Catalytically Generated Amidyl Radicals for Site-Selective Intermolecular C-H Functionalization

催化生成酰胺自由基用于位点选择性分子间 C-H 官能化

• 批准号: 10679463
• 负责人: Jesse Gordon
• 金额: $ 6.95万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679463
• 关键词: Acids; Active Sites; Amides; Anodes; Back; Benchmarking; Catalysis; Catalytic Domain; Charge; Chemical Industry; Chemicals; Complex; Coupled; Dyes; Electrolyses; Electron Transport; Electronics; Energy-Generating Resources; Evolution; Free Radicals; Generations; Goals; Hydrocarbons; Hydrogen Bonding; Ions; Kinetics; Knowledge; Link; Mediator; Methods; Modeling; Molecular; Natural Products; Nitrogen; Pharmacologic Substance; Polymers; Process; Production; Property; Protons; Reaction; Reagent; Research; Side; Site; Solar Energy; Source; Spectrum Analysis; Structure; Sustainable Development; Time; Training; Work; absorption; base; catalyst; design; functional group; improved; inorganic phosphate; oxidation; pressure; prevent; quantum; renewable energy

Project Summary The selective activation and functionalization of C–H bonds is one of the most important and challenging chemical transformations. The ability to activate any targeted C–H bond in a given molecule would immensely expand the scope of synthetically accessible chemical transformations and would be a powerful method of late- stage functionalization of complex molecules such pharmaceuticals, natural products, and commodity chemicals. Furthermore, carrying out these reactions using abundant, non-toxic catalysts and renewable energy sources (e.g., solar energy) is critical for the development of sustainable chemical processes. Achieving selectivity in C– H activation is often difficult due to the presence of numerous C–H bonds of similar strength in a given molecule. Even more challenging is discriminately functionalizing strong C–H bonds in proximity to weaker C–H bonds. Selectivity for C–H activation is often dictated by properties of the substrate, and in such cases, reactivity may be limited to the weakest or most acidic C–H bond. However, catalyst-control of selectivity, wherein the structure of the H-atom abstractor dictates selectivity, offers a powerful method of predictably introducing chemical diversity from hydrocarbon feedstocks. Amidyl radicals are potent H-atom abstractors (BDE(N–H) > 100 kcal mol-1) that are capable of cleaving strong C–H bonds, but their applications in intermolecular C–H activation reactions often rely on pre-functionalized amidyl sources, rendering them stoichiometric reagents. The direct activation of amide N–H bonds to generate amidyl radicals would provide catalytic access to these reactive intermediates and would dramatically improve their utility in C–H functionalization reactions. This proposed research strategy aims to develop new electro- and photocatalytic methods for direct N–H bond activation via proton-coupled electron transfer to generate amidyl radicals for selective C–H activation. By exploiting these modes of N–H bond activation in sterically shielded amide catalysts, the steric pressures imposed the amidyl radicals can dictate site-selectivity. A combination of electrochemical kinetics and photophysical studies, including time-resolved transient absorption spectroscopy and photocrystallography, will be employed to delineate the key structural and electronic features that govern selectivity. Overall, these studies will expand our ability to perform catalytic, site-selective C–H functionalization reactivity using sustainable energy sources.

项目概要 C-H键的选择性激活和功能化是最重要和最具挑战性的问题之一 激活给定分子中任何目标 C-H 键的能力将极大地提高。 扩大了可合成的化学转化的范围，并将成为后期化学转化的一种强有力的方法。 复杂分子（如药物、天然产物和商品化学品）的阶段功能化。 此外，使用丰富的无毒催化剂和可再生能源进行这些反应 （例如太阳能）对于可持续化学工艺的发展至关重要。 由于给定分子中存在大量强度相似的 C-H 键，H 激活通常很困难。 更具挑战性的是在较弱的 C-H 键附近有区别地功能化强 C-H 键。 C–H 活化的选择性通常由底物的性质决定，在这种情况下，反应性可能 仅限于最弱或酸性最强的 C-H 键。 H 原子提取子的数量决定了选择性，提供了一种可预测地引入化学物质的强大方法 烃原料的多样性。 酰胺基是有效的 H 原子提取剂 (BDE(N–H) > 100 kcal) mol-1）能够裂解强C-H键，但它们在分子间C-H活化中的应用 反应通常依赖于预官能化的酰胺源，使它们成为化学计量试剂。 酰胺N-H键的活化产生酰胺自由基将为这些反应性物质提供催化途径 中间体，并将显着提高它们在 C-H 官能化反应中的效用。 研究策略旨在开发新的电催化和光催化方法，通过 质子耦合电子转移产生酰胺基，用于选择性 C-H 激活。 空间屏蔽酰胺催化剂中 N-H 键的活化模式，空间压力施加酰胺基 自由基可以决定位点选择性，电化学动力学和光物理研究的结合， 包括时间分辨瞬态吸收光谱和光晶体学，将用于 总体而言，这些研究将描述控制选择性的关键结构和电子特征。 使用可持续能源进行催化、位点选择性 C-H 官能化反应的能力。