Catalytic Annulations of Itaconimides: Mechanistic Diversity and Opportunities for More Sustainable Organic Synthesis

Abstract

Itaconimides combine an electron-deficient terminal methylene group with a succinimide framework, creating a reactive topology that differs from those of maleimides, citraconimides, and substituted α-alkylidene succinimides. This review critically examines annulation reactions of terminal-methylene itaconimides, defined here as 3-methylenepyrrolidine-2,5-diones bearing an unsubstituted =CH2 group. Catalyst-free and reagent-promoted transformations are first considered as benchmarks for intrinsic reactivity, followed by organocatalytic, nucleophilic phosphine-catalysed, transition-metal-catalysed, and visible-light photoredox processes. Across these reaction classes, the exocyclic alkene functions as a dipolarophile, electrophilic addition site, radical acceptor, or migratory-insertion partner, while catalyst structure and reaction environment govern the subsequent fate of the resulting intermediates. A recurring feature is therefore that catalysis often controls reaction pathway and selectivity, rather than merely enabling alkene activation, allowing divergent access to spirocyclic, fused, and polycyclic products and, in selected cases, high regio-, diastereo-, or enantioselectivity. At the same time, substrate generality remains uneven, with several studies examining only limited variation of the itaconimide component or isolated terminal-methylene examples within broader α-alkylidene succinimide series. Quantitative information on catalyst efficiency, material demand, energy input, and preparative performance is also scarce. These gaps define opportunities for broader substrate validation, stronger mechanistic interrogation, and more rigorous process evaluation in the future development of selective and sustainable itaconimide annulations.