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

在化学系化学合成计划的支持下，北达科他州州立大学的穆昆德·斯比教授正在研究通过立体化学控制合成密集碳环杂环有机化合物(除碳外还含有N、O和S等重原子的环有机化合物)的新方法。具有明确立体化学结构的杂环构建块是天然产物合成、化学生物学和药物化学的宝贵构建块。例如，大多数用于治疗人类疾病的治疗药物都含有杂环亚结构。在光谱的另一端，杂环在材料的制造中也是不可或缺的。思比教授和他的研究生们将要开发的方法被设计成高效、经济和环保的。来自国家科学基金会的资金还将通过培训研究生进入21世纪的劳动力队伍，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。在拨款的第二年，来自主要是本科生机构的10名教职员工将接受介绍扩散有序光谱(DOSY)的培训，这是一种研究溶液结构的最先进方法，使这些教职员工能够将这些知识带回各自的机构教授学生。另一项重要的外联活动是关于杂环化合物的研究生课程，旨在吸引来自不提供此类课程的多个机构的学生。西比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，并控制相对和绝对的立体化学。用于构筑手性四元中心的可靠和催化的方法很少。目前跨越这一障碍的方案通常限于单一反应类型。制定一项在广泛的反应类别中执行的战略将产生重大影响。在这项工作中，Sibi教授和他的同事将使用非手性模板驱动的策略，通过几种重要的合成转化为受阻的手性中心的安装提供可靠和有效的解决方案。这项工作的学术价值主要集中在合成有机化学和机械有机化学上。它将在制备小碳环和杂环方面取得根本性进展，并开发机械工具来了解参与有机转化的活性中间体的结构。这项工作的更广泛的影响是开发了获取碳环和杂环的新的合成方法，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一系列学习工具，这将使所有级别的科学家能够在催化剂的广泛方面进行教育。该奖项反映了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。

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.