Synthesis of 5-amino- and 5-hydroxy-3,3-difluoropiperidinesElectronic supplementary information (ESI) available: Experimental procedures and spectroscopic data for compounds 5a, 6b-d, 8-11 and 13-16 are available. See DOI: 10.1039/c0ob00231c

Synthetic routes toward new 5-amino- and 5-hydroxy-3,3-difluoropiperidines, which are of high interest as building blocks in medicinal chemistry, are described. The key step involves the N -halosuccinimide-induced cyclization of 2,2-difluoro-4-pentenylamines toward 5-halo-3,3-difluoropiperidines, which were used to synthesize 5-amino-3,3-difluoropiperidine. In a second strategy, iodolactonization of 2,2-difluoro-4-pentenoic acid gave the corresponding γ-lactone, which was transformed into 5-hydroxy-3,3-difluoropiperidine. Synthetic routes toward new 5-amino- and 5-hydroxy-3,3-difluoropiperidines involving N -halosuccinimide-induced cyclization of 2,2-difluoro-4-pentenylamines and iodolactonization of 2,2-difluoro-4-pentenoic acid are described.