Studies Towards Nickel/Copper Promoted C-H Bond Functionalizations Assisted By Bidentate Directing Groups

In the last decade,transition-metal-catalyzed or promoted C-H bond functiona-lizations has attracted widespread attention.This strategy provides a very effective method for the construction of carbon-carbon bonds and carbon-heteroatom bonds.However,current methods are mainly focused on the use of noble metal,and using inexpensive metal catalysis is relatively less frequent.Herein,we developed the direct functionalization of C(sp²)-H bond of aromatic hydrocarbon by using inexpensive metal salts,including nickel and copper,as promoter conjunction with using8-aminoquinoline as the directing group,and the carbon-carbon bond and carbon-nitrogen bond are efficiently and selectively constructed.The following thesis is divided into five chapters,including a literature review followed by four research chapters.Chapter 1 commenced with a review on the recent development of C-H activation reaction with nickel or copper salts,specifically emphasizing the development of nickel-,copper-catalyzed or mediated C-H bond functionalizations assisted by various bidentate directing groups.Chapter 2 disclosed a nickel-promoted C(sp²)-H bond cyanation assisted by an8-aminoquinoline directing group.The mild reaction conditions,use of cheap and commercially available reagents,wide functional group tolerance,and operational convenience make this protocol practical to the synthetic community.Varieties of functionalized ortho-cyanated(hetero)aryl nitriles can be selectively synthesized in moderate to good yields.These cyanation products can be easily transformed into various 3-imino-1-oxoisoindolines in a one-pot procedure.Chapter 3 discussed an efficient and mild protocol for the direct conversion of arene C-H bonds to C-NH₂without the need for extra deprotection step,and to the best of our knowledge,this is the first time that the synthesis of primary anilines via nickel-mediated C(sp²)-H activations has been reported.This approach utilizes8-aminoquinoline as the directing group and sodium azide,a cheap and commercially available material,as the nitrogen source.In addition,the reaction is highly selective,only affording the mono-,ortho-aminated benzamides.The reaction tolerates a broad range of substrates with diverse functional groups and the corresponding ortho-aminated benzamides were efficiently synthesized in 41–82%yields.Chapter 4 focused on nickel-promoted amination of inert arene C-H bonds with ammonia gas as the ultimate amino source assisted by an 8-aminoquinoline directing group.By treating various benzamides with simple Ni Cl₂in the presence of K₂CO₃and tetrabutylammonium acetate under NH₃,a variety of substituted benzamides bearing diverse functional groups could be efficiently ortho-aminated to give the corresponding aniline derivatives in yields ranging from 33 to 82%.Other notable features of the reaction include excellent regioselectivity and high monoselectivity.In addition,the KIE values indicated that the C-H activation step may be involved in the rate determining step.On the basis of the mechanistic studies and literature precedents,a plausible mechanism is proposed for this nickel-promoted amination reaction.Chapter 5 demonstrated an efficient method for the dehydrogenative coupling of nitroalkanes with benzamides via copper-promoted 8-aminoquinoline assisted C-H activations.3-Hydroxyimino-1-isoindolinones were obtained when nitromethane was used.On the other hand,3-methylene-1-isoindolinones was produced with higher nitroalkanes.The reaction was found to go through C-H activation,nitroalkylation,Nef-type reaction followed by intramolecular cyclization.