Development of an Asymmetric Amination Process of Unactivated Olefins

未活化烯烃的不对称胺化工艺的开发

• 批准号: 8196399
• 负责人: John Robbins Debergh
• 金额: $ 4.84万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-12 至 2013-09-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196399
• 关键词: Acetamides; Alkenes; Amides; Amination; Amines; Development; Goals; Grant; Investigation; Knowledge; Learning; Ligands; Methodology; Methods; Nitriles; Nitrogen; Pharmaceutical Preparations; Procedures; Process; Reaction; Research; Research Project Grants; Transition Elements; drug development

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.

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产生了对实用和通用胺化方法的需求。这项研究的目的就是开发这样一种方法。在具体目标1中提出了后过渡金属催化的未官能化烯烃的胺化反应。这种方法涉及腈亲核试剂加成到1-烯烃上，形成各种高度官能化的产物，如酰胺、仲胺和氮杂环。这些类型的胺亚基普遍存在于畅销药物和生物重要化合物中。如目标2所示，这种方法最终将扩展到相应的不对称过程，这反过来又将使人们能够从廉价的原料中获得对映体富集的1-手性胺。最后，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。 公共卫生相关性：含氮化合物或胺存在于每一类主要的药物中。尽管它们的重要性，一般和实用的方法来合成胺从廉价和广泛可用的起始材料仍然稀缺。这项研究的目的就是开发这样一种方法。