Supporting Information

Supporting Information Catalytic Site-selective Acylation of Carbohydrates Directed by Cation-n Interaction Guozhi Xiao, 1 Gabriel A. Cintron-Rosado, 2 Daniel A. Glazier, 1,3 Bao-min Xi, 1, Can Liu, 1 Peng Liu, 2 * Weiping Tang 1,3 * 1 School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, United States. 2 Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, United States. 3 Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, United States. Present Addresses: School of Pharmaceutical Science, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China *Correspondence to: weiping.tang@wisc.edu, pengliu@pitt.edu. Table of Contents General remarks... S2 Figure S1. Optimization of conditions... S3 Figure S2. Acylation of 5a by mixed anhydride method... S4 Procedures for site-selective acylation of carbohydrates... S4 Characterization data... S5 Supporting information for DFT calculations... S27 Figure S3. Transition state isomers of (R)-BTM-catalyzed acylation of α-o-glucoside 5a... S27 Figure S4. Transition state isomers of (S)-BTM-catalyzed acylation of α-o-glucoside 5a... S28 Figure S5. Transition state isomers of (R)-BTM-catalyzed acylation of α-o-glucoside 5b... S28 Figure S6. Transition state isomers of (S)-BTM-catalyzed acylation of α-o-glucoside 5b... S28 Figure S7. Transition states of (R)-BTM-catalyzed acylation of xyloside 23... S30 References... S51 Copy of NMR spectra... S52 S1

General remarks: All reactions in non-aqueous media were conducted under a positive pressure of dry argon in glassware that had been oven dried prior to use unless noted otherwise. Anhydrous solutions of reaction mixtures were transferred via an oven dried syringe or cannula. All solvents were dried prior to use unless noted otherwise. Thin layer chromatography was performed using precoated silica gel plates. Flash column chromatography was performed with silica gel (40-63 μm). Infrared spectra (IR) were obtained on a Bruker Equinox 55 Spectrophotometer. 1 H and 13 C nuclear magnetic resonance spectra (NMR) were obtained on a Varian Unity-Inova 400 MHz or 500 MHz recorded in ppm (δ) downfield of TMS (δ = 0) in CDCl 3 unless noted otherwise. Signal splitting patterns were described as singlet (s), doublet (d), triplet (t), quartet (q), quintet (quint),or multiplet (m), with coupling constants (J) in hertz. High resolution mass spectra (HRMS) were performed by Analytical Instrument Center at the School of Pharmacy or Department of Chemistry on an Electron Spray Injection (ESI) mass spectrometer. (RT = room temperature.) S2

Note: MTBE and MeCN were used without drying. S3

In order to examine the scope of the acyl group, we generated a broad range of mixed anhydrides in-situ from the corresponding free carboxylic acid and pivalate anhydride for the acylation reaction (Figure S2). We found that high selectivity could be obtained with many different types of carboxylic acids such as palmitic acid (7a3) and levulinic acid (7a5). Procedure A for (R)-BTM or (S)-BTM catalyzed site selective acylation using anhydride: To a solution of substrate (0.12 mmol, 1.0 equiv) and (R)-BTM or (S)-BTM (0.012 mmol, 10 mol%) in anhydrous CHCl 3 (0.6mL, commercially available CHCl 3 containing either ~0.75% ethanol or amylene as the preservative was dried over sodium sulfate prior to use.) was added diisopropylethyl amine (DIPEA) (0.37 mmol, 3.0 equiv), followed by dropwise addition of isobutyric anhydride (0.31 mmol, 2.5 equiv.) at room temperature. The reaction mixture was stirred at room temperature for 12 h and monitored by TLC. After the reaction was completed, the reaction mixture was quenched with MeOH (1 ml) and the mixture was stirred for an additional 10 minutes. A solution of saturated aqueous NH 4Cl (3 ml) was added. The reaction mixture was extracted with CH 2Cl 2 (3 3 ml). The organic layers were combined, dried with anhydrous Na 2SO 4, filtrated and concentrated under vacuum to give the crude product. Ratios of site selective acylation are determined by 1 H NMR of the crude product. Purification of the crude product by column chromatography on silica gel using the indicated solvent system afforded the desired product. Procedure B for (R)-BTM catalyzed site selective acylation of 5a using mixed anhydride: To a solution of 5a (0.12 mmol, 1.0 equiv) and (R)-BTM (0.012 mmol, 10 mol%) in anhydrous CHCl 3 (0.6 ml, commercially available CHCl 3 containing either~0.75% ethanol or amylene as the preservative was S4

dried over sodium sulfate prior to use.) was added DIPEA (0.37 mmol, 3.0 equiv) and carboxylic acid (0.18-0.30 mmol, 1.5-2.5 equiv.), followed by dropwise addition of Piv 2O (0.18-0.30 mmol, 1.5-2.5 equiv) at room temperature. The reaction mixture was stirred at room temperature for 12 h and monitored by TLC. After the reaction was completed, the reaction mixture was quenched with MeOH (1 ml) and the mixture was stirred for an additional 10 minutes. A solution of saturated aqueous NH 4Cl (3 ml) was added. The reaction mixture was extracted with CH 2Cl 2 (3 3 ml). The organic layers were combined, dried with anhydrous Na 2SO 4, filtrated and concentrated under vacuum to give the crude product. Ratios of site selective acylation are determined by 1 H NMR of the crude product. Purification of the crude product by column chromatography on silica gel using the indicated solvent system afforded the desired product. Characterization data: Methyl 4,6-O-benzylidene-3-O-isobutyryl- -D-glucopyranoside (7a) According to the procedure A, 5a 1 (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 3/1) as a white solid (40 mg, 92%). mp = 206-207 o C. [α] 22 D = +88.8 (c = 0.25, CH 2Cl 2) 1 H NMR (400 MHz, CDCl 3): δ 7.43-7.40 (m, 2H), 7.36-7.31 (m, 3H), 5.49 (s, 1H), 5.30 (t, J = 10.0 Hz, 1H), 4.78 (d, J = 4.0 Hz, 1H), 4.31 (dd, J = 4.8, 10.0 Hz, 1H), 3.87-3.81 (m, 1H), 3.74 (t, J = 10.4 Hz, 1H), 3.67-3.62 (m, 1H), 3.58 (t, J = 9.6 Hz, 1H), 3.45 (s, 3H), 2.65-2.55 (m, 1H), 2.24-2.22 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.4, 137.2, 129.1, 128.3, 126.2, 101.4, 100.4, 78.9, 72.2, 72.1, 69.1, 62.9, 55.7, 34.3, 19.3, 19.0.IR (neat) ν 2927, 2855, 1732, 1344, 1211, 1036, 970, 742. HRMS (ESI) m/z calcd for C 18H 24O 7 (M+Na) + 375.1414, found 375.1415. Methyl 4,6-O-benzylidene-2-O-isobutyryl- -D-glucopyranoside (6a) S5

According to the procedure A, 5a 1 (35 mg, 0.12 mmol), (S)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 3/1) as a colorless oil (41 mg, 94%).[α] 22 D = +53.6 (c = 0.25, CH 2Cl 2) 1 H NMR (400 MHz, CDCl 3): δ 7.50-7.48 (m, 2H), 7.38-7.36 (m, 3H), 5.55 (s, 1H), 4.94 (d, J = 3.6 Hz, 1H), 4.78 (dd, J = 9.6, 4.0 Hz, 1H), 4.29 (dd, J = 10.0, 4.8 Hz, 1H), 4.18 (t, J = 9.6 Hz, 1H), 3.85-3.73 (m, 2H), 3.56 (t, J = 9.6 Hz, 1H), 3.39 (s, 3H), 2.68-2.64 (m, 1H), 1.21 (d, J = 2.4 Hz, 3H), 1.19 (d, J = 2.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3): δ 177.1, 137.2, 129.4, 128.5, 126.5, 102.2, 97.8, 81.5, 73.5, 69.0, 68.9, 62.2, 55.7, 34.0, 19.2, 19.0. IR (neat) ν 2923, 2851, 2360, 1734, 1456, 1193, 1040, 895, 766. HRMS (ESI) m/z calcd for C 18H 24O 7 (M+Na) + 375.1414, found 375.1415. Methyl 4,6-O-methylidene-3-O-isobutyryl- -D-glucopyranoside (7b) According to the procedure A, 5b 2 (21 mg, 0.10 mmol), (R)-BTM (2.5 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), isobutyric anhydride (41 L, 0.25 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.6/1) as a white solid (20 mg, 70%). mp = 135-137 o C. [α] 22 D = +110.2 (c = 1.18, CH 2Cl 2) 1 H NMR (500 MHz, CDCl 3): δ 5.23 (t, J = 9.5 Hz, 1H), 5.03 (d, J = 6.5 Hz, 1H), 4.76 (d, J = 4.0 Hz, 1H), 4.57 (d, J = 6.5 Hz, 1H), 4.17 (dd, J = 10.0, 4.5 Hz, 1H), 3.78-3.72 (m, 1H), 3.64-3.59 (m, 1H), 3.46 (t, J = 8.0 Hz, 1H), 3.43 (s, 3H), 3.31 (t, J = 9.5 Hz, 1H), 2.66-2.59 (m, 1H), 2.14 (d, J = 11.5 Hz, 1H), 1.20 (d, J = 7.0 Hz, 3H), 1.19 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDCl 3) δ 177.5, 100.2, 93.8, 79.0, 72.2, 71.9, 68.9, 63.0, 55.8, 34.3, 19.2, 19.1. IR (neat) ν 2981, 2387, 1732, 1509, 1053. HRMS (ESI) m/z calcd for C 12H 20O 7 (M+Na) + 299.1101, found 299.1102. Methyl 4,6-O-methylidene-2-O-isobutyryl- -D-glucopyranoside (6b) According to the procedure A, 5b 2 (21 mg, 0.10 mmol), (S)-BTM (2.5 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), isobutyric anhydride (41 L, 0.25 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.6/1) as a white solid (25 mg, 91%). mp = 118-120 o C. [α] 22 D = +105.0 (c = 1.03, CH 2Cl 2) 1 H NMR (500 MHz, CDCl 3): δ 5.07 (d, J = 6.0 Hz, S6

