Catalytic Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Sequential Povarov Reaction and Aromatizations

Inherently chiral calix[4]arenes represent a unique type of chiral molecules with significant applications, yet their catalytic enantioselective synthesis remains largely underexplored. We report herein the catalytic enantioselective synthesis of inherently chiral calix[4]arenes through the sequential organocatalyzed enantioselective Povarov reaction and aromatizations. The chiral phosphoric acid catalyzed three-component Povarov reaction involving amino group-substituted calix[4]arenes, aldehydes and (di)enamides desymmetrized the prochiral calix[4]arene substrates, which was followed by various aromatization methods, resulting in a diverse array of novel quinoline-containing calix[4]arenes with good yields and high enantioselectivities (up to 75 % yield, 99 % ee). The large-scale enantioselective synthesis and diverse derivatizations of the chiral calix[4]arene products highlight the value of this method. Furthermore, preliminary exploration into their photophysical and chiroptical properties demonstrate the potential applications of these novel calix[4]arene molecules. A highly modular and efficient enantioselective synthesis of inherently chiral calix[4]arenes has been developed through the sequential chiral phosphoric acid catalyzed Povarov reaction and subsequent aromatizations. With the excellent compatibility of the Povarov reaction and the development of distinct aromatization methods, a wide range of structurally diverse novel quinoline-containing calix[4]arenes were produced with high enantioselectivities. image