Study On The Immobilization Strategy Of Chiral Phasetransfer Catalysts Containing Quaternary Ammonium Salts

Phase-transfer catalysis?PTC?has long been recognized as a versatile method for organic synthesis,because it offers several advantages,such as mild reaction conditions,simple experimental operations,suitability for large-scale synthesis,and the environmentally benign nature of the reaction system.Especially,the well-known cinchona alkaloid and binaphthyl-derived chiral quaternary ammonium salts had been synthesized and successfully applied in numerous asymmetric reactions with excellent catalytic performances,such as ?-alkylation,Mannich reaction,Aldol reaction,cyclization and conjugate addition.However,phase-transfer catalysis is practically limited by the difficult recovery of PTC catalyst,isolation from reaction mixture owing to the formation of stable emulsion.From the point of green chemistry,the heterogenization of chiral PTC catalysts by immobilizing homogeneous catalysts onto solid supports become the most common method to solve these problems and further improve the catalytic efficiency of expensive catalysts.In this paper,homogeneous cinchona alkaloid-based and BINOL-derived chiral quaternary ammonium salts were covalently immobilized onto silica,polymeric microsphere and organosilica hollow nanospheres to achieve the reusability of expensive PTC catalysts with high performance,and enhance their catalytic performance in asymmetric alkylation reactions.This paper performed research work from the three aspects shown as follow:?1?Homogeneous PTC catalyst N-?2-cyanobenzyl?-O?9?-allyl-cinchonium bromide?CDPTC?was synthesized using cinchonidine as starting material.Then the novel type of silica-supported cinchona alkaloid-based quaternary ammonium salt?SiO₂@CDPTC?was prepared by available one-pot synthesis for the first time through click reaction of the sulfhydryl group in 3-mercaptopropyl trimethoxysilane with endocyclic carboncarbon double bond in CDPTC,and subsequent hydrolysis of trimethoxysilane under acid condition.The heterogeneous PTC catalyst SiO₂@CDPTC was characterized by FT-IR,EA,TGA,SEM,TEM and N2 absorption-desorption to systematically study the chemical composition,loading capacity,surface morphology and porous structure.The covalent attachment of homogeneous CDPTC into the inorganic backbone of silica was clearly corroborated by the characteristic peaks of C-S-C,C-Si and Si-O-Si bonds in FT-IR spectroscopy.Based on the content of nitrogen,the loading capacity of CDPTC was calculated to be 0.87 mmol per gram of SiO₂@CDPTC.From TGA curves,it was observed that the thermal decomposition of SiO₂@CDPTC occurred in three steps and total thermal weight loss was 77.1%.The SEM image showed that the heterogeneous SiO₂@CDPTC has micrometer-sized honeycomb-like morphology,and the TEM image further indicated that the uniform diameter of spherical particles SiO₂@CDPTC was approximately 0.3-0.5 um.Furthermore,the more delicate surface morphology of SiO₂@CDPTC with the irregular ribbing at the distances of 0.5-1.5 nm was clearly observed by HRTEM image.The heterogeneous catalyst SiO₂@CDPTC was applied in the model enantioselective ?-alkylation of N-?diphenylmethylene?glycine tert-butyl ester.It was found that various substituted benzyl bromides,both with electron-withdrawing?-CF3 and-F?and electron-donating?-CH3?substituents,afforded the corresponding ?-alkylation products with moderate to excellent enantioselectivities?76.0-96.9% ee?in high yields?80-96%?,except that allyl bromides gave poor yields?10-50%?and enantioselectivities?52.0-67.1% ee?.After the completion of asymmetric ?-alkylation reaction,the silicasupported chiral PTC catalyst was readily recovered in quantitative yield by filtration and reused for five consecutive runs without significant loss in catalytic performances.?2?We endeavoured to introduce styrene moieties as anchorage points at different sites in the framework of Maruoka PTC catalyst through two routes to achieve the covalent immobilization of simplified Maruoka catalyst.In the former case,?R?-9 was bromized to synthesize brominated quaternary ammonium salt?R?