New Synthetic Methods Enabled by Excited-State Redox Chemistry

激发态氧化还原化学实现的新合成方法

• 批准号: 10326380
• 负责人: Robert R Knowles
• 金额: $ 54.21万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326380
• 关键词: Address; Alcohols; Alkenes; Amides; Amines; Biological Process; Catalysis; Cations; Chemistry; Communities; Complex; Coupled; Development; Electron Transport; Equilibrium; Event; Generations; Goals; Health; Human; Hydrogen Bonding; Light; Literature; Mediating; Methods; Organic Chemistry; Organic Synthesis; Outcome; Oxidation-Reduction; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Photons; Process; Protocols documentation; Protons; Reaction; Science; Site; Sulfonamides; Technology; Technology Transfer; Variant; Work; absorption; base; carbonyl compound; catalyst; design; novel; novel strategies; pharmacophore; small molecule; tool; Address; Alcohols; Alkenes; Amides; Amines; Biological Process; Catalysis; Cations; Chemistry; Communities; Complex; Coupled; Development; Electron Transport; Equilibrium; Event; Generations; Goals; Health; Human; Hydrogen Bonding; Light; Literature; Mediating; Methods; Organic Chemistry; Organic Synthesis; Outcome; Oxidation-Reduction; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Photons; Process; Protocols documentation; Protons; Reaction; Science; Site; Sulfonamides; Technology; Technology Transfer; Variant; Work; absorption; base; carbonyl compound; catalyst; design; novel; novel strategies; pharmacophore; small molecule; tool

Project Summary The work described in this proposal aims to develop novel synthetic methods enabled by excited-state redox events to address longstanding challenges in catalysis and synthetic organic chemistry. A primary focus of this proposal is the continued development of proton-coupled electron transfer (PCET) technologies in organic synthesis. In particular we focus on developing PCET-based methods for the catalytic functionalization of aliphatic C-C bonds, including redox-neutral isomerization reactions of cyclic alcohols to form linear carbonyl compounds, and novel methods for the catalytic ring-expansion and ring-contraction of carbocyclic alcohols. We also discuss efforts to develop a new class of chiral amide-based catalysts that can be activated by PCET to generate transient amidyls, which can then mediate enantioselective and site-selective functionalization of aliphatic C-H bonds. A second goal of this work is the development of out-of-equilibrium synthetic methods enabled by excited-state redox events. These technologies provide opportunities to use photon absorption events to drive reaction against a thermochemical gradient, but without requiring generation of excited state substrates. Importantly, these methods provide novel approaches to achieve non-Boltzmann product distributions and reaction outcomes that are not, by definition, possible to obtain using conventional ground- state methods. Applications to the development of light-driven deracemization reactions are presented. A third goal is to advance our efforts in developing photocatalytic methods for olefin hydroamination and hydroetherification. We propose to develop the first general catalytic protocol for intermolecular anti- Markovnikov hydroamination reactions between unactivated olefins with primary alkyl amines to yield secondary amine products, selectively, based on the chemistry of aminium radical cations. PCET-based methods for enantioselective hydroaminations with sulfonamides are also proposed, wherein the asymmetric induction is proposed to arise from direct non-covalent interactions between a chiral H-bond donor and a neutral N-centered radical intermediate. We also present plans to develop analogous intermolecular hydroetherification methods and their enantioselective variants. If successful, these efforts will provide valuable new reactions and concepts for the chemistry communities engaged in the discovery, synthesis, and manufacture of pharmaceuticals and other small-molecule probes of biological function, and thus create a significant benefit to human health.

项目摘要 该提案中描述的工作旨在开发激发卫生的新型合成方法 解决催化和合成有机化学中长期挑战的事件。主要重点 提案是有机质子耦合电子传输（PCET）技术的持续开发 合成。特别是我们专注于开发基于PCET的方法来催化功能 脂肪族C-C键，包括循环醇的氧化还原异构化反应以形成线性羰基 化合物以及碳环醇的催化环膨胀和环收缩的新方法。 我们还讨论了开发新的基于手性酰胺的新类催化剂的努力，这些催化剂可以由PCET激活 为了产生瞬态氨基酯，然后可以介导对映选择性和位点选择性功能化 脂肪族C-H键。这项工作的第二个目标是开发不平衡的合成方法 通过激发卫生氧化还原事件启用。这些技术提供了使用光子吸收的机会 驱动对热化学梯度反应的事件，但不需要产生激发态 基材。重要的是，这些方法提供了实现非Boltzmann产品的新方法 根据定义，分布和反应结果无法使用常规的地面 状态方法。提出了对轻驱动脱囊反应的开发的应用。第三 目的是促进我们为开发烯烃盐水的光催化方法的努力和 水鞘醚化。我们建议开发第一个用于分子间抗分子的一般催化方案 Markovnikov的氢化烯烃与原代烷基胺之间的氢化反应以产生 二级胺产物基于氨基阳离子的化学选择性。基于PCET 还提出了用磺酰胺的对映选择性氢胺化的方法，其中不对称 提出诱导是由手性H键供体与A之间的直接非共价相互作用引起的 中性n个中心的自由基中间体。我们还提出了开发类似分子的计划 水域化方法及其对映选择性变体。如果成功，这些努力将提供有价值的 从事发现，合成和的化学社区的新反应和概念 制造药物和其他小分子生物功能探针，从而创建一个 对人类健康的重大好处。