New precursors for diverse radical reactions enabled by potent photoreductants

强效光还原剂实现多种自由基反应的新前体

• 批准号: 10600016
• 负责人: Zachary Kimble Wickens
• 金额: $ 30.51万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-05 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600016
• 关键词: ALK Pathway; Address; Alkali Metals; Alkenes; Anions; Biomedical Research; Catalysis; Chemistry; Chlorides; Climacteric; Collection; Complement; Coupling; Development; Electrochemistry; Electron Transport; Electrons; Event; Exclusion; Family; Felis catus; Generations; Goals; Health; Human; Hydrogenation; In Situ; Ions; Ketones; Medicine; Methods; Modernization; Molecular Probes; Organic Synthesis; Outcome; Oxidation-Reduction; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Photons; Preparation; Reaction; Reagent; Reducing Agents; Research; Research Proposals; Role; System; Technology; Visible Radiation; carbanion; carbonyl compound; catalyst; cost; design; drug discovery; next generation

PROJECT SUMMARY/ABSTRACT Radical intermediates generated through chemoselective single electron reduction have broad utility in the development of valuable synthetic transformations. As a consequence, photoredox catalysis, which induces single election transfer with exceptional selectivity for radical pathways, has shown great promise as an enabling technology in biomedical research. However, the design underpinning current photoredox catalysts limits the accessible reduction potentials and excludes numerous abundant feedstocks. The selective generation of radical intermediates from substrates inert towards conventional photoredox catalysis is a long- standing challenge with no general solutions. This proposal is based on the discovery that electrochemistry can generate new radical anion photocatalysts that are exceptionally potent excited state reductants but retain the selectivity of typical photoredox catalysts. We will study how these new catalysts can be exploited to develop radical coupling reactions infeasible with modern synthetic tactics. The three specific aims of this research center on exploring distinct but interwoven aspects of this new catalytic platform. Aim 1. We are exploring the ability to generate and exploit the reactivity of aryl radicals from aryl chlorides Aim 2. We are exploring the ability to engage carbonyl compounds in reductive radical coupling reactions Aim 3. We are exploring operationally simple strategies to access radical anion photocatalysts These methods address long-standing challenges in a fundamental class of organic reactions, reductions. These new catalytic systems will offer an expanded and diversified pool of starting materials from which the next generation of drugs and molecular probes will be discovered.

项目概要/摘要 通过化学选择性单电子还原产生的自由基中间体在 开发有价值的合成转化。结果，光氧化还原催化作用，诱导 单一选举转移对激进路径具有特殊的选择性，作为一个 生物医学研究中的使能技术。然而，支撑当前光氧化还原催化剂的设计 限制了可利用的还原潜力并排除了许多丰富的原料。选择性的 从对传统光氧化还原催化呈惰性的底物生成自由基中间体是一个长期的过程 面临没有通用解决方案的挑战。 该提案基于电化学可以产生新型自由基阴离子光催化剂的发现 它们是非常有效的激发态还原剂，但保留了典型光氧化还原催化剂的选择性。 我们将研究如何利用这些新催化剂来开发自由基偶联反应，这是用传统催化剂无法实现的。 现代综合战术。该研究中心的三个具体目标是探索不同但相互交织的 这个新催化平台的各个方面。 目标1.我们正在探索从芳基氯中产生和利用芳基自由基反应性的能力 目标2.我们正在探索使羰基化合物参与还原自由基偶联反应的能力 目标 3.我们正在探索操作简单的策略来获取自由基阴离子光催化剂 这些方法解决了有机反应（还原）这一基本类别中长期存在的挑战。 这些新的催化系统将提供扩大和多样化的起始材料库， 下一代药物和分子探针将会被发现。