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

有了这个奖项，化学系的化学合成计划支持特拉华州大学化学和生物化学系的William J. Chain博士的研究。Chain博士和他的学生团队正在开发芳香族化合物的新反应，以逆转这些分子的正常行为。Chain基团通常以化学方式操纵富含电子的芳香族化合物，使其表现为具有低电子密度的物质。这种策略暂时改变了这些π系统的反应性，并引发了新的碳-碳，碳-氧，碳-氮和碳-硫键的形成，这些键在工业，医药和材料应用中使用的化合物中发现。这些研究有助于培养一个多元化的研究生，本科生和高中生在合成化学。Chain集团还积极参与当地小学，初中和高中的外展活动，以促进科学教育和对STEM（科学，技术，工程和数学）学科的兴奋。虽然Friedel-Crafts反应是芳香取代的成熟方法，但在富电子环境中仍然存在显著的限制。Chain教授和他的研究小组正在通过开发暂时逆转富电子苯胺反应性的方法来解决芳香族官能化技术的这一差距。在一种方法中，邻甲苯胺经由电化学氧化事件转化为氮杂-邻二甲苯（AOX）并用作碳-碳键形成的电子受体。在第二种方法中，苯胺被氧化成相应的N-氧化物，这有利于利用弱N-O键的切除的广泛的键形成和环化。由于与这些新方法相关的极其温和的反应条件，具有富电子芳环的非极性反应的范围和应用得到扩展，从而为有机合成开辟了新的机会。通过合作计算研究，也正在建立对这些过程背后的基本反应性的更好理解。该教育计划的目标是以当地小学、初中和高中为对象，以研究实习的形式将高中生融入研究计划。该奖项反映了NSF的法定使命，并通过使用基金会的智力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 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.