Recent Advances in Transition Metal-Free Strategies for the Transformation of Amides into Carbonyl Compounds

Amides are fundamental functional groups in organic synthesis and play crucial roles in medicinal chemistry and materials science. Traditionally, amide transformations have often relied on transition metal catalysts; however, recent advances have demonstrated efficient transition metal-free strategies for amide bond activation. This review provides a comprehensive overview of emerging methodologies that enable selective formation of C-N, C-C, C-O, C-H, and C-X bonds. Key developments that offer sustainable and practical alternatives to conventional approaches include borate- and boronic acid-mediated transamidations, phosphoric acid-promoted transformations, and radical-based strategies. Additionally, nucleophilic substitutions with carbon, oxygen, and nitrogen-based nucleophiles have expanded the synthetic utility of amides by yielding diverse carbonyl and heterocyclic compounds. Mechanistic insights into these transformations reveal the role of electronic and steric effects in amide reactivity. By categorizing these methodologies based on amide substrates and reaction pathways, this review aims to provide a valuable resource for researchers seeking efficient, metal-free strategies for amide bond manipulation.