One-step synthesis of homochiral O-aryl and O-heteroaryl mandelic acids and their use as efficient 1H NMR chiral solvating agents

Abstract

Job and Buchwald’s one-step copper-promoted arylation of hydroxyl groups was explored and modified so that it could be applied to the coupling of mandelic acid with several halobenzenes and haloheteroarenes. A number of new homochiral O-aryl and O-heteroaryl mandelic acids, generally presenting high enantiomeric purities, were obtained. Although yields were moderate at the best, ranging from 9% to 41%, the reaction was convenient enough to prepare new mandelic acid derivatives, some of which performed as efficient chiral solvating agents (CSAs) for the direct 1H NMR ee value determination of several clinically and pharmacologically relevant amines.