CU-Catalyzed C(aryl)-N and C(aryl)-O Bond-forming Reactions

描述(由申请人提供)：项目摘要以下研究方案的总体目标涉及改进铜催化的C-N和C-O成键反应。铜催化的芳基卤化物亲核取代在医药工业中，特别是药物化学家中，经常被用来生成芳香胺和芳基醚，用于合成潜在的药物靶标。首先，将对催化循环中的中间体进行分离、表征和进一步研究，以深入了解反应机理。这些中间体将用于研究在铜基催化剂体系中观察到的有趣的选择性。第二，新的阴离子和中性配体将被设计并应用于铜催化的C-杂原子交叉偶联，目标是创造出具有更好的催化剂活性和稳定性的体系，并且可以在温和的条件下操作。第三，将开发新的铜催化的碳杂原子键形成反应，并将改进已知的反应用于有机合成。这些反应包括铜催化的芳基碘和溴化物与亲核试剂的反应，以提供受保护和不受保护的酚类、硅烯醇醚、二芳胺和三芳胺。 相关性芳香族氮和芳香族氧化合物通常存在于照相材料和具有潜在治疗应用的药物靶标中。这些结构基序通常是通过铜催化的碳氮键和碳氧键形成反应来合成的。这项拟议的研究旨在改进已知的铜催化成键反应，并开发新的铜催化成键反应，供制药行业的药物化学家以及一般合成有机化学家使用。

DESCRIPTION (provided by applicant): Project Summary The broad aim of the following research proposal involves the improvement of Cu-catalyzed C-N and C- O bond-forming reactions. Copper mediated nucleophilic substitution of aryl halides are frequently used in the pharmaceutical industry, especially by medicinal chemists, to form aromatic amines and aryl ethers, for the synthesis of potential drug targets. First, intermediates in the catalytic cycle will be isolated, characterized and further studied to gain insight into the mechanism of the reaction. These intermediates will be used to study interesting selectivities that have been observed with Cu-based catalyst systems. Second, new anionic and neutral ligands will be designed and applied in Cu-catalyzed C-heteroatom cross-couplings with the goal of creating systems that display better catalyst activity and stability, and which can operate under mild conditions. Third, new Cu-catalyzed C-heteroatom bond-forming reactions will be developed, and known reactions will be refined for use in organic synthesis. These include the Cu-catalyzed reactions of aryl iodides and bromides with nucleophiles to provide protected and unprotected phenols, silyl enol ethers, diaryl amines and triaryl amines. Relevance Aromatic-nitrogen and aromatic oxygen compounds are commonly found in photographic materials and in pharmaceutical targets with potential therapeutic applications. These structural motifs are commonly synthesized by copper-catalyzed carbon-nitrogen and carbon-oxygen bond forming reaction. The proposed research seeks to improve known and develop new copper-catalyzed bond-forming reactions for use by medicinal chemists in the pharmaceutical industry, as well as synthetic organic chemists in general.