1H), 4.89 (d, J = 3.5 Hz, 1H), 4.70 (dd, J = 4.0, 10.0 Hz, 1H), 4.63 (d, J = 6.5 Hz, 1H), 4.15-4.08 (m, 2H), 3.73-3.67 (m, 1H), 3.46 (t, J = 10.5 Hz, 1H), 3.35 (s, 3H), 3.27 (t, J = 9.5 Hz, 1H), 2.63 (m, 1H), 2.42 (d, J = 3.5 Hz, 1H), 1.18 (d, J = 7.0 Hz, 3H), 1.18 (d, J = 7.0 Hz, 3H). 13 C NMR (126 MHz, CDCl 3) δ 177.1, 97.7, 94.0, 81.2, 73.7, 68.9, 68.8, 62.4, 55.7, 34.0, 19.2, 19.0.IR (neat) ν 2981, 2890, 1716, 1472, 1382, 1252, 1153, 1049. HRMS (ESI) m/z calcd for C 12H 20O 7 (M+Na) + 299.1101, found 299.1103. Preparation of substrate C-Methyl 4,6-O-benzylidene- -D-glucopyranoside(11) 3 To a solution of methylmagnesium bromide (4 ml, 12 mmol, 3M in diethylether) in dry diethylether (24 ml) was added at 0 o C a solution of the above 1-bromotetraacetyl glucopyranoside (494 mg, 1.2 mmol) in dry diethylether (7 ml). The reaction mixture was stirred at room temperature for 24 h before pouring into water (47 ml). Acetic acid (4.7 ml) was added to this mixture. The two layers were separated and the organic layer was extracted with water (3 13 ml). The water layers were combined and the water was removed under vacuum. The residue was dissolved in pyridine (12 ml) and Ac 2O (9.4 ml) was added. After stirring overnight, the reaction mixture was quenched with MeOH and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 3/1) to give a mixtureof acetyl protected C-glucosides (256 mg, 61%, / = 1.7/1). The -C-glucoside (108 mg, 0.31 mmol) was separated and dissolved in dichloromethane and methanol (3, v/v = 1/1). NaOMe (3.4 mg, 0.06 mmol) was added. After stirring for 1 h, the reaction mixture was neutralized with an ion-exchange resin (Amberlite IR 120, H + ) and filtrated. The filtrate was concentrated. The residue was purified by column chromatography on silica gel (dichloromethane/methanol = 5/1) to give an intermediate (55 mg, 99%). To a solution of the above intermediate (55 mg, 0.31 mmol) and benzaldehyde dimethyl acetal (0.1 ml, 0.67 mmol) in dry DMF (0.8 ml) was added (S)-(+)-10-camphorsulfonic acid (3.6 mg, 0.015 mmol) at rt. The flask was attached to rotary evaporator and warmed to 50 o C for 3 h. The reaction mixture was quenched with Et 3N (1 ml) and concentrated under vacuum. The residue was purified by column chromatography on silica gel (dichloromethane/methanol = 17/1) to give substrate11 (60 mg, 73%) as a white solid. mp = 175-178 o C.[α] 22 D = -28.1 (c = 0.47, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.48-7.46 (m, 2H), 7.39-7.34 (m, 3H), S7

5.49 (s, 1H), 4.31 (dd, J =4.8, 10.4 Hz, 1H), 3.69-3.63 (m, 2H), 3.45-3.37 (m, 3H), 3.23 (t, J = 8.8 Hz, 1H), 1.29 (d, J = 6.0 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 137.2, 129.5, 128.5, 126.4, 102.0, 81.4, 76.4, 76.3, 75.3, 70.3, 69.1, 18.0.IR (neat) ν 3581, 3419, 3378, 3304, 3013, 2972, 2913, 2885, 1454, 1385, 1261, 1216, 1127, 1057, 1019, 803, 757, 700.HRMS (ESI) m/z calcd for C 14H 18O 5Na (M+Na) + 289.1052, found 289.1045. C-Methyl 4,6-O-benzylidene-3-O-isobutyryl- -D-glucopyranoside (13) According to the procedure A, 11 (22 mg, 0.083 mmol), (R)-BTM (2.1 mg, 8.3 mol), DIPEA (41 L, 0.25 mmol), isobutyric anhydride (34 L, 0.21 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 3/1) as a white solid (25 mg, 90%). mp = 138-140 o C.[α] 22 D = -41.8 (c = 0.85, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.44 (m, 2H), 7.35 (m, 3H), 5.50 (s, 1H), 5.01 (t, J = 9.2 Hz, 1H), 4.34 (dd, J = 5.2, 10.4 Hz, 1H), 3.69 (t, J = 10.4 Hz, 1H), 3.63 (t, J = 9.6 Hz, 1H), 3.52-3.45 (m, 2H), 3.32 (m, 1H), 2.89 (d, J = 5.2 Hz, 1H), 2.63 (m, 1H), 1.32 (d, J = 6.0 Hz, 3H), 1.19 (d, J = 6.8 Hz, 3H), 1.18 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 179.2, 137.3, 129.1, 128.4, 126.1, 101.3, 79.0, 77.5, 77.0, 75.9, 70.6, 69.0, 34.3, 19.2, 19.0, 18.0.IR (neat) ν 3367, 3292, 3068, 3014, 2975, 2874, 2361, 2331, 1736, 1694, 1453, 1387, 1365, 1195, 1130, 1105, 1064, 1029, 961, 750. HRMS (ESI) m/z calcd for C 18H 24O 6Na (M+Na) + 359.1471, found 359.1459. Methyl 4,6-O-(4-methoxyphenyl)methylene-3-O-isobutyryl- -D-glucopyranoside(7c) According to the procedure A, 5c 4 (37 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (1.2 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 8/1 to 6/1) as a white solid (41 mg, 90%). mp = 164-166 o C. [α] 22 D = +95.0 (c = 1.21, CH 2Cl 2) 1 H NMR (400 MHz, CDCl 3): δ 7.34 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.44 (s, 1H), 5.28 (t, J = 9.6 Hz, 1H), 4.78 (d, J = 3.6 Hz, 1H), 4.28 (dd, J = 4.8, S8

10.4 Hz, 1H), 3.83 (m, 1H), 3.77 (s, 3H), 3.71 (t, J = 10.0 Hz, 1H), 3.64 (m, 1H), 3.56 (t, J = 9.6 Hz, 1H), 3.44 (s, 3H), 2.59 (m, 1H), 2.28 (d, J = 11.2 Hz, 1H), 1.17 (d, J = 7.2 Hz, 3H), 1.15 (d, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.4, 160.2, 129.7, 127.5, 113.7, 101.4, 100.3, 78.9, 72.2, 72.0, 69.0, 62.9, 55.7, 55.4, 34.2, 19.2, 19.0. IR (neat) ν 2981, 2886, 2342, 1745, 1495, 1386, 1251, 1045. HRMS (ESI) m/z calcd for C 19H 26O 8 (M+Na) + 405.1519, found 405.1523. Methyl 4,6-O-(4-methoxyphenyl)methylene-2-O-isobutyryl- -D-glucopyranoside(6c) According to the procedure A, 5c 4 (37 mg, 0.12 mmol), (S)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (1.2 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 8/1 to &/1) as a white solid (40 mg, 88%). mp = 126-128 o C. [α] 22 D = +40.6 (c = 0.65, CH 2Cl 2). 1 H NMR (400 MHz, CDCl 3): δ 7.40 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 5.48 (s, 1H), 4.92 (d, J = 4.0 Hz, 1H), 4.76 (dd, J = 4.0, 10.0 Hz, 1H), 4.27 (dd, J = 4.4, 10.0 Hz, 1H), 4.14 (t, J = 9.2 Hz, 1H), 3.82 (m, 1H), 3.78 (s, 3H), 3.71 (t, J = 10.0 Hz, 1H), 3.50 (t, J = 9.6 Hz, 1H), 3.37 (s, 3H), 2.63 (m, 1H), 2.50 (br, 1H), 1.19 (d, J = 6.8 Hz, 3H), 1.18 (d, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.1, 160.4, 129.7, 127.8, 113.9, 102.1, 97.7, 81.5, 73.5, 69.0, 68.9, 62.2, 55.6, 55.5, 33.9, 19.2, 18.9. IR (neat) ν 2935, 1734, 1574, 1468, 1249, 1033, 992, 831. HRMS (ESI) m/z calcd for C 19H 26O 8 (M+Na) + 405.1519, found 405.1522. Methyl 4,6-O-(4-nitrophenyl)methylene-3-O-isobutyryl- -D-glucopyranoside (7d) According to the procedure A, 5d 5 (30 mg, 0.09 mmol), (R)-BTM (2.3 mg, 0.009 mmol), DIPEA (46 L, 0.28 mmol), isobutyric anhydride (38 L, 0.23 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 8/1 to 6/1) as a white solid (15 mg, 40%).mp = 212-214 o C. [α] 22 D = +70.0 (c = 0.90, CH 2Cl 2) 1 H NMR (500 MHz, CDCl 3): δ 8.20 (d, J = 9.0 Hz, 2H), S9

