Diastereomer Interconversion via Enolization: A Case Study.
Fiche publication
Date publication
novembre 2015
Journal
Chirality
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SAPI Janos, Dr GERARD Stéphane
Tous les auteurs :
Renzetti A, Di Crescenzo A, Nie F, Bond AD, Gérard S, Sapi J, Fontana A, Villani C
Lien Pubmed
Résumé
The three-component reaction of indole, isobutyraldehyde, and methyl acetoacetate affords methyl 2-(acetyl)-3-(1H-indol-3-yl)-4-methylpentanoate as a single diastereomer. To investigate the origin of the observed diastereoselectivity, the thermodynamics and kinetics of interconversion of diastereomers 1 and 2 in solution were studied by a combination of (1)H nuclear magnetic resonance (NMR) spectroscopy, high-performance liquid chromatography (HPLC), mass spectrometry, and deuteration experiments. The results indicate that interconversion is both acid- and base-catalyzed, and that the alpha carbon is the only stereolabile center in the molecule. The evidence points to an enolization mechanism for the interconversion process. The selective precipitation of 1 in the presence of the equilibrium 1⇆2 eventually results in the exclusive formation of 1 (crystallization-induced asymmetric transformation).
Mots clés
Acetoacetates, chemistry, Aldehydes, chemistry, Chromatography, High Pressure Liquid, Crystallography, X-Ray, Indoles, chemistry, Proton Magnetic Resonance Spectroscopy, Spectrometry, Mass, Electrospray Ionization, Stereoisomerism
Référence
Chirality. 2015 Nov;27(11):779-83