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You are here: Home Science & Projects Deisa Extreme Computing Initiative Projects 2009 - 2010 Theoretical insights into the mechanisms of organocatalytic asymmetric aldol reactions in aqueous media

Theoretical insights into the mechanisms of organocatalytic asymmetric aldol reactions in aqueous media

Project ORGCAT
Research Area Materials Science
Principal Investigator(s) Marco Masia
Institution(s)
  • University of Sassari, Department of Chemistry, Italy
  • Ruhr-Universität Bochum, Germany
  • Universitat Rovira i Virgili, Departament de Química Física, Spain

Abstract

The development of small organic molecules that catalyze enantioselective reactions in water is currently a highly sought goal in chemistry. In particular, the asymetric organocatalytic aldol reaction, which is a synthetically key carbon-carbon bond-forming reaction, is being extensively studied by many experimental research groups. In fact, it has been recently discovered [Aratake, S. et al. Chem. Commun. 2007, 2524] that the amide of S-proline is able to catalyze the self-aldol reaction of propanal in water with good enantioselectivity. This is the first case of a small organic molecule catalyzing the asymetric, direct aldol reaction in water. The aim of our project is to explore by means of computational simulations the mechanism of such reaction, which is thought to proceed via an enamine intermediate. Specifically, we want to address the following points: a) which is the free energy profile for the reaction; b) which are the key parameters controlling the enantioselectivity of the reaction; c) which hydrogen bonds are fundamental for the reaction, and how do they affect the outcome of the reaction; and, d) which is the role played by the solvent. In order to carry out the study we will employ ab initio molecular dynamics and metadynamics. After having studied this reaction, we will apply the same methodology to the study of the aldol reaction of benzaldehyde with cyclohexanone catalysed by siloxyproline, a very efficient and stereoselective reaction performed in excess of water [Y. Hayashi. et al. Angew. Chem. Int. Ed. 2006, 45, 958], which takes place in a biphasic system.

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