Carbene-catalyzed double esterification enables enantioselective conformational self-locking of pillar[5]arenes.

Abstract

For their chirality, pillar[5]arenes stand out among the most versatile and widely utilized classes of organic host molecules, with numerous applications in materials science and biomedicine. The chirality of these macrocyclic compounds arises from conformational locking induced by sterically demanding substituents. However, preparing enantioenriched pillar[5]arenes often requires laborious chiral or diastereomeric separations. Here, we describe a simple and efficient metal-free protocol for oxidative double esterification of diformylpillar[5]arenes. This method provides a versatile and operationally straightforward route to highly enantioenriched products with broad functional group tolerance, as shown by incorporating biologically active and naturally derived fragments. Moreover, the reaction is readily scalable and enables subsequent derivatization, yielding rotaxane. Therefore, our organocatalytic method for pillar[5]arene self-locking not only streamlines the asymmetric synthesis of enantioenriched macrocyclic hosts but also opens new avenues for the design of chiral functional materials and host-guest systems.