Reaction Of α-Trifluoromethyl Alkenyl Esters

Trifluoromethyl is an important fluorine-containing group,which is widespread in drugs,functional material and pesticides.Therefore,the synthesis of trifluoromethyl-containing compounds has drawn great attention.Specially,the method for synthesizing trifluoromethyl compounds with novel structures by using trifluoromethyl olefin reaction building blocks as a substrate has the superiorities of wide application range,mild reaction conditions,and good selectivity.As part of ongoing efforts in the synthesis of useful trifluoromethyl-containing molecules,(Z)-Trifluoromethyl alkenyl trifluoromethanesulfonate have been discovered and widely applied in the synthesis of trifluoromethyl-containing compounds by our group.On the basis of these work,(Z)-trifluoromethanesulfonate trifluoromethyl alkenyl esters were further applied to the synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes andβ-trifluoromethyl-α,β-enones.Then α-trifluoromethyl alkenyl esters with various structures were synthesized and 4-aryl-1,1,1-trifluorobut-2-en-2-yl acetates were selected as novel trifluoromethyl allylation reagent after screening.4-Aryl-1,1,1-trifluorobut-2-en-2-yl acetates were following applied to the asymmetric trifluoromethylallylation of pyrazolone and indolinone derivatives.(1)An efficient method for the synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes is developed via condensation of(Z)-trifluoromethyl alkenyl triflates and salicylaldehydes.A key intermediate is isolated and it’s proved that the last step of the reaction is to eliminate tetrahydropyrrole under heating conditions.(2)A novel approach to β-trifluoromethyl-α,β-enones via oxidation of 4-aryl-1,1,1-trifluorobut-2-en-2-yl triflates by 4-picoline oxide is developed.Variousβ-trifluoromethyl-α,β-enones are obtained in 73%-87%yields.(3)The first asymmetric trifluoromethylated allylic alkylation of pyrazolones using 4-aryl-1,1,1-trifluorobut-2-en-2-yl acetates as novel trifluoromethylated allylation reagent is described.The double-bond migration of 4-aryl-1,1,1-trifluorobut-2-en-2-yl acetates in the presence of DBU is initial step of this reaction.(4)Pd(OAc)2/(R)-BINAP-catalyzed asymmetric trifluoromethylated allylic alkylation of indolinones using 4-aryl-1,1,1-trifluorobut-2-en-2-yl acetates as trifluoromethylated allylation reagent is developed.Various functionalized chiral indolinones containing trifluoromethylated allyl substituent are obtained in 84%-94%yields,up to 97%ee.