title: Fluorination-free synthesis of a 4,4-difluoro-3,3-dimethylproline derivative.
abstract: A Claisen rearrangement/iodolactamization sequence starting from commercially available trifluoroacetaldehyde methyl hemiacetal, followed by a classical chemical resolution, provided enantiomerically pure 4,4-difluoro-3,3-dimethylproline (S)-1. No hazardous fluorination reagents were used, and the overall yield over 12 steps was greater than 28%.
authors.affiliation: Chemical Research and Development, La Jolla Laboratories, Pfizer, Inc., 10578 Science Center Drive, San Diego, California 92121-1111, USA. lijianc@amgen.com
authors.forename: Lijian
authors.initials: L
authors.lastname: Chen
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: David J
authors.initials: DJ
authors.lastname: Kucera
authors.forename: Katheryn E
authors.initials: KE
authors.lastname: Harrison
authors.forename: Sogole
authors.initials: S
authors.lastname: Bahmanyar
authors.forename: Jill M
authors.initials: JM
authors.lastname: Scott
authors.forename: Daniel
authors.initials: D
authors.lastname: Yazbeck
mesh_terms: D002384:Catalysis; D005461:Fluorine / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D005461:Fluorine; D011392:Proline; C003342:stachydrine