Photoredox-Catalyzed Dearomatization of Indoles with Amines: An Approach to Highly Strained Polycyclic Indolines

Polycyclic indolines are pervasive in a diverse array of biologically active molecules owing to their appealing physiological contributions. Herein, we report a straightforward dearomatization approach that employs a photoredox catalyst in combination with an inexpensive reductant to couple indole derivatives with secondary amines. This dearomative cycloaddition exhibits exceptional diastereoselectivity and delivers highly strained indolines fused with three-dimensional polycyclic scaffolds featuring a bicyclo[3.1.1] substructure, meanwhile accommodating a broad range of functional groups. Preliminary mechanistic studies suggest that this dearomatization involves alkyl-substituted α-amino radicals as the key intermediates, which are derived from the reduction of in situ generated iminium ions. This protocol offers a facile approach for the installation of highly strained polycyclic indolines that are not readily accessible via established approaches and has also been proven effective for the late-stage modification of pharmaceutical molecules.