Exploiting Asymmetric Nitrogen Chlorination for Construction of N -Chloroimine Atropisomers

Abstract

Abstract Enantioselective halogenation has recently expanded from carbon to heteroatomic sulfur and phosphorus centers. However, asymmetric functionalization at nitrogen centers remains challenging. Herein, we report an atroposelective nitrogen-halogenation strategy that utilizes an atropisomeric scaffold, shifting the focus from configurationally unstable pyramidal nitrogen centers to stable axial systems. Starting from readily available diaryl substituted imines, we achieved the first atroposelective sp2-nitrogen chlorination mediated by a chiral phosphoric acid catalyst. Notably, the reaction exclusively favors the sterically congested Z-configured N-chloroimines, which is essential for establishing the axial chirality. Furthermore, the stereochemical induction operates via a remote mode, occurring distal to the stereogenic axis. The synthetic utility of this protocol is demonstrated by a highly stereospecific cyclization with alkene and alkyne, affording valuable atropisomeric 1-arylisoquinoline scaffolds. This strategy provides a new avenue for heteroatom functionalization and axial chirality construction.