Oxidative Activation of C S Bonds with an Electropositive Nitrogen Promoter Enables Orthogonal Glycosylation of Alkyl over Phenyl Thioglycosides

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1 Supporting Information Oxidative Activation of C S Bonds with an Electropositive Nitrogen Promoter Enables Orthogonal Glycosylation of Alkyl over Phenyl Thioglycosides Annabel Kitowski,, Ester Jiménez-Moreno, Míriam Salvadó,, Jordi Mestre, Sergio Castillón, Gonzalo Jiménez-Osés, #, * Omar Boutureira,, * Gonçalo J. L. Bernardes,, * Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge (UK) Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisboa (Portugal) Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C/ Marcel lí Domingo 1, Tarragona (Spain) # Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, Logroño (Spain) Table of Contents 1. General Remarks... S2 2. Experimental Section... S Chemical synthesis... S Kinetic studies by 1 H NMR... S Computational details... S NMR spectra... S41 3. References... S80 S1

2 1. General Remarks The used reagents were purchased from Alfa Aesar, Carbosynth Limited, Fisher Scientific and Sigma Aldrich and were used without further purification. Dry solvents were obtained by distillation after common procedure and distilled H 2 O was used for the reactions. Purification of the compounds was performed by chromatography using Silica Gel 60 (mesh ) from Material Harvest. Thin layer chromatography (TLC) was carried out on silica gel coated glass or aluminium plates (60 F 254, Merck) and the reactions were visualized with 5% sulfuric acid in ethanol and UV light (λ = 254 nm). Proton ( 1 H NMR) and carbon ( 13 C NMR) nuclear magnetic resonance spectra were recorded on a Bruker 500 MHz DCM Cryoprobe or 400 MHz DPX-400 Dual spectrometer. Fluor ( 19 F NMR) nuclear magnetic resonance spectra were measured with a Bruker 400 MHz Avance III HD Smart Probe spectrometer. All spectra were fully assigned using COSY, HSQC, and HMBC, the chemical shifts were quoted on the δ scale in ppm and the solvent peak (CDCl 3 : 1 H = 7.26 ppm, 13 C = ppm) was used as internal standard. Coupling constants J were reported in Hz, using the following splitting abbreviations: s = singlet, d = duplet, t = triplet, dd = duplet from duplet, m = multiplet. High-resolution mass spectroscopy (HRMS) were received from a Thermo Finnigan Orbitrap Classic or from a Waters Xevo G2-S bench top QTOF using positive ion electrospray ionization (ESI) for essential compounds. All reactions in anhydrous conditions were performed using flame-dried flasks, 3 Å molecular sieves (MS) and argon atmosphere. 2. Experimental Section 2.1. Chemical synthesis Ethyl-O-(mesitylensulfonyl)acetohydroxamate 1 Ethyl N-hydroxyacetamidate (1.18 g, 11.4 mmol) was dissolved in DMF (6 ml), triethylamine (1.5 ml) was added and the solution was cooled to 0 ºC. 2-Mesitylensulfonylchloride (2.5 g, 11.4 mmol) was added in small portions and the mixture was vigorously stirred for 30 min. The reaction was diluted with Et 2 O (100 ml) and washed with H 2 O (4 50 ml). The aqueous layers were extracted with Et 2 O and the combined organic layers were dried over MgSO 4 and S2

