Metal-Free Electrocatalysis for Fine-Chemical Synthesis

项目摘要 氧化底物官能化提供了引入新的化学官能度的机会， 结构复杂性。合成电催化为可持续氧化提供了概念平台 技术，避免了化学计量的化学氧化剂的需要，以及伴随的废物， 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，这是电化学策略的货币，不是常见的基本步骤， 重要的综合转型。这一建议的核心假设是， 高价碘电催化将提供一个平台，以获得广泛氧化底物 电化学功能化。这一假设是基于高价碘的丰富化学性质 已知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， 实质上影响精细化学品的合成，例如分子治疗剂。 该提案旨在首先通过电化学产生的高价碘来开发电催化 物种具体地说，所提出的战略利用了以前不受重视的战略， 高价碘物质--单电子途径提供了选择性双电子 以高价碘化合物为基础的化学氧化剂-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使 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偶联的主管介质。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，如氧化C-H官能化。此夕h 对芳基碘氧化中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需的化学洞察力， 扩大了高价碘催化底物氧化的合成范围。这些长期目标 我们的努力是确定新的催化剂支架，使催化剂控制的网站和立体选择性的C-H 功能化，这将提供直接进入复杂的分子结构功能化， 代谢结果的位置，这将影响药物代谢物的评价，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 功能分子 !

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. !