Enantioselective Synthesis of Inherently Chiral Tetraazacalix[4]aromatics from a Chiral Phosphoric Acid-Catalyzed Intramolecular S_NAr Reaction

Inherently chiral calixarenes and heteracalixaromatics (ICCHeC) have been drawing great attention, because of their unique 3D stereochemical structures and tantalizing applications. The majority of ICCHeC arises from the cyclic arrays of different aromatic segments. Examples of ICCHeC generated from various substituents on methylene and heteroatom linkages are extremely rare. Here, we report the enantioselective synthesis of tetraazacalix[1]arene[1]pyridine[2]triazines from a chiral phosphoric acid-catalyzed S_NAr reaction. The inherent chirality of the resulting 1,3-alternate heteracalix[4]aromatics stems from the variation of only one substituent on the bridging nitrogen atom. Enantiomers were very stable, and they did not undergo racemization at an elevated temperature. This study opens a new avenue to design and construct novel and functional ICCHeC that may find useful applications in supramolecular science.