Combining Nickel and Photoredox Catalysis

结合镍和光氧化还原催化

• 批准号: 9176836
• 负责人: David W MacMillan
• 金额: $ 35.85万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9176836
• 关键词: Address; Alcohols; Alkaloids; Amines; Area; Benign; Carbon Dioxide; Carboxylic Acids; Catalysis; Chemicals; Communities; Copper; Coupling; Decarboxylation; Development; Dyes; Electron Transport; Electrons; Esters; Ethers; Genetic Recombination; Goals; Halogens; Hydrogen; Hydrogen Bonding; Individual; Laboratories; Life; Mediating; Methodology; Methods; Molecular; Natural Products; Nickel; Organic Chemistry; Organic Synthesis; Oxalates; Oxidants; Oxidation-Reduction; Participant; Pathway interactions; Photons; Production; Protocols documentation; Reaction; Reagent; Reducing Agents; Research; Research Proposals; Source; Sulfhydryl Compounds; System; Transition Elements; Visible Radiation; Work; absorption; abstracting; aryl halide; base; catalyst; chemical synthesis; design; improved; interest; metal complex; novel; oxidation; programs; scaffold

Abstract. A fundamental goal of our research program is the development of novel synthetic strategies that will allow for the efficient construction of medicinally useful compounds from simple, readily available starting materials. Along these lines, our group has dedicated significant effort to the application of photoredox catalysis to organic synthesis. This field of catalysis employs transition metal complexes or organic dyes which are capable of absorbing visible light. Absorption of a photon promotes a photocatalyst to a long-lived excited state, which may then act as an oxidant or a reductant via single-electron transfer. As such, photoredox catalysts harness visible light as a source of chemical energy, which can be used to overcome significant reaction barriers. Recently, our group and others have demonstrated that photoredox catalysis can be successfully merged with other catalytic platforms in order to capitalize on the strengths of each individual mode of catalysis. We have become particularly interested in exploring reactivity at the interface of photoredox catalysis and transition metal cross-coupling catalysis. In this research proposal, we outline new directions for our photoredox multicatalysis-based research program. The successful completion of the proposed aims will provide access to currently unknown or inaccessible reaction pathways and will allow common and usually “benign” organic compounds to be activated as participants in cross-coupling reactions. In Aim I, we propose to develop an asymmetric decarboxylative cross-coupling via the merger of photoredox and nickel catalysis. In Aim II, we aim to harness the ability of nickel catalysts to activate alkyl halides to accomplish a direct sp3–sp3 cross-coupling. Aim III envisions the development of a nickel- and photoredox- catalyzed method for the conversion of esters into high-value scaffolds via CO2-extrusion- recombination. While Aims I–III focus on the cross-coupling of carboxylic acids, Aim IV proposes the introduction of a new class of readily available coupling partners by employing simple alcohol derivatives in nickel-photoredox cross-coupling. In Aim V, it is our objective to employ three discrete catalysts in order to accomplish C–H arylation of amines, ethers, and alcohols via hydrogen atom transfer and cross-coupling. Aim VI envisions the application of a related triple-catalytic strategy to develop a method for cross-electrophile coupling. In Aim VII, it is our goal to harness photocatalytic control of transition metal oxidation states in order to accomplish a nickel-mediated C–N coupling reaction. Finally, as part of a Diversity Supplement, Aim VIII proposes the construction of the polypyrroloindoline alkaloid isopsychotridine using iterative applications of a copper-catalyzed method developed in our laboratory.

抽象的。我们的研究计划的一个基本目标是开发新的合成 这些策略将允许有效构建药用化合物， 简单、易得的起始材料。沿着这些路线，我们的团队致力于 为光氧化还原催化在有机合成中的应用做出了努力。这个催化领域 使用能够吸收可见光的过渡金属络合物或有机染料。 光子的吸收促进光催化剂进入长寿命的激发态，然后可以起作用。 通过单电子转移作为氧化剂或还原剂。因此，光氧化还原催化剂利用 可见光作为化学能源，可用于克服显着的反应 隔栏.最近，我们的小组和其他人已经证明，光氧化还原催化可以是 成功地与其他催化平台合并，以利用各自的优势 个别催化模式。我们已经变得特别感兴趣的探索反应在 光氧化还原催化和过渡金属交叉偶联催化界面。本研究 建议，我们概述了我们的光氧化还原多催化为基础的研究计划的新方向。 成功完成拟议目标将提供目前未知或 难以接近的反应途径，并将允许常见的和通常“良性”的有机化合物 作为交叉偶联反应的参与者被激活。在目标I中，我们建议制定一项 通过光氧化还原和镍催化的合并的不对称脱羧交叉偶联。在 目的II，我们的目标是利用镍催化剂活化烷基卤化物的能力来实现 直接sp3-sp3交叉偶联。目标III设想开发镍-和光氧化还原- 通过CO2挤出将酯转化为高价值支架的催化方法， 重组虽然目标I-III侧重于羧酸的交叉偶联，但目标IV 提出了引入一类新的现成的耦合伙伴， 在镍-光氧化还原交叉偶联中的简单醇衍生物。在目标五中，我们的目标是 使用三种分立的催化剂以实现胺、醚和芳胺的C-H芳基化， 醇通过氢原子转移和交叉偶联。目标六设想应用一种 相关的三重催化策略来开发交叉亲电偶联的方法。在目标七中， 我们的目标是利用过渡金属氧化态的光催化控制， 完成镍介导的C-N偶联反应。最后，作为多样性补充的一部分， 目的VIII提出了聚吡咯并吲哚啉生物碱isopsychotridine的结构， 我们实验室开发的铜催化方法的迭代应用。