Synthetic Approach to exo-Glycals from 1-C-Vinyl-d-glycopyranose Derivatives via an S_N1′-Substitution Mechanism

Abstract

This paper describes a novel synthetic approach to exo-glycals from 1-C-vinyl-d-glycopyranose derivatives via the S_N1′-type substitution mechanism. The reaction of the 2,3,4,6-tetra-O-benzyl-1-C-vinyl-α-d-glycopyranose derivatives with several tri­methylsilylated nucleophiles was investigated. The reactions in dichloromethane-acetonitrile (1:1) at -78 °C in the presence of 20 mol% trimethylsilyl trifluoromethanesulfonate using allyltrimethylsilane and silyl enol ethers as the nucleophiles stereoselectively afforded the Z-exo-glycal derivatives in good yields.

Key words

exo-glycal - 1-C-vinyl-glycopyranose - S_N1′-type substitution - trimethylsilyl trifluoromethanesulfonate

References and Notes

• 1a Colinas PA. Lieberknecht A. Bravo RD. Tetrahedron Lett.  2002,  43:  9065 
• 1b Lin H.-C. Du W.-P. Chang C.-C. Lin C.-H. Tetrahedron Lett.  2005,  46:  5071 
• 1c Namme R. Mitsugi T. Takahashi H. Shiro M. Ikegami S. Tetrahedron  2006,  62:  9183 
• 2a Coumbarides GS. Motevalli M. Muse WA. Wyatt PB. J. Org. Chem.  2006,  71:  7888 
• 2b Taylor RJK. McAllister GD. Franck RW. Carbohydr. Res.  2006,  341:  1298 
• 2c Colinas PA. Ponzinibbio A. Lieberknecht A. Bravo RD. Tetrahedron Lett.  2003,  44:  7985 
• 2d Lay L. Meldal M. Nicotra F. Panza L. Russo G. Chem. Commun.  1997,  1469 
• 3 Yang W.-B. Yang Y.-Y. Gu Y.-F. Wang S.-H. Chang C.-C. Lin C.-H. J. Org. Chem.  2002,  67:  3773 
• 4 Tomooka K. Nakamura Y. Nakai T. Synlett  1995,  321 
• 5 Praly J.-P. Chen G.-R. Gola J. Hetzer G. Eur. J. Org. Chem.  2000,  2831 
• 6a Yamanoi T. Inoue R. Matsuda S. Katsuraya K. Hamasaki K. Tetrahedron: Asymmetry  2006,  17:  2914 
• 6b Yamanoi T. Oda Y. Matsuda S. Yamazaki I. Matsumura K. Katsuraya K. Watanabe M. Inazu T. Tetrahedron  2006,  62:  10383 
• 6c Yamanoi T. Matsuda S. Yamazaki I. Inoue R. Hamasaki K. Watanabe M. Heterocycles  2006,  68:  673 
• 6d We also reported the Brønsted acid catalyzed intramolecular β-glycosidation of 1-C-alkyl-d-hexopyranoses to form the anhydroketo-pyranoses, see: Yamanoi T. Matsumura K. Matsuda S. Oda Y. Synlett  2005,  2973 ; see also ref. 1c
• 7 Li XL. Ohtake H. Takahashi H. Ikegami S. Tetrahedron  2001,  57:  4297 
• 8 Yamanoi T. Oda Y. Heterocycles  2002,  57:  229 

9

Typical Reaction Procedure (see, Table 1, Entry 4)
A typical reaction procedure is as follows: to a stirred solution of the allyltrimethylsilane (85.1 µL, 0.54 mmol) and 1 (101.2 mg, 0.18 mmol) was added TMSOTf (6.6 µL, 0.036 mmol) in MeCN-CH₂Cl₂ (1:1, 3 mL) at -78 °C in the presence of dry CaSO₄ (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 anhydrous Na₂SO₄, the solvent was evaporated under reduced pressure. The crude product was purified by preparative silica gel TLC (EtOAc-hexane, 1:4) to give 4 (61.2 mg, 58%).
