What is ‘synthetic organic chemistry’?
We are a group of ‘synthetic organic chemists’, but what does this mean exactly? It has nothing to do with organic farming or foodstuffs. The term ‘synthetic’ refers to the fact that we make molecules in a laboratory, and the term ‘organic’ refers to the type of molecules that we make – those containing the elements carbon and hydrogen, and often other elements such as oxygen, nitrogen and sulfur as well.
Why is it relevant?
Products derived from synthetic organic chemistry touch many aspects of our daily lives – from the medicines and drugs we rely on to the beauty products we use and even the preservatives and flavourings in the food we eat. In particular, the pharmaceutical industry relies on the expertise of synthetic organic chemists to design and synthesise potential new drug molecules as well as providing ways to make drugs found in nature in quantities that would be difficult to obtain otherwise. As a group we specialise in ‘method development’, meaning that we work to try to facilitate these processes and discoveries by designing new and more efficient routes to a variety of different molecules. Indeed, much of the research performed within the Willis group is sponsored by pharmaceutical and agrochemicaal companies.
What is ‘transition metal catalysis’?
Our strategy in designing these new and efficient synthetic routes is based on the use of ‘transition metal catalysis’. This means that we invoke the use of a small amount of a ‘transition metal’ (a metal situated in the centre of the periodic table of the elements) to affect the formation of new chemical bonds. Such an approach often results in highly selective reactions (where only a certain part of the molecule reacts) using conditions which are comparatively mild and hence highly tolerant (so that the rest of the molecule remains intact).
What do the Willis group do?
The Willis group focus on synthetic methodology development using transition metal catalysis to form key bonds. We are particularly interested in forming carbon-carbon and carbon-heteroatom bonds (bonds to elements other than carbon or hydrogen, namely nitrogen, oxygen and sulfur) using rhodium, palladium or copper transition metals. Once we have developed a new process, we frequently apply this in the synthesis of a target molecule (often a natural product or a drug) to ‘showcase’ the applicability of our methodology.
Our research is predominantly centred around three project areas:
Sulfur dioxide in catalysis
Sulfur dioxide (SO2) is a toxic gas and therefore its use is unattractive to synthetic organic chemists. However the SO2 group is a common feature in many molecules, particularly those of interest to the pharmaceutical industry. To address this problem, the Willis group have pioneered the use of a specially designed solid which acts as an SO2 surrogate. This can be used in catalytic processes to incorporate the SO2 group via carbon-sulfur and/or sulfur-nitrogen bond formation. Work is ongoing to develop new processes where the SO2 group can be incorporated in molecules in different ways.
Rhodium catalysis for sustainable synthesis
The group has developed rhodium-based catalytic systems whereby carbon-carbon bonds can be formed in a particularly efficient way. Typically, when two compounds undergo reaction and a new bond is formed between them, there is a considerable level of wastage: not all of the atoms present in the starting molecules end up in the product version, some are needed to ‘signpost’ the desired site of bond formation. However, our rhodium-catalysed processes proceed with complete atom economy – that is to say that all the atoms in the starting molecule are conserved and end up rearranged in the product. Continuing research in the group has led to the development of highly selective reactions using mild conditions in which a wide variety of different starting materials can be utilised.
Catalysis for heterocycle synthesis
Heterocycles (cyclic compounds containing one or more heteroatoms) form the key framework of many important molecules. Indeed, such structures are ubiquitous throughout nature and the pharmaceutical and agrochemical industries. In the Willis group, we work to create new routes to heterocycles using palladium and copper catalysis to create carbon-heteroatom bonds. We are particularly interested in devising tandem procedures, whereby two key bonds are made in the same process. Thus, by reacting two non-cyclic starting materials we can access heterocyclic compounds in a highly efficient approach. We have also developed key substrates, whereby one starting molecule can lead to a range of different cyclic products via judicious choice of the reaction components.
The publications and research sections of the web-site provide more information and give a technical description of our work.