ࡱ> 7 BbjbjUU %7|7|L9l8l>; ^t.JLLLLLL$ #pp JJzJJR &JJ 0; J##JSynthesis of C-Aryl and C-Alkyl Glycosides Using Glycosyl Phosphates Emma R. Palmacci, Peter H. Seeberger* Department of Chemistry, Massachusetts Institute of Technology Cambridge, MA 02139 Supplementary Material Supporting Information Available: Detailed experimental procedures and compound characterization data, including 1H, 13C, 31P NMR, spectral data for all described compounds. This material is available free of charge via the internet at  HYPERLINK "http://pubs.acs.org" http://pubs.acs.org. Experimental Section General Methods. All chemicals used were reagent grade and used as supplied except where noted. Dichloromethane (CH2Cl2) and toluene were purified by a JT Baker Cycle-Tainer Solvent Delivery System. Analytical thin-layer chromatography was performed on E. Merck silica gel 60 F254 plates (0.25mm). Compounds were visualized by dipping the plates in a cerium sulfate-ammonium molybdate solution followed by heating. Liquid chromatography was performed using forced flow of the indicated solvent on Sigma H-type silica (10-40 mm). 1H NMR spectra were obtained on a Varian VXR-300 (300 MHz), Varian VXR-500 (500 MHz) or a Bruker 400 (400 MHz) and are reported in parts per million (d) relative to CHCl3 (7.27 ppm). Coupling constants (J) are reported in Hertz. 13C NMR spectra were obtained on a VXR-300 (75 MHz), a Bruker-400 (100 MHz) or a VXR-500 (125 MHz) and are reported in d relative to CDCl3 (77.23 ppm) as an internal reference. 31P spectra were obtained on a VXR-300 (120 MHz) and are reported in d relative to H3PO4 (0.0 ppm) as an external reference. 2-(2 ,3 ,4 ,6 -tetra-O-benzyl-a-D-mannopyranosyl)-3,4,5-trimethoxyphen-1-ol 3. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-mannosyl phosphate (35.0 mg, 0.045 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (2.0 mL) and the solution was cooled to 0 C. 3,4,5 Trimethoxyphenol (25.0 mg, 0.136 mmol) was added followed by the addition of TMSOTf (10.0 L, 0.055 mmol). The reaction mixture was allowed to warm to ambient temperature over 1 h. Triethyl amine (Et3N) (15 L) was added and the solvent was removed in vacuo. Chromatography (5:1 Hexanes:EtOAc) afforded the product as a yellow oil (27.0 mg, 85%). 1H NMR (500 MHz)  8.40 (s, 1H), 7.38 - 7.26 (m, 13H), 7.21 - 7.10 (m, 6H), 6.27 (s, 1H), 4.92 (d, J = 11.0 Hz, 1H), 4.82 (d, J = 0.9 Hz, 1H), 4.70 (app s, 2H), 4.64 (d, J = 12.2 Hz, 1H), 4.62 (d, J = 12.0 Hz, 1H), 4.57 (d, J = 11.0 Hz, 1H), 4.54 4.50 (m, 2H), 4.17 (app t, J = 9.8 Hz, 1H), 3.90 (app d, J = 1.9 Hz, 1H), 3.82 (s, 3H), 3.79 3.71 (m, 6H), 3.70 (s, 3H), 3.57 3.54 (m, 1H). 