7.59 (d, J = 8.5 Hz, 2H), 5.54 (s, 1H), 5.30 (t, J = 11.5 Hz, 1H), 4.79 (d, J = 3.5 Hz, 1H), 4.33 (m, 1H), 3.85 (m, 1H), 3.75 (t, J = 10.5 Hz, 1H), 3.66 (m, 1H), 3.59 (t, J = 9.5 Hz, 1H), 3.46 (s, 3H), 2.65-2.62 (m, 1H), 2.17 (d, J = 11.5 Hz, 1H), 1.19 (d, J = 7.0 Hz, 3H), 1.18 (d, J = 7.0 Hz, 3H). 13 C NMR (126 MHz, CDCl 3): δ 177.4, 148.4, 143.6, 127.4, 123.6, 100.3, 99.9, 79.1, 72.0, 71.9, 69.2, 62.6, 55.9, 34.3, 19.3, 19.0. IR (neat) ν 2925, 2853, 1736, 1524, 1348, 1197, 1065, 853, 746. HRMS (ESI) m/z calcd for C 18H 23NO 9 (M+Na) + 420.1265, found 420.1268. Methyl 4,6-O-(4-nitrophenyl)methylene-2-O-isobutyryl- -D-glucopyranoside (6d) According to the procedure A, 5d 5 (39 mg, 0.12 mmol), (S)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 8/1 to 6/1) as a white solid (39 mg, 82%).mp = 153-155 o C. [α] 22 D = +47.4 (c = 1.55, CH 2Cl 2) 1 H NMR (500 MHz, CDCl 3): δ 8.24 (d, J = 9.0 Hz, 2H), 7.69 (d, J = 9.0 Hz, 2H), 5.64 (s, 1H), 4.96 (d, J = 4.0 Hz, 1H), 4.77 (dd, J = 10.0, 4.0 Hz, 1H), 4.33 (dd, J = 10.0, 4.5 Hz, 1H), 4.20 (t, J = 9.5 Hz, 1H), 3.88-3.83 (m, 1H), 3.79 (t, J = 10.0 Hz, 1H), 3.60 (t, J = 9.0 Hz, 1H), 3.41 (s, 3H), 2.68-2.64 (m, 1H), 2.39 (s, 1H), 1.22 (d, J = 7.0 Hz, 3H), 1.20 (d, J = 7.0 Hz, 3H). 13 C NMR (126 MHz, CDCl 3): δ 177.1, 148.6, 143.5, 127.7, 123.7, 100.4, 97.8, 81.6, 73.6, 69.1, 68.9, 62.0, 55.8, 34.0, 19.2, 19.0. IR (neat) ν 2980, 2890, 1731, 1518, 1463, 1189, 1041, 967, 830, 746. HRMS (ESI) m/z calcd for C 18H 23NO 9 (M+Na) + 420.1265, found 420.1267. Methyl 4,6-O-benzylidene-2-O-isobutyryl- -D-galactopyranoside (15a) According to the procedure A, 14a 1 (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (1.8 ml) were used. The product was S10

isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.3/1) as a colorless oil (37 mg, 85%).[α] 22 D = +5.0 (c = 1.2, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.50 (m, 2H), 7.35 (m, 3H), 5.53 (s, 1H), 5.11 (dd, J = 8.0, 10.0 Hz, 1H), 4.36 (d, J = 8.0 Hz, 1H), 4.31 (dd, J = 1.6, 12.4 Hz, 1H), 4.18 (dd, J = 0.8, 3.6 Hz, 1H), 4.08 (dd, J = 1.6, 12.4 Hz, 1H), 3.74 (dd, J = 3.6, 9.6 Hz, 1H), 3.49 (s, 3H), 3.46 (m, 1 H), 2.62 (m, 1H), 1.18 (d, J = 6.8 Hz, 6H). 13 C NMR (101 MHz, CDCl 3) δ 176.9, 137.5, 129.4, 128.4, 126.6, 101.9, 101.6, 75.7, 71.9, 69.1, 66.7, 56.7, 34.2, 19.2, 19.0. IR (neat) ν 3016, 2971, 2939, 2918, 2877, 2360, 2341, 1736, 1539, 1456, 1387, 1216, 1085, 1057, 1027, 1000.HRMS (ESI) m/z calcd for C 18H 24O 7K (M+K) + 391.1159, found 391.1149. Methyl 4,6-O-benzylidene-3-O-isobutyryl- -D-galactopyranoside (16a) According to the procedure A, 14a 1 (35 mg, 0.12 mmol), (S)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), isobutyric anhydride (50 L, 0.31 mmol) and CHCl 3 (1.8 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.3/1) as a white solid (40 mg, 93%).mp = 160-164 o C.[α] 22 D = +69.2 (c = 2.0, CHCl 3). 1 H NMR (500 MHz, CDCl 3): δ 7.47 (m, 2H), 7.32 (m, 3H), 5.48 (s, 1H), 4.82 (dd, J = 4.0, 10.5 Hz, 1H), 4.37 (d, J = 3.5 Hz, 1H), 4.32 (dd, J = 1.0, 12.5 Hz, 1H), 4.26 (d, J = 8.0 Hz, 1H), 4.05 (dd, J = 2.0, 12.5 Hz, 1H), 4.00 (dd, J = 8.0, 10.5 Hz, 1H), 3.55 (s, 3H), 3.48 (s, 1 H), 2.62 (m, 1H), 2.52 (br, 1 H), 1.16 (d, J = 7.0 Hz, 6H). 13 C NMR (126 MHz, CDCl 3) δ 177.3, 137.8, 129.0, 128.2, 126.2, 104.1, 100.9, 73.7, 73.4, 69.2, 68.7, 66.6, 57.3, 34.1, 19.3, 18.8.IR (neat) ν 3649, 3524, 2980, 2930, 2889, 2361, 2342, 1720, 1454, 1386, 1369, 1203, 1171. HRMS (ESI) m/z calcd for C 18H 24O 7Na (M+Na) + 375.1420, found 375.1409. 4-Methoxylphenyl 4,6-O-benzylidene-2-O-isobutyryl- -D-galactopyranoside (15b) S11

According to the procedure A, 14b 6 (40 mg, 0.11 mmol), (R)-BTM (2.7 mg, 0.011 mmol), DIPEA (54 L, 0.32 mmol), isobutyric anhydride (44 L, 0.27 mmol) and CHCl 3 (1.2 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 8/1 to 4/1) as a white solid (41 mg, 86%).mp = 193-198 o C.[α] 22 D = -26.4 (c = 0.47, CHCl 3). 1 H NMR (500 MHz, CDCl 3): δ 7.52 (m, 2H), 7.38 (m, 3H), 6.98 (m, 2H), 6.80 (m, 2H), 5.55 (s, 1H), 5.33 (dd, J = 8.0, 10.0 Hz, 1H), 4.90 (d, J = 8.0 Hz, 1H), 4.36 (m, 1H), 4.24 (d, J = 3.5 Hz, 1H), 4.09 (m, 1H), 3.81 (m, 1H), 3.75 (s, 3H), 3.56 (br, 1 H), 2.64-2.56 (m, 2H), 1.19 (d, J = 7.0 Hz, 6H). 13 C NMR (101 MHz, CDCl 3) δ 176.9, 155.6, 151.5, 137.4, 129.5, 128.4, 126.6, 118.9, 114.6, 101.6, 100.7, 75.6, 71.9, 71.8, 69.1, 66.8, 55.8, 34.3, 19.4, 19.0.IR (neat) ν 3014, 2963, 2855, 1727, 1509, 1362, 1197, 1067, 1101, 751.HRMS (ESI) m/z calcd for C 24H 28O 8 (M+Na) + 467.1676, found 467.1671. 4-Methoxylphenyl 4,6-O-benzylidene-3-O-isobutyryl- -D-galactopyranoside (16b) According to the procedure A, 14b 6 (40 mg, 0.11 mmol), (R)-BTM (2.7 mg, 0.011 mmol), DIPEA (54 L, 0.32 mmol), isobutyric anhydride (44 L, 0.27 mmol) and CHCl 3 (1.2 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 8/1 to 4/1) as a white solid (40 mg, 84%).mp = 174-179 o C. [α] 22 D = 18.6 (c = 0.50, CHCl 3). 1 H NMR (500 MHz, CDCl 3): δ 7.49 (m, 2H), 7.34 (m, 3H), 7.04 (m, 2H), 6.80 (m, 2H), 5.48 (s, 1H), 4.92 (dd, J = 3.5, 10.0 Hz, 1H), 4.83 (d, J = 8.0 Hz, 1H), 4.40 (d, J = 3.5 Hz, 1H), 4.33 (m, 1H), 4.23 (t, J = 9.0 Hz, 1H), 4.06 (m, 1H), 3.75 (s, 3H), 3.55 (br, 1 H), 2.65 (m, 1H), 2.58 (br, 1H), 1.19 (d, J = 7.0 Hz, 6H). 13 C NMR (101 MHz, CDCl 3) δ 177.3, 155.7, 151.2, 137.8, 129.1, 128.3, 126.3, 119.3, 114.6, 102.9, 100.9, 73.5, 73.4, 69.1, 68.5, 66.7, 55.8, 34.1, 19.3, 18.9. IR (neat) ν 3022, 2965, 2857, 1722, 1509, 1373, 1181, 1064, 757. HRMS (ESI) m/z calcd for C 24H 28O 8 (M+Na) + 467.1676, found 467.1669. 6-O-tert-butylbiphenyl-3-O-isobutyryl-1,2-O-[1-(exo-methoxy)ethyliden]- -D-mannopyranoside (18) S12

