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.

摘要：我们研究计划的一个基本目标是开发新型合成材料。 策略将允许有效地构建具有药用价值的化合物 沿着这些思路，我们的团队专门提供了简单、容易获得的起始材料。 致力于光氧化还原催化在有机合成这一催化领域的应用。 采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，然后可以发挥作用 通过单电子转移作为氧化剂或还原剂因此，光氧化还原催化剂可以利用。 可见光作为化学能源，可用于克服重大反应 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障碍。 与其他催化平台成功合并，以充分利用各自的优势 我们对探索反应性特别感兴趣。 本研究中光氧化还原催化与过渡金属交叉偶联催化的界面。 在提案中，我们概述了基于光氧化还原多重催化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未知的信息 难以进入的途径发生反应，并允许常见且通常是“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，我们建议开发一种 通过光氧化还原和镍催化的合并进行不对称脱羧交叉偶联。 目标二，我们的目标是利用镍催化剂活化卤代烷的能力来实现 直接 sp3-sp3 交叉偶联的目标 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 目标 I-III 重点关注羧酸的交叉偶联，而目标 IV 提议通过采用引入一类新的现成耦合伙伴 在 Aim V 中，我们的目标是研究镍-光氧化还原交叉偶联中的简单醇衍生物。 使用三种独立的催化剂来完成胺、醚和化合物的C-H芳基化 目标VI设想了通过氢原子转移和交叉偶联的醇的应用。 在目标VII中，开发交叉亲电子偶联方法的相关三重催化策略。 我们的目标是利用光催化控制过渡金属氧化态，以便 最后，作为多样性补充的一部分， 目标 VIII 提出使用聚吡咯并吲哚啉生物碱 isopsychotridine 进行构建 我们实验室开发的铜催化方法的迭代应用。