Study On The Construction Of Heterocycles Based On Metal-catalyzed C-H,C-C Bonds Activation

Heterocyclic compounds are important skeleton,which are widely found in natural products,drugs and biologically active molecules.In recent years,transition-metal catalyzed C-H?C-C bonds functionalization to construct heterocyclic compounds has attracted widespread attention.Alkynes and diazo compounds have become the hot topics in the field of organic synthesis because of their multiple reaction sites and high reactivity in organic synthesis,especially in the construction of heterocycles.Thus,utilizing the strategy of C-H?C-C bonds activation with alkynes and diazo compounds to construct heterocycles has attracted our attention.This thesis mainly studies alkynes as C1 or C2 synthon and diazo compounds as C2 synthon by using the strategy of C-H bond functionalization to construct heterocycles.The main research results are achieved as follows:1.Isoquinolinone is an important skeleton in bioactive molecules and natural products.Therefore,building such structure is a hot topic in the field of synthetic chemistry,especially introduction of functional group on the N-chain of isoquinolinone is a challenging topic.Herein,Rh?III?-catalyzed oxazoline-directed C-H bond activation and the formation of isoquinolinone derivatives with diarylalkynes has been investigated.The reaction of alkyne and oxazoline generated an oxazoline cationic intermediate with high activity,which could be captured by the nucleophilic reagent,such as acetate from the reaction system.And then the target compounds were easily obtained through cationic ring-opening of oxazoline ring.An acetylalkoxy group was successfully introduced in the N-chain,which provides chance for further chemical conversion.It is worth noting that copper acetate plays dual roles in this transformation,as an oxidant and a nucleophile.This current protocol features high atom-economy,wide substrates scope and high regioselectivity.2.In the literature,most of alkynes are used as C2 synthon to construct heterocycles.Developing new catalytic system to apply alkynes as a C1 synthon would provide more possibilities for constructing diverse heterocycles.On the other hand,pyrazolidinone is an important structural unit in bioactive molecules.Synthesizing such compounds mainly rely on[3+2]cycloaddition reaction of 1,3-dipoles.Utilizing alkynes as C1 synthon to furnish[4+1]cycloaddition with pyrazolidinones could be easier to introduce useful functional groups,which makes structural modification and chemical transformation conducive.Based on this,[4+1]cycloaddition reaction of pyrazolidinones and propiolates catalyzed by iridium?III?was investigated.The reactions could be completed within 30 min,and novel skeleton of pyrazolo[1,2-a]indazoles could be obtained in up to 99%yields.In this transformation,propiolate was employed as C1 synthon,obviate external oxidant,which meets the requirement of green chemistry.The current protocol features simple operation,mild reaction conditions,high atom-economy,good functional groups tolerance,excellent regioselectivity and short reaction time.3.Indazole is an important skeleton in bioactive molecules,synthesizing such compounds mainly rely on[3+2]cycloaddition reactions.Herein,rhodium?III?-catalyzed[4+1]three component cycloaddition of phenylhydrazine hydrochloride,propiolates and acetone to construct 3H-indazoles was investigated.In this transformation,hydrochloride provides two nitrogen atoms for the target products,and propiolate acts as a C1 synthon.In this process,condensation of phenylhydrazine hydrochloride and acetone first generated hydrazone as a transient directing group.This current protocol features mild reaction conditions,high regioselectivity.Notably,this method provides a new route for the assembly of the 3H-indazoles.4.Direct cleavage of C?C bond of alkynes to construct heterocycles has been developed.However,cleavage of other types of chemical bonds in alkynes is an urgent topic,which can not only retain the inherent chemical reactivity of alkynes,but also provide new chemical reaction sites and enriches the types of heterocycles.Herein,ruthenium?II?-catalyzed the rection of pyrazolidinones with 2-acetylenic via cascade C-H/C-C bond activation to construct 3-alkoxyindoles was investigated.In this reaction,indole ring was first generated,then C?sp³?-C?sp³?bond of alkynes was cleaved by the assistant of NaOAc.Subsequently,alcohol participates to generate the final products.The current protocol features wide range of substrates,good functional group tolerance,excellent regioselectivity and chemical selectivity.Amide and ether group was successfully introduced into the final product,which can be further converted into cyano and other functional groups.5.Recently,the strategy of C-H bond activation to construct heterocycles has been developed,however,most of directing groups need to be prepared in advance which seems to reduce the atom-economy,and external oxidant is also required to complete the catalytic cycle.Thus,generating directing group in situ and obviating external oxidant to activate C-H bond to construct such compounds is desirable.Herein,rhodium?III?-catalyzed three component cascade reaction of phenylhydrazine hydrochloride,?-diazo-?-keto and acetone to construct 1-amino indoles was investigated.In this reaction,hydrazone was first generated in situ starting from phenylhydrazine hydrochloride and acetone as the directing group,and subsequently reacted with?-diazo-?-keto as C2 synthon to obtain a series of diverse N-substituted indoles in up to 87%yields.This protocol features simple operation,excellent regioselectivity,wide range of substrates,high atom-economy,free external oxidant,H₂O and N₂ as the by-product,which meets to requirement of green chemistry.