Catalytic, Regioselective C-H Activation/Oxidation of Substituted Arenes

描述(由申请人提供)：该项目的目标是开发用于芳香族C-H键的区域选择性氧化的新催化剂和方法。该项目最初将侧重于开发用于1，3-二取代芳烃选择性间位氧化的催化剂；长期目标是扩大反应范围，以包括更多不同的底物类别。取代芳烃在药物靶标中普遍存在，因此选择性地将芳烃中传统上不具活性的C-H键官能化将为获得这些生物活性分子提供一种非常有效的途径。我们认为，区域选择性氧化反应将产生于选择性地激活芳烃底物中受阻最小的芳香族C-H键的催化剂的开发。在1，3-二取代芳烃的情况下，我们假设所提出的催化剂与芳环上的取代基之间的空间相互作用将导致最少受阻的间位的选择性官能化，而不是在电子有利的邻位或对位。钯(11)-N-杂环卡宾配合物在钯的配位球附近引入了非常大的取代基，被认为是利用苯基十二烷基乙酸酯选择性引入乙酰氧基的体系。关于Rh(III)催化的高区域选择性反应的报道也使我们建议开发新的方法来研究Rh催化的取代芳烃的乙酰氧基化反应。最后，在芳香族C-H键的选择性氧化方法的开发中获得的见解将被应用于芳香族C-H键的选择性羧化体系的开发。先前的报道表明，非选择性的、催化的乙酰氧基化和羧化反应的反应途径非常相似。因此，预期在乙酰氧基化反应中具有活性和选择性的催化剂也将对取代芳烃中受阻最小的C-H键的羧化反应具有活性和选择性。与公众健康的相关性在建议的研究项目成功完成后，我们将为化学家提供合成取代芳烃的新方法，取代芳烃是药物中常见的分子。我们将开发的反应将是制造这些化合物的一种非常有效的方式，并将改进药物化合物的生产方式。

DESCRIPTION (provided by applicant): The goal of the proposed project is to develop new catalysts and methodology for the regioselective oxidation of aromatic C-H bonds. Initially the project will focus on developing catalysts for the selective meta oxidation of 1,3-disubstituted arenes; the long-term objective is to expand the scope of the reaction to include more diverse substrate classes. Substituted arenes are ubiquitous in pharmaceutical targets, therefore the ability to selectively functionalize the traditionally uncreactive C-H bonds in arenes will provide a very efficient way to access these biologically active molecules. We propose that regioselective oxidation reactions will arise from the development of catalysts that selectively activate the least hindered aromatic C-H bond present in the arene substrate. In the case of 1,3- disubstituted arenes, we hypothesize that steric interactions between the proposed catalysts and substituents on the aromatic ring will lead to selective functionalization of the least hindered meta position, rather than at the electronically favored ortho or para positions. Palladium(ll) N-heterocyclic carbene complexes, which introduce very bulky substituents in close proximity to the coordination sphere of palladium, are proposed for a system which utilizes phenyliodosyl acetate to selectively introduce acetoxy groups . Reports on highly regioselective rhodium (III) catalyzed reactions have also led us to propose the development of new methodology for the rhodium-catalyzed acetoxylation of substituted arenes. Finally, the insight gained in the development of methods for the selective oxygenation of aromatic C-H bonds will be applied in the development of systems for the selective carboxylation of aromatic C-H bonds. Prior reports have shown that the non-selective, catalytic acetoxylation and carboxylation reactions proceed by very similar pathways. Hence, it is expected that catalysts which are active and selective in acetoxylation reactions will also be active and selective for the carboxylation of the least hindered C-H bonds in substituted arenes. Relevance to Public Health Upon successful completion of the proposed research project we will provide chemists with new methods to synthesize substituted arenes, molecules that are commonly found in Pharmaceuticals. The reactions we will develop will be a very efficient way of making these compounds, and will improve the ways that pharmaceutical compounds are produced.