Iridium complexes for the activation and functionalization of carbon hydrogen-bonds in unactivated substrates

用于未活化基质中碳氢键的活化和功能化的铱配合物

• 批准号: 10501978
• 负责人: Nathan David Schley
• 金额: $ 38.54万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10501978
• 关键词: Address; Biological; Boron; Carbon; Catalysis; Chemicals; Complex; Esters; Family; Goals; Health; Human; Hydrogen Bonding; Iridium; Laboratories; Ligands; Methodology; Methods; Molecular Probes; Periodicity; Pharmaceutical Preparations; Preparation; Research; Route; Site; Synthesis Chemistry; System; Technology; Work; biological systems; catalyst; chemical reaction; design; drug candidate; drug synthesis; functional group; improved; programs; tool; unnatural amino acids

Project Summary The goal of our proposed research program is the design of new catalytic methodology for the synthesis of complex organic building blocks via site-selective activation of carbon-hydrogen bonds in simple organic molecules. Our approach makes use of a class of dipyridylarylmethanes as supporting ligands in iridium-catalyzed sp3 C-H borylation catalysis. This family of ligands was recently identified in our laboratory and is designed to borrow features of previous diimine and pentamethylcyclopentadienyl ligands for the same transformation while offering the advantage of modular synthetic routes for their preparation. Our initial studies on this ligand class identified one of the best catalysts for sp3 C-H borylation yet known, which has led us to design a research program that takes advantage of the improved functional group tolerance of this system to expand the scope of suitable substrates. Our proposed work will address challenges presented by the need for selectivity in sp3 C-H borylation, and in so doing will provide access to functionalized alkylboronic ester products with functional groups that were previously inaccessible through C-H activation. Further applications to the synthesis of linker molecules and biologically relevant cyclic boronate esters are proposed. We will also explore applications of dipyridylarylmethane ligands to C-H silylation catalysis, a class of chemical reactions that is substantially underdeveloped by comparison to C-H borylation. In total this program provides enabling technologies in the form of chemical methodology for the synthesis of complex building blocks from simple precursors. These methods will empower synthetic chemists in the synthesis of drug candidates and biological probes by providing tools to address the necessary complexity of molecules that interface with biological systems.

项目概要 我们提出的研究计划的目标是设计新的催化方法 通过碳-氢的位点选择性活化合成复杂的有机结构单元 简单有机分子中的键。我们的方法利用一类二吡啶基芳基甲烷 作为铱催化 sp3 C-H 硼化催化中的支持配体。该配体家族是 最近在我们的实验室中发现，旨在借用以前的二亚胺和 五甲基环戊二烯基配体进行相同的转化，同时提供以下优点： 其制备的模块化合成路线。我们对这一配体类别的初步研究确定了一个 迄今为止已知的 sp3 C-H 硼化反应的最佳催化剂，这促使我们设计了一项研究 利用该系统改进的功能组容差来扩展的程序 适用基材的范围。我们提出的工作将解决以下挑战： 需要 sp3 C-H 硼化的选择性，这样做将提供功能化 具有以前无法通过 C-H 访问的官能团的烷基硼酯产品 激活。进一步应用于连接分子和生物学相关环状化合物的合成 提出了硼酸酯。我们还将探索联吡啶芳基甲烷配体的应用 C-H 硅烷化催化，这是一类尚未充分开发的化学反应 与 C-H 硼化反应的比较。 总的来说，该计划以化学方法的形式提供了支持技术 从简单的前体合成复杂的结构单元。这些方法将赋能 合成化学家通过提供工具来合成候选药物和生物探针 解决与生物系统相互作用的分子的必要复杂性。