A Highly Regio-and Stereoselective Synthesis Of ?-Fluorinated Imides Via Fluorination Of Chiral Enamides

Generally organo-fluorine compounds have unique chemical and biological properties, and has been found in a number of natural products with pharmacological activity, while in organic reactions also has important applications. In recent years, the method of diastereoselective fluorination has became a new strategy to construct a chiral center of a fluorocarbon. Due to its simple and easy to get raw materials as well as simplicity of operation, it has drawn great attention by chemists. Most of the existing methods require the participation of a metal, limitations of the existing methods include low regio- and stereoselectivity.Herein, we disclosed a highly regio- and stereoselective synthesis of ?-fluorinated imides via fluorination of chiral enamides. Features of this reaction include: 1) Evans' chiral auxiliary group control the stereoselective; 2) construct fluorinated stereogenic carbon centers.We chose chiral enamide 183 as substrates, NFSI(N-fluoro-benzenesulfonimide) as the fluorinating agent, and 16 biaryls amide compound containing a chiral center fluorocarbon have been synthesized in acetonitrile containing 2% H2 O at 40 oC. All the compounds have been well characterized by 1H NMR, 13 C NMR, 19 F NMR, IR, and HRMS. In addition, compounds 184 b and ent-184 d were also confirmed by its X-ray crystallography.A plausible mechanism of the reaction process has been proposed. Identified of the intermediate 173 proves the rationality of the mechanism. In addition, we also explored fluorinations of trisubstituted enamides, through structural identification of the product, we got ?-fluorinated ketones.