Protecting Group and Solvent Effects in Electrochemical Glycosylation

Ludovic Drouin; Richard G. Compton; Nicole Fietkau; Antony J. Fairbanks

doi:10.1055/s-2007-986644

LETTER

Protecting Group and Solvent Effects in Electrochemical Glycosylation

Ludovic Drouin^a, Richard G. Compton^b, Nicole Fietkau^b, Antony J. Fairbanks*^a
^a Chemistry Research Laboratory, Oxford University, Mansfield Road, Oxford, OX1 3TA, UK
Fax: +44(1865)275674; e-Mail: antony.fairbanks@chem.ox.ac.uk;
^b Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford, OX1 3QZ, UK

Abstract

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Abstract

An investigation is undertaken into the roles of protecting groups and the solvent in the electrochemical-mediated glycosylation of manno thioglycosides. Herein notable differences are observed between electrochemical and chemical glycosylation.

Key words

carbohydrates - glycosylations - electrochemistry - solvent effects - neighbouring-group effects

Volltext

Referenzen

References and Notes

1a Varki A. Glycobiology 1993, 3: 97

1b Dwek RA. Chem. Rev. 1996, 96: 683

2 Davis BG. J. Chem. Soc., Perkin Trans. 1 2000, 2137

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4b Cheung MK. Douglas NL. Hinzen B. Ley SV. Pannecoucke X. Synlett 1997, 257

4c Grice P. Ley SV. Pietruszka J. Osborn HMI. Priepke HWM. Warriner S. Chem. Eur J. 1997, 3: 431

4d Green L. Hinzen B. Ince SJ. Langer P. Ley SV. Warriner SL. Synlett 1998, 440

4e Douglas NL. Ley SV. Lücking U. Warriner SL. J. Chem. Soc., Perkin Trans. 1 1998, 51

5a Zhang Z. Ollmann IR. Ye X.-S. Wischnat R. Baasov T. Wong C.-H. J. Am. Chem. Soc. 1999, 121: 734

5b Ye X.-S. Wong C.-H. J. Org. Chem. 2000, 65: 2410

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7a Amatore C. Jutand A. Mallet J.-M. Meyer G. Sinaӱ P. J. Chem. Soc., Chem. Commun. 1990, 718

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For a similar approach, see:

8a Yamago S. Kokobu K. Hara O. Masuda S. Yoshida J. J. Org. Chem. 2002, 67: 8584

8b Yamago S. Kokubo K. Yoshida J. Chem. Lett. 1997, 111

9a France RR. Compton RG. Fairbanks AJ. Rees NV. Wadhawan JD. Org. Biomol. Chem. 2004, 2: 2188

9b France RR. Compton RG. Davis BG. Fairbanks AJ. Rees NV. Wadhawan JD. Org. Biomol. Chem. 2004, 2: 2195

10

Typical Procedure for Electrochemical Glycosylation: Electrochemical glycosylation was carried out using galvanostatic system with Pt as auxiliary and working electrodes, and Ag as the reference electrode. Under an atmosphere of argon, glycosyl donor (ca. 70-150 mg, 1 equiv), glycosyl acceptor (ca. 30-70 mg, 1.2 equiv), n-Bu₄NClO₄ (ca. 650 mg), and 3 Å MS were suspended in anhyd MeCN (or CH₂Cl₂, 20 mL) and the reaction mixture was stirred at 25 °C for 30 min prior to commencing electrolysis. Electrolysis was then performed at the required potential (+1.5 V to +2.2 V depending on the donor) until the necessary charge was reached (typically 2.5 F·mol^-1). At this point the mixture was filtered through Celite^®, the filtrate was concentrated under reduced pressure, and the residue was taken up into Et₂O. Any remaining solid was removed by filtration through Celite,^® and the filtrate was again concentrated under reduced pressure. Finally purification by flash column chromatography (typically eluting with PE-EtOAc, 9:1) afforded the desired disaccharide as colourless oil.

