Studies on Fluorination and Aminofluorination Using N-F Reagents

Organofluorine compounds constitute a valuable class in the fields of pharmaceuticals and agrochemicals, because biological activity and physicochemical properties, such as bioavailability, lipophilicity, and metabolic stability, can be improved by the introduction of fluorine atom(s). Therefore, efficient methods for the synthesis of organofluorine compounds have been intensively studied. Development of practical fluorinating reagents is indispensable for this purpose. In this paper, the author reports the synthesis of novel electrophilic fluorinating reagents (N-F reagents) as substitutes for NFSI (N-fluorobenzenesulfonimide) with N-F covalent bond and their application to reactions. The paper describes three main topics: First, selective mono- and difluorination in the α-position of carbonyl compounds are demonstrated by exploiting the fluorinating activity of the tuned N-F reagents. Second, the selective difluorination in the benzylic C-H bonds of N-heterocycles is achieved by using N-F reagent, which readily enables the interaction with N-heterocycles. Third, the aminofluorination of alkenes in the presence of palladium catalyst is also developed by using N-F reagents containing easily transformable substituents.