N?Heterocyclic Carbene-Catalyzed Synthesis Of Dihydropyranone And Dihydropyridone Derivatives

As important six-membered heterocyclic compounds,dihydropyranone and dihydropyridone are widely distributed in various natural products and are important skeletons of many bioactive molecules.As a new technology,organic small molecule catalysis has many different characteristics from metal catalysis and has gradually become one of the most influential directions in the field of drug synthesis and organic chemistry.N-heterocyclic Carbene is a kind of simple,green,mild and non-toxic organic small molecule catalyst.Because of its high reactivity,it has an important application in the synthesis of various heterocyclic compounds,and has gradually produced a huge influence in the field of organic synthesis.It can catalyze a variety of different reactions under the action of bases,especially in the process of reacting with some aldehydes,often show special ability.At present,the use of N-heterocyclic Carbene small molecular catalysts to construct dihydropyranone and dihydropyridone compounds has attracted extensive attention from synthesis experts.In this thesis,cycloaddition reaction based on N-heterocyclic Carbene is studied.Three methods for the synthesis of dihydropyranone and dihydropyridone scaffolds have been developed byα,β-unsaturated acyl azolium and enolate intermediates.This thesis mainly includes the following chapters:Chapter 1: The development history,main structure and important intermediates of N-heterocyclic Carbene are introduced.The research progress of N-heterocyclic Carbene involved in the construction of pyranone and pyridone was introduced.The specific performance is as follows: N-heterocyclic Carbene reacts with carbonyl compounds to form intermediates with different electrical properties,These intermediates construct novel C-O and C-N bonds through intramolecular cyclization,[3 + 3] cyclization and [4 + 2] cyclization.Thus,pyranone and pyridone molecules are constructed.Chapter 2: A method for the [3 + 3] cycloaddition of α-bromoenals and5-aminopyrazole catalyzed by N-heterocyclic Carbene was developed.The scheme has the advantages of simple operation,good functional group compatibility,and can obtain pyrazole[3,4-b]pyridine-6-one with high-yield and high-selectivity in the mild conditions.Chapter 3: A method was developed for the cyclization of α-bromoenals andβ-nitroenylamine catalyzed by N-heterocyclic Carbene.It can synthesize pyrimidine[1,2-a]pyridine-6-one efficiently.In this reaction,the generated dihydropyridone product contains a nitro group,which can be easily converted into a variety of different functional groups,which is extensively applied in the field of pharmaceutical synthesis.Chapter 4: A cycloaddition reaction of α-chloral and 1-hydroxy-2-naphthalinol catalyzed by N-heterocyclic Carbene was developed.In this reaction,the enantioselectivity of the reaction can be controlled by using α-chloral and 1-hydroxy-2-naphthalinol,which are easily prepared,as the starting materials,with the synergistic catalysis of N-heterocyclic Carbene and Br?nsted acid,and the required benzodihydrocoumarin derivatives can be synthesized efficiently with medium to good yield.