The Synthesis Of Supported Chiral Catalysts By RAFT And Its Application In The Synthesis Of Chiral Secondary Alcohol

Optically active alcohol is an extremely important organic synthesis intermediates and natural compounds and bioactive substances contain this structural unit.And the synthesis method has gradually become the hotspot of research.The asymmetric catalytic method is the most ideal and most effective method for preparing chiral secondary alcohols.However,there are still many common problems of small molecule catalyst in the preparation of chiral secondary alcohol,such as how to effectively separate the catalyst and the product,and automated production,and so on.Therefore,the paper studies that uses the reversible addition-fracture chain transfer radical polymerization?RAFT?to prepare polystyrene-supported catalysts with molecular weight Mn controllable and uniform degree of polymerization to solve the above problems.In the preparation of the structured polystyrene-supported pyrrolidine alcohol by RAFT polymerization,we select the use of Grignard route to prepare high activity RAFT reagent-cumyl dithiobenzoate CDB and optimize its reaction conditions,thereby selecting methyl tert-butyl ether as extractant,70?is the optimum reaction temperature and the final yield is increased from 25%to 48.7%.In this experiment,we use N-Boc-L-4-hydroxy-L-proline methyl ester which is in amino and carboxy protected as raw material,through Grignard reaction,substitution reaction,hydrolysis deprotection reaction to prepare styrene monomer FSt with catalytically active sites,then use styrene?St?and functional styrene?FSt?as monomer,CDB as RAFT reagent,AIBN as initiator,utilize RAFT polymerization technology to prepare PS-supported pyrrolidine alcohol.The optimum reaction conditions were as follows:the polymerization time was 8h,the polymerization temperature was 75?,the optimum amount of AIBN was 1.5%.RAFT reagent CDB has good control ability for solution polymerization of styrene monomer,When the amount of CDB is constant and the ratio of n?St?/n?FSt?is different,the molecular weight of the polymer remained substantially unchanged,PDI was less than 1.26.In addition,by changing the amount of CDB can be molecular weight Mn 680g/mol-12975g/mol and the structure of the large molecular chain so as to achieve the purpose of polymerization control.The PS-supported CBS catalyst in the asymmetric reduction of acetophenone means using the PS-supported pyrrolidols as precursors and reacteing with methyl boronic acid to produce polystyrene-supported CBS catalyst.The ee value of the product obtained by the supported catalyst was 94.1%,the yield was 96%,the main product configuration R,and the small molecular catalyst product had an ee value of95.9%,the yield was 98%,the main product configuration S,but the recovery difficulties and high economic costs makes it difficult to achieve industrial production.The recoveries of the catalysts prepared by the RAFT method were 98.6%,while that of the catalysts prepared by the ordinary radical polymerization was 79.5%.The optimum amount of catalyst is 0.1eq;the optimum amount of BH₃·THF is 0.6eq;the catalyst is recovered by simple precipitation filtration and the product ee value of not less than 94%when repeated 4 times.We studied the asymmetric nucleophilic addition reaction of benzaldehyde with diethylzinc catalyzed by polystyrene-supported catalysts and the optimum reaction conditions were as follows:the reaction temperature was 25?,the amount of catalyst was 15mol%,and the dosage of nucleophile Et₂Zn was 1.5eq.We found the recovery rate of the catalyst prepared by RAFT polymerization method was 97.8%,while the recovery rate of the catalyst prepared by the traditional free radical method was 78.9%.The stereoselectivity of the supported catalyst is higher than that of the small molecule catalyst,and the supported catalyst was reused 4 times when the product ee was not less than 92%.