Nucleophilic Aromatic Substitution of Unactivated Aryl Fluorides with Primary Aliphatic Amines by Organic Photoredox Catalysis

In this work, a mild and transition-metal-free approach for the nucleophilic aromatic substitution (S_NAr) of unactivated fluoroarenes with primary aliphatic amines to form aromatic amines is reported. This reaction is facilitated by the formation of cationic fluoroarene radical intermediates in the presence of an acridinium-based organic photocatalyst under blue-light irradiation. Various electron-rich and electron-neutral fluoroarenes are competent electrophiles for this transformation. A wide range of primary aliphatic amines, including amino acid esters, dipeptides, and linear and branched amines are suitable nucleophiles. The synthetic utility of this protocol is demonstrated by the late-stage functionalization of several complex drug molecules.