Regioselective formation of the quinazoline moiety on the upper rim of calix[4]arene as a route to inherently chiral systems

Abstract

The meta- and para-substituted aminocalix[4]arenes immobilized in the cone conformation were acylated to yield the corresponding acyl amides. Subsequent cyclization with aryl or alkyl cyanides afforded the expected quinazolines only in the case of the para-substituted series, while only complex reaction mixtures were obtained for the meta-substituted analogues. This finding was used as a strategy for the preparation of novel inherently chiral calixarenes with strong fluorescence. The structure of the products was proved by the combination of NMR and single crystal X-ray analyses. The dynamic NMR study of quinazoline derivatives revealed the existence of two different atropisomers in solution at lower temperatures. As evidenced by resolution with a chiral HPLC column and by the fluorescence titration experiments, novel quinazolines represent inherently chiral macrocycles of high potential for the design of chiral calixarene-based receptors.