Preparation Of Polystyrene Nanospheres-supported Multifunctional Organocatalyst And Its Application In Asymmetric Tandem Reaction

In recent years,asymmetric organocatalysis have shown excellent catalytic performance in the synthesis of pharmaceutical intermediates,natural products and biologically active compounds.Diaryl proline silyl ether(J?rgensen-Hayashi organocatalyst)has become a star organocatalyst in asymmetric catalysis due to its high activity and high stereoselectivity in asymmetric tandem reactions such as Michael/Aldol,Michael/Henry,Michael/Michael reactions.However,in the J?rgensen-Hayashi organocatalyst-catalyzed reactions,there are some unfavorable factors including large used amount of catalyst(10-30 mol%),an equimolar amount of acid as a cocatalyst and difficult separation from the reaction mixture and reusability after the completion of reaction.From the viewpoint of green chemistry,the immobilization of J?rgensenHayashi organocatalyst to achieve the reusability has received more and more attentions.In this paper,proline derivatives such as ?,?-stilbene proline Pro and ?,?-stilbene proline trimethyl silyl ether ProTMS(J?rgensen-Hayashi catalyst)were prepared by methylation and nucleophilic addition reaction using Boc-L-proline as an raw material.Polystyrene nanosphere Poly(St-co-Pro-co-AA)E were obtained by using Pro,acrylic acid(AA)and styrene(St)as monomers cross-linked by ethylene glycol dimethacrylate via emulsion polymerization.After the reaction of the hydroxyl group in Poly(St-co-Pro-co-AA)E with trimethylsilyltriflate(TMSOTf),polystyrene nanospheresupported multifunctional catalysts Poly(St-co-ProTMS-co-AA)E were prepared and their surface morphology and catalytic performance were further investigated under different preparation conditions such as the used amount of monomers.Furthermore,N2 adsorption-desorption ? SEM ? IR and elemental analysis were used as tools to characterize their structures,surface morphologies and loaded capacities of organocatalysts.The polystyrene nanosphere-supported multifunctional organocatalysts Poly(Stco-ProTMS-co-AA)E were applied in the Michael/Michael/aldol asymmetric tandem reaction of cinnamaldehyde and 2-coumaranone.It was screened out that the hetero-geneous multifunctional organocatalyst 2e4 possessed the best catalytic performance.The effect of solvent,temperature and used amount of catalyst on the catalytic performance was investigated using 2e4.Under the optimum reaction conditions,2e4 displayed the excellent catalytic performances: 38-75 % yield,95->99 %ee,>19:1 dr in the asymmetric Michael/Michael/aldol tandem reaction of various ?,?-unsaturated aldehydes with 2-coumaranone.After the completion of reaction,the supported organocatalyst could be recovered by centrifugation method.In the fifth reused times,it was found that the stereoselectivity began to decrease slightly.The supported catalyst 2e4 was further used to catalyze the [4+2] cycloaddition reaction of ?,?-unsaturated aldehydes with 3-methylcyclohexenylidenemalononitrile.Under the optimized reaction conditions,the substrate scope of [4+2] cycloaddition reaction of ?,?-unsaturated aldehydes were investigated.The desired products were obtained in good 76-86% yield with 87->99 % ee and >19:1 dr.