The amide bond N−C activation represents a powerful strategy in organic synthesis to functionalize the historically inert amide linkage. This personal account highlights recent remarkable advances in transition‐metal‐free activation of amides by N−C bond cleavage, focusing on both (1) mechanistic aspects of ground‐state‐destabilization of the amide bond enabling formation of tetrahedral intermediates directly from amides with unprecedented selectivity, and (2) synthetic utility of the developed transformations. Direct nucleophilic addition to amides enables a myriad of powerful methods for the formation of C−C, C−N, C−O and C−S bonds, providing a straightforward and more synthetically useful alternative to acyl‐metals.

中文翻译：

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酰胺键断裂对酰胺的无过渡金属活化作用

酰胺键N-C活化代表了有机合成中功能强大的策略，以使历史上惰性的酰胺键功能化。本个人陈述着重介绍了通过N-C键断裂在酰胺的无过渡金属活化方面的近期显着进展，重点关注（1）酰胺键基态稳定化的机理方面，从而可以直接由酰胺和四氢呋喃形成四面体中间体空前的选择性，以及（2）已开发的转化方法的综合实用性。酰胺中直接亲核加成为形成C-C，C-N，C-O和C-S键提供了无数强大的方法，为酰基金属提供了直接且在合成上有用的替代方法。