Method Development And Synthetic Application Of Transition Metal Catalyzed C-H Activation And Alkene Difunctionalization

Transition metal-catalyzed C-H activation and vicinal difunctionalization of alkenes have emerged as hot topic in organic synthesis,since these methods could provide straightforward and atom-economic alternatives for the synthesis of synthetically very important building blocks.However,copper catalyzed direct C(sp2)-H bond and C(sp3)-H bond activations remain a challenge.In addition,for the transition metal-catalyzed C-H bond activation reactions,to realize its application in the total synthesis of natural products is one of the difficulties in the research nowadays.On the other hand,vicinal difunctionalization of olefins which act as an effective measure for the construction and transformation of functional groups in the field of organic synthesis,are also be widely researched and applicated.In the past ten years,relevant workers have made great efforts and contributions about transition metal-catalyzed difunctionalization of olefins,and made remarkable progress up to now.But for glycal and other bioactive molecules,there is still lack of report for the relevant research.Therefore,the development of a method for efficiently construct glucose derivatives may have widely application values.This dissertation are mainly focused on directing strategy,and a new bidentate directing group was designed to make systematic research on the activity and mechanism of copper(?)-catalyzed aromatic C(sp2)-H bond methoxylation.In addition to this,a palladium(?)-catalyzed C(sp3)-H functionalization directed by 8-aminoquinouine applied to the synthesis of natural products such as Tryprostatin A,Maremycin A/B and Stephacidin A was completed by us.At last,we developed a palladium(?)-promoted amino-fluorination of protected glycal,which was successfully used for synthesis a series of 2-deoxidize-2-fluoro-pyranose,including the following contents:1.Copper(?)-Catalyzed Methoxylation of Unactivated(Hetero)Aryl C-H Bonds Using a Removable Bidentate AuxiliaryThe methoxylation of unactivated(hetero)aryl C-H bonds directed by our newly developed PIP amide directing group has been achieved which occurs efficiently with catalytic amount of copper(?)salt.Methanol was used directly as solvent and also a source of methoxy reagent.The reaction proceeded under air atmosphere which act as oxidant for the environmentally benign system.Subsequently,the removal of PIP directing group was achieved under a mild condition.Due to the broad substrate scope and high functional group tolerance,a convenient and efficient way for synthesis aromatic carboxylic acid compounds containing methyl ether structure was provided.2.Synthesis of 2,5-Dioxopiperazin Contained Natural Products based on Palladium Catalyzed C-H Activation StrategyA palladium(?)-catalyzed mono-arylation of chiral alanine C(sp3)-H bonds directed by 8-aminoquinoline was developed as a strategy for the synthesis of 2,5-dioxopiperazin contained nutrual products.Tryptophan methyl ester derivatives were obtained by the removal of directing group.The total synthesis of Tryprostatin A,Maremycin A/B and formal synthesis of Stephacidin A were achieved by subsequent transitions.A new strategy was provided for goal-oriented and diversity-oriented synthesis for the above several natural products and analogues by our research.3.Palladium(?)-Catalyzed Amino-Fluorination of Pyranose Glycals and Efficiently Synthesis of 2-Deoxidize-2-Fluoro-PyranoseThe amino-fluoro-difunctionalization of pyranose glycals promoted by palladium(?)with the synergistic effect of dipyridine ligand was developed by our research.A series of 1-amino-2-fluoro-pyranose direvatives were prepared through this method,which have a broad substrate scope and high functional group tolerance.Subsequently,transformations on C-N bond were explored to realize the glycosylation with multiple kinds of nucleophilic reagents,which synthesised a series of 2-deoxidize-2-fluoro-pyranose efficiently.