13C NMR (125 MHz)  153.9, 153.7, 150.2, 138.6, 138.5, 138.4, 138.2, 134.6, 128.8, 128.6, 128.6, 128.5, 128.5, 128.2, 128.2, 127.9, 127.9, 127.8, 127.8, 127.7, 127.6, 107.6, 97.0, 84.2, 79.7, 77.0, 76.8, 75.5, 74.4, 73.6, 72.4, 68.8, 61.1, 60.9, 56.0. IR (thin film): 3364, 2933, 1621, 1495, 1362, 1100 cm-1. [a]24D: +12.7 (c 1.82, CH2Cl2). FAB MS m/z calcd (M+Na) 729.3010 obsd 729.3034. 1-(2 ,3 ,4 ,6 -tetra-O-benzyl-b-D-mannopyranosyl)-naphth-2-ol 4. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-mannosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. 2-Naphthol (7.0 mg, 0.049 mmol) was added followed by the addition of TMSOTf (7.0 L, 0.038 mmol). The reaction mixture was allowed to warm to ambient temperature over 1 h. Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (8:1 Hexanes:EtOAc) afforded the product as a yellow oil (17.0 mg, 79%). 1H NMR (500 MHz)  9.14 (s, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.40 7.20 (m, 15H), 7.14 (d, J = 8.9 Hz, 1H), 7.10 7.04 (m, 2H), 6.96 (d, J = 6.4, 2H), 5.40 (s, 1H), 4.95 (d, J = 10.7 Hz, 1H), 4.72 4.67 (m, 3H), 4.59 (d, J = 10.7 Hz, 1H), 4.56 (d, J = 11.2, 1H), 4.40 (d, J = 11.6, 1H), 4.30- 4.20 (m, 2H), 4.34 4.32 (m, 1H), 3.86 (dd, J = 2.8, 8.5 Hz, 1H), 3.80 (dd, J = 3.7, 6.7 Hz, 1H), 3.67 (m, 1H). 13C NMR (125 MHz)  156.0 138.5, 138.4, 138.3, 138.0, 131.1, 130.2, 129.3, 128.7, 128.6, 128.6, 128.3, 128.1, 128.0, 128.0, 127.9, 127.8, 127.8, 127.4, 126.8, 122.7, 120.4, 120.4, 111.6, 84.0, 80.0, 79.2, 76.4, 75.6, 74.4, 73.6, 72.5, 68.6. IR (thin film): 3343, 3029, 2858, 2847, 1592, 1454, 1096, 734 cm-1. [a]24D: +49.1( (c 0.46, CH2Cl2). FAB MS m/z calcd (M+Na) 689.2879 obsd 689.2866. .2-(2 ,3 ,4 ,6 -tetra-O-benzyl-b-D-mannopyranosyl)-5-benzyloxyphenol 5. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-mannosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. Monobenzyl rescorcinol (11.0 mg, 0.054 mmol) was added and the solution was stirred for 5 min. TMSOTf (8.5 L, 0.047 mmol) was added and the mixture was allowed to stir and warm gradually to ambient temperature. After 1 h, 10 L of Et3N was added and the solvent was removed in vacuo. Chromatography (15:1 Hexanes:EtOAc) afforded the product as a coloress oil (20.9 mg, 82%). 1H NMR (400 MHz)  8.23 (s, 1H), 7.55 7.10 (m, 25H), 6.77 (d, J = 8.5 Hz, 1H), 6.54 (d, J = 2.5 Hz, 1H), 6.43 (dd, J = 2.5, 8.4 Hz, 1H), 5.05 (s, 2H), 4.90 (d, J = 10.7 Hz, 1H), 4.68 (d, J = 2.7 Hz, 1H), 4.62 4.44 (m, 5H), 4.15 (app t, J = 9.6 Hz, 1H), 3.95 (d, J = 2.0 Hz, 1H), 3.78 3.71 (m, 3H), 3.55 (ddd, J = 2.5, 6.0, 9.8 Hz, 1H). 