11 Wulff G. Röhle G. Angew. Chem., Int. Ed. Engl. 1974, 13: 157

12a Balavoine G. Gref A. Fischer J.-C. Lubineau A. Tetrahedron Lett. 1990, 31: 5761

12b Balavoine G. Berteina S. Gref A. Fischer J.-C. Lubineau A. J. Carbohydr. Chem. 1995, 14: 1217

12c Balavoine G. Berteina S. Gref A. Fischer J.-C. Lubineau A. J. Carbohydr. Chem. 1995, 14: 1237

13

Selected data for 4b (α-anomer only): [α]_D ²² +10 (c = 0.7, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 1.33 (s, 3 H, Me), 1.34 (s, 3 H, Me), 1.43 (s, 3 H, Me), 1.52 (s, 3 H, Me), 2.15 (s, 3 H, MeCO), 3.68-3.71 (m, 2 H, H-6a, H-6b), 3.76-3.84 (m, 3 H, H-6′a, H-6′b, H-5a), 3.91-3.95 (m, 2 H, H-4b, H-5b), 3.99 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 9.5 Hz, 1 H, H-3b), 4.22 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 1.5 Hz, 1 H, H-4a), 4.30 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.47 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 4.49 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.53 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.60 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.69 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.70 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.87 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 4.90 (d, J _1b,2b = 1.5 Hz, 1 H, H-1b), 5.40 (dd, J _1b,2b = 2.0 Hz, J _2b,3b = 3.0 Hz, 1 H, H-2b), 5.50 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 7.10-7.36 (m, 15 H, 15 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 21.1 (MeCO), 24.5 (Me), 24.9 (Me), 25.9 (Me), 26.1 (Me), 65.9 (C-4b), 66.1 (C-6), 68.6 (C-6), 68.7 (C-2b), 70.5 (C-3a), 70.6 (C-2a), 70.8 (C-4a), 71.5 (C-5a), 71.8 (CH₂), 73.4 (CH₂), 74.2 (C-5b), 75.1 (CH₂), 78.1 (C-3b), 96.2 (C-1a), 97.9 (C-1b), 108.6 (Cqx), 109.3 (Cqy), 127.5 (ArCH), 127.6 (ArCH), 127.7 (ArCH), 127.8 (2 × ArCH), 127.9 (2 × ArCH), 128.0 (2 × ArCH), 128.3 (4 × ArCH), 128.3 (2 × ArCH), 138.0 (ArC), 138.2 (ArC), 138.4 (ArC), 170.4 (C=O). HRMS (ESI⁺): m/z [M + NH₄ ⁺] calcd for C₄₁H₅₄NO₁₂: 752.3641; found: 752.3649.

