Volume Editor-in-Chief Pavol Kovác v Carbohydrate Chemistry Proven Synthetic Methods Volume This Page Intentionally Left Blank Carbohydrate Chemistry: Proven Synthetic Methods Series Editor: Pavol Kováč National Institutes of Health, Bethesda, Maryland, USA Carbohydrate Chemistry: Proven Synthetic Methods, Volume 1, by Pavol Kováč This Page Intentionally Left Blank Carbohydrate Chemistry | Proven Synthetic Methods Series Carbohydrate Chemistry Proven Synthetic Methods Volume Edited by Pavol Kovác v Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2012 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S Government works Version Date: 20111017 International Standard Book Number-13: 978-1-4398-6693-1 (eBook - PDF) This book contains information obtained from 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1993, 46, 157–170 Contents Foreword by Derek Horton xiii Foreword by Paul Kosma xv Foreword by Bert Fraser-Reid .xvii Introduction xix Contributors xxiii Part I Synthetic Methods Chapter Acetolysis of 6-Deoxysugars Controlled by Armed–Disarmed Effect Emiliano Bedini, Luigi Cirillo, Ian Cumpstey, and Michelangelo Parrilli Chapter NaH/Im2SO2-Mediated Preparation of Hex-2- and Hex-3-Enopyranoside Enol Ethers 11 Emanuele Attolino, Giorgio Catelani, Felicia D’Andrea, Lorenzo Guazzelli, and Marie-Christine Scherrmann Chapter Enhancement of the Rate of Purdie Methylation by Me2S Catalysis 27 Shujie Hou, Thomas Ziegler, and Pavol Kovácˇ Chapter Synthesis of Oligosaccharides by Preactivation-Based Chemoselective Glycosylation of Thioglycosyl Donors 43 Zhen Wang, Gilbert Wasonga, Benjamin M Swarts, and Xuefei Huang Chapter The Use of Hypophosphorous Acid in Radical Chain Deoxygenation of Carbohydrates 53 Karsten Krohn, Ivan Shuklov, Ishtiaq Ahmed, and Alice Voss Chapter Diphenylsulfoxide-Trifluoromethanesulfonic Anhydride: A Potent Activator for Thioglycosides 67 Jeroen D.C Codée, Thomas J Boltje, and Gijsbert A van der Marel ix Functionalization of Terminal Positions of Sucrose—Part II 417 (CH3OH, 1.09) 1H NMR (400 MHz) δ:7.21 (m, 30H, Ar-H), 5.80 (d, 1H, J1,2 = 3.6 Hz, H-1), 4.34 (t, 1H, J3′,4′,5′= 8.6 Hz, H-4′), 4.18 (d, 1H, J3′,4′ = 8.4 Hz, H-3′), 4.11 (d, 2H, J5,6 = 7.1 Hz, H-6), 3.89 (m, 2H, H-5, H-5′), 3.53 (t, J2,3,4 = 9.5 Hz 1H, H-3), 3.45 (d, 2H, J5′,6′ = 11.7 Hz, H-6′), 3.41 (s, 2H, H-1′), 3.27 (t, 1H, J3,4,5 = 11.0 Hz, H-4), 3.09 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 9.3 Hz, H-2) 13C NMR δ: 143.7, 143.6 (quat C-Tr), 136.1, 128.8, 128.0, 127.5, 127.2, 123.8 (CAr), 104.8 (C-2′), 90.9 (C-1), 87.4, 87.1 (2 × CPh3), 79.2, 77.3, 74.7, 74.3, 71.6, 71.2, 70.9 (C-2,3,3′,4,4′,5,5′), 66.1, 64.4, 62.8 (C-1′,6,6′) ESI-MS: 849 [M(C50H50O11) +Na+] Anal: Calcd for C50H50O11: C, 72.62; H, 6.09 Found: C, 72.70; H, 6.02 1′,2,3,3′,4,4′-Hexa-O-Acetyl-6,6′-Di-O-Tritylsucrose (1A) Compound (0.1 g, 0.012 mmol) was dissolved in pyridine (10 mL), acetic anhydride (0.148 g, 0.14 mL) was added, and the mixture was stirred at rt overnight After concentration, the residue was chromatographed (2:1 hexane-EtOAc) to afford the hexaacetate 1A (0.13 g, 96%), mp. = 103°C–105°C, [α]D +69.5 1H NMR δ: 7.23 (m, 30H, Ar-H), 5.84 (d, 1H, J1,2 = 3.9 Hz, H-1), 5.36 (t, 1H, J3′,4′,5′ = 5.2 Hz, H-4′), 5.31 (d, 1H, J3′,4′ = 5.4 Hz, H-3′), 5.21 (m, 2H, J3,4 = 9.3 Hz, H-3, H-4), 4.81 (dd, 1H, J1,2 = 3.2 Hz, J2,3 = 9.2 Hz, H-2), 4.14 (m, 1H, H-6A), 3.96 (d, 1H, J6A,6B = 8.9 Hz, H-6B), 3.33 (m, 4H, H-6′A, H-1′), 3.17 (d, 1H, J5,6 = 9.8 Hz, H-5), 2.75 (dd, 1H, J5′,6′ = 8.0 Hz, H-5′), 2.16 (s, 6H, H-OAc), 1.98 (s, 3H, H-OAc), 1.96 (s, 3H, H-OAc), 1.93 (s, 3H, H-OAc), 1.92 (s, 3H, H-OAc) 13C NMR δ: 170.2, 170.0, 169.5, 168.9 (6 × CO), 143.7, 143.3 (quat C-Tr), 128.8, 128.6, 127.8, 127.7, 127.1, 127.0, 126.8 (CAr), 105.4 (C-2′), 90.1 (C-1), 87.1, 86.9 (2 × CPh3), 86.1, 80.1, 76.2, 70.8, 70.0, 69.2, 68.4 (C-2,3,3′,4,4′,5,5′), 63.9, 63.0, 60.6 (C-1′,6,6′), 20.9, 20.8, 20.6, 20.5, 20.4 (6 × OC(O) CH3) ESI-MS: 1101 [M(C62H62O17) +Na+] Anal: Calcd for C62H62O17: C, 69.00; H, 5.79 Found: C, 68.82; H, 5.63 1′,2,3,3′,4,4′-Hexa-O-Benzyl-6,6′-Di-O-Tritylsucrose (2) Sodium hydride (60% dispersion in mineral oil, 1.74 g, 0.044 mmol) was added in portions at 5°C–10°C to a stirred solution of 6,6′-di-O-tritylsucrose (1, 3.0 g, 3.63 mmol) and imidazole (0.007 g, 0.099 mmol) in DMF (30 mL), and the mixture was stirred at rt for 30 min Benzyl bromide (5.58 g, 3.88 mL, 0.033 mol) was added dropwise at a rate to keep the temperature below 40°C The cooling was removed, and when the starting material was consumed (4–5 h, TLC, 5:1 hexaneethyl acetate), the reaction was quenched by dropwise addition of H2O (with stirring, until effervescence ceased) The mixture was poured into cold H2O (500 mL) and extracted with Et2O (4 × 150 mL) The extracts were washed with H2O (2 ×150 mL, the organic phase was dried with Na2SO4 and concentrated, and the residue was chromatographed (hexane, then gradient 12:1 → 17:3 hexane-EtOAc) to afford 1′,2,3,3′,4,4′-hexa-O-benzyl-6,6′-di-O-tritylsucrose (2) as a white, amorphous solid (4.2 g, 84%), [α]D +20.6 1H NMR δ: 7.20 (m, 60H, Ar-H), 6.40 (d, 1H, J1,2 = 3.6 Hz, H-1), 4.87 (t, 1H, J3′,4′,5′ = 8.9 Hz, H-4′), 4.66 (m, 7H, H-3′, H-4, H-5, 2Ar-CH2), 4.35 (dd, 2H, J5,6 = 3.26, J6A,6B = 11.78, H-6), 4.12 (m, 6H, H-5′, H-2, 2Ar-CH2), 3.93 (d, 1H, J = 9.8 Hz, Ar-CH2), 3.79 (t, 1H, J2,3,4 = 9.2 Hz, H-3), 3.67 (dd, 2H, J5′,6′ = 10.6 Hz, J6′A,6′B = 17.5 Hz, H-6′), 3.54 (t, 2H, J1′A,1′B = 8.2 Hz, H-1′), 3.28 (d, 1H, J = 9.9 Hz, Ar-CH2), 3.06 (d, 1H, J = 9.8 Hz, Ar-CH2), 2.78 (d, 1H, J = 9.0 Hz, Ar-CH2) 13C NMR 418 Carbohydrate Chemistry: Proven Synthetic Methods δ: 143.9, 143.7 (quat C-Tr), 139.0, 138.7, 138.5, 137.6 (Cq benzyl groups), 128.9, 128.8, 128.3, 128.2, 128.1, 127.9, 127.7, 127.4, 127.2, 127.0, 126.7 (CAr), 104.2 (C-2′), 88.1 (C-1), 87.1, 86.7 (2 × CPh3), 85.9, 84.6, 82.0, 80.5, 79.3, 78.3, 77.6, 75.9, 74.7, 73.1, 72.4, 71.9, 70.8 (C-2,3,3′,4,4′,5,5′, 6 × OCH2Ph), 67.1, 62.0, 61.7 (C-1′,6,6′) Anal: Calcd for C92H86O11: C, 80.79; H, 6.34 Found: C, 80.84; H, 6.39 1′,2,3,3′,4,4′-Hexa-O-Benzyl-6,6′-Dichloro-6,6′-Dideoxysucrose (3A) To a stirred solution of 6,6′-dichloro-6,6′-dideoxysucrose (3)3 (0.68 g, 1.794 mmol) in DMF (40 mL), was added powdered KOH (0.90 g, 16.2 mmol), tetrabutylammonium bromide (0.06 g) and benzyl bromide (2.76 g, 1.92 mL, 16.2 mmol) and the mixture was stirred at rt overnight The mixture was partitioned between water (80 mL) and ether (80 mL); the organic phase was separated, washed with water, dried, and concentrated; and the residue was chromatographed (8:1 → 7:1 hexane– EtOAc) to afford 1′,2,3,3′,4,4′-hexa-O-benzyl-6,6′-dichloro-6,6′-dideoxysucrose as a colorless oil (1.27 g, 77%), [α]D +32 1H NMR δ: 7.29 (m, 30H, Ar-H), 5.69 (d, 1H, J1,2 = 3.2 Hz, H-1), 4.90 (dd, 2H, J5,6 = 3.1 Hz, J6A,6B = 10.8 Hz, H-6), 4.74 (d, 1H, J = 10.9 Hz, Ar-CH2), 4.53 (m, 10H, H-1′,2′,3′,4,4′, 2 × Ar-CH2), 4.19 (d, 1H, J = 9.2 Hz, Ar-CH2), 4.10 (d, 2H, J5′,6′ = 4.0 Hz, H-6′), 3.96 (t, 1H, J2,3,4 = 9.2 Hz, H-3), 3.71 (m, 3H, H-5, Ar-CH2), 3.57 (m, 5H, H-5′, 2 × Ar-CH2) 13C NMR δ: 138.6, 138.2, 138.1, 137.9, 137.7 (Cq benzyl groups), 128.4, 127.9, 127.8, 127.6 (CAr), 105.2 (C-2′), 90.3 (C-1), 84.0, 83.3, 81.4, 80.5, 79.7, 78.1, and 70.1 (C-2,3,3′,4,4′,5,5′), 75.5, 75.1, 73.5, 73.1, 72.5, 72.4, 70.7 (C-1′ + OCH2Ph), 45.0, 44.9 (C-6,6′) ESI-MS: 941 [M(C54H56O9Cl2) +Na+] Anal: Calcd for C54H56O9Cl2: C, 70.50; H, 6.14; Cl, 7.71 Found: C, 70.42; H, 6.31; Cl, 7.57 6,6′-Di-O-Acetyl-1′,2,3,3′,4,4′-Hexa-O-Benzylsucrose (4) Tetrabutylammonium acetate (2.81 g, 9.33 mmol) was added to a solution of the foregoing 6,6′-dichloro-6,6′-dideoxy-1′,2,3,3′,4,4′-hexa-O-benzylsucrose (3A) (0.39 g, 0.424 mmol) in toluene (50 mL), the mixture was boiled under reflux for 2 h and then kept at rt overnight After concentration, the residue was dissolved in CH2Cl2 (50 mL), the solution was washed with water (3 × 50 mL), and the aqueous phase was extracted with CH2Cl2 (2×) The organic phases were combined, dried, and concentrated; and chromatography (5:1 → 3:1 hexane/EtOAc) gave as a colorless oil (0.29 g, 72%) [α]D +50.6 1H NMR δ: 7.22 (m, 30H, Ar-H), 5.66 (d, 1H, J1,2 = 3.3 Hz, H-1), 4.95 (d, 1H, J = 10.3 Hz, Ar-CH2), 4.84 (d, 1H, J = 10.2 Hz, Ar-CH2), 4.77 (d, 1H, J = 10.3 Hz, Ar-CH2), 4.57 (m, 8H, H-2′,3,4,4′,6A,6B, Ar-CH2), 4.43 (s, 2H, Ar-CH2), 4.28 (s, 1H, Ar-CH2), 4.10 (m, 5H, H-1′,6″, Ar-CH2), 3.98 (t, 1H, H-3), 3.69 (d, 1H, J = 10.3 Hz, Ar-CH2), 3.50 (m, 3H, H-5, H-5′, Ar-CH2), 1.97 (s, 6H, 2 × OAc) 13C NMR δ: 170.7 (CO), 138.7, 138.1, 137.9, 137.8, 137.7 (Cq benzyl groups), 128.4, 128.0, 127.9, 127.8, 127.6 (CAr), 104.7 (C-2′), 89.8 (C-1), 83.7, 81.8, 81.7, 79.7, 78.2, 77.2, and 69.1 (C-2,3,3′,4,4′,5,5′), 75.6, 74.9, 73.4, 73.0, 72.7, 72.4, 71.1 (C-1′, 6 × OCH2Ph), 64.8, 63.0 (C-6,6′), 20.8, 20.7 (2 × OC(O)CH3) ESI-MS: 989 [M(C58H62O13) +Na+] Anal: Calcd for C58H62O13: C, 72.03; H, 6.46 Found: C, 72.24; H, 6.63 Functionalization of Terminal Positions of Sucrose—Part II 419 1′,2,3,3′,4,4′-Hexa-O-Benzylsucrose (5) Route a 6,6′-Di-O-trityl-1′,2,3,3′,4,4′-hexa-O-benzylsucrose (2, 3.0 g, 2.19 mmol) was dissolved in dichloromethane–methanol (1:3, 60 mL) to which iodine (0.557 g, 2.19 mmol) was added, and the mixture was boiled under reflux for 4–5 h (TLC, 1:1 hexane–EtOAc) Aq 10% sodium thiosulfate was added until the mixture became colorless (∼200 mL), and the product was extracted with diethyl ether (4 × 100 mL) The combined organic extracts were washed with water and brine, dried, and concentrated Chromatography (4:1 → 2:1 → 3:2 hexane–EtOAc) of the residue afforded 1′,2,3,3′,4,4′-hexa-O-benzylsucrose (5) as a colorless oil (1.12 g, 58%), [α]D +40.8 1H NMR δ: 7.26 (m, 30H, Ar-H), 5.49 (d, 1H, J = 2.9 Hz, H-1), 4.86 (d, 2H, 1,2 J6A,6B = 10.6 Hz, H-6), 4.66 (m, 7H, H-3,3′,4,4′, Ar-CH2), 4.46 (3d, 3H, Ar-CH2), 4.32 (m, 2H, Ar-CH2), 4.14 (m, 1H, H-5), 3.98 (m, 2H, H-6′), 3.82 (m, 2H, H-1′), 3.60 (m, 3H, H-5′, Ar-CH2), 3.50 (dd, 1H, J1,2 = 3.2 Hz, J2,3 = 9.6 Hz, H-2), 3.43 (dd, 2H, J = 10.2 Hz, Ar-CH2) 13C NMR δ: 138.6, 138.3, 138.1, 138.0, 137.7 (Cq benzyl groups), 128.4, 127.9, 127.8, 127.7, 127.6 (CAr), 103.9 (C-2′), 90.7 (C-1), 83.5, 81.7, 81.0, 79.9, 79.5, 77.6, and 71.3 (C-2,3,3′,4,4′,5,5′), 75.6, 75.0, 73.4, 73.1, 73.0, 72.5 (C-1′, 6 × OCH2Ph), 61.9, 61.0 (C-6,6′) m/z: 905 [M(C54H58O11) +Na+] Anal: Calcd for