title: Enantioselective Synthesis of 3,3-Difluoropyrrolidin-4-ol, a Valuable Building Block in Medicinal Chemistry.
abstract: In this paper, we report for the first time two enantioselective routes to 4,4-difluoropyrrolidin-3-ol, a valuable building block in medicinal chemistry. In the first route, we took advantage of the C2 symmetry of (3R,4R)-3,4-dihydroxypyrrolidine in which the desired chirality was derived from the chiral pool (l-(+)-tartaric acid). In the second route, we efficiently assembled the pyrrolidine ring in the presence of a gem-difluoro moiety to avoid using potentially hazardous deoxofluorinating reagents and subsequently introduced the chirality by a stereoselective iridium-diamine-catalyzed asymmetric transfer hydrogenation reaction.
authors.affiliation: DCR&T, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
authors.forename: Chong
authors.initials: C
authors.lastname: Si
authors.affiliation: DCR&T, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Fales
authors.affiliation: DCR&T, Lilly Spain S.A., Avda de la Industria 30, Alcobendas Madrid, 28108, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Torrado
authors.affiliation: DCR&T, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
authors.forename: Kwame
authors.initials: K
authors.lastname: Frimpong
authors.affiliation: DCR&T, Lilly Spain S.A., Avda de la Industria 30, Alcobendas Madrid, 28108, Spain.
authors.forename: Talbi
authors.initials: T
authors.lastname: Kaoudi
authors.affiliation: AMRI, 26 Corporate Circle, Albany, New York 12203, United States.
authors.forename: Harold George
authors.initials: HG
authors.lastname: Vandeveer
authors.affiliation: DCR&T, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge