Heterogeneous Directed Hydrogenation of Arenes and Olefins with Chemo- and Stereoselectivity

具有化学和立体选择性的芳烃和烯烃的非均相定向氢化

• 批准号: 10713673
• 负责人: Christina W Li
• 金额: $ 37.38万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713673
• 关键词: 3-Dimensional; Adsorption; Alkenes; Alloys; Amines; Breathing; Carbon; Clinic; Complex; Cycloparaffins; Development; Drug Compounding; Goals; Hydrogenation; Hydroxyl Radical; In Situ; Kinetics; Literature; Metals; Methods; Molecular; Nature; Organic Synthesis; Pharmacologic Substance; Reaction; Research; Site; Spectrum Analysis; Surface; System; base; catalyst; drug-like compound; functional group; metallicity; nanomaterials; nanoparticle; programs; two-dimensional; 3-Dimensional; Adsorption; Alkenes; Alloys; Amines; Breathing; Carbon; Clinic; Complex; Cycloparaffins; Development; Drug Compounding; Goals; Hydrogenation; Hydroxyl Radical; In Situ; Kinetics; Literature; Metals; Methods; Molecular; Nature; Organic Synthesis; Pharmacologic Substance; Reaction; Research; Site; Spectrum Analysis; Surface; System; base; catalyst; drug-like compound; functional group; metallicity; nanomaterials; nanoparticle; programs; two-dimensional

Project Summary/Abstract Heterogeneous noble metal catalysts are commonly used in organic synthesis for the hydrogenation of unsaturated organic functionality because of their fast reactivity and ease of purification. However, heterogeneous catalysts tend to be poorly selective in the presence of other reducible functionality and incapable of achieving stereoinduction due to the two-dimensional nature of the catalyst surface. Taking inspiration from the homogeneous literature on substrate- directed reactivity, the Li group recently demonstrated the first example of a heterogeneous hydroxyl-directed hydrogenation. Using a bimetallic alloy catalyst containing a noble metal and a base metal, we were able to catalyze highly diastereoselective hydrogenations of cyclic olefins by simultaneously adsorbing the hydroxyl directing group onto the base metal atom and the olefin onto the noble metal site. The overarching goal of this proposed research is to demonstrate that directed reactivity using bimetallic alloys is a general strategy to achieve chemo- and stereoselective hydrogenation of drug-like compounds. These selective hydrogenation reactions will be utilized to increase the sp3 content, three-dimensionality, and structural diversity of pharmaceutical candidates. We will develop new bimetallic nanoparticle compositions in order to extend the directed hydrogenation concept to systems that are not accessible using molecular catalysts, including arenes and heteroarenes, amine-directed reactions, and substrates where the directing group and reactive moiety are located remote from one another. We will also explore directing effects in dictating chemo- and regioselectivity in substrates where multiple reducible functional groups are simultaneously present. In parallel with the development of synthetic methods, we will conduct detailed nanomaterials characterization, in-situ surface spectroscopy, and kinetic studies in order to elucidate the surface ensemble required for high directivity. Together, this research program will provide new heterogeneous catalysts and methods for selective, late-stage transformations in biologically-active compounds.

项目摘要/摘要 异质贵族金属催化剂通常用于有机合成中的 不饱和有机功能的氢化，因为它们的快速反应性和易于 纯化。但是，在其他存在的情况下，异质催化剂的选择性往往很差 可还原功能和由于二维而无法实现立体诱导的能力 催化剂表面的性质。从统一文献中汲取灵感 - LI组定向反应性，最近证明了异质的第一个例子 羟基指导的氢化。使用包含高贵金属和一个的双金合金催化剂 碱金属，我们能够催化环状烯烃的高度非对映选择性氢化 通过同时将羟基指导组吸附到碱金属和烯烃上 进入贵族金属遗址。 这项拟议的研究的总体目标是证明使用的反应性 双金合金是实现化学和立体选择性氢化的一般策略 类似药物的化合物。这些选择性氢化反应将用于增加SP3 药物候选者的内容，三维和结构多样性。我们将 开发新的双金属纳米颗粒组成，以扩展定向氢化 使用分子催化剂（包括竞技场和）无法访问的系统的概念 杂种，胺定向反应以及指导组和反应性的底物 部分彼此遥远。我们还将探索指示的指导效应 多个可还原官能团的底物中的化学和区域选择性 同时在场。与合成方法的发展并行，我们将进行 详细的纳米材料表征，原位表面光谱和动力学研究顺序 阐明高方向性所需的表面合奏。一起研究计划 将提供新的异质催化剂和方法，用于选择性，晚期转化 在生物活性化合物中。