Metal-Free Electrocatalysis for Fine-Chemical Synthesis

项目摘要 氧化底物功能化提供了引入新的化学官能化和 结构复杂性。合成电催化为可持续氧化提供了一个概念平台 通过消除对化学计量化学氧化剂和随之而来的废物的需要， 这些试剂。在实践中，许多有机分子缓慢的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，这是电化学策略的流行，并不是常见的基本步骤 具有综合重要性的转变。这一提议的中心假设是 高价碘电催化将为实现广泛的氧化底物提供平台 电化学法功能化。这一假设是建立在高价碘的丰富化学基础上的。 试剂，众所周知，参与选择性双电子氧化，胺化，卤化， 和烷基转移反应。高价碘电催化的成功开发将 对精细化学品的合成产生重大影响，如分子疗法。 这项提议旨在首先通过电化学产生的高价碘来发展电催化 物种。具体地说，拟议的战略利用了一种以前未被赏识的战略来综合 高价碘物种--单电子途径提供了选择性双电子的有效途径 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，电化学生成的羧基能够使 高价碘物种的电合成和电化学生成高价碘物种 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推广到 开发新的综合有用的转化，如氧化C-H官能化。此外， 对芳基碘化合物氧化所涉及的基本步骤的基本了解提供 开发新的高价碘合成方法所需的化学洞察力 扩大高价碘催化底物氧化的合成范围。这些项目的长期目标是 努力寻找新的催化剂骨架以实现催化剂控制的位置和立体选择性的C-H 官能化，可直接获得官能化的复杂分子体系 代谢后果的位置，这将影响药物代谢物的评价和影响 新疗法的发现。总之，拟议的研究工作将提供新的可持续的 合成方法，并扩展可用于合成的变换的合成工具箱 功能分子。 好了！

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. !