Advances in the Catalytic Asymmetric Synthesis of Atropisomeric Hexatomic N‐Heterobiaryls

Abstract Axially chiral hexatomic N‐heterobiaryls are among the most important class of structures with extensive utility in asymmetric catalysis as chiral ligands and organocatalysts, as exemplified by QUINAP and QUINOX. Besides, these atropisomers have attracted broad attention due to their application in drug discovery. Hence, it is not surprising that extensive efforts have been devoted for the pursue of efficient catalytic asymmetric methods for their direct and atroposelective construction. In addition to the direct heteroaryl‐aryl cross‐coupling, which remains as a challenge, a series of creative catalytic asymmetric strategies based on pre‐formed heterobiaryl systems have been developed by taking advantage of the intrinsic property of N atom on the heteroarenes. Generally, the methods employed extensively involved kinetic resolution, dynamic kinetic asymmetric transformation, dynamic kinetic resolution and desymmetrization reaction. A growing number of approaches through stereoselective de novo formation of a six‐membered N‐heteroaromatic ring have also been reported for specific applications in this field. This review summarizes recent advancements of axially chiral hexatomic N‐heterobiaryls construction by means of asymmetric catalysis, including their scope, limitations, mechanisms and applications. magnified image