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Monatshefte für Chemie - Chemical Monthly

, Volume 150, Issue 1, pp 49–58 | Cite as

Synthesis directed towards trans-clerodanes employing an exo-selective Diels–Alder reaction as a key-step

  • Jakob Wåhlander
  • Mohamed Amedjkouh
  • Lise-Lotte GundersenEmail author
Original Paper

Abstract

A potential intermediate in the synthesis of several trans-clerodane natural products has been constructed employing a Diels–Alder reaction as a key-step. Two epimeric exo-adducts were formed in a 4:3 ratio in an EtAlCl2-mediated cycloaddition of O-silylated 2-vinylcyclohex-2-enol and N-tigloylisoxazolidinone. Both isomers were converted to the trans-clerodane intermediate in four steps; reductive removal of the oxazolidinone, followed by O-benzylation, removal of the silyl protecting group, and, finally, a Dess–Martin oxidation of the deprotected alcohol to the corresponding ketone. It was possible to transform both isomers from the cycloaddition into the final target, but the major isomer was converted at greater yields. An interesting discovery made during the work was that the desilylation demanded significantly different conditions depending on which isomer was deprotected. The fact that the cycloaddition not only resulted in an excellent exo-selectivity, but also that the alkene to a large extent approached from the least hindered side, opens the possibility for enantioselective synthesis of the target compound from (R) or (S) diene starting materials in the future.

Graphical abstract

Keywords

Cycloaddition Natural products Oxazolidinone Stereoselective Terpenoid 

Notes

Acknowledgements

The Research Council of Norway is gratefully acknowledged for financial support (Grant No. 209330) to JW and for partly financing the NMR instruments used. This work was also partly supported by the Research Council of Norway through the Norwegian NMR Platform, NNP (Grant No. 226244/F50).

Supplementary material

706_2018_2277_MOESM1_ESM.docx (21.2 mb)
Supplementary material 1 (DOCX 21738 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of OsloOsloNorway

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