C54H58O11: C, 73.45; H, 6.62 Found: C, 73.23; H, 6.84 Conventional acetylation of gave virtually theoretical yield of material, which was identical in all respect with the above described substance Route b Compound (0.22 g, 0.227 mmol, obtained from as described above) was dissolved in methanol (25 mL) containing catalytic amounts of sodium methoxide, and the mixture was stirred for 3 h After concentration, the residue was chromatographed (1:1 hexane–EtOAc) to give colorless oil (0.16 g, 82%), which was identical in all respect to the above-described substance 6,6′- Di-O-Allyl-1′,2,3,3′,4,4′-Hexa-O-Benzylsucrose (6) A solution of 1′,2,3,3′,4,4′-hexa-O-benzylsucrose (5, 0.58 g, 0.66 mmol) in DMF (6 mL) was added dropwise to a slurry of NaH (60% dispersion in mineral oil, 0.095 g, 1.98 mmol) in DMF (10 mL) containing a catalytic amount of imidazole (∼10 mg) The mixture was cooled to 0°C in an ice bath and stirred with exclusion of moisture for 30 min, allyl bromide (0.383 g, 0.274 mL) was then added dropwise, and the mixture was stirred for 5 h at rt Excess of hydride was destroyed by careful addition of water, the mixture was partitioned between water and ether (50 mL each); the organic phase was washed with water, dried, and concentrated; and the product was isolated by column chromatography (4:1 hexane–EtOAc) as a colorless oil (0.50 g, 79%), [α]D +29.9 1H NMR δ: 7.32 (m, 30H, Ar-H), 5.93 (m, 3H, H-1, CH-allyl groups), 5.30 (dd, 4H, JHA,HB = 17.3 Hz, CH2-allyl groups), 5.18 (t, 4H, J3′,4′ = 10.8 Hz, H-3′, H-4′, Ar-CH2), 4.94 (t, 3H, J3,4 = 11.1 Hz, H-4, Ar-CH2), 4.82 (dd, 3H, J6A,6B = 10.9 Hz, H-6, Ar-CH2), 4.72 (d, 1H, J = 10.8 Hz, Ar-CH2), 4.61 (d, 1H, J = 10.8 Hz, Ar-CH2), 4.44 (d, 4H, J6′A,6′B = 7.7 Hz, H-6′, Ar-CH2), 4.14 (dd, 420 Carbohydrate Chemistry: Proven Synthetic Methods 1H, J1,2 = 5.7 Hz, J2,3 = 12.7 Hz, H-2), 4.03 (dd, 4H, JCH2,CH = 5.4 Hz, JCH2A,B = 11.2 Hz, OCH2CH = CH2), 3.70 (t, 1H, J2,3,4 = 10.4 Hz, H-3), 3.61 (m, 5H, H-1′, H-5 Ar-CH2), 3.46 (m, 2H, H-5′, Ar-CH2) 13C NMR δ: 138.6, 138.4, 138.2 (Cq benzyl groups), 134.7, 134.0 (CH allyl groups), 128.3, 128.2, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4 (CAr), 117.2, 117.0 (CH2, allyl groups), 108.2 (C-2′), 102.7 (C-1), 84.7, 82.3, 77.9, 77.3, 77.0, 76.7 (C-2,3,3′,4,4′,5,5′), 75.7, 75.0, 74.8, 72.5, 70.3, 68.9 (C-1′,6,6′, OCH2Ph, OCH2CH = CH2) ESI-MS: 985 [M(C60H66O11) +Na+] 1′,2,3,3′,4,4′-Hexa-O-Benzyl-6,6′-Bis-(O-TertButoxycarbonylmethylsucrose (7) 1′,2,3,3′,4,4′-Hexa-O-benzylsucrose (5, 0.33 g, 0.377 mmol) was dissolved in toluene (15 mL), to which 50% aq sodium hydroxide (15 mL) and tetrabutylammonium bromide (0.01 g, 0.03 mmol) were added tert-Butyl bromoacetate (0.44 g, 0.33 mL, 2.26 mmol) was added dropwise and the mixture was stirred at rt for 4 h Water (30 mL) and diethyl ether (30 mL) were added to the mixture; the organic layer was separated, washed with water, dried, and concentrated; and the product was chromatographed (7:1 hexane– EtOAc) to afford 6,6′-bis-1′,2,3,3′,4,4′-hexa-O-benzyl-(O-tert-butoxycarbonylmethyl) sucrose (7, 0.35 g, 83%) as a colorless oil, [α]D +30.7 1H NMR δ: 7.33 (m, 30H, Ar-H), 5.67 (d, J1,2 = 3.64 Hz, 1H, H-1), 4.91 (d, 1H, J = 10.9 Hz, Ar-CH2), 4.86 (d, 1H, J = 10.9 Hz, Ar-CH2), 4.77 (d, 2H, J = 10.9 Hz, Ar-CH2), 4.72 (d, 2H, J = 10.9 Hz, Ar-CH2), 4.65 (m, 2H, J3′,4′ = 11.5 Hz, H-3′, Ar-CH2), 4.58 (d, 3H, JHA,HB = 7.2 Hz, CH2CO, Ar-CH2), 4.5 (d, 2H, JHA,HB = 7.1 Hz, CH2CO, Ar-CH2), 