| Nitrogen-containing compounds occupy an important position in modern organic chemistry because of their ubiquity in nature.For example,amino acids,linear nitrogen-containing compounds,that is essential for growth and normal metabolis.nitrogen-containing heterocyclic compounds as an important branch of heterocyclic compounds,which are extensively used in agrochemical,medicinal,dye,and ligand chemistry.In this thesis,a series of bioactive nitrogen-containing compounds have been constructed through metal-catalyzed tandem reaction of N-propargylic sulfonylhydrazones.Five chapters are included.Chapter 1:In this chapter there are two aspects:the hydrazone chemistry and domino reactions.Chapter 2:5,6-Dihydropyrazolo[1,5-c]quinazolines,as a kind of important N-containing heterocyclic compounds,have been used as antagonists for a number of biological targets such as adenosine receptor,AMP A,kainate and excitatory amino acid receptor,and Gly/NMDA receptor,as well as inhibitors for phosphodiesterase 10A and IKK.Although several tactics have been developed for the synthesis of the tricyclic scaffolds,they usually rely on the functionalization of substrates with the pyrazole ring preinstalled.Strategies that form both rings of the tricyclic scaffold in a single operation have not been reported.Transition metal-catalyzed intramolecular cyclization of 2-alkynyl anilines to prepare indoles has been well-studied.In this chapter,we treated 2-alkynyl aniline 1 that contains a propargylic hydrazone moiety with a Au(I)catalyst,none of the indole product was obtained.Instead,5,6-dihydropyrazolo[1,5-c]quinazoline 2 was isolated in moderate to excellent yields(Scheme 1).In addition,the synthetic utility of this method is demonstrated through the synthesis of a potential Eg5/Kinesin spindle protein inhibitor.Scheme 1Chapter 3:As a kind of important N-containing heterocyclic compounds,pyrazolo[5,1-a]isoquinoline derivatives,which incorporate both isoquinoline and pyrazolo[1,5-a]pyridine cores,have been used as inhibitors for PTP1B,TC-PTP,CDC25B,and phosphodiesterase 10A,as well as antagonists for a number of biological targets such as CB1 cannabinoid and dopamine D4 receptors.In the past decades,a lot of methods have been developed for the synthesis of these tricyclic scaffolds and one of the most frequently used methods involves the functionalization of substrates with the pyrazole ring pre-installed.Strategies that form both rings of the tricyclic scaffolds through tandem intramolecular cyclization have not been disclosed.As a part of our studies on propargylic sulfonylhydrazones chemistry,N-propargylic sulfonylhydrazones 1 that contain two triple bonds were synthesized and treated with a Cu(II)catalyst,the pyrazolo[5,1-a]isoquinolines were observed as dominant products via H2O-asssisted highly regioselective bicyclization of the N-propargylic sulfonylhydrazones(Scheme 2).In addition,the synthetic utility of this strategy is demonstrated through the synthesis of a potential PTP1B,TC-PTP,CDC25B inhibitor.Chapter 4:The prevalence of the pyrazole unit in medicines,agrochemicals,dyes,and ligands has inspired the development of a lot of efficient strategies for their preparation.And recent drug discovery efforts disclosed new approaches allowing for the efficient assembly of 4-substituted pyrazoles are in high demand.N-propargylic sulfonylhydrazones are useful synthons with multi-reactive sites in organic synthesis.Due to the high reactivities,intermolecular reaction of N-propargylic sulfonylhydrazones is still an attractive yet challenging task.Recently diaryliodonium salts and acetals have been used as efficient electrophilic reagents because of their low toxicities and excellent selectivities.As part of our ongoing efforts in propargylic sulfonylhydrazone chemistry,we proposed that the two electrophilic reagents might activate the triple bond for nucleophilic attack by the hydrazone imine nitrogen atom,leading to the cyclized products.Thus,we treated 1 with corresponding reaction conditions,and the pyrazoles 3 and dihydro-pyrazoles 2 were obtained in moderate to good yields(Scheme 3).Scheme 3Chapter 5:a-Amino ketones are extremely important scaffolds in pharmaceuticals and in modern organic chemistry.Thus,new approaches allowing for the efficient assembly of these skeletons are in high demand.In this chapter,we reported the efficient CS2CO3-promoted synthesis of a-amino ketones through a novel base catalyzed N-N bond cleavage process using a-haloketones,aldehydes,and hydrazines as starting materials in one pot(Scheme 4).Compared with previous procedures for the N-N bond cleavage of hydrazones,this novel N-N bond-cleavage was characterized by high yields,mild reaction conditions,and a broad variety of substrates.And a deuterium-labeling experiment dsclosed that the carbonyl group play a key role in this novel N-N bond-cleavage process.Scheme 4... |
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