C-H Functionalization Assisted By Nitrogen Containing Directing Groups

Direct functionalization of C-H bonds which is characterized by artful strategy of reduced reaction steps and no pre-functionalized substrates has emerged as an efficient and atom economic method for preparing natural compounds and pharmaceutical targets.The study of C-H activation has become a hot spot in organic chemistry.However,it remains a challenge to overcome the high energy of C-H bonds and realize site-and chem-selective C-H activation.This dissertation is mainly focused on transition-metal(include Palladium,Copper and Ruthenium)-catalyzed C-H bonds functionalization via chelation assistance and new strategy to construct C-O,C-X and C-N bond,which includes:1.Palladium-Catalyzed Functionalization of Unactivated β-C(sp~3)-H Bond ofAmides to Synthesize Substitued Oxazolines A method that enabled the expeditious synthesis of oxazolines from amides via pyridine directed Pd-catalyzed C(sp~3)-H functionalization and sequential C-O cyclization has been described.Both methyl and methylene C(sp~3)-H bonds could react efficiently to give the desired oxazolines in good yields.The resulting oxazolines could be further converted into the corresponding β-amino alcohols by hydrolysis.Preliminary studies indicated that the reaction might go through a chlorination/nucleophilic cyclization sequence.2.Copper-catalyzed ortho-Halogenation of Arenes and HeteroarenesA Copper-catalyzed ortho-halogenation of C(sp)-H bonds using a bidentate PIP-amine directing group with NXS(X = Cl,Br,I)has been developed.The reaction was scalable and tolerated a broad range of functional groups and heteroarenes,providing an efficient access to halogenated arenes and heteroarenes.The synthetic potential of this protocol was demonstrated by gram scale synthesis of halogenated arene and easy removal of the PIP directing group.3.Ruthenium-catalyzed meta-Selective CAr-H Benzylation of ArenesA meta-selective CAr-H benzylation of arenes via pyridine directed Ru-catalyzed C-H activation and cross-delydrogenative coupling of inert aromatic C(sp~2)-H bonds with C(sp~3)-H bonds in toluene derivatives has been developed.This reaction showed excellent site-selectivity and tolerated a wide range of functional groups,providing a new strategy for the synthesis of diarylmethane moiety.Preliminary studies suggested that this reaction might proceed through radical mechanism.