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

The regio- and enantio-selective, intermolecular vicinal fluoroamination of alpha-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 CF3 and F groups. Privileged phenethylamine pharmacophores can be generated in which there is complete local partial charge inversion (CF3 delta-/F delta- versus CH3 delta+/H delta+). Crystallographic analyses of representative beta-fluoroamide products reveal highly pre-organized conformations that manifest the stereoelectronic gauche effect.

Automated summary

The regio- and enantioselective intermolecular vicinal fluoroamination of alpha-trifluoromethyl styrenes has been achieved through enantioselective I-I/I-III catalysis, providing facile access to tertiary benzylic stereocenters bearing both CF3 and F groups.