Bisglycosyl Peroxides

Abstract

Tri-O-benzyl-d-glycal treated with per-O-benzyl-2-deoxy-α- or per-O-benzyl-2-deoxy-β-d-glycosyl hydroperoxide affords the corresponding bisglycosyl peroxides. In all cases a new α-glycosidic bond is formed. Formation of the peroxide is not a reversible process; under applied reaction conditions, we did not observe rearrangement of β,α-peroxide into the corresponding α,α-compounds.

peroxides - glycosylations - 2-deoxysugars - glycals - addition reactions

References and Notes

1a Kośnik W. Stachulski A. Chmielewski M. Tetrahedron: Asymmetry  2005,  16:  1975 

1b Corrigendum: Kośnik W. Stachulski A. Chmielewski M. Tetrahedron: Asymmetry  2006,  17:  313 

2a Hamman H.-J. Höft E. Liebscher J. In Peroxide Chemistry, Mechanistic and Preparative Aspects of Oxygen Transfer   Adam W. Wiley-VCH; Weinheim: 2000.  p.381 

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3 Lattanzi A. Cocilova M. Iannece P. Scettri A. Tetrahedron: Asymmetry  2004,  15:  3751 

4a Dwyer CL. Gill CD. Ichihawa O. Taylor RJK. Synlett  2000,  704 

4b Bundu A. Berry NG. Gill CD. Dwyer CL. Stachulski AV. Taylor RJK. Whittall J. Tetrahedron: Asymmetry  2005,  16:  283 

