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.

在化学系化学合成项目的支持下，圣路易斯大学的 Jamie Neely 正在研究铁催化过程，该过程将三种不同的化学构件结合在一起，生成对医学、农业和材料科学有价值的产品。选择铁配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种偶联伙伴相互作用，每种偶联伙伴都在反应途径的特定阶段。最丰富的过渡金属地壳，也是最便宜和毒性最小的方法之一，强调了正在开发的过程的可持续性和潜在实用性，该资助项目的更广泛影响将延伸到提供证据，证明地球上丰富的金属的独特行为。可以补充当前过渡金属催化技术中更常见的稀有贵金属的反应性，参与资助研究的学生将获得涵盖过渡金属催化各个方面的全面教育，使他们有能力变得知识渊博和有能力。有洞察力的该奖项支持的活动包括为圣路易斯地区在科学、技术、工程和数学 (STEM) 领域代表性不足的少数群体学生建立本科暑期研究计划的外展活动。专注于开发氮烯前体（例如叠氮化物）、炔烃和腈或异腈底物的铁催化三组分偶联反应，用于合成增值、正在研究的含氮化合物利用空间拥挤的亚胺铁络合物的[2+2]环加成反应性，该络合物对炔底物的性质高度敏感，从而能够以高区域选择性掺入不对称炔烃。偶联伙伴将为咪唑提供通用和模块化的途径，咪唑是生物活性化合物中普遍存在的结构基序，并进一步应用于制备多种取代的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性，后期的工作旨在优化反应条件并探索三种底物的工艺范围。 -将探索使用异腈的催化偶联以获得具有广泛用途的合成中间体亚胺酰乙烯酮亚胺产品，初步化学计量研究将针对有利于合成中间体的条件。这些观察结果将为以后在铁中催化反应的努力提供信息。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响进行评估，被认为值得支持。审查标准。