Mechanistically guided improvement in radical alkene coupling by base metal catalysts

贱金属催化剂对自由基烯烃偶联的机械引导改进

• 批准号: 9906258
• 负责人: PATRICK L HOLLAND
• 金额: $ 28.7万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-05 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906258
• 关键词: Alcohols; Alkenes; Back; Behavior; Binding; Biological; Carbon; Catalysis; Communities; Complex; Coupled; Coupling; Electron Transport; Environment; Face; Family; Funding; Grant; Growth; Health; Human; Hydrogen; Hydrogen Bonding; Iron; Kinetics; Ligands; Metals; Methods; Natural Products; Organic Synthesis; Outcome; Outcome Study; Pharmaceutical Preparations; Pharmacologic Substance; Phosphoric Acids; Protons; Reaction; Reproducibility; Route; Salts; Series; Silanes; Site; Solvents; Specificity; Spectrum Analysis; Structure; System; Temperature; Testing; Transition Elements; adduct; base; biological preparation; catalyst; design; experience; experimental study; improved; insight; interest; next generation; tool; trend; wasting

Project Summary/Abstract HAT (hydrogen atom transfer) alkene reactions offer the opportunity to functionalize unactivated alkenes under mild conditions, creating highly substituted carbon sites that are prevalent in biologically active molecules. However, the rational design of catalysts for HAT alkene reactions with higher yield, faster rates, and less waste is currently held back by a lack of mechanistic information. A particular challenge is the discovery of structure and reactivity trends for the hydride complexes that perform the key HAT step. The proposed project aims to improve the HAT alkene reactions through study of metal-hydrides and radical intermediates in the catalytic cycle of HAT alkene reactions, starting with alkene cross-coupling and continuing to other alkene hydrofunctionalization reactions. The expected outcome of these studies is that the HAT alkene reactions will become possible at or below room temperature, with high chemoselectivity, regioselectivity, and stereoselectivity. This will include the first examples of enantioselective HAT alkene reactions. The PI, Patrick Holland, is an expert in mechanistic studies with paramagnetic iron-alkyl and iron-hydride compounds, and the project will provide rigorous identification of the structures, spectroscopy, reactions and mechanisms that are relevant to the catalytic cycle. A special focus in the first funding period will be the iron-catalyzed reductive cross-coupling of alkenes, where we will leverage our discovery of important but unrealized aspects of the mechanism such as the presence of proton-coupled electron transfer from metal- alcohol species. The lessons learned will be applied to a broad family of radical C-C and C-N bond coupling reactions catalyzed by Mn, Co, and Fe. These advances will make the HAT alkene reactions milder and higher-yielding, will minimize byproducts/waste, and will accommodate a broader range of substrates for preparation of biologically relevant products. The enantioselective versions of the alkene cross-coupling reactions will provide a new route to heavily substituted, stereodefined carbon sites that are useful in natural products and bioactive molecules.

项目概要/摘要 HAT（氢原子转移）烯烃反应提供了未活化官能化的机会 在温和条件下生成烯烃，产生高度取代的碳位点，这些位点普遍存在于 生物活性分子。然而，HAT烯烃反应催化剂的合理设计 更高的产量、更快的速度和更少的浪费目前由于缺乏机械而受到阻碍 信息。一个特殊的挑战是发现结构和反应性趋势 执行关键 HAT 步骤的氢化物配合物。拟议项目旨在改善 通过研究催化中的金属氢化物和自由基中间体来进行 HAT 烯烃反应 HAT 烯烃反应循环，从烯烃交叉偶联开始并继续进行其他反应 烯烃加氢官能化反应。这些研究的预期结果是 HAT 烯烃反应将在室温或低于室温下进行，具有高化学选择性， 区域选择性和立体选择性。这将包括对映选择性的第一个例子 HAT 烯烃反应。 PI Patrick Holland 是一位机械研究专家 顺磁性烷基铁和氢化铁化合物，该项目将提供严格的 与相关的结构、光谱、反应和机制的鉴定 催化循环。第一个资助期的特别关注点是铁催化还原 烯烃的交叉偶联，我们将利用我们发现的重要但尚未实现的 该机制的各个方面，例如来自金属的质子耦合电子转移的存在 酒精种类。吸取的教训将应用于广泛的激进 C-C 和 C-N 系列 Mn、Co 和 Fe 催化的键偶联反应。这些进步将使 HAT 烯烃反应更温和、产率更高，将最大限度地减少副产物/废物，并将 适应更广泛的底物，用于制备生物相关产品。 烯烃交叉偶联反应的对映选择性版本将为 高度取代的、立体定义的碳位点，可用于天然产物和生物活性 分子。