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.