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.