3 concentrated. Ethyl-O-(mesitylensulfonyl)acetohydroxamate (2.39 g, 74%) was obtained as white solid and was used in the next step without further purification. O-Mesitylsulfonylhydroxylamine (MSH) 1 Ethyl-O-(mesitylsulfonyl)-acetohydroxamate (2.39 g, 8.39 mmol) was dissolved in dioxane (3 ml) and cooled to 0 ºC. Perchloric acid (70%, 1 ml) was added dropwise and the reaction was stirred for 10 min. The solidified mixture was transferred into 100 ml of ice water and the flask was rinsed with H 2 O and Et 2 O. The aqueous layer was extracted with Et 2 O (3 30 ml), the combined organic layers were washed with saturated solution of sodium chloride (2 50 ml) and dried/neutralized with K 2 CO 3. After filtration, the solution was carefully concentrated to a volume less than 50 ml and poured into 50 ml of ice-cold petroleum ether. After crystallization, the desired product was obtained (885 mg, 49%) as a white crystalline solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 7.00 (s, 2H, H3, H5), 2.59 (s, 6H, 2 o/p-ch 3 ), 2.34 (s, 3H, m-ch 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = 141.0, (C-Ar), 22.7 (2 CH 3 ), 21.1 (CH 3 ) ppm. Phenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (1) 2 To a solution of 1,2,3,4,6-penta-O-acetyl-D-glucopyranose (5 g, 12.8 mmol) and thiophenol (1.58 ml, 15.4 mmol) in dry CH 2 Cl 2 (25 ml) under argon, BF 3 OEt 2 (7.89 ml, 64 mmol) was added at room temperature and the reaction was stirred for 5 h. The mixture was poured into a saturated aqueous NaHCO 3 solution and the aqueous layers were extracted with CH 2 Cl 2 (3 50 ml). The combined organic layers were combined, dried over MgSO 4 and concentrated. After purification by column chromatography (1:1 petroleum ether/etoac), phenyl 2,3,4,6-tetra- O-acetyl-1-thio-β-D-glucopyranose 1 was obtained (3.99 g, 71%) as a white solid. 1 H NMR (400 MHz, CDCl 3 ): δ = (m, 5H, Ar), 5.22 (t, J = 9.3 Hz, 1H, H3), 5.03 (t, J = 9.8 Hz, 1H, H4), 4.97 (t, J = 9.6 Hz, 1H, H2), 4.70 (d, J = 10.1 Hz, 1H, H1), (m, 2H, H6a,b), 3.72 (m, 1H, H5), 2.08, 2.07, 2.01, 1.98 (4 s, 4 3H, CH 3 -C=O) ppm. 13 C NMR (100 MHz, CDCl 3 ): S3

4 δ = 170.7, 170.3, 169.5, (4 CH 3 C=O), 133.3, (C1, C2 /3 ), 129.1, (C3, C4, C5 ), 85.9 (C1), 75.9 (C5), 74.1 (C3), 70.1 (C2), 68.3 (C4), 20.9, 20.8, 20.7, 20.6 (4 CH 3 -C=O) ppm. HRMS-ESI + for [M + Na + ] C 20 H 24 NaO 9 S + (m/z): calc ; found Phenyl 1,2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranose (2) 2 To a solution of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (1.23 g, 2.79 mmol) in dry MeOH (15 ml), a NaOMe solution (30%, 1.54 ml) was added at room temperature and the reaction was stirred for 40 min, until all starting material was consumed as monitored by TLC. After neutralization with Dowex 5W (H + -form) for 10 min, the resin was removed by filtration and the solvent was evaporated. The obtained product phenyl β-d-thioglucopyranoside (728 mg, 2.67 mmol) was redissolved in dry DMF (10 ml) and cooled to 10 ºC. Sodium hydride (60% in mineral oil, 641 mg, 26.7 mmol) was added and the mixture was stirred for 1 h while warming up to room temperature. Benzyl bromide (4.57 g, 26.7 mmol) was added and the reaction was stirred for 17 h. The reaction was cooled to 0 ºC and H 2 O (15 ml) were added slowly. The aqueous layer was extracted with EtOAc (3 20 ml) and the combined organic layers were concentrated. The reaction was redissolved in Et 2 O and washed with saturated NaCl solution (3 20 ml). The organic layer was dried over MgSO 4 and concentrated. After purification by column chromatography (6:1 petroleum ether/etoac), phenyl 1,2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranose 2 was obtained (1.25 g, 71% over two steps) as a white solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 7.59 (dd, J = 6.6, 3.0 Hz, 2H, H-Phenyl), (m, 23H, 20 H-benzyl, 3 H-Phenyl), (m, 2H, O-CH 2 -Phenyl), (m, 2H, O-CH 2 -Phenyl), 4.74 (d, J = 10.3 Hz, 1H,, O-CH 2 -Phenyl), 4.68 (d, J = 9.7 Hz, 1H, H1), (m, 4H,, O-CH 2 -Phenyl), 3.80 (dd, J = 10.9, 2.0 Hz, 1H, H6a), (m, 3H, H3, H4, H6b), (m, 2H, H2, H5) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ= 138.5, 138.4, 138.2, 133.9, (4 C1 -Benzyl, C1 -Phenyl), 129.0, 128.6, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, (C2 C5 Benzyl, Phenyl), 87.6 (C1), 86.9 (C6), 80.9 (C2), 79.2 (C5), 77.9 (C4), 75.9, 75.57, 75.20, (4 O-CH 2 - Phenyl), 69.2 (C3) ppm. HRMS-ESI + for [M + Na + ] C 40 H 40 NaO 5 S + (m/z): calc ; found S4