14

Selected data for 5b (α-anomer): [α]_D ²⁰ -6 (c = 1.2 CHCl₃). IR (film): 1732 (s, C=O), 1371 (s, CO) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.21 (s, 9 H, t-Bu), 1.33 (s, 3 H, Me), 1.35 (s, 3 H, Me), 1.43 (s, 3 H, Me), 1.52 (s, 3 H, Me), 3.72 (dd, J _5a,6a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6a), 3.72-3.74 (m, 1 H, H-6b), 3.80 (dd, J _5,6 _′a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6′a), 3.78-3.82 (m, 1 H, H-6′b), 3.83-3.87 (m, 1 H, H-5b), 3.91 (app t, J _3b,4b = 9.5 Hz, J _4b,5b = 9.5 Hz, 1 H, H-4b), 3.95 (d app t, J _4a,5a = 1.5 Hz, J _5a,6a = 6.5 Hz, J _5a,6 _′a = 6.5 Hz, 1 H, H-5a), 3.99 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 9.5 Hz, 1 H, H-3b), 4.22 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 1.5 Hz, 1 H, H-4a), 4.31 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.49 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.50 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.51 (d, J = 13.0 Hz, 1 H, CH₂ of Bn), 4.60 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.68 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.69 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.82 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.88 (d, J _1b,2b = 2.0 Hz, 1 H, H-1b), 5.40 (dd, J _1b,2b = 2.0 Hz, J _2b,3b = 3.0 Hz, 1 H, H-2b), 5.51 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 7.15-7.36 (m, 15 H, 15 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 24.5 (Me), 24.9 (Me), 25.0 (Me), 26.1 (Me), 27.1 (t-Bu), 38.9 (CqPiv), 65.8 (C-5a), 65.9 (C-6), 68.1 (C-2b), 68.8 (C-6), 70.6 (C-3a), 70.7 (C-2a), 70.8 (C-4a), 71,4 (CH₂ of Bn), 71.5 (C-5b), 73.1 (CH₂ of Bn), 74.1 (C-4b), 75.1 (CH₂ of Bn), 78.3 (C-3b), 96.3 (C-1a), 97.8 (C-1b), 108.6 (Cq), 109.3 (Cq), 107.4 (ArCH), 127.4 (2 × ArCH), 127.6 (ArCH), 127.9 (2 × ArCH), 128.1 (2 × ArCH), 128.2 (2 × ArCH), 128.2 (2 × ArCH), 128.3 (2 × ArCH), 138.3, 138.3, 138.4 (ArC), 138.4 (ArCH), 177.6 (C=O). HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₄₄H₅₆NaO₁₂: 799.3664; found: 799.3662. Selected data for 5b (β-anomer): [α]_D ²⁰ -39 (c = 0.2, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 1.24 (s, 9 H, t-Bu), 1.29 (s, 3 H, Me), 1.32 (s, 3 H, Me), 1.42 (s, 3 H, Me), 1.52 (s, 3 H, Me), 3.46 (d app t, J _4,5 = 3.5 Hz, J _5,6 = 3.5 Hz, J _5,6 _′ = 9.5 Hz, 1 H, H-5b), 3.65 (dd, J _2,3 = 3.0 Hz, J _3,4 = 9.5 Hz, 1 H, H-3b), 3.69 (dd, J _5,6 = 10.5 Hz, J _6,6 _′ = 4.0 Hz, 1 H, H-6a), 3.74-3.79 (m, 3 H, H-6b, H-6′b, H-6′a), 3.97 (ddd, J _4,5 = 1.5 Hz, J _5,6 = 10.5 Hz, J _5,6 _′ = 4.0 Hz, 1 H, H-5a), 4.02 (dd, J _3,4 = 9.5 Hz, J _4,5 = 3.5 Hz, 1 H, H-4b), 4.20 (dd, J _3,4 = 8.0 Hz, J _4,5 = 1.5 Hz, 1 H, H-4a), 4.28 (dd, J _1,2 = 5.0 Hz, J _2,3 = 2.5 Hz, 1 H, H-2a), 4.46 (d, J = 11.5 Hz, 1 H, CH₂ of Bn), 4.50 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 4.55 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.56 (dd, J _2,3 = 2.5 Hz, J _3,4 = 8.0 Hz, 1 H, H-3a), 4.63 (br s, 1 H, H-1b), 4.68 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.74 (d, J = 11.5 Hz, 1 H, CH₂ of Bn), 4.83 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 5.50 (d, J _1,2 = 5.0 Hz, 1 H, H-1a), 5.61 (d, J _2,3 = 3.0 Hz, 1 H, H-2b), 7.10-7.40 (m, 15 H, 15 × ArH). ¹³C NMR (100.6 MHz, CDCl₃): δ = 24.3 (Me), 25.0 (Me), 25.9 (Me), 26.0 (Me), 27.2 (t-Bu), 39.0 (CqPiv), 67.5 (C-2b), 67.8 (CH), 68.8 (C-6), 69.0 (C-6), 70.5 (C-3a), 70.6 (C-2a), 70.9 (CH₂ of Bn), 71.2 (C-4a), 73.2 (CH₂ of Bn), 74.2 (CH), 75.1 (CH₂ of Bn), 75.4 (CH), 80.3 (C-3b), 96.2 (C-1a), 99.3 (C-1b), 108.7 (Cq), 109.2 (Cq), 127.4 (ArCH), 127.6 (2 × ArCH), 127.6 (ArCH), 127.6 (ArCH), 128.0 (2 × ArCH), 128.1 (2 × ArCH), 128.2 (2 × ArCH), 128.2 (2 × ArCH), 128.3 (2 × ArCH), 176.6 (C=O), 137.9 (ArC), 138.5 (2 × ArC).

