Enantioselective Reactions with Amide Electrophiles Utilizing Transition-Metal Catalysis

利用过渡金属催化与酰胺亲电子试剂进行对映选择性反应

• 批准号: 10607332
• 负责人: Arismel Tena-Meza
• 金额: $ 4.23万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10607332
• 关键词: Amides; Catalysis; Chemical Structure; Chemistry; Complex; Coupling; Cytolysis; Development; Marketing; Methodology; Methods; Nickel; Organic Chemistry; Organic Synthesis; Pharmaceutical Preparations; Pharmacologic Substance; Play; Process; Reaction; Reporting; Research; Role; Transition Elements; chemical synthesis; drug discovery; interest; small molecule therapeutics; success

Project Summary/Abstract Organic synthesis plays a crucial role in the development of small molecule therapeutics. New methodologies that allow for the introduction of defined stereocenters and difficult-to-access motifs, such as quarternary stereocenters, are particularly desirable. Moreover, there is growing interest in the use of unconventional synthetic building blocks to generate such complexity, as the use of uncommon starting materials provides new strategies and retrosynthetic disconnections that may prove broadly useful. The proposed research involves the use of amides in transition metal-catalyzed reactions to generate enantioenriched products bearing quaternary stereocenters. Although amides have historically been avoided as synthetic building blocks, they have recently been employed in transition metal-catalyzed reactions that proceed via C–N bond activation. However, amide cross-coupling methods that make quaternary stereocenters are rare and no catalytic enantioselective examples have been reported. The success of the proposed studies would push the limits of known amide cross- coupling methodology, provide methods to access defined quaternary stereocenters, and offer new strategies for synthetic chemists to utilize in the construction of drugs and complex molecules.

项目摘要/摘要 有机合成在小分子治疗的发展中起着至关重要的作用。新的 允许引入定义的立体中心和难以访问图案的方法， 例如，季度立体中心，特别需要。而且，对 使用非常规合成构建块来产生这种复杂性，例如不常见的使用 起始材料提供了新的策略和转化合成的断开连接，可能会广泛证明 有用。 提出的研究涉及在过渡金属催化反应中使用酰胺 生成具有第四纪立体中心的映射产品。胺有 从历史上看，避免了作为合成的构件，最近在过渡中雇用了它们 通过C – N键激活进行的金属催化反应。但是，酰胺交叉耦合 使第四纪立体中心的方法很少 据报道。拟议的研究的成功将推动已知的酰胺交叉的极限 耦合方法，提供访问定义的第四纪立体中心的方法，并提供新的 合成化学家的策略用于构建药物和复杂分子。