Non‐Noble Metal Catalysis in Focus: Unlocking Latest Emergent Frontiers in Amide Annulation Through C─H/C─X Activation

In this review non-noble metal catalyzed synthesis of bioactive chiral or achiral heterocycles have been accomplished by annulation of amides via C─H/C─X (X = F, Br, O, S, and C) activation assisted by diverse N-substituted amides as directing group.

Abstract

The non-noble metal-catalyzed annulation of amide molecules through the proximal C─H/C─X (X = halogens, O, S, N, C etc.) has emerged as a transformative approach in contemporary synthetic chemistry, enabling the efficient construction of diverse heterocyclic frameworks. This sustainable strategies address the limitations of noble metal catalysis, offering cost-effective and environmentally benign alternatives through utilizing earth-abundant metals such as Mn, Fe, Co, Ni, and Cu in those methods by harnessing their catalytic potential for activating inert bonds in diverse amides leveraging the inherent directing ability. By incorporating various electrophilic or nucleophilic coupling partners wisely, nonmetal catalysis has provided access toward pharmaceutically active heterocyclic ingredients, mainly spiro-/fused-N-heterocycles like isoquinolones, indolones, indoles, isoquinolines etc. through one-pot atom-economical activation-annulation cascade routes. Additionally, mechanistic studies have discussed in detail to understand the insights of non-noble metal catalyzed amide cyclization toward pharmaceutically active N-heterocyclic scaffolds properly through the individual steps engaged, namely, metal coordination, inert bond activation, bond cleavage, insertion or migratory insertion and eventually cyclization pathway via reductive elimination, which enables this review more valuable and useful to the readers of the aforementioned field and beyond.

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