Informatics-driven Catalyst Design towards Enhanced Iridum(I) Catalysts for Radiolabelling Applications

信息学驱动的催化剂设计，用于放射性标记应用的增强型铱（I）催化剂

• 批准号: 2268649
• 金额: --
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2268649
• 关键词: Informatics; driven; Catalyst; Design; towards

The isotopic labelling of molecules is crucial to ADMET studies within the pharmaceutical industry, and for the elucidation of reaction mechanisms. Foremost amongst the methods for isotope labelling is hydrogen isotope exchange (HIE). In terms of Csp2-H HIE directed by Lewis basic groups, we have developed an extensive range of iridium(I) NHC/phosphine complexes, which accommodate a broad range of directing groups and demonstrate excellent levels of deuterium and tritium incorporation.In an extension of this work, we have applied our emerging catalysts to directed C-H activation and intramolecular C-C bond formation. More specifically, using the carboxylate directing group in a range of benzoic acid derivatives, C-H activation and alkene arylation, using our specifically designed NHC-phosphine chelated complex, has facilitated the synthesis of bi- and tricycles featuring tertiary and quaternary benzylic stereocentres.The objectives of this project will be to:- Further optimise this C-C bond forming process, and expand the substrate scope;- Employ computational techniques and ligand parameterisation to enhance our understanding of the system and guide catalyst design; and- Extend and combine these data driven approaches to related C-C, C-X and C-D bond formation processes.Overall, this approach combines preparative studies with kinetics, mechanistic studies, parameterisation, and a broad range of computational techniques, to allow a data-driven approach to novel catalyst design and reaction optimisation.

同位素标记的分子是至关重要的ADMET研究在制药行业，并阐明反应机制。同位素标记方法中最重要的是氢同位素交换（HIE）。在刘易斯碱性基团导向的Csp 2-H HIE方面，我们开发了一系列铱（I）NHC/膦配合物，它们可容纳广泛的导向基团，并表现出优异的氘和氚掺入水平。在这项工作的扩展中，我们将新兴的催化剂应用于定向C-H活化和分子内C-C键形成。更具体地说，利用羧酸导向基团在一系列苯甲酸衍生物中，C-H活化和烯烃芳基化，使用我们专门设计的NHC-膦螯合络合物，促进了具有叔和季苄基立体中心的双环和三环的合成。本项目的目标是：-进一步优化这种C-C键形成过程，并扩大底物范围;- 采用计算技术和配体参数化来增强我们对系统的理解并指导催化剂设计;和-将这些数据驱动的方法扩展和联合收割机结合到相关的C-C、C-X和C-D键形成过程。总的来说，这种方法将制备研究与动力学结合起来，机械研究、参数化和广泛的计算技术，以允许数据驱动的方法来进行新型催化剂设计和反应优化。