15

Selected data for 6b (α-anomer only): [α]_D ²⁰ -38 (c = 0.3, CHCl₃). IR (film): 3031 (CHAr), 2921 (CH), 1729 (s, C=O), 1497 (s, CH), 1072, 1260 (s, CO) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.33 (s, 3 H, Me), 1.35 (s, 3 H, Me), 1.44 (s, 3 H, Me), 1.53 (s, 3 H, Me), 2.28 (s, 2 × 3 H, 2 × Me_mesitoyl), 2.29 (s, 3 H, Me_mesitoyl), 3.69 (br d, J _6b,6 _′b = 10.5 Hz, 1 H, H-6b), 3.75 (d, J _5a,6a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6a), 3.76 (dd, J _5b,6 _′b = 3.0 Hz, J _6b,6 _′b = 10.5 Hz, 1 H, H-6′b), 3.83 (dd, J _5a,6 _′a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6′a), 3.87-3.90 (m, 2 H, H-4b, H-5b), 3.98 (d app t, J _4a,5a = 1.5 Hz, J _5a,6a = 6.5 Hz, J _5a,6 _′a = 6.5 Hz, 1 H, H-5a), 4.08-4.10 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 9.0 Hz, 1 H, H-3b), 4.25 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 1.5 Hz, 1 H, H-4a), 4.31 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.45 (d, J = 11.5 Hz, 1 H, CH₂ of Bn), 4.47 (d, J = 12.5 Hz, 1 H, CH₂ of Bn), 4.60 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.62 (d, J = 11.0 Hz, 1 H, CH₂ of Bn), 4.63 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.81 (d, J = 11.0 Hz, 2 H, 2 × CH₂ of Bn), 5.05 (d, J _1b,2b = 2.0 Hz, 1 H, H-1b), 5.52 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 5.65 (dd, J _1b,2b = 2.0 Hz, J _2b,3b = 3.0 Hz, 1 H, H-2b), 6.82 (s, 2 H, 2 × ArH), 7.13-7.16 (m, 2 H, 2 × ArH), 7.23-7.40 (m, 13 H, 13 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 20.0 (2 × Me), 21.1 (Me), 24.5 (Me), 24.9 (Me), 26.0 (Me), 26.2 (Me), 65.8 (C-5a), 66.0 (C-6a), 68.8 (C-6b), 69.3 (C-2b), 70.6 (C-3a, C-2a), 70.9 (C-4a), 71.8 (C-5b), 71.9 (CH₂ of Bn), 73.2 (CH₂ of Bn), 74.5 (C-4b), 75.2 (CH₂ of Bn), 76.2 (C-3b), 96.3 (C-1a), 97.6 (C-1b), 108.6 (Cq), 109.4 (Cq), 127.4 (ArCH), 127.5 (ArCH), 127.6 (ArCH), 127.7 (2 × ArCH), 127.9 (2 × ArCH), 128.0 (2 × ArCH), 128.2 (2 × ArCH), 128.2 (2 × ArCH), 128.3 (2 × ArCH), 128.3 (2 × ArCH), 130.6 (Cq), 135.6 (2 × Cq), 138.1 (Cq), 138.3 (Cq), 138.3 (Cq), 139.3 (Cq), 139.3 (Cq), 169.3 (C=O). HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₄₉H₅₈NaO₁₂: 861.3820; found: 861.3818. Anal. Calcd for C₄₉H₅₈O₁₂: C, 70.15; H, 6.97. Found: C, 69.76; H, 6.59.

