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.

在化学系化学合成计划的支持下，圣路易斯大学的杰米·尼利正在研究铁催化的过程，这些过程将三种不同的化学构件结合在一起，产生对医学、农业和材料科学有价值的产品。选择铁络合物作为这些方法的催化剂是因为它们能够以受控的方式与三个偶联伙伴相互作用，每个偶联伙伴都处于反应途径的特定阶段。令人感兴趣的催化剂还有另一个好处，那就是以地壳中最丰富的过渡金属为基础，以及最便宜和毒性最低的金属之一，突出了正在开发的过程的可持续性和潜在的实用价值。该资助项目的更广泛影响将延伸到提供证据，证明富含地球的金属的独特行为可以补充稀有贵金属的反应性，这些稀有贵金属在当前的过渡金属催化技术中更常见。参与资助研究的学生将获得全面的教育，涵盖过渡金属催化的所有方面，使他们有能力成为科学界知识渊博和有洞察力的贡献者。该奖项支持的活动包括为圣路易斯地区科学、技术、工程和数学(STEM)领域中代表性较低的少数族裔学生建立一个本科生暑期研究计划的推广工作。该资助的研究重点是开发铁催化的氮化物前体(例如叠氮化物)、炔烃和腈或异腈底物的三组分偶联反应，用于合成附加值高的含氮化合物。研究中的方法利用了空间密集的亚铁络合物的[2+2]环加成反应活性，这种反应对炔底物的性质高度敏感，允许引入具有高区域选择性的不对称炔烃。丁腈偶联反应将为合成咪唑提供一条通用的模块化路线，咪唑是生物活性化合物中普遍存在的结构基元，它将进一步应用于制备不同取代的N-杂环卡宾。咪唑形成的早期工作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活性，以后的工作旨在优化反应条件并探索针对三种底物的过程的范围。将探索使用异腈的铁催化偶联反应来获得具有广泛用途的作为合成中间体的亚胺基酮亚胺产品。最初的化学计量研究将针对那些有利于三组分耦合而不是初步实验中确定的竞争过程的条件。这些观察结果将为后来使反应在铁中催化的努力提供参考。这一奖项反映了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。