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Stereodivergent Access to C‐N Atropisomers via Phosphonium Salt‐Enabled Desymmetrizing Remote Cyclization/Aromatization Cascade

Yan Guo, Siqiang Fang, Lixiang Zhu, Jintong Song, Jixing Che, Haifeng Xiang, Tianli Wang

2025Angewandte Chemie International Edition6 citationsDOI

Abstract

In this study, we describe a highly efficient organocatalytic enantiodivergent method for synthesizing C-N axially chiral compounds via remote asymmetric cycloaddition/aromatization cascade. By leveraging formally remote stereocontrol from two classes of chiral phosphonium salts sharing identical stereogenic elements, prochiral N-aryl maleimides undergo asymmetric formal [4 + 2] cycloaddition/aromatization in an atropodivergent manner, affording structurally diverse C-N axially chiral products. This approach features broad substrate scope and enables practical, atom-economical synthesis of both enantiomeric configurations of C-N atropisomers under mild conditions, with high efficiency and excellent enantioselectivity. Notably, an unexpected synergistic desymmetrization/dynamic kinetic resolution process was observed in this transformation. Mechanistic studies elucidated the origin of stereochemical induction. Furthermore, the utility of enantioenriched products is demonstrated through downstream transformations and, specifically, in constructing circularly polarized luminescence (CPL)-active C-N axially chiral organic small molecules, which may hold significant potential for chiral optoelectronic applications.

Topics & Concepts

AtropisomerStereocenterChemistryPhosphoniumKinetic resolutionEnantiomerCombinatorial chemistryChromophoreStereochemistryEnantioselective synthesisCascadeEnantiomeric excessStereoselectivityOptically activeAxial chiralityAxial symmetryCascade reactionSubstrate (aquarium)StereoisomerismCatalysisResolution (logic)BiocatalysisAbsolute configurationChirality (physics)Axial and Atropisomeric Chirality SynthesisSynthesis and Properties of Aromatic CompoundsSupramolecular Chemistry and Complexes