Three-component Minisci reaction involving trifluoromethyl radicals promoted by TBHP

Abstract

A three-component Minisci reaction based on radical polarity inversion and mediated by a trifluoromethyl radical is reported in this work. Under transition metal-free conditions, the electrophilic trifluoromethyl radical was added to an electron-rich alkene, generating a nucleophilic alkyl radical, which underwent a Minisci reaction with various electron-deficient N-heteroarenes. This protocol is easily executed using CF₃SO₂Na as the trifluoromethyl radical source under air- and moisture-free conditions, providing a versatile way to obtain trifluoromethyl-containing N-heteroarenes. Pyridines, quinolines, isoquinoline, phenanthridine and acridine were tolerated under the reaction conditions and reacted with both acyclic and cyclic alkenes. The potential of this reaction was demonstrated through a gram-scale preparation of trifluoromethyl-containing N-heteroarene and their various synthetic applications in synthesizing divergent and structurally complex molecules.