Pd/Phosphoramidite Thioether Complex-Catalyzed Asymmetric N-allylic Alkylation Of Hydrazones And Allylic Acetates

Palladium-catalyzed asynmetric iV-allylic alkylation reaction is one of the important strategies for the construction of C-N bonds.With the continuous development of such reactions,many asymmetric N-allylic alkylation reactions involving nitrogen nucleophiles have been studied.However,the asymmetric N-allylic alkylation reaction in which acylhydrazones are involved as a nitrogen nucleophile has rarely been reported.Besides,chiral N-acylhydrazones are an important precursor for the synthesis of chiral amines.Therefore,the synthesis of chiral N-acylhydrazones by palladium-catalyzed asymmetric N-allylic alkylation has certain significance.On the other hand,our group designed and synthesized a series of chiral phosphoramidite/thioether ligands in the early stage.These P,S-ligands exhibited good results in transition metal-catalyzed asymmetric[4+2],[3+2]cycloaddition reactions and asymmetric allylic alkylation of indole.Based on the previous work,this paper applies these Pd/Phosphoramidite Thioether Complex to the asyumetric N-allylic alkylation reaction of acylhydrazones.We synthesized a series of different aldehyde-derived hydrazones and successfully applied these Pd/Phosphoramidite Thioether Complex to the asymmetric N-allylic alkylation of acylhydrazones and allylic acetates.After screening ligands and other reaction conditions,we have found two comparatively dominant chiral P,S-ligands Lla and Lie,their palladium complexes could catalyse the reaction to form the products with different absolute configurations,respectively.The reaction allows for the prepration of^-substituted hydrozones in the S configuration with isolated yield of 62-97%and ee value of 40-99%.And the reaction allows for the prepration of N-substituted hydrozones in the R configuration with isolated yield of 84-95%and ee value of 82-91%.Subsequently,we determined the absolute configuration of the product by X-ray single crystal diffraction.The carbon-carbon double bond of the product was reduced in a derivatization experiment.At the same time,the N-N bond cleavage of the product was also achieved,and a chiral allylamine was synthesized.