Transition Metal-catalyzed Direct Functionalization Of Unactivated C-H Bonds Directed By Bidentate Auxiliaries

Over the last two decades,transition-metal-catalyzed direct C-H functionalization has emerged as an effcient and atom economic method for preparing natural compounds and pharmaceutical targets.To improve the selectivity and activity of C-H bonds,transition-metal catalyzed ligand-directed C-H functionalization reactions have received significant attentions,especially the strong coordination bidentate directing groups because they facilitate catalytic functionalization of inert C(sp~3)-H bonds,and also reflect unique reactivity in some non-noble metals catalyzed direct functionalization of C-H bonds.This dissertation is mainly focused on the studies of bidentate directing group-assisted transition-metal-catalyzed unactivated C-H transformation,which includes:1.Cu and Ni Catalyzed Direct ortho-Alkynylation of Unactivated(Hetero)aryl C-H bondsWe have developed unactivated C(sp~2)-H alkynylation reaction using Cu and Ni as catalyst using bidentate PIP-amine directing group.The reaction of copper/silver-mediated oxidative alkynylation of unactivated(hetero)arl C-H bonds with terminal alkyne has broad substrate scope,high functional-group tolerance,and compatibility with a wide range of heterocycles,providing an efficient synthesis of aryl alkynes;The reaction of nickel-catalyzed alkynylation of benzamides has some advantages.No organic and metallic oxidants and expensive ligands are required.A broad range of benzamides and bromoalkynes bearing various synthetically useful functional groups are compatible with this reaction.The versatility of this protocol has been further demonstrated by the controllable mono-and di-alkynylation.Importantly,substrate/catalyst ratios of up to 200,highlighting the potential of its synthetic applications.2.Ni-Catalyzed Alkenylation of Unactivated C(sp~3)-H bondsWe have developed nickel-catalyzed alkenylation of unactivated C(sp~3)-H bonds with vinyl iodides using bidentate PIP-amine directing group.The catalytic system comprises an inexpensive and air-stable Ni(acac)2 as catalyst and BINOL as the ligand,which is highly efficient for the alkenylation of ?-methyl C(sp~3)-H bonds of abroad range of aliphatic carboxamides.The resulting olefins can serve as versatile handles for the further preparartion.We also demonstrated the synthesis of functionalized carboxamides bearing a-quaternary carbon centers from simple pivalamide via nickel-catalyzed sequential C(sp~3)-H bond functionalization.3.Pd-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C(sp~3)-H bondsWe have developed a general and practical Pd-catalyzed intermolecular silylation of primary and secondary C-H bonds of amino acids and simple aliphatic acids using 8-aminoquinoline as directing group.This method provides divergent and stereoselective access to avariety of optical?-silyl-a-amino acids.It can be readily performed on a gram scale and latestage functionalization of biological small molecules.Moreover,several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this ?-C(sp~3)-H silylation process.