Pd-catalyzed Oxidative Isomerization Of Propargylic Acetates

Propargyl compounds are widely exist in the drug,fine organic and natural products.Propargyl compounds,as important substrates and precursor,has a broad application in the synthesis.In the recent years,people have more understanding about its characteristics and application with the extensive research on propargyl compounds.Owing to the?-electron of alkyne,coordination of propargyl esters with?-acid metal generated active intermediates such as carbene and allene.Then preparative transformations of these intermediates structured a serious of C-C/C-X bonds via cyclization,coupling reaction,nucleophilic substitution,isomerization and oxidation.Propargyl esters have aroused a lot of attention due to its unique performance in synthesis.In the past ten years,reactions of propargyl esters catalyzed by transition metal have been widely reported.According to these research,reactions of propargyl esters were divided to three parts:1,2-acyl migration,1,3-acyl migration and nucleophilic substitution.The active carbene and allene intermediate that generated from propargyl esters transformed smoothly in the further reactions.This strategy played important role in the synthesis of alkynes,olefins,allene,diene,ketene and cyclization products.We have developed a mild and highly efficient Pd???/? ??-catalyzed oxidative isomerization of propargylic acetates to furnish?-acetoxy enones.A variety of polysubstituted vinyl acetate derivatives were obtained in good yields with a broad substrate scope,especially,the tetra-substituted alkenyls were obtained in good yields.The reaction mechanism,consisting of trans acetoxypalladation of a triple bond,isomerization,oxidative addition with PhI?OAc?₂ and alkenyl C-OAc bond reductive elimination has been demonstrated on the basis of the results from control experiments.The alkenyl C-O bond reductive elimination is achieved and investigated firstly.We believe that these findings demonstrated in this communication will be helpful for further development of metal-catalyzed formation of polysubstituted?-acetoxy enones.Enyne cyclization reaction is an efficient way to construct ring frameworks,so it is widely used in the total synthesis of biologically active natural products and drug synthesis.Now,the preliminary exploration on the isomerized cyclization and Suzuki coupling reaction of 1,6-enyne ester has carried out.To our surprise,this reaction provided5-member ring allene frameworks which is different from the usual enyne cyclization products—1,4-diene and 1,3-diene.Possible mechanism was a Pd-catalyzed isomerization of propargylic acetates to generate allene-Pd???intermediate,followed by cyclization and Suzuki coupling reaction.