Syntheses of all possible conformational isomers of O-alkyl-p-t-butylcalix[4]arenes

In p-t-butylcalix[4]arene (1H₄) and its mono-, di-, tri-, and tetra-O-alkyl derivatives (1HR₃, 1H₂R₂, 1HR₃, and 1R₄ respectively), 23 different homologs can exist (including 1H₄). We found that the OH group in the unmodified phenol unit is permeable through the calix[4]arene ring. Thus, several conformational isomers become equivalent after the oxygen-through-the-annulus rotation of the OH group and the number of the possible homologs is reduced to 13 (including 1H₄). We here report the syntheses of all of these possible conformational isomers by using a protection-deprotection method with a benzyl group and metal template effects. The results are very useful for understanding the conformer distribution in 1H₂R₂, 1HR₃, and 1R₄, which has confused calixarene chemists for a long time and is still a matter of discussion.