5 Dussault P. Sahli A. Westermeyer T. J. Org. Chem.  1993,  58:  5469 

6 Dussault P. Woller KR. J. Am. Chem. Soc.  1997,  119:  3824 

7 Dussault P. Eary CT. Woller KR. J. Org. Chem.  1999,  64:  1789 

8

Formation of Bisglycosyl Peroxides; General Procedure: To a stirred solution of hydroperoxides 1, 2, 3, 5 or 7 (0.11 mmol) and tri-O-benzyl-d-glucal or tri-O-benzyl-d-galactal (0.12 mmol) in anhyd CH₂Cl₂ (5 mL) was added (1S)-(+)-10-camphorsulfonic acid (0.08 mmol). The reaction was stirred overnight (glucal) or 2 h (galactal) and quenched with NaHCO₃, then filtered and concentrated to dryness. Column chromatography of the residue with hexane-EtOAc (75:25) gave the respective products.
Bis-3,4,6-tri- O -benzyl-2-deoxy-α-d -glucopyranosyl Peroxide (9): oil; yield: 44.6%; [α]_D +136 (c = 0.64, CH₂Cl₂). IR (film): 1104, 736, 697 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.46 (d, J = 3.4 Hz, 1 H, H-1), 4.42-4.85 (m, 6 H, 3 × Bn), 3.95 (ddd, J = 2.1, 3.2, 9.9 Hz, 1 H, H-5), 3.81 (ddd, J = 5.1, 8.8, 11.7 Hz, 1 H, H-3), 3.78 (dd, J = 3.3, 10.6 Hz, 1 H, H-6a), 3.66 (dd, J = 8.9, 9.9 Hz, 1 H, H-4), 3.65 (dd, J = 2.0, 10.6 Hz, 1 H, H-6b), 2.27 (ddd, J = 1.3, 5.0, 13.5 Hz, 1 H, H-2a), 1.79 (ddd, J = 4.6, 11.7, 13.5 Hz, 1 H, H-2b). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 99.76 (C-1), 77.93, 77.05, 74.89 (Bn), 73.47 (Bn), 71.90 (Bn), 71.55, 68.64 (C-6), 33.17 (C-2). HRMS (ESI): m/z [M + Na]⁺ calcd for C₅₄H₅₈O₁₀Na: 889.3922; found: 889.3930. Anal. Calcd for C₅₄H₅₈O₁₀: C, 74.80; H, 6.74. Found: C, 74.56; H, 6.86.
Bis-3,4,6-tri- O -benzyl-2-deoxy-α-d -galactopyranosyl Peroxide(10): oil; yield: 19.8%; [α]_D +105 (c = 1.16, CHCl₃). IR (film): 1097, 736, 698 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.52 (d, J = 4.4 Hz, 1 H, H-1), 4.40-4.93 (m, 6 H, 3 × Bn), 4.21 (t, J = 6.5 Hz, 1 H, H-5), 3.85 (br s, 1 H, H-4), 3.76 (ddd, J = 2.5, 4.5, 12.4 Hz, 1 H, H-3), 3.70 (dd, J = 6.0, 9.2 Hz, 1 H, H-6a), 3.66 (dd, J = 7.1, 9.2 Hz, 1 H, H-6b), 2.32 (dt, J = 4.6, 12.9 Hz, 1 H, H-2a), 2.01 (dd, J = 4.6, 13.2 Hz, 1 H, H-2b). ¹H NMR (500 MHz, C₆D₆): [18] δ = 5.52 (d, J = 4.2 Hz, 1 H, H-1), 4.10-5.01 (m, 6 H, 3 × Bn), 4.56 (t, J = 6.8 Hz, 1 H, H-5), 3.93-3.96 (m, 3 H, H-6a, H-6b, H-4), 3.76 (ddd, J = 2.5, 4.5, 12.5 Hz, 1 H, H-3), 2.41 (dt, J = 4.6, 12.9 Hz, 1 H, H-2a), 1.91 (dd, J = 4.6, 13.1 Hz, 1 H, H-2b). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 99.84 (C-1), 74.34, 74.29 (Bn), 73.27 (Bn), 72.80, 70.58, 70.43 (Bn), 69.48 (C-6), 28.75 (C-2). HRMS (ESI): m/z [M + Na]⁺ calcd for C₅₄H₅₈O₁₀Na: 889.3922; found: 889.3940. Anal. Calcd for C₅₄H₅₈O₁₀: C, 74.80; H, 6.74. Found: C, 74.63; H, 6.74.
3,4,6-Tri- O -benzyl-2-deoxy-α-d -glucopyranosyl-3,4,6-tri- O -benzyl-2-deoxy-α-d -galactopyranosyl Peroxide (11): oil; yield: 51.3%; [α]_D +150 (c = 0.8, CH₂Cl₂). IR (film): 1101, 736, 697 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.47 (d, J = 4.8 Hz, 1 H, H-1, Glcp), 5.46 (d, J = 4.3 Hz, 1 H, H-1, Galp), 4.37-4.91 (m, 12 H, 6 × Bn), 4.11 (ddd, J = 1.0, 6.4, 7.8, 1 H, H-5, Galp), 4.0 (ddd, J = 2.1, 2.9, 9.9 Hz, 1 H, H-5, Glcp), 3.93 (br s, 1 H, H-4, Galp), 3.83 (ddd, J = 5.1, 8.8, 11.7 Hz, 1 H, H-3, Glcp), 3.80 (dd, J = 3.2, 10.7 Hz, 1 H, H-6a, Glcp), 3.76 (ddd, J = 2.5, 4.5, 10.0 Hz, 1 H, H-3, Galp), 3.71 (dd, J = 2.0, 10.7 Hz, 1 H, H-6b, Glcp), 3.68 (dd, J = 8.9, 9.9 Hz, 1 H, H-4, Glcp), 3.64 (dd, J = 7.9, 9.0 Hz, 1 H, H-6a, Galp), 3.52 (dd, J = 5.3, 9.0 Hz, 1 H, H-6b, Galp), 2.30 (dt, J = 4.7, 13.1 Hz, 1 H, H-2a, Galp), 2.27 (ddd, J = 1.3, 5.2, 13.6 Hz, 1 H, H-2a, Glcp), 1.98 (ddd, J = 1.2, 4.7, 13.2 Hz, 1 H, H-2b, Galp), 1.80 (ddd, J = 4.7, 11.7, 13.6 Hz, 1 H, H-2b, Glcp). ¹H NMR (500 MHz, C₆D₆): [18] δ = 5.51 (d, J = 4.2 Hz, H-1, 1 H, Glcp), 5.43 (d, J = 4.1 Hz, 1 H, H-1, Galp), 4.43-5.02 (m, 12 H, 6 × Bn), 4.48 (dd, J = 5.5, 7.3 Hz, 1 H, H-5, Galp), 4.40 (d, J = 9.6 Hz, 1 H, H-5, Glcp), 3.99 (dd, J = 3.4, 10.9 Hz, 1 H, H-6a, Glcp), 3.96 (br s, 1 H, H-4, Galp), 3.87-3.94 (m, 4 H, H-4, Glcp, H-3, Glcp, H-6b, Glcp, H-6a, Galp), 3.77 (ddd, J = 2.5, 4.5, 12.5 Hz, 1 H, H-3, Galp), 3.74 (dd, J = 5.3, 9.0 Hz, 1 H, H-6b, Galp), 2.41 (dt, J = 4.7, 13.0 Hz, 1 H, H-2a, Galp), 2.08 (dd, J = 4.9, 12.5 Hz, 1 H, H-2a, Glcp), 1.92 (dd, J = 4.5, 13.0 Hz, 1 H, H-2b, Galp), 1.60 (ddd, J = 4.6, 11.3, 13.5 Hz, 1 H, H-2b, Glcp). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 99.97, 99.60 (C-1′, C-1), 77.91, 77.10, 74.88 (Bn), 74.45 (Bn), 74.18, 73.46 (Bn), 73.40 (Bn), 72.70, 71.89 (Bn), 71.50, 70.48, 70.47 (Bn), 68.89, 68.68 (C-6′, C-6), 33.12, 28.84 (C-2, C-2′). HRMS (ESI): m/z [M + Na]⁺ calcd for C₅₄H₅₈O₁₀Na: 889.3922; found: 889.3917. Anal. Calcd for C₅₄H₅₈O₁₀: C, 74.80; H, 6.74. Found: C, 74.41; H, 6.93.
3,4,6-Tri- O -benzyl-2-deoxy-β-d -glucopyranosyl-3,4,6-tri- O -benzyl-2-deoxy-α-d -glucopyranosyl Peroxide (12): oil; yield: 49.3%; [α]_D +30 (c = 0.78, CH₂Cl₂). IR (film): 1096, 736, 697 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.66 (d, J = 3.9 Hz, 1 H, H-1α), 5.09 (dd, J = 2.0, 10.4 Hz, 1 H, H-1β), 4.49-4.88 (m, 12 H, 6 × Bn), 3.94 (ddd, J = 2.1, 4.0, 9.9 Hz, 1 H, H-5α), 3.71-3.82 (m, 5 H, H-3α, H-6aα, H-6bα, H-6aβ, H-6bβ), 3.58-3.63 (m, 2 H, H-4α, H-3β), 3.53 (dd, J = 8.6, 9.3 Hz, 1 H, H-4β), 3.46 (ddd, J = 2.2, 4.2, 9.3 Hz, 1 H, H-5β), 2.31 (ddd, J = 1.3, 5.0, 13.7 Hz, 1 H, H-2eqα), 2.27 (ddd, J = 2.0, 5.0, 12.3 Hz, 1 H, H-2eqβ), 1.87 (ddd, J = 4.9, 11.7, 13.7 Hz, 1 H, H-2axα), 1.55 (m, 1 H, H-2axβ). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 102.38, 101.48 (C-1, C-1′), 79.35, 78.00, 77.72, 76.99, 75.20, 74.93 (Bn), 74.94 (Bn), 73.50 (Bn), 73.43 (Bn), 71.80, 71.75 (Bn), 71.54 (Bn), 69.19, 68.93 (C-6′, C-6), 33.29, 32.80 (C-2, C-2′). HRMS (ESI): m/z [M + Na]⁺ calcd for C₅₄H₅₈O₁₀Na: 889.3922; found: 889.3954. Anal. Calcd for C₅₄H₅₈O₁₀: C, 74.80; H, 6.74. Found: C, 74.24; H, 6.78.
