Arabinosylamine in Asymmetric Syntheses of Chiral Piperidine Alkaloids

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.

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

References

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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¢),
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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) ų, z = 2, F(000) = 716, CAD4 Enraf Nonius, Cu-K_α, 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.

<A NAME="RG33603ST-16">16</A>

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.

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