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

项目摘要 将氟有控制地引入生物相关化合物有助于预防， 诊断和治疗疾病。已证明，在药物设计中部署该元素 调节关键的生化特性，如代谢稳定性、溶解度和活性。之间 氟化结构单元、三氟甲基和邻位二氟化物的不同排列 是靶向基序，因为它们有可能作为甲基的稳定、无毒模拟物， 以诱导手性生物电子等排体。因此，继续发展 可以访问和操纵这两个部分的方法是合成的和药用的。 值为此，高价碘代芳烃（I（III）Ar）已经成为一种有前途的、多用途的， 无金属氟化和三氟甲基化试剂。然而，它们的催化利用 由于与他们的速度和方法相关的根本挑战， 再生，导致寄生副反应并限制底物范围。为了 选择性和可控地安装二氟化和三氟甲基化基序，催化， 需要可持续和可寻址的系统。 这一提议提出了一种新的分子电催化策略，以解决 选择性和安装罕见的邻位二氟C-F键和O-CF 3键。分子 基于已知的I（III）Ar的热化学来开发电催化剂。分子 可以定制电催化剂，从而能够开发出一类新的催化剂， 二氟甲基化和三氟甲基化。激发了I（III）Ar的电化学机理 通过分析相关化合物的现有电化学数据。详细研究 电催化剂产生的速率将提供对有机催化剂的机理的深入了解。 电合成策略预期的选择性的分子电催化剂，以广泛的 不同衬底的阵列也将促进富电子的 第一次用的是基板。除了能够合成氟化和 三氟甲基化合物，这些研究将提供一个框架的发展 用于进一步复杂有机转化的其它分子电催化剂。

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.