CO2 as a traceless directing group for C-H functionalization

CO2 作为 C-H 官能化的无痕导向基团

• 批准号: EP/L014017/1
• 负责人: Igor Larrosa
• 金额: $ 38.45万
• 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: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL014017%2F1
• 关键词: CO2; traceless; directing; group; functionalization

Organic synthesis plays an essential role at the core of other disciplines, both in applied ones - such as drug discovery, or the development of new organic materials and sensors - and in more fundamental areas, such as chemical biology and the understanding of biological interactions at the molecular level. However, despite the many advances in our synthetic arsenal over the last century, this science is still limited in its ability to produce complex structures in an efficient way, hindering progress in all dependent disciplines. In 2009, these limitations were identified in the consultation conducted by the EPSRC, and 'Dial-a-Molecule - 100% efficient synthesis', as it was branded, has become one of the four Grand Challenges in chemical sciences and engineering. This Grand Challenge asks the question: how can we make molecules of interest in days instead of the currently needed years?Traditional synthetic strategies require the presence of reactive functional groups that are used as handles for further functionalization. This requirement is one of the factors dramatically enhancing the difficulty of syntheses. The last two decades have seen the emergence of a more straightforward alternative: the catalytic direct functionalization of C-H bonds. Through this strategy the typically inert C-H bonds, ubiquitous in organic molecules, can be activated by transition metal catalysts and subsequently functionalised. This approach has allowed us to dream of a future where any organic molecule could be synthesised in a direct manner by simply replacing the C-H bonds of a substrate with the required functionalities, as if building a ball-and-stick molecular model with our hands. The development of a full set of C-H functionalisation methodologies will impact on all applied areas, such as the synthesis of pharmaceuticals, agrochemicals, and new materials. Furthermore, their atom efficiency and low waste generation ensures a privileged position among the green chemistry methods.For this strategy to succeed, numerous challenges are still to be overcome. In this research proposal we aim at addressing one of them, called the 'regioselectivity of C-H activation problem': aromatic compounds generally contain many different C-H bonds, so how can chemists select (activate) just one of these bonds in the desired position? In our research we will develop a methodology capable of doing just that: 'selecting' one particular C-H bond in a series of aromatic compounds and transforming it into a different -desired- functionality.

有机合成在其他学科的核心中发挥着至关重要的作用，无论是在应用领域-如药物发现，或新有机材料和传感器的开发-还是在更基础的领域，如化学生物学和分子水平上的生物相互作用的理解。然而，尽管在过去的世纪里，我们的合成武器库取得了许多进展，但这门科学在以有效的方式生产复杂结构的能力方面仍然有限，阻碍了所有相关学科的进步。2009年，EPSRC进行的咨询中确定了这些限制，并且“拨号分子- 100%高效合成”已成为化学科学和工程的四大挑战之一。这个大挑战提出了一个问题：我们如何在几天内而不是目前需要的几年内制造出感兴趣的分子？传统的合成策略需要反应性官能团的存在，其用作进一步官能化的柄。这一要求是显著提高合成难度的因素之一。在过去的二十年里，出现了一种更直接的替代方案：C-H键的催化直接官能化。通过这种策略，在有机分子中普遍存在的典型惰性C-H键可以被过渡金属催化剂活化并随后官能化。这种方法使我们能够梦想未来，任何有机分子都可以通过简单地用所需的功能取代底物的C-H键来直接合成，就像用我们的手建立一个球杆分子模型一样。开发一套完整的C-H功能化方法将影响所有应用领域，如药物，农用化学品和新材料的合成。此外，它们的原子效率和低废物产生确保了其在绿色化学方法中的优越地位。在这项研究中，我们的目标是解决其中之一，称为“C-H活化问题的区域选择性”：芳香族化合物通常含有许多不同的C-H键，那么化学家如何在所需位置选择（活化）这些键中的一个？在我们的研究中，我们将开发一种能够做到这一点的方法：“选择”一系列芳香族化合物中的一个特定的C-H键，并将其转化为不同的-所需的-功能。

项目成果

Ruthenium-Catalyzed C-H Arylation of Benzoic Acids and Indole Carboxylic Acids with Aryl Halides.

• DOI: 10.1002/chem.201605068
• 发表时间: 2017-01-12
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Simonetti M;Cannas DM;Panigrahi A;Kujawa S;Kryjewski M;Xie P;Larrosa I
• 通讯作者: Larrosa I

Recent Progress in Decarboxylative Oxidative Cross-Coupling for Biaryl Synthesis.

• DOI: 10.1002/ejoc.201700121
• 发表时间: 2017-07-07
• 期刊: European journal of organic chemistry
• 影响因子: 2.8
• 作者: Perry GJP;Larrosa I
• 通讯作者: Larrosa I

Salicylic acids as readily available starting materials for the synthesis of meta-substituted biaryls.

• DOI: 10.1039/c4cc09674f
• 发表时间: 2015-02
• 期刊: Chemical communications
• 影响因子: 4.9
• 作者: Junfei Luo;S. Preciado;Igor Larrosa