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1 Electronic Supplementary Information Phenylenediamine catalysis of click glycosylations in water : Practical and direct access to unprotected neoglycoconjugates Aurélie Baron, a Yves Blériot, b Matthieu Sollogoub b and Boris Vauzeilles* a a CRS, Glycochimie Moléculaire et Macromoléculaire, ICMM, UMR 8182, rsay F-910, France; Univ Paris Sud, rsay, F910 b Université Pierre et Marie Curie-Paris 6, Institut de Chimie Moléculaire (FR 2769), Laboratoire de Chimie rganique (UMR CRS 7611), place Jussieu, C. 181, F700 Paris, France. General Methods Thin layer chromatography was performed on Merck 60F 2 sheets with detection by UV and by charring with % ethanolic H 2 S. Unless otherwise stated, TLC was eluted with ethyl acetate / isopropanol / water 3:2:1. Hygroscopic reagents were dried in vacuo immediately prior to weighing. MR spectra were taken on Bruker DPX 20, AM 300, AV 360 or DRX 00 spectrometers, using the residual protonated solvent as internal standard. Chemical shifts! are given in parts per million (ppm). Mass spectra were taken on a ThermoFinnigan Mat 9, with Electrospray ionization in the positive (ESI + ) or negative (ESI - ) mode of detection, or on a Jeol JMS-700, with Fast Atom Bombardment ionization in the positive mode of detection (FAB + ). Residual free copper was first estimated with Quantofic Copper test sticks (Macherey-agel) and then quantified by CHEMets Kit Copper K-310 (CHEMetrics) colorimetric assay. Methyl 3--propargyl-!-D-glucopyranoside: To a solution of methyl,6--benzylidene-3--propargyl-"-d-glucopyranoside 1 (00 mg, 1.6 mmol) in Me (20.0 ml) was added 2.1 g of Dowex 0WX8-H + resin. The suspension was stirred at 0 C overnight. The reaction mixture was filtered off, and neutralized with solid ahc 3, filtered and the solvent was evaporated. The residue was purified by column 1

2 chromatography over silica gel (Petroleum Ether/EtAc 1/) to yield 36 mg (98%) of methyl 3--propargyl-!-D-glucopyranoside as a colourless oil. 1 H MR (360 MHz, MeD-d )!:.6 (d, 1H, J 1,2.0 Hz, H-1);.9 (d, 2H, J 2.0 Hz, CH 2 CCH); 3.80 (dd, 1H, J 6a,6b 12.0, J 6a, 2.0 Hz, H-6a); 3.67 (dd, 1H, J 6b,6a 12.0, J 6b,. Hz, H-6b); 3.7 (dd, 1H, J 3,2 9., J 3, 8. Hz, H-3); 3. (ddd, 1H, J, 10.0, J,6b., J,6a 2.0 Hz, H-); 3.7 (dd, 1H, J 2,3 9., J 2,1.0 Hz, H-2); 3.1 (s, 3H, CH 3 ); 3.36 (dd, 1H, J, 10.0, J,3 8. Hz, H-); 2.81 (t, 1H, J 2. Hz, CH 2 CCH). 13 C MR (90 MHz, DMS-d 6 )!: 99.7 (C-1); 81. (C-3); 81.3 (CH 2 CCH); 76.3 (CH 2 CCH); 72.6 (C-); 71.6 (C-2); 69. (C-); 60.7 (C-6); 9.2 (CH 2 CCH);.3 (CH 3 ). MS (ESI + ) : m/z 2.2 [M+a] +. HRMS (ESI + ) : Calcd. for C 10 H 16 6 a , found acetyl-l-phenylalanine propargylamide : 6' ' ' H 3 2 1' 1 -Acetyl-L-phenylalanine (32 mg, 1.6 mmol) was dissolved in dry CH 2 Cl 2 (6.0 ml) with DMAP (19.0 mg, 0.16 mmol, 0.1 eq.) and EDC HCl (9 mg, 2.3 mmol, 1. eq.). Propargylamine (100 µl, 86.0 mg, 1.6 mmol, 1.0 eq.) was added and the reaction mixture was stirred at room temperature overnight under an argon atmosphere until TLC (CH 2 Cl 2 /Me 9:1) showed complete conversion. The reaction mixture was washed three times with water, and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography over silica gel (CH 2 Cl 2 / Me 9/1) to give 99.0 mg (26 %) of -acetyl-l-phenylalanine propargylamide as a white solid. 1 H MR (300 MHz, CDCl 3 )!: (m, 3H, H-3, H-, H- ); 7.20 (m, 2H, H-2, H-6 ); 6.7 (t, 1H, 3 J.3 Hz, CCH 2 ); 6.1 (d, 1H, J H,2 7. Hz, CH 3 C);.69 (td, 1H, J 2,3 7., J 2,H 7. Hz, H-2); 3.9 (dd, 2H, J.3, J 2. Hz, CH 2 CCH); 3.0 (d, 2H, J 3,2 7. Hz, H-3); 2.19 (t, 1H, J 2. Hz, CH 2 CCH); 1.97 (s, 3H, CH 3 ). 13 C MR (7 MHz, CDCl 3 )!: ( C-1); 170. ( CH 3 C); ( C-1 ); 129. ( C-2, C-6 ); ( C-3, C- ); ( C- ); 79.1 (CH 2 CCH); 71.8 (CH 2 CCH);.6 (C-2); 38.7 (C-3); 29.3 (CH 2 CCH); 23.3 (CH 3 ). MS (ESI + ) : m/z [M+a] +. HRMS (ESI + ) : Calcd. for C 1 H a , found ' H 3' 2

