Enantioselective, Metal-Catalyzed Alkynylations of Oxocarbenium and Iminium Ions

氧碳鎓和亚胺离子的对映选择性金属催化炔基化

• 批准号: 1664981
• 负责人: Mary Watson
• 金额: $ 42万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1664981&HistoricalAwards=false
• 关键词: Enantioselective; Metal; Catalyzed; Alkynylations; Oxocarbenium

Organic molecules containing oxygen and nitrogen atoms are prevalent in pharmaceuticals, natural products, polymers, and other materials. Many of these molecules are chiral, which means that they exist as non-superimposable mirror images. These mirror image structures often behave differently in biological systems. For example, chiral pharmaceuticals typically show different efficacy depending on which mirror-image structure is administered. Given their importance in biological and biomedical applications, it is therefore crucial to prepare these molecules as a single chiral structure, also known as an enantiomer. However, methods to prepare the desired enantiomer of many molecules are limited, and this curbs the discovery of potential medicines and biological probes. In this project, Dr. Mary Watson is developing a strategy using catalysts for the synthesis of oxygen- and nitrogen-containing cyclic compounds that will allow the efficient synthesis of molecules that are currently difficult to prepare as single enantiomers. The catalysts are themselves single enantiomers, and she is also studying the fundamental interactions between the catalyst and the organic substrates to enable broad understanding of the mechanism of these reactions, and especially how the chirality of the catalyst is ultimately conveyed to that of the chiral product. Dr. Watson is actively engaged in outreach activities that build upon her research to provide opportunities for students of all levels to engage in science. Her research program provides excellent training for undergraduate students through significant research opportunities. In addition, through outreach at the University-associated daycare, Dr. Watson is inspiring a diverse group of young children (pre-school through third grade) with excitement about science. With funding from the Chemical Synthesis Program of the Chemistry Division, Dr. Mary Watson of the University of Delaware is developing enantioselective catalytic methods for the synthesis of oxygen and nitrogen heterocycles with tri- and tetrasubstituted alpha-stereocenters. She is investigating the use of chiral copper catalysts to deliver terminal alkynes to cyclic oxocarbenium and iminium ion intermediates. Her focus is to enable efficient synthesis of highly enantioenriched oxygen and nitrogen heterocycle scaffolds that are difficult to prepare via conventional methods. She will also undertake rigorous mechanistic experiments to understand the structure of the active catalyst and determine a rationale for the high enantioselectivity observed in these reactions. Dr. Watson is actively engaged in science, technology, engineering, and mathematics (STEM) outreach programs focused on increasing diversity through student research experiences and demonstration programs at the University-associated daycare, in support of the broader impacts of this project.

含有氧和氮原子的有机分子在药物、天然产物、聚合物和其他材料中普遍存在。 这些分子中的许多是手性的，这意味着它们以不可重叠的镜像存在。 这些镜像结构通常在生物系统中表现不同。例如，手性药物通常显示不同的功效，这取决于施用哪种镜像结构。 鉴于它们在生物和生物医学应用中的重要性，因此将这些分子制备为单一手性结构（也称为对映异构体）至关重要。然而，制备许多分子的所需对映体的方法是有限的，这限制了潜在药物和生物探针的发现。在该项目中，玛丽沃森博士正在开发一种使用催化剂合成含氧和含氮环状化合物的策略，该策略将允许有效合成目前难以制备为单一对映体的分子。催化剂本身是单一的对映异构体，她还研究了催化剂和有机底物之间的基本相互作用，以广泛了解这些反应的机理，特别是催化剂的手性最终如何传递到手性产物。沃森博士积极参与外展活动，以她的研究为基础，为各级学生提供从事科学的机会。她的研究计划通过重大的研究机会为本科生提供了良好的培训。此外，通过与大学相关的日托中心的推广，沃森博士正在激发一群不同的幼儿（从学前班到三年级）对科学的兴奋。在化学部化学合成计划的资助下，特拉华州大学的玛丽沃森博士正在开发对映选择性催化方法，用于合成具有三取代和四取代的α-立构中心的氧和氮杂环。她正在研究使用手性铜催化剂将末端炔转化为环氧碳鎓和亚胺鎓离子中间体。她的重点是使高对映体富集的氧和氮杂环支架，难以通过常规方法制备的有效合成。她还将进行严格的机械实验，以了解活性催化剂的结构，并确定在这些反应中观察到的高对映体选择性的基本原理。沃森博士积极参与科学，技术，工程和数学（STEM）外展计划，重点是通过学生的研究经验和示范计划在大学相关的日托增加多样性，以支持该项目的更广泛的影响。