Metal-Free Electrocatalysis for Fine-Chemical Synthesis

用于精细化学合成的无金属电催化

• 批准号: 10454810
• 负责人: David C Powers
• 金额: $ 36.33万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10454810
• 关键词: Amination; Architecture; Chemicals; Chemistry; Complex; Coupling; Data; Development; Drug Evaluation; Electrochemistry; Electron Transport; Electrons; Goals; Impact evaluation; Iodides; Iodine; Mediator of activation protein; Metabolic; Metals; Methods; Molecular; Organic Synthesis; Oxidants; Pathway interactions; Positioning Attribute; Process; Reaction; Reagent; Research; Site; Structure; Technology; Therapeutic; base; catalyst; chemical function; chemical synthesis; halogenation; insight; interfacial; novel; novel therapeutics; oxidation; prevent; scaffold; wasting

Project Summary Oxidative substrate functionalization provides the opportunity to introduce new chemical functionality and structural complexity. Synthetic electrocatalysis provides a conceptual platform for sustainable oxidation technologies by obviating the need for stoichiometric chemical oxidants, and the attendant waste implied by these reagents. In practice, slow interfacial electron transfer chemistry of many organic molecules prevents widespread application of electrochemical methods to fine-chemical synthesis. Further, single electron-transfer processes, which are the currency of electrochemical strategies, are not common elementary steps in synthetically important transformations. The central hypothesis of this proposal is that development of hypervalent iodine electrocatalysis will provide a platform to achieve a broad array of oxidative substrate functionalization electrochemically. This hypothesis is predicated on the rich chemistry of hypervalent iodine reagents, which are well-known to participate in selective two-electron oxygenation, amination, halogenation, and hydrocarbyl transfer reactions. Successful development of hypervalent iodine electrocatalysis would substantially impact the synthesis of fine chemicals, such as molecular therapeutics. This proposal aims to first develop electrocatalysis via electrochemically generated hypervalent iodine species. Specifically, the proposed strategy leverages a previously unappreciated strategy for the synthesis of hypervalent iodine species – that one-electron pathways provide efficient access to selective two-electron chemical oxidants based on hypervalent iodine compounds – to develop synthetic hypervalent iodine electrocatalysis. Preliminary data indicate that electrochemically generated carboxy radicals enable facile electrosynthesis of hypervalent iodine species and that electrochemically generated hypervalent iodine species are competent mediators of oxidative C–H / N–H coupling. We propose to extend these preliminary results to develop new synthetically useful transformations, such as oxidative C–H functionalization. Further, the fundamental understanding of the elementary steps involved in the oxidation of aryl iodides provides the chemical insight necessary to develop novel methods of hypervalent iodine synthesis that will substantially expand the synthetic scope of hypervalent iodine catalyzed substrate oxidation. A long-term goal of these efforts is to identify new catalyst scaffolds to enable catalyst-controlled site- and stereoselective C–H functionalization which would provide direct access to complex molecular architectures functionalized at positions of metabolic consequence, which would impact the evaluation of drug metabolites and impact the discovery of new therapeutics. Together, the proposed research efforts will provide both new sustainable synthetic methods and expand the synthetic toolbox of transformations that are available for the synthesis of functional molecules. !

项目概要 氧化底物功能化提供了引入新化学功能和 结构复杂性。合成电催化为可持续氧化提供了概念平台 通过消除对化学计量化学氧化剂的需要以及随之而来的浪费来实现技术 这些试剂。在实践中，许多有机分子的缓慢界面电子转移化学阻止了 电化学方法在精细化学合成中的广泛应用。此外，单电子转移 过程是电化学策略的通用过程，但并不是常见的基本步骤 综合上重要的转变。该提案的中心假设是发展 高价碘电催化将为实现广泛的氧化底物提供一个平台 电化学功能化。该假设基于高价碘丰富的化学成分 众所周知，这些试剂参与选择性双电子氧化、胺化、卤化、 和烃基转移反应。高价碘电催化技术的成功开发 显着影响精细化学品的合成，例如分子疗法。 该提案旨在首先通过电化学产生的高价碘开发电催化 物种。具体来说，所提出的策略利用了以前未受重视的策略来综合 高价碘物种——单电子途径提供了选择性双电子的有效途径 基于高价碘化合物的化学氧化剂——开发合成高价碘 电催化。初步数据表明，电化学产生的羧基自由基能够轻松实现 高价碘物质的电合成以及电化学产生的高价碘物质 是氧化 C-H / N-H 偶联的有效介体。我们建议将这些初步结果扩展到 开发新的合成有用的转化，例如氧化C-H官能化。此外， 对芳基碘化物氧化所涉及的基本步骤的基本理解提供了 开发高价碘合成新方法所必需的化学洞察力 扩大高价碘催化底物氧化的合成范围。这些的长期目标 努力寻找新的催化剂支架，以实现催化剂控制的位点和立体选择性 C–H 功能化，这将提供直接访问功能化的复杂分子结构 代谢后果的位置，这将影响药物代谢物的评估并影响 新疗法的发现。总之，拟议的研究工作将提供新的可持续发展 合成方法并扩展可用于合成的转化合成工具箱 功能分子。 ！