3 -Hydroxymethyl-1-("-D-glucopyranosyl)-1H-[1,2,3]-triazole (2) : 6' ' ' 3' 2' 1' Procedure A : To a solution of #-D-glucopyranosyl azide (3.0 mg, 260 µmol, 1 eq.) in H 2 (730 µl) were added propargyl alcohol (1 µl, 1. mg, 260 µmol, 1 eq.), o-phenylenediamine (10 µl, 0. mg per ml of H 2,.2 mg, 39 µmol, 1 mol%), sodium ascorbate (10 µl, 9. mg per ml of H 2,.1 mg, 26 µmol, 10 mol%) and copper sulfate pentahydrate (10 µl, 31.2 mg per ml of H 2, 3.2 mg, 13 µmol, mol%). The reaction mixture was stirred at room temperature under an argon atmosphere for min. After this time, TLC showed complete conversion and activated charcoal (100 mg) was added to the reaction mixture, which was stirred overnight under an air atmosphere. The reaction mixture was then filtered through a celite plug and eluted with water. The solvent was evaporated to dryness to give 66. mg (98%) of - hydroxymethyl-1-("-d-glucopyranosyl)-1h-[1,2,3]-triazole 2 (2) as a colourless oil. 1 H MR (300 MHz, methanol-d)!: 8.13 (s, 1H, H-);.61 (d, 1H, J 1, 2 9. Hz, H-1 );.71 (s, 2H, CCH 2 ); (m, 2H, H-2, H-6a ); 3.72 (dd, 1H, J 6a,6b 12.0, J,6b.0 Hz, H-6b ); (m, 3H, H-3, H-, H- ). 13 C MR (7 MHz, methanol-d)!: 19.1 (C-); 123. (C-); 89. (C-1 ); 81.1 (C- ); 78. (C-3 ); 7.0 (C-2 ); 70.9 (C- ); 62. (C-6 ); 9. (CCH 2 ). Residual copper ~ 0.10 mol%. MS (ESI + ) : m/z 28.1 [M+a] +. HRMS (ESI + ) : Calcd. for C 9 H 1 6 a , found ((Dimethylamino)methyl)-1-("-D-glucopyranosyl)-1H-[1,2,3]-triazole (3) : 6' ' ' 3' 2' 1' Following Procedure A, -((dimethylamino)methyl)-1-("-d-glucopyranosyl)-1h-[1,2,3]- triazole (3) was obtained from #-D-glucopyranosyl azide (1.3 mg, 20 µmol, 1 eq.) in H 2 (600 µl), dimethylaminopropyne (27 µl, 20.8 mg, 20 µmol, 1 eq.), o-phenylenediamine (200 µl, 20.3 mg per ml of H 2,.0 mg, 37. µmol, 1 mol%), sodium ascorbate (100 µl, 9. mg per ml of H 2,.9 mg, 2.0 µmol, 10 mol%) and copper sulfate pentahydrate (100 µl,

