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

项目摘要/摘要 酰胺是广泛存在的官能团，是 蛋白质。而大自然可以通过酶的作用巧妙地裂解酰胺 例如，蛋白水解酶，能够用合成的 化学仍然是一个挑战。酰胺类化合物作为亲电剂的适度合成用途 可以追溯到它们的低反应性，而这反过来又源于众所周知的 酰胺类化合物的共振稳定性。 这项提案针对的是一种新的战略，以利用酰胺官能团 合成子，它依赖于前所未有的镍催化的酰胺C-N的激活 债券。初步结果表明，这种独特的方法是可行和温和的。 C-杂原子和C-C键的构筑方法。我们的研究旨在 确定这一新方法论的范围和局限性 重要的联系，包括具有固定定义的四元中心的sp2-sp3 C-C键。 这些努力在镍的强键活化领域提供了新的机会 催化，以及通过C-N键断裂操纵酰胺的新工具。

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.