Palladium-Catalyzed Enantioselective Carboalkoxylation With A Well Designed Side Armed Xu-Phos Ligand

Transition metals combined with chiral ligands catalyze asymmetric reactions,which is an efficient strategy for construction of chiral structural compounds.Therefore,the development of new chiral ligands is truly important.This work focuses on the two aspects,such as designing new chiral phosphine ligands and palladium-catalyzed enantioselective carboalkoxylation to construct chiral tetrahydrofuran.1.Design and synthesis of novel chiral phosphine ligands with side-arm effectCombining the chiral mode of Xu-Phos with palladium,we introduced the sidearm effect strategy to design a series of new chiral tert-butylsulfinamide phosphine ligands.The installed side arm groups include isopropyl,benzyl and naphthyl.On the other hand,various Grignard reagents or Lithium reagents were added to the imine for obtaining a series of new ligands,which enhanced the diversity of our ligands.In order to improve the side-arm effect,we have made further improvement to the ligand.An additional methoxy group was loaded adjacent to the side-arm group to obtain a new type of chiral ligand with more electron density and stronger side-arm effect.2.Palladium-catalyzed highly enantioselective carboalkoxylation of hydroxy alkenesWe applied our own designed chiral tert-butylsulfinamide phosphine ligand with side-arm group combined with transition metal palladium to successfully realize the asymmetric carboalkoxylation of hydroxyolefin at room temperature for construction of chiral tetrahydrofuran.This reaction conditions are very mild,and the substrates have wide applicability.All kinds of aryl bromide,aryl chloride and alkenyl bromide have good compatibility with good yields and excellent enantioselectivities.This reaction can not only realize the expansion of five-membered and six-membered alcohol substrates,but also be applicable to open-chain alcohols.In addition,our ligands can also achieve the formation of quaternary centers.