RUI: Further Expansion of Sulfone Iminium Reagents and Their Use in Fluorination and Cyanation Methodologies

RUI：亚胺砜试剂的进一步扩展及其在氟化和氰化方法中的应用

• 批准号: 2247109
• 负责人: Patrick Melvin
• 金额: $ 26.82万
• 依托单位: Bryn Mawr College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247109&HistoricalAwards=false
• 关键词: RUI; Further; Expansion; Sulfone; Iminium

With the support of the Chemical Synthesis Program in the Division of Chemistry, Patrick Melvin of Bryn Mawr College is studying the development of highly reactive molecules capable of introducing a fluorine atom into various compounds. Fluorine, an element on the periodic table, has risen in prominence over the last several decades, largely due to a host of beneficial properties that it can impart on organic molecules. This has led to fluorine atoms being introduced to many of the leading pharmaceuticals on the market, often improving the activity of existing drugs while also paving the way for new therapeutics. Given these important enhancements, the Melvin laboratory has devised a new class of reagents, called sulfone iminium fluorides (SIFs), which are capable of incorporating fluorine in the most efficient and expedient ways possible. Research plans here aim to expand the utility of SIFs to tackle even more challenging fluorination reactions, such as the formation of critical phosphorus – fluorine bonds. Additionally, Dr. Melvin is investigating how this reagent class can be altered to not only improve fluorination reactions, but to also enhance the creation of nitriles, a much sought-after functional group on medicinally relevant organic molecules. Beyond the laboratory, Dr. Melvin is bringing his research on sulfone iminium fluorides to the classroom in an upper-level, research-inspired laboratory course at Bryn Mawr College. Finally, to increase chemistry engagement amongst the all-female undergraduate population, Dr. Melvin is developing a week-long “Nobel Prize-winning Chemistry Tutorial”, which offers students a chance to actively connect with current, cutting-edge science.In this research, Patrick Melvin of Bryn Mawr College is further probing the influence of sulfone iminium fluorides (SIFs) on various organic methodologies. Recently, the Melvin laboratory has developed a highly reactive class of SIFs and demonstrated their remarkable propensity for the deoxyfluorination of alcohol and carboxylic acids and their engagement in sulfur fluoride exchange (SuFEx) chemistry. The enhanced reactivity of SIFs leads to rapid and efficient transformations for reactions that have traditionally been challenging and slow. Using these reagents, the Melvin laboratory is investigating their effectiveness on the synthesis of heteroatom – fluorine bonds, namely phosphorus-fluorine and sulfur-fluorine bonds, which have a growing importance in both medicinal and synthetic chemistry. Furthermore, classic deoxyfluorination reactions of carbonyl functional groups will be examined using these reagents with an eye toward circumventing the need for reactive fluoride sources. Efforts are ongoing to modify the SIF structure to enable external base-free deoxyfluorination reactions, which would further elevate the utility of this methodology. Finally, the Melvin laboratory is exploring more extensive alterations to the sulfone iminium core structure to employ this reagent class in cyanation reactions via nucleophilic and electrophilic pathways. This research demonstrates that fluorination methodologies can be significantly improved through careful reagent design and shows real promise for developing new pathways to the installation of important organic functionality; most notably via the crafting of C-F and C-CN bonds.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.

在化学系化学合成计划的支持下，布林莫尔学院的帕特里克·梅尔文正在研究能够将氟原子引入各种化合物的高活性分子的开发。氟是元素周期表上的一种元素，在过去的几十年里，它的地位有所上升，这在很大程度上是因为它可以赋予有机分子一系列有益的性质。这导致氟原子被引入到市场上的许多领先药物中，通常会改善现有药物的活性，同时也为新的疗法铺平了道路。鉴于这些重要的改进，梅尔文实验室设计了一种新的试剂，称为氟化亚磺酸亚胺(SIF)，它能够以最有效和最便捷的方式结合氟。这里的研究计划旨在扩大SIF的用途，以解决更具挑战性的氟化反应，例如形成关键的磷-氟键。此外，梅尔文博士正在研究如何改变这种试剂类别，不仅可以改善氟化反应，还可以促进氰化物的生成，这是一种非常受欢迎的医用相关有机分子官能团。在实验室之外，梅尔文博士正在布林莫尔学院(Bryn Mawr College)开设的一门以研究为灵感的高级实验室课程中，将他对氟化亚砜的研究带到课堂上。最后，为了增加全女性本科生的化学参与度，梅尔文博士正在开发一个为期一周的“诺贝尔奖获奖化学教程”，为学生提供一个积极接触当前尖端科学的机会。在这项研究中，布林莫尔学院的帕特里克·梅尔文进一步探索了磺酸亚胺氟化物(SIF)对各种有机方法的影响。最近，梅尔文实验室开发了一类高活性的SIF，并展示了它们对乙醇和羧酸脱氧氟化的显著倾向，以及它们参与硫氟化物交换(SuFEx)化学的能力。SiF的反应活性增强，导致了传统上具有挑战性和缓慢的反应的快速而有效的转变。利用这些试剂，梅尔文实验室正在研究它们在合成杂原子-氟键方面的有效性，即磷-氟键和硫-氟键，这两种键在药物和合成化学中具有越来越重要的作用。此外，将使用这些试剂检查经典的羰基官能团的脱氧氟化反应，以避免使用反应性氟化物来源。目前正在努力修改SIF结构以实现外部无碱脱氧氟反应，这将进一步提高这一方法的实用性。最后，梅尔文实验室正在探索通过亲核和亲电途径在氰化反应中使用这种试剂类别的更广泛的磺化亚胺核心结构的变化。这项研究表明，通过仔细的试剂设计，氟化方法可以得到显著改进，并显示出开发安装重要有机功能的新途径的真正前景；最明显的是通过制作C-F和C-CN键。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。