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Synthesis 2011(1): 142-146  
DOI: 10.1055/s-0030-1258333
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of (±)-Crispine A via a Nitrosoalkene Hetero-Diels-Alder Addition to Ethyl Vinyl Ether

Efthymia G. Yioti, Ioulia K. Mati, Athanassios G. Arvanitidis, Zoe S. Massen, Elli S. Alexandraki, John K. Gallos*
Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Fax: +30(2310)997679; e-Mail: igallos@chem.auth.gr;
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Publication History

Received 16 September 2010
Publication Date:
15 November 2010 (online)

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Abstract

The synthesis of (±)-crispine A in 9 steps and 24% overall­ yield was achieved using a nitrosoalkene hetero-Diels-Alder­ addition to ethyl vinyl ether as the key step. The synthesis starts from commercial 3,4-dimethoxyphenylacetic acid and uses simple methods, easily accessible materials and inexpensive reagents. An isochroman derivative was unexpectedly formed in an attempted reduction of a dihydro-4H-1,2-oxazine intermediate.

Key words

alkaloids - natural products - total synthesis - hetero-Diels­-Alder reaction - hydrogenation

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10

H-11b of the major isomer 16 is coupled with both neighboring protons, as well as with the methylene protons of the dihydropyridinone ring with J = 2.2 Hz.