A novel and concise synthetic access to chiral 2-substituted-4-piperidone  

作　　者：CHEN BaiLing WANG Bing LIN GuoQiang 

机构地区：[1]Department of Chemistry, Fudan University [2]Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences

出　　处：《Science China Chemistry》2014年第7期945-953,共9页中国科学（化学英文版）

基　　金：CAS Key Laboratory of Synthetic Chemistry of Natural Substances (2008DP173071) for analysis support

摘　　要：A novel and concise synthetic access to enantiopure chiral 2-aryl/alkyl substituted 4-piperidone has been demonstrated.This new route features two key steps:the highly diastereoselective conjugate addition of homochiral lithium amides to trans-β-substituted-α,β-unsaturated methyl esters guaranteed the enantiopurity at 2 position(de>19:1)and the intramolecular attacking of carbanions to methyl esters led to the formation of the piperidone ring.A wide range of substrates,including chiral2-aryl and 2-alkyl-4-piperidones,were successfully synthesized with modest to high yield.Moreover,some non-chiral3-substituted-4-piperidones were also synthesized with enhanced ring-formation yield,implicating the versatility of this method in construction of various piperidine rings.A novel and concise synthetic access to enantiopure chiral 2-aryl/alkyl substituted 4-piperidone has been demonstrated. This new route features two key steps： the highly diastereoselective conjugate addition of homochiral lithium amides to trans-β-substituted-α,β-unsaturated methyl esters guaranteed the enantiopurity at 2 position （de 〉19：1） and the intramolecular attacking of carbanions to methyl esters led to the formation of the piperidone ring. A wide range of substrates, including chiral 2-aryl and 2-alkyl-4-piperidones, were successfully synthesized with modest to high yield. Moreover, some non-chiral 3-substituted-4-piperidones were also synthesized with enhanced ring-formation yield, implicating the versatility of this meth- od in construction of various piperidine rings.

关 键 词：chiral 2-substituted-4-piperidone homochiral lithium amide diastereoselective conjugate addition lithium-iodine ex-change intramolecular carbonyl formation 

分 类 号：TQ25[化学工程—有机化工]