16a Zhu T. Boons G.-J. Tetrahedron: Asymmetry 2000, 11: 199

16b Roussel F. Knerr L. Grathwohl M. Schmidt RR. Org. Lett. 2000, 2: 3043

17

Selected data for 8b (α-anomer): [α]_D ²⁰ -6 (c = 0.7, CHCl₃). IR (film): 3050 (CHAr), 2962 (CH), 1600-2000 (CHAr), 1497 (w, CH) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.31 (s, 9 H, t-Bu), 1.34 (s, 2 × 3 H, 2 × Me), 1.44 (s, 3 H, Me), 1.52 (s, 3 H, Me), 3.69-3.81 (m, 5 H, H-6a, H-6′a, H-6b, H-6′b, H-2b), 3.84-3.85 (m, 1 H, H-5b), 3.90 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 9.5 Hz, 1 H, H-3b), 3.97 (d app t, J _4a,5a = 1.5 Hz, J _5a,6a = 6.5 Hz, J _5a,6 _′a = 6.5 Hz, 1 H, H-5a), 4.02 (app t, J _3b,4b = 9.5 Hz, J _4b,5b = 9.5 Hz, 1 H, H-4b), 4.17 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 1.5 Hz, 1 H, H-4a), 4.32 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.50 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 4.54-4.58 (m, 3 H, CH₂ of Bn), 4.60 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.67 (d, J = 12.5 Hz, 1 H, CH₂ of Bn), 4.69 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.74 (d, J = 12.5 Hz, 1 H, CH₂ of Bn), 4.87 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 5.04 (d, J _1b,2b = 1.5 Hz, 1 H, H-1b), 5.53 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 7.15-7.37 (m, 19 H, 19 × ArH). ¹³C NMR (100.6 MHz, CDCl₃): δ = 24.6 (Me), 25.1 (Me), 26.2 (Me), 26.3 (Me), 34.7 (Cq), 65.3 (C-5a), 65.5 (C-6), 69.3 (C-6), 70.8 (C-3a), 70.9 (C-2a), 71.2 (C-4a), 72.1 (CH₂), 72.2 (CH₂), 72.3 (C-2b), 73.5 (CH₂), 74.3 (C-5b), 75.0 (C-4b), 75.3 (CH₂), 80.2 (C-3b), 96.5 (C-1a), 97.3 (C-1b), 108.8 (Cq), 109.5 (Cq), 125.5 (2 × ArCH), 127.5 (2 × ArCH), 127.6 (ArCH), 127.7 (2 × ArCH), 127.8 (2 × ArCH), 127.9 (2 × ArCH), 128.1 (2 × ArCH), 128.3 (4 × ArCH), 128.4 (2 × ArCH), 135.5 (ArC), 138.6 (ArC), 138.7 (ArC), 138.8 (ArC), 150.7 (ArC). HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₅₀H₆₂NaO₁₁: 861.4184; found: 861.4162. Selected data for 8b (β-anomer): [α]_D ²⁰ -48 (c = 0.1, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 1.30 (s, 9 H, t-Bu), 1.33 (s, 3 H, Me), 1.34 (s, 3 H, Me), 1.44 (s, 3 H, Me), 1.50 (s, 3 H, Me), 3.41 (ddd, J _4b,5b = 9.5 Hz, J _5b,6b = 5.0 Hz, J _5b,6 _′b = 2.0 Hz, 1 H, H-5b), 3.44 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 9.5 Hz, 1 H, H-3b), 3.62 (dd, J _5a,6a = 10.5 Hz, J _6a,6 _′a = 9.5 Hz, 1 H, H-6a), 3.75 (dd, J _5b,6b = 5.0 Hz, J _6b,6 _′b = 10.5 Hz, 1 H, H-6b), 3.79 (dd, J _5b,6 _′b = 2.0 Hz, J _6b,6 _′b = 10.5 Hz, 1 H, H-6′b), 3.89 (app t, J _3b,4b = 9.5 Hz, J _4b,5b = 9.5 Hz, 1 H, H-4b), 4.00 (d, J _2b,3b = 3.0 Hz, 1 H, H-2b), 4.13 (br d, 1 H, H-5a), 4.22 (dd, J _5a,6 _′a = 2.0 Hz, J _6a,6 _′a = 9.5 Hz, 1 H, H-6′a), 4.23 (dd, J _3a,4a = 9.0 Hz, J _4a,5a = 1.5 Hz, 1 H, H-4a), 4.29 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.34 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.40 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.45 (s, 1 H, H-1b), 4.50 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 4.56 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.62 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 9.0 Hz, 1 H, H-3a), 4.63 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.90 (d, J = 10.5 Hz, 1 H, CH₂ of Bn), 4.91 (d, J = 12.5 Hz, 1 H, CH₂ of Bn), 4.98 (d, J = 12.5 Hz, 1 H, CH₂ of Bn), 5.61 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 7.15-7.45 (m, 19 H, 19 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 24.4 (Me), 25.1 (Me), 26.0 (Me), 26.1 (Me), 31.4 (t-Bu), 34.5 (Cq), 68.0 (C-5a), 69.6 (C-6b), 69.9 (C-6a), 70.5 (CH), 70.8 (CH), 70.9 (CH₂), 71.7 (CH), 71.9 (CH), 73.1 (CH₂), 73.4 (CH₂), 74.8 (C-4b), 75.1 (CH₂), 75.8 (CH), 81.9 (CH), 96.4 (C-1a), 102.4 (C-1b), 108.7 (Cq), 109.5 (Cq), 125.1 (2 × ArCH), 127.4 (ArCH), 127.5 (ArCH), 127.5 (2 × ArCH), 127.6 (ArCH), 127.9 (2 × ArCH), 128.0 (2 × ArCH), 128.2 (4 × ArCH), 128.3 (2 × ArCH), 128.6 (2 × ArCH), 135.5 (ArC), 138.1 (ArC), 138.4 (2 × ArC), 150.2 (ArC). HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₅₀H₆₂NaO₁₁: 861.4184; found: 861.4192.

