CAREER: Mechanistic Insights Facilitate the Development of New Bond Forming Processes

职业生涯：机理见解促进新键形成工艺的开发

• 批准号: 2238881
• 负责人: Andy Thomas
• 金额: $ 77万
• 依托单位: Texas A&M 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: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2238881&HistoricalAwards=false
• 关键词: CAREER; Mechanistic; Insights; Facilitate; Development

With support from the Chemical Structure, Dynamics & Mechanisms-B Program of the Chemistry Division under this CAREER award, Andy Thomas of the Department of Chemistry at Texas A&M University is using newly developed rapid injection NMR (RI-NMR) systems to investigate the fundamental reactivity patterns of unstable intermediates. These new reaction monitoring systems have provided new avenues to explore organolithium (Thrust I) and ozonide (Thrust II) intermediates. The ability to investigate the fundamental reactivity patterns of various systems is providing new and, at times, unexpected mechanistic insights to be obtained, allowing for new reactions to be developed. The newly found mechanistic data are being applied to answer several open synthetic challenges that have considerable importance to the field. Specifically, Thrust I is focused on exploring how chiral Lewis bases can create new avenues for the asymmetric construction of carbon-carbon bonds with organolithium reagents; and Thrust II is developing new oxygenation reactions with ozone by exploring the reactivity patterns of primary ozonides. In addition, this program is well suited to impart a broad set of skills to students as the research requires extensive training in organic synthesis, kinetic analysis, and advanced spectroscopic techniques such as rapid-injection NMR spectroscopy. The crux of the research program has been integrated into an education plan that seeks to expand the scientific literacy of all citizens and places a special emphasis on engaging low-income areas. A chemistry workshop has been established to expose 3rd , 4th, and 5th graders to chemistry early on and inspire them to seek careers in STEM. By using unique RI-NMR reaction monitoring systems, this project is focused on the following two objectives: (Thrust I) development of new asymmetric deprotonation substitution sequences with separated ion pairs and (Thrust II) development of asymmetric constructive ozonolysis for carbon-oxygen bond formation. In Thrust I, a variety of chiral Lewis bases will be synthesized and investigated for the asymmetric capture of carbanions. Specifically, the proposed work endeavors to elucidate the key structural features of chiral Lewis bases and organometallic reagents that engender essential activating and controlling functions for the development of highly general and selective carbon-carbon bond forming reactions. Thrust II of this proposal seeks to gain a detailed mechanistic understanding of the steric and electronic control elements that influence the formation of primary ozonides and their subsequent diversification. Specifically, Thrust II addresses the long-standing synthetic challenge of functionalizing oxygen after it is installed into a carbon skeleton – pursuing new modes for alkyl ether formation.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CAREER奖化学分部化学结构、动力学和机理b项目的支持下，德克萨斯a&m大学化学系的Andy Thomas正在使用新开发的快速注入核磁共振（RI-NMR）系统来研究不稳定中间体的基本反应模式。这些新的反应监测系统为探索有机锂（Thrust I）和臭氧化物（Thrust II）中间体提供了新的途径。研究各种系统的基本反应模式的能力提供了新的，有时是意想不到的机制见解，允许开发新的反应。新发现的机械数据正被应用于回答几个对该领域具有相当重要意义的开放式合成挑战。具体来说，推力I的重点是探索手性路易斯碱如何为有机锂试剂的碳-碳键的不对称构建创造新的途径；推力II是通过探索原生臭氧的反应模式来开发新的臭氧氧化反应。此外，该计划非常适合传授给学生广泛的技能，因为研究需要在有机合成，动力学分析和先进的光谱技术（如快速注射核磁共振波谱）方面进行广泛的培训。该研究项目的核心已被纳入一项教育计划，该计划旨在扩大所有公民的科学素养，并特别强调低收入地区的参与。为了让三年级、四年级和五年级的学生尽早接触化学，并激发他们在STEM领域寻求职业发展，我们建立了一个化学研讨会。通过使用独特的RI-NMR反应监测系统，该项目主要致力于以下两个目标：（推力1）开发新的具有分离离子对的不对称去质子化取代序列；（推力2）开发用于碳-氧键形成的不对称建设性臭氧分解。在推力1中，将合成各种手性路易斯碱，并研究其对碳离子的不对称捕获。具体来说，本研究旨在阐明手性路易斯碱和有机金属试剂的关键结构特征，这些特征对高度通用和选择性的碳-碳键形成反应的发展产生必要的激活和控制功能。本建议的第二项重点是详细了解影响初级臭氧化物形成及其随后多样化的空间和电子控制因素的机制。具体来说，Thrust II解决了长期存在的合成挑战，即在将氧安装到碳骨架中后，实现氧的功能化——追求烷基醚形成的新模式。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。

项目成果

Effect of Solvent on the Rate of Ozonolysis: Development of a Homogeneous Flow Ozonolysis Protocol

溶剂对臭氧分解速率的影响：均流臭氧分解方案的开发

• DOI: 10.1021/acs.joc.3c01372
• 发表时间: 2023
• 期刊: The Journal of Organic Chemistry
• 作者: Arriaga, Danniel K.;Kang, Seokmin;Thomas, Andy A.
• 通讯作者: Thomas, Andy A.