NEW DIRECTIONS IN CROSS- COUPLINGS CATALYZED BY NON- PRECIOUS METALS

非贵金属催化交叉耦合的新方向

• 批准号: 9414882
• 负责人: NEIL K GARG
• 金额: $ 1.18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9414882
• 关键词: Acylation; Alkylation; Amides; Area; Biological; Carbon; Carboxylic Acids; Catalysis; Cleaved cell; Complex; Coxibs; Cyclization; Development; Enzymes; Esterification; Heterocyclic Compounds; Ketones; Metals; Methodology; Methods; N acylation; Natural Products; Nature; Nickel; Nitrogen; Peptide Hydrolases; Phase; Process; Proteins; Reaction; Reagent; Synthesis Chemistry; Variant; Vasodilator Agents; c new; functional group; phase 1 study; small molecule; tool

Project Summary/Abstract Amides are prevalent functional groups that serve as the key building blocks of proteins. Whereas Nature can masterfully cleave amides through the action of enzymes such as proteases, the ability to break the C–N bond of amides using synthetic chemistry remains a challenge. The modest synthetic utility of amides as electrophiles can be traced to their low reactivity, which in turn is derived from the well-known resonance stability of amides. This proposal targets a new strategy to harness amide functional groups as synthons, which relies on the unprecedented nickel-catalyzed activation of amide C–N bonds. Preliminary results demonstrate the feasibility and mildness of this unique approach for the construction of C–heteroatom and C–C bonds. Our studies aim to establish the scope and limitations of this new methodology for the construction of important linkages, including sp2–sp3 C–C bonds with stereodefined quaternary centers. These efforts provide new opportunities in the area of strong bond activation by nickel catalysis, along with new tools for the manipulation of amides via C–N bond cleavage.

项目概要/摘要 酰胺是普遍存在的官能团，是 自然界中的蛋白质可以通过酶的作用巧妙地裂解酰胺。 例如蛋白酶，使用合成酶打破酰胺的 C-N 键的能力 酰胺作为亲电子试剂的合成用途仍然是一个挑战。 可以追溯到它们的低反应性，这又源于众所周知的 酰胺的共振稳定性。 该提案的目标是利用酰胺官能团作为新策略 合成子，依赖于前所未有的镍催化酰胺 C-N 活化 初步结果证明了这种独特的可行性和温和性。 我们的研究旨在构建 C-杂原子和 C-C 键。 确定这种新方法的范围和局限性 重要的连接，包括具有立体定义的四级中心的 sp2–sp3 C–C 键。 这些为镍强键激活领域的努力提供了新的机遇 催化，以及通过 C-N 键断裂操作酰胺的新工具。