According to the procedure A, 17 7 (48 mg, 0.10 mmol), (R)-BTM (2.6 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), isobutyric anhydride (41 L, 0.25 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 4/1 + 5% Et 3N) as a colorless foam (45 mg, 82%, dr for the ortho ester (exo/endo) = 10:1).[α] 22 D = -19.5 (c = 1.5, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.69 (m, 4H), 7.44-7.33 (m, 6H), 5.39 (d, J = 2.4 Hz, 1H), 4.96 (dd, J = 4.4, 10.0 Hz, 1H), 4.56 (dd, J = 2.4, 4.0 Hz, 1H), 4.11 (t, J = 9.6 Hz, 1H), 3.95-3.86 (m, 2H), 3.34 (m, 1H), 3.22 (s, 3H), 2.70 (m, 1H), 2.70 (br, 1H), 1.67 (s, 3H), 1.23 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.8 Hz, 3H), 1.05 (s, 9H). 13 C NMR (101 MHz, CDCl 3) δ 177.5, 135.81, 135.80, 132.9, 132.8, 130.17, 130.10, 128.04, 128.01, 124.4, 97.6, 73.9, 73.6, 66.7, 64.3, 49.8, 34.1, 27.0, 26.9, 25.0, 19.38, 19.31, 19.0.IR (neat) ν 3491, 3072, 3049, 2932, 2858, 1732, 1590, 1470, 1428, 1361, 1240, 1206, 1142, 1111, 1086, 1048, 894.HRMS (ESI) m/z calcd for C 29H 40O 8SiNa (M+Na) + 567.2390, found 567.2404. 3-O-isobutyryl-1,2-O-[1-(exo-methoxy)ethyliden]- -L-rhamnopyranoside (21) According to the procedure A, 20 8 (22 mg, 0.10 mmol), (S)-BTM (2.5 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), isobutyric anhydride (41 L, 0.25 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 2.1/1 + 5% Et 3N) as a colorless foam (22 mg, 76%, dr of the ortho ester (exo/endo) = 5:1).[α] 22 D = 63.4 (c = 0.7, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 5.39 (d, J = 2.4 Hz, 1H), 4.87 (dd, J = 4.4, 9.6 Hz, 1H), 4.55 (d, J = 2.4, 4.0 Hz, 1H), 3.63 (t, J = 9.6 Hz, 1H), 3.37 (m, 1H), 3.22 (s, 3H), 2.67 (m, 1H), 1.66 (s, 3H), 1.33 (d, J = 6.0 Hz, 3H), 1.21 (d, J = 7.2 Hz, 3H), 1.20 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.7, 124.3, 97.4, 77.1, 73.9, 71.0, 70.4, 49.8, 34.1, 24.8, 19.2, 19.1, 17.7.IR (neat) ν 3499, 2976, 2936, 2921, 2360, 2338, 1732, 1470, 1385, 1239, 1205, 1147, 1080, 1043, 893, 757.HRMS (ESI) m/z calcd for C 13H 22O 7Na (M+Na) + 313.1263, found 313.1261. Preparation of substrate methyl 2-O-benzyl- -D-xylopyranoside (23) S13

Alcohol S6 9 (600 mg, 1.48 mmol) was dissolved in dry DMF (5 ml). Ag 2O (2.05 g, 8.86 mmol) and BnBr (0.88 ml, 7.39 mmol) were added sequentially. After stirring for 25 h at rt, the reaction mixture was filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 15/1) to give the fully protected product (604 mg, 82%). To a solution of this product (604 mg, 1.2 mmol) in THF (3.4 ml) were treated with TBAF/AcOH = 2/1 (4.9 mmol of TBAF) in THF (3.4 ml) and the reaction mixture was stirred for 6 h at room temperature. The reaction was quenched with 10% NH 4Cl solution and was diluted with CH 2Cl 2. The organic layer was washed with 10% NH 4Cl solution and brine. The aqueous layer was extracted with CH 2Cl 2 three times. The combined organic layer was dried over Na 2SO 4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 3/7) to give compound 26 (171 mg, 55%) as a colorless foam. [α] 22 D = -25.1 (c= 1.67, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.39-7.29 (m, 5H), 4.81 (d, J = 11.6 Hz, 1H), 4.67 (d, J = 4.4 Hz, 1H), 4.51 (d, J =4.4 Hz, 1H), 4.06 (dd, J = 3.6, 12.0 Hz, 1H), 3.72 (t, J = 6.0 Hz, 1H), 3.66 (m, 1H), 3.49 (s, 3H), 3.45 (t, J = 6.0 Hz, 1H), 3.37 (m, 1H), 3.00 (d,j = 7.2 Hz, 1H), 2.95 (d, J = 6.4 Hz, 1H). 13 C NMR (101 MHz, CDCl 3) δ 137.8, 128.7, 128.2, 128.0, 103.0, 78.6, 73.8, 72.7, 69.4, 63.6, 56.6. IR (neat) ν 3385, 2971, 2921, 1738, 1641, 1454, 1381, 1257, 1126, 977, 949, 888. HRMS (ESI) m/z calcd for C 13H 18O 5Na (M+Na) + 277.1052, found 277.1049. Methyl 2-O-benzyl-4-O-isobutyryl- -D-xylopyranoside (24) According to the procedure A, 23 (25 mg, 0.10 mmol), (R)-BTM (2.5 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), isobutyric anhydride (41 L, 0.25 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 3.6/1) as a white solid (29 mg, 90%).mp = 48-50 o C.[α] 22 D = -19.8 (c = 0.67, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.35-7.26 (m, 5 H), 4.86 (d, J = 11.6 Hz, 1H), 4.78 (m, 1H), 4.65 (d, J = 11.6 Hz, 1H), 4.35 (d, J = 6.4 Hz, 1H), 4.05 (dd, J = 5.2, 12.0 Hz, 1H), 3.73 (m, 1H), 3.50 (s, 3H), 3.30-3.25 (m, 2H), 2.55 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H). 13 C S14

NMR (101 MHz, CDCl 3) δ 176.9, 138.3, 128.7, 128.2, 128.1, 104.1, 80.2, 74.2, 72.5, 71.2, 62.2, 56.8, 34.1, 19.12, 19.10.IR (neat) ν 3374, 2971, 2932, 2878, 2348, 1737, 1468, 1387, 1279, 1194, 1157, 1126, 1094, 1024, 951, 753.HRMS (ESI) m/z calcd for C 17H 24O 6Na (M+Na) + 347.1471, found 347.1463. Methyl 2-O-benzyl-3-O-isobutyryl- -D-xylopyranoside (25) According to the procedure A, 23 (22 mg, 0.10 mmol), (S)-BTM (2.5 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), isobutyric anhydride (41 L, 0.25 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.5/1) as a white solid (24 mg, 75%).mp = 70-74 o C. [α] 22 D = -21.5 (c = 0.8, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.38-7.27 (m, 5H), 4.90 (t, J = 7.2 Hz, 1H), 4.80 (d, J = 11.6 Hz, 1H), 4.68 (d, J = 11.6 Hz, 1H), 4.43 (d, J = 5.6 Hz, 1H), 4.04 (dd,j = 4.4, 12.0 Hz, 1H), 3.68 (m, 1H), 3.48 (s, 3H), 3.44-3.36 (m, 2H), 2.55 (m, 1H), 1.17 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 178.0, 138.0, 128.5, 127.99, 127.96, 103.3, 76.9, 74.6, 74.0, 68.8, 64.1, 56.6, 34.2, 19.0.IR (neat) ν 3450, 2972, 2938, 2906, 2876, 2842, 2357, 2343, 1736, 1469, 1388, 1260, 1199, 1160, 1070, 1028, 800, 755, 698.HRMS (ESI) m/z calcd for C 17H 24O 6Na (M+Na) + 347.1471, found 347.1460. Preparation of substrate methyl 4,6-O-dibenzoyl- -D-glucopyranoside (8b) Diol 8a 1 (2.9 g, 10.3 mmol) was dissolved in dry CH 2Cl 2 (30 ml). To the stirred solution at rt, levulinic acid (3.15 ml, 30.9 mmol), 4-dimethylaminopyridine (1.26 g, 10.3 mmol), EDCI (5.91 g, 30.9 mmol) and diisopropylethylamine (10.2 ml, 61.7 mmol) were added sequentially. After stirring for 12 h at rt, the reaction mixture was diluted with CH 2Cl 2, washed with saturated aqueous NaHCO 3 and brine. The organic layer was dried over anhydrous Na 2SO 4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 1:1 to 1:1.5) to give an intermediate (4.15 g, 84%). A solution of this intermediate (2.1 g, 4.4 mmol) in AcOH/H 2O (17.5 ml, 4:1, v/v) was heated at 60 o C. After stirring for 12h at 60 o C, the reaction mixture was concentrated under S15

