Study On Asymmetric Cyclization/Nucleophilic Tandem Reaction Of Diazophosphonate With O-Alkynyl Acetophenone Catalyzed By Chiral Bis(Oxazoline)/AgOTf

Isochroman,as a core skeleton,widely exists in various natural products and drug molecules.At the same time,phosphonate plays an important role in improving the biological activity or efficacy of drugs as a functional group.If phosphonate group can be introduced into the isochroman skeleton,more compounds with the isochroman skeleton can be prepared,more drug molecules with potential biological activity can be provided for the pharmaceutical industry,and it has great research value and application prospect.A series of chiral bisoxazoline ligands were designed and synthesized in this paper.the complexes with metal salts were used to catalyze asymmetric cyclization/nucleophilic tandem reaction of o-alkynyl acetophenone and diazophosphonate.Through the screening of catalysts and optimization of reaction conditions(metal salt,solvent,temperature,concentration,catalyst loading,etc.),the results showed that when chiral bisoxazoline ligandswith adamantyl substitution in 4,4’ position / AgOTf was used as catalyst,excellent yield(up to 98 %)and good ee value(up to 94 %)could be obtained by the reaction,and a series of isochrome derivatives were synthesized.At the same time,the absolute configuration of the product was determined and the product was derivatized.