Transition-metal-catalyzed cascade C–H functionalization for isoindolinone construction

Isoindolinones are privileged nitrogen-containing heterocycles widely found in bioactive molecules, natural products, and functional scaffolds. Compared with conventional approaches based on prefunctionalized substrates, transition-metalcatalyzed cascade C–H functionalization provides a more direct and step-economical strategy for isoindolinone construction. This review summarizes recent advances in isoindolinone synthesis through C(sp3)–H, C(sp2)–H and C(sp)–H activation, with emphasis on Pd-, Rh-, Ru-, Ir-, Co-, and Cu-catalyzed annulation systems. Key coupling partners, including alkenes, alkynes, diazo compounds, isocyanides, nitriles, CO surrogates, strained rings and multicomponent reagents, are discussed in relation to substrate scope, regioselectivity, stereoselectivity and product topology. Particular attention is given to mechanistic features such as cyclometalation, migratory insertion, β-hydride elimination, reductive elimination, carbonylation, radical relay, hydrogen atom transfer and cascade cyclization. Complementary photochemical, electrochemical, mechanochemical and metal-free strategies are also considered. By comparing metal-dependent reactivity and persistent limitations, this review highlights current challenges and future opportunities in directing-group economy, redox sustainability, substrate generality and asymmetric control. The bibliography includes 220 references.