Studies On Developing Novel Synthesis Methods Toward Nitrogen-or Oxygen-containing Heterocycles Based On Rhodium-azavinylcarbenes Involved Or Iodine-catalyzed Reactions

Nitrogen-or oxygen-containing heterocycles as important structural motifs are often found in a variety of pharmaceuticals and biologically active natural products.Their impressive biologically actives constantly catalyze the discovery and development of new pharmaceutical synthesis methodologies to build these structures.This dissertation mainly focuses on developing new synthetic methods and strategies for the rapid and reliable construction of these heterocyclic frameworks from easily available precursors,including four main parts:1)developing a new method for synthesis of 2,5-epoxy-1,4-benzoxazepines based on the finding that 4-oxazolines are easily to hydrolyze;2)developing a novel method for divergent synthesis of 3,6-disubstituted-and 3,5,6-trisubstituted-1,2,4-triazines based on the competitive O-H insertion of rhodium-azavinylcarbenes with N-acylhydrazones;3)developing a new method for synthesis of indigo analogues based on the new reactivity of rhodium-azavinylcarbenes with secondary amides;4)developing a new method for synthesis of dihydrobenzo(naphtho)furans based on our strategy-new designed C1 synthon.In the first part,we found that rhodium-azavinylcarbenes reacted smoothly with aldehydes with excellent chemoselectivity in the Rh-catalyzed reactions of triazoles and salicylaldehydes.Then the reversible ring opening intermediate of 4-oxazoline generated from rhodium-azavinylcarbene and aldehyde was trapped by intramolecular phenolic hydroxyl to afford natural product-like oxa-bridged 2,5-epoxy-1,4-benzoxazepines in good yields.Thus,a novel and efficient route for the construction of these natural product-like derivatives has been developed.When 2-methanesulfonamidyl benzaldehyde was used instead of salicylaldehydes,oxazoles were obtained in moderate yields.In the second part,on the basis of unexpected finding of competitive O-H insertion of rhodium-azavinylcarbenes with N-acylhydrazones,a novel and facile protocol for the divergent synthesis of 3,6-disubstituted-and 3,5,6-trisubstituted-1,2,4-triazines with excellent chemoselectivities in moderate to good yields under mild conditions has been developed through O-H insertion/intramolecular rearrangement/p-TsOH or DBU-catalyzed intramolecular cyclization and oxidation reaction.In this tadem reaction,N-acylhydrazones was used as aze-[3C]or[4C]synthons and 1-sulfonyl-1,2,3-triazoles was used as aze-[2C]synthons differing from the traditional to construct azaheterocycles.Futher transformations of the product could provide structurally important azaheterocycles such as pyridine or pyridazinone-fused triazine in excellent yields.In the third part,new reactivity of rhodium-azavinylcarbenes with secondary amides was discovered and based on this,a novel and facile protocol for constructing natural product-like indigo analogues via rhodium-catalyzed reaction of 1-tosyl-1,2,3-triazoles with isatins has been established.Notably,the carbon-carbon bond was first formed when rhodium-azavinylcarbenes reacting with secondary amides,and it is crucial for this transformation without a hydrogen on the ?-position of secondary amides.In the fourth part,new reactivity of 1,3-dicarbonyl compounds as C1 synthon with nucleophilic and electrophilic properties rather than as normal 1,1-bisnucleophiles was developed.And based on this,a formal[4+1]annulation has been developed to synthesis of biologically important dihydrobenzo(naphtho)furans via I2/TBHP promoted tandem Michael addition/oxidative annulation of readily available 2-(2-nitro-vinyl)-naphthol or 2-(2-nitro-vinyl)-phenols with various malonate esters and its analogues.The reaction path way was testified.This novel strategy makes nucleophilic/electrophilic C1 synthon more available than the widely used ones which need a necessary pre-functionalization step.Importantly,this strategy-new designed C1 synthon can also be used in other cycloaddition reactions.