A facile synthesis of phthalimides from o-phthalaldehyde and amines via tandem cyclocondensation and α-C-H oxidation by an electrochemical oxygen reduction reaction.

Abstract

Electrochemical synthesis of phthalimides from o-phthalaldehyde and amines via tandem cyclocondensation and α-C-H oxygenation of isoindolinone was achieved. The α-C-H oxidation proceeded with molecular oxygen via an oxygen reduction reaction (ORR) on the cathode under electrochemical conditions. The synthetic utility of this protocol was successfully demonstrated by employing gram-scale synthesis and obtaining bioactive molecules such as thalidomide and 2-(2,6-diisopropylphenyl)-5-hydroxyisoindoline-1,3-dione. Mechanistic studies and control experiments indicate that molecular oxygen provides oxygen atoms for the reaction.