Nucleophilic and electrophilic substitutions of difluoropropargyl bromides

Fundamental organic reactions like nucleophilic and electrophilic substitutions have seldom been studied on fluorinated propargyl or allenyl modules, when the carbon atom undergoing substitution is bonded to two fluorine atoms. Herein we report a practical synthesis of difluoropropargyl bromides from substituted acetylenes and dibromodifluorometane using a wide variety of alkyl, aryl or silyl substrates. The synthesis of O-, S- and carboxylic acid derivatives of difluoropropargyl bromide is also described. These compounds are suitable starting materials for the synthesis of electrophilically substituted difluoropropargyl derivatives via magnesium and fluoride promoted reactions. An indium-mediated reaction of silyldifluoropropargyl bromide, followed by electrophilic trapping with bromine led to a very useful bromoallene, which was then used in reactions with nucleophiles (C, O, N, P, S, Hal) to yield a de facto bimolecular nucleophilic substitution of a difluoropropargyl bromide.

Graphical abstractA practical synthesis of difluoropropargyl bromides 1 is reported. These compounds are suitable starting materials for the synthesis of electrophilically substituted 2 via a SE2 mechanism. An indium-mediated reaction of 1 (R = TIPS), followed by electrophilic SE2′ trapping with bromine led to high yields of 4, which reacted with various nucleophiles (Nu) to yield de facto SN2 substitution product 3. Figure optionsDownload full-size imageDownload as PowerPoint slide