Chrial Metal Complexes Catalyzed Enantioselective 1,3-Dipolar Cycloaddition And Mukaiyama-mannich Reaction

The development of new organic synthesis methods can provide a convenient and effective way for the development of pharmaceuticals,pesticides,materials and fine chemicals.It is one of research topics in organic chemistry to explore the cheap and efficient catalysts and the mild reaction conditions,to realize the construction of carbon-carbon bond and carbon-nitrogen bond,further to enable the easy synthesis of complex molecules.This paper mainly focused on the following aspects:First,catalytic asymmetric 1,3-Dipolar cycloaddition between electron-deficient olefins with nitrones were studied,and a series of optical isoxazolidine compounds were prepared.Second,enantioselective Mukaiyama-Mannich addition of enol silicon ethers and N-sulfonyl a-ketiminoesters were developed,affording a range of benzofused 5-membered sultams derivatives bearing chiral quaternary carbon center.Third,a method for the synthesis of a,P-unsaturated alkenyl phosphines by palladium-catalyzed construction of alkenyl Csp2-P bonds was explored.The asymmetric 1,3-dipolar cycloaddition reaction of ?,?-unsaturated acyl carboxylates and nitrones was developed,offering isoxazolidines bearing three adjacent chiral centers in good yields with excellent diastereoselectivities and enantioselectivities,using a vicinal carbonyl-type electron-deficient olefin as dipolarophile,The reaction mechanism is as following:a five-membered ring reaction intermediate by 1,4-coordination pattern was formed,thereby,reducing the HOMO energy of the electron-deficient olefin and activating the substrate.This work further complements well the reaction type involved in the C=C system of a,P-unsaturated acyl carboxylates.A novel approach to chiral 2,3-aryl(alkyl)substituted 4-ester-substituted isoxazolidines compounds has been developed.The Cu(II)-Inda-BOX catalyzed cycloaddition of ?,?-unsaturated acylphosphonates and nitrones is carried out at 0?,giving rising to the corresponding cycloadducts in good yields with excellent regio-,diastereo-and stereoselectivities.The method led to isoxazolidine compounds containing three adjacent chiral centers under mild conditions,while the phosphonates moiety can be easily transformed to other functional groups.The asymmetric Mukaiyama-Mannich addition reaction of aromatic ketone derived silicon ethers and N-sulfonyl a-ketiminoesters was studied.Under optimum reaction conditions(using 2-10 mol%of Ni(C104)·6H2O-BOX as a catalyst,0? or room temperature,CHCI3 as solvent),a series of benzofused 5-membered sultams derivatives bearing chiral quaternary carbon center were obtained in excellent yields(89-99%)and enantioselectivities(84-99%ee).The method can be extended to the romote conjugate system and steric hindered enol silicon ether with the same excellent catalytic results.The Mannich addition products can be derivatized to acridines or multicyclic benzofused sultams.A palladium-catalyzed coupling reaction between halogenated olefins bearing a-electron-withdrawing group with diphenyl phosphine was developed,and affording a series of novel arylmethylidene mediated P,O ligands.The synthetic method can be used as a complement to construct a novel alkenyl Csp,2-P bonds.Furthermore,The alkenyl phosphide products can be applied to different reactions to examine its potential coordination and catalytic properties.