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Catalytic Double Asymmetric Henry Reaction And Its Application In The Synthesis Of Reboxetine

Posted on:2018-04-22Degree:MasterType:Thesis
Country:ChinaCandidate:C LiuFull Text:PDF
GTID:2381330518982992Subject:Physical chemistry
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The catalytic asymmetric Henry reaction is a kind of classical carbon-carbon bond formation reaction,its significance lies not only in the product of beta nitro alcohol by different reaction of other functional groups,but also be the construction of chiral center,achieve chiral proliferation.When the substrate has a chiral center,can use the catalytic asymmetric Henry reaction to construct two stereogenic centers selectively generated,single configuration diastereoisomers,which has very important significance in organic synthesis.The purpose of this dissertation is to develop a new catalytic asymmetric Henry reaction system,which is used as an important method to construct chiral center to synthesize the four enantiomers of Reboxetine,a kind of antidepressant drug.Therefore,this dissertation mainly includes the following two parts:1?Catalytic double asymmetric Henry reactionWith cheap chiral mandelic acid as starting materials,synthesis of chiral substrates,1-tert-Butyldimethylsilyloxy-l-phenyl acetaldehyde.The catalytic double asymmetric Henry reaction was conducted under the conditions of Nitromethane was used as the substrate and solvent,and Cu(OAc)2·H2O was used as the metal salt,and 2-amino phenyl ethanol derivatives were used as ligands.The experimental results show that the 5 mmol%(1S,2R)-1,2-diphenyl-2-piperidino-1-ylethanol(L3*),(1R,2S)-1,2-diphenyl-2-piperidino-1-ylethanol(ent-L3*)ligands and 5 mmol%Cu(OAc)2·H2O generated in situ catalyst in nitromethane solution(1.5 ml/mmol)in catalytic diastereoselectivity asymmetric Henry reaction of nitromethane and 1-tert-Butyldimethylsilyloxy-l-phenyl acetaldehyde can get optimal catalytic effect.2?Synthesis of four diastereoisomers of ReboxetineThe product of catalytic diastereoselectivity asymmetric Henry reaction,1-(tert-Butyldimethylsilyloxy)-3-nitro-l-phenylpropan-2-ol was used as the key synthetic block for the synthesis of the four enantiomers of Reboxetine.The product of nitro alcohol,after several steps,removal of TBS,Pd-C catalytic reduction of hydrogenation,amidation,cyclization,reduction,Boc protected,bromination,hydroxyl on phenol removal 'etherification,removal of Boc,the final product Reboxetine four diastereoisomers were Synthesized successfully.
Keywords/Search Tags:Catalysis, double asymmetric Henry reaction, Reboxetine, diastereoisomers, synthesis
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