Synthesis of 2-pyrolyl-2-hydroxy-2-cyanoacetamide through FeCl3–TBHP mediated hydroxylation of captodative stabilized radical intermediate

A series of 2-hydroxy-2-(4-oxo-1,2-diaryl-4,5,6,7-tetrahydro-1H-3-indolyl)-2-cyanoacetamides have been synthesized through selective CH oxidation of active methylene carbon of cyanoacetamide derivatives using tert-butyl hydroperoxide as oxidant and ferric chloride as radical initiator. In this reaction the tert-butyl oxo radical abstracts hydrogen from the active methylene group of 2-pyrolyl-2-cyanoacetamides to generate a stable captodative radical intermediate. Then recombination of this radical intermediate with tert-butyl oxo radical followed by acid catalysed thermal elimination of the tert-butyl group produces the quaternary hydroxyl cyanoacetamide derivatives in good yield.