Ketopyranoside 2: [α]_D ²¹ +64.4 (c 1.12, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 3.42 (1 H, d, J = 9.6 Hz, H-2), 3.71-3.77 (2 H, m, Ha-6, H-4), 3.82 (1 H, dd, J = 3.4, 11.0 Hz, Hb-6), 3.93-3.95 (1 H, m, H-5), 3.95 (1 H, t, J = 9.6 Hz, H-3), 4.49-4.89 (8 H, m, 4 × CH₂Ph), 5.43 (1 H, dd, J = 1.4, 8.2 Hz, Ha-2′), 5.79-5.87 (2 H, m, Hb-2′, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 68.1 (C-6), 73.4 (CH₂Ph), 75.0 (CH₂Ph), 75.5 (CH₂Ph), 75.9 (CH₂Ph), 76.66, 76.7, 79.1 (C-1), 82.1 (C-2), 84.2 (C-3), 115.8 (CN), 120.2 (CH=CH₂), 132.9 (CH=CH₂). ESI-HRMS: m/z calcd for C₃₇H₃₇O₅N·Na⁺: 598.2564; found: 598.2536.
The reaction (Table 1, entry 2) gave the mixture of exo-glycal 3 and ketopyranoside 5.
Z-exo-Glycal 3: ¹H NMR (600 MHz, CDCl₃): δ = 3.71-3.81 (5 H, m, Ha-2′, H-4, H-5, H-6), 3.74 (1 H, t, J = 6.9 Hz, H-3), 3.97 (1 H, dd, J = 0.7, 6.9 Hz, H-2), 4.03 (1 H, dd, J = 8.2, 13.7 Hz, Hb-2′), 4.51-4.87 (8 H, m, 4 × CH₂Ph), 5.10 (1 H, dt, J = 0.7, 7.6 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 45.2 (C-2′), 68.5 (C-6), 72.5 (CH₂Ph), 73.5 (CH₂Ph), 74.1 (CH₂Ph), 74.3 (CH₂Ph), 77.7, 78.3, 78.4, 84.4 (C-3), 102.8 (C-1′), 153.3 (C-1).
Ketopyranoside 5: ¹H NMR (600 MHz, CDCl₃): δ = 3.42 (1 H, d, J = 9.6 Hz, H-2), 3.71-3.83 (3 H, m, H-4, H-6), 3.94-3.98 (1 H, m, H-5), 3.98 (1 H, t, J = 9.6 Hz, H-3), 4.51-4.87 (8 H, m, 4 × CH₂Ph), 5.40 (1 H, dd, J = 1.4, 11.7 Hz, Ha-2′), 5.65 (1 H, dd, J = 1.4, 18.6 Hz, Hb-2′), 5.98 (1 H, m, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 68.1 (C-6), 73.4 (CH₂Ph), 73.7 (C-5), 75.0 (CH₂Ph), 75.7 (CH₂Ph), 75.9 (CH₂Ph), 77.7 (C-4), 82.6 (C-2), 83.1 (C-3), 93.4 (C-1), 118.6 (CH=CH₂), 130.9 (CH=CH₂). ESI-HRMS (mixture of 3 and 4): m/z calcd for C₃₆H₃₇O₅N₃·Na⁺: 614.2625; found: 614.2657.
Z-exo-Glycal 4: [α]_D ²⁵ +55.6 (c 0.87, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.08 (2 H, m, H-3′), 1.27 (2 H, m, H-2′), 3.01 (1 H, dd, J = 8.6, 9.4 Hz, H-3), 3.04-3.07 (1 H, m, H-5), 3.09-3.18 (3 H, m, H-4, H-6), 3.32 (1 H, dd, J = 1.7, 8.6 Hz, H-2), 4.07-4.50 (8 H, m, 4 × CH₂Ph), 4.65 (1 H, dt, J = 1.7, 9.4 Hz, H-1′), 4.62-4.74 (2 H, m, H-5′), 5.70 (1 H, m, H-4′). ¹³C NMR (150 MHz, CDCl₃): δ = 23.7 (C-2′), 33.8 (C-3′), 68.9 (C-6), 72.4 (CH₂Ph), 73.5 (CH₂Ph), 74.3 (CH₂Ph), 74.4 (CH₂Ph), 77.8, 78.2, 79.2 (C-2), 85.2 (C-3), 109.9 (C-1′), 114.7 (C-5′), 138.5 (C-4′), 148.2 (C-1). ESI-HRMS: m/z calcd for C₃₉H₄₂O₅·Na⁺: 613.2924; found: 613.2954.