4 mg per ml of H 2, 3.1 mg, 12. µmol, mol%). The reaction mixture was stirred at room temperature for min, and activated charcoal was added followed by min of stirring under an air atmosphere. Purification by filtration and evaporation gave 3.7 mg (7%) of - ((dimethylamino)methyl)-1-("-d-glucopyranosyl)-1h-[1,2,3]-triazole (3) as a white solid. 1 H MR (300 MHz, methanol-d)!: 8.12 (s, 1H, H-);.60 (d, 1H, J 1, Hz, H-1 ); 3.89 (dd, 1H, J 2,1 9.0, J 2,3 9.0 Hz, H-2 ); 3.88 (dd, 1H, J 6a,6b 12.0, J 6a, 2.0 Hz, H-6a ); 3.71 (dd, 1H, J 6a,6b 12.0, J,6b.0 Hz, H-6b ); 3.66 (s, 2H, CCH 2 (CH 3 ) 2 ); 3.8 (ddd, 1H, J, 9.0, J,6b.0, J,6a 2.0 Hz, H- ); 3.6 (dd, 1H, J 3, 9.0, J 3,2 8. Hz, H-3 ); 3.9 (dd, 1H, J,3 9.0, J, 9.0 Hz, H- ); 2.29 (s, 6H, 2 CH 3 ). 13 C MR (62. MHz, methanol-d)!: 1.7 (C-); 12.8 (C-); 89.7 (C-1 ); 81.3 (C- ); 78.7 (C-3 ); 7.2 (C-2 ); 71.0 (C- ); 62.6 (C-6 );. (CCH 2 (CH 3 ) 2 );.0 (2 CH 3 ). Residual copper ~ 0.16 mol%. MS (ESI + ) : m/z [M+a] +. HRMS (ESI + ) : Calcd. for C 11 H 20 a , found Ammonium 3-[1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]propanoate () : 6'' '' 3'' '' 2'' 1'' ' 3 ' 2 1 H Following Procedure A, ammonium 3-[1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol- - yl]propanoate () was obtained from #-D-glucopyranosyl azide (1.3 mg, 20 µmol, 1 eq.) in H 2 (600 µl), ammonium -pentynoate (28.8 mg, 20 µmol, 1 eq.), o-phenylenediamine (200 µl, 20.3 mg per ml of H 2,.0 mg, 37. µmol, 1 mol%), ammonium ascorbate (100 µl, 8.3 mg per ml of H 2,.8 mg, 2.0 µmol, 10 mol%) and copper sulfate pentahydrate (100 µl, 31.2 mg per ml of H 2, 3.1 mg, 12. µmol, mol%). The reaction mixture was stirred at room temperature for 2 hours, and activated charcoal was added followed by min of stirring under an air atmosphere. Purification by filtration and evaporation gave 62. mg (78%) of ammonium 3-[1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]propanoate () as a white solid. 1 H MR (20 MHz, methanol-d)!: 7.9 (s, 1H, H- );. (d, 1H, J 1, Hz, H-1 ); 3.87 (dd, 1H, J 6a,6b 12.0, J,6a 1. Hz, H-6a ); 3.86 (dd, 1H, J 1,2 9.0, J 2,3 9. Hz, H-2 ); 3.70 (dd, 1H, J 6a,6b 12.0, J,6b.0 Hz, H-6b ); (m, 3H, H-3, H-, H- ); 3.00 (t, 2H, J 3,2 7.0 Hz, H-3); 2.9 (t, 2H, J 2,3 7.0 Hz, H-2). 13 C MR (62. MHz, methanol-d)!: 18.8 (C- ); (C- ); 89.7 (C-1 ); 81.2 (C- ); 78.6 (C-3 ); 7.2 (C- 2 ); 71.0 (C- ); 62.6 (C-6 ); 36.9 (C-2); 23.0 (C-3). Residual copper ~ 0.0 mol%. MS

