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Synlett 2004(4): 671-674  
DOI: 10.1055/s-2004-817775
LETTER
© Georg Thieme Verlag Stuttgart · New York

Arabinosylamine in Asymmetric Syntheses of Chiral Piperidine Alkaloids

Birgit Kranke, Dominique Hebrault, Martin Schultz-Kukula, Horst Kunz*
Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
Fax: +49(6131)3924786; e-Mail: hokunz@uni-mainz.de;
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Publication History

Received 27 November 2003
Publication Date:
10 February 2004 (online)

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Abstract

The stereodifferentiating potential of arabinosyl ald­imines was utilized in stereoselective syntheses of 2-substituted ­dehydropiperidinones and their further transformation to 2,6-cis-substituted piperidinones. The absolute configuration was proven by X-ray analysis and by the synthesis of the enantiomerically pure alkaloid (+)-dihydropinidine. The presented method offers the ­possibility to synthesize piperidine derivatives enantiomeric to those obtained by the application of the corresponding galactosyl­amine auxiliary.

Key words

carbohydrate auxiliaries - arabinosylamine - domino Mannich-Michael reaction - piperidine alkaloids - conjugate cuprate addition

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Compoumd 6d: [a]D 25 +66.6 (c 1, CHCl3). 1H NMR (200 MHz, CDCl3): d = 6.90 (d, 1 H, J H-6,H-5 = 7.3 Hz, CH=CH), 5.55 (t, 1 H, J H-2 ′ ,H-1 ′ = 9.5 Hz, J H-2 ′ ,H-3 ′ = 9.5 Hz, H-2¢),
5.30-5.20 (m, 1 H, H-4¢), 5.13 (dd, 1 H, J H-3 ′ ,H-2 ′ = 10.0 Hz, J H-3 ′ ,H-4 ′= 3.2 Hz, H-3¢), 4.93 (d, 1 H, J H-5,H-6 = 7.3 Hz, CH=CH), 4.44 (d, 1 H, J H-1 ′ ,H-2 ′ = 9.3 Hz, H-1¢), 4.02 (dd, 1 H, J H-5 ′ a,H-5 ′ b = 13.2 Hz, J H-5 ′ a,H-4 ′ = 2.0 Hz, H-5¢a), 3.80-3.70 (m, 1 H, PrCHN), 3.67 (d, 1 H, J H-5 ′ b,H-5 ′ a = 13.2 Hz, H-5¢b), 2.60 (dd, 1 H, J H-3a,H-3b = 16.6 Hz, J H-3a,H-2 = 6.3 Hz, CHHC=O), 2.34 (d, 1 H, J H-3b,H-3a = 16.6 Hz, CHHC=O), 2.00-1.75 [m, 1 H, (CHH)2CH3], 1.65-1.50 (m, 1 H, (CHH)2CH3), 1.30-1.10 (m, 27 H, piv CH3), 0.86 [t, 3 H, J = 7.3 Hz, (CH2)CH 3] ppm. 13C NMR (50.3 MHz, CDCl3): δ = 192.15 (C=O), 177.21, 176.76 (pivC=O), 149.92 (CH=CH), 99.79 (CH=CH), 92.13 (C-1¢), 71.13, 67.97, 66.06 (C-2¢, C-3¢, C-4¢), 66.22 (C-5¢), 53.48 (PrCHN), 38.97 (CH2C=O), 38.89, 38.82, 38.77 (pivCquart.), 32.66 [(CH2)CH3], 27.21, 27.13, 27.02 (piv-CH3), 18.90 [(CH2)CH3], 13.81 [(CH2)CH3] ppm; X-ray analysis: P212121(orthorhombic), a = 9.8895(13) Å, b = 10.1820(11) Å, c = 30.614(4) Å, V = 3082.7(6) Å3, z = 4, F(000) = 1136, CAD4 Enraf Nonius, Cu-Kα, SIR-92, SHELXL-97. Further details of the crystal structure analysis are available on request from the Cambridge Crystallographic Data Centre quoting the deposit number CCDC 229785.

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X-ray analysis: P1(triclinic), a = 10.1869(6) Å, b = 13.1017(12) Å, c = 15.5126(12) Å, V = 1901.1(3) Å3, z = 2, F(000) = 716, CAD4 Enraf Nonius, Cu-Kα, SIR-92, SHELXL-97. Further details of the crystal structure analysis are available on request from the Cambridge Crystallographic Data Centre quoting the deposit number CCDC 229786.

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Compound 10: [α]D 25 +11.1 (c 1, EtOH). 1H NMR (200 MHz, DMSO): δ = 9.07 (br s, 1 H, NH), 8.68 (1 H, NH), 3.15-2.80 (m, 2 H, H-1, H-6), 1.90-1.00 (m, 13 H, CH2, CH3), 0.87 [t, 3 H, J = 7.1 Hz, (CH2)2CH 3] ppm. 13C NMR (50.3 MHz, DMSO): δ = 55.98, 52.52 (C-2, C-6), 34.82, 29.78, 27.05, 22.01, 18.75, 17.86 (CH2, CH3), 13.68 [(CH2)2 CH3] ppm.