Z-exo-Glycal 6: [α]_D ²⁵ +39.5 (c 0.89, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 2.60 (2 H, m, H-2′), 3.05 (2 H, m, H-3′), 3.65 (1 H, t, J = 7.3 Hz, H-3), 3.70-3.81 (4 H, m, H-4, H-5, H-6), 3.91 (1 H, dd, J = 1.0, 7.3 Hz, H-2), 4.50-4.89 (8 H, m, 4 × CH₂Ph), 5.07 (1 H, dt, J = 1.0, 7.3 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 19.5 (C-2′), 38.7 (C-3′), 68.7 (C-6), 72.5 (CH₂Ph), 73.5 (CH₂Ph), 74.3 (CH₂Ph), 74.4 (CH₂Ph), 77.6, 78.1, 79.1 (C-2), 85.0 (C-3), 108.8 (C-1′), 148.8 (C-1), 199.4 (C-4′). ESI-HRMS: m/z calcd for C₄₄H₄₄O₆·Na⁺: 691.3030; found: 691.3077.
Z-exo-Glycal 7: [α]_D ²⁸ +47.6 (c 0.92, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 0.97 (3 H, s, Me), 0.98 (3 H, s, Me), 2.22 (1 H, dd, J = 8.1, 13.1 Hz, Ha-2′), 2.29 (1 H, dd, J = 7.6, 13.7 Hz, Hb-2′), 3.60 (1 H, t, J = 6.9 Hz, H-3), 3.64-3.71 (4 H, m, H-4, H-5, H-6), 3.83 (1 H, dd, J = 0.7, 6.2 Hz, H-2), 4.80 (1 H, dt, J = 1.4, 7.6 Hz, H-1′), 9.39 (1 H, s, H-4′). ¹³C NMR (150 MHz, CDCl₃): δ = 21.1 (Me), 21.3 (Me), 31.8 (C-2′), 46.3 (C-3′), 68.8 (C-6), 77.6, 77.8, 78.9 (C-2), 84.8 (C-3), 104.6 (C-1′), 150.1 (C-1), 204.6 (C-4′). ESI-HRMS: m/z calcd for C₄₀H₄₄O₆·Na⁺: 643.3030; found: 643.3066.
Z-exo-glycal 8: [α]_D ²⁸ +39.5 (c 0.68, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.11 (9 H, s, t-Bu), 2.36 (1 H, m, Ha-2′), 2.42 (1 H, m, Hb-2′), 2.54 (2 H, dd, J = 6.9, 7.6 Hz, H-3′), 3.66 (1 H, t, J = 7.6 Hz, H-3), 3.69-3.71 (1 H, m, H-5), 3.74-3.81 (3 H, m, H-4, H-6), 3.90 (1 H, dd, J = 1.4, 7.6 Hz, H-2), 4.51-4.84 (8 H, m, 4 × CH₂Ph), 4.98 (1 H, dt, J = 1.4, 7.6 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 19.0 (C-2′), 26.4 (Me), 36.5 (C-3′), 44.0 (C-5′), 68.8 (C-6), 72.5 (CH₂Ph), 73.5 (CH₂Ph), 74.3 (CH₂Ph), 74.4 (CH₂Ph), 77.2 (C-4), 78.2 (C-5), 79.1 (C-2), 85.1 (C-3), 109.3 (C-1′), 148.7 (C-1), 215.4 (C-4′). ESI-HRMS: m/z calcd for C₄₂H₄₈O₆·Na⁺: 671.3343; found: 671.3344.
The reaction (Table 2, entry 4) gave the exo-glycal 10 with a diastereomeric ratio of 3.5:1.
Major isomer of Z-exo-glycal 10: ¹H NMR (600 MHz, CDCl₃): δ = 0.98 (3 H, d, J = 6.9 Hz, Me), 2.07 (2 H, dd, J = 6.9, 7.6 Hz, H-3′), 2.83 (1 H, m, H-2′), 3.66 (1 H, dd, J = 7.6, 8.2 Hz, H-3), 3.64-3.67 (1 H, m, H-5), 3.73-3.80 (3 H, m, H-4, H-6), 3.91 (1 H, dd, J = 1.4, 7.6 Hz, H-2), 4.51-4.81 (7 H, m, 3 × CH₂Ph, CHaHbPh), 4.86 (1 H, dd, J = 1.2, 9.3 Hz, H-1′), 4.87 (1 H, d, J = 11.2 Hz, CHaHbPh), 4.95-5.02 (2 H, m, H-5′), 5.76 (1 H, m, H-4′). ¹³C NMR (150 MHz, CDCl₃): δ = 20.8 (Me), 29.0 (C-2′), 41.6 (C-3′), 68.8 (C-6), 72.7 (CH₂Ph), 73.4 (CH₂Ph), 74.5 (CH₂Ph), 74.6 (CH₂Ph), 77.7, 78.8, 79.3 (C-2), 85.5 (C-3), 115.6 (C-5′), 116.5 (C-1′), 137.3 (C-4′), 147.3 (C-1).
