Recent Synthetic Advancements of C(3)‐Substituted Isoindolinones

Isoindolinones represent a significant structural motif frequently encountered in natural products, pharmaceuticals, and synthetic intermediates. The primary method for their synthesis is the base‐mediated transition metal‐catalyzed intramolecular cyclization of benzamides. This review highlights the various strategies that have been employed over the past ten years to construct the C(3)‐substituted isoindolinone core, which is classified as: 1) C3─C3a connectivity through transition metal/base catalyzed annulation of N ‐alkyl benzamides, 2) N2─C3 connectivity via intramolecular cyclization of ortho ‐alkenyl benzamides using the aza‐Wacker/Michael addition process, 3) N2─C3a connectivity employing a cascade approach of C─H functionalization and intramolecular cyclization of benzamide with unsaturated compounds, 4) N2/C7a connectivity applying transition metal catalyzed carbonylative annulation of benzylamine derivatives, 5) C3─Cα connectivity through nucleophilic/electrophilic substitution to the isoindolinone core, and 6) domino multi‐component reactions of various nucleophiles with ortho ‐formyl benzoic acid derivatives. The majority of the reactions examined in this review utilize easily accessible starting materials, operate under mild conditions, employ inexpensive catalysts, and follow one‐pot procedures that are environmentally friendly and straightforward in execution. This review may enlighten the synthetic community and drug discovery system; researchers will gain insight into the straightforward conclusion of this recent study of C(3)‐substituted isoindolinone, which will be instructional and valued.