Palladium Cellulose Catalyzed Tandem Synthesis Of Nitrogen-containing Heterocycles

Nitrogen-containing heterocyclic compounds are a very important class of organic compounds.Nitrogen-containing heterocyclic compounds have found wide application in the filed of medicine,agriculture,functional materials,which serve as the core framework of many medicines,natural products and organic functional molecules.Therefore,it is of great significance to study the synthesis of nitrogen-containing heterocyclic compounds in the fields of organic chemistry.pharmaceutical chemistry,and material chemistry.However.due to their complex structure and abundant heteroatoms,there are still many disadvantages in the artificial synthesis,such as complicated operation,harsh conditions and low yield.Therefore,it is of great significance and broad application prospects to develop simple and efficient synthetic strategies to synthesis of nitrogen-containing heterocyclic compounds.This manuscript mainly focused on the transition metal(Pd)catalyzed aromatic functionalization for the tandem synthesis of nitrogen-containing compounds.In this paper,we have successfully developed synthetic methods of quinolone-fused isoquinolines,benzocarbazoquinones,phenamidazole-fused quinolines and benzimidazole-fused phenanthidines and corresponding reaction mechanism was also proposed.Using this method of Pd-catalyzed C-H activation not only simplifies the reaction steps and improves the reaction efficiency,but also expands the application scope of substrates and achieves atomic and step economy.In addition,in order to overcome the shortcomings of high price and difficult recovery of palladium catalyst,we work on the development of simple and reliable procedures for immobilization of catalytically active palladium nanoparticles on functionalized cellulose.The main contents were list as follows:(1)Firstly,quinolone and alkynyl bromide were used as starting materials to obtain(Z)-alkenyl bromides by the nucleophilic addition of quinolone to alkynyl halides with subsequent palladium-catalyzed cyclization reaction of the resultant haloalkenes via intramolecular aromatic C-H bond vinylation to give quinolone-fused isoquinoline derivatives in a "one pot"manner.Based on the full exploration of the influence of catalyst,base,solvent and temperature on the reaction,the optimum conditions were showed as following:first,tert-butyl alcohol as solvent,2.0 eq.K3PO4 as base for 24 hours at 110?,then 5 mol%PdCl2 and K2CO3 were added in DMF at 160? for another 10 hours to give the corresponding product in good to excellent yields.On the basic of optimized reaction conditions,the scope and generality of the present process were then explored.Twenty-nine different quinolone-fused isoquinoline compounds were synthesized.The experimental results showed that the method had good scope,and the aromatic group of quinolone and alkynyl bromide all showed good functional group tolerance.They,can be obtained by simple modification of the substrate with different functional groups.Finally,a possible palladium-catalyzed mechanism of the reaction process was proposed.This method for the synthesis of quinolone-fused isoquinoline derivatives had the advantages of simple operation.practical and high efficiency.The result had great application value in the field of organic synthesis and drug synthesis and also provides a reliable theoretical basis for the future synthesis of new drugs and materials.(2)An efficient palladium-catalyzed route for the synthesis of benzocarbazoquinone from o-dibromoarenes and 2-aminonethylquinone was described.The sequentially accomplished reaction comprises intermolecular C-H arylation of 2-arylbenzimidazoles followed by an intramolecular N-arylation reaction promoted by the same Pd catalyst.The optimum reaction conditions was PdCl2(10 mol%)as catalyst,Xphos(20 mol%)as ligand,K2CO3 as base(3.0 eq.)and DMF as solvent(2 mL).The target product benzocarbazoquinones could be obtained at 160? for 72 hours,and the yield could reach 81%.The scope and generality of the present annulation process was then explored by testing a set of structurally diverse 2-aminonethylquinone and o-dibromoarenes.A tandem reaction mechanism.Buchwald-Hartwig amination followed by an intramolecular C-H arylation.was proposed.This method has some advantages.such as high efficiency,good selectivity,mild reaction conditions,and easily operation.(3)Novel heterocyclic aromatic compounds have been widely used in the field of organic optoelectronics.Polycyclic aromatic compounds can effectively control the optical and electrical properties of materials by changing the conjugate length of polycyclic compounds.In this chapter,the efficient palladium-catalyzed route for tandem synthesis of structure-tunable imidazole-fused polyheterocycles from 2-vinyl imidazoles and aryl halides under mild reaction conditions was described.The reaction conditions were optimized as follows:Pd(OAc)2(10 mol%)as catalyst.Xphos(20 mol%)as ligand,K2CO3(3.0 eq.)as base and solvent DMF(2 mL),reaction temperature 160? for 72 h,the target product could be obtained with a yield of 91%.Moreover,2-vinyl imidazoles and iodobenzene compounds substituted by various functional groups can also react with good yields.It is shown that this reaction had a wide range of substrate adaptability.Then,we studied the fluorescence properties of all the products and found that the products have excellent optical properties.Finally,by studying the reaction mechanism in depth,we proposed the possible reaction mechanism:the sequentially accomplished reaction comprises intermolecular Heck arylation of 2-vinyl imidazoles followed by an intramolecular aerobic oxidative C-H amination reaction promoted by the same Pd catalyst.This Pd-catalyzed tandem approach offers a straightforward protocol for the assembly of benzimidazo/phenanthroimidazo[1,2-a]quinolines in moderate to high yields,serving as a useful and efficient tool for the discovery of fluorescent materials.(4)In order to overcome the shortcomings of palladium catalyst,such as high price and difficult to recovery,the recyclable Cell-OPPh2-Pd0 catalysts can be prepared by simple synthetic processes using cheap.easily available and renewable modificatied cellulose as supported material.Starting from 2-arylbenzimidazoles and aryl halides,an efficient palladium-based catalytic method for the synthesis of benzimidazole-fused phenanthridines has been developed.Firstly,the optimum reaction conditions were explored:15 mol%Cell-OPPh2-Pd0 as the catalyst,3.0 equiv.of base,DMF as the solvent at 160? for 72h,and the yield could reach 74%.On the basis of optimizing reaction conditions,the universality and limitation of the reaction were studied.and a series of phenanthridine derivatives with different structures were synthesized.The experimental results showed that the method had good universality,and the aromatic group of 2-arylbenzimidazoles and aryl halides all showed good functional group tolerance.Finally.based on the above results,we proposed the possible reaction mechanism:this reaction sequence comprises intermolecular C-H arylation and intramolecular aerobic oxidative C-H amination,involving the rupture of two C-H bonds,one C-X bond,and one N-H bond in one pot.The Pd?-Pd?-Pd? and Pd?-Pd0-Pd? catalytic cycles work together under the reported conditions to generate phenanthridines with diverse substituents.The reaction process is simple.efficient and environmentally friendly.which provides a useful tool for the synthesis of fluorescent materials and drugs.