Synthesis of Chiral Carbohydrate Ionic Liquids

Abstract

Chiral room temperature ionic liquids, containing a carbohydrate moiety linked at the anomeric centre to an N-methylimidazolium group have been synthesised. The ionic liquids were prepared in a concise manner and provided ready access to both the d- and l-arabino enantiomers. The same strategy enabled the preparation of d-ribofuranose and d-xylofuranose analogues, in excellent yields.

Keywords

synthesis - chiral ionic liquid - carbohydrate - N-methyl­imidazolium

References and Notes

• 1a Boon JA. Levisky JA. Pflug JL. Wilkes JS.
  J. Org. Chem.  1986,  51:  480 
• 1b Welton T. Chem. Rev.  1999,  99:  2071 
• 2a Wasserscheid P. Welton T. Ionic Liquids in Synthesis   Wiley-VCH; Weinheim: 2003. 
• 2b Wasserscheid P. Keim W. Angew. Chem. Int. Ed.  2000,  39:  3772 
• 2c Sheldon RA. Chem. Commun.  2001,  2399 
• 2d Handy ST. Okello M. Tetrahedron Lett.  2003,  45:  8399 
• 2e Xu X. Kotti SRSS. Liu J. Cannon JF. Headley AD. Li G. Org. Lett.  2004,  6:  4881 
• 2f Xiao J.-C. Shreeve JM.
  J. Org. Chem.  2005,  70:  3072 
• For recent reviews, see:
• 3a Baudequin C. Baudoux J. Levillain J. Cahard D. Gaumont AC. Plaqueventa J.-C. Tetrahedron: Asymmetry  2003,  14:  3081 
• 3b Xue H. Verma R. Shreeve JM. J. Fluorine Chem.  2006,  127:  159 
• 3c Singh RP. Verma RD. Meshri DT. Shreeve JM. Angew. Chem. Int. Ed.  2006,  45:  3584 
• 3d Hagiwara R. Lee JS. Electrochemistry  2007,  75:  23 
• 3e Parvulescu VI. Hardacre C. Chem. Rev.  2007,  107:  2615 
• 3f van Rantwijk F. Sheldon RA. Chem. Rev.  2007,  107:  2757 
• 3g Winkel A. Reddy PVG. Wilhelm R. Synthesis  2008,  999 
• 3h Headley AD. Ni B. Aldrichimica Acta  2007,  40:  107 
• 4a Huddleston JG. Willauer HD. Swatloski RP. Visser AE. Rogers RD. Chem. Commun.  1998,  16:  1765 
• 4b Armstrong DW. He L. Liu Y.-S. Anal. Chem.  1999,  71:  3873 
• 4c Huddleston JG. Visser AE. Reichert WM. Willauer HD. Broker GA. Rogers RD. Green Chem.  2001,  3:  156 
• 4d Liu J.-F. Jiang G.-B. Chi Y.-G. Cai Y.-Q. Zhou Q.-X. Hu J.-T. Anal. Chem.  2003,  75:  5870 
• 5 Handy ST. Curr. Org. Chem.  2005,  9:  959 
• 6a Welton T. Coord. Chem. Rev.  2004,  248:  2459 
• 6b Lee S. Chem. Commun.  2006,  1049 
• 7 Baudequin C. Bregeon D. Levillain J. Guillen F. Plaquevent J.-C. Gaumont A.-C. Tetrahedron: Asymmetry  2005,  16:  3921 
• 8a Earle MJ. McCormac PB. Seddon KR. Green Chem.  1999,  1:  23 
• 8b Wang Z. Wang Q. Zhang Y. Bao W. Tetrahedron  2005,  46:  4657 
• 8c Carda-Broch S. Berthod A. Armstrong DW. Anal. Bioanal. Chem.  2003,  375:  191 
• 9a Baudoux J. Judeinstein P. Cahard D. Plaquevert J.-C. Tetrahedron Lett.  2005,  46:  1137 
• 9b Fringuelli F. Pizzo F. Tortoioli S. Vaccaro L. J. Org. Chem.  2004,  69:  7745 
• 9c Tosoni M. Laschat S. Bato A. Helv. Chim. Acta  2004,  87:  2742 
• 10 Baudequin C. Baudoux J. Levillain J. Cahard D. Gaumont AC. Plaqueventa J.-C. Tetrahedron: Asymmetry  2003,  14:  3081 
• 11 Levillian J. Dubant G. Abrunhosa I. Gulea M. Gaumont AC. Chem. Commun.  2003,  2914 
• 12 Pernak J. Feder-Kubis J. Chem. Eur. J.  2005,  11:  4441 
• 13a Génisson Y. Lauthde Viguerie N. André C. Baltas M. Gorrichon L. Tetrahedron: Asymmetry  2005,  16:  1017 
• 13b Ding J. Desikan V. Han X. Xiao TL. Ding R. Jenks WS. Armstrong DW. Org. Lett.  2005,  7:  335 
• 13c Jodry JJ. Mikami K. Tetrahedron Lett.  2004,  45:  4429 
• 13d Bao W. Wang Z. Li Y. J. Org. Chem.  2003,  68:  591 
• 13e Guillen F. Brégeon D. Plaquevent J.-C. Tetrahedron Lett.  2006,  47:  1245 
• 13f Ni B. Headley AD. Tetrahedron Lett.  2006,  47:  7331 
• 14 Brown T. Kadir K. Mackenzie G. Shaw G. J. Chem. Soc., Perkin Trans. 1  1979,  3107 
• 15a Barker R. Fletcher HG. J. Org. Chem.  1961,  26:  4605 
• 15b Austin PW. Hardy FE. Buchanan JG. Baddiley J. J. Chem. Soc.  1964,  2128 
• 15c Finch P. Iskander GM. Siriwardena AH. Carbohydr. Res.  1991,  210:  319 
• 15d Tejima S. Fletcher HG. J. Org. Chem.  1963,  28:  2999 
• 15e Kawana M. Kuzuhara H. Emoto S. Bull. Chem. Soc. Jpn.  1981,  54:  1492 
• 16 Yuan L. Singh G. Tetrahedron Lett.  2001,  42:  6615 
• 19 Cicchillo RM. Norris P. Carbohydr. Res.  2000,  328:  431 

