Enantiomerization Barrier of all-cis C-Me-tetrahydroxy p-tert-butylcalix[4]arene and Atropisomeric Equilibrium of its Tetraacetoxy Derivatives

All-cis C–Me-tetrahydroxy p-tert-butylcalix[4]arene (5) was prepared by exhaustive demethylation (iodocyclohexane/DMF) of its tetramethyl ether derivative 4. The molecule crystallized as a 2:1 adduct of chlorobenzene and the calix[4]arene. The calix macrocycle adopts in the crystal a pinched-cone conformation where all methyls are located at equatorial positions of the macrocycle. The barrier for reversal of the sense of direction of the circular array of intramolecular hydrogen bonds of 5 (an enantiomerization process) is ΔG^‡ = 11.1 kcal mol^–1 (197 K, CD₂Cl₂). Acetylation (acetic anhydride, conc. H₂SO₄) afforded a 7:3 mixture of partial-cone (10) and cone (11) tetraacetoxy derivatives. Both atropisomers were characterized by X-ray crystallography. In contrast to tetraacetoxy p-tert-butylcalix[4]arene, equilibration studies of the tetraacetoxy derivatives of 5 ([D₆]DMSO, 423 K) indicate that the cone atropisomer 11 is populated at equilibrium conditions. The relative stabilization of 11 suggests that the other atropisomeric forms of the tetraacetoxy C–Me-calix[4]arene are destabilized by the presence of methyl substituents located at isoclinal positions of the macrocycle.