Organocatalytic Asymmetric Cascade Reactions

有机催化不对称级联反应

• 批准号: 7052299
• 负责人: David A Nicewicz
• 金额: $ 4.4万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052299
• 关键词: aldehydes; alkylation; amines; catalyst; chemical addition; chemical binding; chemical bond; chemical structure; imines; nitrogenous heterocyclic compound; piperidine; postdoctoral investigator; pyrrolidines; stereoisomer; aldehydes; alkylation; amines; catalyst; chemical addition; chemical binding; chemical bond; chemical structure; imines; nitrogenous heterocyclic compound; piperidine; postdoctoral investigator; pyrrolidines; stereoisomer

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.

描述（由申请人提供）：事实证明，对映选择性神经和魔法催化的途径是非对称键结构的高效手段。隐身介导的过程为单个合成步骤提供了多个键结构的独特机会，这是由于魔源烯胺中间体的伴随形成。尽管文献中已广泛记录了圣经和谜过程的例子，但据报道，在多米诺骨牌序列中结合这两种途径的案例很少见。该提案的目的是开发出由单手性胺有机催化剂催化的不对称胺偶联添加/碳环化反应。感兴趣的碳纤维分类是烷基化，Aldol，Mannich和Michael添加过程。该方法将提供一种高度收敛的方法，用于构建光学活性密集的吡咯烷和哌啶杂环。作为该提案的最终目标，开发的方法将应用于全功能化的吡咯烷丙酰胺A和B. plakoridine a的总合成，这尤其引起了人们的关注，因为其对鼠淋巴瘤L1210细胞的细胞毒性有记录。