Kinetics versus thermodynamics in the proline catalyzed aldol reaction† †Electronic supplementary information (ESI) available: Experimental details, calculated energies, geometries and simulations. See DOI: 10.1039/c6sc01328g

• Published in: Chemical science (Cambridge) Vol. 7; no. 8; pp. 5421 - 5427
• Main Authors: Orlandi, M., Ceotto, M., Benaglia, M.
• Format: Journal Article
• Language: English
• Published: Royal Society of Chemistry 06.05.2016
• Subjects: Chemistry
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c6sc01328g

The reversibility of the reaction was proved and a new rate law was obtained; the use of a Multiple Transition State Approach (MTSA), that includes both kinetics and thermodynamics in the description of the process, successfully rationalizes the chemical and stereochemical outcomes of this paradigmatic reaction for the first time. In this paper the equilibrium properties of the proline catalyzed aldol reaction was studied. The use of well-established methodologies, like reaction progress kinetic analysis and linear free energy relationship analysis, led to the quantification of the reaction reversibility and to its correlation with the substrate electronic activation. Due to these experimental observations, common computational approaches based on a one way transition state analysis become unsuitable. Therefore, a computational model based on the integration of a system of kinetic differential equations associated to the multiple equilibrium reactions was proposed. Such a model was found to successfully rationalize the chemical and stereochemical outcomes of this paradigmatic reaction for the first time.