Enantioselective Synthesis of Inherently Chiral Pillar[5]Arenes Through Copper-Catalyzed Azide-Alkyne Cycloaddition

Pillar[n]arenes have been extensively investigated as carrier materials for applications in host-guest chemistry, nanoscience, information science, materials science, and other domains. Despite its success, the enantioselective synthesis of pillar[n]arenes is challenging and has not yet been achieved. Herein, a novel asymmetric extended side-arm strategy is presented for synthesizing chiral pillar[5]arenes through an iterative copper-catalyzed azide-alkyne cycloaddition reaction. An increase in the steric hindrance on both sides of the macrocyclic molecule efficiently produced a wide range of pillar[5]arenes in high yields with excellent enantioselectivities. Moreover, this principle enables iterative copper-catalyzed azide-alkyne cycloaddition to enantioselectively functionalized pillar[5]arenes with different triazoles using a one-pot process.