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: 10650826
• 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/10650826
• 关键词: Address; Biological; 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; empowerment; 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 我们提出的研究计划的目的是设计新的催化方法论 通过碳 - 氢的位置选择激活的复杂有机构建块的合成 简单有机分子中的键。我们的方法利用了一类二吡啶基甲米甲烷 作为虹膜催化的SP3 C-H Borylation催化中的配体。这个配体家庭是 最近在我们的实验室中确定，旨在借用以前的二米胺的功能 提供相同转化的五甲基环甲基配体，同时提供优势 用于制备的模块化合成路线。我们对这种配体类的最初研究确定了一个 SP3 C-H Borylation的最佳催化剂尚未知道，这使我们设计了一项研究 利用改善该系统功能组耐受性的程序扩展 合适的底物的范围。我们提出的工作将解决 SP3 C-H Borylation中的选择性需求，因此，这样做将提供对功能化的访问权限 烷基晶体酯产品具有以前通过C-H无法访问的官能团 激活。进一步应用接头分子的合成和生物学相关的循环 提出了硼酸酯。我们还将探索二吡啶基甲烷配体的应用 对于C-H硅烷基化催化，一类化学反应基本上不发达 与C-H Borylation进行比较。 总共该程序提供了以化学方法的形式的能力技术 简单前体的复杂构建块的合成。这些方法将授权 合成化学家通过提供工具来合成候选药物和生物探针的合成化学家 解决与生物系统接口的分子的必要复杂性。