Synthesis of Chiral 2,5-Bis(oxazolinyl)thiophenes and Their Application as Chiral Shift Reagents for 1,1′-Bi-2-naphthol

A series of C 2-symmetrical chiral 2,5-bis(4′-alkyloxazolin-2-yl)thiophenes (thiobox) have been synthesized from thiophene-2,5-dicarboxylic acid by sequential amidation with a chiral ethanolamine, conversion of hydroxyl to chloro group, and base-promoted oxazoline ring formation. As demonstrated by (-)-2,5-bis[4′-(S)-isopropyloxazolin-2′-yl]thiophene, these thiobox systems exhibited remarkable chirality recognition of 1,1′-bi-2-naphthol giving rise to pronounced shifts in the 1H NMR signals of the latter axial chiral compound at the positions of C-3, C-4, C-5, and C-8.