Back to Basics: Investigating Structure, Reactivity and Catalysis of Organolithium-Diamine Complexes

这个项目致力于更深入地了解有机化学中的一个基本过程，即使用强碱对弱碳酸进行去质子化。酸碱相互作用和去质子化是在学校化学课上第一次遇到的概念(酸碱滴定)。使用反应性有机锂试剂与二胺络合组成的强碱进行去质子化，已成为近年来有机合成中最有效的工具之一。也可以使用手性二胺(其中自然产生的(/)-司马豆碱是最著名的)来控制产品的立体化学(或手性)。不幸的是，尽管它们在合成中被广泛使用，但人们对这些有机锂-二胺络合物的结构和机理信息知之甚少。在这个项目中，两个小组(英国约克的奥布莱恩)和(瑞典哥德堡的希尔默森)之间将建立具有互补专业知识领域的合作，以揭开有机锂-二胺介导的去质子化过程的复杂性。这项研究将研究二胺与有机锂硫化物的络合动力学和热力学，以及形成的络合物的溶液结构和化学计量比。该项目还将提供大量关于有机锂硫化物与二胺络合的反应的动力学数据，这将为合成化学家提供信息，并使有机锂反应得到优化(在工业和学术界)。所有这些结果将结合起来理解和合理化单配体和双配体催化不对称去质子化过程，这是一个不发达的研究领域，到目前为止还没有得到机制上的关注。这个项目非常重要，并用于处理研发团队，例如，制药公司和阿斯特拉-捷利康专门支持这项研究。

This project is concerned with developing a deeper insight into a fundamental process in organic chemistry, namely deprotonation of a weak carbon acid using a strong base. Acid-base interactions and deprotonation is a concept first met in school chemistry classes (acid-base titrations). Deprotonation using a strong base composed of a reactive organolithium reagent complexed to a diamine has become one of the most powerful tools in organic synthesis in recent times. It is also possible to use a chiral diamine (of which naturally occurring (/)-sparteine is the most famous) to control the stereochemistry (or handedness) of the products. Unfortunately, despite their widespread use in synthesis, very little structural and mechanistic information is known about these organolithium-diamine complexes. In this project, collaboration between two groups (O'Brien, York, UK) and (Hilmersson, Goteborg, Sweden) with complementary areas of expertise will be established to unravel the complexities of organolithium-diamine-mediated deprotonation processes. The research will investigate the kinetics and thermodynamics of complexing diamines to organolithiums as well as the solution structures and stoichiometry of the complexes that are formed. This project will also deliver a considerable body of kinetic data on reactivity of organolithiums complexed to diamines which will inform the synthetic chemists and allow organolithium reactions to be optimised (in industry and academia). All of these results will be combined to understand and rationalise one-ligand and two-ligand catalytic asymmetric deprotonation processes, an under-developed research area, which has received no mechanistic attention thus far. This project is of much importance and use to Process R & D groups of, for example, pharmaceutical companies and Astra-Zeneca are specifically supporting the research.