Photoinduced, Copper-Catalyzed C-N Coupling Reactions

描述(申请人提供)：由于广泛的含氮化合物显示出生物活性，开发形成C-N键的新方法是有机化学中的一个中心挑战。此外，由于分子的两个镜像异构体(“对映异构体”)通常由于生命分子(例如，肽、DNA、RNA和碳水化合物)的“左旋性”而具有不同的生物活性，因此在生物医学领域中需要高效地生成立体异构体纯形式的化合物。最后，发展催化反应是可取的，因为它们往往从效率/经济的角度提供优势。这项提议旨在解决所有这三个挑战，特别是发现催化和对映体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种光诱导、铜催化的构建C-N键的方法的发展。偶联反应预计将在异常温和的条件下进行，对生成不同种类的含氮化合物具有广泛的适用性，并具有良好的立体选择性(如果适用)。此外，该研究计划描述了机理研究(例如，立体化学、质谱学、荧光法和电子顺磁共振光谱学)，这些研究将深入了解这些光诱导的、铜催化的C-N键形成反应的不寻常反应路径，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.