| Transition metal-catalyzed organic reactions play an important role in the field of organic chemistry,and these catalytic reactions are usually composed of elementary reactions.Therefore,the discovery and construction of elementary reactions is the core of achieving these catalytic reactions.In addition to common elementary reactions such as oxidative addition,migratory insertion,transmetallation and reductive elimination,the discovery of metal-carbene and its fundamental[2+2]cycloaddition as well as[2+2]cycloreversion reaction has led to the rapid development of alkene metathesis reaction,and it has been widely used in the synthesis of complex molecules and natural products.Inspired by this,chemists began to work on the exploration of the metathesis reaction of other chemical bonds.Among them,the development of the C-N bond metathesis reaction has always been a challenge.In this tihesis,the new elementary reactions of palladium-catalyzed C-N bond metathesis and C-N/C-O bond cross metathesis have been established according to the reaction characteristics of three-membered palladacycle-complex.On this basis,a series of new catalytic ring-closing reactions based on C-N bond and C-O bond metathesis were constructed to realize the synthesis of functionalized heterocyclic compounds.In addition,using the nucleophilicity of aminals,the elementary reaction of generating three-membered palladacycle-complex from an allyl ammonium salt was constructed,and a new palladium-catalyzed aminomethylation reaction was developed.For example,a-aminomethylation reaction of nitrodienes and dienones,ring-closing aminomethylation reaction of aminodienes and aminals,ring-closing aminomethylation reaction of aminoenynes and aminals,ring-closing aminomethylation reaction of aminodienes and N,O-acetals,ring-closing reaction of enynols and aminals,aminomethylation-aromatization reaction of allyl enynols and aminals.Details are as followings.1.Based on the nucleophilicity of aminals,a new elementary reaction of the construction of three-membered palladacycle-complex through aza-Michael addition was established,and a palladium-catalyzed a-aminomethylation of nitrodienes and dienones was developed.With 5 mol%of Pd(COD)Cl2/P(4-CF3C6H4)3/AgOTf as a catalyst,the ?-aminomethylation of nitrodienes could be achieved in a yield of up to 92%.In addition,the corresponding a-aminomethylated dienones can be obtained in a yield of up to 84%by utilizing 5 mol%of Pd(OAc)2/DPPO as a catalyst.2.Based on the unique structure and characteristics of the three-membered palladacycle-complex,a novel and efficient palladium-catalyzed ring-closing aminomethylation reaction of aminodienes and aminals via C-N bond metathesis has been succesfully established,in which the amino nucleophile of aminodiene preferentially attacked the carbon center of the cyclopalladium complex.With 5 mol%of[Pd(allyl)Cl]2/Xantphos/AgOTf as a catalyst,the corresponding saturated N-heterocycles could be obtained in a yield of up to 89%.The reactions proceed efficiently under mild conditions and exhibit broad substrate generality and functional group compatibility,leading to a wide variety of 5?16-membered N-heterocycles bearing diverse frameworks and functional groups.What's more,the amine-tethered cyclohexa-1,3-dienes could be also employed in the present protocol to afford a series of spirocyclic N-heterocycles.On the other hand,the reaction mechanism was studied by means of separation and characterization experiments of intermediates,kinetic experiments,kinetic isotope labeling experiments,and DFT theoretical calculations,and a possible catalytic reaction mechanism was proposed to consolidate the C-N bond metathesis process.3.A palladium-catalyzed ring-closing aminomethylation reaction of aminoenynes and aminals via C-N bond metathesis has been succesfully established,which provided an efficient method for the synthesis of saturated N-heterocycles containing exo-allenylamine functional group.A wide range of saturated N-heterocycles with different ring-sizes(5-12-membered)were obtained in 30-89%yields with 5 mol%of Pd(Xantphos)(CH3CN)2(OTf)2 as a catalyst.4.A palladium-catalyzed ring-closing aminomethylation reaction of aminodienes and N,O-acetals via C-N bond metathesis was described.A series of saturated N-heterocycles containing a special allylic amine functional group with different ring-sizes(5-16-membered)were obtained in a yield of up to 90%with 5 mol%of Pd(Xantphos)(CH3CN)2(OTf)2 as a catalyst.Compared with the ring-closing reaction of aminodienes and aminals,this reaction system only produced one molecule of methanol as a by-produet,which has higher atomic economy and simpler separation operation.5.Based on the successful establishment of the ring-closing aminomethylation reaction for C-N bond metathesis,a new elementary reaction of C-N/C-O bond cross-metathesis was established with enynols as double nucleophile,in which the hydroxyl group preferentially attacked the carbon center of the cyclopalladium complex.A series of oxygen-containing heterocycles containing a special allenic amine functional group were synthesized in a yield of up to 82%by using 5 mol%of Pd(CH3CN)2Cl2/Xantphos/AgClO4 as a catalyst.6.The synthetic value of this method was further demonstrated in the formal syntheses of nature products by using conventional protocols.Starting from allylamine-substituted piperidine derivatives,the alkaloids jussiaeiine A,kuraramine,isokuraramine,and cytisine could be synthesized through multi-step conversion.In addition,the cyclocelabenzine could be synthesized formally from the tetrahydroisoquinoline compounds,obtained by this method,through simple functional group conversion.7.A palladium-catalyzed chemoselective aminomethylative cyclization and aromatizing ally lic amination of enyne-tethered allylic alcohols with aminals via C-N and C-O bond activation was described.Under optimal reaction conditions,the functionalized naphthalenes derivatives could be constructed in a yield of up to 83%with 5 mol%Pd(Xantphos)(CH3CN)2(OTf)2 as a catalyst. |
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