Decarboxylative Coupling Of Substituted Propiolic Acids And Difluoracetic Acids

In this thesis, decarboxylative coupling reaction of alkynyl propiolic acids or difluoroacetic acids was invetigated. In addition, the deacetonative coupling of 4-aryl-2-methyl-3-butyn-2-ols was also explored. The detailed results are outlined as follows:1.Palladacycle-Catalyzed Decarboxylative Coupling of Alkynyl Carboxylic Acids with Aryl Chlorides under AirA highly efficient and practical protocol for palladacycle-catalyzed decarboxylative coupling of alkynyl carboxylic acids with aryl chlorides was developed. The reaction could proceed smoothly in air within 3 h under optimized reaction conditions(1 mol% of palladacycle, 4 mol% of Xphos, 2.0 equiv K2CO3 in xylene/H2O), affording the corresponding internal alkynes in mostly good to excellent yields. Remarkably, this result represents the first successful examples of this type of decarboxylative cross-coupling using electron-poor, electron-neutral and even inactive sterically hindered electron-rich aryl chlorides as the starting materials(Scheme 1).2.Synthesis of Diarylalkynes via Tandem Sonogashira/Decarboxylative Reaction of Aryl Chlorides with Propiolic AcidA facile and efficient protocol for one-pot synthesis of diarylalkynes via tandem Sonogashira/decarboxylative coupling has been developed. The remarkable features of this reaction include using commercially available aryl chlorides as starting materials and taking the propiolic acid instead of expensive terminal alkynes as an acetylene source(Scheme 2).3.Copper-Mediated Oxidative Decarboxylative Coupling of Arylpropiolic Acids with Dialkyl H-phosphonates in WaterAn efficient, mild and generally applicable protocol for copper-mediated oxidative decarboxylative coupling of aryl-propiolic acids with dialkyl H-phosphonates in water has been developed. Note that the reaction could proceed smoothly under air at relatively low temperature(60 °C), and the addition of isopropanol could successfully suppress the decomposition of dialkyl H-phosphonates in water(Scheme 3).4.Direct Decarboxylative Alkynylation of α, α-Difluoroarylacetic Acids under Transition Metal-Free ConditionsAn efficient and generally applicable protocol for decarboxylative coupling of α, α-difluoroarylacetic acids with ethynylbenziodoxolone(EBX) reagents has been developed, affording α,α-difluoromethylated alkynes bearing various functional groups in moderate to excellent yields. Remarkably, this potassium persulfate (K2S2O8) promoted reaction employed water as a solution under transition metal-free conditions, thus providing a green synthetic approach to α,α-difluoromethylated alkynes(Scheme 4).5. Palladium-Catalyzed Oxidative Deacetonative Coupling of 4-Aryl-2-methyl-3-butyn-2-ols with H-phosphonatesAn efficient and general applicable protocol for palladium-catalyzed oxidative deacetonative coupling of 4-aryl-2-methyl-3-butyn-2-ols with dialkyl H-phosphonates has been developed. This methodology provides a new and practical route to alkynylphosphonates using the inexpensive 4-aryl-2-methyl-3-butyn-2-ols as the alkyne sources. This reaction could also be performed from aryl bromides, 2-methyl-3-butyne-2-ol and dialkyl H-phosphonates using the cheap 2-methyl-3-butyne-2-ol as an alkyne source(Scheme 5).