Enantioselective Molecular Recognition in a Flexible Self-Folding Cavitand

[Image: see text] We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diastereomeric host–guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced-fit behavior with regards to resorcin[4]arene derived self-folding cavitands.