Stereoselective Radical Cross-Coupling of Amino Acids and Imines via Hydrogen-Bond Catalysis

Abstract

Stereochemical control remains one of the most challenging obstacles in developing practical radical transformations. Recent progress in transition-metal-catalyzed radical reactions has shed light on methods for stereoselectively constructing C(sp³)–C(sp³) bonds through a single electron transfer mechanism. However, the field of chiral Brønsted acid-catalyzed stereoselective radical reactions is relatively less studied. Herein, we present a stereoselective radical cross-coupling between abundant amino acids and readily available imine substrates (prepared in situ from aldehydes and anilines) via cooperative catalysis of photoredox and phosphoric acid. This method features good functional group compatibility, providing a diverse range of chiral 1,2-diamine products which are valuable in synthetic utility. Preliminary mechanistic studies indicate that this reaction probably proceeds via both radical–radical cross-coupling pathway and radical nucleophilic addition mechanism.