Transition Metal-catalyzed Bidentate Ligand-directed C-H Bond Activition

Transition metal-catalyzed direct C-H bond functionalization is one of most efficient and straightforward approach for selective C-C and C-hetero bond constructions in organic chemistry.Over the last few decades,significant progress has been made in this area.However,the majority of these transformations relied on second-and third-row transition metals.To develop cost-effective,earth-abundant first-row transition-metal catalysts,represents an attractive alternative.Cobalt catalysis has recently exhibited its great potential in C-H bond functionalization reactions due to its low-cost,environmentally benign and unique catalytic mode.Among them,cobalt-catalyzed bidentate ligand-directed strategy has attracted much attention recently.The use of bidentate-chelation systems allow the tranformations to employ cheaper cobalt catalysts,which has higher functional group tolerance and can effectively promote the conversion of C-H bonds that can not be achieved in traditional systems.Regioselectivity has been one of the major challenges in the field of transition metal-catalyzed C-H bond activation.The use of directing groups is now recognized as one of most reliable strategies for regioselective C-H bond activation.Traditional methods relied on the use of substrates that contain various directing groups.However,extra steps were required for the pre-construction of the substrates and removal of the directing groups,which diminishes the efficiency and compatibility of the reactions.A promising solution to this problem is to employ a catalytic amount of transient ligand that binds reversibly to the substrate and the metal center.In which the desired site-selective C-H bond activation will be achieved without changing the function of the substrates after the catalytic process is finished.This dissertation mainly focuses on Co(II)-catalyzed bidentate ligand-directed C(sp2)-H alkylation and Pd(II)-catalyzed transient directing group promoted C(sp3)-H arylation,which includes:1.Cobalt-catalyzed C(sp2)-H methylation using dicumyl peroxide as both methylating reagent and hydrogen acceptor.The first cobalt-catalyzed direct methylation of C(sp2)-H bond using dicumyl peroxide(DCP)as both the methylating reagent and hydrogen acceptor has been established.The reaction proceeded without the use of any additives,and was proven to be applicable to various amides bearing a 2-pyridinylisopropyl(PIP)directing group,providing an efficient access to o-methyl aryl amides with high functional-group tolerance.Preliminary mechanistic studies suggest a radical process would be involved in the catalytic process.2.Cobalt-catalyzed cross-dehydrogenative coupling reaction between unactivated C(sp2)-H and C(sp3)-H bonds.Catalytic oxidative cross-dehydrogenative coupling between unactivated C(sp2)-H and C(sp3)-H bonds is achieved by the cobalt-catalyzed o-alkylation reaction of aromatic carboxamides containing(pyridin-2-yl)isopropyl amine(PIP-NH2)as a N,N-bidentate directing group.The unique features of this method include structural variety of the aromatic carboxamides and the hydrocarbon substrates,which include alkanes,toluene derivatives,ethers and thioethers.This method has broad substrate scope and high functional group tolerance.Preliminary mechanistic studies by radical trapping experiments,hydrogen/deuterium exchange experiments and kinetic isotope effects suggest that the C(sp2)-H bond is cleaved by the cobalt catalyst and C(sp3)-H bond cleavage is achieved by a radical hydrogen atom abstraction step.3.Catalytic C-H arylation of aliphatic aldehydes enabled by a transient ligand.The direct arylation of aliphatic aldehydes has been established via the Pd(Ⅱ)-catalyzed C(sp3)-H bond functionalization in the presence of 3-aminopropanoic acids as transient directing groups.The reaction showed excellent functional group compatibility and chemoselectivity in which predominant preference of functionalizing unactivated β-C(sp3)-H bonds of methyl groups over others was achieved.In addition,C-H bonds of unactivated secondary sp3 carbons can also be functionalized.Isolation of the palladium intermediate suggest that the catalytic cycle invole a[5,6]-bicyclic palladium intermediate.The extreme popularity and importance of aliphatic aldehydes would result in broad applications of this novel method in organic chemistry and medicinal sciences.