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

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.

项目概要/摘要 多相贵金属催化剂常用于有机合成 不饱和有机官能团的氢化，因为其反应速度快且易于 纯化。然而，多相催化剂在其他物质存在下往往选择性较差。 由于二维的原因，功能可简化并且无法实现立体感应 催化剂表面的性质。从有关基质的同质文献中汲取灵感- 定向反应，李小组最近展示了异质的第一个例子 羟基定向氢化。使用含有贵金属和 贱金属，我们能够催化环烯烃的高度非对映选择性氢化 通过同时将羟基导向基团吸附到贱金属原子和烯烃上 到贵金属位点。 这项研究的总体目标是证明利用定向反应 双金属合金是实现化学和立体选择性氢化的一般策略 药物样化合物。这些选择性氢化反应将用于增加 sp3 候选药物的内容、三维度和结构多样性。我们将 开发新的双金属纳米粒子组合物以扩展定向氢化 无法使用分子催化剂（包括芳烃和 杂芳烃、胺定向反应以及定向基团和反应性基团的底物 部分彼此远离。我们还将探讨口述中的指导效应 具有多个可还原官能团的底物的化学和区域选择性 同时存在。在开发合成方法的同时，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 阐明高方向性所需的表面系综。总之，这个研究计划 将为选择性后期转化提供新的多相催化剂和方法 在生物活性化合物中。