A general Fe-catalysed azidation of iododifluoroketones and its utilization for the synthesis of gem-difluoromethylenated triazoles

Abstract

An iron-catalysed radical azidation of iododifluoroketones with TMSN₃ was developed under mild reaction conditions, providing a concise synthesis of α-difluoroalkylazides. The methyl radical generated from tert-butyl peroxybenzoate enables the XAT (halogen atom transfer) process to give gem-difluoromethylenyl radical, which underwent outer-sphere radical azidation to render the otherwise challenging CF₂–N bond formation with the assistance of iron catalyst. This protocol tolerates both difluoroacetophenone and difluoroketone derivatives with good to excellent yields. The resulting difluorinated azides could be readily transformed into the structurally important triazolyl difluoroketones via the copper(I)-catalysed azide–alkyne cycloaddition (CuAAC), allowing a modular synthesis of CF₂-derived N-containing heterocycles.