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.
Mots clés
geometry
isomer
polymerization
reaction analysis
structure analysis
cyanide
enamine
magnesium derivative
cephalotaxine
Nucleophilic reagents
Aromatic hydrocarbons
3 dioxolane derivative
benzazepine derivative
beta enaminonitrile
carbonyl derivative
Bond geometrics
Resonance
Electron transitions
Condensation
Carrier concentration
methylmagnesium bromide
nitrile
unclassified drug
article
crystallography
drug structure
drug synthesis
electron
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