Trifluoromethanesulfonic Acid Efficiently Catalyzed the Intramolecular Glycosidation of 1-C-Alkyl-d-hexopyranoses to Form the Anhydroketopyranoses Having 6,8-Dioxabicyclo[3.2.1]octane Structures

Abstract

The intramolecular glycosidation of the 1-C-alkyl-d-hexopyranose derivatives to form the anhydroketopyranoses having 6,8-dioxabicyclo[3.2.1]octane structures was investigated. We synthesized several 1-C-alkyl-2,3,4-tri-O-benzyl-d-hexopyranoses and found that only 5 mol% trifluoromethanesulfonic acid efficiently promoted the intramolecular glycosidation to afford the desired anhydroketopyranoses in good yields.

Key words

anhydro form - anhydroketopyranose - 1-C-alkyl-hexo­pyranose - intramolecular glycosidation - trifluoromethanesulfonic acid

References

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• 2a Hanessian S. Total Synthesis of Natural Products: The ‘Chiron’ Approach   Pergamon Press; Oxford: 1983. 
• 2b Bols M. Carbohydrate Building Blocks   John Wiley; New York: 1996.  p.43-48  
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• 7b As the analogues of the 1-C-alkyl-hexopyranose derivatives, the glycosidation using the 1-C-alkoxyalkyl-hexopyranose derivatives was reported. See: Heskamp BM. Veeneman GH. van der Marel GA. van Boeckel CAA. van Boom JH. Tetrahedron  1995,  51:  5657 
• 7c As the 1-C-alkyl-hexofuranose derivative, the glycosidation using 2,3:5,6-di-O-isopropyl-idene-1-C-methyl-d-mannofuranosyl acetate was reported. See: Dondoni A. Marra A. Rojo I. Scherrmann M.-C. Tetrahedron  1996,  52:  3057 
• 8 Yamanoi T. Oda Y. Yamazaki I. Shinbara M. Morimoto K. Matsuda S. Lett. Org. Chem.  2005,  2:  242 
• Compounds 1a-e and 6a were synthesized as follows (Scheme 3). The reaction of 6-O-acetyl-2,3,4-tri-O-benzyl-d-glucopyranose (9) using DMSO-Ac₂O gave the corresponding 6-O-acetyl-2,3,4-tri-O-benzyl-d-glucono-1,5-lactone (10) in the good yield of 92%. The alkyl groups were then introduced into C-1 of 10 by the reaction of the carbonyl group at C-1 with organometallic reagents such as RMgX or RLi. The reaction of 10 with MeLi (2.4 equiv) in dry THF at -78 °C gave 6-O-acetyl-2,3,4-tri-O-benzyl-1-C-methyl-α-d-glucopyranose (11a) and 2,3,4-tri-O-benzyl-1-C-methyl-α-d-glucopyranose (1a) in 14% and 64% yields, respectively. The treatment of 11a using NaOMe in MeOH quantitatively afforded 1a. The reaction using AllMgCl and n-BuLi similarly gave the mixtures of 6-O-acetyl-1-C-allyl-2,3,4-tri-O-benzyl-α-d-glucopyranose (11b) and 1-C-allyl-2,3,4-tri-O-benzyl-α-d-glucopyranose (1b) in 30% and 54% yields, and of 6-O-acetyl-2,3,4-tri-O-benzyl-1-C-n-butyl-d-glucopyranose (11c) and 2,3,4-tri-O-benzyl-1-C-n-butyl-α-d-glucopyranose (1c) in 64% and 12% yields, respectively. The reactions using PhMgCl and PhCH₂MgCl afforded 6-O-acetyl-2,3,4-tri-O-benzyl-1-C-phenyl-α-d-glucopyranose (11d) and 6-O-acetyl-1-C-benzyl-2,3,4-tri-O-benzyl-α-d-glucopyranose (11e) in 89% and 82% yields, respectively, with almost no production of the deacetylated compounds. It seemed that these bulky organometallic reagents were apt to produce the nucleophilic attack on the conformationally fixed carbonyl group at C-1 of 10 rather than on the acetyl group at C-6. The treatment of 11b-e using NaOMe in MeOH quantitatively afforded 1b-e. 2,3,4-Tri-O-benzyl-1-C-methyl-α-d-mannopyranose (6a) was similarly prepared in 82% yield from 6-O-acetyl-2,3,4-tri-O-benzyl-d-manno-1,5-lactone(13). Preparation of 9 and 12 was reported in the following literature. See:
• 9a Koto S. Morishima N. Takenaka K. Kanemitsu K. Shimoura N. Kase M. Kojiro S. Nakamura T. Kawase T. Zen S. Bull. Chem. Soc. Jpn.  1989,  62:  3549 
• 9b Murakata C. Ogawa T. Carbohydr. Res.  1992,  235:  95 
• 9c The oxidation of 9 using pyridinium chlorochromate also gave 10 in a moderate yield. See: Horito S. Asano K. Umemura K. Hashimoto H. Yoshimura J. Carbohydr. Res.  1983,  121:  175 
• 10a Boon G.-J. Isles S. Setala P. Synlett  1995,  755 
• 10b Bernlind C. Oscarson S. J. Org. Chem.  1998,  63:  7780 
• 11 Grindley TB. Glycoscience: Chemistry and Chemical Biology I   Fraser-Reid B. Tatsuta K. Thieme J. Springer; Berlin: 2001.  p.4-51  

