New Catalytic C-H Functionalisations and Oxidative Annulations for Chemical Synthesis

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Chemistry


The efficient formation of carbon-carbon bonds is a central objective in the synthesis of organic molecules, which are required in numerous applications across society. While traditional synthetic methods employing two functionalised starting materials containing carbon-metal or carbon-halogen bonds, for example, have been highly successful, more recent research has focused on forming carbon-carbon bonds directly from two carbon-hydrogen (C-H) bonds. Such C-H functionalisation reactions have the advantages of shorter routes to target molecules (as prior preparation of functionalised precursors is avoided) and the generation of less chemical waste (since a higher proportion of atoms present in the starting materials ends up in the products).

In this research programme, we aim to develop new methods to form cyclic (ring-containing) organic molecules by the formation of two carbon-carbon bonds from two carbon-hydrogen bonds. These reactions will be promoted by small quantities of metal catalysts based around ruthenium, rhodium, palladium, nickel, or other metals. In this way, a diverse range of potentially useful organic molecules may be prepared rapidly and efficiently. Many of these reactions have the potential to form more than one product, and in order to maximise efficiency, catalysts and reaction conditions will be identified to form each of those products selectively, at will. Furthermore, some of the reactions have the potential to form chiral products (compounds that have non-superimposable mirror images). In these cases, we will identify chiral catalysts that enable the selective formation of one enantiomer over the other. This aspect is important, since different enantiomers of functional molecules (such as medicines or agrochemicals) often display different behaviours.

This research will provide valuable information that could be of benefit to all researchers involved in the synthesis of organic compounds. We hope to be able to establish concepts that can be applied in initially unanticipated contexts, ultimately providing positive contributions to science and society.

Planned Impact

This research will benefit:
- Chemists in the pharmaceutical and agrochemical industries. The development of new synthetic methodologies that enable more efficient access to in-demand molecules will streamline the process of developing new medicines and agrochemicals in several ways. First, new methodologies may be used to prepare large arrays of molecules that are employed in biological screening to identify new lead compounds for development. Second, advances in organic
synthesis allow the large-scale synthesis of final drugs/agrochemicals in a more efficient and cost-effective fashion.
- Chemical vendors. Compound vendors that embrace new synthetic methodologies will be able to increase their range of compounds offered for sale, which has broad implications since they underpin important activities conducted by pharmaceutical and agrochemical companies mentioned above.
- Human health and farming. The ability of pharmaceutical companies to streamline their drug development effort through more efficient chemical synthesis can reduce the time interval between identification of potential therapeutic agents and their synthesis for biological evaluation, allowing for more efficient throughput of drugs into the market. Positive consequences for human health can result. Similar factors apply for agrochemical companies, for which more effective synthesis of crop protection agents will have widespread benefits for agriculture.
- The UK economy. The ability to manufacture a greater range of drugs/agrochemicals more efficiently will enable pharmaceutical/agrochemical companies to operate more profitably. These sectors of the chemical industry are major players in the UK economy, being important for wealth creation and employment of thousands of skilled personnel.
- The PDRA researcher on this project. The training of highly skilled personnel in synthetic chemistry is vital to maintain vibrant academic and industrial research communities, which are currently areas of strength in the UK's knowledge-based economy.
- The environment. Industrial activities inevitably affect our environment in one way or another. The key to minimising these impacts to non-harmful and sustainable levels is to conduct these activities in the most efficient manner possible. In this context, reduction of time, labour, power consumption, processing of raw materials, and waste generation are desirable attributes. Advances in catalyst technology will assist in the effort to minimise damage to the environment by making previously lengthy, difficult-to-execute, and wasteful synthetic routes into more concise ones.


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Description We have discovered a new method to make carbocycles - that is, ring-containing organic compounds in which all of the atoms are carbon atoms. This method involves the combination of two types of chemical compound in the presence of a palladium catalyst, and is termed a C-H functionalisation reaction; C-H functionalisation has the potential to provide shorter routes to chemical compounds by dispensing with functional groups traditionally used to form new bonds, and replacing them with the simple carbon-hydrogen bond.
In further work, we have also found a variant of this chemistry works using rhodium catalysis. By using a chiral rhodium complex, we have been able to make the products as single enantiomers (only one of two non-superimposable mirror images).
Exploitation Route This method could potentially be used to prepare biologically active compounds for use in the pharmaceutical or agrochemical industries.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

Description Chemical compounds prepared during this award have been made commercially available via Nottingham Research Chemicals in conjunction with our partner Key Organics. These compounds are chiral ligands, or precursors to chiral ligands, that are potentially useful in asymmetric synthesis. As a result, there were several recorded sales of these compounds. Please see the section entitled "The first chiral BINOL-derived cyclopentadienyl ligand on the market!" of the following flyer for more information:
First Year Of Impact 2016
Sector Chemicals
Impact Types Economic