Mémoire
| Résumé : | Disubstituted maleimides are frameworks that can be found in bioactive natural and synthetic products, and in materials science. A variety of efficient methods for the synthesis of these nitrogen heterocycles have already been reported, but they often lack generality or start from non-convenient starting materials, especially when two different substituents must be introduced on the maleimide skeleton. In this context, we have developed and studied a novel synthesis of non-symmetrical polysubstituted maleimides from readily available N-carboxyethyl-ynamides. Upon treatment with a strong base, these ynamides enable a smooth generation of the corresponding metalated ketenimines, which were further reacted in situ with α-ketoesters to provide disubstituted maleimides in a mild and versatile process. Notably, this method permitted the use of different aromatic α-ketoesters, and both aromatic and aliphatic ynamides were tolerated. Moreover, the temperature was found to have a dramatic influence on the outcome of the reaction and on the final substitution of the nitrogen atom, which could be either protected by a tert-butoxycarbonyl (Boc) group, unprotected, or embedded with a propionate moiety. Selectivity issues between these products remain, however, to be solved. |
