Studies on the Acidities of C2 Symmetrical Chiral Phosphoric Acids Based on a Decahydroquinoxaline Scaffold
Margherita Gazzotti1, Daniele Fumagalli1, Valentina Pifferi1
1Dipartimento di Chimica, Università Degli Studi di Milano, via Golgi 19, Milano 20133, Italy.
Abstract:
The pK a values of 34 new C2-symmetrical chiral phosphoric acids based on a decahydroquinoxaline scaffold were computed by DFT calculations. The pK 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 pK a values are in good agreement with measurements, with differences generally below 1 pK 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.
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