Base-free O-difuoromethylation Of 1,3-Dions With Difluorocarbene

The insertion of O-H bonds by difluorocarbene has became the most widely used strategy for the construction of OCF₂H functionalities,thus,tremendous difluorcarbene reagents has bene continuously developed in the past decades.Those reagents produce difluorocarbene intermediates in different ways,most of them need the presence of a strong base,others need high temperature or low temperature to achieve the transformation.Despite those harsh conditions,some of them also suffer from the use of toxic and environment-unfriendly starting materials with low boiling point.Besides,most of those reagents were developed to achieve O-H bond insertion reaction towards phenols and alcohols,only a few cases could achieve the O-difluoromethylation of 1,3-dicarbonyl compounds.In contrast,the difluoromethylene phosphonium salt?Ph₃P⁺CF₂CO₂^-,PDFA?was developed as a difluorocarbene reagent,which could be efficiently applied in difluorocarbene-related reactions under mild conditions without additional additives.Thus,with this clean and mild difluorocarbenesourceinhand,wehaverealizedthe O-difluoromethylation of cyclic 1,3-dicarbonyl compounds under the reaction conditions:the molar ratio of 1,3-dione and PDFA is 1:2,2 mL toluene was used as reaction solvents;the reaction was performed under N₂ atmosphere at 60 ^oC for 3 hours.After the exploration of substrate scope,we successfully realized the synthesis of 13 difluoromethylated enol compounds from cyclic 1,3-dione by PDFA.However,the limitations was observed when this method is applied to acyclic substrates.In conclusion,PDFA was applied in O-difluoromethylation reaction to give difluoromethyl enol compounds in good yield with high tolerance of functional groups under mild reaction conditions.It was also expected to be used in the late-staged synthesis of complex molecules with 1,3-dicarbonyl substructures.