Asymmetric Synthesis Of Lactams Via N-Heterocyclic Carbene Catalysis

Lactams are core skeletons that have been found in a variety of natural products and pharmaceutical compounds which show broad range of promising biological activities,as a consequence,the synthesis of such compounds in a catalytic and asymmytric manner has attracted considerable attention.On the other hand,recently N-heterocyclic carbene(NHC)has emerged as a powful organocatalyst in asymmetric catalysis due to its unique ability to activate carbonyl compounds.In this thesis,we mainly explore the generation of the nucleophlic a-carbon of aliphatic aldehydes via NHC catalysis,which then undergo asymmetric[2+n]cycloaddition reations with unsaturated imine derivatives to afford lactam compounds bearing potential biological activities in good yields and high stereoselectivies.There are three chapters in this thesis.Chapter 1,first briefly introduced the synthetic methods of lactams and the development of NHC in organic catalysis,then intensively discussed the synthesis of?-lactams,?-lactams and ?-lactams via NHC catalysis.Chapter 2,mainly investigated the NHC-catalyzed formal[2+8]annulation reaction of a-chloro aliphatic aldehydes with azaheptafulvenes to deliver cis-cycloheptatriene-fused y-lactams with good yields,moderate to good diastereoselectivies,and excellent enantioselectivies.This higher order cycloaddition reaction can be readily expanded to gram scale,and the products could be further transformed to other useful compounds via simple operations.Chapter 3,mainly investigated the oxidative NHC-catalyzed formal[2+4]annulation reaction of aliphatic aldehydes with oxindole-derived ?,?-unsaturated ketimines,affording spirocyclic oxindole ?-lactams with good yields,moderate diastereoselectivies,and good to excellent enantioselectivies.Further experiments revealed that the configurations of the double bond on the imine substrate had no impact on the stereoselectivities of the product.