Red Photon-Driven Aminomethylation of Indoles to Access the Sterically Hindered Indolyl Tertiary Amines

Abstract

Introducing amine functionality to readily available feedstock chemicals is an effective strategy to rapidly enhance molecular complexity and access valuable scaffolds. Herein, we have developed a red photon-driven N-aminomethylation of indoles utilizing a n PrDMQA + organic photocatalyst. Under red-photon irradiation, amine radical cations exclusively generate less hindered iminium species, which are then sequentially converted into sterically crowded tertiary amines of interest in organic synthesis, enabling a high-yield N-C(sp 3 ) coupling reaction under mild conditions. This protocol demonstrates a broad substrate scope, allowing late-stage modification of bioactive natural compounds and pharmaceuticals under mild conditions. Controlled experiment and DFT studies on transient intermediates confirmed the mechanistic pathway, highlighting the generation of a kinetically favored iminium ion to generate the library of aminated indole derivatives.