Rhodium‐Catalyzed Enantioselective Synthesis of Planar‐Chiral Macrocycles via De Novo Isoquinoline Formation

De novo formation of the aromatic ring is an attractive strategy for atroposelective synthesis, but its application to planar‐chiral macrocycles remains challenging. Herein, we report a rhodium‐catalyzed enantioselective synthesis of planar‐chiral macrocycles via de novo isoquinoline construction. This method is characterized by high levels of enantioselectivity (up to 96% ee), regioselectivity (up to >20:1 rr), and functional group tolerance, providing a series of isoquinoline‐based macrocyclic atropisomers. Furthermore, the synthetic utility of this protocol is validated via a mmol‐scale reaction and post‐modification process of the product. Mechanistic studies, including deuterium labeling, kinetic isotope effect, and DFT calculations, support C─H bond cleavage as the rate‐determining step and elucidate the origin of the stereoselectivity.