Asymmetric Oxidative Enolate Activation Of Aliphatic Aldehydes Catalyzed By Nitrogen Heterocyclic Carbene

In the field of organic small molecule catalysis,N-Heterocyclic Carbene has the advantages of good selectivity,environmental friendliness and mild reaction conditions,which has received widespread attention in the world and has been widely used after more than 20 years of vigorous development.When carbene reacts with aliphatic aldehydes,its carbonyl carbon will preferentially be activated into an Breslow intermediate to occur Benzoin reaction or Stetter reaction.Secondly,theα-carbon of the aliphatic aldehyde can also be functionalized through the oxidative enolate activation processes in the presence of various external oxidants.However,among these classic oxidants,such as DQ,NFSI,etc.,which are more expensive,and the scope of the electrophiles that have been used under these conditions is still limited.It is still attractive and significant to search for facile and economic strategies for the efficient oxidative enolate activation of aliphatic aldehydes,especially in an enantioselective fashion.In this thesis,DL-proline was used as the aldehyde chlorination catalyst in the presence of N-chlorosuccinimide(NCS)and can effectively promote the formation of the α-chloroaldehyde.Then,the chiral NHC can react with the α-chloroaldehyde to give the azolium enolate intermediate,which can then react with different electrophiles through a [2+4] cycloaddition reaction with high yield and high stereoselectivity with different electrophiles to afforded a variety of chiral spirooxindole compounds / pyranone indole compounds with potential bactericidal activity.This thesis is mainly described from two parts: the first part is to introduce the main strategies for α-carbon activation of aliphatic aldehyde,and research status of the catalytic activation for α-carbon of carbonyl compounds to form enolate intermediates at home and abroad.The second part is to design and synthesize a series of reaction substrates such as oxindole-derived pyrazolinone and oxindole-derived α,β-unsaturated ester,and to establish and screen the asymmetric [2+4] cyclization reaction catalyzed by NHC,so as to achieve α-carbon direct functionalization of the aliphatic aldehyde in cost-effective,green and simple fashion.And synthesize a series of chiral spirooxindole compounds and pyranone indole compounds with moderate to excellent yield,enantio-and diastereoselectivities.