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: 10457262
• 负责人: Hosea Martin Nelson
• 金额: $ 40.72万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457262
• 关键词: Address; Benign; Biomimetics; Boron; Carbon; Catalysis; Chemicals; Chemistry; Communities; Coupling; Cyclization; Development; Drug Compounding; Event; Goals; Inorganic Chemistry; Kinetics; Medicine; Methodology; Methods; Mission; Organism; Pharmaceutical Preparations; Planet Earth; Process; Public Health; Reaction; Research; Research Activity; Salts; Silicon; Societies; Terpenes; Theoretical Studies; Transition Elements; United States National Institutes of Health; catalyst; chemical reaction; chemical synthesis; improved; innovation; novel; nucleophilic substitution; practical application; technology development; therapeutic development; tool

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 几乎所有生物活性化合物，无论是药物或工具分子，都建立在由框架上 碳到碳（CC）键。合成社区的广泛努力证明了这一点 扩大已建立的C -C键形成反应的范围，效率和选择性。最多的 通常使用的方法，例如过渡金属催化的交叉耦合或核底面取代 反应，依靠简单构建块的多步转换为反应伙伴 适当功能化以参与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由于其自然低而昂贵，有毒且不可持续 抽象。尽管这些现有的C – C键形成过程是强大的，但要解决的新方法 关于典型的缺点将支持理论化合物的发展。长期目标 拟议的研究活动是通过 新型C – C键形成反应的发展。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，这些反应具有土壤丰富和生物学良性 催化剂。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，我们提出了新方法，用于合成由硅/硼盐催化的多环萜。 拟议的研究具有创新性，因为它描述了C -C债券形成的方法 方法论领域的教条。它具有创新性，因为它利用了几个领域的工具和概念 化学（反应性中间化学，总合成和基本无机化学） 开发实用的有机转化。所描述的研究很重要，因为他们披露了 形成CC债券的几种新策略是基于催化新概念的。这些概念会 刺激了多样化和创新的实践应用，并激发了理论研究。最终研究 本文档中提出的将通过化学合成和社会通过 对基本化学反应性的理解得到了改善。

项目成果

Teaching an old carbocation new tricks: Intermolecular C-H insertion reactions of vinyl cations.

教老碳正离子新技巧：乙烯基阳离子的分子间C-H插入反应

• DOI: 10.1126/science.aat5440
• 发表时间: 2018-07-27
• 期刊: Science (New York, N.Y.)
• 作者: Popov S;Shao B;Bagdasarian AL;Benton TR;Zou L;Yang Z;Houk KN;Nelson HM
• 通讯作者: Nelson HM

Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C-H Bonds.

• DOI: 10.1021/acs.orglett.0c01745
• 发表时间: 2020-10-16
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Bagdasarian AL;Popov S;Wigman B;Wei W;Lee W;Nelson HM
• 通讯作者: Nelson HM

Correction: Cesium carbonate mediated C-H functionalization of perhalogenated 12-vertex carborane anions.

• DOI: 10.1039/d2cc90180c
• 发表时间: 2022-06-01
• 期刊: CHEMICAL COMMUNICATIONS
• 影响因子: 4.9
• 作者: Lovera, Sergio O.;Bagdasarian, Alex L.;Guo, Juchen;Nelson, Hosea M.;Lavallo, Vincent
• 通讯作者: Lavallo, Vincent