[4+2] Defluorocycloaddition of Perfluoroalkyl Alkynes and Benzylamines: Synthesis of meta-Fluoroalkylated Pyridin-4-amines

Abstract

Pyridines represent privileged heterocycles, and the ability to produce fluorinated pyridines from polyfluorinated substances through selective defluorofunctionalization is a new addition to their synthesis. Herein, an unprecedented formal [4+2] defluorocycloaddition of perfluoroalkyl alkynes and benzylamines under metal-free conditions is described. By leveraging the functionalization of four C(sp³)–F bonds on two vicinal sterically hindered perfluoroalkyl carbons of perfluoroalkyl alkynes, a diverse array of meta-fluoroalkylated pyridin-4-amines were synthesized with good functional group tolerance. The mechanistic studies revealed a sequence of hydroamination, successive defluorination, 6π-electrocyclization, aromatization, and amination.