5 (ESI - ) : m/z [M] -. HRMS (ESI - ) : Calcd. for C 11 H a , found [1 -("-D-Glucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]-methyl 2-acetamido-2-deoxy-"-Dglucopyranoside () : 6'' '' 3'' '' 2'' 1'' ' 3 H 2 ' 1 6 Following Procedure A, [1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]-methyl 2- acetamido-2-deoxy-"-d-glucopyranoside () was obtained from #-D-glucopyranosyl azide (11 mg, 60 µmol, 1 eq.) in H 2 (170 µl), propargyl 2-acetamido-2-deoxy-#-Dglucopyranoside 3 (1 mg, 60 µmol, 1 eq.), o-phenylenediamine (22 µl, 0. mg per ml of H 2, 9.1 mg, 8.0 µmol, 1 mol%), sodium ascorbate (22 µl, 9. mg per ml of H 2, 11.1 mg, 6.0 µmol, 10 mol%) and copper sulfate pentahydrate (22 µl, 31.2 mg per ml of H 2, 7.0 mg, 28.0 µmol, mol%). The reaction mixture was stirred at room temperature for 2 hours, and activated charcoal was added followed by overnight stirring under an air atmosphere. Purification by filtration and evaporation gave 27. mg (9%) of [1 -("-Dglucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]-methyl-2-acetamido-2-deoxy-"-dglucopyranoside () as a white solid. 1 H MR (360 MHz, methanol-d)!: 8.18 (s, 1H, H- );.61 (d, 1H, J 1, Hz, H-1 );.91 (d, 1H, J 12. Hz, CCH a H b );.78 (d, 1H, J 12. Hz, CCH a H b );.7 (d, 1H, J 1,2 8. Hz, H-1); 3.91 (dd, 1H, 2 J 12.0, 3 J 1. Hz, H-6a or H-6a ); 3.88 (dd, 1H, 2 J 12.0, 3 J 2.0 Hz, H-6a or H-6a ); 3.88 (dd, 1H, J 2,1 9.0, J 2,3 9.0 Hz, H-2 ); 3.71 (dd, 1H, 2 J 12.0, 3 J. Hz, H-6b or H-6b ); 3.70 (dd, 1H, 2 J 12.0, 3 J.0 Hz, H-6b or H- 6b ); 3.60 (dd, 1H, J 3, 10.0, J 3,2 8. Hz, H-3); 3.9 (dd, 1H, J 2,1 8., J 2,3 8. Hz, H-2); 3.8 (dd, 1H, J 3,2 9.0, J 3, 9.0 Hz, H-3 ); 3.0 (dd, 1H, J,3 9.0, J, 9. Hz, H- ); 3.9 (dd, 1H, J,3 10.0, J, 8.0 Hz, H-); (m, 2H, H-, H- ); 1.92 (s, 3H, CH 3 ). 13 C MR (90 MHz, methanol-d)!: 17.1 (C=); 1.9 (C- ); 12.8 (C- ); (C-1); 89.8 (C-1 ); 81.3 (C-3); 78. (C-3 ); 78.2 (C-); 7.9 (C-); 7.3 (C-2 ); 72.3 (C- ); 71.1 (C- ); 63.0 (C-6 or C-6 ); 62.8 (CCH 2 ); 62. (C-6 or C-6 ); 7.6 (C-2); 23.1 (CH 3 ). Residual copper ~ 0.31 mol%. MS (ESI + ) : m/z 87.0 [M+a] +. HRMS (ESI + ) : Calcd. for C 17 H a , found

6 Methyl 3--[1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]-methyl-!-dglucopyranoside (6): 6'' '' 3'' '' 2'' 1'' ' ' Following Procedure A, methyl 3--[1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol- -yl]- methyl-!-d-glucopyranoside (6) was obtained from #-D-glucopyranosyl azide (11 mg, µmol, 1 eq.) in H 2 (160 µl), methyl 3--propargyl-"-D-glucopyranoside (129 mg, µmol, 1 eq.), o-phenylenediamine (220 µl, 0. mg per ml of H 2, 8.9 mg, 82. µmol, 1 mol%), sodium ascorbate (220 µl, 9. mg per ml of H 2, 10.9 mg,. µmol, 10 mol%) and copper sulfate pentahydrate (220 µl, 31.2 mg per ml of H 2, 6.9 mg, 27. µmol, mol%). The reaction mixture was stirred at room temperature for min, and activated charcoal was added followed by overnight stirring under an air atmosphere. Purification by filtration and evaporation gave mg (98%) of methyl 3--[1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]- triazol- -yl]-methyl-!-d-glucopyranoside (6) as a white solid. 1 H MR (360 MHz, methanol-d)!: 8.18 (s, 1H, H- );.60 (d, 1H, J 1, Hz, H-1 );.00 (d, 1H, J 12.0 Hz, CCH a H b C);.9 (d, 1H, J 12.0 Hz, CCH a H b C);.67 (d, 1H, J 1,2 3. Hz, H-1); (m, 2H, H-2, H-6a ); 3.81 (dd, 1H, J 6a,6b 12.0, J 6a, 2. Hz, H-6a); 3.71 (dd, 1H, J 6b,6a 11., J 6b,. Hz, H-6b ); 3.68 (dd, 1H, J 6b,6a 12.0, J 6b,. Hz, H-6b); (m, H, H-3, H-, H-, H-, H- ); 3.61 (dd, 1H, J 3,2 9., J 3, 9.0 Hz, H-3); 3.1 (dd, 1H, J 2,3 9., J 2,1 3. Hz, H-2); 3.2 (s, 3H, CH 3 ). 13 C MR (90 MHz, methanol-d)!: 17.1 (C- ); 12.2 (C- ); 101. (C-1); 89.8 (C-1 ); 8.3 (CH); 81.3 (CH); 78.6 (CH); 7.3 (C-2 ); 73.7 (2 CH); 71. (CH); 71.1 (CH); 67.0 (CCH 2 C); 62.7, 62.6 (C-6, C-6 );.8 (CH 3 ). Residual copper ~ 0.0 mol%. MS (ESI + ) : m/z 60.1 [M+a] +. HRMS (ESI + ) : Calcd. for C 16 H a , found

