Transition Metal-Catalyzed Nitrogenation of Hydrocarbons

俄克拉荷马大学的肯尼思·M·尼古拉斯教授的这一提议涉及到利用过渡金属通过开发新的、高效和选择性的金属催化C-N键形成反应来形成新的碳-氮键。这一方法将适用于胺类化合物和含氮杂环化合物的合成，既可作为合成中间体，也可作为药物等最终产品。有待研究的几个反应包括：1)确定CPM催化的烯丙基胺与硝基芳烃反应的合成范围和活性氮化物种；2)提高CPM催化的硝基芳烃与炔烃和其他硝基化合物还原环加成反应的方便性、效率和合成活性；3)开发有效的对映选择性羟胺类化合物并阐明铜催化的烯丙基胺化反应的机理；4)发现金属催化的饱和和芳香烃的直接胺化反应。如上所述，不仅将研究这些反应的合成方面，而且还将研究这些反应的机理。这项研究的重要性体现在以下几个方面。烯丙基胺单元存在于许多天然和非天然产品中，是合成精制的宝贵构件。吲哚核存在于多种具有生物效力的吲哚生物碱中，以及有价值的合成衍生物中，包括特定靶向的吲哚咔唑天然产物。芳香族和饱和底物的直接胺化也将为合成重要的脂肪族和芳香胺提供新的、具有合成价值的路线。此外，金属介导的方法从容易获得的原料出发，有望具有高度的区域和化学选择性、对官能团的容忍、经济、环境友好以及对现有方法的补充或优于现有方法。新的合成方法将拓宽金属络合物与各类有机化合物相互作用的一般理解范围，并有可能在合成有机化学中得到广泛应用，这对制备具有生物活性的化合物和聚合物等有用材料具有重要意义。此外，理科研究生和本科生将与数量不成比例的女性和代表不足的少数群体成员一起接受培训。还将继续与美国和意大利的博士和本科生机构的计算和实验科学家进行合作。

This proposal by Prof. Kenneth M. Nicholas of the University of Oklahoma involves using transition metals to form new carbon-nitrogen bonds by developing new, efficient and selective metal catatyzed C-N bond-forming reactions. This methodology will be applicable to the synthesis of amine compounds and nitrogen heterocycles, both as synthetic intermediates and as end-products such as pharmaceuticals. Several of the reactions to be examined include: 1) establishing the synthetic scope and identifying the active nitrogenating species in CpM-catalyzed allylic aminations with nitroarenes, 2) improving the convenience, efficiency and demonstrating the synthetic utility of the CpM-catalyzed reductive cycloaddition of nitroarenes with alkynes and other nitrosophiles, 3) developing effective enantioselective hydroxylamine equivalents and elucidating the mechanism of the Cu-catalyzed allylic aminations, and 4) discovering metal-catalyzed direct amination reactions of saturated and aromatic hydrocarbons. As indicated, not only will the synthetic aspects of these reactions be examined but also the mechanisms of these reactions will be studied. The importance of this study is reflected in the following. The allyl amine unit is found in many natural and unnatural products and is a valuable building block for synthetic elaboration. The indole nucleus is featured in the diverse and biologically potent indole alkaloids as well as in valuable synthetic derivatives, including the specifically targeted indolocarbazole natural products. The direct aminations of aromatic and saturated substrates will also provide novel, synthetically valuable routes to important aliphatic and aromatic amines. Further, the metal-mediated processes leading to these compounds proceed from readily available starting materials and are expected to be highly regio- and chemoselective, functional group tolerant, economical, environmentally-friendly, and complementary or superior to existing methods.Broader Impacts. The new synthetic methods will widen the general scope of the understanding of how metal complexes interact with various classes of organic compounds and they also have the potential for wide applications in synthetic organic chemistry, which can have important implications for making useful materials such as biologically active compounds and polymers. In addition, graduate and undergraduate students in science will be trained along with a disproportionate number of women and members of under-represented minority groups. There will also be continued collaborations with computational and experimental scientists at Ph. D.-granting and undergraduate institutions in the U.S. and Italy.