Ring Expansion(Reduction) Reaction Of Cyclamine C-N Bond Cleavage

As one of the most abundant chemical bonds,C-N bond is widely found in organic molecules and biomacromolecules.However,due to the high dissociation energy of C-N bond,how to achieve efficient and highly selective C-N bond fracture is still a big challenge in the field of organic synthesis.In recent years,the activation of C-N bond has become one of the hottest topics in organic chemistry with the research on the catalytic activation of inert chemical bonds by transition metals.When C-N bond in itrogen-containing heterocyclic compounds breaks,it can provide both nitrogen source and carbon source,which makes the utilization rate of atoms reach high yield,in line with the concept of green chemistry.Based on this,different ring nitrogenous compounds were designed and synthesized in the new catalytic system to provide a new and effective method for the synthesis of important organic framework structures.The research in this paper includes the following four parts:[4+ 1]cycloaddition reaction:we have developed a Rh-catalyzed high chemical and regionally selective[4+1]cycloaddition reaction of 3-methylene azacyclopbutane with diazonium,which provides a general method for the synthesis of polysubstituted 4-methylene proline derivatives.Competitive experiments show that the rate of cycloaddition reaction is obviously faster than that of C-H and O-H insertion and cyclopropanation of olefin in rhodium carbyn chemistry,which indicates that this general method has potential applicability.The results of intramolecular[4+1]cycloaddition reaction showed that various tricyclic bridged ring;small to medium-sized N-containing heterocyclic compounds could be synthesized by this method,which was difficult to be synthesized by other conventional methods,indicating that this method had a significant contribution to the synthesis of compounds containing tricyclic bridged ring structural characteristics.In addition,4-methylene proline can be introduced into drugs and natural products by this method.In addition,diazo does not need to be added in the amplification reaction,and the amount of rhodium acetate catalyst can be reduced to 0.1 mol%,which provides a possibility for the method in drug synthesis.[4+ 2]cycloaddition reaction:we have developed Metal regulated high chemical and regional selectivity[4+2]cycloaddition of 3-benzylidene azacyclobutane with olefin,providing a general method for the synthesis of polysubstituted 3-benzylidene piperidine derivatives.The mechanism experiment shows that different configurations of olefin have no effect on the configuration of the obtained product,which fully indicates that the reaction is carried out stepwise.In addition,when the site of the heterocyclic ring contains methyl substituents,the C-N bond with high steric resistance will be selectively activated due to the more stable carbocation generated after fracture.In addition,the substrate type indicates that this method has a wide substrate range and is suitable for polysubstituted aryl olefin,such as 1,2,3-trisubstituted styrene and heterocyclic olefin,and can achieve more than half of the production,which provides a synthesis method for a series of 3-methylene piperidine derivatives with quaternary carbon centers and high steric resistance.[n-1]norfloxacin reaction and[5-1+ 2]cycloaddition reaction:The novel deamination radical carbon-carbon bond coupling reaction was realized by the sulfonyl azide/rearrangement sequence reaction of cyclic amine compounds,which opened up a new synthetic route for the construction of carbocyclic rings.Unlike the first two topics:the cycloaddition reaction of a single C-N bond cleavage,in which two C-N bonds are simultaneously cleaved to form a carbon-carbon bond.Such elimination mode and reduction elimination in metal catalysis have the same effect.The intermediate of the dearmination reaction is a stable dialkylamine,which is then activated by azidesulfonyl group to obtain C(Sp3)-C(Sp3)coupling products.The key intermediate in the metal-catalyzed coupling reaction is an unstable dialkyl metal intermediate,which is directly subjected to reduction elimination to obtain a C(Sp3)-C(Sp3)coupling product.In addition,the presence of a nitrogen atom facilitates the C-H bond functionalization/deamination continuous reaction at the a-position,and achieves a molecularly indistinguishable intramolecular C(Sp3)-C(Sp3)bond coupling condensed ring reaction.The reaction conditions are simple and the substrate range is wide.Mechanistic studies indicate that this reaction may be a diradical process.In addition,based on the above strategy,the[5-1 + 2]cycloaddition reaction of a cyclic amine compound with an olefin has been successfully carried out,and a general method for synthesizing a trans-tetrahydronaphthalene derivative is provided.Mechanistic studies show that the deamination reaction is a stepwise free radical reaction mechanism.[4 + 2]cycloaddition reaction:we have developed an N-benzylidene azacyclopbutane based oxidation series reaction promoted by AgOAc and acetic acid.It provides a general method for the synthesis of acetylated quinoline derivatives and various heterocyclic compounds with pyridine ring.Advantages:the substrate is highly tolerant,does not require nitrogen protection,and the reaction time is short.Mechanistic studies show that:When different acids are used,different substituted quinoline derivatives can be obtained.The reaction can modify the drug as well as the natural product,and the pyridine ring can be introduced later.Asymmetric phenanthroline ligands can also be synthesized,which broadens the range of methods using phenanthroline ligands in the methodology.This part of the work in cooperation with Shuang Wang,and has been published in Orgnic Letter.