-10.Then the 6,6'-styrene-functionalized simplified Maruoka catalyst?R?-11 was achieved through effective Suzuki coupling reaction of?R?-10 with p-styryl boronic acid.For the other route,the styrene-functionalized simplified Maruoka PTC catalyst?R?-12 with styrene moieties on the positions of quaternary ammonium salt was achieved through simple quarternization reaction of?R?-8 with bis-?4-?4-vinylphenyl?butyl?amine.Subsequently,the novel polymer microsphere-supported Maruoka PTC catalysts,donated as poly[Stco-AA-co-?R?-11] and poly[St-co-AA-co-?R?-12] respectively,were prepared by suspension polymerrization of?R?-11 or?R?-12 with styrene and acrylamide monomers using EGDMA as crosslinking agent and PVA as dispersant.The polymer microsphere-supported chiral Maruoka PTC catalysts were character-ize by FT-TR,SEM,N2 absorption-desorption and applied in benchmark enantioselective ?-alkylation reaction to study the structure-activity relationship.It was found that the surface morphology and porous feature of microsphere had a significant influence on catalytic performances in the heterogeneous ?-alkylation reaction.The poly[St-coAA-co-?R?-11] with the relatively larger surface area?33.5 m2/g?displayed the better catalytic performance.Meanwhile,due to the anchor position of styrene remote to quaternary ammonium catalytic site,poly[St-co-AA-co-?R?-11]?81-96%,96-97 %ee?displayed the superior yields and enantioselectivities to poly[St-co-AA-co-?R?-12]?78-88%,88-95 %ee?.In the heterogeneous enantioselective ?-alkylation of N-?diphenylmethylene?glycine tert-butyl ester with various electrophiles,poly[St-co-AA-co-?R?-11] afforded the corresponding products in high yields?76-96%?and enantioselectivites?88-97% ee?.Moreover,the recovered poly[St-co-AA-co-?R?-11] exhibited the higher catalytic activity than the fresh poly[St-co-AA-co-?R?-11] owing to the improved mass transfer,and achieve the yield of 96% with good enantioselectivity?91 %ee?within a shorter 48 h in the fifth run.?3?Chiral Maruoka PTC catalyst-functionalized hollow nanospheres were successfully synthesized by covalent immobilization of simplified Maruoka PTC catalyst?R?-11 onto mercapto-functionalized hollow organosilica material.For the first carrier,core-shell microsphere PS/PVP@B&M was synthesized by co-condensation of 1,2-bis?triethoxysilyl?ethane with 3-mercaptopropyl trimethoxysilane using polystyrene as hard template.The hollow organosilica microsphere B&M was obtained by etching template by extraction with DMF.For the other one,hollow mesoporous silica B#M was obtained through co-condensation of BTEE and MPTMS using polystyrene and cetyltrimethylammonium bromide as dual templates and then chemical etching.The hollow organosilica material supported Maruoka PTC catalysts,denoted as B&M@?R?-11 and B#M@?R?-11 respectively,were achieved through click reaction of chiral Maruoka phase-transfer catalyst with hollow organosilica microsphere B&M or hollow mesoporous silica B#M.The SEM images showed that the heterogeneous PTC catalyst B&M@?R?-11 has nanospherical particles with ethyl-bridged organosilica in the shell which benefit for the mass transfer effect in heterogeneous catalysis.In the model asymmetric ?-alkylation reaction,the ?-alkylation products with good enantioselectivities?85.3-90.8% ee?were obtained in high 85-96% yields.The heterogeneous PTC catalysts B#M@?R?-11 has nanospherical particles mixed with amorphous structure.In the same asymmetric reaction of N-?diphenylmethylene?-glycine tert-butyl ester with benzyl bromides,the corresponding ?-alkylation products were obtained in high yields?75-96%?with enantioselectivities of 80.5-91.2% ee.In conclusion,a series of heterogeneous recoverable silica-supported cinchonaderived PTC catalyst and polymer microsphere,organosilicon hollow microspheres and hollow mesoporous organosilica-supported simplified Maruoka PTC catalysts were successfully prepared.The immobilization of homogeneous PTC catalysts solved the recycling problem of valuable cinchona and binaphthyl-derived chiral PTC catalysts and provided an important strategy to improve the catalytic efficiency of homogeneous chiral quaternary ammonium salts PTC catalysts.