| This thesis mainly focused on two aspects,one is the transition metal(such as Cu,Ag and Au)catalyzed synthesis of bioactive nitrogen-containing compounds via the transfer,rearrangement or electrocyclization reactions of N-propargylic hydrazones;The other is we designed and synthesized a new type of phosphorus-doped porous organic polymer nanocatalyst(Pd NPs@POP),which was used for highly efficient and chemoselective hydrogenation of varieties of nitroarenes and ?,?-unsaturated compounds.Four chapters are included.Chapter 1:4-Arylidenepyrazolones are important molecular motifs and exist in many natural products,drugs,and bioactive frameworks.They have been used as antagonists for a variety of biological targets,such as effective inhibitors for HIV-1 integrase,orthopoxvirus,H1N1 and H5N1 neuraminidases.To date,the preparation of 4-arylidenepyrazolone derivatives usually relies on the condensation of substituted aldehydes(or their acetal or imine precursors)with 2-pyrazolin-5-ones,which are in turn obtained by the Knorr condensation of ?-ketoesters with substituted hydrazines.To the best of our knowledge,the use of a ?-acidic transition-metal catalyzed cyclization to access this family of compounds has not been disclosed.In this chapter,We developed a novel method for the synthesis of various 4-arylidenepyrazolones from N-propioloyl hydrazones by gold catalyzed cyclization/1,3-migration cascade(Scheme 1).(?) Scheme 1Chapter 2:The pyridazine-derived structures form the core of many cormmercial drugs and drug candidates.Among those pyridazine derivatives,dihydropyridazine(including 1,4-dihydropyridazine and 1,6-dihydropyridazine)derivatives show versatile pharmacological activities.The former have been used as antagonists for various targets to treat inflammation and diabetes and as antifungal or antibiotic reagents.The latter has been used as anti-hypertensive,coronary insufficiency therapeutic and spasmolytic agents.For these reasons,a variety of strategies have been developed for the synthesis of 1,4-dihydropyridazines.Nevertheless,methods for the preparation of 1,6-dihydropyridazines remain rare and usually rely on the cycloaddition of aromatic diazonium salts with dienes or[4+2]cycloaddition of a-halogenated hydrazones with alkenes.In this chapter,we developed a general and efficient method for the synthesis of 1,6-dihydropyridazines from easily available N-propargylhydrazones.The reactions proceed through a Ag-catalyzed[3,3]rearrangement/1,3-H shift/67? aza-electrocyclization process and are high-yielding with a broad substrate scope under extremely mild conditions.In addition,we have also developed a new synthetic route to functionalized pyridazinones(Scheme 2).(?) Scheme 2Chapter 3:Recently,ketenimines generated from the copper-catalyzed azide-alkyne cycloaddition(CuAAC),represent a class of useful reactive intermediates,which shine light on the novel construction approaches to varieties of heterocycles.We designed and synthesized N-propargylic sulfonyl hydrazone bearing a terminal alkyne,which could react with sulfonyl azides to give 4,5-dihydropyrazolo[1,5-a]pyrimidines.Pyrazolo[1,5-a]pyrimidine-derived structures are important molecular motif and form the core of varieties of pharmaceuticals and pesticides,such as zaleplon(hypnotic drug),ocinaplon(anxiolytic drug),indiplon,and pyrazophos(a fungicide and insecticide).To date,the preparation of this family of compounds usually relies on the condensation of aminopyrazole with 1,3-dicarbonyl or ?,?-unsaturated carbonyl compounds and their analogues.In this chapter,we developed a general and efficient approach to obtain 4,5-dihydropyrazolo[1,5-a]pyrimidines via cascade transformation of the easily available N-propargylic sulfonylhydrazones with sulfonyl azides under mild conditions and the reaction are high-yielding with broad substrate scope.The novel method complemented the classic condensation reactions and made the pre-prepared aminoparazole unnecessary (Scheme 3).(?) Scheme 3Chapter 4:Due to the limitation of homogeneous catalysis in the difficult separation of product and catalyst,the heterogeneous catalysts are desperately in demand for industrial applications because of the recovering and recycling of the catalysts.Nevertheless,to develop heterogeneous catalysts with not only high catalytic activity,but also selectivity towards the nitro group or C=C bond of?,?-unsaturated carbonyl compounds is a dominating challenge.For the reduction of nitro group,the hydrogenation process is sometimes performed under drastic(for example,T>100? or P>1.0 atm H2).For the selective hydrogenation of C=C bonds,great efforts have been made to achieve the aimed products,but high H2 pressure,high temperature,toxic solvent,or various additives like amines,pyridines and diphenylsulfide are sometimes inevitable.Recently,some N,O,and S-doped POPs have also been designed and applied to the hydrogenation reactions.However,attempts to use P-doped POPs to catalyze hydrogenation reactions have not been reported.In this chapter,a new type of phosphorus-doped porous organic polymer(POP)has been readily synthesized through Heck reaction,which could be used not only as a support but also a ligand for Pd nanoparticles.The dual-functional material supported Pd nanocatalyst was used for highly efficient and chemoselective hydrogenation of varieties of nitroarenes and ?/?-unsaturated compounds.No obvious aggregation and loss of catalytic activity of the new nanocatalyst were observed after 10 times in the reaction of p-nitroanisole reduction. (Scheme 4).(?) Scheme 4... |
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