Synthesis of α-Fluoroamides with a C-F Quaternary Stereogenic Center by Electrophilic Fluorination: One-Pot Four-Component Strategy

An efficient method for the synthesis of alpha-fluoroamides having C-F quaternary stereogenic center was achieved by a one-pot four-component strategy under mild reaction conditions. A variety of alpha-fluoroamides was synthesized by using 1,3-dicarbonyl, isocyanide, acetylenedicarboxylate and N-fluorobenzenesulfonimide (NFSI) systems with good to excellent yields up to 93 %. The current protocol proceeds through the unstable 3-fluoro 4H-pyran intermediate, which is key for the reaction and further it can be hydrolyzed due to the high electronegativity of the fluorine atom to produce the desired alpha-fluoroamides.