Deoxyfluorination using Metal fluorides

含有碳氟键的有机氟化合物被用于各种应用，包括用于治疗疾病的药物、高性能先进材料和用于向不断增长的人口供应食品的农用化学品。许多资源的有限性，包括对化学工业的有限环境容忍，要求我们向更可持续和更安全的化学过渡。线性生产路线消耗稀缺资源，其增值产品被降解为废物，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一个原因。在此背景下，采用符合当今性能指标（如高性能、安全性和可持续性）的规程生产含氟化学品的创新至关重要。在这种情况下，我们的目标是用安全和廉价的金属碱氟（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，使用氟化钾代替常用的脱氧氟化试剂（如二乙胺三氟化硫），将现成的醇转化为含氟化学品。脱氧氟化试剂来自SF4， SF4本身是一种危险化学品，由危险化学品氟化氢制备。我们目前的方法是基于Gouverneur小组之前对“氢键相转移催化”新概念的研究，该概念用于用氢键供体尿素催化剂活化碱金属氟化物。具体来说，我们提出了酒精和氟化钾的双重活化过程，将现成的外消旋醇转化为对药物具有重要意义的对映体富集的氟化基序。

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.