Rational Design, Synthesis, and Catalytic Enantioselective Derivatization of an achiral ansa-Macrocycle

A pyrrole-based achiral atropisomeric macrocycle 1a was rationally designed. Density functional theory (DFT) calculations predicted that 1a possesses atropisomeric rigidity comparable to common cyclophanes, while exhibiting enhanced nucleophilicity. This combination indicates broad application potential in planar chiral derivatization. I successfully synthesized the achiral macrocycle 1a, and nuclear magnetic resonance (NMR) studies confirmed its atropisomeric nature. Furthermore, I investigated the planar chiral derivatization of 1a with electrophiles. Under the chiral phosphoric acid (CPA) catalysis, this derivatization proceeded with moderate stereoselectivity.