Metal‐Free K₂S₂O₈ Mediated Synthesis of 3‐(Substituted)‐2‐Arylisoindolin‐1‐One Derivatives With Cascade C−N/C−C Bond Formations Via Radical Cyclization

Abstract

A facile technique was demonstrated for the synthesis of 2‐hydroxy‐2‐[N‐(alkyl/aryl/heteroaryl)‐3‐oxoisoindolin‐1‐yl]‐1H‐indene‐1,3(2H)‐diones by using a metal‐ free persulfate‐mediated one pot three‐component reaction. The reaction involved the combination effect of TBAB (PTC) and K2S2O8 with the addition of the amine to phthalaldehyde and 2,2‐dihydroxyindane‐1,3‐dione to generate isoindolin‐1‐one in‐situ, followed by cyclization.This lactamization process facilitated the formation of C–N bonds under controllable and ambient reaction conditions. A variety of 2‐hydroxy‐2‐[N‐(substituted)‐3‐oxoisoindolin‐1‐yl]‐1H‐indene‐1,3(2H)‐diones were successfully synthesized through a radical pathway from isoindolin‐1‐one, involving C‐C bond formation. The method demonstrated high functional group compatibility and a wide substrate scope, resulting in moderate to good yields of the desired products. Additionally, the mechanistic analyses demonstrated that isoindolin‐1‐one might be a significant intermediate being involved in the reaction. X‐ray diffraction analysis was used to examine the crystal structures of synthesized 2‐hydroxy‐2‐[N‐(substituted)‐3‐oxoisoindolin‐1‐yl]‐1H‐indene‐1,3(2H)‐diones. Furthermore, it seems that the reaction mechanism involves a radical pathway.