Design and synthesis of novel cyclopentadienyl metal complexes, and their application towards enantioselective metal catalysed C-H activation

本项目福尔斯属于EPSRC催化和合成有机化学研究领域。在过去的十年中，C-H活化已成为有机金属化学的一个关键领域。这种方法消除了对在反应性位点处预官能化的基底的需要，而是依赖于附近的“定向基团”来确定官能化位点。这使得分子的合成步骤比传统的交叉偶联方法更少，效率更高。这些益处是工业和合成化学家等高度期望的。C-H活化的一个挑战是合成对映体富集的产物，这将是许多工业中采用C-H活化的关键。许多研究小组采用的方法是通过手性配体和添加剂（例如手性膦、羧酸等）获得对映体控制，导致原位形成手性金属络合物。不太常见的控制来自使用手性金属络合物，这是预先合成的。这些配合物在2013年首次应用于对映选择性C-H活化。从那时起，文献中只报道了3类可调Cp手性支架，但大多数都需要大量步骤来合成。最近，我们的小组发现了几个新的C（SP3）-H活化反应，使用铑和钴配合物的非手性Cp配体。这些反应具有可进行后续转化的定向基团。这在C-H活化中是不常见的，其中许多导向基团不容易衍生化。钴C（SP3）-H活化的实例在文献中很少，并且没有发表对映选择性的实例。该项目的总体目标是采用我们实验室最近开发的反应，并采用手性Cp铑和钴络合物在转化过程中提供对映体控制。我们最初的目标是合成新的Cp配体，其在性质上是双功能的，具有多个位点与金属结合，因为这种方法在文献中还没有被探索。双官能配体将提供调节金属反应性和对映选择性的额外方式。我们将利用这些手性配体合成相应的铑和钴金属配合物，并研究它们在C-H活化反应中的反应活性和控制，重点是我们实验室开发的那些。该项目的第二个目标是发现新的C-H活化反应，以伴随对映选择性方法。总之，本项目将致力于开发新型手性Cp配体及其在对映选择性C-H活化反应中的应用。在整个过程中，我们将研究Cp配体及其复合物的结构-活性关系，这将为未来的Cp配体设计提供见解。

This project falls within the EPSRC Catalysis, and Synthetic Organic Chemistry research areas.Over the past decade C-H activation has emerged as a key field in organometallic chemistry. This approach eliminates the need for substrates to be pre-functionalized at the site of reactivity, instead relying on nearby 'directing groups' to determine the site of functionalization. This allows for molecules to be synthesised with fewer steps and higher efficiency than traditional cross-coupling methods. These benefits are highly desirable to industry and synthetic chemist alike. One challenge for C-H activation is the synthesis of enantioenriched products, which are will be key to adoption of C-H activation in many industries. The approach taken on by many groups is to gain enantiocontrol through chiral ligands and additives (e.g. chiral phosphines, carboxylic acids, etc.), leading to formation of a chiral metal complex in situ. Less commonly control comes from use of chiral cyclopentadienyl (Cp) metal complexes, which are presynthesised. These complexes were applied to enantioselective C-H activation first in 2013. Since then only 3 classes of tuneable Cp chiral scaffolds have been reported in the literature, however most require a significant number of step to synthesise. Recently our group discovered several new C(SP3)-H activation reactions, employing rhodium and cobalt complexes baring achiral Cp ligands. These reactions have directing groups which can undergo subsequent transformation. This is uncommon in C-H activation where many directing groups are not easily derivativatized. Examples of cobalt C(SP3)-H activation are few in the literature, and no enantioselective examples have been published. The overall aim of this project would be to take the recently developed reactions from our lab and employ chiral Cp Rhodium and Cobalt complexes to provide enantiocontrol during the transformation. Our initial objective would be the synthesis of novel Cp ligands which are bifunctional in nature, having multiple sites with which to bind to the metal, as this approach has not been explored in the literature. The bifunctional ligands would provide an additional way of tuning the metals reactivity, and enantioselectivity. We will the corresponding rhodium and cobalt metals complexes using these chiral ligands and investigate their reactivity and control in C-H activation reactions, focusing on those developed in our lab. A secondary object of this project will be the discovery of new C-H activation reactions, to accompany the enantioselective approaches. In summary, this project will focus on development of new chiral Cp ligands and their application to enantioselective C-H activation reactions. Throughout we will investigate the structure-activity relationships of Cp ligands and their complexes, which will provide insights into future Cp ligand design.