| Pyridinium salts are a class of six-membered nitrogen heterocyclic compounds with rich physical and chemical properties.And they play an important role in the fields of natural organic,life science,material science and chemical industry.The methodological research of dearomatization and functionalization of pyridinium salts has become the hot topic of pyridinium salt chemistry.In addition,pyridinium salts presented versatile applications,among which the base-mediated ring-opening,to various hetercyclic compounds,has attracted synthetic interest.However,the transformation of substituents on the N atom in pyridinium molecules is merely reported.Thus,the synthesis of novel pyridinium salts and their new reactions would be of great significance in the field of theory and application.The physical and chemical properties of organic compounds could have significant changes by introducing trifluoromethyl groups into specific sites.The N-CF3 pyridinium salts formed by bonding a trifluoromethyl group to the N atom of the pyridine ring have always been a target synthon in organic synthetic chemistry.However,the synthesis and application of N-CF3pyridinium salts are extremely challenging and rarely reported due to the limitation of the synthetic method of N-CF3 compounds.Our research group has been devoted to the study of trifluoromethylation reactions for a long time,and an externally coordinated CF3-containingλ3-iodane（Ph ICF3Cl）was successfully prepared in 2018.In this thesis,N-CF3 pyridinium salts were synthesized by using Ph ICF3Cl and electron-rich pyridines,and a series of new applications based on the N-CF3 pyridinium salts were explored.The thesis has been divided into the following parts:1.The types,synthetic methods and ring-opening reactions of pyridinium salts were summarized,and the ring-opening reactions of pyridinium salts promoted by hydroxide and amines were elaborated in this chapter.2.The direct N-trifluoromethyl reaction of pyridine was realized using Ph ICF3Cl as efficient trifluoromethylating reagent under mild conditions.Electron-rich pyridines were selected as substrates,the N-CF3 pyridinium salts were successfully prepared.Moreover,the electrochemical properties of N-CF3 pyridinium salts were preliminarily explored.The reduction potential and maximum absorption wavelength were determined by cyclic voltammetry experiments and UV-Vis spectroscopy experiments,and the feasibility of developing such N-CF3 pyridinium salts as trifluoromethylating reagent was analyzed.The simple and mild conditions for preparing N-CF3 pyridinium salts would provide convenience for the transformation and application based on N-CF3 pyridinium salts.3.We described an alternative reassembly and functionalization of N-CF3 pyridinium salts under basic conditions.The reaction provides a simple and efficient route to valuable 2-functionalized nicotinaldehydes by forming multi chemical bonds,including C=O,C-C,C-N and C-O/S/N.The transformations proceeded with high yields under mild conditions and tolerated a wide range of O/S/N nucleophiles.The reaction included the initial hydrolytic ring-opening of pyridine ring,followed by defluorination,intramolecular nucleophilic addition,intermolecular nucleophilic substitution and dehydrofluorination.New use of the CF3 group as multiple functional group in domino reaction was developed.More importantly,the hydrolyzation-mediated ring-opening-recyclization reaction mechanism of the reaction was deeply understood according to DFT calculation results,which provided a theoretical basis for the research on the ring-opening reaction of N-CF3 pyridinium salts.4.The CF3 of N-CF3 pyridinium salts was successfully developed as C1 synthons to construct a series of 2-aminobenzoxazoles and 2-aminobenzothiazoles.The reaction proceeded with Zincke-type ring-opening reaction,elimination of HF and intermolecular cyclization.The mono-fluorine amide salt is highly active,which was formed during the reaction progress,could react with the easily available o-aminophenols or o-aminothiophenols to synthesize corresponding azoles.The reaction tolerated mild conditions,good to excellent yields and broad substrate range,providing an alternative method for the synthesis of functionalized benzoxazoles and benzothiazoles.5.The N-CF3 pyridinium salts were successfully developed as an important class of synthons for the preparation of a series of triazine derivatives through the three-component reaction of N-CF3 pyridinium salts with amidines and secondary amines（or methanol）.The reaction of N-CF3 pyridinium salts with amidines and secondary amines to construct a series of asymmetric di-substituted triazine compounds was realized.This method is featured mild conditions and tolerated a set of secondary amines,including acyclic secondary amines and cyclic secondary amines.The synthesis of symmetric triazines from benzamidines and N-CF3pyridinium salts was realized in the presence of methanol and potassium carbonate.The successful preparation of triazine derivatives greatly enriched the reaction types of N-CF3pyridinium salts and provided the possibility for the preparation of other heterocyclic compounds.In summary,we successfully developed direct N-trifluoromethylation of pyridines using Ph ICF3Cl as efficient trifluoromethylating reagent under mild conditions.And these newly prepared N-CF3 pyridinium salts were developed to be C1 synthons.An alternative reassembly and functionalization of N-CF3 pyridinium salts under basic conditions to construct a series of valuable 2-functionalized nicotinaldehydes was reported.In addition,the synthesis of benzoxazole,benzothiazole and triazine compounds based on the N-CF3 pyridinium salts was realized,which greatly enriched the reaction types of pyridinium salts and provided a new way for the synthesis of heterocyclic compounds.The establishment of a new reaction mode based on N-CF3 pyridinium salts is of great significance for the development of pyridinium salts chemistry and fluorine chemistry. |
