Uncovering Competing Cross-Coupling Catalytic Cycles Through Rich Data Analysis of Reaction Outcomes Gained by High-throughput Experiment Screening

通过对高通量实验筛选获得的反应结果进行丰富的数据分析，揭示竞争的交叉偶联催化循环

• 批准号: 2742606
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2742606
• 关键词: Uncovering; Competing; Cross; Coupling; Catalytic

Pd-catalyzed Suzuki-Miyaura Cross-Coupling (SMCC) reactions are widely employed in the pharmaceutical sector, from research discovery and scale-up processes through to manufacture. Despite extensive work on Pd-catalyzed SMCC reactions, involving substrate scoping, catalyst development, and mechanistic work, there remain significant challenges when new cross-coupling substrates (reagents) are tested. The reasons for lower than expected yields of products are typically associated with competing side reactions, especially protodeborylation, protodehalogenation and hydrolysis processes. To understand these competing processes better we will employ a Chemspeed ISYNTH robotic system, combining high throughput experimentation (HTE) and data analytics, with the primary aim of generating a large number of reaction outcomes (leading to the creation of a valuable dataset). We are then able to integrate the data from the reaction outcomes using a bespoke design of experiment approach. There we will assess both quantitative (amounts) and categorical (groupings) variables for the different SMCC reactions (employing various substrate reactivity profiles). We expect trends to emerge in the reactivity profiling. As a consequence, this research project will directly address the urgent need to identify rules governing the reactivity of libraries of pi-rich and pi-deficient organic substrates. As a secondary off-shoot from our work, the approaches developed in HTE and data analytics will be broadly transferable to other catalytic processes.

Pd催化的Suzuki-Miyaura交叉偶联（SMCC）反应广泛应用于制药行业，从研究发现和放大过程到生产。尽管对Pd催化的SMCC反应进行了广泛的研究，涉及底物范围，催化剂开发和机械工作，但在测试新的交叉偶联底物（试剂）时仍然存在重大挑战。产物产率低于预期的原因通常与竞争性副反应有关，特别是脱硼基化、脱卤化和水解过程。为了更好地了解这些相互竞争的过程，我们将采用Chemspeed ISYNTH机器人系统，结合高通量实验（HTE）和数据分析，主要目的是生成大量的反应结果（从而创建有价值的数据集）。然后，我们能够使用定制的实验设计方法整合反应结果的数据。在那里，我们将评估不同SMCC反应的定量（量）和分类（分组）变量（采用各种底物反应性特征）。我们预计反应性分析中会出现趋势。因此，本研究项目将直接解决迫切需要确定规则的丰富和缺乏pi的有机基板库的反应性。作为我们工作的次要分支，HTE和数据分析中开发的方法将广泛应用于其他催化过程。