Copper-catalyzed alkoxylation as key step to convert isatin to oxazinoindol-2-one derivatives

The treatment of N-alkyl-5,7-dibromoisatin derivatives through the copper-catalyzed sequential processes consisting of intra/intermolecular alkoxylation/amination or double alkoxylation provided the pyrrolo[1, 2,3-de]-1,4-benzoxazine derivatives. Moreover, the alkoxylation/arylation process proceeded in a one-pot fashion under tandem copper-palladium catalysis affording 5-(hetero)aryl substituted hetero-tricyclic systems. Biological evaluation of the synthesized compounds showed antiproliferative activity on the low micromolar range.