from first principles PP-I-1

PP-III-44Rationalisation of the Catalytic Role of Triazole-Linkers in AsymmetricAldol Reactions in Water Catalysed by Polystyrene-SupportedHydroxyprolineKarlsson E.A., Pericàs M.A.Institute of Chemical Research of Catalonia, Tarragona, Spainekarlsson@iciq.esWhile investigating a newly developed polystyrene-supported hydroxyproline catalyst for thepurpose of asymmetric cross-aldol reactions [1], water was found to be an optimal solvent forenantio- and diastereoselectivity, in contrast with polar organic solvents such as DMSO andDMF. In a following study where different strategies for linking hydroxyproline to thepolystyrene resin were compared [2], it was furthermore discovered that the presence of a1,2,3-triazole unit as a linking group was essential for high enantioselectivity, in addition tothe use of water as solvent. The 1,2,3-triazole unit, introduced by the means of a coppercatalysed1,3-dipolar cycloaddition between an alkyne and an azide for the purpose of catalystimmobilization, and initially considered as an innocent linking group was thus shown toactively take part in the catalysis and positively influence enantioselectivity.This effect has been rationalised computationally by means of DFT methodology. The fourpossible diastereomeric transition states in model aldol reactions were calculated employing acombination of a continuous solvation model (PCM), and explicit water molecules. It wasthus demonstrated that the formation of a bridge, consisting of three water molecules,between the triazole and the carboxylic group of the proline would lead to increasedstabilization of the transition states leading to the favoured enantiomer, and thus result inincreased enantioselectivity compared to the situation where either the triazole unit or water isabsent.References:[1] D. Font, C. Jimeno, M. A. Pericàs, Org. Lett. 8 (2006) 4653.[2] D. Font, S. Sayalero, A. Bastero, C. Jimeno, M. A. Pericàs, Org. Lett. 10 (2008) 337.197