Nouveaux modèles du NADH en série oxazolyl-3 dihydro-1,4 pyridine: synthèse, réactivité, rôle de la complexation dans la réactivité

Abstract

A new class of NADH models is described: they contain the 3-oxazolyl-1,4-dihydropyridine structure. They have been synthesized by regioselective addition at the 4 position of organometallic derivatives (one of them bearing a chiral group) on 3-(4,4-dimethyl-2-oxazolyl)pyridine. The 1,4-dihydropyridine structure is obtained after quaternarization and reduction by sodium dithionite. Quaternarization through Zincke's reaction leads to models having a chiral group at the pyridine nitrogen. This chirality is necessary to induce asymmetry at the 4 carbon in the corresponding 1,4-dihydropyridine. This asymmetry plays an important role in the low enantioselectivity of reduction of a prochiral substrate such as methyl benzoylformate. The chemical reactivity of the models has been studied by performing the reduction of p-nitrobenzaldehyde in the presence of magnesium perchlorate. All models gave quantitative yields. However, reactions are slower than those performed, in the same conditions, with N-benzyl-1,4-dihydronicotinamide (BNAH). A 13C nmr study shows that this behaviour is probably a consequence of the high complexation of magnesium with the oxazoline moiety.