Theoretical mechanistic study of the TBD-catalyzed intramolecular aldol reaction of ketoaldehydes.

Date publication

juillet 2010

Auteurs

Membres identifiés du Cancéropôle Est :
Dr WAGNER Alain

Tous les auteurs :
Hammar P, Ghobril C, Antheaume C, Wagner A, Baati R, Himo F

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/20545376

Résumé

The intramolecular aldol reaction of acyclic ketoaldehydes catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is investigated using density functional theory calculations. Compared to the proline-catalyzed aldol reaction, the use of TBD provides a unique and unusual complete switch of product selectivity. Three mechanistic pathways are proposed and evaluated. The calculations provide new insights into the activation mode of bifunctional guanidine catalysts. In the favored mechanism, TBD first catalyzes the enolization of the substrate and then the C-C bond formation through two concerted proton transfers. In addition, the computationally predicted stereochemical outcome of the reaction is in agreement with the experimental findings.

Référence

J Org Chem. 2010 Jul 16;75(14):4728-36.