12

Typical Intramolecular Glycosidation Procedure (Table 1, Entry 4).
A typical glycosidation procedure is as follows. To a stirred solution of TfOH (0.48 µL, 0.0054 mmol) was added 1a (50 mg, 0.11 mmol) in MeCN (2 mL) at 0 °C in the presence of dry MgSO₄ (ca. 100 mg) in an Ar atmosphere. The resulting mixture was stirred for 2 h. The reaction was then quenched by the addition of a sat. NaHCO₃ solution (5 mL). The reaction mixture was extracted with EtOAc, and the organic layer was washed with H₂O and a sat. NaCl solution. After the organic layer was dried over Na₂SO₄, the solvent was evaporated under reduced pressure. The crude product was purified by preparative silica gel TLC (EtOAc-hexane = 1:2) to give 2a (45 mg, 93%).
Compound 2a: [α]_D ²³ -47.7 (c 1.54, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.49 (3 H, s, H-2′), 3.23 (1 H, s, H-4), 3.31 (1 H, s, H-2), 3.59 (1 H, s, H-3), 3.75 (1 H, dd, J = 6.2 Hz, J = 6.9 Hz, H-7a), 3.96 (1 H, d, J = 6.9 Hz, H-7b), 4.34-4.39 (3 H, m, OCH ₂Ph and OCHaHbPh), 4.53 (1 H, m, OCHaHbPh), 4.53 (1 H, d, J = 6.2 Hz, H-1), 4.58-4.61 (2 H, m, OCH ₂ Ph). ¹³C NMR (150 MHz, CDCl₃): δ = 21.0 (C-2′), 65.5 (C-7), 71.0 (OCH₂Ph), 71.2 (OCH₂Ph), 72.3 (OCH₂Ph), 74.5 (C-2), 75.2 (C-3), 75.7 (C-1), 77.3 (C-4), 107.0 (C-5). HRMS (ESI): m/z calcd for C₂₈H₃₀O₅Na⁺: 469.1991; found: 469.2032.
Compound 2b: [α]_D ²³ +7.6 (c 4.57, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 2.56 (1 H, dd, J = 7.6 Hz, J = 14.4 Hz, H-2′a), 2.64 (1 H,dd, J = 7.6 Hz, J = 14.4 Hz, H-2′b), 3.24 (1 H, s, H-4), 3.26 (1 H, s, H-2), 3.54 (1 H, s, H-3), 3.66 (1 H, dd, J = 6.2 Hz, J = 6.9 Hz, H-7a), 3.94 (1 H, d, J = 6.9 Hz, H-7b), 4.29-4.34 (3 H, m, OCH ₂Ph and OCHaHbPh), 4.41-4.52 (3 H, m, OCH ₂Ph and OCHaHbPh), 4.56 (1 H, d, J = 5.5 Hz, H-1), 5.03-5.05 (2 H, m, H-4′), 5.77 (1 H, m, H-3′). ¹³C NMR (150 MHz, CDCl₃): δ = 38.1 (C-2′), 65.7 (C-7), 70.9 (OCH₂Ph), 71.5 (OCH₂Ph), 72.2 (OCH₂Ph), 74.6 (C-2), 74.9 (C-3), 75.5 (C-1), 76.2 (C-4), 107.2 (C-5), 118.4 (C-4′), 132.0 (C-3′). HRMS (ESI): m/z calcd for C₃₀H₃₂O₅Na⁺: 495.2147; found: 495.2195.
