Approaches for Directed Olefin Hydroamination

定向烯烃加氢胺化方法

• 批准号: 8596362
• 负责人: Juana Du
• 金额: $ 3.29万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2014-05-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8596362
• 关键词: Affinity; Alkenes; Amines; Binding; Carbon; Complex; Development; Goals; Health; Human; Ligands; Link; Mediating; Metals; Methods; Nitrogen; Organic Synthesis; Palladium; Pharmacologic Substance; Phosphines; Process; Reaction; Relative (related person); Research; Research Proposals; Rhodium; Route; Ruthenium; Site; Solutions; Structure; System; Transition Elements; analog; base; catalyst; design; direct application; drug development; functional group; insight; interest; metal complex; method development; pi bond; public health relevance; research study; solid state; stem; tool

DESCRIPTION (provided by applicant): Nitrogen-containing motifs are ubiquitous in biologically active molecules. Thus, the development of new methods for the selective incorporation of nitrogen into organic structures is essential for the synthesis of medicinally important compounds. One efficient strategy for the formation of carbon-nitrogen bonds is hydroamination, the addition of an amine across a double bond. If this transformation could be directed to occur with high levels of regio- and stereoselectivity, the hydroamination of olefins would be an atom-economical method for synthesizing a wide range of nitrogen-containing molecules. The goal of this research proposal is to develop the first substrate-directed hydroamination of olefins into a synthetically useful transformation. This objective will be achieved through the use of cationic transition metal complexes that are able to exploit the coordinating ability of common polar functional groups to direct the addition of an amine across an unsaturated carbon-carbon bond. Several catalyst systems based upon late transition metals will be studied for their ability to mediate this transformation. The catalyst structures studied i this proposal will include ruthenium complexes containing a tethered ¿,¿-bidentate ligand framework, rhodium complexes of bidentate, bisphosphine ligands, and chelate-stabilized, ?2-olefin palladium complexes. Mechanistic studies to help identify the factors that govern the reactivity and selectivity of each catalyst system will also be conducted. These studies will include a complete characterization of the organometallic catalysts and their corresponding olefin complexes, both in solution and in the solid-state. Experiments to characterize how the amine, the olefin, and the directing group interact with the metal will be carried out. The relativ binding affinities of these components will also be determined. In addition, experiments to determine the stereochemical course of hydroamination will be conducted. Finally, these new catalysts will be employed to synthesize amine-analogues of medicinally important compounds. Because carbon-heteroatom bonds are ubiquitous in biologically relevant structures, substrate-directed hydroamination can be a powerful strategy for accessing a wide range of structurally diverse pharmaceutical derivatives with high atom economy. The selectivity and predictability of this approach will enable more efficient routes to biologically and pharmaceutically relevant structures in the drug development process.

描述（通过应用提供）：含氮基序无处不在，在生物学活性分子中。这，开发将氮选择性掺入有机结构中的新方法对于合成具有药物重要的化合物至关重要。形成碳氮键的一种有效策略是氢化，是在双键中添加胺。如果可以指示这种转化以高水平的区域和立体选择性发生，则烯烃的氢化将是合成各种含氮分子的原子经济方法。这项研究建议的目的是将烯烃的第一个底物指导的氢化为合成有用的转换。通过使用阳离子过渡金属复合物来实现该目标，这些金属络合物能够利用公共极性官能团的协调能力指导胺在不饱和的碳碳键中添加。基于晚期过渡金属的几种催化剂系统将研究其介导这种转换的能力。研究I的催化剂结构该提案将包括含有束缚的„，ood的配体框架，鸟酸盐的犀牛配合物，双膦配体和樱桃稳定的，？2-烯烃钯络合物。还将进行机械研究，以帮助确定控制每个催化剂系统反应性和选择性的因素。这些研究将包括在溶液和固态中的有机催化催化剂及其相应的烯烃复合物的完整表征。将如何进行胺，烯烃和指导组与金属相互作用的实验。这些组件的相对结合亲和力也将得到确定。此外，还将进行确定氢化立体化学过程的实验。最后，这些新的催化剂将用于合成具有药物重要化合物的胺分析。由于碳杂质键在生物学相关的结构中无处不在，因此底物指导的水疗可以成为一种有力的策略，用于访问具有高原子经济的各种结构多样性的药物衍生物。这种方法的选择性和可预测性将使在药物开发过程中具有更有效的生物学和药物相关结构的途径。