Transition metal assisted fluorinations

在这个由化学部门化学合成计划资助的项目中，路易斯维尔大学化学系的Gerald B. Hammond教授将研究氟-金活化过程，该过程可以介导串联序列，从而导致新的金属介导的亲核加成/偶联/氟化反应，这反过来又应该导致有机氟化合物的有效合成。尽管氟具有改变化合物的物理化学性质的独特能力，但将其引入小分子通常是很麻烦的。事实上，氟化脂肪族和环系的合成需要繁琐的试剂或合成程序，这些试剂或合成程序依赖于一小部分商业含氟构建块。本研究基于机理的方法将使脂肪族有机氟化合物（如氟酮和氟杂环）以药物化学友好的方式合成，利用能够进行金属介导的氟化、氧化或偶联的阳离子金属物种，以及现成的炔或烯烃作为起始材料。最终，对氟产生的阳离子物种提出的工作将对氟和过渡金属的相互作用产生实质性的见解。该项目更广泛的影响是，其定义明确的模块适合培养有机氟化学领域的年轻一代学生和博士后，尽管氟在医药或农用化学领域的重要性日益增加，但与其他工业化国家相比，美国的少数科学家开展了这一研究领域。该项目将影响广泛定义的制造领域，因为它将以多样化的方式和较少的合成步骤随时获得氟化化合物。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Gerald B. Hammond of the Department of Chemistry at the University of Louisville will investigate fluorine-gold activation processes that can mediate tandem sequences leading to novel metal-mediated nucleophilic addition/coupling/fluorination reactions, which, in turn, should lead to efficient synthesis of organofluoro compounds. Even though fluorine has a unique ability to modify the physico-chemical properties of a compound, its introduction on small molecules is usually cumbersome. Indeed, the syntheses of fluorinated aliphatic and cyclic systems require tedious reagents or synthetic procedures that rely on a small pool of commercial fluorine-containing building blocks. The mechanism-based approach of this research will enable the synthesis of aliphatic organofluoro compounds, such as fluoroketones and fluoroheterocycles in a medicinal chemistry-friendly manner, utilizing cationic metal species capable of metal-mediated fluorinations, oxidations or couplings, and readily available alkynes or alkenes as starting materials. Ultimately, the work proposed on fluorine-engendered cationic species will yield substantial insights on the interaction of fluorine and transition metals. The broader impact of this project is that its well-defined modules are suitable for training a younger generation of students and postdoctoral fellows in organofluorine chemistry, a research area that is performed by a handful of scientists in the U.S., compared to other industrialized nations, despite the ever-increasing importance of fluorine in the medicinal or agrochemical fields. This project will impact the manufacturing field broadly defined because it will give ready access to fluorinated compounds in a diversified manner and with fewer synthetic steps.