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 将氟引入与生物学相关的化合物中有助于防止， 诊断和治疗疾病。该元素在药物设计中的部署已被证明 调节关键的生化特性，例如代谢稳定性，溶解度和活性。之中 氟化的构件，三氟甲基和替代性二氟化物的不同阵列 是有针对性的基序，因为它们有可能充当甲基或甲基稳定的无毒模仿或 分别诱导手性生物膜。因此，持续发展 可以访问和操纵这两个部分的方法学是合成和药用的 价值。为此，高价值的碘苯酚（i（iii）AR）已成为一种有前途的，多才多艺的和 无金属荧光和三氟甲基化剂。但是，它们的催化利用 由于与其速率和方法相关的基本挑战，仍然很少 再生，导致寄生侧反应并限制底物范围。为了 有选择地，可控制地安装差异和三氟甲基化基序，一种催化， 需要可持续和可寻址的系统。 该提案提出了一种新的分子电催化策略，以解决 选择性并安装罕见的海囊差异C-F键和O-CF3键。分子 电催化剂是根据I（iii）AR的已知热化学性质开发的。分子 可以定制电催化剂，从而可以开发一类新的催化剂 扩散和三氟甲基化。 I（iii）AR的电化学机制受到启发 通过分析有关相关化合物的现有电化学数据。详细研究 电催化剂的生成速率将提供有关有机机制的见解 电气合成策略。分子电催化剂对宽的预期选择性 一系列不同的底物还将促进富含电子的受控扩散 第一次底物。除了能够合成氟化和 三氟甲基化化合物，这些研究将为开发的框架提供一个框架 其他分子电催化剂，用于进一步的复杂有机转化。