Mechanism-based Development of New Nickel-catalyzed Stereospecific Cross-electrophile Coupling Reactions

在化学系化学合成项目的支持下，位于欧文的加州大学的Elizabeth Jarvo教授正在研究开发新的镍催化过程，以形成碳-碳键。镍比通常用于催化CC键形成的金属在地球上更丰富，因此从环境可持续性的角度来看，使用它的合成方法是有利的;然而，镍的化学性质很复杂，尚未得到很好的理解。为了克服实现有效和可靠的镍催化形式的挑战，工艺开发与详细的机械实验相结合，旨在阐明负责控制反应选择性的基本属性。正在调查的方法提供了新的方法的承诺，简单的前体转化为增值产品的潜在应用，作为药剂，农用化学品，和其他先进的材料。资助项目的更广泛的影响延伸到累积到社会的好处，因为教授Jarvo和她的同事从事各种教育和推广活动。其中，独特的LEAPS（物理科学实验室实验和活动）计划旨在增加中学生对化学研究的参与和认识，这些学生来自传统上在STEM（科学，技术，工程和数学）领域代表性不足的群体。在其他支持的活动，同样促进扩大参与科学企业，指导和职业发展研讨会，针对女性和其他少数民族教师，研究生和本科生也正在努力追求的首席研究员和她的团队。资助的研究重点是研究新的镍催化的酯，磺酰胺和酰亚胺的分子内交叉亲电偶联反应。预计这些努力将提供有用的方法，后期功能化以及策略的合成1，1-二芳基烷烃和杂环，药物化学的重要部分。正在进行的机理实验将告知新的镍催化反应的合理设计，并将尝试识别关键的催化中间体，以解决现有的知识差距有关的反应途径。正在进行的研究的一个中心目标是获得实验证据，建立必要的支持一个和/或两个电子的基本氧化还原步骤的镍络合物导航交叉亲电偶联催化循环的配体功能。在反应循环期间镍的氧化态变化的奇数或偶数性质是烷基亲电试剂在交叉偶联和交叉亲电试剂偶联反应中的反应的立体化学结果的关键决定因素。最终，通过完善镍催化反应机理的基本理解，该研究旨在消除阻碍有机合成更广泛采用贱金属催化歧管的重大障碍，即机理模糊性。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。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Elizabeth Jarvo of the University of California at Irvine is studying the development of new nickel-catalyzed processes for the formation of carbon-carbon bonds. Nickel is more earth-abundant than the metals typically used to catalyze CC bond formation and so synthetic methods that use it are advantageous from the standpoint of environmental sustainability; however, the chemistry of nickel is complex and not well understood. To overcome the challenges of realizing effective and reliable forms of nickel catalysis, process development is being coupled with detailed mechanistic experiments designed to elucidate the fundamental attributes responsible for the control of reaction selectivity. The methods under investigation offer the promise of new approaches for the conversion of simple precursors into value added products with potential applications as pharmaceutical agents, agrochemicals, and other advanced materials. The broader impacts of the funded project extend to the benefits accrued to society as Professor Jarvo and her coworkers engage in a variety of educational and outreach activities. Among them, the unique LEAPS (Laboratory Experiments and Activities in Physical Sciences) program is directed at increasing participation in, and awareness of, chemical research by middle school students from groups traditionally underrepresented in STEM (science, technology, engineering and mathematics) fields. In other supported activities that likewise promote broadening participation in the scientific enterprise, mentoring and career-development workshops that target female and other minority faculty, graduate students, and undergraduate students are also being diligently pursued by the lead investigator and her team.The funded research focuses on study of new nickel-catalyzed intramolecular cross-electrophile coupling reactions of esters, sulfonamides, and imides. It is anticipated that these efforts will provide useful methods for late-stage functionalization as well as strategies for the synthesis of 1,1-diarylalkanes and heterocycles, important moieties for medicinal chemistry. Mechanistic experiments being performed will inform on the rational design of new nickel-catalyzed reactions and the identification of key catalytic intermediates will be attempted to address existing knowledge gaps concerning reaction pathways. A central aim of the research being pursued is to obtain experimental evidence establishing the ligand features necessary to support one- and/or two-electron elementary redox steps as nickel complexes navigate the cross-electrophile coupling catalytic cycle. The odd or even nature of oxidation state changes at nickel during the reaction cycle is a critical determinant for the stereochemical outcome of reactions of alkyl electrophiles in cross-coupling and cross-electrophile coupling reactions. Ultimately, by refining basic understanding of the mechanism of nickel-catalyzed reactions, the research seeks to remove a significant obstacle that has hindered the wider adoption of base metal catalytic manifolds for organic synthesis, namely, mechanistic ambiguity.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.