I2/DMSO-mediated substrate selective oxidation of tetrahydro indole-2,4-dione towards 4-hydroxy isatins and 5,6-dihydro-1H-indole-2,4-dione derivatives

Abstract

We report an efficient synthetic route for the synthesis of tetrahydro indole-2,4-diones from readily available β-enaminones and glyoxal and subsequent I₂/DMSO-mediated oxidation/aromatization of tetrahydro indole-2,4-dione to produce 4-hydroxyisatin derivatives. The key aspect of this protocol includes the dual catalytic activity of molecular iodine in the presence of DMSO. Mechanistic study suggested that this reaction is substrate selective as corresponding aromatization and sp³ C–H oxidation stops in the presence of 6,6-disubstituted tetrahydro indole-2,4-dione. Additionally, a thorough investigation into the synthesis of tetrahydro indole-2,4-dione follows acid-catalyzed cyclization/dehydration/enol–keto tautomerism from β-enaminones and glyoxal.