Mechanistic Study of Intramolecular Aldol Reactions of Dialdehydes

• Published in: European Journal of Organic Chemistry 2008-07, Vol.2008 (19), p.3397-3402
• Main Authors: Duarte, Filipe J. S., Cabrita, Eurico J., Frenking, Gernot, Santos, A. Gil
• Format: Article
• Language: English
• Subjects: Aldol reactions; Asymmetric catalysis; Density functional calculations; Transition states
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200800222

Transition states associated with the C–C bond‐formation step in proline‐catalyzed intramolecular aldol reactions of 1,7‐dialdehydes were studied using density functional theory methods (DFT), at the B3LYP/6‐31G(d,p) level. A polarizable continuum model (PCM) was used to describe solvent effects. Two reactive channels, corresponding to the anhydrous system or to the explicit inclusion of water have been analysed. Computational data allow us to rationalize the intramolecular aldol reaction experimental outcome, validating the proposed enamine‐based mechanism, as well as to suggest the importance of water in the control of the reaction stereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) TSs associated with the C–C bond‐formation step in proline‐catalyzed intramolecular aldol reactions of 1,7‐dialdehydes are studied using DFT methods. Two reactive channels, corresponding to the anhydroussystem or to the explicit inclusion of water are analysed. Theoretical data allows the rationalization of the experimental results and validates the proposed mechanism.