Synthesis of Functionalized ABAC- and ABCD-Type Inherently Chiral Heteracalix[4]aromatics

Despite their interesting stereochemistry and potentialapplicationsin (supramolecular) chemistry and chiroptical materials, inherentlychiral macrocyclic compounds remain rare and are largely unexplored.We report herein a fragment coupling method to construct ABAC- andABCD-type inherently chiral heteracalix[4]aromatics. The synthesisinvolves SNAr CuI-catalyzed Ullmann coupling and aliphaticnucleophilic substitution reactions as key steps using readily availablestarting materials. Postmacrocyclization functionalization reactionsenabled the production of amino-substituted and (benzo[d])imidazole-2-(thi)one-bearing heteracalix[4]aromatics. EnantiopureABCD-type macrocycles were obtained from resolution.

Automated summary

Despite their rarity, inherently chiral macrocyclic compounds have interesting stereochemistry and potential applications in (supramolecular) chemistry and chiroptical materials. In this study, a fragment coupling method was used to construct ABAC- and ABCD-type inherently chiral heteracalix[4]aromatics. The synthesis involved key steps of SNAr CuI-catalyzed Ullmann coupling and aliphatic nucleophilic substitution reactions using readily available starting materials. Postmacrocyclization functionalization reactions allowed the production of various amino-substituted and (benzo[d])imidazole-2-(thi)one-bearing heteracalix[4]aromatics, and enantiopure ABCD-type macrocycles were obtained through resolution.