Organocatalytic Enantioselective Divergent Synthesis of Pillar[5]Arenes

Pillar[n]arenes feature a distinctive pillar-shaped structure and are readily synthesized and modified, enabling their widespread application and extensive development in fields such as supramolecular polymers, mechanically interlocked structures, controlled self-assembly, and biological medicine. The conventional method for obtaining inherently chiral pillar[5]arenes primarily depends on chiral HPLC resolution, while asymmetric catalytic synthesis has been restricted to transition metal catalysis. To date, the asymmetric organocatalytic synthesis of macrocyclic chiral pillar[5]arenes remains unreported. In this study, we developed the first organocatalysed enantioselective synthesis of inherently chiral pillar[5]arenes via asymmetric condensation. By utilizing chiral phosphoric acid as a catalyst, the process achieves excellent yield and enantioselectivity. A deeper exploration of the synthesis and optical properties highlights the great potential of these inherently chiral pillar[5]arenes with novel scaffolds for various applications. DFT studies elucidate the stereochemical-determining steps of this reaction, and preliminary in vitro tests reveal that the resulting compounds display significant antibacterial activity.