Cyclization of Vinylketene Dithioacetals: A Synthetic Strategy for Substituted Thiophenes

A synthetic strategy for the synthesis of substituted thiophenes is described by the one-pot reaction of indoles with ketene dithioacetals under mild reaction conditions. Promoted by triflic acid (TfOH), the reaction of indoles with the easily available alpha-acetyl ketene dithioacetals resulted in the formation of vinylketene dithioacetals via condensation instead of the well known nucleophilic addition-alkylthio elimination process. In thepresence of CuBr2, vinylketene dithioacetals can cyclize into the corresponding substituted thiophenes. This transformation may benefit from the acidic reaction conditions and the steric effects of the 2-substituted indoles.

Automated summary

A synthetic strategy for the synthesis of substituted thiophenes involves a one-pot reaction of indoles with ketene dithioacetals under mild conditions. The reaction, promoted by triflic acid (TfOH), leads to the formation of vinylketene dithioacetals instead of the usual nucleophilic addition-alkylthio elimination process. In the presence of CuBr2, the vinylketene dithioacetals cyclize to form substituted thiophenes, benefiting from the acidic reaction conditions and steric effects of the 2-substituted indoles.