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Synlett 2011(18): 2693-2696  
DOI: 10.1055/s-0031-1289543
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Ireland-Claisen Rearrangement/Lactonisation Cascade as a Key Step in Studies Towards the Synthesis of (-)-Euonyminol:

Matthew J. Webbera, Matthew Westonb, Damian M. Graingera,b, Stacy Lloyda, Sarah A. Warrena, Lyn Powellc, Alexander Alanined, Jeffrey P. Stonehousee, Christopher S. Framptonf, Andrew J. P. Whitea, Alan C. Spivey*a,b
a Department of Chemistry, South Kensington Campus, Imperial College, London SW7 2AZ, UK
Fax: +44(20)75945841; e-Mail: a.c.spivey@imperial.ac.uk;
b Department of Chemistry, University of Sheffield, Brook Hill, Sheffield S3 7HF, UK
c AstraZeneca Process Research and Development, Charter Way, Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK
d F. Hoffmann-La Roche Ltd, Pharma Research & Early Development, pRED, Medicinal Chemistry, Grenzacherstraße, CH-4070 Basel, Switzerland
e AstraZeneca R and D, Charnwood, Department of Medicinal Chemistry, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK
f Pharmorphix® Solid State Services, Sigma-Aldrich Group, 250 Cambridge Science Park, Milton Road, Cambridge, CB4 0WE, UK
Further Information

Publication History

Received 30 August 2011
Publication Date:
19 October 2011 (online)

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Abstract

Progress towards the asymmetric total synthesis of (-)-euonyminol is described with the focus on the installation of the ­oxygenation pattern on the lower rim of the molecule. An Ireland-Claisen rearrangement/lactonisation cascade has been developed and studies towards further elaboration have uncovered an intriguing tunable diastereoselective α-bromination of the resulting γ-lactone.

Key words

Ireland-Claisen - Celastraceae - bromination - euonyminol - sesquiterpene

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19

Product 18 was not fully characterised due to lack of material and this line of investigation has not been pursued further to allow verification of the stereochemistry at C-11.