Metal-Free Functionalization of Electron Rich Aromatic Systems: ortho-Quinone Methides, Aza-ortho-Xylylenes, and N,N-Dialkylaniline N-Oxides in Synthesis

化学部化学合成计划支持威廉·链教授的项目。Chain教授是特拉华大学化学与生物化学系的教员。他正在开发新的反应类别，这种反应通过反转正常的极性从而促进分子的反应性。反转极性意味着通常表现为带负电荷的分子表现为带正电荷的分子。这一变化促进了一系列新的碳-碳、碳-氧、碳-氮和碳-硫键的形成，这些键位于化学结构的核心，在工业、化学和医疗应用中有许多用途。Chain教授的研究小组为所有年龄段的学生提供最高水平的教育和培训。它还为通常在科学领域代表性较低的学生提供了机会。Chain教授积极参与当地小学、初中和高中的外展活动，以促进科学教育和学生对科学学科的参与。这些活动包括在Chain教授的实验室为有前途的高三学生进行暑期研究实习。这些实习机会鼓励学生对大学学习和科学职业的兴趣。自1800年中后期查尔斯·弗里德尔和詹姆斯·克拉夫茨在S的开创性工作以来，人们已经描述了一系列芳香族取代反应。尽管有这些工作，但在富电子环境中仍然存在局限性；富电子芳香体系的官能化可以通过暂时的反应性倒置来控制。在有机合成中，以可控和可预测的方式生成和使用高活性中间体是有机合成中的一个关键工具。在这方面的合成策略是操纵潜在的芳香族化合物和/或暂时参与杂原子结合的电子对，并利用这些能量结构形成稠密的碳-碳和碳-杂原子键。该奖项探索了两种可用于苯酚和苯胺的反应性多种多样。在第一反应流形中，硅基保护的苯酚和苯胺被转化为邻苯二酚甲基(QOMS)和氮杂邻二甲苯(AOXs)。这些受保护的物种与硅烯醇醚或硅基酮缩醛混合，通过使用易于分配和处理的氟化物来源处理，在共轭加成反应中释放亲电和亲核参与者。在第二个反应流形中，苯胺被氧化成相应的N-氧化物，这有助于一系列键的形成，这些键利用了弱N-O键的切除。通过这些温和的反应条件，扩大了富电子芳环Upolung反应的范围和能力。教育计划包括扩展到当地的小学、初中和高中，并将高中生作为研究实习生纳入研究计划。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor William Chain. Professor Chain is a faculty member in the Department of Chemistry & Biochemistry at the University of Delaware. He is developing new classes of reactions that that are facilitated by reversing the normal polarity and hence reactivity of molecules. Reversing the polarity means that molecules that normally behave as if they are negatively charged behave as if they are positively charged. The change facilitates the formation of a wide array of new carbon-carbon, carbon-oxygen, carbon-nitrogen, and carbon-sulfur bonds that lie at the heart of chemical structures that serve many purposes in industrial, chemical, and medical applications. Professor Chain's research group provides the highest level of education and training for students at all ages. It also offers opportunities for students typically underrepresented in science. Professor Chain is actively engaged in outreach activities in local elementary, middle, and high schools to promote science education and engagement of students in science disciplines. These activities include summer research internships in Professor Chain's laboratory for promising high school seniors. These internships encourage student interest in university studies and careers in the sciences. An array of aromatic substitution reactions have been described since the seminal work of Charles Friedel and James Crafts in the mid to late 1800's. Despite this body of work, there are still limitations in electron-rich settings; functionalization of electron-rich aromatic systems can be controlled by virtue of a temporary inversion of reactivity. Generating and engaging highly reactive intermediates in a controlled and predictable manner by an umpolung strategy is a critical tool set in organic synthesis. Synthetic strategies in this regard are the manipulation of latent aromatic compounds and/or the temporary engagement of heteroatom-bound electron pairs and harnessing these energetic structures to form congested carbon-carbon and carbon-heteroatom bonds. This award explores two reactivity manifolds available to phenols and anilines. In the first reactivity manifold, silyl-protected phenols and anilines are converted to ortho-quinone methides (QOMs) and aza-ortho-xylylenes (AOXs). These protected species are mixed with silyl enol ethers or silyl ketene acetals to release both the electrophilic and nucleophilic participants in conjugate addition reactions by treatment with easily dispensed and handled fluoride sources. In the second reactivity manifold, anilines are oxidized to the corresponding N-oxides, which facilitates an array of bond formations that take advantage of the excision of the weak N-O bond. By virtue of these mild reaction conditions, the scope and capability of umpolung reactions with electron rich aromatic rings is expanded. The educational plan includes outreach to local elementary, middle, and high schools with integration of high school students into the research program in as research interns.