Electrochemically Generated Hypervalent Iodoarenes: An Addressable and Sustainable Catalytic Platform for Difluorination and Trifluoromethylation

电化学生成高价碘芳烃：二氟化和三氟甲基化的可寻址且可持续的催化平台

• 批准号: 9794008
• 负责人: Anna Wuttig
• 金额: $ 6.12万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-27 至 2021-08-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794008
• 关键词: Acids; Affect; Alcohol consumption; Alcohols; Alkenes; Attention; Benchmarking; Biochemical; Biological; Cathodes; Chemistry; Complex; Data; Development; Diagnosis; Disease; Drug Design; Effectiveness; Electrochemistry; Electrolytes; Electrons; Elements; Fluorides; Fluorine; Generations; Mediator of activation protein; Metabolic; Metals; Methodology; Methods; Modification; Molecular; Molecular Target; Natural regeneration; Oxidants; Periodicity; Property; Protons; Reaction; Side; Solubility; Source; Structure; Substrate Specificity; System; Targeted Research; Techniques; Testing; Time; base; catalyst; design; improved; insight; methyl group; prevent

Project Abstract The controlled introduction of fluorine into biologically relevant compounds helps prevent, diagnose, and treat disease. The deployment of this element in drug design has been shown to modulate key biochemical properties, such as metabolic stability, solubility, and activity. Among the diverse-array of fluorinated building blocks, trifluoromethyl groups and vicinal difluorides are targeted motifs due to their potential to serve as stable, non-toxic mimics of methyl groups or to induce chiral bioisosteres, respectively. Therefore, the continued development of methodologies that can access and manipulate both moieties are of synthetic and medicinal value. To this end, hypervalent iodoarenes (I(III)Ar) have emerged as a promising, versatile, and metal-free fluorinating and trifluoromethylating agent. However, their catalytic utilization remains rare due to fundamental challenges associated with the rate and methods of their regeneration, resulting in parasitic side reactions and limiting the substrate scope. In order to selectively and controllably install difluorinated and trifluoromethylated motifs, a catalytic, sustainable, and addressable system is required. This proposal puts forth a new molecular electrocatalytic strategy to solve challenges of selectivity and to install rare vicinal difluoride C-F bonds and O-CF3 bonds. Molecular electrocatalysts are developed based on the known thermal chemistry of I(III)Ar. The molecular electrocatalysts can be tailored, enabling the development of a new class of catalysts for difluorination and trifluoromethylation. The electrochemical mechanism of I(III)Ar is inspired by the analysis of existing electrochemical data on related compounds. Detailed studies of the rate of electrocatalyst generation will provide insights into the mechanism of the organic electrosynthesis strategy. The anticipated selectivity of the molecular electrocatalyst to a wide array of differing substrates will also facilitate the controlled difluorination of electron-rich substrates for the first time. In addition to enabling the synthesis of fluorinated and trifluoromethylated compounds, these studies will provide a framework for the development of other molecular electrocatalysts for further complex organic transformations.

项目摘要 受控地将氟引入生物相关化合物有助于防止， 诊断、治疗疾病。该元素在药物设计中的部署已被证明可以 调节关键的生化特性，例如代谢稳定性、溶解度和活性。之中 多种氟化结构单元、三氟甲基和邻位二氟化物 是目标基序，因为它们有可能作为甲基的稳定、无毒的模拟物或 分别诱导手性生物等排体。因此，持续发展 可以访问和操纵这两个部分的方法是合成的和药用的 价值。为此，高价碘芳烃 (I(III)Ar) 已成为一种有前途的、多功能的、 无金属氟化剂和三氟甲基化剂。然而，它们的催化利用 由于其速度和方法相关的根本挑战，仍然很少见 再生，导致寄生副反应并限制底物范围。为了 选择性地、可控地安装二氟和三氟甲基化基序，一种催化、 需要可持续且可寻址的系统。 该提案提出了一种新的分子电催化策略来解决 选择性并安装稀有的邻二氟C-F键和O-CF3键。分子 电催化剂是基于已知的 I(III)Ar 热化学而开发的。分子 电催化剂可以定制，从而能够开发出新型催化剂 二氟化和三氟甲基化。 I(III)Ar的电化学机理受到启发 通过分析相关化合物的现有电化学数据。详细研究了 电催化剂的生成速率将有助于深入了解有机物的机理 电合成策略。分子电催化剂的预期选择性广泛 不同基质的阵列也将促进富电子的受控二氟化 首次使用基材。除了能够合成氟化和 三氟甲基化化合物，这些研究将为开发提供框架 用于进一步复杂有机转化的其他分子电催化剂。