Studies On Synthesis Of Trifluoromethyl Ketones And Ynones Using Carboxylic Acids As Acyl Sources

Carboxylic acids are not only nature-aboundunt but also important chemicals.They are cheap,readily available,easily handled and widely used in pharmaceuticals,materials,synthesis and catalysis.The studies on the activation and functionalization of carboxylic acids are of significance in science ans economy for higher value utilization of carboxylic acids and late modification of related functional molecules.Herein,we used carboxylic acids activated in-situ by anhydrides as acyl source to couple with TMSCF₃and terminal alkynes to produce value-added trifluoromethyl ketones and ynones,respectively.The specific contents come as follows:Part 1.Carboxylic acids as acyl source to couple with TMSCF₃producing trifluoromethyl ketones:carboxylic acids were activated in-situ by TFAA（trifluoroacetic anhydride）to generate a mixing anhydride.Meanwhile,TMSCF₃generated CF₃^-ion by the aid of Cs F and DMAP.The resulting CF₃^-ion subsequently nucleophilically attacked the cobonyl group of the mixing anhydride,followed by elimination of TFA to produce the target product trifluoromethyl ketones.The reaction showed wide substrate scope,both electron-deficient and electron-rich aromatic carboxylic acids could participate in the reaction,producing the expected trifluoromethyl ketones.This reaction was applicable to the modification of probenecid,adapalene,telmisartan,endoflavonoids,and scaled up to gram.The results well demonatrated its synthetic value in organic synthesis.Part 2.Carboxylic acids as acyl source to couple with terminal alkynes producing ynones:the carboxylic acida were activated in-situ by Boc₂O to produce a mixing anhydride,followed by ccross coupling with terminal alkynes through Pd/Cu cooperative catalysis.This reaction showed wide substrate scope.Various carboxylic acids could couple with terminal alkynes to produce the corresponding ynones.Many functional groups such as-OCH₃,-N（CH₃）₂,-F and-CF₃all were tolerated in the present catalytic system.In addition,this reaction could be applied to the synthesis of complicated molecules.Those results well demonstrated its potential synthetic value in organic synthesis.