N-heterocyclic Carbene Catalyzed Oxidative Esterification And ?-functionization

N-Heterocyclic carbene(NHC)as organocatalyst,has diversified structures and can generate multiple reaction modes.NHC catalysis has been widely used in the synthesis of numerous biologically and medically i mportant heterocyclic compounds.In recent years,NHC-catalyzed generation of ?,?-unsaturated acylazolium intermediates and their subsequent reactivity with bis nucleophiles has received increasing attention.A wide variety of bisnucleophiles can react with the ?,?-unsaturated acylazoliums to form various five-to seven-membered heterocycles and carbocycles.This dissertation described an NHC-catalyzed oxidative esterification and ?-functionization reaction.In the first part,it elucidated an NHC-catalyzed intermolecular oxidative esterification reaction.By using a tandem isomerization/cyclisation strategy,a series of medically important 2-substituted benzoxazinones were synthesized.This catalytic system are compatible with multiple functional groups an d allows for rapid assembly of a wide scope of valuable benzoxazinones from using commercially available substrates under mild conditions.To the best of our knowledge,this is the most widely applicable method for the preparation of benzoxazinones.The mild condition and low catalyst loading of the system renders it as a very practical method for drug synthesis.For example,our method was used to the preparation of anticancer drug molecule Erastin.Then,it displayed an unprecedented NHC-catalyzed enantioselective ?-amination of ?-bromoenals with o-benzodiamines by utilizing a proton-shuttling strategy.This formal [4+3] annulation protocol yielded the corresponding 1,5-benzodiazepines in high yield and excellent enantiomeric excess.The proton transfer step was concerned to play a crucial role in the annulation process.The optically active 1,5-benzodiazepines obtained by our method as building blocks and pharmacophores provided potentially alternative routes in the synthesis of valuable molecules in drug discovery.At last,an NHC-catalyzed ?-indolation of ?-bromoenals with indol nucleophile was developed.This is the first report of NHC-catalyzed nonannulation ?-functionization reaction via ?,?-unsaturated acylazolium.Remote asymmetric ?-functionization of ?,?-unsaturated acylazolium intermediates remains to be a significant challenge.