vacuum to give the colorless syrup. This product (401 mg, 1.03 mmol) was dissolved in dry CH 2Cl 2 (5 ml). To the solution was added 4-dimethylaminopyridine (25 mg, 0.21 mmol) and Et 3N (0.9 ml, 6.17 mmol), followed by slow addition of BzCl (0.36 ml, 3.08 mmol). After stirring for 6 h at rt, the reaction mixture was diluted with CH 2Cl 2, washed with saturated aqueous NaHCO 3 solution and brine. The organic layer was dried over anhydrous Na 2SO 4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 1/1.5) to give an intermediate (470 mg, 76% for two steps). This intermediate (470 mg, 0.79 mmol) was dissolved in dry CH 2Cl 2 (8 ml). Subsequently, pyridine (5 ml), acetic acid (3.3 ml) and hydrazine hydrate (0.31 ml, 6.29 mmol) were added. After stirring for 5 h, the reaction mixture was quenched by the addition of acetone (10 ml) and the solvents were removed under vacuum. The crude product was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 1:2) to give compound 8b (160 mg, 51%) as a colorless foam. [α] 22 D = 21.7 (c = 0.87, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 8.01-7.95 (m, 4H), 7.95-7.48 (m, 2H), 7.39-7.33 (m, 4H), 5.24 (t, J = 9.6 Hz, 1H), 4.57 (dd, J = 2.8, 12.0 Hz, 1H), 4.41 (dd, J = 5.6, 12.0 Hz, 1H), 4.31 (d, J = 7.6 Hz, 1H), 3.92 (m, 1H), 3.84 (m, 1H), 3.55 (m, 1H), 3.54 (s, 3H), 3.28 (d, J = 4.4 Hz, 1H), 3.24 (d, J = 2.4 Hz, 1H). 13 C NMR (101 MHz, CDCl 3) δ 166.4, 166.3, 133.7, 133.2, 130.1, 129.89, 129.85, 129.3, 128.6, 128.5, 103.6, 74.9, 74.3, 72.1, 72.0, 63.7, 57.4.IR (neat) ν 3452, 3017, 2962, 2920, 2849, 2360, 2340, 1722, 1451, 1270, 1115, 1068, 1026, 756. HRMS (ESI) m/z calcd for C 21H 22O 8Na (M+Na) + 425.1212, found 425.1207. Methyl 4,6-O-dibenzoyl-2-O-isobutyryl- -D-glucopyranoside (9b) According to the procedure A, 8b (29 mg, 0.07 mmol), (R)-BTM (1.8 mg, 0.007 mmol), DIPEA (36 L, 0.22 mmol), isobutyric anhydride (29 L, 0.18 mmol) and CHCl 3 (0.7 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 2.2/1) as a colorless foam (31 mg, 91%).[α] 22 D = 0.9 (c = 1.1, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 8.01-7.96 (m, 4H), 7.56-7.49 (m, 2H), 7.39-7.34 (m, 4H), 5.31 (t, J = 9.6 Hz, 1H), 4.92 (dd, J = 8.0, 9.6 Hz, 1H), 4.61 (dd, J = 3.2, 12.0 Hz, 1H), 4.48 (d, J = 7.6 Hz, 1H), 4.43 (dd, J = 5.6, 12.0 Hz, 1H), 3.97 (m, 1H), 3.92 (t, J = 9.6 Hz, 1H), 3.49 (s, 3H), 2.60 (m, 1H), 1.19 (d, J = 6.8 Hz, 3H), 1.18 (d, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.0, 166.4, 166.2, 133.7, 133.3, 130.1, 129.89, 129.80, 129.2, 128.6, 128.5, 101.9, 74.2, 74.1, 72.5, 72.0, 63.5, 57.1, 34.2, S16

19.1, 19.0. IR (neat) ν 3404, 2972, 2937, 2882, 2360, 2331, 1728, 1452, 1380, 1276, 1159, 1072, 952. HRMS (ESI) m/z calcd for C 25H 28O 9Na (M+Na) + 495.1631, found 495.1630. Preparation of substrate dimethylthexylsilyl 4,6-O-benzylidene- -D-glucopyranoside (8c) Triol S7 10 (300 mg, 1.12 mmol) was dissolved in dry CH 2Cl 2 (3 ml), and imidazole (229 mg, 3.36 mmol) was added. The solution was stirred at rt for 5 min. TDSCl (0.26 ml, 1.34 mmol) was then added and the reaction mixture was stirred at rt overnight. The reaction mixture was diluted with CH 2Cl 2 and washed with 1 M HCl. The organic layer was then dried over anhydrous Na 2SO 4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 2:1) to give 8c (298 mg, 65%) as a colorless foam. [α] 22 D = -27.4 (c = 2.0, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.48-7.45 (m, 2H), 7.35-7.32 (m, 3H), 5.49 (s, 1H), 4.59 (d, J = 7.6 Hz, 1H), 4.28 (dd, J = 5.2, 10.4 Hz, 1H), 3.74 (t, J = 10.0 Hz, 2H), 3.52 (t, J = 9.2 Hz, 1H), 3.43-3.35 (m, 2H), 3.11 (br, 1H), 2.60 (br, 1H), 1.64 (m, 1H), 0.89 (d, J = 2.4 Hz, 3H), 0.87 (d, J = 2.4 Hz, 3H), 0.86 (s, 6H), 0.17 (s, 3H), 0.16 (s, 3H). 13 C NMR (101 MHz, CDCl 3) δ 137.2, 129.4, 128.5, 126.5, 102.09, 102.07, 98.17, 98.15, 80.9, 76.6, 73.1, 68.8, 66.6, 34.1, 25.0, 20.3, 20.1, 18.7, 18.6, -1.7, -3.0. IR (neat) ν 3401, 3016, 2961, 2871, 1466, 1380, 1256, 1215, 1184, 1099, 1011, 836, 752, 698. HRMS (ESI) m/z calcd for C 21H 34O 6SiNa (M+Na) + 433.2022, found 433.2014. Dimethylthexylsilyl 4,6-O-benzylidene-3-O-isobutyryl- -D-glucopyranoside (10c) According to the procedure A, 8c (40 mg, 0.098 mmol), (R)-BTM (2.5 mg, 0.0098 mmol), DIPEA (48 L, 0.29 mmol), isobutyric anhydride (40 L, 0.24 mmol) and CHCl 3 (0.7 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 4/1) as a colorless foam (45 mg, 96%). [α] 22 D = -34.3 (c = 1.5, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.43-7.40 (m, 2H), 7.35-7.30 (m, 3H), 5.48 (s, 1H), 5.18 (t, J = 9.2 Hz, 1H), 4.69 (d, J = 7.2 Hz, 1H), 4.31 (dd, J = 4.8, 10.4 Hz, 1H), 3.77 (t, J = 9.6 Hz, 1H),3.68 (t, J = 9.6 Hz, 1H), 3.52-3.47 (m, 2H), 2.60 (m, 1H), 2.43 (br, 1H), 1.64 (m, 1H), 1.18 (d, J = 6.4 Hz, 3H), 1.17 (d, J = 6.8 Hz, 3H), 0.89 (d, J = 2.4 Hz, 3H), 0.87 (d, J = 2.8 Hz, 3H), 0.86 (s, 6H), 0.17 (s, S17

6H). 13 C NMR (101 MHz, CDCl 3) δ 177.4, 137.2, 129.1, 128.3, 126.2, 101.47, 101.45, 98.64, 98.61, 78.8, 75.5, 73.5, 68.9, 66.8, 34.27, 34.20, 25.0, 20.3, 20.1, 19.2, 19.0, 18.7, 18.6, -1.7, -3.0. IR (neat) ν 3452, 2969, 2934, 2874, 1727, 1468, 1378, 1257, 1187, 1155, 1091, 1020, 836, 753, 697.HRMS (ESI) m/z calcd for C 25H 40O 7SiNa (M+Na) + 503.2441, found 503.2431. Preparation of substrate methyl 4,6-O-benzylidene- -D-galactopyranosyl-(1 6)-2,3,4-O-tribenzyl- -Dmannopyranoside (26) Thioglycoside donor S8 11 (394 mg, 0.69 mmol) and acceptor S9 12 (293 mg, 0.63 mmol) were dissolved in dry CH 2Cl 2 (7 ml). To this solution was added 4Å Molecular sieves (600 mg). The reaction mixture was stirred for 30 min, and it was cooled to 0 o C. NIS (343 mg, 1.5 mmol) was added, followed by dropwise addition of TMSOTf (50 L, 0.28 mmol). The reaction mixture was allowed to warm to room temperature. After stirring for 3 h, the reaction mixture was quenched with Et 3N (1 ml), filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 2:1 to 1:1) to give the disaccharide (476 mg, 82%). The above disaccharide (470 mg, 0.51 mmol) was dissolved in dry CH 2Cl 2 and MeOH (2 ml, 1/1, v/v). To this solution was added 30% NaOMe in MeOH (0.2 ml, 1.0 mmol). After stirring overnight, the reaction mixture was quenched with acetic acid and concentrated under vacuum. The residue was purified by column chromatography on silica gel (CH 2Cl 2/MeOH = 30/1) to give product (330 mg, 90%) as a colorless foam. [α] 22 D = 11.9 (c = 0.8, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.49 (m, 2H), 7.35-7.24 (m, 18H), 5.53 (s, 1H), 4.94 (d, J = 10.8 Hz, 1H), 4.75-4.67 (m, 3H), 4.65 (d, J = 10.8 Hz, 1H), 4.59 (s, 2H), 4.39 (d, J = 8.0 Hz, 1H), 4.81 (m, 1H), 4.24 (m, 1H), 4.18 (m, 1H), 4.05 (m, 1H), 3.95-3.89 (m 2H), 3.87-3.84 (m, 2H), 3.81-3.76 (m, 2H), 3.67 (m, 1H), 3.42 (m, 1H), 3.35 (br, 1H), 3.31 (s, 3H), 2.56 (m, 1H). 13 C NMR (101 MHz, CDCl 3) δ 138.6, 138.5, 138.2, 137.8, 129.3, 128.6, 128.57, 128.56, 128.4, 128.2, 128.0, 127.9, 127.8, 127.7, 126.6, 103.7, 101.6, 99.3, 80.2, 75.5, 75.3, 75.2, 74.5, 73.1, 72.7, 72.3, 71.7, 71.0, 69.3, 67.8, 67.0, S18

