Calochorturils: Chiral Bowl-Shaped Cavitands Obtained by Anisotropic Tangential Substitution

Substitution of the extended tribenzo-cyclononatriene transforms an achiral cavitand into a chiral host molecule. Calculations of the continuous chirality measure (CCM) predict that tangential substitution induces greater distortion of the unsubstituted bowl-shaped cavitand than radial substitution. We achieved the new cavitands through regioselective synthesis and named them Calochorturils (CTs) after the chiral C3-symmetric Calochortus venustus tulip. Resolving them into optically pure enantiomers using chiral HPLC enabled their characterization by optical rotation and circular dichroism spectroscopy. Their absolute configuration was determined by X-ray crystallography of an enantiomerically pure triply etherified CT with (S)-BINOL. A comparison of CCM calculations for several solid-state CT derivatives with gas-phase models shows satisfactory agreement. The racemization rate constant for the bowl-to-bowl inversion, krac = 7.1 × 10–6 s–1, corresponds to an activation free energy barrier of ΔG# = 115.1 kJ mol–1. Notably, the CT skeleton is configurationally more stable than the CTV framework, with a 27 h half-life at 334 K in chloroform, compared with 8 h of CTV. Thus, CT derivatives can be handled in solution at room temperature without a significant loss of optical purity.