Study On Selective Hydrogen Evolution/Transfer Functionalization Of Nitrogen Heterocycles

Nitrogen heterocycles are an important class of organic compounds,which exist widely in nature and are used to develop drugs,functional materials,dyes,ligands,sensors,and agrochemicals.These are the material foundations of indispensable products related to the national economy,people's livelihood,and sustainable social development.In recent years,the hydrogen evolution coupling reaction has developed rapidly in organic methodology.Compared with the traditional coupling reaction,this method has significant advantages.It does not require pre-preparation of the substrate and the use of an oxidizing agent,and the atom economy is high.If the hydrogen released in the hydrogen evolution coupling reaction is further utilized,the hydrogen transfer coupling reaction can be developed,which not only has the characteristics of the hydrogen evolution coupling reaction,but has high atom utilization and step economy.Therefore,the selective functionalization of nitrogen heterocycles through hydrogen evolution or hydrogen transfer coupling strategy has important scientific and practical significance,which provides the possibility for the diversified synthesis of nitrogen heterocycles and is beneficial to the development of new functionalized products.The research work of this paper is as follows:(1)In chapter 2,based on the hydrogen evolution strategy,we developed the iridium-catalyzed hydrogen evolution coupling reaction of aromatic nitrogen heterocycles and aryl boronic acid,and realized the arylation reaction of aromatic nitrogen heterocycles at the?-position.Provides a new method for the synthesis of 2-aryl aromatic nitrogen heterocycles.The reaction uses[Cp*Ir Cl₂]₂ as a catalyst and L-proline as an additive.In the reaction,H₂O not only acts as the solvent for the reaction,but promotes the reaction and the regeneration of the iridium catalyst through the hydrogen evolution process.The reaction has good chemical selectivity and wide substrate applicability.The types of nitrogen heterocycles are very rich,including different aromatic nitrogen heterocycles such as quinoline,quinoxaline,naphthyridine,pyrazine and pyrimidine.Common aryl boronic acid and heteroaryl boronic acid can be well suited for this system.In addition,the reaction has very good functional group compatibility,including alkyl,alkoxy,halogen,ester,nitro,cyano.These remaining functional groups can be further transformed.The hydrogen evolution coupling reaction containing pyridyl aryl boronic acid and aromatic nitrogen heterocycle can be used to prepare N^N-type bidentate ligands.This method can be used directly to modify the structure of aromatic nitrogen heterocyclic active molecules.(2)In Chapter 3,based on the hydrogen evolution strategy,we developed the hydrogen evolution coupling reaction of ruthenium-catalyzed saturated cyclic amines and phenol derivatives,and realized the functionalization of the?-position of saturated cyclic amines.The reaction uses Ru₃(CO)₁₂/Xantphos as the catalytic system,and the addition of p-TSA can significantly promote the reaction.The reaction is a direct cross-coupling between the C-H bond of sp³ and sp²,with hydrogen as the only by-product.The substrate of saturated cyclic amine has two?reaction sites,both of which can selectively obtain monofunctionalized products.The developed hydrogen evolution coupling reaction has the advantages of good chemical selectivity,high atom utilization,wide substrate universality,and good functional group compatibility.(4)In Chapter 4,based on the hydrogen transfer coupling strategy,we developed a ruthenium-catalyzed hydrogen transfer coupling reaction of saturated cyclic amines and hydroxyquinoline derivatives.It realizes the functionalization of?-position of saturated cyclic amine,reduces the pyridyl group in quinoline,and develops a new method for the synthesis of functionalized tetrahydroquinoline.The reaction uses Ru₃(CO)₁₂/Xantphos/p-TSA as the catalytic system,and the hydrogen donor from saturated cyclic amine and external formic acid.Different from the previous hydrogen transfer coupling reaction,saturated cyclic amine is used as the coupling reagent of the reaction,and it is also an inert hydrogen donor.Although saturated cyclic amines have two?-sites,the reaction can selectively obtain a single?-position functionalized product.The reaction has good chemical selectivity,high atom economy and step economy,wide substrate applicability and functional group compatibility.This method can modify the structure of complex biologically active molecules,providing a basis for the further development of new functional molecules.In summary,through the hydrogen evolution/hydrogen transfer coupling strategy,the functionalization reaction of the aromatic nitrogen heterocyclic and the aliphatic nitrogen heterocyclic compound?-position has been developed respectively.It provides a new method for the construction of C-C bonds of nitrogen heterocyclic compounds.These research works are helpful to the design of catalytic hydrogen evolution/hydrogen transfer coupling reactions,and it is conducive to the development of organic synthesis methodology.