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Synthesis 2009(20): 3411-3418  
DOI: 10.1055/s-0029-1216946
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

The Synthesis of Functionalised Bicyclo[3.3.1]nonanes Related to Huperzine A

Jarrod Ward, Alison B. Johnson, George R. Clark, Vittorio Caprio*
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland 1142, New Zealand
Fax: +64(9)3737422; e-Mail: v.caprio@auckland.ac.nz;
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Publikationsverlauf

Received 10 June 2009
Publikationsdatum:
21. August 2009 (online)

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Abstract

Radical cyclisation-based synthetic routes to the core structure of huperzine A, are described. Cyclisation of (2-pyridyl)methyl radicals derived from two model [(2-phenylseleno­methyl)-3-pyridyl]cyclohexenones, proceeds in 6-exo-trig mode to give bicyclo[3.3.1]nonanes. Cyclisation yields are related to the substitution pattern and relative stereochemistry about the enone ring. Cyclisation precursors were accessed by either conjugate addition of a (3-pyridyl)cuprate onto an enone or by Diels-Alder cycloaddition of a (3-pyridyl)-substituted alkene with Rawal’s diene.

Key words

huperzine A - radical cyclisation - cuprate - selenium - Diels-Alder

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19

X-ray crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-734079. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB12 1EZM UK [fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk].