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，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 以及有机合成中经常执行的过程。然而，我们控制氧化的能力 在复杂环境中高效、精确和最少浪费地保留功能基团的状态 在很大程度上处于萌芽阶段。由于电化学具有许多独特的特征， 有吸引力的方法，以满足有机合成的流行趋势。特别地，电催化-a 集成电化学和小分子催化的过程-具有实质上 改进了合成电化学的范围，并提供了广泛的有用转化。 尽管电催化具有吸引人的属性和在能源相关领域中的广泛应用， 在合成有机化学中很少使用。因此，有一个明确的动力， 新的催化策略，以提高合成电化学的范围，并提供新的平台， 反应发现和合成创新。为此，我们开发了一种新的催化方法， 结合电化学和氧化还原金属催化用于烯烃的氧化双官能化， 以获得各种各样的邻近功能化结构。这些有希望的结果使我们设想 电催化策略最终将成为解决各种长期问题的有力工具， 存在的合成问题。这里描述的每个项目都适用于我们的总体战略， 电催化以解决有机合成中的突出挑战。具体来说，我们的目标是发展 反应如氯膦酰化、氯（杂）芳基化和氟三氟甲基化， 环烷醇的开环官能化以制备远程官能化的酮; 异腈的分子间1，1-双官能化以制备亚氨酰氯;以及经由亚氨酰氯的C-N偶联， C-H键的活化。这些氧化转化要么是目前未知的，要么具有显著的 反应范围、效率或选择性的限制。我们亦会进行深入研究， 典型的物理有机和电化学技术，以获得深入了解反应机制。 这些拟议的转变的发展和机制的理解将代表 有机合成领域的重大进展。