Asymmetric [2+x] Annulation Reactions Of Aliphatic Aldehydes Via Oxidative N-heterocyclic Carbene Catalysis

In 1943,Ukai and co-workers first reported a benzoin condensation reaction of aryl aldehydes catalyzed by Vitamin B₁ which contains a thiazolium salt unit.Ever since then,N-heterocyclic carbenes?NHCs?has emerged as a powerful organocatalyst in modern organic synthesis.After several decades'rapid development,nowadays,NHCs not only mediate the traditional benzoin and Stetter reaction by turning the carbonyl carbon of aldehydes to an acyl anion intermediate,but more importantly,they can promote the direct asymmetric functionalization of the ?,?,?,and ?-carbon of various carbonyl compounds including aldehydes,ketenes,carboxylic acids,acyl halides,and esters.In this thesis,we mainly focus on the NHC catalyzed in situ generation of enolate intermediates via direct activation of the ?-carbon of aliphatic aldehydes under oxidative reaction conditions,and the use of those enolate intermediates to develop highly stereoselective [2+x]annulation reactions for the construction of various chiral biologically valuable polyheterocyclic compounds.There are three chapters in this thesis.Chapter 1 first briefly introduced the direct?-carbon activation of aliphatic aldehydes in organocatalysis and the development of NHC as an organocatalyst,then intensively discussed the NHC catalyzed generation of enolate intermediates from direct?-carbon activation of various carbonyl compounds.Chapter 2 mainly investigated an oxidative NHC catalyzed enantioselective[2+2]annulation reaction of aliphatic aldehydes with isatin-derived ketimines to afford spirooxindole ?-lactams bearing two vicinal stereogenic centers with moderate to good yields,good diastereoselectivities and excellent enantioselectivities.This process achieved the direct ?-carbon functionalization of simple aliphatic aldehydes under mild conditions via NHC catalysis.Chapter 3 documented an asymmetric[2+3]annulation reaction of aliphatic aldehydes with azomethine imines enabled by oxidative NHC catalysis,furnishing bicyclic pyrazolidinones bearing two vicinal tertiary stereogenic centers with moderate to good yields,excellent diastereoselectivities and enantioselectivities.Two five-membered transition states were proposed to rationalize the stereochemical outcome.