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Under superacid conditions, aromatic amines are directly and regioselectively 1,1-difluoroethylated. Low temperature in situ NMR studies confirmed the presence of benzylic α-fluoronium and α-chloronium ions as key intermediates in the reaction. This method has a wide substrate scope and can be applied to the late-stage functionalization of natural alkaloids and active pharmaceutical ingredients., (© 2021 Wiley-VCH GmbH.)

The first direct selective synthesis of novel gem-chlorofluorinated nitrogen-containing building blocks in superacid is reported. The dramatic role of the chlorine atom on the reaction is shown by in situ NMR experiments and allows the involvement of a novel original superelectrophilic activation process in superacid HF/SbF(5) to be postulated.

This paper describes the scope and limitations of the hydrofluorination reaction in superacid HF/SbF(5). On the basis of experimental studies of polyfunctional substrates' behaviour, the dramatic effect of substitution on the superelectrophilic character of ammonium-carbenium dications was emphasized. This reaction was applied to the synthesis of novel fluorinated key building blocks. Furthermore, the hydrofluorination reaction and the discovered homodimerization/fluorination reaction were applied to the synthesis of highly valued fluorinated diamines.

A range of unsaturated amines and sulfonamides were converted to beta-fluoro nitrogen analogues after hydrofluorination in superacid HF-SbF(5), based on the formation of highly reactive electrophilic intermediates.

Upon activation under superacid conditions, functionalized tailor-made N-SCF3 sulfenamides served as reagents for the trifluoromethylthiolation of aromatic amines. This method has a broad substrate scope and can be used for the late-stage functionalization of complex molecules such as alkaloids or steroids. Mechanistic studies based on in situ low-temperature NMR spectroscopy revealed the involvement of dicationic superelectrophilic intermediates. [ABSTRACT FROM AUTHOR]

Superacid activation of N‐SCF3 sulfenamide reagents generates diprotonated superelectrophilic species for the trifluoromethylthiolation of aromatic amines, as shown by T. Billard, S. Thibaudeau, and co‐workers in their Communication on page 173 ff. This method can be used for the late‐stage functionalization of complex biomolecules such as alkaloids and steroids. [ABSTRACT FROM AUTHOR]

An efficient and straightforward regio-controlled route to β-fluoro-γ-chlorinated amines was developed via an ammonium–chloronium superelectrophilic activation in superacid HF/SbF 5 . Through halogen directing effect the method was extended to a variety of (poly)halofluorinated building blocks amenable for further synthetic modifications. The direct synthesis of chlorofluorinated analogues of bioactive compounds via this process confirmed the ability to use this strategy for further applications in medicinal chemistry. [ABSTRACT FROM AUTHOR]