α-Arylated amine moieties constitute a structural motif found in vast amount of therapeutic drugs. Of particular importance, the presence of polyfluorinated aromatics in these drugs is a desired functionality because it increases metabolic stability, lipophilicity, and binding affinity of pharmaceuticals. Utilization of a polyfluoroaryl compounds as the source for aryl group have not been thoroughly investigated due to the strong BDE of C–F bonds (145 kcalmol-1 ). Current approaches to generate these C(sp3)–C(sp2) bonds have been limited to the use of alkyl carboxylic acids and carboxylic acid derivatives to generate alkyl radicals that then engage in nucleophilic aromatic substitutions with hexafluorobenzene. To this day, only one example of photoredox perfluoroarylation of amines exists, but the method is limited to the use of perfluoropyridines as the aromatic substrate and pyrrolidines as the amine source. Examples of functionalization of non-cyclic amines with a wide range of perfluorobenzene derivatives remains elusive. Herein, we present a photoredox-mediated C–H activation strategy of alkyl amines to generate α-perfuoroarylated amines. This reaction proceeds using a metal-free photocatalyst capable of performing an oxidation of the alkyl amine followed by deprotonation of the resulting radical cation to generate the reactive a-amino radical. This stable radical in turn reacts with the polyfluoroaryl compounds to generate the desired product. Mechanistic work, substrate scope, and reaction optimization will be presented.

Photochemical synthesis of α-arylated amines from polyfluoroaryl compounds

ACS Spring 2022

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