Compound 2c: [α]_D ²³ -36.7 (c 1.08, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.84 (3 H, t, J = 6.9 Hz, H-5′), 1.16 (1 H, m, H-3′a), 1.25 (2 H, m, H-4′), 1.36 (1 H, m, H-3′b), 1.75 (1 H, m, H-2′a), 1.90 (1 H, ddd, J = 13.1 Hz, J = 3.4 Hz, J = 13.7 Hz, H-2′b), 3.25 (1 H, s, H-4), 3.31 (1 H, s, H-2), 3.60 (1 H, s, H-3), 3.70 (1 H, dd, J = 6.9 Hz, J = 6.2 Hz, H-7a), 3.98 (1 H, d, J = 6.9 Hz, H-7b), 4.32-4.40 (3 H, m, OCH ₂Ph and OCHaHbPh), 4.49-4.57 (3 H, m, OCH ₂Ph and OCHaHbPh), 4.59 (1 H, d, J = 6.2 Hz, H-1). ¹³C NMR (150 MHz, CDCl₃): δ = 14.0 (C-5′), 22.9 (C-4′), 24.1 (C-3′), 32.9 (C-2′), 65.6 (C-7), 70.9 (OCH₂Ph), 71.4 (OCH₂Ph), 72.0 (OCH₂Ph), 74.7 (C-2), 75.0 (C-3), 75.4 (C-1), 76.2 (C-4), 107.9 (C-5). HRMS (ESI): m/z calcd for C₃₁H₃₆O₅Na⁺: 511.2460; found: 511.2510.
Compound 2d: [α]_D ²³ -3.5 (c 2.71, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 3.39 (1 H, s, H-4), 3.50 (1 H, s, H-2), 3.68 (1 H, s, H-3), 3.81 (1 H, dd, J = 5.5 Hz, J = 6.2 Hz, H-7a), 4.03 (2 H, dd, J = 12.4 Hz, J = 3.4 Hz, OCH ₂Ph), 4.07 (1 H, d, J = 6.9 Hz, H-7b), 4.34 (2 H, dd, J = 12.4 Hz, J = 3.4 Hz, OCH ₂Ph), 4.56 (1 H, d, J = 13.1 Hz, OCHaHbPh), 4.67 (1 H, d, J = 13.1 Hz, OCHaHbPh), 4.79 (1 H, d, J = 6.2 Hz, H-1). ¹³C NMR (150 MHz, CDCl₃): δ = 65.6 (C-7), 71.0 (OCH₂Ph), 71.6 (OCH₂Ph), 72.2 (OCH₂Ph), 74.6 (C-2), 76.2 (C-3), 76.3 (C-1), 77.6 (C-4), 106.9 (C-5). HRMS (ESI): m/z calcd for C₃₃H₃₂O₅Na⁺: 531.2147; found: 531.2196.
Compound 5d: [α]_D ²³ -74.5 (c 0.47, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 3.55 (1 H, s, H-2), 3.77 (1 H, d, J = 5.5 Hz, H-4), 3.86 (1 H, d, J = 5.5 Hz, H-3), 3.94 (1 H, dd, J = 8.2 Hz, J = 5.5 Hz, H-7a), 3.95 (1 H, d, J = 11.7 Hz, OCHaHbPh), 4.04 (1 H, d, J = 11.7 Hz, OCHaHbPh), 4.42 (1 H, d, J = 8.2 Hz, H-7b), 4.44 (1 H, d, J = 12.4 Hz, OCHa′Hb′Ph), 4.45 (1 H, d, J = 12.4 Hz, OCHa′Hb′Ph), 4.53 (1 H, d, J = 12.4 Hz, OCHa′′Hb′′Ph), 4.63 (1 H, d, J = 6.2 Hz, H-1), 4.66 (1 H, d, J = 12.4 Hz, OCHa′′Hb′′Ph). ¹³C NMR (150 MHz, CDCl₃): δ = 66.1 (C-7), 71.2 (OCH₂Ph), 72.4 (OCH₂Ph), 73.3 (OCH₂Ph), 75.0 (C-3), 75.4 (C-1), 76.9 (C-2), 77.7 (C-4), 107.6 (C-5). HRMS (ESI): m/z calcd for C₃₃H₃₂O₅Na⁺: 531.2147; found: 531.2178.