13C NMR (100 MHz) 160.0, 158.1, 138.5, 138.4, 138.1, 137.2, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.7, 127.7, 115.4, 106.7, 103.7, 84.3, 82.6, 79.7, 78.6, 78.4, 75.6, 74.9, 74.5, 73.6, 72.4, 70.1, 68.9. IR (thin film): 3381, 3030, 2868, 1594, 1453, 1147, 736, 696 cm-1. [a]24D: +1.64( (c 1.14, CH2Cl2), ESI MS m/z (M+Na) calcd 745.3136 obsd 745.3113. 3 ,4 ,5 -trimethoxyphenyl-2,3,4,6-tetra-O-benzyl-a-D-glucopyranoside 6. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. 3,4,5-Trimethoxy phenol (8.9 mg, 0.049 mmol) was added followed by the addition of TMSOTf (7.0 L, 0.038 mmol). After 15 min, Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (5:1 Hexanes:EtOAc) afforded the product as a coloress oil (13.0 mg, 79%). 1H NMR (500 MHz)  7.41  7.20 (m, 20H), 6.35 (s, 2H), 5.40 (d, J = 3.5 Hz, 1H), 5.06 (d, J = 10.8 Hz, 1H), 4.91  4.81 (m, 4H), 4.68 (d, J = 12.0 Hz, 1H), 4.59 (d, J = 12.0 Hz, 1H), 4.48 (d, J = 10.7, 1H), 4.46 (d, J = 10.8, 1H), 4.18 (t, J = 9.2 Hz, 1H), 3.92  3.88 (m, 1H), 3.79  3.76 (m, 10H), 3.75  3.70 (m, 4H), 3.59 (dd, J = 2.0, 10.6, 1H). 13C NMR (125 MHz)  153.6, 153.5, 137.6, 137.6, 137.7, 138.8, 128.7, 128.7, 128.6, 128.6, 128.3, 128.3, 128.2, 128.2, 128.1, 128.0, 128.0, 96.0, 94.5, 80.0, 77.4, 76.0, 75.4, 73.7, 70.9, 68.5, 61.2, 56.3. FAB MS m/z (M+H) calcd 729.3010 obsd 729.3034. 2 -Naphthol-2,3,4,6-tetra-O-benzyl-a-D-glucopyranoside 7. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. 2-Naphthol (7.0 mg, 0.049 mmol) was added followed by the addition of TMSOTf (7.0 L, 0.038 mmol). After 15 min, Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (5:1 Hexanes:EtOAc) afforded the product as a coloress oil (12.8 mg, 59%). 1H NMR (500 MHz)  7.81  7.77 (m, 2H), 7.72 (d, J = 8.2 Hz, 1H), 7.46  7.26 (m, 30H), 7.16  7.12 (m, 2H), 5.62 (d, J = 3.3 Hz, 1H), 5.12  5.09 (m, 1H), 5.00  4.82 (m, 5H), 4.71 (d, J = 12.2 Hz, 1H), 4.62  4.58 (m, 2H), 4.50 (d, J = 10.4 Hz, 1H), 4.40 (d, J = 12.0 Hz, 1H), 4.28 (app t, J = 9.5 Hz, 1H), 3.94  3.80 (m, 4H), 3.74  3.70 (m, 2H), 3,59 (dd, J = 2.1, 11.0 Hz, 1H). 13C NMR (125 MHz)  154.5, 139.0, 138.7, 138.3, 138.2, 138.2, 138.0, 134.5, 134.5, 130.1, 129.9, 129.6, 29.6, 128.7, 127.7, 128.7, 128.6, 128.6, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0, 128.0, 128.0, 128.0, 128.0, 127.8, 127.8, 127.5, 127.4, 126.5, 124.5, 124.4, 119.4, 119.2, 111.6, 110.9, 102.0, 95.6, 84.9, 82.3, 82.2, 79.9, 77.9, 77.9, 77.6, 77.4, 76.0, 76.0, 75.5, 75.4, 73.6, 73.6, 71.0, 69.1, 68.4. FAB MS m/z (M+Na) calcd 689.2879 obsd 689.2860. 2-(2 ,3 ,4 ,6 -tetra-O-benzyl-b-D-glucopyranosyl)-3,4,5-trimethoxyphen-1-ol 9. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. 