Synthesis of isoindolines and isoindolinones by palladium catalyzed reactions

Abstract

1soindolin-l-ones (or 2,3-dihydro-l H-isoindol-l-one (phthalimidine) and 1soindoline (2,3-dihydro-1H-isoindole) moieties are integral parts of some natural products and have generated considerable interest in recent years for their biological and medicinal properties. A number of 2-substituted isoindolin-l-one was synthesized and their in vitro antimicrobial activity was evaluated. A highly regio-and stereoselective method for the synthesis of (Z)-3-aryl(alkyl)idene isoindolinones through palladium-copper catalysis is described. The reactions were carried out by heating a mixture of 2-iodobenzamides and its N-substituted derivatives and alkynes in DMF/THF at 80-85 DC / room temperature for 16 h / 24 h in presence ofbis(triphenyl phosphine) palladium (II) chloride, copper (I) iodide and triethylamine to yield 2-alkynyl benzamide which could then be cyclized with NaOEt in EtOH to the 3-aryl(alkyl)idene isoindolinones. In certain cases, the isoindolinones could be directly obtained by the palladium-copper catalyzed reaction. It was attempted to synthesize 3-substituted isoindoline from 2-iodobenzamides and also from 3-substituted isoindolin-l-ones but failed. The synthesized compounds showed poor growth inhibition against antibiotic-susceptible standard and clinically isolated strains of gram-positive and gram-negative bacterial as well as human fungal pathogens.