Inherently chiral homo-heteracalixarenes: design and synthesis via an enantioselective intramolecular Sonogashira cross-coupling reaction

Abstract

Recent research has seen growing interest in synthesizing inherently chiral macrocycles, driven by their potential applications in chiral supramolecular chemistry. We present herein our design and synthesis of a series of novel inherently chiral macrocycles. These compounds, termed homo-heteracalixarenes, feature a 1,2-diphenylethyne fragment that replaces one of the aryl-heteroatom-aryl linkages found in classic heteracalix[4]aromatics. De novo macrocyclization of linear achiral substrates via an intramolecular Sonogashira cross-coupling reaction affords the 17- or 18-membered chiral cyclophanes in modest yields with up to 90% ee. The strained bent alkyne moiety within the macrocycle provides a key reactive handle for macrocycle-to-macrocycle derivatization. Further, we showed the unique macrocyclic structures and demonstrated interesting chiroptical properties of the obtained enantioenriched homo-calixarenes and their derivatives.