Umpolung Methods with Electron Rich Aromatic Systems: Aza-ortho-Xylylenes, and N,N-Dialkylaniline N-Oxides in Synthesis

富电子芳族体系的 Umpolung 方法：合成中的氮杂邻二甲苯和 N,N-二烷基苯胺 N-氧化物

基本信息

批准号：
1955159
负责人：
William Chain
金额：
$ 45万
依托单位：
University of Delaware
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955159&HistoricalAwards=false
关键词：
Umpolung Methods Electron Rich Aromatic

项目摘要

With this award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Dr. William J. Chain of the Department of Chemistry and Biochemistry at the University of Delaware. Dr. Chain and his team of students are developing new reactions of aromatic compounds that reverse the normal behavior of these molecules. The Chain group is manipulating normally electron-rich aromatic compounds chemically such that they behave as species with low electron density. This strategy temporarily changes the reactivity of these pi-systems and triggers the formation of new carbon-carbon, carbon-oxygen, carbon-nitrogen, and carbon-sulfur bonds that are found in compounds used in industrial, medicinal, and material applications. These studies are serving to train a diverse group of graduate, undergraduate, and high school students in synthetic chemistry. The Chain group is also actively engaged in outreach activities in local elementary, middle, and high schools to promote science education and excitement towards STEM (science, technology, engineering, and mathematics) disciplines. While Friedel-Crafts reactions are well-established processes for aromatic substitution, there are still significant limitations in electron-rich settings. Professor Chain and his research group are addressing this gap in aromatic functionalization technology by developing ways to temporarily invert the reactivity of electron-rich anilines. In one approach, ortho-toluidines are being converted to aza-ortho-xylylenes (AOXs) via an electrochemical oxidation event and used as electron-acceptors for carbon-carbon bond formation. In a second approach, anilines are being oxidized to the corresponding N-oxides, which facilitates a wide array of bond formations and cyclizations that take advantage of the excision of the weak N–O bond. By virtue of the extremely mild reaction conditions associated with these new processes, the scope and application of umpolung reactions with electron rich aromatic rings is expanded thereby opening up new opportunities for organic synthesis. A better understanding of the fundamental reactivity behind these processes is also being established through collaborative computational studies. The educational plan is targeting outreach to local elementary, middle, and high schools with integration of high school students into the research program in the form of research internships.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.

通过该奖项，化学系的化学综合计划支持特拉华大学化学与生物化学系威廉·J·链的研究。 Chind博士和他的学生团队正在开发芳香化合物的新反应，以扭转这些分子的正常行为。链组正常操纵富含电子的芳族化合物化学化合物，使它们作为具有低电子密度的物种的作用。该策略暂时改变了这些PI系统的反应性，并触发了在工业，医疗和材料应用中使用的化合物中发现的新的碳碳，碳氧，碳氧，碳氮和碳硫键的形成。这些研究正在培训一组毕业生，本科和高中生的综合化学学生。连锁小组还积极从事当地小学，中学和高中的外展活动，以促进科学教育和对STEM（科学，技术，工程和数学）学科的兴奋。尽管Friedel-Crafts反应是芳香替代的完善过程，但电子富裕设置仍然存在显着局限性。 Chain教授及其研究小组正在通过开发暂时扭转富含电子苯胺的反应性的方法来解决芳族功能化技术的这一差距。在一种方法中，正通甲叶酸酯通过电化学氧化事件转化为AZA-ortho-xylylenes（AOX），并用作碳碳键形成的电子受体。在第二种方法中，Anilines被氧化为相应的N-氧化物，该氧化物构成了广泛的键形成和环化，从而利用了弱N – O键的惊喜。由于与这些新过程相关的极端反应条件，umpolung反应用电子富含电子环的范围和应用扩大，从而为有机合成开辟了新的机会。通过协作计算研究，可以更好地理解这些过程背后的基本反应性。该教育计划将以研究实习的形式将高中学生整合到研究计划中的当地小学，中学和高中的范围。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子的智力优点和更广泛的影响来通过评估来获得的支持。