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Synthesis 2009(19): 3251-3258  
DOI: 10.1055/s-0029-1216935
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Access to All-trans 5-Alkylpiperidine-3,4-diols: Application to the Asymmetric Synthesis of the 1-N-Iminosugar (+)-Isofagomine

Arnaud Rivesa, Yves Génisson*a, Vanessa Faugerouxa, Nathalie Saffonb, Michel Baltasa
a SPCMIB, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 9, France
Fax: +(33)(5)61556011; e-Mail: genisson@chimie.ups-tlse.fr;
b SFTCM, FR2599, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 9, France
Further Information

Publication History

Received 9 March 2009
Publication Date:
28 August 2009 (online)

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Abstract

Access to 3,4-disubstituted N-benzylprolinol derivatives is described that, after optimization of the ring-enlargement reaction conditions, could be efficiently transformed into the corresponding 3-hydroxypiperidines. This approach was applied to the asymmetric synthesis of (+)-isofagomine relying on regio- and stereoselective oxirane opening with the cyanide anion of a pivotal epoxypyrrolidine.

Key words

iminosugar - piperidine - ring enlargement - epoxide opening

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Crystal data for 12: C14H16N2O, M = 228.29, orthorhombic, P2 (1)2 (1)2 (1), a = 4.8314 (4) Å, b = 9.9404 (8) Å, c = 25.912 (2) Å, α = β = γ = 90˚, V = 1244.44 (18) ų, Z = 4, ρcalcd = 1.218 mg/m³, F(000) = 488, λ = 0.71073 Å, T = 173 (2) K, crystal size 0.70 × 0.10 × 0.10 mm³, 4458 reflections collected (2407 independent, R int = 0.0408), R1 [I > 2σ(I)] = 0.0510, wR2 [all data] = 0.1115, largest diff. peak and hole: 0.202 and -0.164 e˙Å-³. CCDC 722378 contains the supplementary crystallographic data for 12. It can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk].

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Crystal data for 16: C15H19NO3, M = 261.31, monoclinic, P2 (1), a = 9.3250 (2) Å, b = 4.80970 (10) Å, c = 15.5678 (4) Å, α =  γ = 90˚, β = 102.439 (2)˚, V = 681.83 (3) ų, Z = 2, ρcalcd = 1.273 mg/m³, F(000) = 280, λ = 0.71073 Å, T = 173 (2) K, crystal size 0.8 × 0.10 × 0.10 mm³, 10163 reflections collected (3246 independent, R int = 0.0214), R1 [I > 2σ(I)] = 0.0476, wR2 [all data] = 0.1289, largest diff. peak and hole: 0.252 and -0.172 e˙Å-³. CCDC 722379 contains the supplementary crystallographic data for 16. It can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk].

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SHELXL-97, Program for Crystal Structure Refinement: Sheldrick, G. M., University of Göttingen, 1997.