Automating the Understanding of Catalytic Aldehyde Synthesis

自动化催化醛合成的理解

• 批准号: 2605992
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2605992
• 关键词: Automating; Understanding; Catalytic; Aldehyde; Synthesis

Aldehydes are key intermediates in the chemical synthesis of active pharmaceutical ingredients (APIs). Aryl aldehydes are typically made by the metalation of an aryl halide with an s-block reagent followed by addition to dimethylformamide (Bouveault synthesis). This approach has its disadvantages: it requires the formation of organometallic intermediates, shows limited functional group tolerance, and it generates considerable waste. A more efficient alternative is the catalytic formylation of aryl halides with CO/H2 mixtures. Despite the potential of this catalytic approach, it does not find widespread use due to the limited understanding of the reaction. Currently, it is not clear what the best process is to screen for new catalysts, it is not obvious which variables to focus on to expand the substrate scope, and open questions remain as to how best to scale the process up. If a detailed mechanistic understanding of catalytic formylation could be developed it could be used to underpin a broader application of this method in the synthesis of APIs. In this project, we will use a combination of automation, kinetic analysis (VTNA), DFT calculations and synthetic chemistry to develop deep insight into the palladium catalysed formylation

醛是活性药物成分 (API) 化学合成的关键中间体。芳基醛通常通过芳基卤化物与 s-嵌段试剂的金属化，然后添加到二甲基甲酰胺中来制备（布沃合成）。这种方法有其缺点：它需要形成有机金属中间体，显示出有限的官能团耐受性，并且产生大量废物。更有效的替代方案是用 CO/H2 混合物催化芳基卤化物甲酰化。尽管这种催化方法具有潜力，但由于对反应的了解有限，它并未得到广泛应用。目前，尚不清楚筛选新催化剂的最佳工艺是什么，也不清楚应关注哪些变量来扩大底物范围，并且如何最好地扩大工艺规模仍存在悬而未决的问题。如果能够对催化甲酰化形成详细的机理理解，则可以用来支持该方法在 API 合成中更广泛的应用。在这个项目中，我们将结合使用自动化、动力学分析 (VTNA)、DFT 计算和合成化学来深入了解钯催化甲酰化反应