4.41 (t, J = 10.18 Hz, 2H, Ar-CH2), 4.13 (s, 2H, H-6), 4.04 (d, J = 14.7 Hz, 2H, H-6), 3.96 (d, J = 14.8 Hz, 2H, H-6′), 3.87 (m, 2H, H-4, H-5′), 3.80 (m, 2H H-4′, H-5), 3.72 (t, 1H, J3,4 = 10.9 Hz, H-3), 3.65 (m, 2H, H-2, Ar-CH2), 3.52 (m, 3H, Ar-CH2) 1.44 (s, 18H, tertbutyl) 13C NMR δ: 169.4, 169.2 (2 × CO), 139.0, 138.8, 138.3, 138.0 (6 × Cq benzyl), 128.3, 127.9, 127.7, 127.6, 127.5 (CAr), 104.6 (C-2′), 90.1 (C-1), 83.8, 82.4, 81.9, 81.4, 81.3 (C-2,3,3′,4,4′,5,5′), 79.7 (C(CH3)3), 75.4, 74.8, 73.4, 72.9, 72.7, 72.5, 72.3, 71.1, 70.5, 69.8, 69.0 (6 × OCH2Ph, 2 × CH2COO, C-1′,6,6′), 28.1 (C(CH3)3) ESI-MS: 1133.4 [M(C66H78O15) +Na+] Anal: Calcd for C66H78O15 × H2O: C, 70.21; H, 7.09 Found: C, 70.18; H, 7.13 1′,2,3,3′,4,4′-Hexa-O-Benzyl-6,6′-Bis-(O-2-Hydroxyethyl) Sucrose (8) Route a 6,6′-Di-O-allyl-1′,2,3,3′,4,4′-hexa-O-benzylsucrose (6) (0.39 g, 0.409 mmol) was dissolved in THF (6 mL) and a solution of NaIO4 (0.526 g, 2.45 mmol) in H2O (6 mL) was added, followed by OsO4 (0.04 mL of a 2% solution in toluene) The resulting mixture was stirred at rt for 1.5 h and then partitioned between water (100 mL) and ether (80 mL) The organic phase was separated, dried, and concentrated The residue was dissolved in 1:1 CH2Cl2–MeOH (10 mL) and cooled to −78°C NaBH4 (0.21 g, 5.54 mmol) was added in several portions, the mixture was stirred for 1 h at −78°C and then for 2 h at rt Water (20 mL) was added, and the product was extracted with CH2Cl2 (25 mL) The organic layer was dried and concentrated, and the crude product was chromatographed (hexane/EtOAc, 1:1 then 2:3) to afford the title compound as a pale yellow oil (0.185 g, 47%), [α]D +44.3 IR (film) ν: 2916, 2866, 1454, 1086, 1072, 736, 697 cm−1; 1H NMR δ: 7.30 (m, 30H, Ar-H), 6.13 (d, J1,2 = 3.2 Hz, 421 Functionalization of Terminal Positions of Sucrose—Part II 1H, H-1), 4.96 (d, 1H, J = 10.9 Hz, Ar-CH2), 4.79 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 11.2 Hz, H-2), 4.68 (m, 2H, Ar-CH2), 4.63 (m, 6H, H-6,H-6′, H-3, H-4), 4.48 (m, 5H, Ar-CH2), 4.13 (m, 2H, H-5, Ar-CH2), 3.90 (m, 3H, Ar-CH2, H-5′), 3.64 (m, 4H, CH2 from 2-hydroxyethyl), 3.57 (s, 1H, Ar-CH2), 3.53 (m, 2H, CH2 from 2-hydroxyethyl), 3.46 (m, 2H, CH2 from 2-hydroxyethyl), 3.39 (t, 2H, J = 11.0 Hz), 3.30 (m, 4H, H-1′,H-3′, H-4′) 13C NMR δ: 139.2, 138.8, 138.2, 138.1, 137.9 (6 × C benzyl), 128.3, 128.1, 127.9, q 127.7 (CAr), 104.0 (C-2′), 87.7 (C-1), 83.3, 82.0, 79.0, 78.9, and 71.9 (C-2,3,3′,4,4′,5,5′), 75.2, 74.6, 73.4, 73.0, 72.9, 72.5, 72.3, 68.4, 61.7 (C-1′,6,6′, 6 × OCH2Ph, 4 × CH2 from 2-hydroxyethyl) ESI-MS: 993.5 [M(C58H66O13) +Na+] Anal: Calcd for C58H66O13 × 0.5 H2O: C, 71.07; H, 6.89 Found: C, 71.01; H, 7.12 4.369 4.337 4.316 4.188 4.106 4.140 4.122 4.104 4.087 3.892 3.649 3.626 3.502 3.463 3.434 3.305 3.296 3.281 3.226 3.111 3.101 3.087 3.078 5.007 5.786 7.674 7.668 7.637 7.466 7.448 7.426 7.286 7.282 7.244 7.223 7.206 7.188 Route b Compound (0.150 g, 0.135 mmol) was dissolved in dry THF (12 mL), to which a suspension of LiAlH4 (0.107 g, 2.804 mmol) in THF (4 mL) was added, and the mixture was stirred at rt for 3 h EtOAc (10 mL) was added, followed by aqueous saturated sodium sulfate solution (2 mL) to destroy excess of the hydride Inorganic salts were filtered off and washed with EtOAc The solvents were removed in vacuum and chromatography of the residue (1:2 hexane–EtOAc) gave (0.09 g, 69%), which was identical in all respects to the independently prepared material