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Synlett 2013; 24(12): 1501-1504
DOI: 10.1055/s-0033-1339197
letter
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of Ketoses by Aldol Reaction Using Water-­Compatible Prolinamide Catalysts in Aqueous Media

Daisuke Miura
Department of Chemistry, College of Science and Technology, Meisei University, Hodokubo, Hino, Tokyo 191-8506, Japan   Fax: +81(42)5917485   Email: machinam@chem.meisei-u.ac.jp
,
Takashi Fujimoto
Department of Chemistry, College of Science and Technology, Meisei University, Hodokubo, Hino, Tokyo 191-8506, Japan   Fax: +81(42)5917485   Email: machinam@chem.meisei-u.ac.jp
,
Ayumi Tsutsui
Department of Chemistry, College of Science and Technology, Meisei University, Hodokubo, Hino, Tokyo 191-8506, Japan   Fax: +81(42)5917485   Email: machinam@chem.meisei-u.ac.jp
,
Tomoya Machinami*
Department of Chemistry, College of Science and Technology, Meisei University, Hodokubo, Hino, Tokyo 191-8506, Japan   Fax: +81(42)5917485   Email: machinam@chem.meisei-u.ac.jp
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Further Information

Publication History

Received: 27 April 2013

Accepted after revision: 21 May 2013

Publication Date:
20 June 2013 (online)

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Abstract

Prolinamido-glycosides, water-compatible organocatalysts, are capable of catalyzing the stereoselective aldol reaction in aqueous media. The aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one with aldehydo sugars in the isopropylidene form gave ketoses stereoselectively. The stereochemistry of these aldol reactions has been investigated in terms of the influence of conformational effects, and the results demonstrate that the configuration of the catalysts and the conformation of substrates are a determining factor in the stereochemical outcome of the reaction. Each of d-psicose and d-tagatose was selectively obtained from 2,3-O-isopropylidene-d-glyceraldehyde. Likewise, d-glycero-d-glucooctulose, whose structure was established by X-ray crystallography, was obtained from 2,3:4,5-di-O-isopropylidene-aldehydo-d-arabinose.

Key words

carbohydrates - aldol reaction - stereoselective synthesis - diastereoselectivity - catalysis
 

