Copper-Catalyzed Asymmetric Propargylic Substitution Of ?-Keto Esters

In organic chemistry,the propargylic substitution reaction is one of the most important elementary reactions,especially the copper-catalyzed asymmetric propargylic substitutionreaction plays a very important role in the building the carbon hetroatom bond,chiral cyclic sketelon and carbon-carbon triple bond.After more than tenyears of development,although many nucleophiles has been successfully applied to the propargylic substitution reaction and has made some important progress,the development of this field still has many limitations,such as the number of the chiral catalysts that can be used in this field is limited.The copper-catalyzed asymmetric propargylic substitution and its relevant conversion reactions are still one of the most longstanding and challenging tasks in organic chemistry.At present,the copper-catalyzed asymmetric propargylic substitutionreaction of benzofuranones with phenyl propargylic esters has been reported,but the same reaction of?-keto esters with propargylic esters respectively has no successful example.In this paper,our main task is the synthesis of a series of chiral ligands.The first copper-catalyzedpropargylicsubstitutionreactionof?-ketoesterswith3-Pentafluorophenyl-1-propyne has been successfully developed by using a structurally rigid chiral copper/ketimine P,N,N-ligand catalyst system.A series of benzocyclic?-keto esters that has a quaternary stereogenic center at C2 position was sythesised.Because of the diverse biological activities,the research of how to get the products has important practical value and theoretical significance.By optimizing the conditions such as catalysts?copper salt?alkali additives?reaction temperature and solvent on the enantioselectivity and reaction activity,we can get the best reaction conditions that ligand is?S?-L4,copper salt is Cu?CH₃CN?₄BF₄,alkali additives is ⁱPr₂NEt,the reaction temperature is-20^oC,the solvent is methanol.This reaction has high yields and excellent enantioselectivities under the mild reaction conditions and it can build a quaternary stereogenic center at C2 position.