3,4,6-Tri- O -benzyl-2-deoxy-β-d -glucopyranosyl-3,4,6-tri- O -benzyl-2-deoxy-α-d -galactopyranosyl Peroxide (13): oil; yield: 44%; [α]_D +39 (c = 0.8, CH₂Cl₂). IR (film): 1093, 736, 697 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.68 (d, J = 4.5 Hz, 1 H, H-1, Galp), 5.12 (dd, J = 2.0, 10.3 Hz, 1 H, H-1, Glcp), 4.40-4.93 (m, 12 H, 6 × Bn), 4.05 (br t, J = 6.3, 6.4 Hz, 1 H, H-5, Galp), 3.85 (br s, 1 H, H-4, Galp), 3.68-3.80 (m, 3 H, H-5, Glcp, H-4, Glcp, H-3, Galp), 3.63 (dd, J = 6.2, 9.5 Hz, 1 H, H-6a, Galp), 3.52-3.58 (m, 2 H, H-3, Glcp, H-6b, Galp), 3.46-3.51 (m, 2 H, H-6a, Glcp, H-6b, Glcp), 2.21-2.30 (m, 2 H, H-2a, Galp, H-2a, Glcp), 2.04 (m, 1 H, H-2b, Galp), 1.50 (m, 1 H, H-2b, Glcp). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 102.33, 102.19 (C-1, C-1′), 79.35, 77.79, 75.24, 74.88 (Bn), 74.27 (Bn), 74.25, 73.46 (Bn), 73.37 (Bn), 72.89, 71.49 (Bn), 71.02, 70.45 (Bn), 69.74, 69.29 (C-6′, C-6), 33.30, 28.63 (C-2, C-2′). HRMS: (ESI): m/z [M + Na]⁺ calcd for C₅₄H₅₈O₁₀Na: 889.3922; found: 889.3885. Anal. Calcd for C₅₄H₅₈O₁₀: C, 74.80; H, 6.74. Found: C, 74.77; H, 7.00.
3,5-Di- O -benzyl-2-deoxy-α-d -ribofuranosyl-3,4,6-tri- O -benzyl-2-deoxy-α-d -galactopyranosyl Peroxide (14): oil; yield: 29%; [α]_D +101 (c = 0.9, CHCl₃). IR (film): 1095, 735, 697 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.63 (dd, J = 2.3, 6.6 Hz, 1 H, H-1, Ribf), 5.49 (d, J = 4.2 Hz, 1 H, H-1, Galp), 4.37-4.92 (m, 10 H, 5 × Bn), 4.25-4.30 (m, 2 H, H-4, Ribf, H-5, Galp), 4.05 (ddd, J = 3.8, 5.2, 8.0 Hz, 1 H, H-3, Ribf), 3.95 (br s, 1 H, H-4, Galp), 3.82 (ddd, J = 2.5, 4.7, 12.4 Hz, 1 H, H-3, Galp), 3.66 (dd, J = 7.9, 9.1 Hz, 1 H, H-6a, Galp), 3.59 (dd, J = 5.4, 9.1 Hz, 1 H, H-6b, Galp), 3.57 (dd, J = 3.6, 10.6 Hz, 1 H, H-5a, Ribf), 3.50 (dd, J = 3.7, 10.6 Hz, 1 H, H-5b, Ribf), 2.34 (ddd, J = 6.6, 8.0, 14.6 Hz, 1 H, H-2a, Ribf), 2.30 (ddd, J = 4.7, 12.4, 13.2 Hz, 1 H, H-2a, Galp), 2.00 (ddd, J = 1.2, 4.7, 13.2 Hz, 1 H, H-2b, Galp), 1.93 (ddd, J = 2.3, 3.8, 14.6 Hz, 1 H, H-2b, Ribf). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 105.69, 100.05 (C-1′, C-1), 82.26, 77.76, 74.43 (Bn), 74.29, 73.48 (Bn), 73.37 (Bn), 72.82, 71.66 (Bn), 70.43 (Bn), 70.41, 69.35, 69.09 (C-5′, C-6), 36.10, 28.89 (C-2′, C-2). HRMS (ESI): m/z [M + Na]⁺ calcd for C₄₆H₅₀O₉Na: 769.3347; found: 769.3310.
3,5-Di- O -benzyl-2-deoxy-β-d -ribofuranosyl-3,4,6-tri- O -benzyl-2-deoxy-α-d -galactopyranosyl Peroxide (15): oil; yield: 30%; [α]_D +17 (c = 0.64, CH₂Cl₂). IR (film): 1095, 736, 697 cm^-1. ¹H NMR (500 MHz, CDCl₃): [18] δ = 5.83 (dd, J = 3.2, 6.4 Hz, 1 H, H-1, Ribf), 5.57 (br d, J = 4.4 Hz, 1 H, H-1, Galp), 4.40-4.94 (m, 10 H, 5 × Bn), 4.34 (ddd, J = 2.8, 5.8, 7.0 Hz, 1 H, H-3, Ribf), 4.05-4.09 (m, 2 H, H-4, Ribf, H-5, Galp), 3.92 (br s, 1 H, H-4, Galp), 3.76 (ddd, J = 2.5, 4.7, 12.4 Hz, 1 H, H-3, Galp), 3.61 (d, 2 H, H-5a, Ribf, H-5b, Ribf), 3.60 (dd, J = 5.8, 10.0 Hz, 1 H, H-6a, Galp), 3.47 (dd, J = 7.0, 10.0 Hz, 1 H, H-6b, Galp), 2.26 (ddd, J = 4.8, 12.4, 13.4 Hz, 1 H, H-2a, Galp), 2.16 (ddd, J = 4.4, 6.4, 14.6 Hz, 1 H, H-2a, Ribf), 2.07 (ddd, J = 3.2, 7.0, 14.6 Hz, 1 H, H-2b, Ribf), 2.02 (ddd, J = 1.0, 4.7, 13.4 Hz, 1 H, H-2b, Galp). ¹³C NMR (125 MHz, CDCl₃): [18] δ = 107.91, 101.53 (C-1′, C-1), 83.56, 79.42, 74.38 (Bn), 74.20, 73.40 (Bn), 73.36 (Bn), 72.87, 71.36 (Bn), 71.28 (Bn), 70.75, 70.48, 69.32 (C-5′, C-6), 36.26, 28.66 (C-2′, C-2). HRMS (ESI): m/z [M + Na]⁺ calcd for C₄₆H₅₀O₉Na: 769.3347; found: 769.3367.

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18

¹H and ¹³C NMR resonances for phenyl groups are not reported.