title: Applications and limitations of the I2-mediated carbamate annulation for the synthesis of piperidines: five- versus six-membered ring formation.
abstract: A protecting-group-free synthetic strategy for the synthesis of piperidines has been explored. Key in the synthesis is an I2-mediated carbamate annulation, which allows for the cyclization of hydroxy-substituted alkenylamines into piperidines, pyrrolidines, and furans. In this work, four chiral scaffolds were compared and contrasted, and it was observed that with both d-galactose and 2-deoxy-d-galactose as starting materials, the transformations into the piperidines 1-deoxygalactonorjirimycin (DGJ) and 4-epi-fagomine, respectively, could be achieved in few steps and good overall yields. When d-glucose was used as a starting material, only the furan product was formed, whereas the use of 2-deoxy-d-glucose resulted in reduced chemo- and stereoselectivity and the formation of four products. A mechanistic explanation for the formation of each annulation product could be provided, which has improved our understanding of the scope and limitations of the carbamate annulation for piperidine synthesis.
authors.affiliation: School of Chemical and Physical Sciences, Victoria University of Wellington , P.O. Box 600, Wellington, New Zealand.
authors.forename: Hilary M
authors.initials: HM
authors.lastname: Corkran
authors.forename: Stefan
authors.initials: S
authors.lastname: Munneke
authors.forename: Emma M
authors.initials: EM
authors.lastname: Dangerfield
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Stocker
authors.forename: Mattie S M
authors.initials: MS
authors.lastname: Timmer
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry*; D003500:Cyclization; D005643:Fucose / Q000737:chemistry*; D050112:Imino Pyranoses / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D002219:Carbamates; D050112:Imino Pyranoses; D010880:Piperidines; D017485:1-Deoxynojirimycin; D005643:Fucose; C105643:fagomine; C032727:piperidine; C090092:migalastat