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

Year: 2026

Type: article

Abstract: 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.

Source: ACS Omega

DOI: 10.1021/acsomega.5c13291

Authors: Margherita Gazzotti, Daniele Fumagalli, Valentina Pifferi, Laura Raimondi, Sergio Rossi

Institution: University of Milan

Language: English

Topic: Chemical Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $1,935

Funders: Università degli Studi di Milano, Ministero dell’Istruzione, dell’Università e della Ricerca, NextGenerationEU