55.2. IR (neat) ν 3659, 3441, 2980, 2889, 2358, 2338, 1727, 1454, 1366, 1260, 1216, 1093, 1027, 968. HRMS (ESI) m/z calcd for C 41H 46O 11Na (M+Na) + 737.2938, found 737.2945. Methyl 4,6-O-benzylidene-3-O-isobutyryl- -D-galactopyranosyl-(1 6)-2,3,4-O-tribenzyl- -Dmannopyranoside (28) According to the procedure A, 26 (62 mg, 0.087 mmol), (S)-BTM (2.2 mg, 0.0087 mmol), DIPEA (43 L, 0.26 mmol), isobutyric anhydride (35 L, 0.22 mmol) and CHCl 3 (0.5 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.7/1) as a colorless foam (63 mg, 93%). [α] 22 D = 72.7 (c = 1.6, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ δ 7.48 (m, 2H), 7.36-7.24 (m, 18H), 5.48 (s, 1H), 4.94 (d, J = 11.2 Hz, 1H), 4.83 (dd, J = 4.0, 10.8 Hz, 1H), 4.75-4.66 (m, 3H), 4.64 (d, J = 10.8 Hz, 1H), 4.59 (s, 2H), 4.45 (d, J = 8.0 Hz, 1H), 4.36 (m, 1H), 4.32 (m, 1H), 4.26 (m, 1H), 4.09-4.01 (m 2H), 3.92-3.84 (m, 3H), 3.82-3.76 (m, 2H), 3.46 (m, 1H), 3.30 (s, 3H), 2.64 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H), 1.18 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.3, 138.58, 138.55, 138.2, 138.0, 129.0, 128.5, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 126.3, 104.0, 100.9, 99.2, 80.2, 75.3, 75.2, 74.5, 73.6, 73.5, 73.0, 72.3, 71.6, 69.2, 68.5, 68.1, 66.7, 55.1, 34.1, 19.3, 18.9.IR (neat) ν 3464, 3029, 2972, 2936, 2906, 2877, 2838, 2359, 2341, 1732, 1454, 1366, 1138, 1051, 1027, 752, 698.HRMS (ESI) m/z calcd for C 45H 52O 12Na (M+Na) + 807.3356, found 807.3348. Methyl 4,6-O-benzylidene-2-O-isobutyryl- -D-galactopyranosyl-(1 6)-2,3,4-O-tribenzyl- -Dmannopyranoside (27) S19

According to the procedure A, 26 (62 mg, 0.087 mmol), (R)-BTM (2.2 mg, 0.0087 mmol), DIPEA (43 L, 0.26 mmol), isobutyric anhydride (35 L, 0.22 mmol) and CHCl 3 (0.5 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.2/1) as a white solid (57 mg, 84%). mp = 76-80 o C.[α] 22 D = 12.9 (c = 0.9, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ δ 7.51-7.49 (m, 2H), 7.36-7.25 (m, 18H), 5.54 (s, 1H), 5.16 (dd, J = 8.0, 10.0 Hz, 1H), 4.93 (d, J = 10.8 Hz, 1H), 4.72 (s, 2H), 4.68 (d, J = 1.6 Hz, 1H), 4.59 (m, 3H), 4.56 (d, J = 8.0 Hz, 1H), 4.33 (m, 1H), 4.18 (m, 1H), 4.15 (m, 1H), 4.05 (m 1H), 3.89-3.73 (m, 5H), 3.70 (m, 1H), 3.43 (br, 1H), 3.31 (s, 3H), 2.56 (m, 1H), 1.18 (d, J = 6.8 Hz, 3H), 1.17 (d, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 177.0, 138.68, 138.66, 138.4, 137.6, 129.4, 128.5, 128.4, 128.09, 128.08, 127.85, 127.80, 127.74, 127.73, 126.6, 101.6, 101.2, 99.0, 80.5, 75.8, 75.4, 75.1, 74.7, 73.0, 72.27, 72.25, 72.1, 71.8, 69.1, 68.8, 66.6, 54.9, 34.2, 19.1, 19.0. IR (neat) ν 3659, 3571, 2980, 2884, 2837, 2359, 2338, 1737, 1454, 1365, 1216, 1196, 1094, 1059, 1026, 968. HRMS (ESI) m/z calcd for C 45H 52O 12Na (M+Na) + 807.3356, found 807.3347. 4,6,4,6 -di-o-benzylidine-2,2 -di-o-propionyl-, -D-trehalose (30) According to the procedure A, 29 13 (62 mg, 0.12 mmol), (S)-BTM (3.0 mg, 0.012 mmol), DIPEA (119 L, 0.72 mmol), propionic anhydride (46 L, 0.36 mmol) and CHCl 3 (1.2 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.5/1) as a white solid (54 mg, 72%). mp = 260-262 o C. [α] 22 D = +396.2 (c = 0.33, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.45 (m, 4H), 7.37-7.35 (m, 6H), 5.50 (s, 2H), 5.33 (dd, J = 2.8 Hz, 2H), 4.85 (dd, J = 2.8, 7.6 Hz, 2H), 4.21 (t, J = 7.6 Hz, 2H), 4.15 (dd, J = 3.6, 8.0 Hz, 2H), 3.85 (m, 2H), 3.70 (t, J = 8.4 Hz, 2H), 3.54 (t, J = 7.6 Hz, 2H), 2.68 (br, 2H), 2.47 (m, 4H), 1.17 (t, J = 6.0 Hz, 6H). 13 C NMR (101 MHz, CDCl 3) δ 174.1, 137.0, 129.5, 128.5, 126.4, 102.3, 92.7, 81.2, 73.1, 68.8, 63.1, 27.5, 9.1.IR (neat) ν 3527, 3020, 2926, 2855, 1743, 1719, 1460, 1427, 1375, 1313, 1214, 1145, 1116, 1085, 1004, 988.HRMS (ESI) m/z calcd for C 32H 38O 13Na (M+Na) + 653.2210, found 653.2223. S20

4,6,4,6 -di-o-benzylidine-3,3 -di-o-propionyl-, -D-trehalose (31) According to the procedure A, 29 13 (62 mg, 0.12 mmol), (R)-BTM (3.0 mg, 0.012 mmol), DIPEA (119 L, 0.72 mmol), propionic anhydride (46 L, 0.36 mmol) and CHCl 3 (2.4 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 2.5/1 to 2/1) as a white solid (58 mg, 77%).mp = 147-150 o C. [α] 22 D = +151.9 (c = 1.4, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.39 (m, 4H), 7.06-6.98 (m, 6H), 6.07 (t, J = 10.0 Hz, 2H), 5.49 (s, 2H), 5.31 (d, J = 3.6 Hz, 2H), 4.54 (d, J = 12.8 Hz, 2H), 4.29 (dd, J = 4.8, 10.0 Hz, 2H), 4.22 (m, 2H), 3.79 (m, 4H), 3.68 (m, 2H), 2.13 (q, J = 7.6 Hz, 4H), 0.96 (t, J = 7.6 Hz, 6H). 13 C NMR (101 MHz, CDCl 3) δ 176.6, 136.4, 128.6, 127.5, 126.6, 101.9, 94.2, 79.7, 72.9, 71.1, 69.3, 63.4, 28.4, 9.1. IR (neat) ν3473, 2982, 2941, 2864, 1722, 1454, 1406, 1372, 1322, 1274, 1199, 1142, 1121, 985, 749. HRMS (ESI) m/z calcd for C 32H 38O 13Na (M+Na) + 653.2210, found 653.2223. Preparation of substrate neohesperidin dihydrochalcone derivative (32) Commercially available neohesperidin dihydrochalcone (1.84 g, 3.0 mmol) was dissolved in dry DMF (6 ml). The reaction mixture was cooled to 0 o C. Dry K 2CO 3 (1.86 g, 13.5 mmol) was added, followed by slow addition of MeI (0.7 ml, 11.25 mmol). The reaction mixture was allowed to warm to room temperature. After stirring for 18 h at rt, the reaction mixture was filtered and concentrated under vacuum to give an intermediate. This intermediate (1.96 g, 3.0 mmol) and imidazole (613 mg, 9.0 mmol) were dissolved in dry DMF (10 ml). The reaction mixture was cooled to 0 o C. TBDPSCl (0.88 ml, 3.4 mmol) was added slowly. After stirring for 20 h at 0 o C, the reaction was quenched by MeOH (1 ml), concentrated under vacuum to give an intermediate. To a solution of this intermediate (2.68 g, 3.0 mmol) and S21

dimethoxypropane (1.1 ml, 8.92 mmol) in dry DMF (3 ml) was added TsOH H 2O (572 mg, 3.0 mmol) at rt. After stirring for 4 h, the reaction mixture was diluted with CH 2Cl 2, washed with saturated asueous NaHCO 3 solution and brine. The organic layer was dried over anhydrous Na 2SO 4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (CH 2Cl 2/MeOH = 30/1) to give an intermediate (1.05 g, 51% for 3 steps). This intermediate (840 mg, 0.92 mmol) was dissolved in dry THF (8 ml) and 70% HF Py (0.36 ml, 13.6 mmol) was added. After stirring for 8 h at rt, the reaction mixture was quenched by saturated aqueous NaHCO 3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na 2SO 4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (CH 2Cl 2/MeOH = 13:1 to 9:1) to give an intermediate (528 mg, 85%). To a solution of this intermediate (385 mg, 0.55 mmol) and benzaldehyde dimethyl acetal (0.17 ml, 1.11 mmol) in dry DMF (2.8 ml) was added (S)-(+)-10-camphorsulfonic acid (10.4 mg, 0.045 mmol) at rt. The flask was attached to a rotary evaporator and warmed to 50 o C for 3h. The reaction mixture was quenched with Et 3N (1 ml) and concentrated under vacuum. The residue was purified by column chromatography on silica gel (Hexane/Ethyl acetate = 3/4) to give product (337 mg, 78%) as a colorless foam. [α] 22 D = 38.8 (c = 0.5, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.48-7.45 (m, 2H), 7.38-7.36 (m, 3H), 6.77-6.71 (m, 3H), 6.20 (s, 2H), 5.62 (s, 1H), 5.52 (s, 1H), 5.05 (d, J = 7.6 Hz, 1H), 4.35 (dd, J = 4.8, 10.8 Hz, 1H), 4.19 (d, J = 6.0 Hz, 1H), 4.02-3.92 (m, 4H), 3.84 (s, 3H), 3.83 (s, 3H), 3.79 (t, J = 10.0 Hz, 1H), 3.71 (s, 6H), 3.61-3.52 (m, 2H), 3.40 (m, 1H), 3.03-2.99 (m, 2H), 2.95-2.91 (m, 2H), 2.74 (br, 1H), 2.15 (d, J = 4.0 Hz, 1H). 1.49 (s, 3H), 1.33 (s, 3H), 1.33 (d, J = 6.4 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 203.4, 159.4, 157.9, 148.7, 147.2, 136.8, 134.1, 129.4, 128.3, 126.3, 120.2, 115.3, 111.9, 111.3, 109.4, 101.9, 99.7, 97.5, 93.2, 80.3, 78.4, 76.2, 75.8, 74.8, 74.3, 68.5, 66.1, 65.9, 55.9, 55.8, 46.4, 29.4, 28.0, 26.2, 17.3. IR (neat) ν 3470, 2969, 2937, 2919, 2849, 2360, 2342, 1716, 1697, 1604, 1516, 1497, 1458, 1416, 1374, 1261, 1219, 1126, 1085, 1054, 1028, 804. HRMS (ESI) m/z calcd C 41H 50O 15Na (M+Na) + 805.3047, found 805.3002. S22

