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

亚胺环化/偶氮甲叉基环加成级联反应制备生物碱在本研究中，我们打算开发两种通过级联环化反应构建天然产物的创新方法。在我们的一个项目中，我们在双环化级联中使用亚胺离子。我们开始设置第一个环化（Vilsmeier-Haack），这是非常具有挑战性的，并最终产生了两个出版物（Org. Lett. 2005，7，4431和J. Org. Chem. 2006，71，704）。双环化反应的初步结果表明，该策略对模型体系有效。因此，拟议的研究旨在确定双环化策略的范围和限制，并在构建天然产物与这种新的合成策略，以显示其适用性。我们的第二个项目也利用了我们最近开发的Vilsmeier-Hack环化，但目标完全不同。事实上，Vilsmeier-Haack环化产物仍然是一种亚胺离子，我们使用它来生成甲亚胺叶立德，与第一个项目中发现的第二次亚胺环化相比，它可以经历完全不同类型的环化（环加成）。这种策略（亚胺环化-甲亚胺叶立德环加成）现在提供了在一次操作中产生生物学上感兴趣的生物碱的三环核心的可能性。我们正在通过对起始化合物进行简单的调节，将该反应级联的范围扩展到广泛的不同生物碱骨架来进行该项目。我们还打算将这种合成策略应用于天然产物的构建。

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.