Guido Verniest; Riccardo Surmont; Eva Van Hende; Arvid Deweweire; Frederik Deroose; Jan Willem Thuring; Norbert De Kimpe
• Keywords: Electrophilic substitution

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 suitable δ-chloro-α,α-difluoroimines. The latter imines can be synthesized via electrophilic fluorination of the corresponding δ-chloroimines using NFSI (N-fluorodibenzenesulfonimide) in acetonitrile. After hydride reduction imino bond subsequent intramolecular substitution chloride atom, were obtained good yields. In addition, this methodology was applied to establish first N-protected 3,3-difluoropipecolic acid, fluorinated amino acid.