7 Tris((1-("-D-glucopyranosyl)-1H-[1,2,3]-triazol--yl)methyl)amine (7): 6' ' 6' ' ' 3' 2' ' 1' 2' 1' 3' 1' 2' Following procedure A, tris((1-"-d-glucopyranosyl)-1h-[1,2,3]-triazol--yl)methyl)amine (7) was obtained from triprop-2-ynylamine (22 µl, 20.3 mg, 1. µmol), #-D-glucopyranosyl azide (9 mg, 63. µmol, 3 eq.), sodium ascorbate (18 µl, 9. mg per ml of H 2, 9.2 mg, 6. µmol, 0.30 eq.), copper sulfate pentahydrate (18 µl, 31.2 mg per ml of H 2,.8 mg, 23.2 µmol, 0.1 eq.) and o-phenylenediamine (370 µl, 20.3 mg per ml of H 2, 7. mg, 69. µmol, 0. eq.) in H 2 (1110 µl). The reaction mixture was stirred at room temperature for min, then activated charcoal was added followed by overnight stirring under an air atmosphere. Purification by filtration through an alumina plug and evaporation gave mg (92%) of tris((1-"-d-glucopyranosyl)-1h-[1,2,3]-triazol--yl)methyl)amine as white powder. 1 H MR (300 MHz, D 2 /methanol-d 1:1)!: 8.22 (s, 3H, 3 H-);.68 (d, 3H, J 1, Hz, 3 H-1 ); 3.97 (dd, 3H, J 2,1 9.0, J 2,3 9.0 Hz, 3 H-2 ); 3.90 (dd, 3H, J 6a,6b 12., J 6a, 2.0 Hz, 3 H-6a ); 3.83 (s, 6H, 3 CH 2 C); 3.76 (dd, 3H, J 6a,6b 12., J,6b.0 Hz, 3 H-6b ); 3.67 (ddd, 3H, J, 9., J,6b.0, J,6a 2.0 Hz, 3 H- ); 3.66 (dd, 3H, J 3,2 9.0, J 3, 9.0 Hz, 3 H-3 ); 3.8 (dd, 3H, J,3 9.0, J, 9. Hz, 3 H- );. 13 C MR (7 MHz, D 2 / methanol-d 1:1)!: 1.1 (3 C-); 12.3 (3 C-); 89.1 (3 C-1 ); 80. (3 C- ); 77.8 (3 C-3 ); 73.8 (3 C-2 ); 70. (3 C- ); 62.0 (3 C-6 ); 8. (3 CH 2 C). Residual copper below detection limit. MS (ESI + ) : m/z [M+a] +. HRMS (ESI + ) : Calcd. for C 27 H a , found ' ' ' 6' 7

8 -(1 -Methyl-1H-imidazol- -yl)-1-("-d-glucopyranosyl)-1h-[1,2,3]-triazole (8) : 6'' '' 3'' '' 2'' 1'' ' ' 2' Procedure B : To a solution of #-D-glucopyranosyl azide (6. mg, 31 µmol, 1 eq.) in H 2 (23 µl) and tbu (628 µl), were added -ethynyl-1-methyl-1h-imidazole (32.9 µl, 33. mg, 31 µmol, 1 eq.), o-phenylenediamine (12 µl, 0. mg per ml of H 2,.1 mg, 7.1 µmol, 1 mol%), sodium ascorbate (12 µl, 9. mg per ml of H 2, 6.2 mg, 31. µmol, 10 mol%) and copper sulfate pentahydrate (12 µl, 31.2 mg per ml of H 2, 3.9 mg, 1.7 µmol, mol%). The reaction mixture was stirred at room temperature under an argon atmosphere for one hour. After this time, TLC showed complete conversion. The solvents were evaporated and the residue was dissolved in Me/H 2, (1/1), ( ml), activated charcoal (~10 mg) was added and the suspension was stirred under an air atmosphere overnight. The reaction mixture was then filtered through a celite plug and eluted with Me/H 2 (1/1). The solvent were evaporated to dryness to give 86.6 mg (89%) of -(1 -methyl-1h-imidazol- -yl)-1-("-dglucopyranosyl)-1h-[1,2,3]-triazole (8) as a white solid. 1 H MR (360 MHz, methanol-d)!: 8.8 (s, 1H, H-); 7.7 (s, 1H, H-2 ); 7.31 (s, 1H, H- );.73 (d, 1H, J 1, Hz, H-1 );.00 (dd, 1H, J 2,1 9.0, J 2,3 9.0 Hz, H-2 ); 3.91 (dd, 1H, J 6a,6b 12.0, J 6a, 2.0 Hz, H-6a ); 3.8 (s, 3H, CH 3 ); 3.7 (dd, 1H, J 6a,6b 12.0, J 6b,.0 Hz, H-6b ); 3.68 (ddd, 1H, J, 9., J,6b.0, J,6a 2.0 Hz, H- ); 3.67 (dd, 1H, J 3, 9.0, J 3,2 9.0 Hz, H-3 ); 3.9 (dd, 1H, J,3 9.0, J, 9. Hz, H- ). 13 C MR (7 MHz, methanol-d)!: 11.3 (C-2 ); (C-); (C- ); 12.3 (C- ); (C-); 89.0 (C-1 ); 80. (C- ); 77. (C-3 ); 73.6 (C-2 ); 70.3 (C- ); 61.7 (C-6 ); 33.7 (CH 3 ). Residual copper ~ 0.0 mol%. MS (ESI + ) : m/z 33.1 [M+a] +. HRMS (ESI + ) : Calcd. for C 12 H 17 a , found (1 -Hydroxycyclohexyl)-1-("-D-glucopyranosyl)-1H-[1,2,3]-triazole (9) : 6'' '' 3'' '' 2'' 1'' 6' 1' 2' 3' ' ' 8

