Direct Access to Chiral β-Fluoroamines with Quaternary Stereogenic Center through Cooperative Cation-Binding Catalysis

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• 作者：Venkataramasubramanian Vaithiyanathan ; Mun Jong Kim ; Yidong Liu ; Prof. Hailong Yan and Prof. Choong Eui Song
• 刊名：Chemistry - A European Journal
• 出版年：2017
• 出版时间：January 26, 2017
• 年：2017
• 卷：23
• 期：6
• 页码：1268-1272
• 全文大小：844K
• ISSN：1521-3765

文摘

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.