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An Improved Practical Route to (±)‐Epibatidine through L ‐Proline Catalyzed Intramolecular Michael Addition
Author(s) -
Huang Xiangui,
Shi Hongwei,
Ren Jiangmeng,
Liu Guixia,
Tang Yun,
Zeng Bubing
Publication year - 2012
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201200298
Subject(s) - chemistry , intramolecular force , yield (engineering) , epibatidine , benzoic acid , ketone , catalysis , proline , michael reaction , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , amino acid , biochemistry , receptor , materials science , nicotinic agonist , nicotinic acetylcholine receptor , metallurgy
This paper describes a rapid and practical synthetic route involving six‐step reactions towards the diastereoselectively synthesis of (±)‐ endo ‐Epibatidine, starting from 6‐chloro‐3‐pyridinecarboxaldehye. The effective Henry reaction gave precursor ( E )‐6‐(6‐chloropyridin‐3‐yl)‐5‐nitrohex‐5‐en‐2‐one ( 3a ) which could be used in the next step. Various benzoic acid derivatives were used to optimize intramolecular Michael addition of ketone to pyridinylnitroolefins to provide the key intermediate 3‐(6‐chloropyridin‐3‐yl)‐4‐nitrocyclohexanone ((±)‐ 7a ) with high yield.