Inherently chiral alpha-picolyloxy-p-tert-butylcalix[5]arene crown ethers: Synthesis, structure proof, and enantioselective HPLC resolution

Reaction of alpha-picolyloxy-p-tert-butylcalix[5]arene with tri- to pentaethylene glycol ditosylates and K2CO3 regioselectively affords racemic (1,2)-bridged crown ether derivatives in the cone conformation. Their structure is firmly established by NMR spectroscopy and by comparison with appropriate (1,3)-bridged crown-6 regioisomers, synthesized by unequivocal sequences. The enantiomeric resolution of racemates has been achieved by direct HPLC separation, using enantioselective stationary phases. The enantiomers of the (1,2)-bridged crown-5 derivative exhibit one of the largest separation factors (alpha) so far reported for inherently chiral calixarenes.