Palladium-catalyzed CH Activation/decarboxylation Coupling Reaction Was Used To Construct Functionalized Azole Derivatives

Transition metal-catalyzed decarboxylative coupling is one of the most efficient synthetic methods for selective C–C bond formation,and it has attracted attention from scientists worldwide.The key advantage of this reaction is that it draws on stable and easily prepared carboxylic acids as the coupling substrates.Compared with the traditional coupling reaction,this kind of methods avoids the use of stoichiometric organometallic reagents and produces CO₂ as the waste instead of toxic metal salts,thus having less environmental pollution.In this paper,palladium-catalyzed decarboxylative coupling of a sieries of carboxylic acids,such as 1,4-disubstituted 1,2,3-triazole carboxylic acid,?-oxocarboxylic acids and oxazole or thiazole carboxylic acid,were studied to construct functionalized azole derivatives.The main contents are as follows:Chapter 1 reviewed the recent progress in transition metal-catalyzed decarboxylative coupling,including the decarboxylative aromatization and decarboxylative acylation reactions of aryl carboxylic acids,alpha-ketonic acids and heterocyclic carboxylic acids via carbon-hydrogen bond activation for direct construction of carbon-carbon bond.Meanwhile,we have also described the applications of azoles containing compounds in various fields such as organic synthesis,materials,medicinal chemistry and food additives.Chapter 2 developed a selective decarboxylative/C–H activation methodology that allows the coupling of a variety of aryl acids with benzo heterocycles directed by the 1,2,3-triazole ring based on a Pd-catalyst system.The reaction had good functional group tolerance,and a series of 1,2,3-triazole derivatives with thiazole or oxazole heterocycles can be obtained in high yield.In addition,we performed some controlled experiments which fully verified the mentioned function.Based on the experimental results and literature reports,a tentative mechanism of the reaction was described.In Chapter 3,an efficient palladium-catalyzed decarboxylative C–H acylation is explored using?-oxocarboxylic acids as the acyl source directed by 1,2,3-triazole ring.The resulted coupling products were obtained in 47-81%yield via Pd-catalyzed process.This method enriches the applications of C-H activation and decarboxylative couping,making it a valuable and practical approach for the synthesis of functional 1,2,3-triazoles bearing diaryl ketone skeleton.Several control experiments suggested that a free radical process can be excluded in this reaction.The result of kinetic isotope effect is k_H/k_D=2.6,which proves that the C–H bond cleavage may be the rate-limiting step.In Chapter 4,the decarboxylative aromatization of 2-aryl-4-methyl oxazole-5-carboxylic acids or 2-aryl oxazole-4-carboxylic acids with polyfluorobenzenes were studied.The optimal reaction conditions were determined by exploring different catalysts,bases,ligands and solvents.The heterocyclic derivatives containing an oxo?thiazole?ring were obtained under the optimal conditions by extending the substrates scope of the two types of carboxylic acids.At the same time,on the basis of literature reports and experimental observations,a possible reaction mechanism of this reactin was proposed.In Chapter 5,the work of palladium-catalyzed decarboxylative arylation and acylation of aryl carboxylic acids,?-oxocarboxylic acids and heterocyclic carboxylic acids were summarized.The outlooks were also proposed.