Enantioselective, Metal-Catalyzed Alkynylations of Oxocarbenium and Iminium Ions

含有氧和氮原子的有机分子广泛存在于药品、天然产品、聚合物和其他材料中。这些分子中有许多是手性的，这意味着它们以不可叠加的镜像形式存在。这些镜像结构在生物系统中的行为通常不同。例如，手性药物通常根据所用镜像结构的不同而显示不同的疗效。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的手性结构，也称为对映体是至关重要的。然而，制备许多分子的所需对映体的方法受到限制，这限制了潜在药物和生物探针的发现。在这个项目中，Mary Watson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，该策略将允许高效合成目前难以作为单一对映体制备的分子。催化剂本身是单一对映体，她还在研究催化剂和有机底物之间的基本相互作用，以使人们能够更广泛地了解这些反应的机理，特别是如何最终将催化剂的手性传递到手性产品的手性。沃森博士积极参与以她的研究为基础的外展活动，为所有层次的学生提供参与科学的机会。她的研究项目通过重要的研究机会为本科生提供了极好的培训。此外，通过在与大学相关的托儿所开展外展活动，沃森博士正在激励一群不同的幼儿(从学龄前到三年级)对科学充满热情。在化学系化学合成计划的资助下，特拉华大学的玛丽·沃森博士正在开发三取代和四取代α-立体中心合成氧和氮杂环的对映选择性催化方法。她正在研究使用手性铜催化剂将末端炔传递到环氧卡宾和亚胺离子中间体。她的重点是能够高效地合成用传统方法难以制备的高度对映体富含氧和氮的杂环支架。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选择性的理论基础。Watson博士积极参与科学、技术、工程和数学(STEM)推广计划，重点是通过与大学相关的托儿所的学生研究经验和示范计划来增加多样性，以支持该项目的更广泛影响。

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.