Silver-catalyzed Defluorinative 1,3-butadienation Of Fluoroalkyl Ketones

In recent years,fluorinated organic compounds have been widely used in many fields such as materials science,polymer chemistry,pesticides,and pharmaceutical industry.This is mainly due to the unique properties of the C-F bond,which can greatly alter the chemical reactivity and physical properties of molecules.The combination of fluorine atoms or fluorinated moieties into organic compounds or polymers has become a research focus of scientists.Difluoromethylene is a very important structural segment in organic compounds as the biological isomorph of hydroxy（-OH）and sulfhydryl（-SH）.Trifluoromethyl compounds are abundant sources and low cost,so selective defluorination of trifluoromethyl compounds is an easy way to obtain some fluorinated compounds,which can selectively obtain difluoro or monofluoro compounds.However,at present,defluorination of trifluoromethyl group faces two major problems:（1）the bond energy of the C-F bond is high and difficult to break;（2）when defluorination occurs,the bond dissociation energy（BDE）of the C-F bond decreases,making it easy to defluorate excessively.Up to now,the activation of a single C-F bond in CF₃ group mainly occurs in substrates withπelectron system,including olefins,carbonyl derivatives and aromatics,which are directly linked to the CF₃ group.πelectron system can accept electrons from nucleophiles,low valence metals or electrochemical means,and then induce the elimination of fluoride anions.Allyl fluoride,which contains both alkenyl units and fluoroalkyl groups,is an important structural unit in drugs and bioactive molecules and is a kind of attractive organic fluoride.In addition,allyl fluoride exhibits unique reactivity and selectivity compared to other organic halides and can be used as a good precursor for the synthesis of a variety of fluorinated compounds.Currently,the synthesis of such important organic fluorides is limited by a narrow substrate range,incompatibility of important functional groups,and the use of expensive and toxic fluorides.The carbene-initiated defluorination functionalization strategy provides a new direction for C-F bond activation.Based on this strategy,we developed a carbene-initiated fluorinated1,3-butadienation reaction of fluoroalkyl ketones.A series of 1,3-butadiene compounds were successfully prepared by the reaction between N-sulfonylhydrazone derived from fluoroalkyl ketone and allene propanol catalyzed by Tp^Br3Ag.The reaction process mainly includes allene propanol nucleophilic attack on silver carbene to form metal coordination ylide,selective cleavage of C-F bond to form allyl dienyl ether,and finally Claisen rearrangement to form C（sp³）-C（sp²）bond.Silver plays an important role in selective defluorination and the Claisen rearrangement.This reaction not only realizes the selective 1,3-butadienation of the C-F bond,but also provides a simple method for the preparation ofα-difluoro-β-vinyl allyl ketones.This method has a wide range of substrates,good tolerance of functional groups,and is compatible with the first and second cascade allyl alcohols with a variety of substituents.It has important application value in drug synthesis and structural modification of natural products.