Protecting Group and Solvent Effects in Electrochemical Glycosylation

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.

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

References and Notes

<A NAME="RD19707ST-1A">1a</A> Varki A. Glycobiology  1993,  3:  97 

<A NAME="RD19707ST-1B">1b</A> Dwek RA. Chem. Rev.  1996,  96:  683 

<A NAME="RD19707ST-2">2</A> Davis BG. J. Chem. Soc., Perkin Trans. 1  2000,  2137 

<A NAME="RD19707ST-3">3</A> Mootoo DR. Konradsson P. Udodong U. Fraser-Reid B. J. Am. Chem. Soc.  1988,  110:  5583 

<A NAME="RD19707ST-4A">4a</A> Grice P. Ley SV. Pietruszka J. Priepke HWM. Walter EPE. Synlett  1995,  781 

<A NAME="RD19707ST-4B">4b</A> Cheung MK. Douglas NL. Hinzen B. Ley SV. Pannecoucke X. Synlett  1997,  257 

<A NAME="RD19707ST-4C">4c</A> Grice P. Ley SV. Pietruszka J. Osborn HMI. Priepke HWM. Warriner S. Chem. Eur J.  1997,  3:  431 

<A NAME="RD19707ST-4D">4d</A> Green L. Hinzen B. Ince SJ. Langer P. Ley SV. Warriner SL. Synlett  1998,  440 

<A NAME="RD19707ST-4E">4e</A> Douglas NL. Ley SV. Lücking U. Warriner SL. J. Chem. Soc., Perkin Trans. 1  1998,  51 

<A NAME="RD19707ST-5A">5a</A> Zhang Z. Ollmann IR. Ye X.-S. Wischnat R. Baasov T. Wong C.-H. J. Am. Chem. Soc.  1999,  121:  734 

<A NAME="RD19707ST-5B">5b</A> Ye X.-S. Wong C.-H. J. Org. Chem.  2000,  65:  2410 

<A NAME="RD19707ST-5C">5c</A> Burkhart F. Zhang Z. Wacowich-Sgarbi S. Wong C.-H. Angew. Chem. Int. Ed.  2001,  40:  1274 

<A NAME="RD19707ST-6">6</A> Noyori R. Kurimoto I. J. Org. Chem.  1986,  51:  4320 

<A NAME="RD19707ST-7A">7a</A> Amatore C. Jutand A. Mallet J.-M. Meyer G. Sinaӱ P. J. Chem. Soc., Chem. Commun.  1990,  718 

<A NAME="RD19707ST-7B">7b</A> Marra A. Mallet J.-M. Amatore C. Sinaӱ P. Synlett  1990,  572 

<A NAME="RD19707ST-7C">7c</A> Mallet J.-M. Meyer G. Yvelin F. Jutand A. Amatore C. Sinaӱ P. Carbohydr. Res.  1993,  244:  237 

<A NAME="RD19707ST-7D">7d</A> Amatore C. Jutand A. Meyer G. Bourhis P. Machetto F. Mallet J.-M. Sinaӱ P. Tabeur C. Zhang Y.-M. J. Appl. Electrochem.  1994,  24:  725 

For a similar approach, see:

<A NAME="RD19707ST-8A">8a</A> Yamago S. Kokobu K. Hara O. Masuda S. Yoshida J. J. Org. Chem.  2002,  67:  8584 

<A NAME="RD19707ST-8B">8b</A> Yamago S. Kokubo K. Yoshida J. Chem. Lett.  1997,  111 

<A NAME="RD19707ST-9A">9a</A> France RR. Compton RG. Fairbanks AJ. Rees NV. Wadhawan JD. Org. Biomol. Chem.  2004,  2:  2188 

<A NAME="RD19707ST-9B">9b</A> France RR. Compton RG. Davis BG. Fairbanks AJ. Rees NV. Wadhawan JD. Org. Biomol. Chem.  2004,  2:  2195 

<A NAME="RD19707ST-10">10</A>

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.

<A NAME="RD19707ST-11">11</A> Wulff G. Röhle G. Angew. Chem., Int. Ed. Engl.  1974,  13:  157 

<A NAME="RD19707ST-12A">12a</A> Balavoine G. Gref A. Fischer J.-C. Lubineau A. Tetrahedron Lett.  1990,  31:  5761 

<A NAME="RD19707ST-12B">12b</A> Balavoine G. Berteina S. Gref A. Fischer J.-C. Lubineau A. J. Carbohydr. Chem.  1995,  14:  1217 

<A NAME="RD19707ST-12C">12c</A> Balavoine G. Berteina S. Gref A. Fischer J.-C. Lubineau A. J. Carbohydr. Chem.  1995,  14:  1237 

<A NAME="RD19707ST-13">13</A>

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.

<A NAME="RD19707ST-14">14</A>

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).

<A NAME="RD19707ST-15">15</A>

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.

<A NAME="RD19707ST-16A">16a</A> Zhu T. Boons G.-J. Tetrahedron: Asymmetry  2000,  11:  199 

<A NAME="RD19707ST-16B">16b</A> Roussel F. Knerr L. Grathwohl M. Schmidt RR. Org. Lett.  2000,  2:  3043 

<A NAME="RD19707ST-17">17</A>

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.

<A NAME="RD19707ST-18">18</A> Smoot JT. Pornsuriyasak P. Demchenko AV. Angew. Chem. Int. Ed.  2005,  44:  7123 

<A NAME="RD19707ST-19">19</A>

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).

<A NAME="RD19707ST-20">20</A>

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).

<A NAME="RD19707ST-21">21</A> See for example: Ziegler T. Kovac P. Glaudemans CPJ. Liebigs Ann. Chem.  1990,  613 

<A NAME="RD19707ST-22A">22a</A> Braccini I. Derouet C. Esnault J. Hervé du Penhoat C. Mallet J.-M. Michon V. Sinaӱ P. Carbohydr. Res.  1993,  246:  23 

<A NAME="RD19707ST-22B">22b</A> Sinaӱ P. Pure Appl. Chem.  1991,  63:  519 

<A NAME="RD19707ST-22C">22c</A> Marra A. Esnault J. Veyrières A. Sinaӱ P. J. Am. Chem. Soc.  1992,  114:  6354 ; and references contained therein

<A NAME="RD19707ST-23A">23a</A> Marra A. Mallet J.-M. Amatore C. Sinaӱ P. Synlett  1990,  572 

<A NAME="RD19707ST-23B">23b</A> Mehta S. Pinto BM. Carbohydr. Res.  1998,  310:  43 

<A NAME="RD19707ST-24">24</A>

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.