9 Following Procedure B, -(1 -hydroxycyclohexyl)-1-("-d-glucopyranosyl)-1h-[1,2,3]- triazole (9) was obtained from #-D-glucopyranosyl azide (.3 mg, 270 µmol, 1 eq.) in H 2 (107 µl) and tbu (39 µl), 1-ethynylcyclohexanol (3.6 µl, 33. mg, 270 µmol, 1 eq.), o- phenylenediamine (216 µl, 20.3 mg per ml of H 2,. mg, 0. µmol, 1 mol%), sodium ascorbate (108 µl, 9. mg per ml of H 2,.3 mg, 27.0 µmol, 10 mol%) and copper sulfate pentahydrate (108 µl, 31.2 mg per ml of H 2, 3. mg, 13. µmol, mol%). The reaction mixture was stirred at room temperature for min, and solvents were evaporated. The residue was dissolved in Me/H 2 (1/1), and activated charcoal was added followed by overnight stirring under an air atmosphere. Purification by filtration and evaporation gave 87. mg (98%) of -(1 -hydroxycyclohexyl)-1-("-d-glucopyranosyl)-1h-[1,2,3]-triazole (9) as a white solid. 1 H MR (300 MHz, methanol-d)!: 8.0 (s, 1H, H-);.8 (d, 1H, J 1, Hz, H-1 ); 3.91 (dd, 1H, J 2,1 9.0, J 2,3 9.0 Hz, H-2 ); 3.88 (dd, 1H, J 6a,6b 12.0, J 6a, 1. Hz, H-6a ); 3.71 (dd, 1H, J 6b,6a 12.0, J 6b,. Hz, H-6b ); (m, 1H, H- ); 3.6 (dd, 1H, J 3, 9.0, J 3,2 9.0 Hz, H-3 ); 3.9 (dd, 1H, J,3 9.0, J, 8. Hz, H- ); (m, 10H, H-2,3,,,6 ). 13 C MR (7 MHz, methanol-d)!: 17.1 (C-); (C-); 89.7 (C-1 ); 81.2 (C- ); 78.7 (C-3 ); 7.1 (C-2 ); 71.0 (C- ); 70. (C-1 ); 62. (C-6 ); 70. (2 CH 2 ); 26.7 (C- ); 23.2 (2 CH 2 ). Residual copper ~ 0.07 mol%. MS (ESI + ) : m/z 32.2 [M+a] +. HRMS (ESI + ) : Calcd. for C 1 H a , found Phenyl-1-("-D-glucopyranosyl)-1H-[1,2,3]-triazole (10) : 6'' '' 3'' '' 2'' 1'' 1' 2' 6' 3' ' ' Following Procedure B, -phenyl-1-("-d-glucopyranosyl)-1h-[1,2,3]-triazole (10) was obtained from #-D-glucopyranosyl azide (6.1 mg, 312 µmol, 1 eq.) in H 2 (12 µl) and tbu (62 µl), ethynylbenzene (3.0 µl, 31.9 mg, 312 µmol, 1 eq.), o-phenylenediamine (20 µl, 20.3 mg per ml of H 2,.1 mg, 6.8 µmol, 1 mol%), sodium ascorbate (12 µl, 9. mg per ml of H 2, 6.2 mg, 31.2 µmol, 10 mol%) and copper sulfate pentahydrate (12 µl, 31.2 mg per ml of H 2, 3.9 mg, 1.6 µmol, mol%). The reaction mixture was stirred at room temperature for min, and solvents were evaporated. The residue was dissolved in Me/H 2 (1/1), and activated charcoal was added followed by overnight stirring under an 9