3,4,5-Trimethoxy phenol (8.9 mg, 0.049 mmol) was added followed by the addition of TMSOTf (7.0 L, 0.038 mmol). The reaction mixture was allowed to warm to ambient temperature over the following 4h. Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (15:1 Hexanes:EtOAc) afforded the product as a coloress oil (13.0 mg, 57%) and the O-glycoside (3.0 mg, 13%). 1H NMR (500 MHz)  7.54 (br s, 1H), 7.38  7.05 (m, 20H), 6.31 (s, 1H), 5.00 (d, J = 11.0 Hz, 1H), 4.90  4.85 (m, 3H), 4.58 (d, J = 11.9 Hz, 1H), 4.56 (d, J = 10.7 Hz, 1H), 4.45 ( app t, J = 12.5 Hz, 2H), 4.09 (d, J = 10.7 Hz, 1H), 3.82 (t, J = 9.1, 1H), 3.86  3.74 (m, 12H), 3.71  3.68 (m, 1H), 3.61  3.58 (m, 1H). 13C NMR (75 MHz)  154.3, 152.7, 151.9, 138.9, 138.1, 137.8, 135.7, 128.6, 126.6, 128.5, 128.4, 128.2, 128.0, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 109.2, 97.5, 86.5, 80.8, 78.7, 75.8, 75.5, 75.3, 73.6, 68.2, 61.5, 61.0, 56.1. IR (thin film): 3369.1, 2858.9, 1611.9, 1494.2, 1363.4, 1075.6 cm-1. [a]24D: +7.0( (c 1.42, CH2Cl2). FAB MS m/z (M+H) calcd 729.3010 obsd 729.3034. 1-(2 ,3 ,4 ,6 -tetra-O-benzyl-b-D-glucopyranosyl)-naphth-2-ol 10. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. 2-Naphthol (7.0 mg, 0.049 mmol) was added followed by the addition of TMSOTf (7.0 L, 0.038 mmol). The reaction mixture was allowed to warm to ambient temperature over the following 4 h. Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (10:1 Hexanes:EtOAc) afforded the product as a coloress oil (16.0 mg, 60%) and the O-glycoside (2.0 mg, 9%). 1H NMR (500MHz)  8.64 (s, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.80 (app t, J = 9.5 Hz, 2H), 7.44  7.10 (m, 20H), 7.08 (t, J = 7.6 Hz, 1H), 6.96 (app t, J = 7.6 Hz, 2H), 6.30 (d, J = 7.4 Hz, 2H), 5.40 (d, J = 9.8 Hz, 1H), 5.00 (d, J = 11.0 Hz, 1H), 4.90 (d, J = 12.2 Hz, 2H), 4.62 (d, J = 12.2 Hz, 1H), 4.58 (d, J = 10.7 Hz, 1H), 4.50 (d, J = 12.2 Hz, 1H), 4.20 (d, J = 9.8 Hz, 1H), 4.06 3.98 (m, 2H), 3.89 (app t, J = 9.2 Hz, 1H), 3.84 3.80 (m, 1H), 3.78 3.70 (m, 2H), 3.40 (d, J = 9.8 Hz, 1H). 13C NMR (125 MHz)  155.0, 138.9, 138.2, 137.0, 132.9, 130.7, 129.0, 128.9, 128.7, 128.6, 128.6, 128.3, 128.1, 128.1, 128.1, 128.0, 128.0, 127.8, 127.8, 127.8, 126.8, 123.3, 123.1, 120.0, 114.8, 86.4, 82.1, 78.9, 77.3, 77.1, 76.8, 76.7, 75.9, 75.6, 75.5, 73.6, 68.0. 2-(2 ,3 ,4 ,6 -tetra-O-benzyl-b-D-glucopyranosyl)-5-benzyloxyphenol 11. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. Monobenzyl rescorcinol (11.0 mg, 0.054 mmol) was added and the solution was stirred for 5 min. TMSOTf (8.5 L, 0.047 mmol) was added and the mixture was allowed to stir and warm gradually to ambient temperature. After 6 h, 15 L of Et3N was added and the solvent was removed in vacuo. Chromatography (15:1 Hexanes:EtOAc) afforded the product as a coloress oil (15.7 mg, 62%). 