Trifluoroethanol as a Unique Additive for the Chemoselective Electrooxidation of Enamines to Access Unsymmetrically Substituted NH‐Pyrroles

An electrochemical method for the synthesis of unsymmetrically substituted NH-pyrroles is described. The synthetic strategy comprises a challenging heterocoupling between two structurally diverse enamines via sequential chemoselective oxidation, addition, and cyclization processes. A series of aryl- and alkyl-substituted enamines were effectively cross-coupled from an equimolar mixture to synthesize various unsymmetrical pyrrole derivatives up to 84 % yield. The desired cross-coupling was achieved by tuning the oxidation potential of the enamines by utilizing a "magic effect" of the additive trifluoroethanol (TFE). Additionally, extensive computational studies reveal the unique role of TFE in promoting the heterocoupling process by regulating the activation energies of the reaction steps through H-bonding and C-H⋅⋅⋅π interactions. Importantly, the developed electrochemical protocol was found to be equally efficient for the homocoupling of enamines to form symmetric pyrroles up to 92 % yield.