Synthesis And Application Of Pentaerythritol Supported Chiral Imidazolidin-4-one Catalysts

Chiral imidazolidin-4-one,designed and developed by Macmillan's group,is one of the most efficient chiral organocatalysts for its high efficiency and selectivity in asymmetric reactions.However,its practical use in reactions is still hindered due to the need for high catalyst loading and difficulties in recovering the catalyst from the reaction mixture.One obvious way to overcome these problems is to immobilizing or attaching the catalyst unit on a recyclable supports such as PEG,siliceous and polymer-coated mesocellular foam(MCF),fluorous tag,poly(methyl-hydrosiloxane)(PHMS),ionic liquid,and tetraaryl-phosphonium salt.The immobilization of chiral catalysts on a support allows easy recovery and recycling of catalysts in the process of facilitating product isolation and purification.Pentaerythritol,as a new support,are of high interest due to its low molecular weight,special molecular structure,and higher loading capacity than many other traditional polymer support such as PEG,dendrimer and polysterene.Owing to its dendrimer-like structure,we believe that pentaerythritol used as a support not only can solve the problem of recovering which meet the requirement of moderN green chemistry for sustainability,but also may enhance the catalytic performance like traditional dendrimer supports do,even without generation growing.Based on excellent catalytic performance of chiral imidazolidin-4-one and structural properties of pentaerythritol,we designed and synthesized pentaerythritol supported chiral imidazolidin-4-ones,and investigated their catalytic performance in Diels-Alder reactions.Using L-tyrosine methyl ester hydrochloride as a chiral starting materials,chiral imidazolidin-4-ones with reactive functional group was synthesized,and then immobilized on pentaerythritol,dipentaerythritol,tripentaerythritol with ether bond or 1,2,3-triazole as the linkage.Six kind of supported chiral catalysts were designed,but only three of them were successfully synthesized.The synthesis of both two kind of tripentaerythritol supported catalysts and dipentaerythritol supported catalyst wih 1,2,3-triazole as the linkage were failed.We speculated that the huge intramolecular steric may be the reason of the failure.The three catalysts synthesized successfully were charaterized by IR,1H NMR,13C NMR,LC MS,and their structures were consistent to the data.By studing the solubility of the three supported catalysts,it found that all the three supported catalysts can be precipitated from ether,and recovered yield is 90?95%.Three pentaerythritol supported catalysts were applied to asymmetric Diels-Alder reaction between unsaturation aldehyde and cyclopentadiene.First step was to discuss the affect of different temperature,solvent,acid addition,reaction time and the catalyst amount(based on the amount of catalysis monomer)and get the best reaction condition(25 ?,CH3CN/H2O=95/5,HClO4 as acid addition,reaction time was 24h,20%of catalysis monomer).Under this best reaction condition,we compared the performance of three supported catalysts and non-supported imidazolidin-4-ones catalyst,and found that pentaerythritol supported catalyst with the ether bond linkage has the best catalytic ability.Under the best reaction condition,the scope of Diels-Alder reactions catalyzed by pentaerythritol supported chiral imidazolidin-4-one was probed by using the different substrate with 80?96%Yeild,endo/exo 34/66?48/52,92?99%endo ee,90?98%exo ee.These catalysts can be easily separated from the reaction mixture by precipitation,and recycled 4 times without a significant loss on catalytic activity.In conclusion,a high loading and recyclable pentaerythritol supported chiral imidazolidin-4-one was developed through the simple synthesis route,and which was applied in enantioselective Diels-Alder reactions providing the desired products in good yields with excellent enantioselectivities.It is worth mentioning that the pentaerythritol supported imidazolidin-4-one catalyst,whose high loading capacity is comparable with the original Macmillan's catalyst,can be readily recovered from the reaction mixture by simple precipitation and filtration.The enantioselectivity of the recovered catalyst remained almost intact for at least four reaction cycles,while the chemical efficiency of the recovered catalyst slowly eroded upon its iterative reuse.