Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)₂PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through ¹H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)₂PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of ¹H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by ³¹P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (R_s)". Significantly, this class of CSAs based on (alkaloid)₂linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.