A novel catalyst for asymmetric aldol reactions: Modelling the effect of Homoboroproline as asymmetric catalyst

Chiral amino boronic acids have a wide field of application including enzyme inhibitors, anti-cancer agents, molecular sensors and catalysts. As catalysts, they draw considerable amount of attention. Recently, Whiting et al. have synthesized proline based amino boronic acids and have showed that they are efficient catalysts in the asymmetrical aldol reaction between acetone and p-nitrobenzaldehyde. Since it is suggested that the reaction mechanism proceeds through enamine, as in proline-catalyzed aldol reactions, this new catalyst is identified as homoboroproline. Although the mechanisms of proline-catalyzed aldol reactions have been of great interest both experimentally and theoretically and have been examined in detail, asymmetrical aldol reaction occuring in the presence of homoboroproline is quite new and its mecahnism has been modelled in the present thesis study for the first time. The mechanism has been modelled by Density Functional Theory (DFT) PCM/M06-2X/6-31(d,p) method in acetone, taking into account differentorientations of the aldehyde. By means of Gibbs free energy activation barrier calculations, the mechanism has been clarified and factors that give rise to enantioselectivity have been explained. Through the mechanism demonstrated by the present thesis study, it will be possible to develop path models which will enable obtaining drug active substances possessing chiral alcohol centers in enantioselective fashion.