Photoredox-catalyzed chemo- and regioselective synthesis of homopropargyl amines via radical–radical cross-coupling

Abstract

The propargylation of imines is an effective means for constructing of homopropargyl amines, which are widely used in the synthesis of bioactive compounds and complex functional molecules. The traditional method involves nucleophilic addition to imines; however, the use of transition metals, harsh conditions, and limited tolerance of functional groups do not align with the principles of green synthesis. Herein, we developed an alternative metal-free catalyzed protocol that involves the propargylation of imines. Mechanistic studies demonstrate that the reaction likely involves the photocatalytic generation of α-amino radicals and propargyl radicals, followed by radical–radical cross-coupling. DFT calculations show that the C–C coupling of the α-aminyl radical and propargyl radical (ΔH = −36.74 kcal mol⁻¹) is the most favorable. This method offers mild conditions, good functional group compatibility, readily available raw materials, a wide substrate scope, and excellent chemo- and regioselectivity. Furthermore, the homopropargyl amines could undergo various functional transformations under general conditions.