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Synlett 2002(10): 1637-1640
DOI: 10.1055/s-2002-34215
LETTER
© Georg Thieme Verlag Stuttgart · New York

The Asymmetric Synthesis of d-Galactose via an Iterative syn-Glycolate Aldol Strategy

Stephen G. Davies*, Rebecca L. Nicholson, Andrew D. Smith
The Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QY, UK
e-Mail: steve.davies@chem.ox.ac.uk;
Further Information

Publication History

Received 2 August 2002
Publication Date:
23 September 2002 (online)

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Abstract

The asymmetric synthesis of d-galactose has been completed in eight steps and in >14% yield from simple starting materials via an iterative syn-glycolate aldol strategy.

Key Words

asymmetric synthesis - monosaccharides - iterative glycolate aldol reaction - d-galactose

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Experimental Procedure for Aldol Reactions: CF3SO3H (1.2 equiv) was added to BEt3 (1 M in hexanes, 1.2 equiv) at r.t. then warmed to 40 °C for 10 minutes before cooling to 0 °C and subsequent addition via cannula to a solution of N-acyl-oxazolidin-2-one (1 equiv) in CH2Cl2. After 10 minutes, i-Pr2NEt (1.4 equiv) was added and the reaction mixture stirred for a further 20 minutes before cooling to -78 °C and the addition of freshly distilled aldehyde (1.1 equiv). After 30 minutes the reaction mixture was warmed to 0 °C and stirred for a further hour before the addition of MeOH-H2O2 (v/v, 1:1). The reaction mixture was extracted with CH2Cl2, washed with brine, dried and concentrated in vacuo before purification by flash column chromatography.

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Experimental Procedure for DIBALH Reduction: DIBALH (1 M in hexanes, 2 equiv) was added to a stirred solution of N-acyl-oxazolidin-2-one (1 equiv) in anhydrous CH2Cl2 at
-78 °C. After 30 minutes, the reaction mixture was quenched with saturated aqueous NH4Cl solution and stirred for a further 20 minutes. The resultant emulsion was filtered through Celite®, dried and concentrated in vacuo before purification by flash column chromatography.

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1H NMR data for tetrose 8; δH (400 MHz, CDCl3) 0.01, 0.04 [2 × 3 H, s, Si(CH3)2 t-Bu], 0.86 [9 H, s, SiC(CH 3 )3], 3.53 [1 H, dd, J = 9.8 Hz, 4.9, C(4)H A ], 3.61 [1 H, dd, J = 9.8 Hz, 5.6, C(4)H B ], 3.88 [1 H, dd, J = 4.5 Hz, 1.3, C(2)H], 4.16-4.19 [1 H, m, C(3)H], 4.48 [2 H, ABq, J = 12.2 Hz, OCH 2 Ph], 4.57 [1 H, AB, J = 12.0 Hz, C(2)OCH A HBPh], 4.77 [1 H, AB, J = 12.0 Hz, C(2)OCH A H BPh], 7.27-7.37 (10 H, m, PhH), 9.76 (1 H, d, J = 1.3 Hz, CHO).

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1H NMR data for lactone 10; δH (400 MHz, CDCl3) 2.56 (1 H, d, J = 2.3 Hz, OH), 3.68-3.76 [2 H, m, C(6)H 2 OBn], 4.08-4.11 [1 H, m, C(3)H], 4.17 [1 H, t, J = 2.3 Hz, C(4)H], 4.32 [1 H, d, J = 9.7 Hz, C(2)H], 4.43-4.47 [1 H, m, C(5)H], 4.52 [2 H, ABq, J = 11.7 Hz, C(6)H2OCH 2 Ph], 4.62 [1 H, d, J = 11.2 Hz, C(4)OCH A HBPh], 4.72 [1 H, d, J = 11.2 Hz, C(2)OCH A HBPh], 4.85 [1 H, d, J = 11.2 Hz, C(4)OCHA H B Ph], 5.19 [1 H, d, J = 11.2 Hz, C(2)OCHA H B Ph], 7.21-7.43 (15 H, m, PhH).

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Commercially available from the Aldrich Chemical company.