17

Selected Data
Compound 14 (X = Cl): [α]_D ^²8 +28 (c 1.1, CHCl₃). IR (film): ν_max = 3429, 3143, 3064, 3032, 2923, 2870, 1634, 1578, 1556, 1454, 1364, 1264, 1157, 1090, 1030, 748, 701, 638 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 3.60 (3 H, s), 3.62
(1 H, dd, J = 2.8, 10.9 Hz), 3.82 (1 H, dd, J = 3.0, 10.9 Hz), 4.13 (1 H, m), 4.23 (1 H, t, J = 6.8 Hz), 4.41 (1 H, d, J = 11.1 Hz), 4.48 (1 H, d, J = 11.1 Hz), 4.53 (1 H, d, J = 11.9 Hz), 4.64 (2 H, d, J = 6.3Hz), 4.57 (1 H, m), 4.69 (1 H, d, J = 11.9 Hz), 6.46 (1 H, d, J = 5.8 Hz), 7.22-7.40 (16 H, m), 7.73
(1 H, m), 9.40 (1 H, s) ppm. ^¹³C NMR (100 MHz, CDCl₃):
δ = 36.0, 68.0, 72.5, 73.5, 78.2, 81.0, 82.6, 87.3, 121.5, 122.5, 128.1, 127.9, 128.1, 128.2, 128.3, 128.5, 128.6, 135.5, 136.4, 137.1, 137.2 ppm. ESI-MS: m/z calcd C₃₀H₃₃N₂O₄: 485.2435; found: 485.2423. Glass-transition temperature: 18 ˚C.
Compound 15 (X = PF₆ ^-): [α]_D ^²8 +14 (c 1.1, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 3.41 (3 H, s), 3.57 (1 H, dd, J = 3.2, 10.9 Hz), 3.75 (1 H, dd, J = 3.3, 10.8 Hz), 4.09 (1 H, m), 4.17 (1 H, t, J = 6.7 Hz), 4.37 (1 H, d, J = 10.8 Hz), 4.43-4.50 (5 H, m), 4.62 (1 H, d, J = 11.8 Hz), 6.05 (1 H, d, J = 5.6 Hz), 7.05 (1 H, t, J = 1.7 Hz), 7.15-7.36 (15 H, m), 7.39
(1 H, t, J = 1.7 Hz), 8.56 (1 H, br s) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 35.9, 68.2, 73.3, 73.4, 73.5, 78.6, 81.3, 82.3, 87.4, 121.3, 122.7, 127.7, 127.9, 128.0, 128.1, 128.2, 128.3, 128.5, 128.6, 134.9, 136.2, 137.1, 137.2 ppm. ^³¹P NMR (160 Hz, CDCl₃): δ = -142.9 (sept., J = 712.7 Hz) ppm. Glass-transition temperature -23 ˚C.
Compound 16: [α]_D ^²8 +9.5 (c 1.05, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 3.48 (3 H, s, NCH₃), 3.59 (1 H, dd, J = 3.2, 10.9 Hz), 3.76 (1 H, dd, J = 3.2, 10.9 Hz, H-5, H-5′), 4.09 (1 H, m, H-4), 4.18 (1 H, t, J = 6.4 Hz, H-3), 4.38 (1 H, d, J = 11.0 Hz), 4.45 (1 H, d, J = 11.0 Hz), 4.46-4.53 (4 H, H-2), 4.61 (1 H, d, J = 11.8 Hz), 6.22 (1 H, d, J = 5.5 Hz), 7.16-7.36 (16 H), 7.53 (1 H, t, J = 1.7 Hz,), 8.75 (1 H, br s) ppm. ^¹³C (100 MHz, CDCl₃): 35.7, 67.9, 72.2, 73.1, 75.0, 78.3, 80.9, 82.1, 87.1, 121.1, 122.1, 127.4-128.4, 134.9, 136.3, 137.0, 137.1 ppm. ^¹9F (376.5 MHz, CDCl₃): -151.0 ppm. Glass-transition temperature -36 ˚C.
Compound 19: [α]_D ^²8 +22.3 (c 1.3, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 3.46 (1 H, dd, J = 3.2, 10.6 Hz), 3.52
(1 H, dd, J = 3.5, 10.6 Hz), 3.77 (3 H, s), 4.01 (1 H, dd, J = 1.8, 5.1 Hz), 4.41-4.62 (8 H, m), 6.25 (1 H, d, J = 5.8 Hz), 7.19-7.36 (16 H, m), 7.54 (1 H, s), 9.28 (1 H, s) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 36.0, 69.7, 72.5, 73.3, 73.4, 76.4, 76.9, 77.3, 78.1, 84.7, 87.9, 121.6, 122.1, 127.6, 127.8, 127.9, 128.0, 128.1, 128.3, 128.4, 136.5, 136.8, 137.3 ppm. Glass-transition temperature 16 ˚C.
Compound 22: ^¹H NMR (400 MHz, CDCl₃): δ = 3.67-3.76 (2 H, m), 3.93 (3 H, s), 4.05 (1 H, m), 4.22 (1 H, t, J = 5.3 Hz), 4.35-4.46 (3 H, m), 4.51 (1 H, d, J = 11.9 Hz), 4.59
(1 H, d, J = 11.9 Hz), 4.62-4.69 (2 H, m), 6.30 (1 H, d, J = 3.7 Hz), 7.08 (1 H, br s), 7.11-7.36 (15 H, m), 7.39 (1 H, br s), 9.26 (1 H, br s) ppm. ^¹³C (100 MHz, CDCl₃): δ = 36.3, 68.7, 72.5, 73.3, 75.0, 75.3, 78.0, 82.1, 85.0, 121.1, 122.1, 127.7, 128.5, 135.1, 137.3, 137.7, 137.8, 137.9 ppm.
Compound 23: ^¹H NMR (400 MHz, CDCl₃): δ = 3.42 (3 H, s), 3.63 (1 H, dd, J = 2.1, 11.0 Hz), 3.89 (1 H, dd, J = 2.5, 11.0 Hz), 4.12 (1 H, m), 4.20 (1 H, t, J = 7.7 Hz), 4.38 (1 H, d, J = 10.5 Hz), 4.47 (1 H, d, J = 10.5 Hz), 4.60 (1 H, d, J = 11.9 Hz), 4.75 (1 H, dd, J = 5.8, 7.2 Hz), 4.85 (1 H, d, J = 11.9 Hz), 6.02 (1 H, d, J = 5.7 Hz), 7.06 (1 H, br s), 7.23-7.39 (10 H, m), 7.69 (1 H, br s), 8.96 (1 H, br s) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 36.1, 68.0, 72.6, 73.5, 78.1, 80.9, 82.6, 87.3, 121.6, 122.4, 127.7, 128.5, 135.8, 136.5, 137.2, 137.3.

