Regio‐ and Enantioselective Intermolecular Aminofluorination of Alkenes via Iodine(I)/Iodine(III) Catalysis

The regio‐ and enantio‐selective, intermolecular vicinal fluoroamination of α‐trifluoromethyl styrenes has been achieved by enantioselective I(I)/I(III) catalysis. Leveraging C (2)‐symmetric resorcinol‐based aryl iodide catalysts, it has been possible to intercept the transient iodonium intermediate using simple nitriles, which function as both the solvent and nucleophile. In situ Ritter reaction provides direct access to the corresponding amides (up to 89 % yield, e.r. 93 : 7). This main group catalysis paradigm inverts the intrinsic regioselectivity of the uncatalyzed process, thereby providing facile access to tertiary, benzylic stereocenters bearing both CF(3) and F groups. Privileged phenethylamine pharmacophores can be generated in which there is complete local partial charge inversion (CF(3) ( δ−)/F( δ−) versus CH(3) ( δ+)/H( δ+)). Crystallographic analyses of representative β‐fluoroamide products reveal highly pre‐organized conformations that manifest the stereoelectronic gauche effect.