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。我们研究计划的基本目标是开发新型合成 将允许有效构建具有药物有用的化合物的策略 简单，容易获得的起始材料。沿着这些线，我们的小组致力于 努力将光毒素催化在有机合成中。这个催化领域 采用能够吸收可见光的过渡金属复合物或有机染料。 光子的吸收会促进光催化剂到长期的激发态，然后可以作用 作为氧化物或通过单电子转移还原的氧化物。因此，Photoredox催化剂线束 可见光作为化学能源，可用于克服重大反应 障碍。最近，我们的小组和其他人证明了光毒素催化可以是 成功与其他催化平台合并，以利用每个平台的优势 单个催化模式。我们已经对探索反应性特别感兴趣 光电氧催化和过渡金属交叉偶联催化的界面。在这项研究中 提案，我们概述了基于Photoredox多催化的研究计划的新方向。 拟议的目标的成功完成将为当前未知或 无法访问的反应途径，将允许常见且通常“良性”有机化合物 被激活为交叉偶联反应的参与者。在目标一世中，我们建议开发 通过Photoredox和镍催化剂的合并，不对称的脱羧交叉偶联。在 AIM II，我们旨在利用镍催化剂激活烷基卤化物的能力 直接SP3 – SP3交叉耦合。 AIM III设想开发镍和光毒素 催化方法将酯通过二氧化碳 - 排骨转化为高价值支架 重组。目的I – III专注于羧酸的交叉偶联，AIM IV 提案通过采用新的一类新的可用耦合伙伴的介绍 简单的酒精衍生物在镍 - 光介毒蛋白中的交叉偶联中。在AIM V中，我们的目标是 员工三个离散催化剂，以完成胺，醚和 通过氢原子转移和交叉偶联的醇。 AIM VI设想应用 相关的三催化策略，以开发一种交叉噬菌体耦合的方法。在AIM VII中， 我们的目标是利用过渡金属氧化状态的光催化控制以进行 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， AIM VIII建议使用使用多吡咯洛洛林生物碱异托替骑利的构建 在我们的实验室中开发的铜催化方法的迭代应用。