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

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.