RUI: Silyloxypyrone-Based [5+2] Cycloadditions: Mechanisms, Methods, and Mentorship

RUI：基于甲硅烷氧基吡喃酮的 [5 2] 环加成：机制、方法和指导

• 批准号: 1954588
• 负责人: Timothy Mitchell
• 金额: $ 23.1万
• 依托单位: Board of Trustees of Illinois State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1954588&HistoricalAwards=false
• 关键词: RUI; Silyloxypyrone; Based; 5+2; Cycloadditions

The Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor T. Andrew Mitchell in the Department of Chemistry at Illinois State University. Often referred to as the central science, chemistry continues to demonstrate extensive utility. Organic chemistry advances biology, medicine, physics, materials, economic development, national defense, and environmental sustainability. Professor Mitchell and his students study important bond-forming reactions called cycloadditions. These reactions perform a crucial function within the discipline of organic synthesis by enabling efficient and selective transformations of flat molecules to three-dimensional building blocks that are embedded within biologically active compounds. Although new reaction discoveries are intellectually fascinating, Dr. Mitchell is equally passionate about training next generation scientists to ask important questions within an organic chemistry CORE (Collaboration, Outreach, Research, Education) curriculum in preparation for the chemical workforce. Collaboration invites students in a research laboratory to work with a range of other scientists. Creativity, teamwork, presentation, deeper understanding, and characterization of new compounds are taught in this environment. For example, students learn to think on their feet and engage in nuanced scientific discussions during lab work and group meetings. Outreach provides opportunities for high school students, many from underrepresented groups, to participate in research experiences during the summer. Research in the undergraduate environment opens the door for greater sophistication through mentorship, critical reasoning, and exposure to state-of-the-art instrumentation as students take ownership of knowledge acquired in coursework. Education in the classroom includes guiding students toward confident inquiry while using various technological platforms to enhance content delivery. The main intellectual merit objectives of this project are to expand the mechanistic understanding and the practical utility of silyloxypyrone-based [5+2] cycloadditions toward construction of otherwise inaccessible natural and unnatural heterocyclic scaffolds. The Mitchell research group utilizes kinetic isotope effects, linear free energy relationship studies based on the Hammett equation, and collaborative theoretical calculations to elucidate various mechanistic scenarios of silyloxypyrone-based [5+2] cycloadditions. These studies expand the knowledge of [5+2] cycloadditions and lead to new directions such as asymmetric induction, intermolecular variants, and others. Broader impacts illustrate the superb training ground of [5+2] cycloadditions for next generation scientists. Several activities are integrated with discovery through our CORE (Collaboration, Outreach, Research, Education) program. This research has potential impact on the US chemical industry.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.

美国国家科学基金会化学部的化学合成项目支持T.伊利诺伊州立大学化学系的安德鲁·米切尔（Andrew Mitchell）。通常被称为中心科学，化学继续展示广泛的实用性。有机化学促进了生物学、医学、物理学、材料、经济发展、国防和环境可持续性。米切尔教授和他的学生研究重要的成键反应，称为环加成。这些反应在有机合成学科中发挥着至关重要的作用，使扁平分子能够有效和选择性地转化为嵌入生物活性化合物中的三维结构单元。虽然新的反应发现在智力上很吸引人，但米切尔博士同样热衷于培训下一代科学家在有机化学核心（协作，外联，研究，教育）课程中提出重要问题，为化学劳动力做准备。协作邀请学生在研究实验室与一系列其他科学家一起工作。创造力，团队合作，演示，更深入的理解和新化合物的表征都在这个环境中教授。例如，学生们学会思考他们的脚，并在实验室工作和小组会议期间进行细致入微的科学讨论。外联活动为高中生提供了机会，许多来自代表性不足的群体，在夏季参加研究经验。在本科环境中的研究通过导师制，批判性推理和接触最先进的仪器为学生掌握课程中获得的知识打开了更复杂的大门。课堂教育包括引导学生进行自信的探究，同时使用各种技术平台来增强内容交付。该项目的主要智力价值目标是扩大对基于硅氧基吡喃酮的[5+2]环加成的机械理解和实际效用，以构建否则难以获得的天然和非天然杂环支架。Mitchell研究小组利用动力学同位素效应、基于Hammett方程的线性自由能关系研究和协作理论计算来阐明基于甲硅烷基氧基吡喃酮的[5+2]环加成的各种机制方案。这些研究扩展了[5+2]环加成的知识，并导致了新的方向，如不对称诱导，分子间变体等。更广泛的影响说明了下一代科学家[5+2]环加成的绝佳训练场地。通过我们的CORE（协作，推广，研究，教育）计划，几项活动与发现相结合。 这项研究对美国化学工业具有潜在的影响。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。

项目成果

Boron-tethered oxidopyrylium-based [5 + 2] cycloadditions

硼系氧化吡咯鎓基 [5×2] 环加成

• DOI: 10.1016/j.tetlet.2022.154094
• 发表时间: 2022
• 期刊: Tetrahedron Letters
• 影响因子: 1.8
• 作者: Corrie, Seth I.;Pearce, Aaron C.;Grabowski, Jacob P.;Randolph, Kee A.;Guo, Wentao;Tantillo, Dean J.;Andrew Mitchell, T.
• 通讯作者: Andrew Mitchell, T.