Kinetically-Persistent Carbocationsin C-H Insertion Reactions and Biomimetic Cyclization Cascades

C-H 插入反应和仿生环化级联中的动力学持久碳阳离子

• 批准号: 10570774
• 负责人: Hosea Martin Nelson
• 金额: $ 41.02万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10570774
• 关键词: Kinetically; Persistent; Carbocationsin; Insertion; Reactions

Project Summary Nearly all bioactive compounds, whether drug or tool molecule, are built upon frameworks composed of carbon-to-carbon (C–C) bonds. This is evidenced by extensive efforts from the synthetic community aimed at expanding the scope, efficiency, and selectivity of established C–C bond forming reactions. Many of the most commonly employed methods, such as transition metal-catalyzed cross-coupling or nucleophilic substitution reactions, rely on the multi-step conversion of simple building blocks into reactions partners that are appropriately functionalized to partake in C–C bond forming events. Furthermore, many of the transition metal catalysts that are used in these processes are expensive, toxic, and unsustainable due to their low natural abundance. While these existing C–C bond forming processes are powerful, new methods that address the aforementioned shortcomings would facilitate the development of therapeutic compounds. The long-term goal of the proposed research activities is to address this challenge at the fundamental level through the development of novel C–C bond forming reactions. This proposal outlines the first step in achieving this goal through the development of new electrophilic reactions that feature Earth-abundant and biologically benign catalysts. Specifically, we describe C–H arylation processes that are catalyzed by silicon/boron salts. Moreover, we propose new methods for the synthesis of polycyclic terpenes catalyzed by silicon/boron salts. The proposed research is innovative because it describes approaches to C–C bond formation that challenge dogmas in the methodology field. It is innovative because it leverages the tools and concepts of several field of chemistry (reactive intermediate chemistry, total synthesis and fundamental inorganic chemistry) into the development of practical organic transformations. The described studies are significant because they disclose several new strategies to form C–C bonds that are premised on new concepts in catalysis. These concepts will spur diverse and innovative practical applications, and inspire theoretical study. Ultimately the research proposed in this document will contribute to medicine through chemical synthesis and to society through an improved understanding of fundamental chemical reactivity.

项目摘要 几乎所有的生物活性化合物，无论是药物还是工具分子，都是建立在由以下组成的框架上的： 碳-碳（C-C）键。合成社区的广泛努力就证明了这一点，旨在 扩大了已建立的C-C键形成反应的范围、效率和选择性。许多最 常用的方法，如过渡金属催化的交叉偶联或亲核取代 反应，依赖于简单的结构单元到反应伙伴的多步转化， 适当官能化以参与C-C键形成事件。此外，许多过渡金属 在这些方法中使用的催化剂是昂贵的、有毒的，并且由于它们的低天然活性而不可持续。 丰饶。虽然这些现有的C-C键形成过程是强大的，但解决C-C键形成过程的新方法仍然存在。 上述缺点将促进治疗化合物的开发。远景目标 拟议的研究活动之一是通过以下方式在基本层面应对这一挑战： 开发新的C-C键形成反应。这一提议概述了实现这一目标的第一步 通过开发新的亲电反应， 催化剂的具体而言，我们描述了由硅/硼盐催化的C-H芳基化过程。 此外，我们提出了硅/硼盐催化合成多环萜烯的新方法。 拟议的研究是创新的，因为它描述了C-C键形成的方法，挑战了 方法论领域的教条。它是创新的，因为它利用了几个领域的工具和概念， 化学（反应中间体化学，全合成和基础无机化学） 发展实际的有机转化。所描述的研究是重要的，因为它们揭示了 几种形成C-C键的新策略，它们与催化学中的新概念有关。这些概念将 刺激多样化和创新的实际应用，并激发理论研究。最终，研究 本文件中提出的将通过化学合成为医学做出贡献，并通过 提高对基本化学反应性的理解。