Metal-free molecular editing of indole via tandem reaction: Access to 2-aryl-3-aryldiazenylindole for theranostic applications

A practical molecular editing strategy has been established for the direct and consecutive C-3 diazenylation and C-2 arylation of indoles with aryltriazenes under metal-free and ambient conditions. A sequence of tandem reactions has been developed via the sustained release of aryldiazonium species from aryltriazenes to achieve the controlled multiple bond sequential cleavage and formation. This strategy enables the chemo-controlled consecutive C-H functionalization of indole at two adjacent reactive sites (C-2 versus C-3) without pre-functionalization of the reactive sites and even without the assistance of the directing group, metal catalyst, or ligand. Detailed mechanistic experiments and DFT (density functional theory) calculations supported a sequence of tandem reaction mechanisms. The synthetic importance of this methodology is evident from the simple operation, good functional group tolerance, gram-scale synthesis, late-stage modification of pharmaceuticals, and <i>in vitro</i> cytotoxicity evaluation.