10 air atmosphere. Purification by filtration and evaporation gave 93.0 mg (97%) of -phenyl-1- ("-D-glucopyranosyl)-1H-[1,2,3]-triazole (10) as a white solid. 1 H MR (20 MHz, methanol-d)!: 8.7 (s, 1H, H-); 7.8 (dd, 2H, 3 J 7.0, J 1. Hz, H-2, H-6 ); 7. (tt, 2H, 3 J 7.0, J 1. Hz, H-3, H- ); 7.3 (tt, 1H, 3 J 7.0, J 1. Hz, H- );.66 (d, 1H, J 1, Hz, H- 1 ); 3.96 (dd, 1H, J 2,1 9.0, J 2,3 9.0 Hz, H-2 ); 3.91 (dd, 1H, J 6a,6b 12.0, J 6a, 1. Hz, H- 6a ); 3.7 (dd, 1H, J 6b,6a 12.0, J 6b,.0 Hz, H-6b ); 3.61 (ddd, 1H, J, 9.0, J,6b.0, J,6a 1. Hz, H- ); 3.61 (dd, 1H, J 3, 8., J 3,2 9.0 Hz, H-3 ); 3.3 (dd, 1H, J,3 8., J, 9.0 Hz, H- ). 13 C MR (62. MHz, methanol-d)!: 19.0 (C-); (C-1 ); (C- 3, ); (C- ); (C-2,6 ); 121. (C-); 89.9 (C-1 ); 81.3 (C- ); 78.6 (C-3 ); 7.2 (C-2 ); 71.0 (C- ); 62. (C-6 ). Residual copper ~ 0.07 mol%. MS (ESI + ) : m/z [M+a] +. HRMS (ESI + ) : Calcd. for C 1 H 17 3 a , found acetyl-l-phenylalanine (1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]-triazol--yl)methylamide (11) : 6'' '' 3'' '' 2'' 1'' ' Following Procedure B, -acetyl-l-phenylalanine (1 -("-D-glucopyranosyl)-1 H-[1,2,3 ]- triazol--yl)methylamide was obtained from #-D-glucopyranosyl azide (3.2 mg, 29 µmol, 1 eq.) in H 2 (103 µl) and tbu (18 µl), -acetyl-l-phenylalanine propargylamide (63.6 mg, 29 µmol, 1 eq.), o-phenylenediamine (207 µl, 20.3 mg per ml of H 2,.2 mg, 38.9 µmol, 1 mol%), sodium ascorbate (10 µl, 9. mg per ml of H 2,.1 mg, 26.0 µmol, 10 mol%) and copper sulfate pentahydrate (10 µl, 31.2 mg per ml of H 2, 3.2 mg, 13.0 µmol, mol%). The reaction mixture was stirred at room temperature for min, and solvents were evaporated. The residue was dissolved in Me/H 2, and activated charcoal was added followed by overnight stirring under an air atmosphere. Purification by filtration and evaporation gave 98.2 mg (8%) of -acetyl-l-phenylalanine (1 -("-D-glucopyranosyl)-1 H- [1,2,3 ]-triazol--yl)methylamide (11) as a slightly beige solid. ''' ''' ' 3''' 6''' H 2''' 1''' H 1 H MR (360 MHz, dimethylsulfoxide-d6)!: 7.8 (s, 1H, H- ); (m, H, H-Ar);.8 (d, 1H, J 1, 2 9. Hz, H-1 );.8 (dd, 1H, J 2,3b 9., J 2,3a.0 Hz, H-2);.31 (s, 2H, CH 2 H); (m, 1H, 10

