Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.
Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.
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DOI：
10.1038/nature14615
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发表时间：
2015-08-06
期刊：
影响因子：
64.8
通讯作者：
Garg NK
中科院分区：
文献类型：
--
作者：
Hie L;Fine Nathel NF;Shah TK;Baker EL;Hong X;Yang YF;Liu P;Houk KN;Garg NK
酰胺是一种常见的官能团，已经被研究了一个多世纪。它们是蛋白质的关键组成部分，存在于广泛的其他天然和合成化合物中。酰胺被认为是较差的亲电试剂，这通常归因于酰胺键的共振稳定性。大自然可以很容易地通过蛋白酶等酶的作用来分解酰胺，而利用合成化学有选择地破坏酰胺的C-N键的能力是相当困难的。在这篇论文中，我们证明了酰胺C-N键可以用镍催化剂激活和切割。我们已经使用这种方法将酰胺转化为酯，这是一个具有挑战性和不发达的转化。反应方法在异常温和的反应条件下进行，并避免使用大量过量的醇亲核试剂。密度泛函理论（DFT）计算提供了深入了解这种不寻常的转化的热力学和催化循环。我们的研究结果为利用酰胺官能团作为合成子提供了一种新的策略，并有望为酰胺在非贵金属催化下构建碳杂原子或碳碳键的进一步应用提供燃料。
Amides are common functional groups that have been well studied for more than a century. They serve as the key building blocks of proteins and are present in an broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to resonance stability of the amide bond. Whereas Nature can easily cleave amides through the action of enzymes, such as proteases, the ability to selectively break the C–N bond of an amide using synthetic chemistry is quite difficult. In this manuscript, we demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. We have used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory (DFT) calculations provide insight into the thermodynamics and catalytic cycle of this unusual transformation. Our results provide a new strategy to harness amide functional groups as synthons and are expected fuel the further use of amides for the construction of carbon–heteroatom or carbon–carbon bonds using non-precious metal catalysis.