18 Smoot JT. Pornsuriyasak P. Demchenko AV. Angew. Chem. Int. Ed. 2005, 44: 7123

19

Selected data for 10b (α-anomer only): [α]_D ¹⁹ -61 (c = 0.3, CHCl₃). IR (film): 3010 (w, CHAr), 2988 (w, CH), 1728 (s, C=O), 1601, 1595, 1500, 1452 (m, C=CAr), 1263, 1060 (s, CO) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.36 (s, 2 × 3 H, 2 × Me), 1.43 (s, 3 H, Me), 1.63 (s, 3 H, Me), 3.89 (dd, J _5a,6a = 6.5 Hz, J _6a,6 _′a = 11.0 Hz, 1 H, H-6a), 3.97 (dd, J _5a,6 _′a = 6.5 Hz, J _6a,6 _′a = 11.0 Hz, 1 H, H-6′a), 4.12 (d app t, J _4a,5a = 2.0 Hz, J _5a,6a = 6.5 Hz, J _5a,6 _′a = 6.5 Hz, 1 H, H-5a), 4.34 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 2.0 Hz, 1 H, H-4a), 4.35 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-3a), 4.50 (dd, J _5b,6b = 3.0 Hz, J _6b,6 _′b = 12.0 Hz, 1 H, H-6b), 4.59 (br d app t, J _4b,5b = 10.0 Hz, J _5b,6b = 3.0 Hz, J _5b,6 _′b = 3.0 Hz, 1 H, H-5b), 4.67 (dd, J _2a,3a = 2.0 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.69 (dd, J _5b,6 _′b = 3.0 Hz, J _6b,6 _′b = 12.0 Hz, 1 H, H-6′b), 5.16 (d, J _1b,2b = 2.0 Hz, 1 H, H-1b), 5.57 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 5.74 (dd, J _1b,2b = 2.0 Hz, J _2b,3b = 3.0 Hz, 1 H, H-2b), 5.91 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 10.0 Hz, 1 H, H-3b), 6.14 (app t, J _3b,4b = 10.0 Hz, J _4b,5b = 10.0 Hz, 1 H, H-4b), 7.25-7.28 (m, 2 H, 2 × ArH), 7.33-7.45 (m, 7 H, 7 × ArH), 7.48-7.53 (m, 1 H, ArH), 7.55-7.62 (m, 2 H, 2 × ArH), 7.84 (dd, J _A,B = 8.5 Hz, J _A,X = 1.5 Hz, 2 H, 2 × ArH), 7.96 (dd, J _A,B = 8.5 Hz, J _A,X = 1.5 Hz, 2 H, 2 × ArH), 8.06 (dd, J _A,B = 8.5 Hz, J _A,X = 1.5 Hz, 2 H, 2 × ArH), 8.12 (dd, J _A,B = 8.5 Hz, J _A,X = 1.5 Hz, 2 H, 2 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 24.6 (Me), 25.1 (Me), 26.1 (Me), 26.4 (Me), 63.0 (C-6b), 66.8 (C-5a), 67.0 (C-4b), 67.7 (C-6a), 69.0 (C-5b), 70.4 (C-3b), 70.5 (C-2b), 70.8 (C-3a), 71.0, 71.1 (C-2a, C-4a), 96.5 (C-1a), 98.0 (C-1b), 108.9 (Cq), 109.6 (Cq), 128.4 (2 × ArCH), 128.5 (2 × ArCH), 128.6 (2 × ArCH), 128.7 (2 × ArCH), 129.2 (ArC), 129.3 (ArC), 129.5 (ArC), 129.8 (2 × ArCH), 129.9 (2 × ArCH), 129.9 (2 × ArCH), 130.0 (2 × ArCH), 130.1 (ArC), 133.1 (ArCH), 133.3 (ArCH), 133.5 (ArCH), 133.6 (ArCH), 165.5 (C=O), 165.5 (C=O), 165.6 (C=O), 166.4 (C=O). HRMS (ESI⁺): m/z [M + NH₄ ⁺] calcd for C₄₆H₅₀NO₁₅: 856.3175; found: 856.3167).

