Construction of Hollow Mesoporous Organic Polymer Nanospheres Supported Chiral Multicatalyst and Study on Interaction Mechanism between Multiple Catalysts
Author:Xie Guang Xin
Supervisor:ma xue bing
Optically active molecules with multiple chiral centers are key structures for the construction of bioactive chiral drugs.“Multi-catalysed/multi-components asymme-tric organocascade”is an important strategy for building optically active molecules in high activity and excellent stereoselectivity,which has great creativity and advanta-ge to construct novel structures.Homogenization of multiple catalysts is the most effective strategy to reduce the cost of synthesis.However,several key scientific pro-blems and technologies should be urgently solved:（1）The lack of a simple strategy for the immobilization of various expensive homogeneous chiral catalysts;（2）String-ent requirements for catalytic mass transfer in complex heterogeneous organocascades owing to the transmission of multi-components to the surface of multi-catalysts;（3）the detrimental interactions of multiple catalysts often lead to significant reduction in stereoselectivity,which is difficult to meet the demand for the high-purity of optically active molecules.In this paper,a simple strategy for the immobilization of multiple catalysts is developed,and a multiple catalysts-functionalized hollow mesoporous organic poly-meric nanosphere is constructed.By regulating the mesoporous structure,morphology,particle size of organic polymeric catalyst support and controllable functionalization strategy of multiple catalysts,the key scientific issues such as the mass transfer of reactants and the interactions among multiple catalysts in heterogeneous“Multi-catalysed/multi-components asymmetric organocascade”is effectively solved to con-struct a highly efficient heterogeneous"Multi-catalysed/multi-components asymme-tric cascade reactions".The second chapter was aimed at mass transfer limitation of catalyst carrier to fabricate the hollow structure through PS-templated method and mesoporous shell via metal ion adsorption,in-situ metal salt expansion and porogen removal,respectively.The hollow mesoporous organic polymer nanospheres with large specific surface area(138.4 m2 g-1)and pore volume(0.47 cc g-1)significantly improved the mass transfer of reactants inside the backbone of carrier structure.The hollow mesoporous organic polymer microspheres were sulfonated by ClSO3H at room temperature to give the high acid exchange capacity of 2.67 mmol g-1.The star chiral organocatalyst 9-amino（9-deoxy）-cinchonidine(0.98 mmol g-1)could be available anchored by simple acid-base interaction.The hollow mesoporous organic polymeric nanosphere has the characteristics of small particle size（180 nm）,regular spherical morphology,hollow and mesoporous shell（2-15 nm）.In the catalytic asymmetric aldol reaction and double-Michele organocascade reactions,the yield,diastereoselectivity and enantiose-lectivity of the hollow mesoporous organic polymeric nanosphere displayed the high-er catalytic performances than those of corresponding mesopore-dificient structure.Meanwhile,the synergistic catalytic mechanism between two catalysts in the catalytic reaction was discussed in depth,which optimal molar ratio is SO3H/CDNH2=1.01/1.During the recycling process,the hollow mesoporous organic polymer nanosphere has good mechanical stability and exhibits good reusability（after 5 cycles,63%yield,90%ee and 92:8 D.r.）.The third chapter focused on the influence of the transmission distance of react-ants on the mass transfer in the catalyst carrier,and further improves the mass transfer of reactants.The hollow mesoporous organic polymer nano-bowls（HMOPBs）were prepared by adjusting the polymerization time to controll the outer shell thickness.The as-fabricated HMOPBs had a structure with hollow interior,mesoporous shell and thin shell thickness（16 nm）and possessed large specific surface area of 185.7 m2 g-1,which resulted in the higher reaction activity than the corresponding sphere in the sulfonation process.The sulfonated HMOPBs had the acid content of 2.85 mmol H+g-1 and can effectively immobilized 9-amino（9-deoxy）-quinucine（QNNH2）with the high loading capacity of QNNH2(1.35 mmol g-1).Due to the thinner shell thickness and mesopore-abundant structure,the mass transfer in the catalytic process was signi-ficantly improved,and the excellent catalytic performance（92-98%ee,93:7-96:4 D.r.）was obtained in the asymmetric double-Michael organocascade for bulky 2,4-substi-tuted reactants.The QNNH2-functionlized hollow mesoporous organic polymeric nanosphere had a good reusability(5th cycle:51%yield,93%ee and 92:8 D.r.).In the fourth chapter,the negative interactions of multicatalysts in heterogene-ous“multi-catalysed/multi-components asymmetric organocascade”are solved by the partition isolation strategy.Using hollow mesoporous nanosphere as a starting carrier,double-shelled hollow mesoporous organic polymeric nanosphere was prepared via suspension polymerization and acid-base interaction,in which chiral primary amine（QNNH2）was anchored by sulfonic acid into the inner shell and proline（ProTMS）was covalently anchored into the outer shell.The multifunctional double-shelled nanosphere with the inner shell thickness of 36 nm and the outer shell thickness of 29 nm possessed the large specific surface area(68.6 m2 g-1)and pore volume(0.30 cc g-1).The loading capacities of inner QNNH2 and outer ProTMS were 0.43 mmol g-1 and 1.33 mmol g-1,respectively.Driven by the concentration difference of reactants inside and outside the sphere,the Michael addition/α-ammonia cascade could be carried out sequentially in the inner and outer shell according to the order of homo-geneous reaction mechanism.Catalytic experiments showed that the reactants achieve Michael addition under the synergistic catalysis of the outer ProTMS and carboxylic acid,and the reaction intermediate penetrated into the inner shell to produce the final product promoted by an inner catalyst combination of QNNH2/SO3H,where the detri-mental interactions of QNNH2 and SO3H with the first-step Michael addition was avoided.Therefore,it was observed that the stereoselectivity of the Michael addition/α-amination organocascade was enhanced from the 70%ee and anti/syn=70:30 in one-pot homogeneous catalysis to 82%ee and anti/syn=84:16.In summary,a novel hollow mesoporous polystyrene catalyst support with small size and regular morphology was prepared through functional polymerization by us-ing low-cost,readily available styrene as a monomer in this paper.The functional nanosphere,nano-bowl and double-shelled nanosphere showed significantly improved mass transfer,and could solve the basic scientific problems such as synergistic catalysis and compartmental catalysis of multiple catalysts by effectively regulating and controlling the interactions of heterogeneous multiple catalysts.In the complex heterogeneous"multi-catalyzed/multi-component asymmetric organocascade",the as-fabricated well-shaped heterogeneous multiple catalysts had the good to excellent catalytic performances and reusability.