Adaptive Defluoroamination of Aryl Fluorides: Harnessing the Catalytic Potential of a Unique Zinc Amide Compound

The activation and functionalization of C‐F bonds, the strongest bonds between carbon and any other element, via C‐N bond formation to generate complex molecules has remained a compelling challenge. Herein, we present a ligand‐centered redox‐controlled effective strategy employing a zinc amide catalyst (C) to achieve facile defluoroamination of fluoroarenes with several N‐ nucleophiles (>90 substrates) under mild conditions. Notably, this adaptable protocol works readily with most types of fluoroarenes and a diverse range of N‐H moieties that include secondary and primary amines, indoles, azoles, and amides under the same reaction conditions, and encouragingly, offers excellent functional group compatibility. Intriguingly, we also demonstrated its application in one‐pot synthesis of (un)symmetrical triaryl amines from primary amine itself and the selective activation of C‐F bonds to access F‐containing amines, relevant to drug synthesis. Finally, detailed mechanistic probes via active‐intermediate‐capture, EPR analysis, and various control experiments, indicate that the reaction proceeds through a radical‐mediated C‐N coupling pathway. Importantly, use of Zn(II) center as a template to hold two amide moieties together in C enables facile intramolecular electron transfer to generate the radical intermediates for the present protocol. Finally, the practical utility of this methodology was showcased by synthesizing various drug derivatives.