1H NMR (500 MHz)  7.82 (s, 1H), 7.42  7.20 (m, 25H), 7.02 (m, 1H), 6.60 (d, J = 3.7, 1H), 6.54 (dd, J = 3.7, 1H), 5.07 (s, 2H), 5.04 (d, J = 10.7 Hz, 1H), 4.97 (d, 11.0 Hz, 1H), 4.89 (d, J = 11.3, 1H), 4.84 (d, J = 10.7 Hz, 1H), 4.60 (d, J = 12.0 Hz, 1H), 4.55 (d, J = 10.7 Hz, 1H), 4.40 (d, J = 10.1, 1H), 3.98 (d, J = 9.5 Hz, 1H), 3.94 3.84 (m, 3H), 3.78 3.65 (m, 4H), 3.56 (ddd, J = 2.4, 2.4, 9.8 Hz, 1H). 13C NMR (125 MHz)  160.3, 160.0, 138.8, 138.2, 138.0, 137.5, 137.5, 137.1, 130.1, 128.9, 128.8, 128.6, 128.5, 128.2, 128.1, 128.1, 128.0, 128.0, 127.8, 127.7, 116.0, 109.7, 107.1, 104.1, 86.2, 81.9, 81.5, 78.7, 75.8, 75.5, 75.5, 73.6, 70.1, 68.1. IR (thin film): 3367, 3030, 2865, 1593, 1453, 1148, 1026, 734 cm-1. [a]24D:  1.72( (c 0.58, CH2Cl2). ESI MS m/z (M+Na) calcd 745.3136 obsd 745.3125. 2-(3 ,4 ,6 -tri-O-benzyl-2-pivaloyl-b-D-glucopyranosyl)-3,4,5-trimethoxyphen-1-ol 13. Dibutyl 3,4,6-tri-O-benzyl-2-pivaloyl-b-D-glucosyl phosphate (1.19 g, 1.60 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (60 mL) and the solution was cooled to 0 C. TMSOTf (0.30 mL, 1.68 mmol) was added and the reaction was allowed to warm to ambient temperature. After 12 h, saturated NaHCO3 (100 mL) was added to the mixture and the aqueous layer was extracted with CH2Cl2 (3 x 100 mL). The organic layers were combined and the solvent was removed in vacuo to afford a yellow oil. Chromatography (10:1 Hexanes:EtOAc) afforded the product as a white crystalline solid (0.237 g, 21%). 1H NMR (500 MHz) d 7.50 (br s, 1H), 7.38 - 7.18 (m, 15H), 6.30 (s, 1H), 5.50 (t, J = 9.8 Hz, 1H), 4.90 (d, J = 10.1 Hz, 1H), 4.84 (d, J = 11.3 Hz, 1H), 4.80 (d, J = 11.0 Hz, 1H), 4.75 (d, J = 11.3 Hz, 1H), 4.59 (d, J = 12.2 Hz, 1H), 4.51 (d, J = 11.0 Hz, 1H), 4.45 (d, J = 12.2 Hz, 1H), 4.01 (t, J = 9.5 Hz, 1H), 3.90 (s, 3H), 3.86 - 3.78 (m, 5H), 3.74 (s, 3H), 3.70 (dd, J = 2.1, 9.8 Hz, 1H), 3.65 (ddd, J = 2.1, 8.1, 9.8 Hz, 1H), 1.01 (s, 9H). 13C NMR (125 MHz)  176.9, 154.4, 153.1, 151.4, 138.2, 137.9, 134.9, 128.9, 128.7, 128.6, 128.5, 128.4, 128.2, 128.0, 128.0, 127.7, 127.4, 107.3, 97.7, 84.5, 79.0, 77.6, 75.3, 75.3, 74.4, 73.6, 71.7, 68.0, 61.5, 61.0, 60.0, 38.8, 27.3. IR (thin film): 2934, 1734, 1617, 1455, 1136 cm-1. [a]24D: +22.7 (c=0.75, CH2Cl2). FAB MS m/z calcd (M+Na) 723.3144 obsd 723.3139. 14. O-Gly: 1H NMR (500 MHz) d 7.38-7.15 (m, 15H), 6.30 (s, 2H), 5.32 (dd, J = 7.9, 9.5 Hz, 1H), 4.90 (d, J = 7.9 Hz, 1H), 4.86-4.71 (m, 4H), 4.59-4.49 (m, 5H), 3.82-3.78 (m, 4H), 3.69-3.62 (m, 11H), 1.20 (s, 9H). 