Studies On The Sythesis Of Isoxazoles, Parazoles, And Chalcones From Terminal Alkynes

Isoxazoles, pyrazoles, and chalcones represent an interesting structural motif found frequently in various bioactive molecules and natural products, having been used in medicines, pesticides, and herbicides. The development of convenient and efficient methods for the synthesis of isoxazoles、 pyrazoles, and chalcones has attracted considerable attention. Until now, methods for synthesis of isoxazoles, pyrazoles and chalcones frequently suffer from drawbacks, such as multistep reactions, harsh reaction conditions, and low atom economy.In the present study, a simple method was developed for synthesis of3,5-disustituded isoxazoles via intermolecular Cope-type hydroamination of1,3-dialkynes and hydroxylamine in the absence of metal catalyst. Our research demonstrated that under optimized conditions (1,3-dialkynes0.4mmol, hydroxylamine hydrochloride1.0mmol, NEt31.6mmol, DMSO3.0mL,110℃,20h), symmetric1,3-dialkynes reacted with hydroxylamine and produced single product. When unsymmetric1,3-dialkynes reacted with hydroxylamine, the difference between substituents R1and R2influenced greatly on the reaction results. When substituents R1and R2were aryl groups, there were two products. The ratio of two products depended on the Hammett substituent constants of substituents on aryl. When R1was an aryl group which containing electron-withdrwing substituent and R" was an alkyl group, there was only one product. The new method for synthesis of3,5-disustituded isoxazoles via one-pot two steps reaction of terminal alkynes was developed. This protocol showed good tolerance for aryl alkynes, alkyl alkynes, and heterocyclic alkynes, the best yield was94%.In the present study, a simple method was developed for synthesis of3,5-disustituded pyrazoles via intermolecular Cope-type hydroamination of1,3-dialkynes and hydrazine in the absence of acid, base, and metal catalyst. Our research demonstrated that under optimized conditions (1,3-dialkynes0.4mmol, hydrazine1.2mmol, DMSO3.0mL,60℃,20h), symmetric1,3-dialkynes reacted with hydrazine and produced single product. When unsymmetric1,3-dialkynes reacted with hydrazine, the difference between substituents R1and R2influenced greatly on the reaction results. When substituents R1and R2were electron-donating groups, there were two products. The ratio of two products depended on the ability of electron-donating groups. When R1was a electron-withdrawing group and R2was a electron-donating group, there was only one product. The new method for synthesis of3,5-disustituded pyrazoles via one-pot two steps reaction of terminal alkynes was developed. This protocol showed good tolerance for aryl alkynes, alkyl alkynes, and heterocyclic alkynes, the best yield was92%.In the present study, palladium-catalyzed carbonylative addition of aryl halides to terminal arylalkynes was developed, this was a new method to synthesize chalcones. Under optimized conditions (PdCl210mol%, DPPB20mol%, aryl halide0.5mmol, arylalkynes1.5mmol, CO20atm, DMF3.0mL,120℃), this protocol showed good tolerance for aryl halides and terminal arylalkynes, the best yield was91%. Our research demonstrated that bidentate ligand and coordinative solvent played a key role in the reaction, DPPB was the best ligand and DMF was the best solvent; the hydrogen of carbonylative addition product came from terminal alkyne, and hydrogen oxide played a role of transfering hydrogen from terminal alkyne to product.