described above 500,000,000 400,000,000 O HO HO OH O HO O 300,000,000 OH O O OH 200,000,000 100,000,000 7.0 6.0 5.0 ppm (t1) 4.0 1.7023 5.5102 5.0810 2.8583 2.2084 1.0048 1.0000 39.7806 20.0433 2.6934 3.0 7.0 6.0 OAc O O 5.0 ppm (t1) 4.0 3.0 1.3124 2.9627 O 0.2217 O 2.100 1.983 1.963 1.933 1.922 O 3.367 3.351 3.344 3.317 3.274 3.249 3.178 3.154 2.782 2.742 150 O 4.149 4.136 3.976 3.954 HO 1.0110 0.2511 AcO AcO O 0.2449 0.2419 O 0.2214 5.845 5.833 5.377 5.364 5.351 5.317 5.309 5.230 5.207 5.184 4.822 4.814 4.799 4.791 HO HO 1.0000 0.2143 7.5047 4.9347 7.483 7.445 7.404 7.388 7.359 7.343 7.272 7.253 7.235 7.213 7.194 7.175 87.410 87.066 79.189 79.076 79.357 77.939 76.722 76.118 74.684 74.316 71.625 71.242 70.938 68.098 64.357 62.776 60.407 90.942 104.700 128.808 127.699 127.506 127.154 123.702 130.000 149.605 146.971 143.026 422 Carbohydrate Chemistry: Proven Synthetic Methods OH 1A OAc O 2.0 400,000,000 300,000,000 OH O 200,000,000 OH 100,000,000 100 ppm (t1) 400,000,000 300,000,000 OAc 200,000,000 OAc 100,000,000 7.0 6.0 O 5.0 ppm (t1) 4.0 3.0 2.796 2.773 O 1.0308 O O 1.0172 OBn O 3.074 O 1.0513 O ppm (t1) OAc 1.2037 1.1277 2.1258 2.2511 AcO AcO 6.4503 O 4.358 4.349 4.328 4.225 4.202 4.154 4.053 3.942 3.918 3.787 3.663 3.541 3.267 100 2.3347 4.874 4.747 6.399 6.392 7.505 7.486 7.468 7.394 7.237 7.176 7.165 6.912 6.894 6.763 6.748 150 7.4040 BnO BnO 1.1001 1.0000 2.8519 2.1722 63.1826 22.7740 0.0000 20.888 20.776 20.627 20.570 20.401 30.912 90.134 87.097 88.940 88.109 80.065 76.206 70.757 69.985 69.171 68.377 63.665 62.997 60.605 106.414 128.770 128.622 127.796 127.709 127.141 127.017 126.808 143.683 143.260 170.175 169.894 169.527 168.859 Functionalization of Terminal Positions of Sucrose—Part II 423 OAc 50 OBn OBn OBn 250,000,000 1A 200,000,000 OAc 150,000,000 OAc O 100,000,000 50,000,000 0 300,000,000 250,000,000 200,000,000 O 150,000,000 100,000,000 50,000,000 7.50 7.00 6.50 Cl O 6.00 100 ppm (t1) O O 90 5.50 5.00 ppm (t1) 80 4.50 4.00 5.1349 BnO 110 3.3363 120 O 1.0496 BnO BnO BnO O 1.0377 2.0817 130 O 11.8614 O 4.922 4.914 4.095 4.007 4.750 4.882 4.669 4.647 4.620 4.585 4.557 4.523 4.500 4.471 4.454 4.406 4.302 4.196 4.175 4.004 3.960 3.707 3.549 3.522 140 5.696 5.688 7.291 7.259 BnO BnO 1.9888 1.0000 33.3712 88.124 87.130 86.710 86.878 84.606 82.014 80.524 78.078 78.322 75.881 74.699 73.107 72.422 71.908 70.808 67.001 61.991 61.735 104.172 143.876 143.746 143.606 138.984 138.700 138.471 137.500 128.919 128.779 128.330 128.237 128.075 127.830 127.675 127.378 127.162 127.023 126.711 424 Carbohydrate Chemistry: Proven Synthetic Methods 150,000,000 OBn OBn 100,000,000 OBn O 50,000,000 70 60 OBn 3A 3.50 100,000,000 OBn OBn Cl 50,000,000 7.0 6.0 BnO O O ppm (t1) OBn O OAc 5.0 ppm (t1) 4.0 3.0 2.0 1.602 100 1.972 O 6.1501 OAc O 3.1319 O 1.1039 BnO BnO BnO 2.2790 5.1591 1.1561 Cl 10.5853 150 4.960 4.935 4.858 4.846 4.832 4.784 4.758 4.632 4.604 4.523 4.426 4.281 4.103 3.977 3.726 3.713 3.899 3.604 5.660 5.654 7.298 7.283 7.261 BnO BnO 1.0163 2.1399 1.0000 31.4197 44.997 44.901 90.302 83.972 83.338 81.412 80.535 79.880 78.077 75.523 75.112 73.474 73.073 72.534 72.380 70.664 70.147 105.171 138.592 138.227 138.068 137.928 137.870 128.413 127.947 127.836 127.812 Functionalization of Terminal Positions of Sucrose—Part II 425 400,000,000 OBn 300,000,000 OBn OBn Cl 3A 200,000,000 100,000,000 50 500,000,000 OBn 400,000,000 300,000,000 OBn 200,000,000 100,000,000 7.50 7.00 6.50 O 6.00 5.50 5.00 ppm (t1) 4.50 4.00 3.558 3.458 3.432 O 4.1313 O 3.1944 BnO ppm (t1) O 2.0956 O O 2.1035 OAc 1.0265 OH BnO 2.0819 BnO BnO 3.2661 BnO BnO 4.878 4.851 4.770 4.683 4.484 4.478 4.455 4.400 4.327 4.148 4.137 4.128 3.966 3.816 100 7.5752 5.493 5.488 150 2.1476 1.0000 31.6084 7.280 7.263 7.245 0.00000 20.834 20.722 89.774 83.688 81.832 81.736 79.668 78.227 75.803 74.871 73.441 72.887 72.674 72.360 71.082 69.089 64.807 63.035 104.714 138.602 138.106 137.933 137.840 137.709 128.400 120.000 127.863 127.792 127.629 170.663 426 Carbohydrate Chemistry: Proven Synthetic Methods OBn OBn 50 OBn OBn 3.50 400,000,000 300,000,000 OBn OAc 200,000,000 100,000,000 0 200,000,000 OBn 150,000,000 OH 100,000,000 50,000,000 7.50 7.00 6.50 O O 6.00 100 90 ppm (t1) 5.50 5.00 ppm (t1) 80 70 4.50 4.00 0.9705 BnO 110 2.0216 O O 1.7633 BnO BnO 120 O 0.9120 O O 4.972 4.844 4.806 4.732 4.627 4.600 4.451 4.431 4.160 4.146 4.128 4.114 4.026 4.012 3.897 3.860 3.476 3.451 3.438 OH 0.9963 1.0868 0.4895 0.5374 130 BnO 5.367 5.268 5.183 BnO BnO 2.1102 6.948 5.936 5.922 5.910 5.895 7.334 7.207 140 1.0000 7.6131 83.633 81.733 80.972 79.858 79.501 77.044 75.551 74.982 73.392 73.077 72.961 72.477 71.285 61.943 60.984 90.660 103.894 128.386 127.924 127.708 127.761 127.590 138.608 138.291 138.110 138.040 138.679 Functionalization of Terminal Positions of Sucrose—Part II 427 200,000,000 OBn OBn 150,000,000 OBn OH 100,000,000 50,000,000 60 OBn OBn O 3.50 400,000,000 300,000,000 OBn 200,000,000 100,000,000 8.0 7.0 BnO BnO 120 O O BnO 6.0 O O 5.0 O O 110 100 ppm (t1) O 4.0 ppm (t1) 90 3.0 2.0 1.7937 O O 18.7614 130 BnO 0.5720 O 2.2290 2.1459 2.4011 1.7459 1.7149 1.2662 1.7766 3.1272 BnO BnO 1.0590 1.1113 1.0631 1.1691 2.1318 3.1897 2.2795 2.1289 5.668 4.926 4.898 4.872 4.845 4.783 4.756 4.730 4.703 4.669 4.640 4.692 4.574 4.544 4.504 4.435 4.418 4.384 4.133 4.061 4.024 3.981 3.944 3.871 3.861 3.783 3.736 3.706 3.656 3.617 3.534 3.504 3.470 2.169 1.626 1.439 7.301 7.266 7.236 140 0.0200 32.7510 77.561 77.313 76.888 76.679 75.658 74.805 74.638 72.451 70.263 68.908 84.558 82.258 102.679 117.200 117.020 138.606 138.427 136.207 134.700 134.029 128.334 128.182 127.923 127.842 127.751 127.636 127.562 127.400 428 Carbohydrate Chemistry: Proven Synthetic Methods O 80 O OBn OBn OBn O 1.0 250,000,000 OBn 200,000,000 OBn OBn 150,000,000 100,000,000 50,000,000 70 350,000,000 300,000,000 250,000,000 200,000,000 O 150,000,000 100,000,000 50,000,000 –50,000,000 7.0 100 ppm (t1) O O BnO O O 6.0 5.0 ppm (t1) 4.0 7.4477 2.3342 2.2154 2.2191 1.0506 3.8000 150 2.2315 BnO BnO O 3.3950 O 1.0331 O 2.6465 BnO 8.4834 O 4.6559 O 4.977 4.948 4.800 4.800 4.781 4.772 4.741 4.682 4.674 4.641 4.624 4.533 4.512 4.437 4.433 4.477 4.473 4.440 4.130 4.100 4.000 3.990 3.900 3.800 3.878 3.853 3.850 3.614 3.575 3.473 3.403 3.378 3.302 3.274 O 6.133 6.131 BnO BnO 34.9968 1.0000 7.327 7.310 7.284 7.264 7.251 28.123 90.077 83.765 82.429 81.921 81.356 81.274 79.884 76.436 74.777 73.897 72.910 72.706 72.516 72.323 71.146 70.547 69.768 69.042 104.633 138.806 138.814 138.277 137.983 128.264 127.870 127.714 127.574 127.483 168.419 168.236 Functionalization of Terminal Positions of Sucrose—Part II OBn OBn O 3.0 429 O OBn 250,000,000 200,000,000 OBn O 150,000,000 OBn O 100,000,000 50,000,000 50 400,000,000 OH 300,000,000 OBn 200,000,000 OH 100,000,000 430 83.640 82.187 78.204 78.071 75.417 74.837 73.841 73.233 73.033 72.706 72.403 72.130 68.604 61.887 87.952 104.000 128.404 128.321 128.023 127.807 