Azomethine Ylides-based Asymmetric Catalysis And Their Applications

As a kind of very important reactive intermediates in asymmetric catalysis,azomethine ylides have been widely used in the asymmetric synthesis of chiral nitrogen-containing heterocycles and unnatural amino acids during the last ten years.This thesis mainly focuses on azomethine ylides-based novel asymmetric 1,3-dipolar cycloaddition and 1,6-conjugate addition and their applications,providing elegant and efficient access to structurally and biologically important pyrrolidines and unnatural ?-amino acids with excellent stereoselectivities,including the following three aspects of research work:1.Copper(1)catalyzed 1,3-dipolar cycloaddition of azomethine ylides with ?-phthalimidonitroetheneThree dihydroimidazole based novel chiral N,O-ligands with "synergistic steric effects" were designed and synthesized.These N,O-ligands have been successfully applied in Cu(I)catalyzed 1,3-dipolar cycloaddition of azomethine ylides with ?-phthalimidonitroethene,affording the desired products in high yields(76-98%),excellent diastereo-(93:7-98:2 dr)and enantio-selectivities(90-99%ee).In addition,highly functionalized 3,4-diaminopyrrolidines in high optical purity could be generated efficiently from the cycloadducts via subsequent raney Ni-catalyzed reduction and deprotection of phthalyl.2.Copper(1)catalyzed 1,3-dipolar cycloaddition of azomethine ylides with ?-phthaliminoacrylate estersThe first CuBF4/Ph-Phosferrox complex catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with ?-phthaliminoacrylate esters was developed under mild conditions,providing the desired pyrrolidine ?-amino acid derivatives in high yields(81-98%)with excellent diastereo-and enantioselectivities(>20:dr,92->99%ee).This process provides new opportunities for the asymmetric synthesis of structural diversified and biologically important free pyrrolidine ?-amino acids.3.Copper(?)catalyzed 1,6-conjugate addition/aromatization of azomethine ylides to para-quinone methidesA straightforward and highly efficient synthetic approach for the synthesis of ?,?-bis-Aryl-?-amino acid esters via catalytic asymmetic 1,6-conjugate addition/aromatization of azomethine ylides to para-quinone methides was developed for the first time.The CuBF4/Ph-Phosferrox catalytic system exhibited excellent efficiency with 1 mol%catalyst loading,providing desired products in high yields(90-98%)with good to excellent diastereoselectivities(90:10-99:1 dr)and excellent enantioselectivities(95->99%ee).Importantly,this protocol was amenable to gram-scale synthesis of novel unnatural amino acid esters with only 0.5 mol%of catalyst,and the corresponding adducts can be easily converted to enantiopure vicinal amino alcohols,valuable chiral building blocks for the synthesis of novel chiral oxazolidinones and pyox ligands.