Enamides and ynamides to generate molecular complexity

Overview & Synopsis

The work described in this thesis manuscript focused first on the development of a domino reaction from N-imides equipped enamidyl vinyl ketones. Secondly, the reactivity of ynamides towards diazo compounds was studied to access, on one hand, to difluorinated amido-furans and on the other hand to a new synthesis of N-allenamides.Tertiary enamides integrated into cross-conjugated dienones underwent a domino-reaction involving N-acyliminium ion trapping followed by a Nazarov cyclization. Psychoactiv substructures i.e diazepines fused with cyclopentenones were thus obtained with very good yields.A copper-catalyzed addition of difluorinated diazoacetone to ynamides made it possible to develop a new synthesis of difluorinated amidofurans highly valued in medicinal chemistry and phytochemistry. These compounds were then used as platforms to achieve the synthesis of more complex heterocycles.The particular reactivity of ynamides towards diazo compounds has enabled us to develop a new synthesis of terminal N-allenamides. By using judisciously functionnalized diazo compounds, we obtained push-pull N-allenamides substituted in position  by a CF3, CF2H or a CF3CF2 moiety.