Azidodifluoromethanide (N3CF2–): In Situ Generation and Nucleophilic Addition to Aldehydes

A facile one-pot approach for the azidodifluoromethylation of aldehydes via in situ-generated azidodifluoromethenide (N₃CF₂^-) utilizing commercially available TMSCF₂Br and NaN₃ is disclosed. The formed O-silyl ether products are obtained in yields of up to 91% in short reaction times at ambient temperature. Examples of both inter- and intramolecular [3 + 2] azide-alkyne cycloaddition reactions of the installed azidodifluoromethyl handles are also presented, demonstrating the prospective synthetic and biochemical functionality and utility.