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New strategy for the synthesis of ladybird beetle azaphenalene alkaloids using a combination of allylboration and intramolecular metathesis. Total synthesis of (±)-Hippocasine and (±)-epi-Hippodamine

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Abstract

A new strategy for assembly a tricyclic skeleton of ladybirds azaphenalene alkaloids (coccinellides) was developed based on the combination of allylboration reaction and intramolecular metathesis. The first key step is the 1,2-organolithiation of 4-picoline with (4,4-dieth-oxybutyl)lithium with subsequent reductive allylation with triallylborane leading to trans-2-allyl-6-(4,4-diethoxybutyl)-4-methyl-1,2,3,6-tetrahydropyridine. The 4,4-diethoxybutyl substituent was further converted to 4-acetoxy-5-hexenyl in four steps, then, the product obtained was involved in the second key step, the intramolecular allylic amination upon treatment with a [Pd] or an [Ir] catalyst giving diastereomeric bicyclic terminal dienes (∼1: 1), which were separated by chromatography. The stereochemistry of one of the dienes is the same as that in alkaloid Hippocasine. The third key step (the intramolecular metathesis reaction) includes the final assembly of the azaphenalene system. The tricyclic derivative obtained contains two differently substituted C=C bonds, selective hydrogenation of one of which (Pd/C) leads to (±)-Hippocasine, whereas exhaustive hydrogenation gives (±)-epi-Hippodamine.

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Authors and Affiliations

  1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991, Moscow, Russian Federation

    N. Yu. Kuznetsov & Yu. N. Bubnov

  2. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 ul. Vavilova, 119991, Moscow, Russian Federation

    N. Yu. Kuznetsov, S. E. Lyubimov, I. A. Godovikov & Yu. N. Bubnov

Authors
  1. N. Yu. Kuznetsov
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  2. S. E. Lyubimov
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  3. I. A. Godovikov
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  4. Yu. N. Bubnov
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Correspondence to N. Yu. Kuznetsov or Yu. N. Bubnov.

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On the occasion of the 80th anniversary of the N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0529–0537, February, 2014.

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Kuznetsov, N.Y., Lyubimov, S.E., Godovikov, I.A. et al. New strategy for the synthesis of ladybird beetle azaphenalene alkaloids using a combination of allylboration and intramolecular metathesis. Total synthesis of (±)-Hippocasine and (±)-epi-Hippodamine . Russ Chem Bull 63, 529–537 (2014). https://doi.org/10.1007/s11172-014-0464-3

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  • DOI: https://doi.org/10.1007/s11172-014-0464-3

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