Metal-stabilized Dipole Design And Applications

Nitrogen containing heterocyclic compounds are widely existed in natural alkaloids,pharmaceutical agents and many kinds of advanced materials.The development of construction of N-containing heterocycles has long been considered as a very important area in modern organic synthesis.Dipolar cycloaddition reactions have been proved to be one of the most efficient tools in annulation reaction because of the variety of dipolar precursors and their excellent synthetic efficiency.However,traditional thermal-driven dipolar reactions have some drawbacks such as the poor stability of dipolar intermediates,simple reactivity and the difficulty on asymmetric introduction.In the past several years,the application of transition metal catalysts into dipolar cycloaddition reactions has provided new opportunities in the further advancement of this research field.In this dissertation,the recent advancements in this area were reviewed and several new metal containing dipolar reactions were investigated based on new synthons designing and new reactions developing.My first project dealt with an unprecedented decarboxylation/cycloaddition sequence of cyclic allylic carbamates with sulfur ylides through the enantioselective trapping of Pd-stabilized dipolar intermediates.A series of biologically and synthetically important 3-vinyl indolines were rapidly assembled with high reaction efficiency and stereoselectivity.Detailed investigations revealed the wide substrate scope,the high enantioselectivity and several powerful applications.We then further developed a catalytic asymmetric[3+2]cycloaddition reaction of chiral palladium-containing N1-1,3-dipoles with methyleneindolinones.The reaction allows an efficient construction of 3,3'-pyrrolinyl spirooxindoles with high yields and excellent stereoselectivity(up to 93%yield,19:1 dr and>99%ee).It was demonstrated that this methodology could be applied to the synthesis of complex polycyclic structures.In addition,a new kind of transition metal containing dipolar precursor has been successfully designed and synthesized,which could generate an unprecedented 1,4-dipolar intermediate in the presence of copper.Based on this discovery,we have developed a Cu-catalyzed decarboxylative amination/hydroamination sequence of propargylic carbamates with various nucleophiles for the first time.It features an earth-abundant metal catalyst,mild conditions and high efficiency.Further one-pot treatments of the key intermediates using an acid or a base enables the controllable and divergent synthesis of two types of functionalized indoles.Moreover,experiments to demonstrate the synthetic potential of this methodology were performed.Polycyclic indolines are the common and core structural motif of many biologically interesting indole alkaloids.We also developed two copper-catalyzed cascade reactions between propargylic carbamates and indoles.By doing so,one-step and divergent synthesis of structurally distinct polycyclic indolines,quinoline-fused indolines,C(3a)-indolyl furoindolines and pyrrolo-indolines,were achieved in high synthetic efficiency and selectivity.Finally,based on the experience and new knowledge we have gained through the research work mentioned above,a copper catalyzed propargylation/intramolecular Friedel-Crafts reaction sequence was developed.Numerous 3,3'-biindole architectures were synthesized in high yields via simple operations.By introduction of chiral ligands,the first catalytic asymmetric construction of axial chiral biindole methodology has also been developed which could furnish the products with up to 91:9 er.