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

基于机理的新型镍催化立体特异性交叉亲电偶联反应的开发

• 批准号: 2155024
• 负责人: Elizabeth Jarvo
• 金额: $ 52.5万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2155024&HistoricalAwards=false
• 关键词: Mechanism; based; Development; New; Nickel

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.

在化学系化学合成计划的支持下，加州大学欧文分校的伊丽莎白·贾沃教授正在研究镍催化形成碳-碳键的新工艺的开发。与通常用于催化CC键形成的金属相比，镍的稀土含量更丰富，因此从环境可持续性的角度来看，使用镍的合成方法是有利的；然而，镍的化学成分复杂，并未得到很好的了解。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，旨在阐明控制反应选择性的基本属性。正在研究的方法为将简单的前体转化为附加值产品提供了新的方法，具有潜在的应用前景，如药剂、农用化学品和其他先进材料。由于贾沃教授和她的同事从事各种教育和外联活动，该资助项目的更广泛影响延伸到为社会带来的惠益。其中，独特的LEAPS(实验室实验和物理科学活动)计划旨在提高中学生对化学研究的参与和意识，这些学生来自STEM(科学、技术、工程和数学)领域传统上代表性较低的群体。在同样促进更广泛参与科学事业的其他得到支持的活动中，针对女性和其他少数族裔教职员工、研究生和本科生的指导和职业发展研讨会也正在由首席研究员和她的团队勤奋地进行。受资助的研究侧重于研究新的镍催化的酯、磺胺和亚胺的分子内交叉亲电偶联反应。预计这些努力将为后期官能化提供有用的方法，以及合成1，1-二芳基烷烃和杂环的策略，这些都是药物化学的重要部分。正在进行的机械实验将为新的镍催化反应的合理设计提供信息，并将试图确定关键的催化中间体，以解决有关反应途径的现有知识差距。正在进行的研究的一个中心目标是获得实验证据，以确定当镍配合物在交叉亲电偶联催化循环中导航时，支持单电子和/或双电子基本氧化还原步骤所必需的配体特征。在反应周期中镍的氧化状态变化的奇偶性是交叉偶联和交叉亲电偶联反应中烷基亲电体反应立体化学结果的关键决定因素。最终，通过完善对镍催化反应机理的基本理解，这项研究试图消除阻碍贱金属催化歧管广泛应用于有机合成的一个重要障碍，即机理上的模棱两可。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。