New Routes to fluorocarbons using fluoroboranes

使用氟硼烷生产碳氟化合物的新途径

• 批准号: EP/X021858/1
• 负责人: Michael Ingleson
• 金额: $ 55.88万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX021858%2F1
• 关键词: New; Routes; fluorocarbons; using; fluoroboranes

Fluorinated molecules have risen to the forefront of modern scientific advances. From Teflon to pharmaceuticals (including blockbuster drugs, e.g. Lipitor), the controlled formation of carbon-fluorine bonds has imparted revolutionary biological and structural effects. However, the current methods to form carbon-fluorine bonds generally rely on highly reactive fluorine sources that limit widespread application and use. This grant will develop fluorine sources based on boron-fluorine bonds that enable the formation of carbon-fluorine bonds using new and orthogonal reactivity to current methods. Boron offers a sustainable choice for catalysis with low physiological and environmental toxicity. This makes it an ideal choice for applications in the pharmaceutical and agrichemical sectors. The boron-fluorine bond is usually considered to be relatively inert, but our deep understanding of boron chemistry will enable the reactivity of B-F bonds to be switched on. This project will achieve this by rationally tuning the structure about boron to enable the capture of fluorine from simple, inexpensive stable sources (e.g. MF) and subsequently transfer it to simple and complex molecular frameworks. Three methods to do this have been identified: 1. Phase-transfer Catalysis; 2. Fluorine transfer and trapping of activated substrates; 3. Transfer of fluorine and boron to unactivated substrates. These methods share a common theme of boron-fluorine bond formation and subsequent fluorine transfer, but they are not inter-reliant. Each method will be developed separately and addresses a different synthetic need. Phase-transfer catalysis will take fluorine from the solid or aqueous (water) phase and transfer it to the reactive, organic phase. The structure about boron will be used to control the position and facial selectivity of the transfer. Fluorine transfer to activated and unactivated substrates will exploit an activated boron-fluorine bond. Key to this will be activation of the boron-fluorine bond on approach to the substrate and the structure about boron will be used to enhance this interaction and ensure boron-fluorine bond activation. All three methods will be used to explore and understand the fundamentals of boron-fluorine bonding, how to effect high yielding fluorine transfer to substrates, and how rational modifications to borane structure can be used to enable new reactivity. All of the methods will culminate in the application of the new reactivity to industry relevant targets - new active pharmaceutical ingredients, agrichemicals and materials precursors.

氟化分子已经上升到现代科学进步的前沿。从特氟龙到药物（包括重磅炸弹药物，如立普妥），碳氟键的受控形成赋予了革命性的生物和结构效应。然而，目前形成碳-氟键的方法通常依赖于限制广泛应用和使用的高反应性氟源。这笔赠款将开发基于硼-氟键的氟源，使碳-氟键的形成使用新的和正交的反应，以目前的方法。硼为催化提供了一种可持续的选择，具有低生理和环境毒性。这使其成为制药和农业化学领域应用的理想选择。硼-氟键通常被认为是相对惰性的，但我们对硼化学的深入理解将使B-F键的反应性能够被打开。本项目将通过合理调整硼的结构来实现这一目标，使氟能够从简单，廉价的稳定来源（例如MF）中捕获，并随后将其转移到简单和复杂的分子框架中。已经确定了三种方法来做到这一点：1。相转移催化; 2.活化底物的氟转移和捕获; 3.将氟和硼转移到未活化的基质上。这些方法具有硼-氟键形成和随后的氟转移的共同主题，但它们不是相互依赖的。每种方法将单独开发，并解决不同的合成需求。相转移催化将氟从固体或水（水）相转移到反应性有机相。硼的结构将被用来控制转移的位置和面选择性。氟转移到活化和未活化的基材将利用活化的硼-氟键。其关键将是在接近衬底时激活硼-氟键，并且关于硼的结构将用于增强这种相互作用并确保硼-氟键激活。所有这三种方法都将用于探索和理解硼-氟键合的基本原理，如何实现高产氟转移到衬底，以及如何合理修改硼烷结构以实现新的反应性。所有这些方法都将最终应用于工业相关目标的新反应性-新的活性药物成分，农用化学品和材料前体。