title: Asymmetric synthesis of gem-difluoromethylenated dihydroxypyrrolizidines and indolizidines.
abstract: An asymmetric synthesis of gem-difluoromethylenated dihydroxypyrrolizidines and indolizidines is described. The fluoride-catalyzed nucleophilic addition of PhSCF(2)SiMe(3) (1) to chiral imides was achieved in satisfactory yields to provide mixtures of syn- and anti-isomers 6-9 with moderate to good diastereoselectivities. Reductive cleavage of the phenylsulfanyl group followed by intramolecular radical cyclization of the syn-isomers 6-9 occurred under refluxing conditions to afford the corresponding gem-difluoromethylenated 1-azabicyclic compounds 10-13 in moderate yields as a separable mixture of cis- and trans-isomers. The cis-isomers of compounds 10 and 12 and trans-13 were readily transformed to gem-difluoromethylenated dihydroxypyrrolizidines 20 and 27 and indolizidine 28, respectively, by reductive cleavage of the hydroxyl group and organometallic addition followed by hydrogenolysis.
authors.affiliation: Center of Excellence for Innovation in Chemistry (PERCH-CIC) and Department of Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
authors.forename: Watcharaporn
authors.initials: W
authors.lastname: Thaharn
authors.forename: Teerawut
authors.initials: T
authors.lastname: Bootwicha
authors.forename: Darunee
authors.initials: D
authors.lastname: Soorukram
authors.forename: Chutima
authors.initials: C
authors.lastname: Kuhakarn
authors.forename: Samran
authors.initials: S
authors.lastname: Prabpai
authors.forename: Palangpon
authors.initials: P
authors.lastname: Kongsaeree
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.forename: Vichai
authors.initials: V
authors.lastname: Reutrakul
authors.forename: Manat
authors.initials: M
authors.lastname: Pohmakotr
mesh_terms: D000478:Alkylation; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D054836:Indolizidines / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D053961:Azabicyclo Compounds; D054836:Indolizidines; D011759:Pyrrolidines