title: Divergent chemical synthesis of prolines bearing fluorinated one-carbon units at the 4-position via nucleophilic 5-endo-trig cyclizations.
abstract: N-[3-(Trifluoromethyl)homoallyl]sulfonamides, prepared via ring opening of (S)-glycidyl ethers or 2-aryloxiranes with 1-(trifluoromethyl)vinyllithium, underwent intramolecular addition or S(N)2'-type reaction in the normally disfavored 5-endo-trig fashion, leading to 2-substituted 4-(trifluoromethyl)- or 4-(difluoromethylene)pyrrolidines. Both alpha- and beta-face-selective hydrogenation of the 4-difluoromethylene group afforded syn- and anti-4-(difluoromethyl)pyrrolidines, respectively. These sequences, followed by the oxidation of a 2-hydroxymethyl or 2-aryl group, successfully provided prolines with a trifluoromethyl, difluoromethylene, or difluoromethyl group at the 4-position, including optically active prolines.
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nadano
authors.forename: Yu
authors.initials: Y
authors.lastname: Iwai
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.forename: Junji
authors.initials: J
authors.lastname: Ichikawa
mesh_terms: D002244:Carbon / Q000737:chemistry*; D003500:Cyclization; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D006845:Hydrocarbons, Fluorinated; D013449:Sulfonamides; D002244:Carbon; D011392:Proline