C-H Bond Functionalization And Synthesis Of Polysubstituted N-heterocyclic Compounds

Traditional methods for C-X bond（X=C,N,O,S,P…）construction commonly need organohalogen compounds and organometal reagents,most o f substrates,which are frequently prepared through multi-reaction procedures and hard reaction conditions,are required to functionalize in advance,corresp^onding products are generated in poor regioselectivity,many organic disinfection by-products are also generated in these processes.Therefore,the reciprocal transformat ions among organic compounds in effectivity,high regioselectivity and gently are important content of contemporary organic chemistry.With the development of scientific technology,several disadvantages of traditional C-X bond construction have been impro ved,C-H bond direct functionalization provide an abstract option for traditional C-X bond formation.Using this method,the final products can be generated from several simple substrates without any complicated reactions.In addition to the higher atom economy,these procedures also have other abstract advantages,such as energy-and time-saving,the fewer disinfection by-products and higher combined efficiency.In consequence,C-H bond functionalization has become one of the most attractive areas.Heterocyclic compounds are recognized as a crucial class of scaffolds,which are widely existed in nature world and have consanguineous relationships with bioscience and materials science.Nowadays,most of pharmaceuticals,pesticides and dye materials also have been reported to construct with heterocycle skeletons.Therefore,it is one of the great projects to explore effective and environmental methods for the synthesis of heterocyclic compounds.Several explorative researches for transition-metal/ I2-mediated functionalization of C-H bond and nitrogen heterocycles construction have been developed by our group,as shown in the following 4 parts: Part Ⅰ: Iodine-mediated Functionalization of C（sp²）-H Bond and Construction of C-S BondOrganosulfur compounds are important building blocks for the synthesis many functional materials,bioactive and pharmaceutical compounds.We have developed a method of iodine and TFA conefficient C（sp²）-H bond functionalization and C-S bond constructions with aromatic amines and sulfonyl hydrazides.In this process,various substituents on the sulfonyl hydrazides are tolerated in the thiolation which generates the desired products in moderate to good yields and high regioselectivity.Part Ⅱ: Iodine/AgF₂-mediated C（sp³）-H bond halogenations of polysubstituted 2-methylquinolineOrganic molecules containing halogenated functional groups are recognized as a crucial class of scaffolds,which are widely applied in pharmaceutical chemistry,agrochemistry and functional material science.In this procedure,we have initially achieved C（sp³）-H bond functionalization of 2-methylquinoline with iodine,and corresp^onding 2-（iodomethyl）quinoline was obtained.2-（Iodomethyl）quinoline was then fluorated with AgF₂ through a halide exchange pathway.In these processes,most of substituted 2-methylquinolines are tolerated,gave both iodoquinolines and fluoroquinolines in high regioselectivity and good yields.Part Ⅲ: Cu/O₂ catalytic oxidation formation of substituted quinolinesQuinolines and their derivatives have attracted the highest attentions of scientists due to their privileged scaffold motifs of physicochemical properties,biological activities and pharmaco logical values.In past several years,various considerable strategies for the synthesis of such quinoline derivatives have been developed.In addition,as a type of classical reaction system,C u/O₂ catalytic oxidation system has also attracted attentions.In this work,various substituted quinolines were generated from 2-（1-phenylvinyl）aniline and 2-methylquinoline with CuCl₂·2H₂O as catalyst under O₂ atmosp^here.We have successfully developed a simple and effective mehods for quinolines synthesis,various substrates were tolerance and easily to get in this procedure.Part Ⅳ: Metal-free synthesis of substituted cinnolinesIn this work,we have successfully synthesized substituted quinolines with tert-butyl nitrite and 2-（1-phenylvinyl）aniline as initial materials.In this procedures,tert-butyl nitrite was both oxidant and reactant,which offered nitrogen atoms for C/N-N bonds construction.This reaction performed smoothly in ethyl alcohol without any employment of metal catalyst,and generation of toxic byproduct.In addition,various substrates were tolerated in this reaction,and corresp^onding products were generated in high yields.