Iron-Catalyzed Batch/Continuous Flow C–H Functionalization Module for the Synthesis of Anticancer Peroxides

Iron-catalyzed
dehydrogenative cross-coupling of carbonyl compounds
with aliphatic peroxide was developed under mild conditions. A library
of linear alkylated and arylated peroxides are synthesized in good
to excellent yield. This method is highly selective and general for
a range of biologically important derivatives of 2-oxindole, barbituric
acid, and 4-hydroxy coumarin with a good functional group tolerance
and without the cleavage of the peroxide bond. This peroxidation reaction
is upscalable to grams and also synthesizable in continuous flow with
increased safety in short duration. Mechanistic investigation reveals
Fe-(II) undergoes redox type process to generate the radical intermediates,
which subsequently recombine selectively to form the stable peroxides.
The potential of peroxides is evaluated by cell viability assay and
found to exhibit the good anticancer activity with minimum IC50= 5.3 μM.