Studies On The Bifunctional Building Blocks And N,N'-Cyclic Azomethine Imine Ylides In The Construction Of Nitrogen- And Phosphine-Containing Heterocycles

Organophosphonic heterocycle and C3-azacyclic-oxoindole are the core skeletons in many natural and non-natural compounds with biologically activities.Therefore,developing efficient methods to construct these skeletons are of great significance for the discovery of new drugs.Our researches in this dissertation are based on two building blocks of o-vinylphosphonylated salicylaldehydes and isatin-derived N,N?-cyclic azomethine imines,which included the stereoselective construction of 3,4-dihydrophosphoruscoumarin skeleton and the synthesis of C3-azocyclic-oxoindoles.An efficient anti-selective synthetic strategy of 3,4-disubstituted dihydrophosphacoumarin skeleton has been established by using o-vinylphosphonylated salicylaldehydes as bifunctional building blocks with tetrahydroisoquinolines via aza-Michael/Aldol tandem reactions,which provided various 3-aminomethyl-4-hydroxy-phosphadihydrocoumarin compounds under simple and catalyst-free conditions in considerable yields(22 examples,67-89%).The methods for the syntheses of various C3-azocyclo-oxoindoles were established by isatin-derived N,N?-cyclic azomethine imines as building blocks:(1)A reaction of isatin-derived N,N'-cyclic imide yelides underwent isomerization then Michael added to tetraethyl bisphosphate ethylene(VBP)in the presence of base catalysis was unexpectedly discovered,and the reaction was developed into a method for the construction of skeleton containing bisphosphonate/?-aminophosphate/3,3'-disubstituted oxindole(13 examples new compounds were synthetized in 78-88% yields).(2)The isomerization of isatin-derived N,N'-cyclic azomethine imines was developed into a synthetic method for 3-hydroxypyrazoles or C3-azacyclic-oxoindole derivatives(17 examples new compounds were synthetized in 70-96% yields).(3)A chitosan-catalyzed three-component Knoevenagel/Michael tandem reaction in water was developed by using the isomerization product of N,N'-cyclic azomethine imines as a synthetic block,and 3,3'-disubstituted oxindoles bearing two different heterocycles of chromene and pyrazolone at the C3 position were were synthetized in75-97% yields.