Transition Metal-catalyzed C-H Bond Activations Directed By Carboxylic Acid Derivatives

Transition-metal catalyzed or mediated C-H activation reactions provide effective methods for the construction of C-C and C-X bonds.Consequently,these reactions are used in large quantities in medicine and natural products,providing important role to the development of organic chemistry.Herein,we discuss the development of transition-metal catalyzed or mediated C?sp²?-H/C?sp³?-H activation reactions using copper,cobalt,and palladium salts to promote such reactions.The following thesis is divided into five key chapters,including a literature review and four research chapters.Chapter 1 begins a review of the development of C-H activation reactions focus on copper,cobal and palladium-catalyzed reactions,with particular discussion of the development of palladium-catalyzed enantioselective C-H activation of carboxylic acids.Chapter 2 will discuss a new method for the highly monoselective ortho-trifluoromethylation of benzamides assisted with an 8-aminoquinoline directing group.Simple copper salt CuBr was used as the promoter and Togni reagent II was utilized as the CF₃ source.The reaction tolerated a wide variety of functional groups and various substituted ortho-trifluoromethylated benzamides were efficiently synthesized in good yields.The experimental results suggest that this reaction is likely to involve a radical process and the cleavage of the ortho C-H bond may be involved in the rate-determining step.Chapter 3 focuses on a novel cobalt-promoted arylation of benzamide derivatives with arylboronic acids using 8-aminoquinoline as the directing group.A notable feature of this newly developed protocol is that not only arene derived amides can react efficiently,but acrylamides can also be arylated under the standard conditions in good yields.The reaction tolerated a wide variety of functional groups and various ortho-arylated benzamides were efficiently synthesized in good to excellent yields.Chapter 4 demonstrates an efficient method for the highly mono-selective ortho-methylthiolation of benzamides and acrylamides assisted with an8-aminoquinoline directing group.Simple Co-salt Co?acac?₃ was used as the catalyst and DMSO was utilized as the methylthiolation source.In addition,ethylthioethers could also be successfully obtained directly using diethyl sulfoxide as the solvent in high yield.A plausible mechanism for the cobalt-promoted methylthiolation is proposed based on radical and KIE experiments.Chapter 5 demonstrates ligand-enabled enantioselective C?sp³?-H cross-coupling of free carboxylic acids with aryl-and vinylboron reagents.The key to the success of this method was the use of the bidentate MPAA ligands or MPAAM ligands.This reaction provides an alternative approach to the enantioselective synthesis of cyclopropanecarboxylic acids and cyclobutanecarboxylic acids containing?-chiral tertiary and quaternary stereocenters.The synthetic utility of this reaction was also demonstrated by converting the chiral carboxylic acid into the chiral cyclopropyl amine without loss of optical activity.