Organocatalytic Asymmetric Cascade Reactions

描述（由申请人提供）：对映选择性亚胺和烯胺催化途径已被证明是不对称键结构的高效手段。由于伴随形成烯胺中间体，因此直接介导的过程在单个合成步骤中提供了多键构建的独特机会。尽管文献中已经广泛记载了immagnesium和enamine过程的例子，但在多米诺骨牌序列中将这两种途径结合起来的报告案例很少。本研究的目的是发展一种单一手性胺有机催化剂催化的不对称胺共轭加成/碳环化反应。感兴趣的碳环化是烷基化、羟醛、曼尼希和迈克尔加成过程。这种方法将提供一个高度收敛的方法，用于构建光学活性的密集官能化的吡咯烷和哌啶杂环。作为本提案的最终目标，所开发的方法学将应用于全官能化吡咯烷plakoridine A和B的全合成。普拉可定A由于其对鼠淋巴瘤L1210细胞的细胞毒性而特别令人感兴趣。

DESCRIPTION (provided by applicant): Enantioselective imminium and enamine catalyzed pathways have proven to be highly effective means for asymmetric bond constructions. Imminium mediated processes provide unique opportunities for multiple bond constructions in a single synthetic step because of concomitant formation of enamine intermediates. Though examples of both imminium and enamine processes have been extensively documented in the literature, reported cases uniting the two pathways in a domino sequence are rare. It is the intent of this proposal to develop imminium catalzyed asymmetric amine conjugate addition/carbocyclization reactions catalyzed by a single chiral amine organocatalyst. The carbocyclizations of interest are alkylation, aldol, Mannich, and Michael addition processes. This methodology would provide a highly convergent method for the construction of optically active densely functionalized pyrrolidine and piperidine heterocycles. As a final goal of this proposal, the methodology developed will be applied to the total syntheses of the fully- functionalized pyrrolidines plakoridines A and B. Plakoridine A is of particular interest due to its documented cytotoxicity towards murine lymphoma L1210 cells.