C-C And C-X Bond Formation Reactions Promoted By Copper,Silver And Iron Salts

The construction of carbon-carbon and carbon-hetereoatom bonds remains a significant challenge to modern organic chemist.Recently,transition-metal catalyzed or mediated cross-coupling reactions provide effective methods for the construction of such bonds;consequently,these reactions are highly applicable to medicine,pesticide,natural products and materials.Herein,we discuss the development of novel,highly efficient,highly selective carbon-carbon and carbon-heteroatom bond formation reactions using copper,silver and iron salts to catalyze such reactions.The following thesis is divided into six key chapters,which encompass a literature review followed by five research chapters.Chapter 1 commences with a general review on the development of cross-coupling reactions with particular focus on copper,silver and iron-catalyzed reactions,specifically emphasizing the development of copper-mediated auxiliary-assisted C-H bond functionalization reactions.Chapter 2 examines copper-mediated,chelation-assisted ortho C-H bond arylation of benzamide derivatives using arylboronic acid with the aid of an 8-amino quino line directing group.To determine optimized reaction conditions,benzamide derivatives were reacted with arylboronic acid while varying the copper salt,base additive,solvent and temperature.To highlight the uniqueness of this new transformation,a proposed mechanism will be discussed based on a series of control experiments and previous literature reports.Chapter 3 will discuss our efforts towards a synthesis of phenanthridin-6(5H)-ones via a copper-catalyzed cyclization of 2-phenylbenzamides.The optimized reaction conditions obtained from the cyclization of 2-phenylbenzamides using various copper salts,base additives,solvents and temperatures will be discussed.Moreover,stereoelectronic factors were investigated by substituting the 2-phenylbenzamides with various electron-withdrawing and electron-donating groups.The experimental results suggest that the electrophilic attack of the benzene ring by the copper center is the core for this reaction.Chapter 4 focuses on the synthesis of N-alkyl isatins via oxidative cyclization of N-alkyl-2-bromo(chloro)acetanilides.Our initial studies demonstrated that the reaction is very sensitive to the type of solvent,consequently requiring dimethyl sulfoxide(DMSO)in the reaction vessel either as a solvent or an additive.Further research demonstrates that the reaction works very well with a wide variety of N substituted isatins to furnish good yields.This chapter will also provide insight into the reaction mechanism and discuss experiments supporting why the reaction proceeds through a Friedel-Crafts cyclization process.Chapter 5 demonstrates the development of a new method for the synthesis of(E)-vinyl phosphonates and phosphine oxides via styrenes with phosphonates and phosphine oxides.The discussion will focus on how the optimized reaction conditions were obtained by varying the silver salt,oxidant,additive and solvent when reacting styrenes with phosphonates and phosphine oxides.In addition,two plausible mechanisms for the silver-catalyzed coupling reactions are proposed based on a radical intermediate.Chapter 6 will discuss an efficient method for the synthesis of substituted oxindoles via iron-mediated hydrometalation-cyclization of N-arylacrylamides.In order to obtain the optimum reaction conditions,numerous reaction were conducted using different catalysts,oxidants,solvents and temperatures.A variety of substituted N-arylacrylamides were subject to the optimized conditions to furnish good yields.To explore the reaction mechanism in detail,we performed a free radical capture experiment and intermolecular competition experiment supporting that the reaction proceeds through a hydrometalation-cyclization reaction process.