Solvent-controlled and selective synthesis of mono- and bis-indolyl products in Brønsted acid catalyzed aza-Friedel–Crafts reactions of indoles with cyclic imines

Abstract

Studies to investigate the selectivity and scope of acid-catalyzed aza-Friedel–Crafts reactions of seven-membered cyclic imine dibenzo[b,f][1,4]oxazepines with various indoles have been carried out. In the presence of 10 mol% trifluoroacetic acid (TFA), the selectivity of this reaction can be controlled in different solvents, affording mono-indole substituted products in THF and bis-indole substituted products in DCM as major products. Unsymmetric bis-indole substituted products can be obtained via a sequential procedure. Structurally diverse indole derivatives can be constructed using cyclic imines as the substrates with the reaction featuring: mild conditions, solvent-controlled efficient selectivity, and no need for metals but using easy accessible TFA as a catalyst. Moreover, the potential anti-tumor activity of the new functionalized indole products obtained has been studied by MTT assays.