Modular chemocatalysts for tunable and predictable C-H functionalization

用于可调节和可预测的 C-H 官能化的模块化化学催化剂

• 批准号: 2247217
• 负责人: Jennifer Schomaker
• 金额: $ 50.29万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247217&HistoricalAwards=false
• 关键词: Modular; chemocatalysts; tunable; predictable; functionalization

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.

在化学系化学催化和化学合成项目的支持下，Jennifer M。威斯康星州大学的Schomaker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物，农用化学品，聚合物和燃料的构建块。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，当分子中存在多个不同的C-H键时，仅在一个特定的C-H键处实现所需反应的选择性是具有挑战性的。在这个项目中，Schomaker教授的小组正在扩展低成本银催化剂的设计，以高产率将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。这些催化剂产生更少的废物，从单一起始材料提供几种有用的产品，并简化了含有至少一个C-N键的选定商业药物的制备。在更广泛的影响方面，Schomaker教授参与了一些外展计划，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，以及与行业合作伙伴合作，使她的实验室研究和新催化剂对行业具有吸引力。研究生和本科生通过接触其化学的真实的世界应用并接受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键可调官能化为升级的C-N键。为了解决这个问题，Schomaker教授正在追求新催化体系的基本理解和实际应用，该体系能够通过金属催化的氮烯转移过程实现C-H键到C-N键的化学，位点和立体选择性转化的可预测催化剂控制。她还计划扩展这些催化剂的效用，以选择性地将C-H键转化为更有价值的C-C和C-O键。这些研究将结合联合收割机的机械，光谱和计算研究（密度泛函理论和更高水平的从头算方法，例如CASSCF）来了解不同且易于制备的N-和P-供体配体的特征如何影响：1）所得金属氮烯和卡宾的电子结构，2）反应中间体的动力学行为，3）底物和催化剂之间的非共价相互作用以控制C-H官能化的位点选择性，以及最后，4）开发用于对映选择性氮烯转移的通用、模块化和容易获得的催化剂的能力。最终，这项工作的目的是建立通用的设计原则，以可持续地促进非定向C-H功能化，超越先天的反应性偏好。通过将这些原理应用于各种过渡金属催化的C-H键氧化，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的氧化剂，以及与工业合作伙伴在针对药物支架后期修饰方面的合作。该奖项反映了NSF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。