Synthesis of Inherently Chiral Homo-heteracalixaromatics

There is a resurgence of research interest in inherently chiral calixarenes and heteracalixaromatics. However, the examples of macrocyclic ring-expanded homocalixarenes and heterocalixaromatics of inherent chirality are not known. Here we report an efficient method to construct inherently chiral N₂,O₂-linked homo-heteracalixaromatics from reductive amination reactions between bis-aldehydes and aliphatic diamines. Examples of post-macrocyclization derivatization were also demonstrated. Enantiomers were obtained from resolution and did not undergo racemization at an elevated temperature. This study provides a new strategy to design novel and functional inherently chiral macrocycles that have potential applications in supramolecular chemistry.