New entries toward 3,3-difluoropiperidines.
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.
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Guido
G
Verniest
Riccardo
R
Surmont
Eva
E
Van Hende
Arvid
A
Deweweire
Frederik
F
Deroose
Jan Willem
JW
Thuring
Norbert
N
De Kimpe
D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry
D017611:Fluorine Compounds; D010880:Piperidines