Mandelic Acid-Mediated Enantiomeric Enrichment of a Resorcinarene-Based Dissymmetric Coordination Capsule.

Resorcinarene-based coordination capsules provide rigid, well-defined cavities that can exhibit helicity under chiral induction, a feature that has previously been exploited using axially chiral biphenyl compounds and tartaric acid derivatives. However, these approaches generally require well-designed templates tailored to the capsule structures. In this study, it was discovered that commercially available mandelic acid functions as an effective and operationally simple additive for inducing chirality in an empty-cavity Cu(I) capsule without the requirement for templates. Chiral induction was achieved by introducing mandelic acid through either treatment of a preformed racemic capsule or during its assembly. Both approaches generated helically biased capsules, as confirmed by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy, with optical purities approaching unity (up to ∼97% ee) under optimized conditions. Mechanistic investigations using NMR spectroscopy, electrospray ionization mass spectrometry, and electron spin resonance spectroscopy indicated that the oxidation of Cu(I) to Cu(II) played a key role in the induction process, and that this was mediated by interactions with the carboxylate group of mandelic acid. This study therefore presents a straightforward and highly effective protocol for accessing an enantiomerically enriched resorcinarene-based coordination capsule, expanding its potential as a confined chiral reaction space and a functional chiral material.