Photoredox-Catalyzed Dearomatization of Indoles with Amines: An Approach to Highly Strained Polycyclic Indolines
Junlei Wang, Guofen Wei, Ji Luo, Jiadong Cheng, Daohai Zhang, Xue‐Mei Chen, Fang Tan, Tonghao Yang, Hongqing Li, Binbin Huang
Abstract
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.