Regioselective, Nucleophilic Activation of C-F Bonds in o-Fluoroanilines

Abstract

Reactions of fluorinated anilines with stoichiometric Ti(NMe2)4 in mesitylene (typically for 23 h at 120 °C) afforded moderate to high yields of the corresponding N,N-dimethyl-o-phenylenediamine derivatives resulting from defluoroamination of a fluorine atom ortho to the NH2 of the starting aniline. Reactivity increased with additional ring fluorination in general accordance with established regiochemical (activating and deactivating) trends. Based on results, we propose a metal-mediated, SNAr-based mechanism. We report the scope and limitations of this reaction and discuss trends in reactivity according to a putative mechanistic scheme.