Palladium-catalyzed Tandem Enantiose Lective Ring-opening/cyclization Reactio N Of Cyclobutanones

Quaternary carbon chiral centers widely exist in bioactive natural products and pharmaceutical molecules,and different configurations may lead to different biological activities.Therefore,the enantioselective synthesis of compounds containing quaternary carbon chiral centers is one of the eternal topics in organic synthesis.Compared with the five-membered ring and six-membered ring,the ring tension of four-membered ring compounds increases significantly due to the decrease of bond angle.With the influence of ring tension and carbonyl group,cyclobutanones are more likely to open and expand rings with electrophilic reagents when they undergo ketoenol tautomerism.The strategy of constructing compounds containing quaternary carbon chiral centers with cyclobutanones has attracted extensive attention of chemists.The d-orbitals of transition metals can provide empty orbitals or lone pair electrons and have strong redox properties,so they are widely used in organic synthesis.In recent years,transition metals such as rhodium,palladium and nickel have been used to catalyze the asymmetric synthesis of cyclobutanones,and many reports have been reported on the highly selective construction of compounds containing quaternary carbon chiral centers.Among them,the palladium catalyst has been widely used because of its high catalytic efficiency,wide substrate applicability,and moderate reaction temperature.Although palladium-catalyzed asymmetric synthesis of cyclobutanones has been reported,only a few of them are coupled with simple molecules.So far,it has not been reported that the alkyl metal intermediates produced by the asymmetric reaction of cyclobutanones can further catalyze the cyclization of other molecules.Therefore,we have studied the palladium-catalyzed enantioselective cyclization of cyclobutanones with phenylethynylene derivatives which have ortho nucleophilic substituents,and a series of compounds containing indanone substituents with quaternary carbon chiral centers were obtained.(1)In the palladium-catalyzed enantioselective cyclization of cyclobutanones with2-aminophenylethynylenes,we achieved the first alkyl palladium-induced Cacchi reaction in a one-pot manner under mild and low toxicity conditions,with a maximum yield of 90% and > 99.5:0.5 er.Moreover,indanone substituted indoles containing both quaternary carbon chirality and a chiral axis can be obtained by adjusting the structure of phenylethynylene derivatives,and the resulting diastereomers can be separated by column chromatography.The substitution of substituents on the substrates proved that the reaction was universal.(2)In the palladium-catalyzed enantioselective cyclization of cyclobutanones with other phenylacetylene derivatives,we tried a series of other phenylacetylene derivatives which contain nucleophilic substituents,such as the hydroxyl group,carboxyl group,imine.Although we had successfully seperated the indanone substituted benzofuran and isoquinoline derivatives after investigating of reaction conditions,and the enantioselectivity could rise to 95:5 er,the yield can't be further improved,we still need to optimize reaction conditions to construct indanone substituted benzofuran and isoquinoline derivatives with excellent yield and high enantioselectivity.Through the research on palladium-catalyzed enantioselective cyclization of cyclobutanones,we have enriched the reaction types of cyclobutanone compounds,provided a new strategy for expanding the application scope of cyclobutanones,and also provided the possibility for new reaction systems.