Enantioselective Synthesis of Calix[4]arenes with C–C Axial and Inherent Chirality via Palladium/Chiral Norbornene Cooperative Catalysis

Abstract

The catalytic asymmetric synthesis of inherently chiral calix[4]arenes, a distinct class of chiral macrocycles with significant application in asymmetric catalysis, chiral recognition and functional materials, remains a formidable challenge. Moreover, strategies for the simultaneous introduction of multiple stereogenic elements within these scaffolds in a single transformation are highly desirable yet underdeveloped. Herein, we report a one-step protocol that concurrently install both C–C axial and inherent chirality in a calix[4]arene system through palladium/chiral norbornene (Pd/NBE*) cooperative catalysis. This approach provides direct access to a diverse array of five- and six-membered benzo-fused calix[4]arenes (30 examples) with consistently high enantioselectivity and diastereoselectivity. Notably, the obtained products can be readily transformed into monophosphine ligands bearing both C–C axial and inherent chirality, which exhibit excellent stereocontrol in a silver-catalysed asymmetric [3+2] cyclization reaction. Preliminary photophysical and chiroptical studies reveal that these dual-chiral calix[4]arenes exhibit promising glum factors, demonstrating their potential as versatile chiral scaffolds for advanced organic optoelectronic materials.