Crystallographic/experimental electron density characterizations and reactions with nucleophiles of beta-enaminonitriles possessing a pyrrolobenzazepine core.
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 N(9) 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.
Pizzonero
Mathieu
M
Laboratoires BIOCIS (UMR 8076), PPB (UMR 8612), and Cristallographie Bio-inorganique, Faculté de Pharmacie, Université Paris-Sud, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
Keller
Laurent
L
Dumas
Françoise
F
Ourevitch
Michèle
M
Morgant
Georges
G
Spasojević-de Biré
Anne
A
Bogdanović
Goran
G
Ghermani
Nour Eddine
NE
D'Angelo
Jean
J
D001552:Benzazepines / Q000737:chemistry*; D003461:Crystallography; D004583:Electrons; D006248:Harringtonines / Q000138:chemical synthesis; D000077863:Homoharringtonine; D008958:Models, Molecular; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry*
D001552:Benzazepines; D006248:Harringtonines; D009570:Nitriles; D000077863:Homoharringtonine