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

项目摘要/摘要 多相贵金属催化剂是有机合成中常用的催化剂。 不饱和有机官能团的氢化，因为它们具有快速的反应性和易加性 净化。然而，当其他催化剂存在时，多相催化剂往往选择性较差。 可减少的官能度和由于二维而不能实现立体归纳 催化剂表面的性质。从关于衬底的同类文献中获得灵感- 定向反应性，Li组最近展示了第一个多相 羟基定向氢化。使用含有贵金属的双金属合金催化剂和 贱金属，我们能够催化环烯烃的高度非对映选择性加氢。 通过将羟基导向基团同时吸附到贱金属原子和烯烃上 在贵金属遗址上。 这项拟议研究的首要目标是证明使用 双金属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。这些选择性加氢反应将被用来提高SP3 候选药物的内容、立体化和结构多样性。我们会 开发新的双金属纳米颗粒组合物以扩大定向加氢 概念到无法使用分子催化剂访问的体系，包括芳烃和 杂芳烃、胺定向反应和底物中的导向基团和反应性 一部分位于彼此相距较远的地方。我们还将探索在口述中的导演效果 多个可还原官能团在底物中的化学选择性和区域选择性 同时呈现。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 以阐明高方向性所需的表面系综。总的来说，这项研究计划 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。

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.