20

Selected data for 12b (α-anomer): [α]_D ²⁴ -14 (c = 0.9, CHCl₃). IR (film): 3020 (w, CHAr), 2934 (w, CH), 1725 (s, C=O), 1601, 1598, 1500, 1452 (m, C=CAr), 1270, 1069 (s, CO), 711 (m, CH) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.34 (s, 2 × 3 H, 2 × Me), 1.44 (s, 3 H, Me), 1.58 (s, 3 H, Me), 3.81 (dd, J _5a,6a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6a), 3.94 (dd, J _5a,6 _′a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6′a), 4.07 (d app t, J _4a,5a = 1.5 Hz, J _5a,6a = 6.5 Hz, J _5a,6 _′a = 6.5 Hz, 1 H, H-5a), 4.13 (dd, J _1b,2b = 1.5 Hz, J _2b,3b = 3.0 Hz, 1 H, H-2b), 4.26 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 1.5 Hz, 1 H, H-4a), 4.34 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.45 (dd, J _4b,5b = 10.0 Hz, J _5b,6b = 5.0 Hz, J _5b,6 _′b = 2.5 Hz, 1 H, H-5b), 4.48 (dd, J _5b,6b = 5.0 Hz, J _6b,6 _′b = 12.0 Hz, 1 H, H-6b), 4.57 (dd, J _5b,6 _′b = 2.5 Hz, J _6b,6 _′b = 12.0 Hz, 1 H, H-6′b), 4.64 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.65 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.69 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 5.11 (d, J _1b,2b = 1.5 Hz, 1 H, H-1b), 5.55 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 5.69 (dd, J _2b,3b = 3.0 Hz, J _3b,4b = 10.0 Hz, 1 H, H-3b), 6.06 (app t, J _3b,4b = 10.0 Hz, J _4b,5b = 10.0 Hz, 1 H, H-4b), 7.15-7.38 (m, 11 H, 11 × ArH), 7.45-7.53 (m, 3 H, 3 × ArH), 7.92-8.10 (m, 6 H, 6 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 24.7 (Me), 25.1 (Me), 26.1 (Me), 26.2 (Me), 63.6 (C-6b), 66.2 (C-5a), 66.7 (C-6a), 67.4 (C-4b), 69.1 (C-5b), 70.7 (C-2a), 70.8 (C-3a), 71.1 (C-4a), 72.4 (C-3b), 73.1 (CH₂ of Bn), 75.7 (C-2b), 96.5 (C-1a), 97.9 (C-1b), 108.8 (Cq), 109.5 (Cq), 127.6, 128.4, 128.5, 129.9 (16 × ArCH), 127.7 (ArCH), 129.4 (ArC), 129.5 (ArC), 130.0 (ArC), 132.9 (ArCH), 133.3 (2 × ArCH), 137.8 (ArC), 165.5 (C=O), 165.9 (C=O), 166.4 (C=O). HRMS (ESI⁺): m/z [M + NH₄ ⁺] calcd for C₄₆H₅₂NO₁₄: 842.3382; found: 842.3422. Selected data for 12b (β-anomer): [α]_D ²⁴ -7 (c = 0.2, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 1.33 (s, 2 × 3 H, 2 × Me), 1.42 (s, 3 H, Me), 1.55 (s, 3 H, Me), 3.75 (dd, J _5a,6a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6a), 3.89 (dd, J _5a,6 _′a = 6.5 Hz, J _6a,6 _′a = 10.5 Hz, 1 H, H-6′a), 4.00 (dd, J _1b,2b = 1.5 Hz, J _2b,3b = 3.5 Hz, 1 H, H-2b), 4.02 (d app t, J _4a,5a = 2.0 Hz, J _5a,6a = 6.5 Hz, J _5a,6 _′a = 6.5 Hz, 1 H, H-5a), 4.09 (ddd, J _4b,5b = 10.0 Hz, J _5b,6b = 2.0 Hz, J _5b,6 _′b = 4.0 Hz, 1 H, H-5b), 4.23 (dd, J _3a,4a = 8.0 Hz, J _4a,5a = 2.0 Hz, 1 H, H-4a), 4.25 (app t, J _3b,4b = 10.0 Hz, J _4b,5b = 10.0 Hz, 1 H, H-4b), 4.32 (dd, J _1a,2a = 5.0 Hz, J _2a,3a = 2.5 Hz, 1 H, H-2a), 4.58 (dd, J _5b,6b = 2.0 Hz, J _6b,6 _′b = 12.0 Hz, 1 H, H-6b), 4.62 (dd, J _2a,3a = 2.5 Hz, J _3a,4a = 8.0 Hz, 1 H, H-3a), 4.63 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.68 (d, J = 12.0 Hz, 1 H, CH₂ of Bn), 4.79 (dd, J _5b,6b = 4.0 Hz, J _6b,6 _′b = 12.0 Hz, 1 H, H-6b), 5.05 (d, J _1b,2b = 1.5 Hz, 1 H, H-1b), 5.43 (dd, J _2b,3b = 3.5 Hz, J _3b,4b = 10.0 Hz, 1 H, H-3b), 5.53 (d, J _1a,2a = 5.0 Hz, 1 H, H-1a), 7.16-7.31 (m, 5 H, 5 × ArH), 7.36-7.47 (m, 6 H, 6 × ArH), 7.53-7.61 (m, 3 H, 3 × ArH), 8.01-8.11 (m, 6 H, 6 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 24.7 (Me), 25.1 (Me), 26.1 (Me), 26.3 (Me), 64.1 (C-6b), 66.2 (C-5a), 66.2 (C-4b), 66.4 (C-6a), 70.7 (C-2a), 70.8 (C-3a), 71.1 (C-4a), 71.6 (C-5b), 73.1 (CH₂ of Bn), 74.7 (C-3b), 76.2 (C-2b), 96.5 (C-1a), 97.8 (C-1b), 108.9 (Cq), 109.5 (Cq), 127.6, 128.4, 128.5, 128.6, 130.0 (16 × ArCH), 127.8 (ArCH), 129.7 (2 × ArC), 130.0 (ArC), 133.2 (ArCH), 133.4 (2 × ArCH), 138.0 (ArC), 166.9 (C=O), 167.2 (2 × C=O).

