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.

项目摘要/摘要 酰胺是普遍的官能团，它是 蛋白质。而大自然可以通过酶的作用来精心清除酰胺 例如蛋白酶，使用合成的能力破坏酰胺的C – N键 化学仍然是一个挑战。酰胺作为电子载体的适度合成效用 可以追溯到它们的低反应性，这又源自众所周知 酰胺的共振稳定性。 该建议针对一种新策略来利用酰胺函数组 合成子，依赖于前所未有的酰胺C型的镍催化激活 债券。初步结果证明了这种独特的可行性和温和性 构建C – Heteroatom和C -C键的方法。我们的研究旨在 建立这种新方法的范围和局限性 重要的联系，包括带有立体置季中心的SP2 – SP3 C -C键。 这些努力为镍的牢固激活领域提供了新的机会 催化，以及通过C – N键裂解来操纵酰胺的新工具。

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