New Synthetic Opportunities with N-Alkenylnitrones and N,O-Dialkenylhydroxylamines

在化学系化学合成项目的支持下，伊利诺伊大学芝加哥分校（UIC）的劳拉·安德森（Laura Anderson）正在开发新的反应，通过非常规的策略，利用两种尚未开发的反应中间体（N-烯基硝基酮和N， o -二烯基羟胺）的反应活性，快速组装新的分子支架。安德森博士和她的团队正在确定模块化的方法，从可获得的试剂中产生这些化学关键，并控制重排活性的选择性，以形成具有明确三维结构的更稳定的化合物。这项工作的目标是提高合成效率，扩大化学空间。这一领域的改进有望有助于生物活性分子的发现、可及性和研究，以及新材料的开发。这些活动还将为不同群体的研究生和本科生提供培训。安德森博士计划通过在有机化学入门课程中组织本科生研究报告来宣传本科生研究机会的好处，并通过领导一个委员会来促进包容性，为UIC有抱负的本科生化学家建立队列建设机会，这是一个少数民族服务机构。在有机合成中，为了支持对具有新性质的新化合物的需求，提高效率以快速获得所寻求的分子靶点和扩大化学空间以包括新的分子结构仍然是两个关键需求。安德森教授的团队专注于开发N-烯基硝基和N， o -二烯基羟胺的独特反应性，以解决合成挑战，并提高对这些多功能和不寻常的合成物的反应性的基本理解。具体来说，Anderson博士和她的团队正在开发：(i)不对称合成氮杂啶氮酮的扭矩选择反应；（ii）氮杂啶氮酮的非对映选择性官能化，（iii）取代基效应控制N-烯基异恶唑啉的重排，以及（iv）金属催化的炔加成方法生成N， o -二烯基羟胺及其不对称重排为1,4-二羰基化合物。这些研究的结构多样的产品正在被纳入医药和农业化学文库进行活性测试。正在研究的基础反应性有望扩大周环反应和级联反应的合成工具箱。这些活动还将培养研究生和本科生在化学实验和设计方面的能力，并用于吸引学生参与化学相关职业道路上的各种机会。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 support from the Chemical Synthesis Program in the Division of Chemistry, Laura Anderson of the University of Illinois at Chicago (UIC) is developing new reactions to rapidly assemble novel molecular scaffolds through unconventional strategies that use the reactivity of two underdeveloped reactive intermediates, N-alkenylnitrones and N,O-dialkenylhydroxylamines. Dr. Anderson and her team are determining modular ways to generate these chemical linchpins from accessible reagents and to control the selectivity of the rearrangement activity to form more stable compounds with defined three-dimensional structures. This work is targeting improved synthetic efficiency to expand chemical space. Improvements in this area are expected to contribute to the discovery, accessibility, and study of biologically active molecules, as well as the development of new materials. These activities will also provide training for a diverse group of graduate and undergraduate students. Dr. Anderson plans to publicize the benefits of undergraduate research opportunities by organizing undergraduate research presentations in introductory organic chemistry courses and promoting inclusivity by leading a committee to establish cohort-building opportunities for aspiring undergraduate chemists at UIC, which is a minority serving institution.Improving efficiency to enable rapid access to sought after molecular targets and expanding chemical space to include new molecular architectures remain two critical needs in organic synthesis to support demands for new compounds with novel properties. Professor Anderson’s group is focused on developing the unique reactivity of N-alkenylnitrones and N,O-dialkenylhydroxylamines to address synthetic challenges and improve fundamental understanding of the reactivity of these versatile and unusual synthons. Specifically, Dr. Anderson and her team are developing: (i) torquoselective reactions for the asymmetric synthesis of azetidine nitrones; (ii) diastereoselective functionalizations of azetidine nitrones, (iii) substituent effects to control the rearrangements of N-alkenylisoxazolines, and (iv) metal-catalyzed alkyne addition methods for the generation N,O-dialkenylhydroxylamines and their asymmetric rearrangement to 1,4-dicarbonyl compounds. The architecturally diverse products of these studies are being included in medicinal and agrichemical libraries for activity testing. The foundational reactivity being investigated are expected to expand the synthetic toolbox of pericyclic and cascade reactions. These activities will also train graduate and undergraduate students in chemical experimentation and design, as well as be used to engage students in the types of opportunities available in chemistry-related career paths.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.