21 See for example: Ziegler T. Kovac P. Glaudemans CPJ. Liebigs Ann. Chem. 1990, 613

22a Braccini I. Derouet C. Esnault J. Hervé du Penhoat C. Mallet J.-M. Michon V. Sinaӱ P. Carbohydr. Res. 1993, 246: 23

22b Sinaӱ P. Pure Appl. Chem. 1991, 63: 519

22c Marra A. Esnault J. Veyrières A. Sinaӱ P. J. Am. Chem. Soc. 1992, 114: 6354 ; and references contained therein

23a Marra A. Mallet J.-M. Amatore C. Sinaӱ P. Synlett 1990, 572

23b Mehta S. Pinto BM. Carbohydr. Res. 1998, 310: 43

24

Typical Procedure for Chemical Glycosylation Mediated by (4-BrC ₆ H ₄ ) ₃ NSbCl ₆: Under an atmosphere of argon, glycosyl donor (ca. 30-90 mg, 1 equiv), glycosyl acceptor (ca. 20-50 mg, 1.2 equiv) and 3 Å MS were suspended in anhyd MeCN (or CH₂Cl₂, 10 mL) and the reaction mixture was stirred at r.t. for 30 min prior to addition of (4-BrC₆H₄)₃NSbCl₆ (ca. 120-340 mg, 3 equiv). After 3 h, the mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was then purified by flash column chromatography (typically eluting with PE-EtOAc, 9:1) to afford the desired disaccharide as a colourless oil.