Template Driven Access to Highly Congested Stereocenters: Synthetic and Mechanistic Studies

在化学系化学合成（SYN）项目的支持下，北达科他州立大学的Mukund Sibi教授正在研究在立体化学控制下合成密集碳环杂环有机化合物（除碳外还含有N、O、S等重原子的环状有机化合物）的新方法。具有明确立体化学性质的杂环化合物是天然产物合成、化学生物学和药物化学的重要组成部分。例如，大多数用于治疗人类疾病的药物都含有杂环亚结构。在光谱的另一端，杂环在材料制造中也是不可或缺的。西比教授和他的研究生们将开发的方法是高效、低成本和环保的。美国国家科学基金会的资助还将通过培养研究生进入21世纪的劳动力，对人类能力建设产生重大影响。外展活动也是该奖项的一部分。在资助的第二年，来自主要本科院校的10名教员将接受关于DOSY（扩散有序光谱学）介绍的培训，这是一种研究溶液结构的最先进方法，使这些教员能够将这些知识带回各自的机构教授学生。另一项重要的推广活动是一门关于杂环的研究生课程，旨在吸引来自多个没有开设此类课程的机构的学生。Sibi教授和他的学生正在开发新的方法来安装所有的碳四元中心，控制相对和绝对立体化学。构建手性四元中心的可靠的催化方法很少。目前克服这一障碍的方案通常仅限于单一反应类型。制定一种策略，在广泛的反应类别中执行，将产生重大影响。在这项工作中，Sibi教授及其同事将使用非手性模板驱动策略，通过利用几个重要的合成转换，为受阻手性中心的安装提供可靠和有效的解决方案。这项工作的智力价值集中在合成和机械有机化学上。它将在小碳环和杂环的制备方面取得根本性的进展，并开发机械工具来理解有机转化中反应中间体的结构。这项工作的更广泛的影响是开发了新的合成方法来获取碳环和杂环，作为学术界和化学工业研究人员的重要工具。该计划提供了从基础到高级的连续学习工具，这将能够在催化的广泛方面教育各个层次的科学家。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。

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Professor Mukund Sibi from North Dakota State University, is studying new ways to synthesize crowded carbocyclic heterocyclic organic compounds (cyclic organic compounds containing heavy atoms such as N,O and S in addition to carbon) with control of stereochemistry. Heterocyclic building blocks with defined stereochemistries are valuable building blocks for natural product synthesis, chemical biology and medicinal chemistry. For example, a majority of therapeutics used to treat human diseases contain heterocyclic substructures. On the other end of the spectrum, heterocycles are also integral in the manufacture of materials. The methods to be developed by Professor Sibi and his graduate students are designed to be efficient, cost effective, and eco-friendly. The funding from the National Science Foundation will also make a significant impact on human capacity building by training graduate students to enter the 21st century workforce. Outreach activities are also part of this award. In the second year of the grant, ten faculty members from primarily undergraduate institutions will receive training on Introduction of DOSY (Diffusion Ordered Spectroscopy) a state-of-the-art method to study solution structure, enabling these faculty to takes such knowledge back to their respective institutions to teach students. Another outreach activity of significance is a graduate course on heterocycles designed to engage students from multiple institutions where such courses are not offered. Professor Sibi and his students are developing new methods for the installation of all carbon quaternary centers with control over relative and absolute stereochemistry. Reliable and catalytic methods for the construction of chiral quaternary centers are sparse. Current protocols to surmount this barrier are generally limited to a single reaction type. The development of a strategy that performs across a broad class of reactions would deliver significant impact. In this work, Professor Sibi and co-workers will use an achiral-template-driven strategy to deliver reliable and effective solutions for the installation of hindered chiral centers by utilizing several important synthetic transformations. The intellectual merit of the work is focused on synthetic and mechanistic organic chemistry. It will make fundamental advances in the preparation of small carbo- and heterocycles and develop mechanistic tools to understand the structure of the reactive intermediates involved in organic transformations. Broader impacts of the work are the development of new synthetic methodology for accessing carbo- and heterocycles as important tools for researchers in academia as well as the chemical industry. The program offers a continuum of learning tools from basic to advanced, which will enable educating scientists across all levels in broad aspects of catalysis.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.