Oxidative Strategies for the Synthesis of N-Alkyl and N-Aryl Pyridinium Salts

在化学系化学合成计划的支持下，坦普尔大学的Sarah Wengryniuk正在研究制备一类重要的化学物质的新方法，称为N-烷基和N-芳基吡啶盐。这些带正电荷的含氮化合物参与细胞过程，存在于各种有用的功能材料中，它们可用作漱口水等产品中的抗菌剂。此外，吡啶鎓盐充当通常存在于活性药物成分中的亚基的有价值的前体。该资助项目将侧重于开发使用环境友好工艺生产吡啶盐的新方法，包括使用无毒的碘基氧化剂和电化学方法。所选择的方法将允许获得比以前更多样化的吡啶盐，促进药物的制造，并且它们的研究也将有助于推进新兴的化学合成技术。该奖项的更广泛的影响将扩展到使教授Wengryniuk继续她的重大努力，以促进指导和促进妇女在科学，技术，工程和数学（干）。具体而言，在先前设立的杰出妇女科学领袖倡议的主持下，PI将开发一个女性导师/女性学员匹配计划，并在坦普尔大学建立一个年度女性化学研讨会系列，为女学生提供科学和专业的导师机会。将通过两种策略研究芳基吡啶鎓盐，这两种策略由于它们的反应性而提供了与早期方法相比无与伦比的多功能性。第一个目标将建立在PI在氮连接碘（III）试剂领域的既定研究计划基础上，开发用于烯烃和芳烃C-H键的无金属氧化官能化的杂环基团转移反应。第二个目标在试剂平台和靶支架两者中补充第一个目标。因此，通过使用电化学氧化，自由基阳离子中间体将被利用作为经由C-H胺化合成2，4，6_三取代的吡啶鎓盐的手段，为新兴的交叉偶联柄提供新的进入点。在整个过程中，资助项目的总体目标是提供创新和使能的方法，通过氧化策略获得N-烷基和N-芳基吡啶鎓盐。这些努力的成功不仅将为氮杂环丁烷合成和自由基交叉偶联提供多种支架，还将推动氮连接高价碘试剂化学和基于电化学的合成方法。该奖项反映了NSF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 the support of the Chemical Synthesis Program in the Division of Chemistry, Sarah Wengryniuk of Temple University is studying new approaches for the preparation of an important class of chemical substances called N-alkyl and N-aryl pyridinium salts. These positively charged, nitrogen-containing compounds are involved in cellular processes, found in a variety of useful functional materials, and they can be used as antimicrobial agents in products such as mouthwash. Furthermore, pyridinium salts serve as valuable precursors to subunits that commonly occur in active pharmaceutical ingredients. The funded project will focus on the development of new methods to generate pyridinium salts using environmentally benign processes, including the use of non-toxic iodine-based oxidants and electrochemical methods. The chosen approaches will allow for access to a more diverse range of pyridinium salts than was previously possible, facilitating the manufacture of pharmaceuticals, and their study will also help to advance emerging technologies for chemical synthesis. The broader impacts of the award will extend to enabling Professor Wengryniuk to continue her significant efforts to advance the mentorship and promotion of women in science, technology, engineering, and mathematics (STEM). Specifically, under the auspices of the previously established Outstanding Women Leaders in Science (OWLS) initiative, the PI will develop a female mentor/female mentee match program and establish an annual Women in Chemistry seminar series at Temple University to provide scientific and professional mentorship opportunities for female students.The synthesis of N-alkyl and N-aryl pyridinium salts will be investigated by two strategies that offer unrivalled versatility as compared to earlier approaches by virtue of their reactivity umpolung. The first aim will build upon the PI's established research program in the area of nitrogen-ligated iodine(III) reagents, with the development of heterocyclic group transfer reactions for a metal-free oxidative functionalization of alkenes and arene C–H bonds. The second aim complements the first in both reagent platform and target scaffolds. Thus, through the use of electrochemical oxidation, radical cation intermediates will be leveraged as a means of synthesizing 2,4,6-trisubstituted pyridinium salts via C–H amination, providing new points of entry to emerging cross coupling handles. Throughout, the overarching goal of the funded project is to provide innovative and enabling methods to access N-alkyl and N-aryl pyridinium salts by oxidative strategies. Success in these endeavors will not only provide access to diverse scaffolds for azacycle synthesis and radical cross couplings, but also advance both nitrogen-ligated hypervalent iodine reagent chemistry and electrochemistry-based synthetic methods.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.