Construction of Fluorinated Tertiary Allylamines via Three-component Photocatalytic Defluorinative Aminoalkylation of gem-Difluoroalkenes

Abstract

The incorporation of fluorinated tertiary allylamine motifs into bioactive compounds holds significant importance owing to their notable physiological properties. Herein, we report a concise defluorinative aminoalkylation protocol facilitated by a photoredox catalytic system in conjunction with a cost-effective reductant. This methodology allows for the three-component coupling of secondary amines, aldehydes or ketones, and gem-difluoroalkenes to yield fluorinated tertiary allylamines, demonstrating broad functional group tolerance. Mechanistic studies suggest that the transformation is initiated by the single-electron reduction of in-situ formed iminium ions to generate alkyl-substituted α-aminoalkyl radicals, followed by a radical addition-elimination sequence. This photocatalytic strategy offers a straightforward approach for constructing structurally complex fluorinated tertiary allylamines that are otherwise difficult to access via conventional synthetic methods. The practical utility of this protocol is further highlighted by successful applications in the late-stage functionalization of pharmaceutical molecules.