Triaryl Oxonium Ions: A mild strategy to functionalised arynes.

三芳基氧鎓离子：功能化芳烃的温和策略。

• 批准号: 2446204
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2446204
• 关键词: Triaryl; Oxonium; Ions; mild; strategy

Onium ions are ubiquitous reagents in synthetic chemistry. Iodonium salts and ylides of sulfonium and phosphonium ions are invaluable synthetic tools. However, the formation of oxonium ions and their use in synthesis is significantly more limited. Trialkyl oxonium ions were first discovered in 1937 by the reaction of an epoxide with an ether in the presence of a Lewis acid and they have been used as strong alkylating agents ever since. Triaryl oxonium ions first emerged in 1957 and exhibit enhanced stability compared with their alkyl counterparts and undergo electrophilic aromatic substitution reactions. Despite this, they have largely been forgotten - demonstrated by the fact that triaryl oxonium ions are incredibly rare in the chemical literature with fewer than 10 distinct scaffolds. Furthermore, there are no reports of them being used as aryne precursors despite aryne formation being a proposed decomposition pathway under basic conditions and other onium ions, such as iodonium salts, being used for aryne generation. Iodonium ions form arynes under strongly basic conditions or with adjacent trimethylsilyl groups that can be activated by fluoride. Fluoride activation of trimethylsilylaryltriflates is the most common method to generate o-arynes, however, sensitive functional groups are generally installed at the end as they are not compatible with the conditions require to install the reactive moieties. This incompatibility, synthetic challenges and the use of fluoride or strong bases results in arynes being rarely used in complex molecules and late stage functionalisation despite their synthetic potential for complexity generation and diverse reactivity.We aim to develop a mild and scalable synthetic route to the desired oxonium ions. We would subsequently test their ability to generate arynes under basic conditions, optimise their reactivity and then apply it to complex systems with sensitive functional groups to expand the reach of aryne chemistry. Furthermore, the high leaving group ability of oxonium ions should allow us to generate arynes from substrates where the traditional methodology fails. Pursuit of increasing the efficiency and scope of the aryne chemistry closely aligns with the EPSRC grand challenge of 100% efficient synthesis in the chemical sciences. It is also hoped that the methodology being developed will be utilised to aid synthetic chemists constructing complex molecules from polyaromatic hydrocarbons to drug discovery and beyond. This project falls within the EPSRC Physical Chemistry (Synthetic Organic Chemistry) research area.

在合成化学中，氧离子是普遍存在的试剂。碘鎓盐和锍、磷鎓离子的叶立德是非常宝贵的合成工具。然而，氧鎓离子的形成和它们在合成中的应用明显更受限制。三烷基氧鎓离子是在1937年通过环氧化物与醚在刘易斯酸存在下的反应首次发现的，从那时起它们就被用作强烷基化剂。三芳基氧鎓离子最早出现于1957年，与其烷基对应物相比具有更高的稳定性，并进行亲电芳香取代反应。尽管如此，它们在很大程度上被遗忘了-这一事实证明，三芳基氧鎓离子在化学文献中非常罕见，只有不到10种不同的支架。此外，没有关于它们被用作芳炔前体的报道，尽管芳炔的形成是在碱性条件下提出的分解途径，并且其他鎓离子如碘鎓盐被用于芳炔的产生。碘离子在强碱性条件下或与相邻的三甲基甲硅烷基形成芳炔，这些基团可以被氟化物活化。三甲基甲硅烷基芳基三氟甲磺酸酯的氟化物活化是产生邻-芳炔的最常见方法，然而，敏感官能团通常安装在末端，因为它们与安装反应性部分所需的条件不相容。这种不相容性、合成挑战以及氟化物或强碱的使用导致芳炔很少用于复杂分子和后期官能化，尽管它们具有复杂性生成和多样反应性的合成潜力。我们的目标是开发一种温和且可扩展的合成路线以获得所需的氧鎓离子。随后，我们将测试它们在碱性条件下生成芳炔的能力，优化它们的反应性，然后将其应用于具有敏感官能团的复杂系统，以扩大芳炔化学的范围。此外，氧鎓离子的高离去基团能力应该允许我们从传统方法失败的底物生成芳炔。追求提高芳炔化学的效率和范围与EPSRC在化学科学中100%高效合成的巨大挑战紧密结合。人们还希望，正在开发的方法将被用来帮助合成化学家构建复杂的分子，从多环芳烃到药物发现等等。该项目属于EPSRC物理化学（合成有机化学）研究领域的福尔斯。