CO2 as a traceless directing group for C-H functionalization

有机合成在其他学科的核心中发挥着至关重要的作用，无论是在应用学科--如药物发现或新有机材料和传感器的开发--还是在更基本的领域，如化学生物学和在分子水平上理解生物相互作用。然而，尽管我们的合成武器库在上个世纪取得了许多进展，但这门科学在以有效方式制造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。在2009年，EPSRC进行的咨询中发现了这些限制，并且被称为“Dial-a-分子-100%高效合成”已成为化学科学和工程领域的四大挑战之一。这个巨大的挑战提出了一个问题：我们如何在几天内制造出感兴趣的分子，而不是目前需要的几年？传统的合成策略需要存在反应性官能团，这些官能团被用作进一步官能化的手柄。这一要求是显著增加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法：C-H键的催化直接官能化。通过这一策略，有机分子中普遍存在的典型的惰性C-H键可以被过渡金属催化剂激活并随后功能化。这种方法让我们梦想着未来任何有机分子都可以直接合成，只需用所需的官能团取代底物的C-H键，就像用我们的手建立一个球棒分子模型一样。一整套C-H功能化方法的开发将影响到所有应用领域，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在绿色化学方法中的优势地位。要使这一战略取得成功，仍有许多挑战需要克服。在这项研究中，我们旨在解决其中之一，称为‘C-H激活的区域选择性问题’：芳香化合物通常包含许多不同的C-H键，那么化学家如何在所需的位置上只选择(激活)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：在一系列芳香化合物中‘选择’一个特定的C-H键，并将其转化为不同的所需功能。

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.