Studies On The Palladium-catalyzed Cross Coupling Of Carboxylic Acids With Terminal Alkynes

As a kind of important intermediates in organic synthesis,internal alkynes have been widely applied in synthesis of functional molecule such as medicine and metrial.Therefore,how to synthesis aromatic alkynes efficiency and environment-friendly is always focused by Synthetic chemists.Now,synthesis of internal alkynes is always rely on Sonogashira cross-coupling reaction ctaalyzed by transition metals.Although the methods is efficient,high toxic and prepared substrate organohalide reagent will degrade atomic and step economy of the reaction.Carboxylic acid,large scale production of chemical products,is exists widely in nature.In this paper,the C-H arylation and acylation of terminal alkynes catalyzed by palladium were carried out using cheap and easily available carboxylic acids instead of organic halides as raw materials.The corresponding aromatic internal alkynes and conjugated alkynes were synthesized efficiently.The specific research contents are as follows:（1）Pd-catalyzed C-H arylation of terminal alkynes with carboxylic acids to synthesize aromatic internal alkynes.The aromatic carboxylic acids were activated online by anhydrides in one pot method.In the system of Pd₂dba₃/Xantphos as catalyst and ligand,ethylene glycol dimethyl ether（DME）was used as solvent,and converted to internal alkynes at 130℃for 12 h.In the reaction,the oxidant does not need to exist,so we avoid the phenomenon of a large number of terminal alkynes homocoupling in the reaction,and control the dosage of terminal alkynes in a reasonable range.In addition,aliphatic terminal alkynes,aromatic terminal alkynes and aromatic carboxylic acids containing cf3o,TMS,CN,ome,CF3,F and CL were obtained in high yield under this reaction condition,and the retention of functional groups reflected the excellent functional group tolerance of this pathway.In addition,the success of the amplification reaction and the activity of some bioactive aromatic carboxylic acids in the reaction reflect the application value of the reaction.Here,we provide a green and environment-friendly synthetic route for aromatic internal alkynes with mild conditions,wide substrate applicability,good atom economy and step economy.（2）Palladium catalyzed C-H acylation of terminal alkynes with carboxylic acids to synthesize ynones.Terminal alkynes and aromatic carboxylic acids were activated by anhydrides to synthesize alkynones in palladium and copper catalytic systems.In the Pd（dppp）Cl₂/Cu Cl catalytic system,the carboxylic acid was activated online by Boc₂O,and benzoic acid reacted with phenylacetylene at 100℃for 12 h in cyclohexane to form ynones.Compared with the widely used method of preparing ynone from acyl halide compounds,the synthesis of ynone using carboxylic acid as substrate will make the preparation of it more economical and environmentally friendly.Among the reaction conditions currently explored,we have achieved C-H acylation of terminal alkynes under mild reaction conditions by using cheap and easily available anhydride to activate carboxylic acid in one pot method.