Metal-free Arylations for Green Chemistry

Organic Chemistry is mainly dealing with the synthesis of molecules. For efficient synthesis, we must have reasonable insight into the way in which bonds between atoms can be formed or broken and how molecules can react with each other. In this proposal we make use of the special properties of an interesting class of molecules containing iodine atoms. We propose to synthesise novel reagents and investigate reactions using these reagents in only catalytic amounts. This means that one catalyst molecule will have the potential to create thousands of new molecules with special properties. The development of these new iodine reagents and their application in various reactions allowing the selective transfer of aromatic moieties form the main part of this proposal. The target structures which are obtained in these reactions are found in natural products and in many pharmaceuticals. A fast and metal-free access to such compounds will therefore enable their fast synthetic access and enhance the development of new bioactive molecules.

Hypervalent iodine chemistry is a growing area of research and has made a large impact on synthetic chemistry. Catalytic processes are nowadays often used in the synthesis of fine chemicals and in the pharmaceutical industry. We propose to develop reliable methods for efficient stereoselective arylations with catalytic amounts of reagents without the use of potentially toxic metals. If successful, this development will have a substantial impact on industrial research as arylations are commonly carried out using expensive transition metal catalysis. The real impact is the ability to develop drugs and pharmaceutical intermediates more quickly and more cheaply. For a blockbuster drug (defined by annual sales >$1M) a delay in its discovery by one month represents a financial loss to the developer of ~$100K, notwithstanding the cost to patients' quality of lives and allowing access to the drug to a much wider global population. With the fundamental research programme outlined in this application, we will be able to contribute to such far reaching goals in the near future.