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

在化学系化学合成计划的支持下，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，通过非传统策略快速组装新型分子支架，该策略利用两种不发达的反应中间体N-烯基硝酮和N，O-二烯基羟胺的反应性。安德森博士和她的团队正在确定模块化的方法，以从可获得的试剂中产生这些化学关键链，并控制重排活动的选择性，以形成具有明确三维结构的更稳定的化合物。这项工作旨在提高合成效率，以扩大化学空间。这一领域的改进有望有助于生物活性分子的发现、可获得性和研究，以及新材料的开发。这些活动还将为不同的研究生和本科生群体提供培训。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为UIC的有抱负的本科生化学家建立队列建立机会来促进包容性。UIC是一所少数族裔服务机构。提高效率以实现快速访问所需的分子靶标和扩大化学空间以包括新的分子结构仍然是有机合成中的两个关键需求，以支持对具有新性质的新化合物的需求。安德森教授的团队致力于开发N-烯基硝酮和N，O-二烯基羟胺的独特反应性，以应对合成挑战，并提高对这些多功能和不寻常合成子的反应性的基本了解。具体地说，安德森博士和她的团队正在开发：(I)不对称合成氮杂环丁硝酮的扭曲选择性反应；(Ii)氮杂环丁硝酮的非对映选择性官能化；(Iii)控制N-烯基异恶唑重排的取代基效应；以及(Iv)金属催化的炔加成方法，用于生成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化的产品正被纳入用于活性测试的药物和农业化学图书馆。正在研究的基础反应性有望扩大周环和级联反应的合成工具箱。这些活动还将培训研究生和本科生在化学实验和设计方面，以及用于让学生参与与化学相关的职业道路上的机会类型。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 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.