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Synlett 2003(1): 0051-0054
DOI: 10.1055/s-2003-36227
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Short Enantioselective Synthesis of Naturally Occurring Muscarine Alkaloids from 1,4-Hexadiene

Jens Hartung*, Patricia Kunz, Stefanie Laug, Philipp Schmidt
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
Fax: +49(931)8884606; e-Mail: hartung@chemie.uni-wuerzburg.de;
Further Information

Publication History

Received 24 September 2002
Publication Date:
18 December 2002 (online)

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Abstract

Short enantioselective syntheses of naturally occurring muscarine alkaloids 1a-d starting from (Z)-1,4-hexadiene (2) and its E-configured isomer 4 have been devised. Key transformations in both sequences were (i) asymmetric dihydroxylation of 1,4-hexadienes 2 and 4 and (ii) application of a novel diastereoselective bromoetherification of (2S,3R)-5-hexene-2,3-diol (3) (40% ee) and (2S,3S)-5-hexene-2,3-diol (5) (90% ee) which was initiated by a vanadium(V)-catalyzed oxidation of bromide using tert-butyl hydroperoxide as primary oxidant.

Key words

bromide - cyclization - muscarine alkaloids - oxidation - tetrahydrofuran - vanadium

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17

(Z)-1,4-Hexadiene(2) (Fluka) (E)-1,4-hexadiene(4) (Chemsampco) are commercially available and were used as recieved.

20

R f values of hexenediols (SiO2, Et2O): 0.61 for (2S,3R)-5-hexene-2,3-diol(3), [19] 0.59 for (2S,3S)-5-hexene-2,3-diol(5), [19] 0.69 for (Z)-4-hexene-1,2-diol and for (E)-4-hexene-1,2-diol. Ee values of diols 3 and 5 were determined by GC on a β-Dex-325 column (Supelco).

25

Hartung, J.; Greb, M.; pehar, K.; Köhler, F.; Kluge, M.; Csuk, R. in preparation.

31

Analytical data (1H NMR and 13C NMR in D2O) obtained for alkaloids 1a-d matched with the values reported in the literature; [10-13] 1a: 40% ee; [α]D 25 = +6.0° (c = 1.0, EtOH); 1b: 40% ee; [α]D 25 = -13.1° (c = 1.9, EtOH); 1c: 90% ee; [α]D 25 = +19.8° (c = 0.9, EtOH); 1d: 90% ee; [α]D 25 = +14.6° (c = 2.2, EtOH). [32]