CAS: Iron-Catalyzed Three-Component Coupling Methods via Iron Azametallacyclobutene Complexes

CAS：铁氮杂金属环丁烯配合物的铁催化三组分偶联方法

• 批准号: 2247744
• 负责人: Jamie Neely
• 金额: $ 50万
• 依托单位: Saint Louis University
• 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: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247744&HistoricalAwards=false
• 关键词: CAS; Iron; Catalyzed; Three; Component

With the support of the Chemical Synthesis Program in the Division of Chemistry, Jamie Neely of Saint Louis University is studying iron-catalyzed processes that join together three distinct chemical building blocks to generate products that are of value to medicine, agriculture, and materials science. The choice of iron complexes as the catalysts for these methods is rooted in their ability to interact with the three coupling partners in a controlled fashion, each at a specific stage of the reaction pathway. The catalysts of interest have the added benefit of being based on the most abundant transition metal in the Earth’s crust, as well as one of the least expensive and least toxic, accentuating the sustainability and potential practical utility of the processes under development. The broader impacts of the funded project will extend to providing evidence that the distinct behavior of Earth-abundant metals can complement the reactivity of the rare precious metals that are more commonly deployed in current transition metal-catalyzed technology. Students participating in the funded research will gain a comprehensive education encompassing all aspects of transition metal catalysis, providing them with the capacity to become knowledgeable and insightful contributors to the scientific community. The activities supported by the award include outreach efforts directed toward establishing an undergraduate summer research program for students from minority groups underrepresented in science, technology, engineering, and mathematics (STEM) from the Saint Louis area.The funded research is focused on the development of iron-catalyzed three-component coupling reactions of nitrene precursors (e.g., azides), alkynes, and nitrile or isonitrile substrates for the synthesis of value-added, nitrogen-containing compounds. The methods under investigation capitalize on [2+2] cycloaddition reactivity of sterically congested iron imide complexes that is highly sensitive to the nature of the alkyne substrate, allowing for the incorporation of unsymmetrical alkynes with high regioselectivity. Reactions of nitrile coupling partners will provide a general and modular route to imidazoles, a pervasive structural motif in biologically active compounds, with further application to the preparation of diversely substituted N-heterocyclic carbenes. Early efforts in imidazole formation will focus on translating the stoichiometric behavior observed in preliminary studies to catalytic reactivity, with later work aimed at optimizing reaction conditions and exploring the scope of the process with respect to each of the three substrates. Iron-catalyzed coupling using isonitriles will be explored to access imidoyl ketenimine products that have broad utility as synthetic intermediates. Initial stoichiometric studies will target conditions that favor three-component coupling over a competing process identified in preliminary experiments. These observations will inform later efforts to render the reaction catalytic in iron.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.

在化学合成计划中，圣路易斯大学的杰米·尼利（Jamie Neely）正在研究铁催化的过程，这些过程将三个不同的化学基础结合在一起，以产生对医学，农业和材料科学具有价值的产品。将铁复合物作为这些方法的催化剂的选择植根于它们以受控方式与三个耦合伙伴相互作用的能力，每个伴侣在特定的特定方面都具有基于地球壳中最丰富的过渡金属的额外好处，以及最不昂贵的，最不昂贵的毒性和最不毒性的可持续性和潜在的实用性和潜在的实用性，而不是造成的。资助项目的更广泛的影响将扩展到提供证据表明，土壤丰富的金属的独特行为可以完成当前过渡金属催化技术中更常用的稀有贵金属的反应性。参加资助研究的学生将获得一项全面的教育，其中包括过渡金属催化的各个方面，从而使他们有能力成为科学界的知识渊博和有见地的贡献者。该奖项支持的活动包括旨在建立一项针对来自圣路易斯地区科学，技术，工程和数学代表性不足的学生的本科夏季研究计划，该计划的重点是开发铁 - 催化的三组分促进硝基元素和nInrenrene nitrene nitrene and nitrene andky andky andy anky anky anky andy anky anky anky anky anky anky anky anky andy anky andy，含氮的化合物合成增值的异硝基底物。投资下的方法资本利用了[2+2]的环载含铁酰亚胺复合物对碱基底物性质高度敏感的含酰胺酰亚胺复合物的反应性，从而可以掺入具有高调节性选择性的不对称炔烃。氮耦合伴侣的反应将为生物活性化合物中普遍存在的结构基序提供一般的模块化途径，并进一步应用于制备多样化的N-杂化型卡伯酮。咪唑形成的早期努力将集中于将初步研究中观察到的化学计量行为转化为催化反应性，后来的工作旨在优化反应条件并探索相对于三个底物的每个过程的范围。将探索使用异硝基酯的铁催化耦合，以访问具有合成中间体的广泛实用性的咪多酰酮类产品。最初的化学计量研究将针对有利于三组分耦合的条件，而不是初步实验中确定的竞争过程。这些观察结果将在以后的努力中为铁中的反应催化提供依据。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准被认为是通过评估来获得的支持。