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.
Keywords: bioisostere; difluoroethylation; late-stage functionalization; superacid; superelectrophile.
© 2021 Wiley-VCH GmbH.