Synthesis and optical resolution of naphthalene-containing inherently chiral calix[4]arenes derived by intramolecular ring closure or stapling of proximal phenyl units

Abstract

New methods for the preparation of inherently chiral calix[4]arenes have been developed. The molecular asymmetry in these calix[4]arenes is created by an asymmetrical disposition of naphthalene rings on the upper rim. In compound 1, monoformylcalix[4]arene 5 was transformed into naphthalene-containing calix[4]arene by ring closure. In compound 2, p-chloromethyl groups are intramolecularly cross-linked with 3-hydroxymethyl-2-naphthol. This ‘stapling reaction’ results in a syn isomer 2a and an anti isomer 2b, the latter being classified into an inherently chiral calix[4]arene. Racemic anti 2 could be ‘perfectly’ optically resolved by an HPLC method with a chiral-packed column. The chiral products were thoroughly characterized by various spectroscopic methods. These results indicate that the naphthalene skeleton is very useful for creating molecular asymmetry in calix[4]arenes.