Development of an Asymmetric Amination Process of Unactivated Olefins

说明(申请人提供)：含氮化合物作为合成中间体和生物活性试剂的重要性产生了实际和一般胺化程序的需要。拟议研究的目标就是开发这样一种方法。在具体目标1中提出的是后过渡金属催化的非官能化烯烃的胺化反应。这种方法包括在1-烯烃上加成丁腈亲核试剂，以形成各种高度官能化的产品，如酰胺、仲胺和氮杂环。这些类型的胺亚单位普遍存在于畅销药物和具有生物重要性的化合物中。如目标2所示，这一方法最终将扩展到相应的不对称过程，这反过来将允许从廉价的起始材料中获得对映体丰富的1-手性胺。最后，在这两个具体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。 与公共卫生相关：在每一类主要药物中都发现了含氮化合物或胺。尽管它们很重要，但从廉价和可广泛获得的起始原料合成胺的一般和实用方法仍然很少。拟议研究的目标就是开发这样一种方法。

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.