5 Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (3) 2 1,2,3,4,6-Penta-O-acetyl-D-glucopyranose (5 g, 12.8 mmol) and ethanthiol (1.14 ml, 15.4 mmol) were dissolved in dry CH 2 Cl 2 (25 ml) and BF 3 Et 2 O (7.89 ml, 64 mmol) was added slowly. The reaction mixture was stirred for 6 h, before poured into saturated aqueous NaHCO 3 solution and extracted with CH 2 Cl 2. The organic layer was dried over MgSO 4, filtrated and concentrated. Product 3 was obtained after column chromatography (3:1 hexane/etoac) as white solid (4.77 g, 95%). 1 H NMR (500 MHz, CDCl 3 ): δ = 5.22 (t, J = 9.4 Hz, 1H, H3), 5.08 (t, J = 9.8 Hz, 1H, H4), 5.03 (t, J = 10 Hz, H2), 4.49 (d, J = 10.1 Hz, 1H, H1), 4.24 (dd, J = 12.4 Hz, J = 5.0 Hz, 1H, H6), 4.13 (dd, J = 12.3 Hz, J = 2.3 Hz, 1H, H6), 3.70 (ddd, J = 10.1 Hz, J = 5.0 Hz, J = 2.4 Hz, 1H, H5), 2.70 (m, 2H, SCH 2 ), 2.07, 2.05, 2.02, 2.00 (4 s, 12H, 4 CH 3 ), 1.27 (t, J = 7.5 Hz, 1H, SCH 2 CH 3 ) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 170.8, 170.3, (CH 3 CO), 83.7 (C1), 76.0 (C5), 74.1 (C3), 69.9 (C2), 68.5 (C4), 62.3 (C6), 24.3 (SCH 2 CH 3 ), 20.9, 20.8, 20.7 (CH 3 CO), 14.9 (SCH 2 CH 3 ) ppm. HRMS-ESI + for [M + Na + ] C 16 H 24 NaO 9 S + (m/z): calc ; found ,3,4,6-Tetra-O-acetyl-D-glucopyranose (3a) 8 Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose 3 (10 mg, mmol) was dissolved in dry CH 2 Cl 2 (1.6 ml). MSH (27.4 mg, mmol) and K 2 CO 3 (6.9 mg, 0.05 mmol) were added and the reaction was stirred at room temperature for 16 h. The mixture was diluted with CH 2 Cl 2 and washed with saturated aqueous Na 2 CO 3 and NaCl solutions. The crude was purified by column chromatography (from 1:1 petroleum ether/etoac to EtOAc) to afford 3a (7 mg, 80%) as an inseparable α/β mixture as a white solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 5.54 (t, J = 9.8 Hz, 1H, H3), 5.47 (t, J = 3.4 Hz, 1H, H1), 5.26 (t, J = 9.5 Hz, 1H, H3 ), 5.09 (td, J = 9.7 Hz, J = 1.8 Hz, 1H, H4), 4.92 (dd, J = 10.2 Hz, J = 3.6 Hz, 1H, H2), 4.74 (t, J = 8.1 Hz, 1H, H4 ), (m, 1H, H5), (m, 2H, H6a/b), (m, 1H, OH), 2.10, 2.09, 2.04, 2.02 (4 CH 3 O) ppm. 13 C NMR (10 MHz, CDCl 3 ): δ = 170.9, 170.3, 170.2, (4 C(OCH 3 )), 90.4 (C1), 71.2 (C2), 69.9 (C3), 68.5 (C4), 62.1 (C6), 61.9 (C5), 20.9, 20.8, 20.7, 20.7 (4 CH 3 O) ppm. HRMS- ESI + for [M + Na + ] C 14 H 20 NaO + 10 (m/z): calc ; found S5

