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.

在化学系化学合成项目的支持下，布林莫尔学院的帕特里克·梅尔文正在研究开发能够将氟原子引入各种化合物的高活性分子。过去几十年来，氟原子的重要性日益突出，很大程度上是由于它可以赋予有机分子许多有益的特性，这导致氟原子被引入到市场上的许多领先药物中，通常可以提高现有药物的活性。鉴于这些重要的改进，梅尔文实验室设计了一种新型试剂，称为氟化亚胺（SIF），它能够以最有效和最便捷的方式掺入氟。此处的目标是扩大 SIF 的实用性，以解决更具挑战性的氟化反应，例如关键磷-氟键的形成。此外，Melvin 博士正在研究该试剂的作用。改变类别不仅可以改善氟化反应，还可以增强腈的生成，腈是医学相关有机分子中备受追捧的官能团。 除了实验室之外，梅尔文博士还将他对氟化亚胺的研究带到了实验室。最后，为了提高全女性本科生的化学参与度，梅尔文博士正在开发为期一周的“诺贝尔奖获得者”课程。 “化学教程”为学生提供了一个积极接触当前前沿科学的机会。在这项研究中，布林莫尔学院的帕特里克·梅尔文最近进一步探讨了氟化亚胺（SIF）对各种有机方法的影响。 Melvin 实验室开发了一种高反应性的 SIF，并展示了它们对醇和羧酸脱氧氟化及其参与氟化硫交换 (SuFEx) 的显着倾向SIF 增强的反应性可实现传统上具有挑战性且缓慢的反应的快速有效转化，梅尔文实验室正在研究它们对杂原子-氟键（即磷-氟和硫-氟键）的有效性。此外，将使用这些试剂来检查羰基官能团的经典脱氧氟化反应，以避免反应性的需要。正在努力修改 SIF 结构以实现外部无碱脱氧氟化反应，这将进一步提高该方法的实用性。最后，梅尔文实验室正在探索对砜亚胺核心结构进行更广泛的改变以使用该试剂。这项研究表明，通过仔细的试剂设计可以显着改进氟化方法，并显示出开发安装重要有机物的新途径的真正前景。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。