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Metal catalysed C–H bond activation strategies for chemical synthesis & cancer biology

Final Report Summary - CHACT_RHAZ (Metal catalysed C-H bond activation strategies for chemical synthesis & cancer biology)

Despite the changing face of organic chemistry one aspect remains persistent: the ability to make molecules to order is something that, even now, is still unique to the synthetic chemist. What is changing in synthesis is the way that we go about achieving our goal. More than ever it is essential to consider the impact of atom economy, catalysis and stereocontrol as chemical synthesis strives to become 'green'. The area of metal catalysed C-H bond activation is a rapidly developing field in chemical synthesis as it addresses many of the aforementioned deficiencies of conventional metal chemistry. However, despite its importance the field is still in its infancy and if it is going to become a central paradigm for chemical synthesis then a great deal of investigation needs to be invested in its development.

Over the past decade, there has been much attention on C-H arylation of arenes since the product biaryl unit is frequently found in many important biologically interesting compounds, pharmaceutical reagents and functional polymers. However, these processes have been limited to the functionalisation of a C-H bond adjacent to a directing group (ortho C-H functionalisation). Clearly, full potential can only be realised when other positions of arene ring can be arylated.

The researcher has successfully developed a novel site-selective C-H bond functionalisation process employing inexpensive copper catalysts. The use of hypervalent iodine compounds allows arylation to occur at the meta C-H bond relative to a carbonyl directing group. This exquisite regiocontrol allows access to a variety of interesting compounds that are not easy to obtain via traditional chemistry. In particular, the methodology facilitates facile conversion of drug molecules, such as ibuprofen, into biaryl analogues for further biological studies. The researcher also discovered a condition for metal-free C-H arylation. This finding offers exciting potentials for further developments since it avoids the use of metal catalyst, which in many cases is difficult to separate from products and affects the quality of the desired materials.