Optically Pure Calix[6]tris-ammoniums: Syntheses and Host−Guest Properties toward Neutral Guests

Optically pure calix[6]arenes bearing chiral amino arms 4, 7, and 10 have been synthesized in
high yields from the known symmetrically 1,3,5-trismethylated calix[6]arene. For both compounds
7 and 10, the key step consists of an efficient selective alkylation on the narrow rim of the calix[6]arene with Ba(OH)2 as the base. All of these chiral calix[6]tris-amines possess a similar flattened
cone conformation with the cavity occupied by the methoxy groups. In contrast to 4 and 7, upon
protonation, the enantiopure calix[6]arene 10 can switch to the opposite flattened cone conformation
through self-assembly of its ammonium arms in an ion-paired cap which closes the cavity. As shown
by NMR host−guest studies and an X-ray structure, the obtained polarized host (10·3H+) behaves
as a remarkable endo-receptor for small polar neutral molecules. Thanks to the tris-cationic chiral
binding site of 10·3H+, it was shown that the guests experience a chiral environment upon inclusion.
Finally, the first example of enantioselective molecular recognition inside the cavity of a calix[6]arene has been evidenced with a racemic 1,2-diol guest.