Crystallographic/experimental electron density characterizations and reactions with nucleophiles of β-enaminonitriles possessing a pyrrolobenzazepine core - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Organic Chemistry Année : 2004

Crystallographic/experimental electron density characterizations and reactions with nucleophiles of β-enaminonitriles possessing a pyrrolobenzazepine core

Résumé

In connection with a total synthesis of cephalotaxine (1a), we have examined the addition of various nucleophilic reagents to [ABC] subunits 2 and 7 possessing a pyrrolobenzazepine core. In fact, this reaction implicates invariably the carbonyl group of 2. Regarding the reaction of 7 with nucleophiles, the most striking aspect is the complete lack of reactivity of the enaminonitrile moiety. For instance, the condensation of 7 with methylmagnesium bromide involves exclusively the cleavage of the dioxole ring, yielding regioisomers 9 and 10. With the aim of understanding the unexpected reactivity of 2 and 7 toward nucleophiles, crystallographic studies of 2 and 7 and an experimental electron density determination of 7 were carried out. The marked reactivity of the carbonyl group of 2 was interpreted by invoking the weakness of the amide resonance, due to a pronounced delocalization of the N9 lone pair over the enaminonitrile moiety. The electron density study of 7 reveals this electron delocalization along the enaminonitrile fragment, highlighted and quantified through the bond geometries, topological indicators, and atomic charges, a phenomenon that is responsible for the failure of the addition of nucleophilic species.
Fichier principal
Vignette du fichier
hal-02296123 Article-joc.pdf (1.79 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02296123 , version 1 (30-09-2020)

Identifiants

Citer

M. Pizzonero, L. Keller, F. Dumas, M. Ourevitch, G. Morgant, et al.. Crystallographic/experimental electron density characterizations and reactions with nucleophiles of β-enaminonitriles possessing a pyrrolobenzazepine core. Journal of Organic Chemistry, 2004, 69 (13), pp.4336-4350. ⟨10.1021/jo049681x⟩. ⟨hal-02296123⟩
30 Consultations
64 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More