Intramolecular Aryne Cycloadditions and Rearrangements

分子内芳炔环加成和重排

• 批准号: 6877071
• 负责人: KEITH R. BUSZEK
• 金额: $ 24.11万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877071
• 关键词: alkaloids; biological products; chemical reaction; chemical structure; chemical synthesis; cholinesterase inhibitors; conformation; diene; intermolecular interaction; stereochemistry

DESCRIPTION (provided by applicant): The long term goals of this proposal are to understand the structural, electronic, conformational and steric parameters that lead to the various types of interesting and novel intramolecular aryne cycloadditions (IMACs) and rearrangements, and to develop these processes into a powerful set of applications for the construction of complex and important natural products. To accomplish these goals we will design, synthesize and investigate various systems that lead to some of the important classes of IMACs such as the [4+2], [2+2] and [2+2] with rearrangement, Type II [4+2], and ene reaction manifolds. With the exception of our own work just six other examples of intramolecular aryne cycloaddition chemistry have been reported in the literature, and all of these have been limited to the [4+2] reaction manifold and then only with aromatic dienes. The need to explore this suite of reactions is therefore compelling and of high intellectual merit. We will examine these cycloaddition manifolds from both synthetic as well as mechanistic perspectives. Significantly, we believe this proposal represents the first ever systematic attempt to assess the comprehensive reaction profile of arynes with respect to their intramolecular cycloaddition behavior. Moreover, these processes have the potential to generate new and exciting structural motifs that would be difficult or impossible to prepare by existing technologies and methods. This study will provide an important foundation and contribute significantly to the understanding of aryne cycloaddition chemistry. Our published and preliminary studies with respect to the [4+2], tandem [2+2]cycloaddition-rearrangement, and ene processes clearly demonstrate, inter alia, the proof of concept and the intrinsic value of pursuing this line of research further. We will also synthesize the selective cholinesterase inhibitor galanthamine as a demonstration of the synthetic potential of intramolecular aryne cycloaddition chemistry in the construction of a wide range of complex and architecturally diverse natural products.

描述（由申请人提供）：本提案的长期目标是了解导致各种类型有趣和新颖的分子内芳香环加成（imac）和重排的结构，电子，构象和立体参数，并将这些过程发展成为构建复杂和重要天然产物的强大应用程序。为了实现这些目标，我们将设计、合成和研究导致一些重要类型的imac的各种系统，如[4+2]、[2+2]和[2+2]重排、II型[4+2]和烯反应流形。除了我们自己的工作外，文献中只报道了六个分子内芳环加成化学的例子，所有这些都局限于[4+2]反应歧管，然后只与芳香二烯反应。因此，探索这一系列反应的需要是令人信服的，而且具有很高的智力价值。我们将从合成和机械的角度来研究这些环加成流形。值得注意的是，我们认为这一提议代表了有史以来第一次系统地评估芳烃分子内环加成行为的综合反应谱。此外，这些工艺有可能产生新的和令人兴奋的结构基元，这是现有技术和方法难以或不可能制备的。该研究将为进一步了解芳烷环加成化学提供重要的基础和重要的贡献。我们关于[4+2]，串联[2+2]环加成重排和烯过程的已发表和初步研究清楚地表明，除其他外，概念的证明和进一步开展这一研究的内在价值。我们还将合成选择性胆碱酯酶抑制剂加兰他明，以证明分子内芳环加成化学在构建广泛的复杂和结构多样的天然产物方面的合成潜力。