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

在化学结构、动力学机制-B计划的支持下，德克萨斯农工大学化学系的安迪托马斯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提供了新的途径，探索有机锂（推力I）和臭氧化物（推力II）的中间体。研究各种系统的基本反应模式的能力正在提供新的，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在被应用于回答几个开放的合成挑战，这些挑战对该领域具有相当重要的意义。具体来说，第一推力的重点是探索如何手性刘易斯碱可以创造新的途径与有机锂试剂的碳-碳键的不对称建设;和第二推力正在开发新的氧化反应与臭氧通过探索初级臭氧的反应模式。此外，该计划非常适合向学生传授广泛的技能，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NMR光谱）方面进行广泛的培训。该研究计划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。一个化学研讨会已经建立，以暴露第三，第四和第五年级的学生化学早期，并激励他们寻求在干职业。通过使用独特的核磁共振反应监测系统，该项目的重点是以下两个目标：（推力I）开发新的不对称去质子化取代序列与分离的离子对和（推力II）开发不对称建设性臭氧分解碳氧键的形成。在第一部分，我们将合成各种手性刘易斯碱，并研究其对碳负离子的不对称捕获。具体而言，拟议的工作致力于阐明手性刘易斯碱和有机金属试剂的关键结构特征，产生必要的激活和控制功能的发展高度通用和选择性的碳-碳键形成反应。该提案的第二个目标是对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元素进行详细的机械理解。特别是，Thrust II解决了长期存在的合成挑战，即在氧被安装到碳骨架中后将其功能化--追求烷基醚形成的新模式。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审查标准进行评估，被认为值得支持。

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.