GOLD CATALYSED ROOM TEMPERATURE DIRECT C-H ARYLATION OF ARENES AND HETEROARENES

Organic synthesis underpins the basic science of drug discovery. It plays a major role in all aspects from isolation and characterization of natural products with potential pharmacological activity, to the synthesis of libraries of compounds such as small molecules, natural products and their derivatives to be tested for the treatment of diseases. However, despite the many advances, this science is still limited in its ability to reproduce most of the complex biological compounds with interesting medicinal activities that can be found in Nature. In general, laboratory syntheses of these natural products represent enormous efforts requiring multiple steps yielding often just a few milligrams of the precious compound. These syntheses generally cannot be implemented in industry, since the production of usable amounts of material would require far too many resources, resulting in prohibitive costs. Thus, organic synthesis still has a long way to go to be able to facilitate the preparation of complex molecules that could result in better, more selective and efficient, medicines. A methodology commonly used in synthesis is called cross-coupling, and consist in the coupling of two small molecules to form a bigger one. To be able to perform a cross-coupling, both molecules need to be functionalized in the positions to be joined. This means that special chemical groups (metals and halogens) have to be introduced in each of the molecules, which often results in the addition of several steps of synthesis. In addition, these groups are lost at the end of the cross-coupling reaction generating (sometimes toxic) metal containing waste products.To address these problems, C-H activation methodologies are being developed nowadays as a tool that can allow the cross-coupling of two molecules without the need for one or both of them to be functionalized. It works by using a catalyst that can activate a C-H bond in the molecule during the cross-coupling reaction. Catalysts are molecules that can promote other molecules to undergo reactions, and very small amounts are necessary. The research in this proposal aims at developing a general methodology for C-H arylation. For this, a whole new type of catalysts will be designed and prepared. In this methodology the use of the metal as an activating group in one of the molecules will be avoided, therefore reducing the problem of the generation of toxic waste metals to the generation of a simple hydrogen atom. In addition, the methodology will be able to work at convenient temperatures (25 oC) instead of the usual high temperatures (140 oC) employed. This is important to ensure that the methodology is compatible with as many substrates as possible, avoiding side reactions. The successful completion of this research will provide powerful tools for chemists to use in the synthesis of medicines, materials and other compounds.