Transition Metal-Catalyzed Nitrogenation of Hydrocarbons

Kenneth M.俄克拉荷马州大学的Nicholas博士通过开发新的、有效的和选择性的金属催化C-N键形成反应，利用过渡金属形成新的碳-氮键。 这种方法将适用于合成胺化合物和氮杂环，既作为合成中间体，也作为最终产品，如药物。 要检查的几种反应包括：1）确定了CpM催化的烯丙基胺化反应的合成范围，并鉴定了活性氮化物种; 2）改进了CpM催化的硝基芳烃与炔及其它亚硝酰的还原环加成反应的简便性、高效性，并证明了其合成实用性，3）开发了有效的对映选择性羟胺等价物，阐明了铜催化烯丙基胺化反应的机理; 4）发现了金属催化的饱和烃和芳烃的直接胺化反应。 正如所指出的，不仅将检查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方面。 烯丙基胺单元存在于许多天然和非天然产物中，是合成加工的有价值的构建单元。 吲哚核在多种多样的具有生物学活性的吲哚生物碱以及有价值的合成衍生物中具有重要意义，包括特异性靶向的吲哚并咔唑天然产物。 芳族和饱和底物的直接胺化也将提供新的、合成有价值的重要脂族和芳族胺的途径。 此外，这些化合物的金属介导过程从容易获得的起始材料开始，预计具有高度的区域选择性和化学选择性、官能团耐受性、经济性、环境友好性，并且是现有方法的补充或上级。 新的合成方法将拓宽金属配合物如何与各种有机化合物相互作用的理解的一般范围，并且它们也具有在合成有机化学中广泛应用的潜力，这对于制造有用的材料如生物活性化合物和聚合物具有重要意义。此外，科学专业的研究生和本科生将接受沿着培训，其中妇女和代表性不足的少数群体成员的人数不成比例。 也将继续与计算和实验科学家在博士合作。在美国和意大利的授予和本科院校。

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.