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

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. <i>De novo</i> macrocyclization of linear achiral substrates <i>via</i> 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.