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

在化学系化学合成项目的支持下，圣路易斯大学的杰米·尼利（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，产生对医学、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基于它们能够以受控的方式与三个偶联伙伴相互作用，每个偶联伙伴在反应途径的特定阶段。我们感兴趣的催化剂还有一个额外的好处，即它是基于地壳中最丰富的过渡金属，也是最便宜、毒性最小的金属之一，强调了正在开发的工艺的可持续性和潜在的实际效用。资助项目的更广泛影响将扩展到提供证据，证明地球上丰富的金属的独特行为可以补充稀有贵金属的反应性，稀有贵金属在当前过渡金属催化技术中更常用。参与资助研究的学生将获得全面的教育，包括过渡金属催化的各个方面，使他们有能力成为科学界知识渊博和有见地的贡献者。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族裔学生建立本科暑期研究项目的推广工作。受资助的研究重点是发展铁催化的三组分偶联反应，包括亚硝基前体（例如叠氮化物）、炔和腈或异腈底物，用于合成增值的含氮化合物。所研究的方法利用了对炔底物性质高度敏感的立体拥挤的亚胺铁配合物的[2+2]环加成反应性，允许具有高区域选择性的不对称炔的掺入。咪唑是生物活性化合物中普遍存在的结构基序，丁腈偶联伙伴的反应将为咪唑的合成提供一条通用和模块化的途径，并进一步应用于制备不同取代的n -杂环羰基。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，后期工作旨在优化反应条件并探索三种底物的过程范围。将探索利用异硝基铁催化偶联获得作为合成中间体具有广泛用途的咪甲酰基酮亚胺产品。初步的化学计量学研究将针对有利于三组分耦合的条件，而不是在初步实验中确定的竞争过程。这些观察结果将为以后使该反应在铁中具有催化作用提供信息。该奖项反映了美国国家科学基金会的法定使命，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。

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.