18

General Procedure
The 2,3,5-tri-O-benzylsugar (1 mmol) was dissolved in dry CH₂Cl₂ (10 mL) and cooled to 0 ˚C under Ar atmosphere. Propane-1,3-diyldioxyphosphoryl chloride (2 mmol) was added, followed by 1-methylimidazole (2.5 mmol). The mixture was allowed to warm up to r.t. and stirred overnight (16 h). The reaction was then quenched with sat. NaHCO₃ (10 mL) and the organic layer washed with H₂O (2 × 10 mL) and dried (Na₂SO₄). The solvent was then removed in vacuo to give the crude sugar phosphate, which was re-dissolved in dry CH₂Cl₂ (10 mL) under an Ar atmosphere and cooled to -78 ˚C. trimethylsilyl triflate (cat.) was added and the mixture stirred for 2 min. 1-Methylimidazole hydrochloride (2 mmol) was then added. The reaction mixture was allowed to warm up to r.t. and stirred until TLC (CHCl₃-MeOH, 80:20) showed the reaction had gone to completion (4 h). The mixture was then diluted with CH₂Cl₂ (10 mL) and washed with sat. aq NaHCO₃ (2 × 20 mL) and H₂O (2 × 20 mL). The organic layer was dried (Na₂SO₄) and concentrated in vacuo to give a crude product, that was further purified by column chromatography (CHCl₃-MeOH, 80:20).
Silver nitrate test for ionic liquids with anions other than chloride, derived via metathesis: The ionic liquid (1 mg) is dissolved in MeOH-deionized H₂O (1:1; 1 mL). The resulting solution is tested with 0.1 M AgNO₃ (2 drops). No precipitation was observed in BF₄ and PF₆ ionic liquids.