Neohesperidin dihydrochalcone derivative (33) According to the procedure A, 32 (53 mg, 0.068 mmol), (R)-BTM (1.7 mg, 0.0068 mmol), DIPEA (34 L, 0.20 mmol), acetic anhydride (10 L, 0.10 mmol) and CHCl 3 (0.7 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1/1) as a colorless foam (47 mg, 84%).[α] 22 D = -46.7 (c = 1.5, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.42-7.39 (m, 2H), 7.35-7.32 (m, 3H), 6.76-6.71 (m, 3H), 6.20 (s, 2H), 5.48 (s, 1H), 5.43 (t, J = 9.6 Hz, 1H), 5.22 (s, 1H), 5.15 (d, J = 7.6 Hz, 1H), 4.34 (dd, J = 4.8, 10.4 Hz, 1H), 4.05 (m, 2H), 3.97 (dd, J = 5.6, 7.2 Hz, 1H), 3.87-3.78 (m, 2H), 3.83 (s, 3H), 3.82 (s, 3H), 3.75 (m, 1H), 3.70 (s, 6H), 3.67 (m, 1H), 3.37 (m, 1H), 3.03-2.99 (m, 2H), 2.94-2.90 (m, 2H), 2.37 (d, J = 3.6 Hz, 1H), 2.12 (s, 3H), 1.48 (s, 3H), 1.32 (s, 3H), 1.29 (d, J = 6.0 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 203.4, 170.0, 159.1, 158.1, 148.9, 147.3, 136.8, 134.2, 129.3, 128.4, 126.2, 120.3, 115.7, 112.0, 111.3, 109.7, 101.7, 99.6, 98.3, 93.4, 78.4, 78.1, 76.2, 75.9, 74.6, 74.0, 68.7, 66.6, 66.3, 56.1, 56.0, 55.9, 46.5, 29.5, 28.2, 26.4, 21.0, 17.4. IR (neat) ν 3458, 3018, 2937, 2840, 50, 1696, 1594, 1515, 1463, 1415, 1372, 1334, 1222, 1197, 1136, 1084, 1030, 988.HRMS (ESI) m/z calcd C 43H 52O 16Na (M+Na) + 847.3153, found 847.3126. S23

Methyl 4,6-O-benzylidene-3-O-propanoyl- -D-glucopyranoside (7a1) According to the procedure B, 5a 1 (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), propionic acid (14 L, 0.18 mmol), Piv 2O (38 L, 0.18 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1/1) as a white solid (38 mg, 91%).mp = 172-175 o C. [α] 22 D = +85.6 (c = 0.25, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.42 (m, 2H), 7.33 (m, 3H), 5.47 (s, 1H), 5.31 (t, J = 9.6 Hz, 1H), 4.78 (d, J = 3.6 Hz, 1H), 4.30 (dd, J = 4.8, 10.4 Hz, 1H), 3.84 (m, 1H), 3.73 (t, J = 10.0 Hz, 1H), 3.63 (m, 1 H), 3.56 (t, J = 9.6 Hz, 1H),3.44 (s, 3H), 2.39 (q, J = 7.6 Hz, 2H), 1.13 (t, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 174.7, 137.2, 129.2, 128.3, 126.3, 101.6, 100.3, 78.8, 72.3, 72.0, 69.1, 62.9, 55.7, 27.8, 9.3.IR (neat) ν 3473, 3455, 3019, 2965, 2897, 2359, 2341, 1737, 1261, 1215, 1087, 1073, 1056, 1021, 981.HRMS (ESI) m/z calcd for C 17H 22O 7Na (M+Na) + 361.1263, found 361.1256. Methyl 4,6-O-benzylidene-3-O-hexynoyl- -D-glucopyranoside (7a2) According to the procedure B, 5a (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), 5-hexynoic acid (21 L, 0.18 mmol), Piv 2O (38 L, 0.18 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.5/1) as a white solid (43 mg, 91%). mp = 134-136 o C.[α] 22 D = +75.3 (c = 1.65, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.43 (m, 2H), 7.34 (m, 3H), 5.47 (s, 1H), 5.32 (t, J = 9.6 Hz, 1H), 4.78 (d, J = 3.2 Hz, 1H), 4.30 (dd, J = 4.8, 10.0 Hz, 1H), 3.85 (m, 1H), 3.73 (t, J = 10.0 Hz, 1H), 3.64 (m, 1 H), 3.57 (t, J = 9.6 Hz, 1H), 3.45 (s, 3H), 2.50 (t, J = 7.6 Hz, 2H), 2.21 (m, 3H), 1.92 (s, 1 H), 1.84 (m, 2H). 13 C NMR (101 MHz, CDCl 3) δ 173.2, 137.1, 129.2, 128.4, 126.3, 101.6, 100.3, 83.5, 78.8, 72.4, 71.9, 69.2, 69.0, 62.9, 55.7, 33.2, 23.9, 17.8.IR (neat) ν 3441, 3281, 2961, 2916, 2869, 2850, 2360, 2341, 1736, 1451, 1367.HRMS (ESI) m/z calcd for C 20H 24O 7Na (M+Na) + 399.1420, found 399.1406. S24

Methyl 4,6-O-benzylidene-3-O-palmitoyl- -D-glucopyranoside (7a3) According to the procedure B, 5a (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), palmitic acid (70 mg, 0.27 mmol), Piv 2O (51 L, 0.27 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 3/1) as a white solid (61 mg, 94%).mp = 100-103 o C.[α] 22 D = +43.2 (c = 0.6, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.43 (m, 2H), 7.34 (m, 3H), 5.47 (s, 1H), 5.32 (t, J = 9.6 Hz, 1H), 4.78 (d, J = 4.0 Hz, 1H), 4.30 (dd, J = 4.8, 10.0 Hz, 1H), 3.85 (m, 1H), 3.73 (t, J = 10.0 Hz, 1H), 3.66 (dd, J = 3.6, 9.6 Hz, 1H), 3.56 (t, J = 9.6 Hz, 1H), 3.44 (s, 3H), 2.35 (t, J = 7.6 Hz, 2H), 1.61 (m, 2H), 1.24-1.19 (m, 24H), 0.86 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3) δ 174.1, 137.2, 129.1, 128.3, 126.3, 101.6, 100.3, 78.9, 72.2, 72.0, 69.1, 62.9, 55.7, 34.6, 32.1, 29.89, 29.87, 29.85, 29.83, 29.81, 29.6, 29.5, 29.4, 29.1, 25.2, 22.8, 14.3.IR (neat) ν 3019, 2958, 2923, 2853, 2360, 2341, 1729, 1540, 1457, 1368, 1260, 1215, 1073, 1056, 1020, 994.HRMS (ESI) m/z calcd for C 30H 48O 7Na (M+Na) + 543.3298, found 543.3285. Methyl 4,6-O-benzylidene-3-O-phenylacetyl- -D-glucopyranoside (7a4) According to the procedure B, 5a (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), phenylacetic acid (34 mg, 0.25 mmol), Piv 2O (50 L, 0.25 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1.3/1) as a white solid (45 mg, 90%).mp = 188-191 o C.[α] 22 D = +69.0 (c = 0.17, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.34 (m, 5H), 7.25 (m, 2H), 7.20 (m, 3H), 5.43 (s, 1H), 5.35 (t, J = 9.6 Hz, 1H), 4.78 (d, J = 4.0 Hz, 1H), 4.31 (dd, J = 4.8, 10.0 Hz, 1H), 3.85 (m, 1H), 3.75-3.65 (m, 4H), 3.56 (t, J = 9.6 Hz, 1H), 3.44 (s, 3H), 2.26 (br, 1H). 13 C NMR (101 MHz, CDCl 3) δ 171.7, 137.1, 134.1, 129.2, 129.1, 128.6, 128.3, 127.1, 126.3, 101.5, 100.3, 78.8, 72.9, 71.9, 69.0, 62.8, 55.7, 41.5.IR (neat) ν 3380, 3066, 3016, 2980, 2949, 2919, 2883, 2360, 2340, 1734, 1558, 1471, 1368, 1216, 1140, 1063, 993.HRMS (ESI) m/z calcd for C 22H 24O 7Na (M+Na) + 423.1420, found 423.1407. S25

