Photoinduced, Copper-Catalyzed C-N Coupling Reactions

描述（由申请人提供）：由于大量含氮化合物具有生物活性，因此开发形成C-N键的新方法是有机化学的核心挑战。此外，由于分子的两种镜像异构体（“对映异构体”）通常由于生命分子的“手性”而具有不同的生物活性（例如，肽、DNA、RNA和碳水化合物），生物医学界需要有效地产生立体异构纯形式的化合物。最后，催化反应的发展是可取的，因为从效率/经济的角度来看，它们往往提供优势。该提案旨在解决所有这三个挑战，特别是发现催化和对映选择性合成含氮化合物的新方法。特别是，该研究计划描述了第一个光诱导，铜催化的C-N键的构建方法的发展。预计偶联反应在异常温和的条件下进行，具有广泛的适用性，用于生成不同家族的含氮化合物，并以良好的立体选择性（适用时）进行。此外，研究计划描述了机械研究（例如，立体化学、质谱、荧光测定法和电子顺磁共振光谱法），这将提供对这些光诱导、铜催化的C-N键形成反应的不寻常反应途径的洞察，这些反应可能通过自由基中间体进行。

DESCRIPTION (provided by applicant): Because a wide array of nitrogen-containing compounds exhibit bioactivity, the development of new methods for the formation of C-N bonds is a central challenge in organic chemistry. Furthermore, because the two mirror-image isomers ("enantiomers") of a molecule generally have different biological activity due to the "handedness" of the molecules of life (e.g., peptides, DNA, RNA, and carbohydrates), there is a need in the biomedical community to efficiently generate compounds in stereoisomerically pure form. Finally, the development of catalyzed reactions is desirable, since they often offer advantages from the standpoints of efficiency/economy. This proposal is directed at addressing all three of these challenges, specifically, the discovery of new methods for the catalytic and enantioselective synthesis of nitrogen-containing compounds. In particular, the research plan describes the development of the first photoinduced, copper-catalyzed methods for the construction of C-N bonds. The coupling reactions are anticipated to proceed under unusually mild conditions, to have broad applicability for the generation of diverse families of nitrogen-containing compounds, and to proceed with good stereoselectivity (when applicable). Furthermore, the research plan describes mechanistic studies (e.g., stereochemical, mass spectrometry, fluorometry, and electron paramagnetic resonance spectroscopy) that will provide insight into the unusual reaction pathway of these photoinduced, copper-catalyzed C-N bond-forming reactions, which likely proceed through a radical intermediate.