3-(2 ,3 ,4 ,6 -tetra-O-benzyl-a-D-mannopyranosyl)-1-propene 16. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-mannosyl phosphate (37.0 mg, 0.048 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. Allyl trimethylsilane (9.3 L, 0.59 mmol) was added followed by the addition of TMSOTf (10.0 L, 0.055 mmol). After 30 min, Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (15:1 Hexanes:EtOAc) afforded the product as a coloress oil (25.2 mg, 93%). 1H NMR (500 MHz)  7.38  7.18 (m, 20H), 5.80  5.70 (m, 1H), 5.05  4.98 (m, 2H), 4.72  4.64 (m, 3H), 4.62  4.50 (m, 5H), 4.08  3.95 (m, 2H), 3.88  3.70 (m, 5H), 3.62 (dd, J = 3.1, 4.6 Hz, 1H), 2.41  2.30 (m, 2H). FAB MS m/z calcd (M+Na) 587.2743 obsd 587.2768. 3-(2 ,3 ,4 ,6 -tetra-O-benzyl-a-D-glucopyranosyl)-1-propene 17. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. Allyl trimethylsilane (6.7 L, 0.042 mmol) was added followed by the addition of TMSOTf (7.0 L, 0.038 mmol). After 30 min, Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (10:1 Hexanes:EtOAc) afforded the product as a coloress oil (7.6 mg, 55%). 1H NMR (500 MHz)  7.36  7.25 (m, 17H), 7.13  7.11 (m, 2H), 5.86  5.76 (m, 1H), 5.14  5.05 (m, 2H), 4.94 (d, J = 10.7 Hz, 1H), 4.81 (d, J = 10.4 Hz, 1H), 4.81 (d, J = 10.7 Hz, 1H), 4.70 (d, J = 11.6 Hz, 1H), 4.61 (d, J = 12.2 Hz, 1H), 4.50  4.45 (m, 2H), 4.14 (quint, J = 5.2 Hz, 1H), 3.82 3.74 (m, 2H), 3.70 (dd, J = 3.4, 10.7 Hz, 1H), 3.66 3.60 (m, 3H), 2.52 2.47 (m, 2H). 13C NMR (125 MHz) 138.9, 138.4, 138.4, 138.3, 134.9, 128.6, 128.6, 128.5, 128.2, 128.2, 128.1, 128.0, 128.0, 128.0, 127.8, 127.8, 117.1, 82.6, 80.3, 78.3, 75.7, 75.3, 73.9, 73.7, 73.2, 71.3, 69.1. IR (thin film): 3030, 2918, 1495, 1453, 1360, 1088, 732 cm-1. [a]24D: +13.0( (c= 0.94, CH2Cl2). FAB MS m/z calcd (M+Na) 587.2743 obsd 587.2768. 2-(2 ,3 ,4 ,6 -tetra-O-benzyl-a-D-mannopyranosyl)-cyclopentan-1-one 18. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-mannosyl phosphate (23.0 mg, 0.030 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. Trimethylsiloxy cyclopentene (6.9 L, 0.039 mmol) was added followed by the addition of TMSOTf (6.0 L, 0.033 mmol). After 30 minutes, Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (10:1 Hexanes:EtOAc) afforded the product as a colorless oil (15.2 mg, 84%). 