Studies On The Construction Of Chiral Nitrogen-containing Heterocyclic Compounds By Asymmetric Cycloaddition Of Azomethine Ylides

Based on the great value of chiral nitrogen-containing heterocyclic compounds in many fields such as organic synthesis and innovative drug research and development,in this paper,we devoted to developing the asymmetric[3+3],[3+2]cycloaddition of azomethine ylides to construct chiral nitrogen-containing heterocyclic compounds with potential pharmacological activities,research mainly includes the following two aspects:(1)Iridium-catalyzed asymmetric[3+3]cycloaddition of aromatic branched allyl alcohols with azomethine ylides to form poly substituted chiral tetrahydroisoquinolines;(2)Copper-catalyzed asymmetric[3+2]cycloaddition of azomethine ylides with racemic 2-ester aziridines to form chiral azabicyclo[3.1.0]hexane derivatives.In the first part,iridium was used to catalyze the asymmetric allyl alkylation reaction of aromatic branched allyl alcohols with azomethine ylides,then CF3CO2H promoted the intramolecular Pictet-Spengler reaction and afforded the polysubstituted chiral tetrahydroisoquinolines in one step with moderate to excellent yields(up to 96%)and stereoselectivities(6:1-16:1 dr,94->99%ee).This method could also be used to synthesize other piperidine fused ring compounds.In the second part,the Cu(MeCN)4BF4/(R)-Fesulphos was used to catalyze the asymmetric[3+2]cycloaddition of azomethine ylides with racemic 2-ester aziridines to form chiral azabicyclo[3.1.0]hexane derivatives with excellent yields(up to 49%)and enantioselectivities(up to>99%).When the 3-substituent of the racemic aziridines was aryl,it could also realize the asymmetric kinetic resolution and achieve the optically pure azirines.