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

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Abstract

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 method in construction of various piperidine rings.

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Authors and Affiliations

  1. Department of Chemistry, Fudan University, Shanghai, 200433, China

    Bai-Ling Chen, Bing Wang & Guo-Qiang Lin

  2. Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China

    Guo-Qiang Lin

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  1. Bai-Ling Chen
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  2. Bing Wang
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  3. Guo-Qiang Lin
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Correspondence to Bing Wang or Guo-Qiang Lin.

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Chen, BL., Wang, B. & Lin, GQ. A novel and concise synthetic access to chiral 2-substituted-4-piperidone. Sci. China Chem. 57, 945–953 (2014). https://doi.org/10.1007/s11426-014-5065-3

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