Compound 2e: [α]_D ²³ -35.1 (c 2.32, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 2.97 (1 H, d, J = 13.4 Hz, H-2′a), 3.23 (1 H, s, H-4), 3.29 (1 H, s, H-2), 3.34 (1 H, d, J = 13.7 Hz, H-2′b), 3.45 (1 H, dd, J = 6.9 Hz, J = 6.2 Hz, H-7a), 3.60 (1 H, s, H-3), 3.91 (1 H, d, J = 6.9 Hz, H-7b), 4.33 (3 H, m, OCH ₂Ph and OCHaHbPh), 4.43 (1 H, d, J = 12.4 Hz, OCHa′Hb′Ph), 4.50 (1 H, d, J = 12.4 Hz, OCHaHbPh), 4.53 (1 H, d, J = 5.5 Hz, H-1), 4.56 (1 H, d, J = 13.0 Hz, OCHa′Hb′Ph). ¹³C NMR (150 MHz, CDCl₃): δ = 39.5 (C-2′), 65.7 (C-7), 70.9 (OCH₂Ph), 71.5 (OCH₂Ph), 72.0 (OCH₂Ph), 74.5 (C-2), 74.9 (C-3), 75.3 (C-1), 76.8 (C-4), 107.2 (C-5). HRMS (ESI): m/z calcd for C₃₄H₃₄O₅Na⁺: 545.2304; found: 545.2354.
Compound 5e: [α]_D ²³ -19.3 (c 1.97, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 2.95 (1 H, d, J = 14.4 Hz, H-2′a), 3.43 (1 H, d, J = 14.4 Hz, H-2′b), 3.48 (1 H, d, J = 1.4 Hz, H-2), 3.52 (1 H, dd, J = 6.9 Hz, J = 5.5 Hz, H-7a), 3.56 (1 H, d, J = 4.8 Hz, H-4), 3.81 (1 H, dd, J = 5.5 Hz, J = 1.4 Hz, H-3), 4.12 (1 H, d, J = 6.9 Hz, H-7b), 4.26 (1 H, d, J = 11.7 Hz, OCHaHbPh), 4.40 (1 H, d, J = 5.5 Hz, H-1), 4.43-4.51 (5 H, m, OCH ₂Ph × 2 and OCHaHbPh). ¹³C NMR (150 MHz, CDCl₃): δ = 39.1 (C-2′) 65.9 (C-7), 71.2 (OCH₂Ph), 71.3 (OCH₂Ph), 73.0 (OCH₂Ph), 74.2 (C-3), 75.1 (C-1), 76.2 (C-2), 76.5 (C-4), 107.8 (C-5). HRMS (ESI): m/z calcd for C₃₄H₃₄O₅Na⁺: 545.2304; found: 545.2352.
Compound 7a: [α]_D ²³ +12.1 (c 2.4, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.52 (3 H, s, H-2′), 3.48 (1 H, s, H-2), 3.53 (1 H, d, J = 5.5 Hz, H-4), 3.78-3.81 (2 H, m, H-3 and H-7a), 4.18 (1 H, d, J = 7.6 Hz, H-7b), 4.38 (1 H, d, J = 12.4 Hz, OCHaHbPh), 4.44-4.50 (4 H, m, H-1 and OCH ₂Ph and OCHaHbPh), 4.53-4.56 (2 H, m, OCH ₂Ph). ¹³C NMR (150 MHz, CDCl₃): δ = 20.9 (C-2′), 65.7 (C-7), 71.2 (OCH₂Ph), 71.7 (OCH₂Ph), 73.1 (OCH₂Ph), 74.1 (C-3), 75.1 (C-1), 76.3 (C-2), 77.1 (C-4), 107.1 (C-5). HRMS (ESI): m/z calcd for C₂₈H₃₀O₅Na⁺: 469.1991; found: 469.2030.

Scheme 3