Novel Strategies for the Assembly of Carbon-Boron Bonds via the Photoinduced Generation of Boryl-Radicals

通过光诱导产生硼基自由基组装碳硼键的新策略

• 批准号: EP/V015982/2
• 负责人: Meera Mehta
• 金额: $ 10.17万
• 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: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV015982%2F2
• 关键词: Novel; Strategies; Assembly; Carbon; Boron; Novel; Strategies; Assembly; Carbon; Boron

Boron-containing small organic molecules are one of the most important class of compounds in modern synthetic chemistry due to their use in the Nobel Prize-winning hydroboration-oxidation and Suzuki cross-coupling. Borylated building-blocks are routinely used in the preparation of high-value materials both in academia and industry. Therefore, the invention of novel chemical reactions that form C-B bonds in unprecedented ways is of strategic importance to facilitate the discovery, evolution and manufacture of molecules that impact our society.In general, boron-based functionalities are introduced into organic molecules using two-electron processes like the reaction of Grignards with B-electrophiles or the aromatic C-H borylation using transition metal catalysis. The overarching aim of this project is to explore a complementary approach where C-B bonds are assembled through the reactivity of B-centred radicals (boryl radicals). The use and application of these reactive intermediates is considerably underdeveloped but can provide many orthogonal and complementary solutions to current ionic and metal-mediated borylation strategies.The project is divided in three Aims that will target specific challenges relevant to the preparation of borylated materials.Aim 1. We develop a photochemical approach for the generation of boryl radicals from amine-boranes, a class of stable and abundant materials. These open-shell intermediates will be used to achieve direct and selective C-H borylation of N-heterocycles, one of the most important motifs in pharmaceutical and agrochemical materials. This reactivity will provide a novel approach to functionalise these high-value molecules with a selectivity orthogonal to the one displayed by current metal-catalysed methodologies. We will also benchmark the applicability of the chemistry by applying it to a series of "real-world" substrates of industrial interest that will be provided through a collaboration with Janssen Pharmaceutical. Furthermore, we will evaluate the use of these novel borylated materials in main-stream cross-coupling reactions. Aim 2. Here we will develop divergent multicomponent reactions based on the intramolecular cyclization of boryl radicals. We will use our knowledge in radical cascades to provide unprecedented borylation-functionalization processes. This chemistry involves the generation of homo-allylic amine-boryl radicals that will undergo an intramolecular cyclization followed by a diversification through a final reaction with a broad range of trapping agents. We will evaluate the full scope and limitation of this reactivity and also apply it to the preparation of blockbuster drug analogues. Aim 3. This strategy for olefin borylation-functionalization will be expanded by merging it with nickel catalysis. This will enable the development of an innovative dual photoredox-nickel platform for tandem radical borylation and cross-coupling that will generate in a divergent manner complex and densely functionalised materials.A relevant aspect will be investigating the scalability of the various processes that we will develop. This part of the project will be executed through a collaboration with Janssen Pharmaceutical that will allow to use their state-of-the-art flow-chemistry facilities.Overall, this project will provide novel reactivity modes for the formation of C-B bonds exploring the reactivity of boryl radicals in photoredox catalysis. Given the importance of borylated building blocks in a synthetic, bio-organic, medicinal and material chemistry, this project will facilitate the discovery, development and manufacture of high-value materials with overall impact to the well-being of UK society.

含硼的小有机分子是现代合成化学中最重要的化合物之一，因为它们在诺贝尔奖获奖的液压氧化和铃木交叉偶联中使用。经常使用型建筑块用于在学术界和工业中的高价值材料制备中。因此，以前所未有的方式形成C-B键的新型化学反应的发明对于促进影响我们社会的分子的发现，进化和制造具有战略意义。通常，使用两种电源过程将基于硼基的功能引入有机分子中，例如使用两种电源工艺，例如使用Grignards与B-Electration Cateral catelation catlation catlation catlation catlation catlation catlation或Aronic aromant aromant aromant aromant aromant aromant aromant aromant aromant aromant acronic aronic aromant aromant aromant aromant aromant aromant aromant aromant acmonation。该项目的总体目的是探索一种补充方法，其中C-B键通过B中心自由基（Boryl自由基）的反应性组装。这些反应性中间体的使用和应用是明显欠发达的，但可以为当前的离子和金属介导的boryation策略提供许多正交和互补的解决方案。该项目分为三个目标，这些挑战针对的是与Borypated Materials相关的特定挑战。我们开发了光化的botical sergials and Onsermine and Onderival and Onderival and Ondersine by and by and abore and abore and rador s的渐进式，既定的宽度范围，又是宽敞的辐射，并将其置于宽度的范围内，并且是宽敞的辐射，并将其置于bory sermine a的范围内。 材料。这些开放式中间体将用于实现N-杂环的直接和选择性C-H型，这是药物和农业化学材料中最重要的基序之一。这种反应性将提供一种新颖的方法，以与当前金属催化方法所显示的那种方法具有选择性正交的这些高价值分子的功能。我们还将通过将化学应用于一系列工业利益的“现实世界”基质来基准，通过与Janssen Pharmaceutical合作提供。此外，我们将评估这些新型植物材料在主流交叉偶联反应中的使用。 AIM 2。在这里，我们将基于Boryl自由基的分子内环化发展不同的多组分反应。我们将利用自由基级联的知识来提供前所未有的Borylation功能化过程。该化学涉及产生同酰胺胺 - 鸟类自由基，这些自由基将经历分子内环化，然后通过与广泛的捕获剂的最终反应进行多样化。我们将评估这种反应性的全部范围和局限性，并将其应用于大片药物类似物的制备。 AIM 3。烯烃型官能化策略将通过将其与镍催化融合来扩展。这将使创新的双光电氧基 - 尼克平台开发用于串联自由基的植物和交叉耦合，该平台将以不同的方式生成复杂且功能齐全的材料。该项目的这一部分将通过与Janssen Pharmaceutical的合作来执行，该项目将允许使用其最先进的流化学设施。此外，该项目将为C-B Bonds的形成提供新颖的反应性模式，以探索Photoredox催化中Boryl自由基的反应性。鉴于在合成的，生物有机，药物和材料化学中，bory的构建基块的重要性，该项目将有助于发现，开发和制造高价值材料，对英国社会的福祉产生总体影响。