Development of Synthetic Methods for the Late-Stage Modification of Synthetic Intermediates: The Arene-Limited Nondirected C–H Activation of Arenes and the Direct C–H Activation of Aliphatic Carboxylic Acids

向基于可再生资源的可持续能源系统和化学价值链的过渡创造了对更高效、更节约资源的合成方法的持续需求，以满足全球对药物、农药或部分功能材料等复杂有机分子日益增长的需求。在这种情况下，碳氢键的直接官能化方法非常有吸引力，因为它们具有缩短合成胭脂和减少废物产生的潜力。然而，这种方法的开发具有挑战性，因为要官能化的C-H键在化学上非常稳定，因此是惰性的。同时，典型的有机分子具有各种不同的C-H键，因此在这种过程中，选择性几乎是微不足道的。由于C-H功能化方法的巨大潜力仍然没有得到充分开发，这些方法是大量研究工作的中心。本项目的目的是研究钯催化芳香族和脂肪族底物C-H活化的策略，目前还没有合适的方法具有足够的反应活性和选择性。对于芳香族C-H键的功能化，我们最近发现了一种基于两个互补配体的催化体系。我们的目标是使用并在概念上进一步发展这种方法，用于定向无基芳香族底物的官能化，可以用作限制试剂。为了使脂肪族底物功能化，游离酸将被用作极具吸引力的导向基团。在该小组以前研究的基础上，我们的目标是开发新的配体和反应条件，以实现这一目标。总体而言，这些研究有望为复杂有机分子的功能化提供综合有用的方法，有助于解决上述社会挑战。

The transition to sustainable energy systems and chemical value chains based on renewable resources creates a continued demand for ever more efficient and resource saving synthetic methods, in order to meet the growing global demand for complex organic molecules such as drugs, pesticides, or parts of functional materials. In this context methods for the direct functionalization of carbon-hydrogen bonds are very attractive, since they hold the potential to shorten synthetic rouges and reduce waste production. Such methods are, however, challenging to develop, since the C–H bonds to be functionalized are chemically very stable and thus inert. At the same time typical organic molecules possess a variety of different C–H bonds, such that selectivity is all but trivial in such processes. Due to the substantial potential of C–H functionalization methods that still remains underexploited, such methods are at the center of substantial research efforts. The aim of this project is to study strategies for the palladium-catalyzed C–H activation of aromatic and aliphatic substrates, for which no suitable methods with sufficient reactivity and selectivity are currently available. For the functionalization of aromatic C–H bonds, we have recently discovered a catalyst system based on the use of two complementary ligands. We aim to use and conceptually further develop this approach for the functionalization of directing group-free aromatic substrates that can be employed as the limiting reagent. To functionalize aliphatic substrates, free carboxylic acids are to be used as highly attractive directing groups. Building upon previous studies in the group we aim to develop novel ligands and reaction conditions in order to achieve this goal. Overall, these studies are expected to deliver synthetically useful methods for the functionalization of complex organic molecules, which can contribute to addressing the abovementioned societal challenges.