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.

项目摘要 我们建议的研究计划的目标是设计新的催化方法 碳氢选择性活化法合成复杂有机构筑块 简单有机分子中的键。我们的方法利用了一类联吡啶基芳基甲烷 在Ir催化的SP3C-H硼化反应中作为支撑配体。这一系列的配体是 最近在我们的实验室中确定，旨在借鉴以前的双亚胺和 用于相同转化的五甲基环戊二烯配体，同时提供 为其制备提供模块化的合成路线。我们对这类配体的初步研究确定了一种 已知的最好的SP3C-H硼化催化剂，这导致我们设计了一项研究 利用该系统改进的功能组容差进行扩展的计划 合适底物的范围。我们拟议的工作将应对 在SP3 C-H硼化反应中需要选择性，这样做将提供官能化的途径 含有以前无法通过C-H访问的官能团的烷基硼酸酯产品 激活。进一步应用于连接体分子和生物相关环的合成 提出了硼酸酯的合成方法。我们还将探索联吡二甲基芳基甲烷配体的应用 到C-H硅基化催化，这类化学反应在很大程度上是不发达的 与C-H硼化反应进行比较。 总体而言，该计划以化学方法学的形式为 从简单的前体合成复杂的积木。这些方法将使 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。