138.354 138.975 138.408 138.318 138.136 Carbohydrate Chemistry: Proven Synthetic Methods 200,000,000 OH O BnO BnO BnO 150,000,000 OBn O 250,000,000 O OBn O O 100,000,000 OBn OH 50,000,000 140 130 120 110 100 ppm (t1) 90 80 70 60 REFERENCES Mach, M.; Jarosz, S.; Listkowski, A., J Carbohydr Chem., 2001, 20(6), 485–493; Jarosz, S.; Listkowski, A., J Carbohydr Chem., 2003, 22, 753–763 Szarek, W A.; Zamojski, A.; Tiwari, K N.; Ison, E.R., Tetrahedron Lett., 1986, 27, 3827; Ramasamy, K S.; Bandaru, R.; Averett, D., Synth Comm., 1999, 29, 2881–2894 Whistler, R L.; Anisuzzaman, A K M., Methods Carbohydr Chem., 1980, 8, 227–231 Jarosz, S.; Listkowski, A.; Lewandowski, B.; Ciunik, Z.; Brzuszkiewicz, A., Tetrahedron, 2005, 61, 8485–8493 GENERAL CHEMISTRY Carbohydrate Chemistry Proven Synthetic Methods Volume Long gone are the days when synthetic publications included parallel preparative experiments to document reproducibility of the experimental protocols and when journals required such documentation The new Proven Synthetic Methods Series addresses concerns to chemists regarding irreproducibility of synthetic protocols, lack of characterization data for new compounds, and inflated yields reported in many chemical communications—trends that have recently become a serious problem Volume One of Carbohydrate Chemistry: Proven Synthetic Methods includes more detailed versions of protocols previously published for the synthesis of oligosaccharides, C-glycosyl compounds, sugar nucleotides, click chemistry, thioglycosides, and thioimidates, among others The compilation of protocols covers both common and less frequently used synthetic methods as well as examples of syntheses of selected carbohydrate intermediates with general utility The major focus of this book is devoted to the proper practice of state-of-the-art preparative procedures, including: • References to the starting materials used, reaction setup, work-up and isolation of products, followed by identification and proof of purity of the final material • General information regarding convenience of operation and comments on safety issues • Versatile and practically useful methods that have not received deserved, longlasting recognition or that are difficult to access from their primary sources • Copies of 1D NMR spectra of compounds prepared, showing purity of materials readers can expect Exploring carbohydrate chemistry from the academic points of view, the Carbohydrate Chemistry: Proven Synthetic Methods Series provides a compendium of preparatively useful procedures checked by chemists from independent research groups Carbohydrate Chemistry | Proven Synthetic Methods Series K12999 an informa business w w w c r c p r e s s c o m 6000 Broken Sound Parkway, NW Suite 300, Boca Raton, FL 33487 711 Third Avenue New York, NY 10017 Park Square, Milton Park Abingdon, Oxon OX14 4RN, UK www.crcpress.com ... Carbohydrate Chemistry: Proven Synthetic Methods, Volume 1, by Pavol Kováč This Page Intentionally Left Blank Carbohydrate Chemistry | Proven Synthetic Methods Series Carbohydrate Chemistry Proven. . .Carbohydrate Chemistry Proven Synthetic Methods Volume This Page Intentionally Left Blank Carbohydrate Chemistry: Proven Synthetic Methods Series Editor: Pavol Kováč... Kováč for his initiative in launching a new series Carbohydrate Chemistry: Proven Synthetic Methods This promises to revive the concept of the Methods series and make it accessible to today’s