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

有机合成是药物发现的基础科学。从分离和鉴定具有潜在药理活性的天然产物，到合成用于治疗疾病的小分子、天然产物及其衍生物等化合物文库，它在各个方面都发挥着重要作用。然而，尽管取得了许多进展，但这门科学在复制大多数复杂的生物化合物的能力方面仍然有限，这些化合物具有在自然界中可以找到的有趣的药用活性。一般来说，实验室合成这些天然产物需要付出巨大的努力，需要多个步骤才能产生这种珍贵的化合物，往往只有几毫克。这些合成通常不能在工业上实施，因为生产可用数量的材料需要太多的资源，导致高昂的成本。因此，有机合成仍有很长的路要走，才能促进复杂分子的制备，从而产生更好、更具选择性和更有效的药物。合成中常用的一种方法被称为交叉偶联，它是将两个小分子偶联形成一个较大的分子。为了能够进行交叉偶联，两个分子都需要在要连接的位置上进行官能化。这意味着必须在每个分子中引入特殊的化学基团(金属和卤素)，这通常会导致增加几个合成步骤。此外，这些基团在交叉偶联反应结束时丢失，产生(有时是有毒的)含金属废物。为了解决这些问题，目前正在开发C-H活化方法，作为一种工具，可以允许两个分子之间的交叉偶联，而不需要对其中一个或两个进行官能化。它的工作原理是使用一种催化剂，可以在交叉偶联反应中激活分子中的C-H键。催化剂是可以促进其他分子发生反应的分子，需要极少量的催化剂。本方案的研究旨在开发一种通用的C-H芳基化方法。为此，将设计和制备一种全新的催化剂。在这种方法中，将避免使用金属作为其中一个分子中的活化基，从而将产生有毒废金属的问题减少为产生一个简单的氢原子。此外，该方法将能够在方便的温度(25摄氏度)下工作，而不是通常使用的高温(140摄氏度)。这对于确保该方法与尽可能多的底物兼容、避免副反应非常重要。这项研究的成功完成将为化学家在药物、材料和其他化合物的合成中使用提供强有力的工具。

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.