Mapping of Some Further Alkylation-Initiated Pathways to Polyheterocyclic Compounds from Indigo and Indirubin

The reaction of indigo with two equivalents of the electrophile ethyl bromoacetate with caesium carbonate as a base result in the formation of structurally complex polyheterocyclics, including a fused spiroimidazole and a spiro[1,3]oxazino derivative, together with a biindigoid-type derivative, through a convenient one-pot reaction. Further assessment of the reaction using five equivalents of the electrophile gave rise to other molecules incorporating the 2-(7,13,14-trioxo-6,7,13,14-tetrahydropyrazino[1,2-<i>a</i>:4,3-<i>a</i>']diindol-6-yl) scaffold. The reaction of ethyl bromoacetate with the less reactive indirubin resulted in the synthesis of three derivatives of a new class of polyheterocyclic system via a cascade process, although yields were low. These compounds were derived from the parent indolo[1,2-<i>b</i>]pyrrolo[4,3,2-<i>de</i>]isoquinoline skeleton. Despite the modest yields of the reactions, they represent quick cascade routes to a variety of heterocycles from cheap starting materials, with these structures otherwise being difficult to synthesise in a traditional stepwise manner. These outcomes also contribute significantly to the detailed understanding of the indigo/indirubin cascade reaction pathways initiated by base-catalysed <i>N</i>-alkylation.