Organocatalytic Fluorinations with Fluoride Salts

用氟化物盐进行有机催化氟化

• 批准号: EP/R010064/1
• 负责人: Veronique Gouverneur
• 金额: $ 62.46万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR010064%2F1
• 关键词: Organocatalytic; Fluorinations; Fluoride; Salts

Fluorine is a unique element of the periodic table that impacts hugely on society because many pharmaceuticals, agrochemicals and anaesthetics owe their important properties to the presence of fluorine atoms within their structures. For example, the small and highly electronegative fluorine atom plays a remarkable role in medicinal chemistry. Selective installation of fluorine into a therapeutic or diagnostic small molecule candidate can enhance molecular properties such as improved metabolic stability and enhanced membrane permeation. Fluorine substitution as a strategy to increase binding affinity of drug candidates to target protein has also been documented in a number of cases. One of the challenges associated with the discovery and production of these compounds is the availability of highly efficient and cost effective catalytic methods for carbon-fluorine (C-F) bond formation. To date, many chemists worldwide have actively worked in this area of research, and developed a range of processes for this purpose, but the reactions discovered to date employ expensive fluorine source derived from F2, a gas yellow in colour that is highly reactive and corrosive. Only a minority of these processes make use of cheaper fluoride salts, but these then require expensive transition metal catalysts, and suffer from narrow substrate scope.With this project, we propose to develop and study a novel catalytic reaction for carbon-fluorine bond formation, that benefits from the use of cost effective fluoride salts and cost effective catalysts made of purely organic materials and free from transition metal ions. The design of our system allows for easy chemical modification and hence simple coarse or fine-tuning of the catalysts structure and reactivity profile. The catalytic process that we have designed for fluoride activation is mechanistically unprecedented, and will be applied to the preparation of important fluorinated molecules for immediate application in medicinal chemistry. Accordingly these new catalytic fluorination and the products of these reactions will be of great value to chemists in industry and academia alike, and have the potential to impact widely on society by improving health and quality of life.

氟是元素周期表中的一种独特元素，对社会产生了巨大的影响，因为许多药物，农用化学品和麻醉剂的重要特性都归功于其结构中氟原子的存在。例如，小而高电负性的氟原子在药物化学中起着显着的作用。将氟选择性地安装到治疗或诊断小分子候选物中可以增强分子性质，例如改善的代谢稳定性和增强的膜渗透。氟取代作为增加候选药物与靶蛋白的结合亲和力的策略也已在许多情况下被记录。与这些化合物的发现和生产相关的挑战之一是用于碳-氟（C-F）键形成的高效和成本有效的催化方法的可用性。迄今为止，世界各地的许多化学家都在这一研究领域积极工作，并为此开发了一系列工艺，但迄今为止发现的反应使用来自F2的昂贵氟源，F2是一种高度反应性和腐蚀性的黄色气体。这些方法中只有少数使用廉价的氟化物盐，但这些方法需要昂贵的过渡金属催化剂，并且受到狭窄的底物范围的影响。通过本项目，我们建议开发和研究一种用于碳-氟键形成的新型催化反应，该反应受益于使用具有成本效益的氟化物盐和由纯有机材料制成且不含过渡金属离子的具有成本效益的催化剂。我们的系统的设计允许容易的化学改性，因此简单的粗或微调的催化剂结构和反应特性。我们为氟化物活化设计的催化过程在机械上是前所未有的，并将被应用于制备重要的氟化分子，以立即应用于药物化学。因此，这些新的催化剂和这些反应的产物将对工业界和学术界的化学家具有巨大价值，并有可能通过改善健康和生活质量对社会产生广泛影响。

项目成果

Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study.

• DOI: 10.1021/jacs.1c13434
• 发表时间: 2022-03-16
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Wang J;Horwitz MA;Dürr AB;Ibba F;Pupo G;Gao Y;Ricci P;Christensen KE;Pathak TP;Claridge TDW;Lloyd-Jones GC;Paton RS;Gouverneur V
• 通讯作者: Gouverneur V

Impact of Multiple Hydrogen Bonds with Fluoride on Catalysis: Insight from NMR Spectroscopy.

• DOI: 10.1021/jacs.0c09832
• 发表时间: 2020-11-18
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Ibba F;Pupo G;Thompson AL;Brown JM;Claridge TDW;Gouverneur V
• 通讯作者: Gouverneur V

Hydrogen Bonding Phase-Transfer Catalysis with Alkali Metal Fluorides and Beyond.

• DOI: 10.1021/jacs.2c00190
• 发表时间: 2022-03-30
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Pupo, Gabriele;Gouverneur, Veronique
• 通讯作者: Gouverneur, Veronique

Multigram synthesis of N-alkyl bis-ureas for asymmetric hydrogen bonding phase-transfer catalysis.

用于不对称氢键相转移催化的 N-烷基双脲的多克合成。

• DOI: 10.1038/s41596-021-00625-y
• 发表时间: 2021
• 期刊: Nature protocols
• 影响因子: 14.8
• 作者: Vicini AC