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

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）：对映选择性氨基和烯胺催化途径已被证明是不对称键构建的高效手段。最小介导过程提供了独特的机会，在一个单一的合成步骤中多个键的构建，因为伴随形成的烯胺中间体。虽然在文献中已经广泛记录了最小和enamine过程的例子，但报道的将两种途径结合在多米诺骨牌序列中的病例很少。本研究旨在开发单手性胺类有机催化剂催化的不对称胺偶联加成/碳环化反应。感兴趣的碳环化是烷基化，醛醇，曼尼希和迈克尔加成过程。该方法为构建具有光活性的密集官能化吡咯烷和哌啶杂环提供了一种高度收敛的方法。作为本提案的最终目标，所开发的方法将应用于全功能化吡咯烷类plakoridines a和b的全合成。Plakoridine a由于其对小鼠淋巴瘤L1210细胞的细胞毒性而特别令人感兴趣。