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

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

• 1a Haines AH, Lamb AJ. Carbohydr. Res. 1999; 321: 197
• 1b Dondoni A, Merino P. J. Org. Chem. 1991; 56: 5294
• 2a List B, Lerner RA, Barbas CF. III. J. Am. Chem. Soc. 2000; 122: 2395
• 2b Sakthivel K, Not W, Bui T, Barbas CF. III. J. Am. Chem. Soc. 2001; 123: 5260
• 2c Notz W, Tanaka F, Barbas CF. III. Acc. Chem. Res. 2004; 37: 580
• 2d Córdva A, Notz W, Barbas CF. III. Chem. Commun. 2002; 3024
• 2e Nyberg AI, Usano A, Pihko PM. Synlett 2004; 1891
• 3a Suri JT, Pamachary DB, Barbas CF. III. Org. Lett. 2005; 7: 1383
• 3b Enders D, Grondal C. Angew. Chem. Int. Ed. 2005; 44: 1210
• 3c Kazmaier D. Angew. Chem. Int. Ed. 2005; 44: 2186
• 3d Grondal C, Enders D. Tetrahedron 2006; 62: 329
• 3e Ibrahem I, Córdva A. Tetrahedron. Lett. 2005; 46: 3363
• 3f Markert M, Mahrwald R. Chem. Eur. J. 2008; 14: 40
• 3g Northrup AB, MacMillan DW. C. J. Am. Chem. Soc. 2002; 124: 6798
• 3h Northrup AB, Mangion IK, Hettche F, MacMillan DW. C. Angew. Chem. Int. Ed. 2004; 43: 2152
• 3i Casas J, Engqvist M, Ibrahem I, Kaynak B, Córdva A. Angew. Chem. Int. Ed. 2005; 44: 1343
• 3j Palyman N, Niewczas I, Majewski M. Tetrahedron. Lett. 2007; 48: 9195
• 3k Niewczas I, Majewski M. Eur. J. Org. Chem. 2009; 33
• 3l Enders D, Narine AA. J. Org. Chem. 2008; 73: 7857
• 4a Dickerson TJ, Janda KD. J. Am. Chem. Soc. 2002; 124: 3220
• 4b Dickerson TJ, Lovell T, Meijler MM, Noodleman L, Janda KD. J. Org. Chem. 2004; 69: 6603
• 4c Rogers CJ, Dickerson TJ, Brogan AP, Janda KD. J. Org. Chem. 2005; 70: 3705
• 5a Pedatella S, De Nisco M, Mastroianni D, Naviglio D, Nucci A, Caputo R. Adv. Synth. Catal. 2011; 353: 1443
• 5b Burroughs L, Vale ME, Gilks JA, Forintos H, Hayes CJ, Clarke PA. Chem. Commun. 2010; 46: 4776
• 5c Scheffler U, Mahrwald R. J. Org. Chem. 2012; 77: 2313
• 6 Tsutsui A, Takeda H, Kimura M, Fujimoto T, Machinami T. Tetrahedron. Lett. 2007; 48: 5213
• 7a Chérest M, Felkin H, Prudent N. Tetrahedron. Lett. 1986; 69: 2199
• 7b Anh NT. Top. Curr. Chem. 1980; 88: 146
• 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
• 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
• 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.
• 12a Majewski M, Nowak P. J. Org. Chem. 2000; 65: 5152
• 12b Majewski M, Nowak P. Synlett 1999; 1447
• 12c Grondal C, Enders D. Tetrahedron 2006; 62: 329
• 12d Suri JT, Mitsumori S, Albertshofer K, Tanaka F, Barbas CF. III. J. Org. Chem. 2006; 71: 3822
• 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
• 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.
• 15a Wolfrom ML, Thompson A. J. Am. Chem. Soc. 1946; 68: 1453
• 15b Richtmyer NK, Bodenheimer TS. J. Org. Chem. 1962; 27: 1892
• 15c Cieplak M, Ceborska M, Cmoch P, Jarosz S. Tetrahedron: Asymmetry 2012; 23: 1213
• 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.

Conformational studies of the acyclic aldopentoses by NMR analysis were established by Horton and the term ‘sickle’ was introduced to designate the conformation generated from the extended, planar, zigzag form by rotation through 120° about an internal carbon–carbon bond. ₅ G ^– denotes the sickle conformation obtained by 120° clockwise rotation of the remote atom along the C-5–C-6 bond. For the sickle conformations, see:
• 17a Horton D. Pure Appl. Chem. 1975; 42: 301
• 17b Horton D, Wander JD. J. Org. Chem. 1974; 39: 1859
• 17c Horton D, Wander JD. Carbohydr. Res. 1969; 10: 279
• 17d Baker DC, Horton D. Carbohydr. Res. 1979; 69: 117
• 17e Horton D, Thomas S, Gallucci J. Carbohydr. Res. 2006; 341: 2211
• 17f Vejcik SM, Horton D. Carbohydr. Res. 2007; 342: 806
• 17g Horton D, Markovs RV. Carbohydr. Res. 1980; 80: 263
• 17h Horton D, Kokrady SS. Carbohydr. Res. 1980; 80: 364
• 17i Horton D, Wander JD. Carbohydr. Res. 1970; 13: 33
• 17j Horton D, Wander JD. Carbohydr. Res. 1970; 15: 271
• 17k Horton D, Wander JD. Adv. Carbohydr. Chem. Biochem. 1976; 32: 15
• 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.