Kinetically-Persistent Carbocations in C-H Insertion Reactions and Biomimetic Cyclization Cascades

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证明了这一点，目的是 扩大已建立的C-C成键反应的范围、效率和选择性。许多最重要的 常用的方法，如过渡金属催化的交叉偶联或亲核取代 反应，依赖于简单构建块到反应伙伴的多步骤转换，这些反应伙伴 适当地官能化，以参与C-C键形成事件。此外，许多过渡金属 这些过程中使用的催化剂价格昂贵、有毒，而且由于其天然含量低而不可持续。 富足。虽然这些现有的C-C键形成过程是强大的，但新的方法解决了 上述缺点将促进治疗性化合物的发展。长期目标 拟议研究活动的一部分是在根本层面上解决这一挑战 新型C-C成键反应的研究进展。该提案概述了实现这一目标的第一步。 通过开发新的亲电反应，这些反应具有丰富的地球和生物无害的特点 催化剂。具体地说，我们描述了硅/硼盐催化的C-H芳基化过程。 此外，我们还提出了硅/硼盐催化合成多环萜烯的新方法。 这项拟议的研究具有创新性，因为它描述了挑战C-C键形成的方法 方法论领域的教条。它具有创新性，因为它利用了以下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) 发展实用的有机转型。所描述的研究具有重要意义，因为它们揭示了 以催化中的新概念为前提的几种形成C-C键的新策略。这些概念将 激发多样化、创新性的实践应用，启发理论研究。最终，这项研究 将通过化学合成为医学做出贡献，并通过 提高了对基本化学反应的理解。

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.