Modular chemocatalysts for tunable and predictable C-H functionalization

在化学系化学催化和化学合成计划的支持下，威斯康星大学的Jennifer M.Schomaker教授正在研究开发新的地球资源丰富且廉价的催化剂，将石油和生物可再生资源中的原料化学品转化为制药、农用化学品、聚合物和燃料的宝贵构件。碳-氢(C-H)键是有机化合物中最常见的化学键，它可以转化为更有价值的键，包括碳-氮(C-N)键。然而，当一个分子中有多个不同的C-H键时，只在一个特定的C-H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教授的团队正在扩大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上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，从一种起始材料中产生几种有用的产品，并简化至少包含一个C-N键的选定商业药物的制备。在更广泛的影响方面，Schomaker教授参与了教育公众，特别是年轻女性参与科学的外联计划。她的研究旨在通过展示如何将水用作环境可持续的溶剂、探索减少废流的高效电化学方法以及与行业合作伙伴合作，使她的实验室的研究和新型催化剂对工业具有吸引力。研究生和本科生从这些更广泛的影响中受益，他们接触到了他们的化学在现实世界中的应用，并得到了来自工业同行的共同指导。该项目正在进行的工作有望导致开发基于银、铁和铜的低成本模块化催化剂，用于将C-H键可调为更高的C-N键。为了解决这个问题，Schomaker教授致力于新催化系统的基本理解和实际应用，这些新催化系统能够实现可预测的催化剂控制，通过金属催化的氮键转移过程实现C-H键到C-N键的化学、位置和立体选择性转化。她还计划扩大这些催化剂的用途，选择性地将C-H键转化为更有价值的C-C和C-O键。这些研究将结合机理、光谱和计算研究(密度泛函理论和更高水平的从头计算方法，如CASSCF)来了解不同的和容易制备的N和P给体配体的特征如何影响：1)生成的金属硝烯和卡宾的电子结构，2)反应中间体的动态行为，3)底物和催化剂之间的非共价相互作用以控制C-H官能化的位置选择性，最后，4)开发通用的、模块化的和易于获得的催化剂用于对映体选择性的硝烯转移。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C-H功能化，覆盖先天的反应性偏好。通过将这些原理应用于各种过渡金属催化的C-H键氧化反应，这项工作的科学影响将得到扩大。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，以及与工业合作伙伴合作，针对药物支架的后期修改。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.