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

Abstract

In this work, a mild and transition-metal-free approach for the nucleophilic aromatic substitution (SN Ar) 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.