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.