| As one of the most important branch of organic chemistry, diazo chemistry has been used as important synthesis tool by organic chemists due to the diversity and high efficiency of its reactions. In this field, diazo compounds can convert to metal carbene intermediates in the presence of transition metal complex. These metal carbene intermediates are widely used in organic synthesis due to their special reactivity. Our group has developed a series of metal carbene intermediates participated multi-component reactions (MCRs) based on the trapping of active ylide intermediates or zwitterionic intermediates. This type of MCRs allows the formation of several bonds in a single synthetic operation.to construct complicate compounds containing multiple chiral centers. Among them, heterocyclic compounds are one of the most important medicine intermediates, and the development of synthetic approaches to complicate heterocyclic compounds has being our research emphasis.In this thesis, we firstly developed a series of MCRs based on the strategy of the trapping of active ylide intermediates or zwitterionic intermediates with electrophiles to construct complicate oxindole derivatives. Additionally, we proposed a strategy to construct heterocyclic compounds based on the intramolecular trapping of active ylide intermediates or zwitterionic intermediates with electrophilic species. We firstly proposed and developed a new strategy based on the intramolecular trapping of active ylide intermediates with electrophilic groups to construct five-membered heterocyclic compounds containing multiple chiral centers. In the meantime, we reported a formal [3+2] annulation reaction based on the intramolecular electrophilic trapping of zwitterionic intermediates generated from electrophilic enol carbene intermediates to construct C2,C3-fused indoline derivatives.Chapter 1 was an overview of related literatures including diazo compounds, metal carbene, yilde chemistry, zwitterionic intermediates and heterocyclic compounds. A brief introduction of the designed strategies and content of this dissertation were also presented.In chapter 2, we developed CuSO4-catalyzed three-component reactions of a-diazo esters, water and isatins, and a series of 3-hydroxylindolin-2-one derivatives were achieved in a highly environmentally benign and economical protocol. In this transformation, water plays dual roles as both a reactant and the solvent, and the final products were readily separated by simple extraction of the reaction mixture. The methodology can be used to construct 3-hydroxylindolin-2-one derivatives with different isatins and diazo compounds in good yields and moderate diastereoselectivities.In chapter 3 and chapter 4, we discussed novel multi-component reactions of indoles,3-diazooxindoles and different electrophiles based on the aldol-type or Mannich-type trapping of zwitterionic intermediates, and a series of 3,3’-disubstituted 3-indol-3’-yloxindoles were constructed efficiently. 3-(2-Hydroxy-substituted)-3-indol-3’-yloxindoles were achieved via Rh2(OAc)4-catalyzed three-component reactions of 3-diazooxindoles with indoles and ethyl glyoxylate or formalin in high yields, and the products easily underwent further synthetic transformations to the key intermediates for the total synthesis of (±)-gliocladin C. The Rh2(OAc)4/chiral phosphoric acid co-catalyzed four-component reactions of indoles,3-diazooxindoles, arylamines and ethyl glyoxylate offered an extremely efficient strategy for the construction of 3,3’-disubstituted 3-indol-3’-yloxindoles with excellent diastereoselectivities (>95:5 dr) and high to excellent enantioselectivities.In chapter 5 and chapter 6, we proposed a novel strategy to construct heterocyclic compounds based on the intramolecular trapping of active ylide intermediates with electrophilic groups. In this strategy, we designed to install the ylide precursors and the trapping units in one single substrate. The metal carbene-induced ylide intermediates formed in situ from diazo compounds and the ylide precursors in the presence of transition metal complex, would undergo intramolecular trapping process with suitable electrophilic units to give heterocyclic compounds containing multiple chiral centers. With this strategy we proposed, we developed highly efficient methods for the synthesis of 3-hydroxy-2,2,3-trisubstituted indolines, multi-substituted tetrahydrofurans and pyrrolidines via intramolecular aldol-type trapping of onium ylide intermediates with ketone units.In chapter 7, we developed a diversity-oriented one-pot three-component reaction of diazo compounds with anilines and 4-oxo-enoates based on the trapping of active ylide intermediates via switchable reaction pathways. Due to the advantages of meeting the high demand of biological evaluations by providing molecules containing maximum complexities and structural diversities in minimum synthetic steps, diversity-oriented synthesis (DOS) has become an important area in the disciplines of medicinal chemistry and chemical biology. As controlled by adding sequences of the substrates and changing of reaction conditions, this three-component reaction can undergo two pathways to generate either pyrrolidines or linear α-amino ester derivatives starting from same participants.In chapter 8, we demonstrated a chiral rhodium-catalyzed dearomatizing [3+2] annulation of indoles and enoldiazoacetamides. Electrophilic enol carbene intermediates generated from enoldiazo compounds can be viewed as 1,3-dipoles possessing electrophilic character at the vinylogous position and nucleophilic character at metal carbene carbon, and this metal carbene intermediates can take part in [3+3] annulation reactions with stable 1,3-dipoles or [3+2] annulation with unsaturated compounds having nucleophilic character. Herein, we developed a Rh2(S-MSP)4-catalyzed formal [3+2] annulation reaction of indoles and enoldiazoacetamides based on the intramolecular electrophilic trapping of zwitterionic intermediates to construct cyclopenta-fused indolines in highly regio- and enantioselectivities. |
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