Catalytic Enantioselective Synthesis of DMAP-based Inherently Chiral Macrocycles

In contrast to classical central, axial, planar, and helical chirality, inherent chirality represents a distinct form of molecular chirality. The catalytic asymmetric synthesis of novel inherently chiral macrocycles bearing catalytically active functional groups remains a frontier at the interface of asymmetric synthesis and supramolecular catalysis. Herein, we report a Pd/PC-Phos-catalyzed highly enantioselective macrocyclization that enables the de novo construction of DMAP-based inherently chiral macrocycles, affording up to 74% yield and 90% ee. This study lays the groundwork for the construction and application of functionalized inherently chiral molecules.