title: Direct Access to Chiral β-Fluoroamines with Quaternary Stereogenic Center through Cooperative Cation-Binding Catalysis.
abstract: A direct route to chiral β-fluoroamines with tetrasubstituted C-F centers through the organocatalytic Mannich reaction of α-fluoro cyclic ketones and α-amidosulfones by using a chiral oligoethylene glycol as a cation-binding catalyst and KF as a base is reported. For most substrates, nearly perfect enantioselectivities were achieved even at very high temperatures (>80 °C). The salient features of this process include a) a transition-metal-free and operationally simple procedure, b) direct use of α-amidosulfones as bench-stable precursors of sensitive imines, c) direct enolization of racemic α-fluoro cyclic ketones, and d) excellent stereoselectivity up to 99 % enantiomeric excess and >20:1 diastereoselectivity (anti/syn). Thus, this protocol is easily scalable and provides a new approach for the synthesis of biologically relevant products with tetrasubstituted C-F centers. Furthermore, this protocol was also successfully extended to generate C-Cl and C-Br quaternary stereogenic centers.
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon, 440-746, Korea.
authors.forename: Venkataramasubramanian
authors.initials: V
authors.lastname: Vaithiyanathan
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon, 440-746, Korea.
authors.forename: Mun Jong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Innovative Drug Research Centre (IDRC), School of Pharmaceutical Sciences, Chongqing University, 55 Daxuecheng South Rd., Chongqing, 401331, P.R. China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Innovative Drug Research Centre (IDRC), School of Pharmaceutical Sciences, Chongqing University, 55 Daxuecheng South Rd., Chongqing, 401331, P.R. China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon, 440-746, Korea.
authors.forename: Choong Eui
authors.identifier: http://orcid.org/0000-0001-9221-6789
authors.initials: CE
authors.lastname: Song
keywords: Mannich reaction; cation-binding catalysis; chiral oligoethylene glycol catalyst; quaternary stereogenic center; β-fluoroamines