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

合成 N-烷基和 N-芳基吡啶鎓盐的氧化策略

基本信息

批准号：
2154640
负责人：
Graham Dobereiner
金额：
$ 47.7万
依托单位：
Temple University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154640&HistoricalAwards=false
关键词：
Oxidative Strategies Synthesis Alkyl Aryl

项目摘要

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.

在化学系化学合成项目的支持下，天普大学的 Sarah Wengryniuk 正在研究制备一类重要化学物质的新方法，这些化学物质称为 N-烷基和 N-芳基吡啶鎓盐，这些带正电荷的氮-盐。含有化合物参与细胞过程，存在于各种有用的功能材料中，并且它们可以用作漱口水等产品中的抗菌剂此外，吡啶鎓盐可以作为有价值的前体。该资助项目将重点开发使用环境友好型工艺生产吡啶鎓盐的新方法，包括使用无毒的碘基氧化剂和电化学方法。获得比以前更多样化的吡啶盐，促进药品的制造，他们的研究也将有助于推进化学合成的新兴技术，该奖项的更广泛影响将扩大到使教授能够获得支持。 Wengryniuk 女士将继续努力推动科学、技术、工程和数学 (STEM) 领域女性的指导和晋升。具体来说，在之前设立的杰出女性科学领袖 (OWLS) 计划的支持下，PI 将制定相关计划。女导师/女学员匹配计划，并在天普大学设立年度女性化学研讨会系列，为女学生提供科学和专业的指导机会。N-烷基和N-芳基的合成吡啶鎓盐将通过两种策略进行研究，与早期方法相比，它们凭借其反应性极化而具有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的基础上。随着杂环基团转移反应的发展，用于烯烃和芳烃 C-H 键的无金属氧化官能化，第二个目标在试剂平台和目标方面补充了第一个目标。因此，通过使用电化学氧化，自由基阳离子中间体将被用作通过 C-H 胺化合成 2,4,6-三取代吡啶盐的手段，为新兴的交叉偶联手柄提供新的切入点。该资助项目的总体目标是提供创新且可行的方法，通过氧化策略获得 N-烷基和 N-芳基吡啶鎓盐，并在这些努力中取得成功。不仅将为氮杂环合成和自由基交叉偶联提供多种支架，而且还将推进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，并通过使用评估被认为值得支持基金会的智力价值和更广泛的影响审查标准。