Pd-catalyzed Coupling Reactions Involving Aryl Sulfonyl Hydrazones And Halogenated Aromatics

Polycyclic compounds have attracted the attention of organic chemists due to their wide application in various fields such as industry,agriculture,and medicine.Arylvinyls and 9-bisarylfluorenes with arylmethane moieties can be found in pesticide intermediates and fluorescent materials;in addition,skeleton compounds represented by substituted pyrazoles have a variety of biological activities,which can be used for pharmacological chemistry,such as antibacterial,antiviral,antitumor,etc.These complicated skeletons require the simultaneous construction of multiple chemical bonds,such as C-C,C-N,C-S bonds,etc.The multi-step synthesis reaction has disadvantages such as complicated operation,cumbersome synthesis process,high cost and long reaction time.The one-pot multi-step reaction method can solve the above problems.As important diazo precursors and nitrogen sources,arylsulfonyl hydrazones are effective reagents for the construction of polycyclic compounds due to their easy availability,low toxicity,and stability.In this thesis,polycyclic compounds represented by arylethenes,arylmethanes and substituted pyrazoles were synthesized by a one-pot multi-step method using arylsulfonyl hydrazones as precursors or intermediates.A series of new methods are provided for the synthesis of polycyclic skeletons,due to the advantages of simple operation,low cost,and environmental friendliness.The research contents are as follows:Firstly,a practical one-pot multi-steps reaction of arylsulfonyl hydrazones with p-bromobenzeneboronic acid for the synthesis of polycyclic compounds was established,involving the formation of one Csp³-Csp²and one Csp²-Csp² bonds in efficient and selective way.27 of polyarylethylenes and 20 of 9-bisarylfluorenes were obtained in good yields.This strategy used cheap and easily available starting materials,isolated-free intermediates,easy operation,a wide substrate scope,good functional group compatibility,and was suitable for large-scale synthesis.It provides a new method for the green and efficient synthesis of functionalized polyarylethylenes and 9-bisarylfluorenes.Secondly,an efficient method for the synthesis of organophosphonic acid esters through the palladium-catalyzed alkenylation of aryl halides withβ-diazo phosphonate derived from arylsulfonyl hydrazones has been established,involing the formation of Csp²-Csp² double bonds.Various（hetero）aryl halides and sulfonyl hydrazones with different phosphate groups could be used as the coulpling partners.32 of 2,2-disubstituted vinyl phosphonate derivatives were obtained in moderate to excellent yields.The strategy uitilized readily available raw materials,simple conditions,a wide substrate scope,and was suitable for gram-scale synthesis.Further derivation of the product proved its potential application.Subsequently,a palladium-catalyzed C-N coupling reaction of pyrazol-5-amines with arylbromides was developed by using aryl sulfonylhydrazonearylsulfonyl hydrazones as the nitrogen source of pyrazole heterocycles.N-arylated products were obtained with excellent yields and good functional group.In addition,the 1,4-migration and 1,6-migration of sulfonyl groups under Cs₂CO₃ promoted were investigated.1,6-migration products and 1,4-migration products were obtained with good substrate scope and functional group compatibility.Mechanistic studies reveal that the Ts-migration is achieved through an intermolecular pathway.Finally,the TBAI-promoted sulfenylation of N-arylated products was investigated.Multisubstituted 1H-pyrazol-3-amine arylthioether compounds were constructed using pyrazol-5-amine as substrate.which underwent N-S bond breakage and C-S bond formation.The system has a wide substrates scope and good functional group compatibility.28 polysubstituted aromaticsulfide 1H-pyrazol-3-amines were efficiently constructed.The product was suitale to gram-scale synthesis and could be transformed into more complicated structures.Mechanistic investigations suggest thiosulfate（Ar SO₂SAr）is formed as an important intermediate during thesulfenylation,and the generated arylsulfinic acid can promote the removal of Ts group.