11 H-6a ); 3.70 (dd, 1H, J 2,1 9., J 2,3 9.0 Hz, H-2 ); (m, 2H, H-6b, H- ); 3.38 (dd, 1H, J 3,2 9.0, J 3, 9.0 Hz, H-3 ); 3.23 (dd, 1H, J,3 9.0, J, 9.0 Hz, H- ); 2.99 (dd, 1H, 2 J 3a,3b 13., J 3a,2.0 Hz, H-3a); 2.7 (dd, 1H, 2 J 3a,3b 13., J 3b,2 9. Hz, H-3b); 1.76 (s, 3H, CH 3 ). 13 C MR (7 MHz, methanol-d)!: (C-1); 173. (CH 3 C=); 16. (C- ); 138. (C-1 ); 130. (C-2, C-6 ); (C-3, C- ); (C- ); 123. (C- ); 89.7 (C-1 ); 81.3 (C- ); 78.6 (C-3 ); 7.2 (C-2 ); 71.1 (C- ); 62.6 (C-6 ); 6.6 (C-2); 39.0 (C-3); 3.9 (CH 2 H); 22.6 (CH 3 ). Residual copper ~ 0.08 mol%. HRMS (FAB + ) : Calcd. for C 20 H 27 7 a , found Undecyl-1-("-D-glucopyranosyl)-1H-[1,2,3]-triazole (12) : 6'' '' 3'' '' 2'' 1'' 1' 2' 3' ' ' 6' 7' 8' 9' 10' 11' Procedure C : To a solution of #-D-glucopyranosyl azide (10.3 mg, 68 µmol, 1 eq.) in H 2 (6 µl) and tbu (1370 µl), were added tridec-1-yne (163 µl, mg, 68 µmol, 1 eq.), o- phenylenediamine (27 µl, 0. mg per ml of H 2, 11.1 mg, µmol, 1 mol%), sodium ascorbate (27 µl, 9. mg per ml of H 2, 13.6 mg, 68. µmol, 10 mol%) and copper sulfate pentahydrate (27 µl, 31.2 mg per ml of H 2, 8. mg, 3.2 µmol, mol%). The reaction mixture was stirred at room temperature under an argon atmosphere for 2 hours. After this time, TLC showed complete conversion. The reaction mixture was stirred one hour under an air atmosphere, and activated charcoal (~10 mg) was added and the suspension was stirred under an air atmosphere overnight. The reaction mixture was then filtered through a celite plug and washed with H 2 /tbu (1/1). Elution with AC/H 2 gave after concentration to dryness, 22.1 mg (8%) of -undecyl-1-("-d-glucopyranosyl)-1h-[1,2,3]-triazole (12) as a white solid. 1 H MR (20 MHz, methanol-d)!: 7.9 (s, 1H, H-);.6 (d, 1H, J 1, Hz, H-1 ); 3.88 (dd, 1H, J 2,1 9.0, J 2,3 8. Hz, H-2 ); 3.88 (dd, 1H, J 6a,6b 12.0, J 6a, 1. Hz, H- 6a ); 3.71 (dd, 1H, J 6b,6a 12.0, J 6b,.0 Hz, H-6b ); 3.6 (ddd, 1H, J, 9.0, J,6b.0, J,6a 1. Hz, H- ); 3.6 (dd, 1H, J 3, 9.0, J 3,2 8. Hz, H-3 ); 3.8 (dd, 1H, J,3 9.0, J, 9.0 Hz, H- ); 2.71 (t, 2H, J 1, 2 7. Hz, H-1 ); 1.67 (tt, 2H, J 2, 1 = J 2, Hz, H-2 ); (m, 16H, H-3,,,6,7,8,9,10 ); 0.90 (t, 3H, J 11, Hz, H-11 ). 13 C MR (62. MHz, methanol-d)!: 19. (C-); 122. (C-); 89.7 (C-1 ); 81.3 (C- ); 78.7 (C-3 );

12 (C-2 ); 71.0 (C- ); 62. (C-6 ); 33.2 (CH 2 ); 30.9 (2 CH 2 ); 30.8 (CH 2 ); 30.7 (CH 2 ); 30.6 (2 CH 2 ); 30. (CH 2 ); 26. (CH 2 ); 23.9 (CH 2 ); 1.6 (C-11 ). Residual copper ~ 0.06 mol%. MS (ESI + ) : m/z 08.2 [M+a] +. HRMS (ESI + ) : Calcd. for C 19 H 3 3 a , found Kinetic effect of added o-phenylenediamine Reaction of #-glucosyl azide (0.2 M) with propargyl alcohol (0.2 M) in the presence of copper sulfate (.0 mol%, 12. mm) and sodium ascorbate (10.0 mol%, 2.0 mm) was performed with or without added o-phenylemenediamine (1.0 mol%, 37. mm). The conversion was followed by 1 H-MR spectroscopy (00 MHz) in D 2 under Ar, and estimated by integration of the H-2 signal of the starting material (! 3.2 ppm) and anomeric signal of the product (!.7 ppm). The reactions were initiated by copper sulfate addition. References (1) A. J. Fairbanks and P. Sinaÿ, Synlett, 199, 3, 277. (2) B. L. Wilkinson, L. F. Bornaghi, S.-A. Poulsen, and T. A. Houston, Tetrahedron, 2006, 62, 811. (3) B. Vauzeilles, B. Dausse, S. Palmier and J.-M. Beau, Tetrahedron Lett., 2001, 2, 767. S. I. van Kasteren, H. B. Kramer, H. H. Jensen, S. J. Campbell, J. Kirkpatrick,. J. ldham, D. C. Anthony and B. J. Davis, ature, 2007, 6, 110. () L. L. Rossi and A. Basu, Bioorg. Med. Chem. Lett., 200, 1,

13 Me Me

14 Ph H H Ph H H

15 2 2

16 3 3

17

18 AcH AcH

19 6 Me 6 Me

20

21 8 8

22 9 9

23 10 10

24 11 H Ph H 11 H Ph H

25 12 12