Iminium cyclization/azomethine ylid cycloaddition cascades for alkaloid syntheses - synthèse d'alcaloïdes par cyclisations d'iminiums/cycloaddition d'ylure d'axométhine en tandem

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IMINIUM CYCLIZATIONS/AZOMETHINE YLID CYCLOADDITION CASCADES FOR ALKALOID SYNTHESESIn this research proposal, we intend to develop two innovative ways of constructing natural products through cyclization reactions in cascade. In one of our projects, we are using iminium ions in a double cyclization cascade. We started by setting the first cyclization (Vilsmeier-Haack), which was greatly challenging and ended up giving rise to two publications (Org. Lett. 2005, 7, 4431 and J. Org. Chem. 2006, 71, 704). Our preliminary results of double cyclization showed that the strategy works on a model systems. The proposed research is thus aimed at determining the scope and limitation of the double cyclization strategy and at constructing natural products with this new synthetic strategy to show its applicability. Our second project is also taking advantage of our recently developed Vilsmeier-Hack cyclization but toward a completely different end. In fact, the Vilsmeier-Haack cyclization product is still an iminium ion that we used to generate an azomethine ylid that could undergo a completely different type of cyclization (cycliaddition) compared to a second iminium cyclization as found in the first project presented. This strategy (iminium cyclization - azomethine ylid cycloaddition) now offers the possibility to create tricyclic cores of biologically interesting alkaloids in one operation. We are pursuing this project by expanding the scope of this reaction cascade to a wide range of different alkaloid skeletons by simple modulation on the starting compound. We also intend to apply this synthetic strategy to the construction of natural product as well.