Charge density of a putative intermediary product in the total synthesis of the cephalotaxine

International audienceA high resolution diffraction measurement have been performed on a putative precursor of cephalotaxine; using a Brücker CCD detector. The compound crystallizes in P21/n space group (V = 1174.49(2) Å-3). 161121 reflections were collected leading to 10690 independent reflections up to 1,11 Å-1 (Rint = 0,0215). Multipole refinement (Hansen and Coppens model [1]) converges with reliability factors (R(F) = 0,0283 and GOF = 1,32). Electron deformation maps show up a strong delocalization over the four cycles. The calculation of the atomic net charges deduced from a k refinement are in agreement with the reactivity (or the non-reactivity) of the compound. The topological properties at the bond critical points (3,-1) are reported and are also in a quite good agreement with the chemistry. Finally the electrostatic potential has been calculated [2] and two different representations are used in order to characterize the compound: 3D isopotential surfaces, and 3D isodensity molecular surface colored by the electrostatic potential (figure). [1] Hansen N. Coppens P.

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

International audienceIn 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

Apports de la diffraction des rayons X et de la densité électronique expérimentale à l’étude d’intermédiaires de synthèse de la céphalotaxine

International audienc

Charge density of a putative synthetic intermediate in the total synthesis of the cephalotaxine

International audienc

Apports de la diffraction des rayons X et de la densité électronique expérimentale à l’étude d’intermédiaires de synthèse de la céphalotaxine

International audienc

Charge density of a putative synthetic intermediate in the total synthesis of the cephalotaxine

International audienc