1H NMR (500 MHz)  7.40  7.20 (m, 35H), 5.20 (app s, 0.5H), 5.06 (d, J = 11.3 Hz, 1H), 4.90 (d, J = 10.7 Hz, 1H), 4.82 (d, J = 11.9 Hz, 1H), 4.74 (d, J = 11.9 Hz, 1H), 4.70 (d, J = 11.6 Hz, 1H), 4.66 4.46 (m, 7H), 4.36 (d, J = 2.4 Hz, 1H), 4.22 (app t, J = 6.1 Hz, 0.5H), 4.00 3.92 (m, 2H), 3.84 3.80 (m, 2H), 3.78 3.70 (m, 3H), 3.66 (dd, J = 2.8, 9.5 Hz, 1H), 3.64 3.60 (m, 0.5H), 3.58 3.53 (m, 0.5H), 3.44 3.40 (m, 2H), 2.56 2.48 (m, 2H), 2.32 2.24 (m, 3H), 2.18 2.24 (m, 3H), 2.18 2.06 (m, 2H), 2.05 1.97 (m, 2H), 1.94 1.85 (m, 2H), 1.76 1.67 (m, 2H). 13C NMR (125 MHz) 219.9, 219.4, 139.2, 138.7, 138.6, 138.5, 138.5, 128.7, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 128.0, 128.0, 127.9, 127.8, 127.8, 127.7, 127.7, 127.7,85.2, 80.2, 77.0, 75.6, 75.4, 75.3, 74.7, 74.6, 74.5, 73.9, 73.7, 73.6, 73.6, 73.2, 72.6,72.6, 72.1, 71.5, 69.9, 69.2, 49.9, 48.8, 39.3, 38.9, 29.9, 27.5, 24.5, 20.8. IR (thin film): 3029, 2917, 1732, 1453, 1095 cm-1. FAB MS m/z calcd (M+Na) 629.2849 obsd 629.2874. 2-(2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl)-cyclopentan-1-one 19. Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-glucosyl phosphate (25.0 mg, 0.032 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to 0 C. Trimethylsiloxy cyclopentene (6.9 L, 0.039 mmol) was added followed by the addition of TMSOTf (6.0 L, 0.033 mmol). After 2 h, Et3N (10 L) was added and the solvent was removed in vacuo. Chromatography (10:1 Hexanes:EtOAc) afforded the product as a coloress oil (9.3 mg, 68%). 3 -acetoxyphenyl-2,3,4,6-tetra-O-benzyl-a-D-mannopyranoside Diphenyl 2,3,4,6-tetra-O-benzyl-a-D-mannosyl phosphate (35.0 mg, 0.045 mmol) was coevaporated with toluene, dissolved in CH2Cl2 (1.0 mL) and the solution was cooled to -10 C. Monoacetyl rescorcinol (13.0 mg, 0.091 mmol) was added and the solution was stirred for 5 min. TMSOTf (9.0 L, 0.049 mmol) was added and the mixture was allowed to stir and warm gradually to ambient temperature. After 2h, 10 L of Et3N was added and the solvent was removed in vacuo. Chromatography (15:1 Hexanes:EtOAc) afforded the product as a coloress oil (22.3 mg, 73%). 1H NMR (500 MHz)  7.40  7.29 (m, 18H), 7.18  7.15 (m, 2H), 6.90 (ddd, J = 0.9, 2.4, 8.2 Hz, 1H), 6.82 (t, J = 2.1 Hz, 1H), 6.75 (ddd, J = 0.9, 2.1, 8.2 Hz, 1H), 5.60 (d, J = 2.1 Hz, 1H), 4.90 (d, J = 10.6 Hz, 1H), 4.78 (app s, 2H), 4.72 4.66 (m, 3H), 4.53 (d, J = 11.0 Hz, 1H), 4.46 (d, J = 11.9 Hz, 1H), 4.15 (t, 9.5 Hz, 1H), 4.08 (dd, J = 3.0, 9.5 Hz, 1H), 3.95 (app t, J = 2.1 Hz, 1H), 3.84 3.78 (m, 2H), 3.70 3.66 (m, 1H), 2.28 (s, 3H). 13C NMR (75 MHz) 169.4, 157.0, 151.5, 138.5, 138.3, 138.1, 130.0, 128.5, 128.4, 128.3, 128.0, 128.0, 127.9, 127.8, 127.8, 127.8, 127.7, 127.6, 115.5, 114.0, 110.0, 96.5, 80.0, 75.4, 74.7, 74.5, 73.5, 72.9, 72.7, 72.7, 68.9, 21.4. PAGE  Palmacci, et al. 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