Efficient synthesis of 2-alkylidene-3-iminoindoles,indolo[1,2-b]isoquinolin-5-ones,delta-carbolines,and indirubines by domino and sequential reactions of functionalized nitriles

The sodium hydride mediated cyclization of arylacetonitriles with oxalic acid bis(imidoyl) dichlorides, aza-analogues of oxalyl chloride, afforded functionalized 2-alkylidene-3-iminoindoles with very good regio- and E/Z selectivity. Excellent chemoselectivities were observed for functionalized substrates. Based on these results a domino "cyclization-lactamization" reaction of bis(imidoyl) chlorides with methyl 2-(cyanomethyl)benzoate was developed. This process allowed a convenient one-pot synthesis of indolo[1,2-b]isoquinolin-5-ones related to tryptanthrin. A new and convenient synthesis of delta-carbolines by intramolecular electrocyclization-elimination reactions of 2-alkylidene-3-iminoindoles was developed. It was shown that delta-carbolines selectively bind to triplex or duplex DNA (intercalation). Indirubine analogues were prepared by deprotection and lactonization of functionalized 2-alkylidene-3-iminoindoles.