Palladium-Catalyzed Arylative Dearomatization Reaction Of Indoles

Indoline represent a privileged heterocyclic scaffold that appears in numerous natural compounds and alkaloids,which renders its synthesis a focus of current research effort.Dearomatization of indoles is a reliable and efficient access to the synthsis of indolines.In this dissertation,we have developed palladium-catalyzed intramolecular arylative dearomatizations of indoles based on a Heck process.By trapping with hydride source and bis(pinacolato)diboron,dearomative mono-functionalization of indole via enantioselective reductive-Heck reaction and bifunctionalization through arylation/borylation have been developed respectively.The new enantioselective arylative dearomatization of indoles via reductive-Heck reaction was developed with hydride source as trapping reagent.After the systematic optimization of reaction condition through solvent screening,examination of hydride source,investigation of chrial ligands and so on,the optimal condition was defined as: palladium acetate as catalyst,sodium formate as hydride sources and base,(R)-BINAP as chiral ligand,N-substituted indoles as substrate,the intramolecular asymmetric arylative dearomatization of indoles proceeded efficiently in methanol.The reaction affords 31 examples of optically active tetracyclic indolines bearing C2-quaternary stereocenters centers in modest to good yields(15-89%)with excellent enantioselectivities(22-99% ee).The Pd-catalyzed dearomative bisfunctionalization of indoles via an intramolecular Heck-type mechanism was developed with bis(pinacolato)diboron as trapping reagent.After the systematic optimization of reaction condition through solvent screening,examination of base and reaction temperature,investigation of ligands and so on,the optimal condition was defined as: palladium acetate as catalyst,triphenylphosphine as ligand,bis(pinacolato)diboron as trapping reagent,potassium carbonate as base,N-substituted indoles as substrate,the intramolecular dearomative bisfunctionalization of indoles proceeded efficiently in dichloromethane.The reaction affords 17 examples of borylated indolines in modest to good yields(53-92%)and excellent dr from simple indoles.