Methyl 4,6-O-benzylidene-3-O-4-oxopentanoyl- -D-glucopyranoside (7a5) According to the procedure B, 5a (28 mg, 0.10 mmol), (R)-BTM (2.5 mg, 0.010 mmol), DIPEA (50 L, 0.30 mmol), 4-oxopentanoic acid (23 L, 0.23 mmol), Piv 2O (46 L, 0.23 mmol) and CHCl 3 (1.0 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1/2) as a white solid (34 mg, 90%). mp = 148-150 o C.[α] 22 D = +79.6 (c = 0.97, CHCl 3). 1 H NMR (400 MHz, CDCl 3): δ 7.44-7.41 (m, 2H), 7.35-7.31 (m, 3H), 5.47 (s, 1H), 5.31 (t, J = 10.0 Hz, 1H), 4.79 (d, J = 4.0 Hz, 1H), 4.29 (dd, J = 4.4, 10.0 Hz, 1H), 3.85 (m, 1H), 3.73 (t, J = 10.4 Hz, 1H), 3.67 (m, 1H), 3.57 (t, J = 9.6 Hz, 1H), 3.44 (s, 3H), 2.74 (m, 2H), 2.63 (m, 2H), 2.43 (d, J = 10.4 Hz, 1H), 2.11 (s, 3H). 13 C NMR (101 MHz, CDCl 3) δ 206.8, 172.9, 137.1, 129.2, 128.3, 126.3, 101.6, 100.2, 78.8, 72.8, 71.9, 69.1, 62.9, 55.7, 38.4, 29.9, 28.3.IR (neat) ν 3446, 3408, 3019, 2918, 2852, 1734, 1707, 1449, 1408, 1366, 1331, 1304, 1262, 1215, 1179, 1139, 1082, 993, 750, 697. HRMS (ESI) m/z calcd for C 19H 24O 8Na (M+Na) + 403.1369, found 403.1370. Methyl 4,6-O-benzylidene-3-O-acetyl- -D-glucopyranoside According to the procedure B, 5a (35 mg, 0.12 mmol), (R)-BTM (3.1 mg, 0.012 mmol), DIPEA (62 L, 0.37 mmol), acetic acid (9 L, 0.16 mmol), Piv 2O (33 L, 0.16 mmol) and CHCl 3 (0.6 ml) were used. The product was isolated by column chromatography on silica gel (Hexane/Ethyl acetate = 1/1) as a white solid (34 mg, 86%).mp = 180-182 o C. [α] 22 D = +118.9 (c = 1.0, CHCl 3). 1 H NMR (500 MHz, CDCl 3): δ 7.42 (m, 2H), 7.33 (m, 3H), 5.47 (s, 1H), 5.31 (t, J = 8.0 Hz, 1H), 4.78 (d, J = 3.2 Hz, 1H), 4.30 (dd, J = 3.6, 8.0 Hz, 1H), 3.85 (m, 1 H), 3.73 (t, J = 8.4 Hz, 1H), 3.65 (m, 1H), 3.56 (t, J = 7.6 Hz, 1H), 3.45 (s, 3H), 2.67 (d, J = 9.2 Hz, 1H), 2.10 (s, 3H). 13 C NMR (126 MHz, CDCl 3) δ 171.2, 137.2, 129.2, 128.4, 126.3, 101.7, 100.3, 78.8, 72.4, 72.0, 69.1, 62.9, 55.7, 21.2.IR (neat) ν 3019, 2937, 2868, 1735, 1369, 1245, 1215, 1059, 1047, 996, 748, 698, 667. HRMS (ESI) m/z calcd for C 16H 20O 7Na (M+Na) + 347.1107, found 347.1103. S26

Supporting Information for DFT Calculations Conformational Search of Transition States Careful conformational searches of all transition state structures were performed by systematically altering the dihedral angle of the forming O C bond in the acylation transition state and changing the direction of the acylated catalyst approaching the substrate. The carbonyl of the acylated (R)- or (S)-BTM catalyst may approach the catalyst either syn to the C H bond on the carbon that is being acylated (referred to here as C H down ), or anti to that C H bond (referred to as C H up ). The two different approaches position different O-containing groups on the substrate to interact with the positively charged acylated catalyst. For example, in the (R)-BTMcatalyzed acylation of the C3-OH group in α-o-glucoside 5a, the C4-OR is placed above the cationic catalyst in the C H down conformer 7a-TS1, while the C2-OH is placed above the cationic catalyst in the C H up TS conformer 7a-TS1 (Figure S3). The lowest energy C H down and C H up TS isomers for the acylation of α-o-glucosides 5a and 5b with (R)- and (S)-BTM catalysts are shown in Figure S3-S6. In all low-energy TS conformers, there exists some level of cation-n interaction with either an OH or OR group on the substrate. The magnitude of the stabilizing cation-n interactions is significantly impacted by the stereochemical environment around the O lone pair. A detailed analysis of factors that control the stability of the acylation transition state is provided below. Figure S3. Transition state isomers of (R)-BTM-catalyzed acylation of α-o-glucoside 5a. S27

Figure S4. Transition state isomers of (S)-BTM-catalyzed acylation of α-o-glucoside 5a. Figure S5. Transition state isomers of (R)-BTM-catalyzed acylation of α-o-glucoside 5b. Figure S6. Transition state isomers of (S)-BTM-catalyzed acylation of α-o-glucoside 5b. 1. C H up versus C H down conformers. The C H up conformation leads to more significant steric repulsions between the acylated catalyst and the adjacent carbons on the substrate (i.e. C2 and C4 in C3-acylation TSs and C1 and C3 in C2-acylation TSs). Indeed, most of the lowest energy TS conformers calculated have the C H down conformation to minimize the S28

steric repulsions between the catalyst and the substrate. The only two exceptions are the (S)-BTMcatalyzed C3-acylation TS of α-o-glucosides 5a and 5b, in which the C H up conformers(7a- TS2 and 7b-TS2) are0.9 and 0.8 kcal/mol lower than in energy than the corresponding C H down conformers(7a-ts2 and 7b-TS2, see Figures S4 and S6). Here the C H down conformers 7a- TS2 and 7b-TS2 aredestabilized due to the unfavorable steric repulsions between the axial OMe group and the catalyst. It should be noted that although 7a-TS2 is stabilized by a cation-π interaction with the benzylidene protecting group on the substrate, it is still less stable than 6a- TS2, due to the unfavorable steric interactions in this C H up conformation. 2. Cation-n interactions. Since the nature of the cation-n interactions is most likely a chargediploe type electrostatic interaction, 14 its strength is expected to be dependent upon the distance of the O atom and the cationic catalyst. In nearly all favored transition states with strong cation-n interactions (e.g., 7b-TS1, 6a-TS2, 6b-TS2), the distance between the O atom and the amidine carbon in the catalyst is shorter than 3 Å. The only exception is 7a-TS1, in which the O C distance is 3.22 Å. This longer distance is necessary to achieve the favorable cation-π interaction with the benzylidene protecting group. In contrast, the corresponding O C distance with the axial OMe group in 6a-TS1 and 6b-TS1 and with the C2-OH in 7a-TS2 and 7b-TS2 that is blocked by the adjacent axial OMe are all significantly longer than 3 Å, indicating significantly diminished cationn interactions in these disfavored TSs. In summary, although there are a number of TS conformers in each acylation pathway, the most favorable acylation TS always adapts the C H down conformation to avoid substratecatalyst steric repulsions, and involves a stabilizing cation-n interaction as evidenced by a short distance between the oxygen atom and the cationic catalyst. In reactions with the benzylidene protected glucoside 5a, cation-π interaction also contributes to the stability of the acylation transition state. Computed Selectivity of the Acylation of α-o-glucoside 5b and Xyloside 23 The most stable transition states of the C3- and C2-acylation of α-o-glucoside 5b with the (R)- and (S)-BTM catalysts are shown in Figures S5 and S6. The DFT calculations predicted the same major product as in the reactions with the benzylidene-protected α-o-glucoside 5a. C3-acylation is favored in the reaction with the (R)-BTM catalyst, while C2-acylation is favored in the reaction with (S)-BTM. The geometries of the C2-acylation TSs (6b-TS1 and 6b-TS2) are grossly similar to the corresponding TSs with 5a (6a-TS1 and 6a-TS2, respectively), while the geometries of the C3-acylation TSs (7b-TS1 and 7b-TS2) are somewhat different from those in the reaction with 5a (7a-TS1 and 7a-TS2). In the absence of the benzylidene-protecting group, the cation-π interaction is not possible. Thus, cation-n interaction becomes the only factor that stabilizes the C3-acylation TS. Nonetheless, the relative energies between the TS isomers are in fact similar in the reactions S29

with 5a and 5b. This indicates that the cation-n interaction is the dominant factor that controls the site-selectivity. Similar to the (R)-BTM-catalyzed reaction of 5a, the (R)-BTM-catalyzed acylation of 5b is C3 selective. The (R)-BTM-catalyzed C3-acylation TS (7b-TS1) is stabilized by a strong cation-n interaction with the C4-OR group on the substrate, as evidenced by the short O C distance (2.82 Å). In 6b-TS1, the cation-n interaction is much weaker because the axial OMe group on C1 is not perfectly oriented towards the positively charged aromatic system in the acylated catalyst. The corresponding O C distance between the O lone pair and the catalyst in 6b-TS1 is significantly longer (3.12 Å). In the reaction with the (S)-BTM catalyst, the site-selectivity is reversed to favor C2-acylation, because 6b-TS2 is stabilized by a strong cation-n interaction, while the cation-n interaction in the C3-acylation TS (7b-TS2) is much weaker due to the steric repulsions between the catalyst and the C1 axial OMe group on the substrate. The most stable transition states of the (R)-BTM-catalyzed C4- and C3-acylation of xyloside 23 are shown in Figure S7. Both transition states are stabilized by cation-n interactions with either the C3- or C4-OH group. The DFT calculations indicate the C4-acylation transition state 24-TS1 is 0.8 kcal/mol more stable than 25-TS1, consistent with the experimentally observed selectivity for C4-acylation. Compared to 25-TS1, the C4-acylation transition state 24-TS1 is stabilized due to less steric hindrance around the forming C O bond. The adjacent methylene group (C5) does not clash with the carbonyl on the catalyst, which allows the C4 H that is pointing towards carbonyl to slightly rotate away from the carbonyl to decrease steric contact with the catalyst in 24-TS1. Figure S7. Transition states of (R)-BTM-catalyzed acylation of xyloside 23. S30