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

美国国家科学基金会化学部的化学合成计划支持伊利诺伊州立大学化学系T·安德鲁·米切尔教授的研究。化学通常被称为中心科学，继续显示出广泛的实用价值。有机化学促进了生物、医学、物理、材料、经济发展、国防和环境的可持续发展。米切尔教授和他的学生研究重要的成键反应，称为环加成反应。这些反应在有机合成学科中发挥着至关重要的作用，它使平面分子能够有效和选择性地转化为嵌入到生物活性化合物中的三维构件。尽管新的反应发现在智力上令人着迷，但米切尔博士同样热衷于培训下一代科学家，让他们在有机化学核心(协作、拓展、研究、教育)课程中提出重要问题，为化学工作者做好准备。合作邀请研究实验室的学生与一系列其他科学家一起工作。新化合物的创造力、团队合作、陈述、更深入的理解和表征都是在这种环境中教授的。例如，在实验室工作和小组会议期间，学生们学习用脚思考，并参与细微差别的科学讨论。外展为高中生提供了在暑期参加研究体验的机会，其中许多学生来自代表性不足的群体。本科生环境中的研究通过指导、批判性推理和接触最先进的工具打开了通向更复杂的大门的大门，因为学生掌握了在课程中获得的知识。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加强内容交付。该项目的主要智力价值目标是扩大基于硅氧基吡喃酮的[5+2]环加成反应的机理理解和实用价值，用于构建原本难以接近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硅氧基吡喃酮的[5+2]环加成反应的各种机理情景。这些研究扩展了[5+2]环加成反应的知识，并导致了不对称诱导、分子间变异等新的方向。更广泛的影响说明了为下一代科学家提供的[5+2]环加成的极好培训场地。通过我们的核心(协作、外联、研究、教育)计划，有几项活动与探索相结合。这项研究对美国化学工业具有潜在的影响。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。

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.