An electrocatalytic approach to discovering new synthetic transformations

发现新合成转化的电催化方法

• 批准号: 10463625
• 负责人: Song Lin
• 金额: $ 30.88万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463625
• 关键词: Address; Alkenes; Anodes; Area; Biomedical Research; Catalysis; Characteristics; Chemicals; Chlorides; Complex; Coupled; Coupling; Development; Electrochemistry; Electrodes; Electrolyses; Electron Transport; Generations; Goals; Hydrogen; Hydrogen Bonding; Industrialization; Ketones; Lead; Mediator of activation protein; Metals; Methods; Modernization; Organic Chemistry; Organic Synthesis; Oxidation-Reduction; Preparation; Process; Reaction; Research; Role; Speed; Structure; Synthesis Chemistry; Techniques; Technology; Therapeutic Agents; Transition Elements; Work; bioactive natural products; catalyst; chemical bond; functional group; improved; innovation; insight; novel; outcome prediction; oxidation; pi bond; small molecule; tool; trend; wasting

Project Summary This proposal focuses on uncovering new electrocatalytic technologies that facilitate the synthesis of bioactive compounds. Improving the synthetic efficiency of medicinally active organic compounds is crucial to modern biomedical research. Oxidation and reduction reactions are among the most important and frequently executed processes in organic synthesis. However, our ability to manipulate the oxidation states of functional groups in complex settings with high efficiency, precision, and minimal waste remains in a largely nascent stage. Owing to its many distinct characteristics, electrochemistry represents an attractive approach to meet the prevailing trends in organic synthesis. In particular, electrocatalysis—a process that integrates electrochemistry and small-molecule catalysis—has the potential to substantially improve the scope of synthetic electrochemistry and provide a wide range of useful transformations. Despite its attractive attributes and extensive applications in energy-related fields, electrocatalysis has been used only sparingly in synthetic organic chemistry. Thus, there exists a clear impetus for inventing new catalytic strategies to improve the scope of synthetic electrochemistry and provide new platforms for reaction discovery and synthetic innovations. Toward this end, we developed a new catalytic approach that combines electrochemistry and redox-metal catalysis for the oxidative difunctionalization of alkenes to access a diverse array of vicinally functionalized structures. These promising results led us to envision that electrocatalytic strategies will ultimately emerge as powerful tools for solving a wide range of long- standing synthetic problems. Each of the projects described herein applies our general strategy of electrocatalysis to address a prominent challenge in organic synthesis. Specifically, we aim to develop reactions such as the chlorophosphonylation, chloro(hetero)arylation, and fluorotrifluoromethylation of alkenes; ring-opening functionalization of cycloalkanols to make remotely functionalized ketones; intermolecular 1,1-difunctionalization of isonitriles to make imidoyl chlorides; and C–N coupling via the activation of C–H bonds. These oxidative transformations are either currently unknown or have significant limitations in reaction scope, efficiency, or selectivity. We will also carry out in-depth studies using canonical physical organic and electrochemical techniques to gain insights into the reaction mechanisms. The development and mechanistic understanding of these proposed transformations will represent significant advances for the field of organic synthesis.

项目摘要 这项提案的重点是发现新的电催化技术，以促进合成 生物活性化合物。提高药用活性有机化合物的合成效率 对现代生物医学研究至关重要。氧化和还原反应是最重要的反应之一。 以及在有机合成中频繁执行的过程。然而，我们操纵氧化的能力 功能基团在复杂环境中的状态，具有高效率、精确度和最小的浪费残留 在很大程度上处于新生阶段。由于其许多不同的特点，电化学代表着一种 具有吸引力的方法，以满足有机合成的主流趋势。特别是，电催化-a 集成了电化学和小分子催化的过程-有可能大幅 改进合成电化学的范围，提供广泛的有用的转化。 尽管电催化具有诱人的特性和在能源相关领域的广泛应用，但它已经 仅在合成有机化学中少量使用。因此，发明存在着明显的推动力。 新的催化策略，以扩大合成电化学的范围，并为 反应发现和合成创新。为此，我们开发了一种新的催化方法 将电化学和氧化还原金属催化相结合用于烯烃的氧化去功能化 以访问附近功能化结构的多样化阵列。这些令人振奋的结果让我们设想 电催化策略最终将成为解决广泛的长期问题的有力工具 难以解决的合成问题。这里描述的每个项目都适用我们的总体战略 解决有机合成中的一个突出挑战的电催化。具体来说，我们的目标是开发 氯膦甲基化、氯(杂)芳基化和氟三氟甲基化等反应 烯烃；环烷醇的开环功能化，以制备远程官能化酮； 异腈分子间的1，1-二官能化反应生成亚胺基氯化物； C-H键的活化。这些氧化转化要么是目前未知的，要么是具有重大意义的 在反应范围、效率或选择性方面的限制。我们还将进行深入研究，使用 经典的物理、有机和电化学技术，以深入了解反应机理。 对这些提议的转变的发展和机械理解将代表 有机合成领域的重大进展。