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

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能够将氟原子引入各种化合物的高活性分子的发展。 氟是元素周期表上的一种元素，在过去几十年中变得越来越突出，这主要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许多领先的药物中，通常可以提高现有药物的活性，同时也为新的治疗方法铺平道路。 鉴于这些重要的改进，Melvin实验室设计了一类新的试剂，称为砜亚胺氟化物（SIF），能够以最有效和最方便的方式掺入氟。 这里的研究计划旨在扩大SIF的实用性，以解决更具挑战性的反应，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类试剂，不仅可以改善氢化反应，而且还可以增强腈的生成，腈是医学相关有机分子上一种非常受欢迎的官能团。 在实验室之外，梅尔文博士将他对砜亚胺氟化物的研究带到了布林莫尔学院的一门高水平的、以研究为灵感的实验室课程中。 最后，为了提高全女生本科生对化学的参与度，梅尔文博士正在开发一个为期一周的“诺贝尔奖获奖化学实验”，为学生提供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正在进一步探索砜亚胺氟化物（SIF）对各种有机方法的影响。 最近，Melvin实验室开发了一类高反应性的SIF，并证明了它们对醇和羧酸的脱氧能力的显著倾向，以及它们在硫氟交换（SuFEx）化学中的参与。 SIF的增强的反应性导致了传统上具有挑战性和缓慢的反应的快速和有效的转化。 使用这些试剂，Melvin实验室正在研究它们在合成杂原子-氟键（即磷-氟键和硫-氟键）方面的有效性，这些键在医药和合成化学中的重要性越来越大。 此外，将使用这些试剂检查羰基官能团的经典脱氧核苷反应，着眼于规避对反应性氟化物源的需要。 正在努力修改SIF结构，以实现外部无碱脱氧核糖核酸反应，这将进一步提高这种方法的实用性。 最后，Melvin实验室正在探索对砜亚胺核心结构进行更广泛的改变，以通过亲核和亲电途径在氰化反应中使用这类试剂。 这项研究表明，通过仔细的试剂设计，可以显着改善的方法，并显示真实的承诺，为开发新的途径，以安装重要的有机功能，最显着的是通过制作的C-F和C-CN bonds.This奖项反映了NSF的法定使命，并已被认为是值得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的支持。

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.