Studies on the Acidities of C ₂ Symmetrical Chiral Phosphoric Acids Based on a Decahydroquinoxaline Scaffold

High Resolution Image Download MS PowerPoint Slide The p K a values of 34 new C 2 -symmetrical chiral phosphoric acids based on a decahydroquinoxaline scaffold were computed by DFT calculations. The p K a values were computed in DMSO and acetonitrile using two computational methods: the isodesmic approach and the linear free energy scaling relationship (LFESR) approach. Both methods were first benchmarked against experimental data for BINOL-derived chiral phosphoric acids and then applied to a wide series of decahydroquinoxaline-based chiral phosphoric acids, highlighting trends in acidity correlated to the electronic nature of substituents on the decahydroquinoxaline scaffold. Experimental validation by potentiometric titration confirmed that the predicted p K a values are in good agreement with measurements, with differences generally below 1 p K a unit. These results provide a deeper understanding of the relationship between structure and acidity in CPAs and represent a simulating model for the rational design of next-generation chiral phosphoric acid catalysts in stereoselective transformations.