Ultrasonic and mechanochemical strategies for the synthesis of oxindole scaffolds mediated by hypervalent iodine(iii) reagents.

We report a rapid and efficient methodology for the synthesis of 6H-isoindolo[2,1-a] indol-6-one scaffolds 18a-k mediated by hypervalent iodine(iii) reagents using ultrasonic and mechanochemical activation strategies. These non-conventional approaches significantly enhance reaction rates and reduce reaction times compared to conventional methods. This protocol employs readily accessible starting materials under mild conditions to afford structurally diverse oxindole derivatives in good to excellent yields (60-93%) with broad functional group tolerance. Ultrasonic irradiation facilitates rapid molecular interactions via acoustic cavitation, while mechanochemical activation under liquid-assisted grinding (LAG) conditions enables efficient transformation using only a small amount of solvent. This approach demonstrates strong operational robustness across a range of substrates and offers a practical alternative to conventional solution-phase synthesis. The hypervalent iodine(iii) reagent serves as an effective oxidant and cyclization promoter, enabling selective formation of the oxindole core. This study demonstrates the effectiveness of integrating ultrasonic and mechanochemical activation techniques with hypervalent iodine chemistry for the non-conventional activation strategy for the construction of functionalized heterocycles.