Modular chemocatalysts for tunable and predictable C-H functionalization

在化学系化学催化和化学合成项目的支持下，威斯康星大学的Jennifer M. Schomaker教授正在研究开发新的地球丰富和廉价的催化剂，将来自石油和生物可再生资源的原料化学品转化为有价值的药品、农用化学品、聚合物和燃料的基石。碳氢键（C-H）是有机化合物中最常见的化学键类型，它可以转化为更有价值的键，包括碳氮键（C-N）。然而，当一个分子中存在多个不同的碳氢键时，仅在一个特定的碳氢键上实现所需反应的选择性是具有挑战性的。在这个项目中，Schomaker教授的团队正在扩展低成本银催化剂的设计，以高产量将C-H键转化为C-N键，并利用这一知识开发基于地球丰富的金属铁和铜的更便宜的催化剂。这些催化剂产生的废物更少，从一种原料中产生几种有用的产品，并且简化了含有至少一个C-N键的选定商业药物的制备。就更广泛的影响而言，Schomaker教授参与了推广项目，以教育和吸引公众，特别是年轻女性参与科学。她的研究旨在通过展示如何将水用作环境可持续溶剂，探索有效的电化学方法来减少废物流，以及与工业伙伴合作，使她的实验室的研究和新的催化剂对工业有吸引力。研究生和本科生通过接触他们的化学在现实世界中的应用以及接受来自工业界同事的共同指导，从这些更广泛的影响中受益。该项目正在进行的工作预计将导致开发基于银、铁和铜的低成本模块化催化剂，用于将C-H键可调功能化为升级的C-N键。为了解决这个问题，Schomaker教授正在寻求新的催化系统的基本理解和实际应用，这些系统能够通过金属催化的硝基转移过程实现对C-H键到C-N键的化学、位置和立体选择转化的可预测的催化剂控制。她还计划扩展这些催化剂的用途，选择性地将碳-氢键转化为更有价值的碳-碳和碳-氧键。这些研究将结合机械、光谱和计算研究（密度泛函理论和更高水平的从头算方法，如CASSCF），以了解多种易于制备的N-和p -供体配体的特征如何影响：1)所得金属亚硝基烯和羰基的电子结构，2)反应中间体的动力学行为，3)底物与催化剂之间的非共价相互作用以控制C-H功能化的位点选择性，最后，4)开发通用的，模块化的，易于获取的对映选择性亚硝基烯转移催化剂的能力。最终，这项工作旨在建立通用的设计原则，以可持续地促进非定向碳氢化合物功能化，从而超越先天反应性偏好。通过将这些原理应用于各种过渡金属催化的C-H键氧化，将扩大这项工作的科学广泛影响。其他更广泛的影响包括使用非氯化溶剂进行这些转化的能力，使用电化学方法取代化学计量氧化剂，以及与工业伙伴合作针对药物支架的后期修饰。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Catalysis and the Chemical Synthesis Programs in the Division of Chemistry, Professor Jennifer M. Schomaker of the University of Wisconsin is studying the development of new earth abundant and inexpensive catalysts to transform feedstock chemicals from petroleum and biorenewable sources into valuable building blocks for pharmaceuticals, agrochemicals, polymers, and fuels. The carbon-hydrogen (C–H) bond is the most common type of chemical bond in organic compounds and it can be transformed into more valuable bonds, including carbon-nitrogen (C–N) bonds. However, it is challenging to achieve selectivity for a desired reaction at only one specific C–H bond when there are multiple different C–H bonds in a molecule. In this project, Professor Schomaker’s group is expanding the design of low-cost silver catalysts to transform C–H bonds into C–N bonds in high yields and using this knowledge to develop even less expensive catalysts based on the earth abundant metals iron and copper. These catalysts generate less waste, deliver several useful products from a single starting material, and streamline the preparation of selected commercial drugs that contain at least one C–N bond. In terms of broader impacts, Professor Schomaker participates in outreach programs to educate and engage the general public, especially young women, in science. Her studies are aimed at making her laboratory’s research and new catalysts appealing to industry by showing how water can be used as an environmentally sustainable solvent, exploring efficient electrochemical methods to reduce waste streams, and collaborating with industry partners. Graduate and undergraduate students benefit from these broader impacts through exposure to real world applications of their chemistry and by receiving co-mentoring from industrial colleagues.The work being carried out in this project is expected to lead to the development of low-cost, modular catalysts based on silver, iron and copper for the tunable functionalization of C–H bonds to upgraded C–N bonds. To address this issue, Professor Schomaker is pursuing both the fundamental understanding and the practical applications of new catalytic systems able to achieve predictable catalyst control of the chemo-, site-, and stereoselective transformations of C–H bonds to C–N bonds through metal-catalyzed nitrene transfer processes. She also plans to extend the utility of these catalysts to selectively transform C–H bonds into more valuable C–C and C–O bonds. These investigations will combine mechanistic, spectroscopic, and computational studies (density functional theory and higher-level ab initio methods such as CASSCF) to understand how the features of diverse and easily prepared N- and P-donor ligands influence: 1) the electronic structures of the resulting metal nitrenes and carbenes, 2) the dynamic behavior of reactive intermediates, 3) non-covalent interactions between the substrate and catalyst to control site-selectivity of the C–H functionalization, and finally, 4) the ability to develop general, modular, and readily accessible catalysts for enantioselective nitrene transfers. Ultimately, this work aims to establish universal design principles to sustainably facilitate non-directed C–H functionalization that overrides innate reactivity preferences. The scientific broader impacts of this work will be expanded by applying these principles to a diverse range of transition metal-catalyzed C–H bond oxidations. Additional broader impacts include the ability to use non-chlorinated solvents for these transformations, the employment of electrochemical methods to replace stoichiometric oxidants, and the collaboration with industrial partners in targeting late-stage modifications of drug scaffolds.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.