Minor isomer of Z-exo-glycal 10: ¹H NMR (600 MHz, CDCl₃): δ = 0.99 (3 H, d, J = 6.9 Hz, Me), 2.00 (1 H, m, H-3′), 2.83 (1 H, m, H-2′), 3.90 (1 H, dd, J = 1.4, 7.6 Hz, H-2), 4.51-4.81 (7 H, m, 3 × CH₂Ph, CHaHbPh), 3.64-3.68 (2 H, m), 3.73-3.80 (3 H, m), 4.85-4.89 (2 H, m, CHaHbPh, H-1′), 4.95-5.02 (2 H, m, H-5′), 5.76 (1 H, m, H-4′). ¹³C NMR (150 MHz, CDCl₃): δ = 21.0 (Me), 29.5 (C-2′), 41.8 (C-3′), 68.8 (C-6), 72.6 (CH₂Ph), 73.4 (CH₂Ph), 74.4 (CH₂Ph), 74.6 (CH₂Ph), 77.7, 78.8, 79.3 (C-2), 85.5 (C-3), 115.6 (C-5′), 116.3 (C-1′), 137.5 (C-4′), 147.1 (C-1). ESI-HRMS (diastereomeric mixture of 10): m/z calcd for C₄₀H₄₄O₅·Na⁺: 627.3081; found: 627.3127.
The reaction (Table 2, entry 5) gave the exo-glycal 11 with a diastereomeric ratio of 2:1.
Major isomer of Z-exo-glycal 11: ¹H NMR (600 MHz, CDCl₃): δ = 1.10 (3 H, d, J = 6.9 Hz, Me), 2.92 (1 H, dd, J = 6.9, 15.1 Hz, Ha-3′), 2.99 (1 H, dd, J = 6.9, 15.1 Hz, Hb-3′), 3.40 (1 H, m, H-2′), 3.58 (1 H, t, J = 7.6 Hz, H-3), 3.59-3.62 (1 H, m, H-5), 3.63-3.80 (3 H, m, H-4, H-6), 3.87 (1 H, dd, J = 1.4, 7.6 Hz, H-2), 4.50-4.95 (8 H, m, 4 × CH₂Ph), 4.88 (1 H, dd, J = 1.4, 8.9 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 21.1 (Me), 26.7 (C-2′), 46.3 (C-3′), 68.5 (C-6), 72.6 (CH₂Ph), 73.5 (CH₂Ph), 74.37 (CH₂Ph), 74.4 (CH₂Ph), 77.5 (C-5), 78.2 (C-4), 79.1 (C-2), 85.0 (C-3), 115.1 (C-1′), 147.8 (C-1), 199.3 (C-4′).
Minor isomer of Z-exo-glycal 11: ¹H NMR (600 MHz, CDCl₃): δ = 1.10 (3 H, d, J = 6.9 Hz, Me), 2.87 (1 H, dd, J = 8.9, 15.1 Hz, Ha-3′), 3.08 (1 H, dd, J = 5.5, 15.1 Hz, Hb-3′), 3.36 (1 H, m, H-2′), 3.55-3.80 (5 H, m, H-3, H-4, H-5, H-6), 3.87-3.88 (1 H, m, H-2), 4.50-4.95 (8 H, m, 4 × CH₂Ph), 4.94 (1 H, dd, J = 1.4, 8.9 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 21.2 (Me), 26.7 (C-2′), 45.8 (C-3′), 68.8 (C-6), 72.5 (CH₂Ph), 73.5 (CH₂Ph), 74.3 (CH₂Ph), 74.5 (CH₂Ph), 77.6 (C-5), 78.4 (C-4), 79.1 (C-2), 85.2 (C-3), 115.3 (C-1′), 147.7 (C-1), 199.6 (C-4′). ESI-HRMS (diastereomeric mixture of 11): m/z calcd for C₄₅H₄₆O₆·Na⁺: 705.3187; found: 705.3160.
