Enantioselective Synthesis of Macrocyclic Planar Chiral Metacyclophanes via Desymmetrization

Planar chiral cyclophanes have garnered significant attention as privileged scaffolds due to their crucial roles in various chemical applications. Although the field of catalytic enantioselective synthesis of planar chiral cyclophanes has witnessed substantial progress, the majority of the advancements have been centered on paracyclophanes. In contrast, the development of methods for the synthesis of planar chiral metacyclophanes has remained relatively underexplored. Herein, we present a reliable synthetic strategy for the construction of planar chiral [ n ]metacyclophanes via an enantioselective desymmetric Povarov reaction, followed by oxidative aromatization. This strategy exhibits remarkable functional group tolerance, affording a diverse array of [ n ]metacyclophane-quinoline derivatives with a broad substrate scope and acceptable enantioselectivity. The successful transformation of [ n ]metacyclophanes into planar chiral catalysts highlights their potential application in catalyzing the construction of noncarbon central chirality. Computational studies indicated that π–π stacking is essential for enantioselectivity.