Mild PIFA-Mediated Synthesis of Benzo[4,5]thiazolo[3,2-a]indoles via Oxidative Cyclization

Abstract

We report a novel synthetic approach for the synthesis of benzo[4,5]thiazolo[3,2-a]indoles. This strategy relies on a straightforward cyclization of 1-(2-(methylthio)phenyl)-1H-indoles using (bis(trifluoroacetoxy)iodo)benzene (PIFA) as an oxidant. The reaction proceeds smoothly in MeCN at room temperature within 15 minutes, affording 28 diversely substituted benzo[4,5]thiazolo[3,2-a]indoles in good to excellent yields. The viability of the method was confirmed with the preparation of melatonin and tryptophan derivatives, along with a late-stage diversification via Barluenga-Valdés cross-coupling. Detailed mechanistic investigations support PIFA-mediated cyclization via a thionium ion intermediate.