Deoxyfluorination using Metal fluorides

含有碳-氟键的有机氟化合物用于各种应用，包括治疗疾病的药物、高性能先进材料和用于向不断增长的人口提供食物的农用化学品。许多资源的有限性，包括对我们化学工业的有限环境容忍度，要求向更可持续和安全的化学过渡。线性生产路线消耗了稀缺资源，其增值产品被浪费，这是气候变化、生物多样性减少以及粮食、水和能源短缺等全球危机的根源。在这种情况下，采用符合当今性能指标（如高性能、安全性和可持续性）的协议生产含氟化合物的创新至关重要。在这种情况下，我们的目标是从安全和廉价的金属碱氟化物如氟化钾合成急需的有机氟化合物。具体而言，该提案旨在发明一种新的反应，以使用氟化钾代替常用的脱氧硫试剂[例如三氟化二乙氨基硫]将容易获得的醇转化为含氟化合物，所述脱氧硫试剂衍生自SF 4，SF 4本身是一种由危险化学品氟化氢制备的危险化学品。我们目前的方法是基于Gouverneur集团以前的研究新概念的“氢键相转移催化”的活化碱金属氟化物与氢键供体尿素催化剂。具体而言，我们提出了一个双重激活过程的醇和氟化钾转化容易获得的外消旋醇对映体富集的氟化图案，是重要的药物。

Organofluorine compounds that contain a carbon-fluorine bond are used in a variety of applications, including pharmaceutical drugs to treat diseases, high-performance advanced materials, and agrochemicals for food supply to a growing population. The finite nature of many resources including the limited environmental tolerance towards our chemical industry requires transitioning towards more sustainable and safe chemistry. The linear route of production, in which scarce resources are consumed and their value-added products are degraded to waste, is a route cause of global crises such as climate change, diminished biodiversity, as well as food, water, and energy shortages. Within this context, innovation to produce fluorochemicals applying protocols that meet today's performance metrics, such as high performance, safety, and sustainability, is vital. In this context, our goal is to synthesize critically needed organofluorine compounds from safe and inexpensive metal alkali fluoride such as potassium fluoride. Specifically, this proposal aims at inventing a new reaction to convert readily available alcohols into fluorochemicals using potassium fluoride instead of commonly used deoxyfluorination reagents [e.g. diethylaminosulfur trifluoride] that are derived from SF4, a hazardous chemical itself prepared from the dangerous chemical hydrogen fluoride. Our current approach is based on the Gouverneur group's previous studies on the new concept of "Hydrogen Bonding Phase Transfer Catalysis" for the activation of alkali metal fluorides with a hydrogen bond donor urea catalyst. Specifically, we propose a dual activation process for both the alcohol and potassium fluoride to convert readily available racemic alcohols into enantioenriched fluorinated motifs that are of importance for a pharmaceutical drug.