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

金催化芳烃和杂芳烃的室温直接 C-H 芳基化

• 批准号: EP/G031649/1
• 负责人: Igor Larrosa
• 金额: $ 38.95万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG031649%2F1
• 关键词: GOLD; CATALYSED; ROOM; TEMPERATURE; DIRECT

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.

有机合成支撑着药物发现的基础科学。从具有潜在药理活性的天然产物的分离和表征，到小分子、天然产物及其衍生物等化合物文库的合成，用于疾病治疗的测试，它在各个方面都发挥着重要作用。然而，尽管取得了许多进步，这门科学在复制自然界中发现的大多数具有有趣药用活性的复杂生物化合物的能力方面仍然受到限制。一般来说，这些天然产物的实验室合成需要付出巨大的努力，需要多个步骤才能产生通常只有几毫克的珍贵化合物。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将需要太多的资源，导致成本过高。因此，有机合成还有很长的路要走，才能促进复杂分子的制备，从而产生更好、更有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，它包括两个小分子偶联以形成一个更大的分子。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功能化。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（有时有毒的）含金属废物。为了解决这些问题，目前正在开发碳氢活化方法，作为一种工具，可以允许两个分子交叉偶联，而不需要其中一个或两个分子被功能化。它的工作原理是使用一种催化剂，在交叉偶联反应中激活分子中的C-H键。催化剂是一种能够促进其他分子发生反应的分子，需要的量非常小。本提案的研究旨在开发一种通用的C-H基化方法。为此，一种全新的催化剂将被设计和制备。在这种方法中，将避免在其中一个分子中使用金属作为活化基团，从而将产生有毒废金属的问题减少到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℃）下工作，而不是通常使用的高温（140℃）。这对于确保该方法与尽可能多的底物兼容，避免副反应是很重要的。这项研究的成功完成将为化学家合成药物、材料和其他化合物提供有力的工具。

项目成果

A silver-free system for the direct C-H auration of arenes and heteroarenes from gold chloride complexes

• DOI: 10.1039/c3cy00240c
• 发表时间: 2013-01-01
• 期刊: CATALYSIS SCIENCE & TECHNOLOGY
• 影响因子: 5
• 作者: Ahlsten, Nanna;Perry, Gregory J. P.;Larrosa, Igor
• 通讯作者: Larrosa, Igor