Asymmetric Synthesis of Inherently Chiral Tetraoxacalix[2]arene[2]pyridines via SNAr‐Based Cross‐Cyclotetramerization

Potassium phosphate‐promoted cross‐cyclotetramerization of 2,6‐dichloro‐3‐nitropyridine 1 with resorcinol derivatives 2 gave rise to thermodynamically favored 1,3‐alternate tetraoxacalix[2]arene[2]pyridines and kinetically controlled 1,2‐alternate isomers. The kinetic product could convert into its 1,3‐alternate conformational isomer by a macrocycle to macrocycle conversion pathway. Enantiomerically enriched C2‐symmetric inherently chiral tetraoxacalix[2]arene[2]pyridines were synthesized via a Cinchonine‐derived chiral phase‐transfer catalyst (PTC). This synthesis involved the cross‐cyclotetramerization of 1 with 2, featuring a key enantioselective intramolecular aromatic nucleophilic substitution (SNAr) step.