Development of an Asymmetric Amination Process of Unactivated Olefins

描述（由申请人提供）：含氮化合物作为合成中间体和生物活性剂的重要性创造了对实用和通用胺化程序的需求。本研究的目标就是开发这样一种方法。在Specific Aim 1中提出了一个晚期过渡金属催化的非功能化烯烃胺化反应。这种方法包括将腈亲核试剂加成到1-烯烃上，形成各种高功能化产物，如酰胺、仲胺和氮杂环。这些类型的胺亚基普遍存在于最畅销的药物和重要的生物化合物中。如Aim 2所述，该方法最终将扩展到相应的不对称过程，这反过来又将使从廉价的起始材料获得富集对映体的1-手性胺。最后，在两个特定目标中描述的拟议研究对学术和工业环境中的药物开发具有重要意义。

DESCRIPTION (provided by applicant): The importance of nitrogen-containing compounds as synthetic intermediates and biologically active agents has created the need for practical and general amination procedures. The goal of the proposed research is to develop such a method. Proposed in Specific Aim 1 is a late transition metal-catalyzed amination reaction of unfunctionalized olefins. This approach involves the addition of nitrile nucleophiles to 1-alkenes to form a variety of highly functionalized products, such as amides, secondary amines, and nitrogen heterocycles. These types of amine subunits are prevalent in top-selling drugs and biologically important compounds. As illustrated in Aim 2, this methodology will ultimately be extended to the corresponding asymmetric process, which in turn, would grant access to enantioenriched 1-chiral amines from inexpensive starting materials. Finally, the proposed research described in both Specific Aims has significant implications in drug development in academic and industrial settings. PUBLIC HEALTH RELEVANCE: Nitrogen-containing compounds, or amines, are found in every major class of medicinal drugs. Despite their importance, general and practical methods to synthesize amines from inexpensive and widely available starting materials remain scarce. The goal of the proposed research is to develop such a method.