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

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 H-1 NMR ee value determination of several clinically and pharmacologically relevant amines.