Z-exo-Glycal 14: [α]_D ²⁸ +14.8 (c 1.76, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 2.58 (2 H, m, H-2′), 3.05 (2 H, t, J = 6.9 Hz, H-3′), 3.51-3.53 (1 H, m, H-5), 3.60 (1 H, dd, J = 3.4, 9.6 Hz, H-3), 3.80-3.81 (2 H, m, H-6), 3.97 (1 H, dd, J = 0.7, 3.4 Hz, H-2), 4.21 (1 H, dd, J = 8.9, 9.6 Hz, H-4), 4.38-4.96 (8 H, m, 4 × CH₂Ph), 4.91 (1 H, dt, J = 0.7, 7.6 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 19.7 (C-2′), 38.3 (C-3′), 69.1 (CH₂Ph), 69.3 (C-6), 71.2 (CH₂Ph), 73.4 (CH₂Ph), 74.0 (C-4), 74.2 (C-2), 75.1 (CH₂Ph), 80.2 (C-5), 82.0 (C-3), 115.0 (C-1′), 148.2 (C-1), 199.5 (C-4′). ESI-HRMS: m/z calcd for C₄₄H₄₄O₆·Na⁺: 691.3030; found: 691.3011.
E-exo-Glycal 14: ¹H NMR (600 MHz, CDCl₃): δ = 2.17-2.22 (1 H, m, Ha-2′), 2.27-2.34 (1 H, m, Hb-2′), 2.85-2.96 (2 H, m, H-3′), 3.46 (1 H, dt, J = 3.4, 9.6 Hz, H-5), 3.60 (1 H, dd, J = 2.8, 9.6 Hz, H-3), 3.76 (2 H, d, J = 3.4 Hz, H-6), 4.17 (1 H, dd, J = 8.9, 9.6 Hz, H-4), 4.63 (1 H, dd, J = 0.7, 2.8 Hz, H-2), 4.42-4.64 (8 H, m, 4 × CH₂Ph), 5.39 (1 H, dt, J = 0.7, 8.2 Hz, H-1′). ¹³C NMR (150 MHz, CDCl₃): δ = 20.5 (C-2′), 38.3 (C-3′), 68.7 (C-2), 69.52 (C-6), 69.53 (CH₂Ph), 71.6 (CH₂Ph), 73.4 (CH₂Ph), 74.6 (C-4), 75.3 (CH₂Ph), 80.7 (C-5), 82.3 (C-3), 115.3 (C-1′), 138.5 (C-1), 198.6 (C-4′). ESI-HRMS: m/z calcd for C₄₄H₄₄O₆·Na⁺: 691.3030; found: 691.3036.
Z-exo-Glycal 15: [α]_D ²⁸ +58.3 (c 1.27, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 2.09 (2 H, m, H-3′), 2.24 (2 H, m, H-2′), 3.66 (1 H, dd, J = 2.7, 8.2 Hz, H-3), 3.66-3.68 (1 H, m, Ha-6), 3.75 (1 H, dd, J = 6.2, 9.6 Hz, Hb-6), 3.86 (1 H, dt, J = 2.1, 6.2 Hz, H-5), 4.07 (1 H, t, J = 2.7 Hz, H-4), 4.25 (1 H, dd, J = 0.7, 7.6 Hz, H-2), 4.45-4.89 (8 H, m, 4 × CH₂Ph), 4.94 (1 H, dd, J = 0.7, 10.3 Hz, Ha-5′), 5.00 (1 H, J = 0.7, 17.2 Hz, Hb-5′), 5.08 (1 H, dt, J = 0.7, 6.9 Hz, H-1′), 5.80 (1 H, m, H-4′). ¹³C NMR (150 MHz, CDCl₃): δ = 23.8 (C-2′), 33.8 (C-3′), 68.7 (C-6), 72.90 (CH₂Ph), 72.91 (CH₂Ph), 73.4 (CH₂Ph), 73.9 (CH₂Ph), 74.5 (C-4), 77.2 (C-2), 78.1 (C-5), 81.5 (C-3), 111.7 (C-1′), 114.6 (C-5′), 138.6 (C-4′), 148.2 (C-1). ESI-HRMS: m/z calcd for C₃₉H₄₂O₅·Na⁺: 613.2924; found: 613.2881.