New Directions in Cross-Couplings Catalyzed by Non-Precious Metals

非贵金属催化交叉偶联的新方向

• 批准号: 9892311
• 负责人: NEIL K GARG
• 金额: $ 17.12万
• 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 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892311
• 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; 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.

项目总结/摘要 酰胺是普遍的官能团，其充当生物活性的关键构件。 proteins.而大自然可以通过酶的作用巧妙地切割酰胺 例如蛋白酶，使用合成的酶来断裂酰胺的C-N键的能力， 化学仍然是一个挑战。酰胺类亲电试剂的适度合成应用 可以追溯到它们的低反应性，这反过来又来自于众所周知的 酰胺的共振稳定性。 该提案的目标是利用酰胺官能团作为 它依赖于前所未有的镍催化活化酰胺C-N 债券初步结果证明了这种独特的可行性和温和性 C-杂原子和C-C键的构建方法。我们的研究旨在 建立这种新方法的范围和限制， 重要的连接，包括sp2-sp3 C-C键与立体定向的季中心。 这些努力为镍的强键活化领域提供了新的机会 催化，沿着通过C-N键断裂操纵酰胺的新工具。

项目成果

Activation of C-O and C-N Bonds Using Non-Precious-Metal Catalysis.

• DOI: 10.1021/acscatal.0c03334
• 发表时间: 2020-10-16
• 期刊: ACS catalysis
• 影响因子: 12.9
• 作者: Boit TB;Bulger AS;Dander JE;Garg NK
• 通讯作者: Garg NK