Atropisomeric Aryl–Hydrazone Frameworks: Discovery and Organocatalytic Enantioselective Construction

Abstract

The expanding utility of axial chirality across the chemical sciences has intensified the search for structurally novel atropisomeric skeletons. Drawing inspiration from the electronic properties of aryl–amides, we have developed a new class of atropisomeric aryl–hydrazone architectures. Their atroposelective construction was accomplished via stereospecific addition of hydrazines to axially chiral vinyl quinone methides, generated in situ from aryl–alkynes under chiral Brønsted acid catalysis. This transformation exhibits remarkable Z/E- and enantioselectivity, along with broad functional group compatibility. The key to overcoming this synthetic challenge lies in the precise enantiocontrol of the transient aryl–enamine species, which subsequently undergoes stereospecific enamine-to-imine tautomerization to afford the Z-configured atropisomers. Furthermore, the chiral Brønsted acid acts as a sophisticated proton shuttle, enabling a privileged pathway for the seamless transfer of stereochemical information while enhancing selectivity through precise spatial discrimination of the enamine conformers. This work not only expands the repertoire of atropisomeric frameworks but also delivers atropisomers with excellent structural and axial stability, positioning them as promising candidates for asymmetric catalysis and materials science.