  • References and Notes

  • 6 Tsutsui A, Takeda H, Kimura M, Fujimoto T, Machinami T. Tetrahedron. Lett. 2007; 48: 5213
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  • 8 2,2-Dimethyl-1,3-dioxan-5-one (3) was synthesized by the method of Doyle and co-workers from tris(hydroxymethyl)aminomethane hydrochloride, see: Forbes DC, Ene DG, Doyle MP. Synthesis 1998; 879
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  • 9 2,3-O-Isopropylidene-d-glyceraldehyde (4) was prepared from d-mannitol as described by Schmid, see: Schmid CR, Bryant JD, Dowlatzedah M, Phillips JL, Prather DE, Schantz RD, Sear NL, Vianco CS. J. Org. Chem. 1991; 56: 4056
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  • 10 General Procedure for the Aldol Reaction of Prolinamido-glycosides Freshly distilled aldehydo sugar 4 or 9 (1.0 equiv) and 3 (1.1 equiv) were added to a stirred solution of the catalyst 1 or 2 (0.1 equiv) in H2O (100 equiv), and the solution was stirred at r.t. After TLC indicated consumption of the starting materials, the solution was diluted with EtOAc, washed with H2O, dried (Na2SO4), and concentrated to dryness. The residue was purified by column chromatography on silica gel with CHCl3–EtOAc, to afford the uloses 5, 8, and 10. After completion of the reactions, the catalysts 1 and 2 could be separated by an extraction. Concentration of the aqueous layer, followed by recrystallization from 2-PrOH gave up to 75% recovery of the catalyst. Use of recovered 1 and 2 for the aldol reactions showed that the second aldol reactions were indistinguishable from the first aldol reactions in terms of yield and diastereoselectivity.
  • 11 It is noteworthy that the foregoing reactions did not proceed at all when commercial 2,2-dimethyl-1,3-dioxan-5-one (3) and 2,3-O-isopropylidene-d-glyceraldehyde (4) were used, but when the reagents were freshly prepared, and distilled before use, the reactions progressed satisfactorily.
  • 13 2,3:4,5-Di-O-isopropylidene-aldehydo-D-arabinose (9) was prepared from D-arabinose as described by Horton, see: Eitelman SJ, Horton D. Carbohydr. Res. 2006; 341: 2658
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  • 14 Compound 10: [α]D 26.1 +99° (c 1.0, CHCl3); mp 94.0–95.5 °C. 1H NMR (600 MHz, CDCl3): δ = 1.34 (s, 3 H, IP), 1.36 (s, 3 H, IP), 1.42 (s, 3 H, IP), 1.43 (s, 3 H, IP), 1.44 (s, 3 H, IP), 1.48 (s, 3 H, IP), 3.18 (br s, 1 H, 4-OH), 3.99 (dd, 1 H, J 7,8 = 4.55 Hz, J 8a,8b = 8.51 Hz, H-8a), 4.01 (dd, 1 H, J 3,4 = 8.43 Hz, J 4,5 = 1.83 Hz, H4), 4.04–4.08 (m, 2 H, H-1a, H-7), 4.19 (t, 1 H, J 5,6 = 7.77 Hz, H-6), 4.19 (dd, 1 H, J 8a,8b = 8.51 Hz, H-8b), 4.19 (dd, 1 H, J 4,5 = 1.83 Hz, J 5,6 = 7.77 Hz, H-5), 4.30 (d, 1 H, J 1a,1b = 17.5 Hz, H-1b), 4.42 (d, 1 H, J 3,4 = 8.43 Hz, H-3). 13C NMR (150 MHz, CDCl3): δ = 23.4 (IP), 23.6 (IP), 25.3 (IP), 26.6 (IP), 26.6 (IP), 27.0 (IP), 66.6 (C-1), 67.7 (C-8), 68.3 (C-4), 72.8 (C-3), 75.8 (C-6), 77.2 (C-7), 78.4 (C-5), 101.3 (IP), 109.1 (IP), 109.7 (IP), 211.5 (C-2). ESI-TOFMS: m/z calcd for [C19H32O6 + Na]+: 379.02097; found: 379.02043. It crystallizes in the orthorhombic space group P212121 with cell parameters a = 9.553(2) Å, b = 10.880(18) Å, c = 18.020(3) Å, and Z = 4, CCDC-931166.
  • 16 The aldol reactions of 2,3;4,5-di-O-isopropylidene-aldehydo-l-arabinose using either 1 nor 2 failed under the same conditions. Because of its extremely slow reaction rate when compared with its enantiomer, only trace amounts of aldol product were observed.
  • 18 Compound 11: [α]D 25.2 +27° (c 1.0, CHCl3). 1H NMR (600 MHz, CHCl3-d): δ = 1.33 (s, 3 H, IP), 1.37 (s, 3 H, IP), 1.41 (s, 3 H, IP), 1.42 (s, 3 H, IP), 1.46 (s, 3 H, IP), 1.47 (s, 3 H, IP), 2.11 (s, 3 H, Ac), 3.72 (t, 1 H, J 5,6 = 7.27 Hz, H-6), 3.95 (q, 1 H, J 7,8a = 7.27 Hz, J 8a,8b = 8.30 Hz, H-8a), 4.01 (d, 1 H, J 1a,1b = 17.3 Hz, H-1a), 4.10–4.13 (m, 2 H, H7, H-8b), 4.28 (d, 1 H, 1 H, J 1a,1b = 17.3 Hz, H-1b), 4.44 (dd, 1 H, J 4,5 = 2.56 Hz, J 5,6 = 7.27 Hz, H-5), δ 4.53 (d, 1 H, J 3,4 = 8.45 Hz, H-3), 5.34 (dd, 1 H, J 3,4 = 8.45 Hz, J 4,5 = 2.57 Hz, H-4). 13C NMR (150 MHz, CDCl3): δ = 20.9 (Ac), 23.4 (IP), 24.2 (IP), 25.1 (IP), 26.2 (IP), 26.6 (IP), 27.3 (IP), 66.9 (C-1), 67.2 (C-8), 69.0 (C-4), 71.8 (C-3), 76.8 (C-7), 77.0 (C-6), 77.3 (C-5), 101.2 (IP), 109.7 (IP), 109.8 (IP), 170.0 (Ac), 206.7 (C-2). ESI-TOFMS: m/z calcd for [C19H30O9 + Na]+: 425.17875; found: 425.17802.