6 Ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranose (4) 2 To a solution of ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose 3 (300 mg, 764 µmol) in dry MeOH (4 ml), a NaOMe solution (30%, 420 µl) was added at room temperature and the reaction was stirred for 1 h, until all starting material was consumed as monitored by TLC. After neutralization with Dowex 5W (H + -form) for 10 min, the resin was removed by filtration and the solvent evaporated. The obtained ethyl thioglucopyranoside was used in the next step without further purification. Ethyl thioglucopyranoside (162 mg, 720 µmol) was dissolved in dry DMF (4 ml) and cooled to 10 ºC. Sodium hydride (60% in mineral oil, 241 mg, 7.20 mmol) was added and the mixture was stirred for 1 h while warming up to room temperature. Benzyl bromide (861 µl, 7.20 mmol) was added and the mixture was stirred for 15 h. The reaction was cooled down to 0 ºC and H 2 O (2 ml) was added slowly. The solution was extracted with CH 2 Cl 2 (3 10 ml) and the combined organic layers were washed with saturated NaCl solution (3 20 ml). After column chromatography (10:1 petroleum ether/etoac), ethyl 2,3,4,6-tetra-Obenzyl-1-thio-β-D-glucopyranose 4 was obtained (274 mg, 61% over two steps) as a white solid. 1 H NMR (400 MHz, CDCl 3 ): δ = (m, 18H, H-Benzyl), 7.17 (dd, J = 7.0, 2.6 Hz, 2H, H- Benzyl), 4.92 (d, J = 10.6 Hz, 2H, O-CH 2 -Phenyl), (m, 2H, O-CH 2 -Phenyl), 4.74 (d, J = 10.1 Hz, 1H, O-CH 2 -Phenyl), (m, 3H, O-CH 2 -Phenyl), 4.46 (d, J = 9.7 Hz, 1H, H1), (m, 1H, H4), (m, 2H, H6a/b), 3.61 (t, J = 9.4 Hz, 1H, H3), (m, 2H, H2, H5), (m, 2H, S-CH 2 CH 3 ), 1.33 (t, J = 7.4 Hz, 3H, S-CH 2 CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = , , , ( 4 C1 -Benzyl), 128.5, 128.3, 128.0, ( C2 -C5-Benzyl), 86.8 (C6a/b), 85.1 (C1), 78.2 (C3), 75.7 (CH 2 -OBenzyl), 75.6 (CH 2 -OBenzyl), 74.8 (CH 2 -OBenzyl), 73.5 (CH 2 -OBenzyl), 69.4 (C6), 69.1 (C4), 62.3 (S-CH 2 -CH 3 ), 15.2 (S-CH 2 - CH 3 ) ppm. HRMS-ESI + (m/z) for [M + H + ] C 36 H 41 O 5 S + : calc ; found ; for [M + Na + ] C 36 H 40 NaO 5 S + : calc ; found ,3,4,6-Tetra-O-benzyl-D-glucopyranose (4a) 9 S6

7 Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose 3 (10 mg, mmol) was dissolved in dry CH 2 Cl 2 (1.6 ml). MSH (18.4 mg, mmol) and K 2 CO 3 (4.7 mg, mmol) were added and the reaction was stirred at room temperature for 16 h. The mixture was diluted with CH 2 Cl 2 and washed with saturated aqueous Na 2 CO 3 and NaCl solutions. The crude was purified by column chromatography (2:1 petroleum ether/etoac) to afford 4a (10.2 mg, 60%) as an inseparable α/β mixture as a white solid. 1 H NMR (500 MHz, CDCl 3 ): δ = (m, 18H, H-Benzyl), 7.14 (ddd, J = 7.7, 5.7, 2.4 Hz, 2H, H-Benzyl), 5.23 (d, J = 3.5 Hz, 1H, H1), (m, 2H, O-CH 2 - Phenyl), (m, 2H, O-CH 2 -Phenyl), (m, 2H, O-CH 2 -Phenyl), 4.49 (d, J = 11.5 Hz, 2H, O-CH 2 -Phenyl), 4.03 (ddd, J = 10.2, 4.0, 2.1 Hz, 1H, H5), 3.96 (t, J = 9.3 Hz, 1H, H3), (m, 1H, H4), (m, 2H, H6a/b), (m, 1H, H2) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 138.8, 138.6, 138.3, (4 C1 -Benzyl), 128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128.1, 128.0, 127.8, (C2 -C5 -Benzyl), 91.5 (C1), 84.7, 83.3, 81.9, 80.2, 75.9, 75.2, 74.9, 73.7, 73.47, 70.52, 69.0, HRMS-ESI + for [M + Na + ] C 34 H 36 NaO + 6 (m/z): calc ; found Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-1-thio-α-D-mannopyranose (5a) 3 BF 3 Et 2 O (210 µl, 1.71 mmol) and thiophenol (72 µl, mmol) were added to a solution of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-fluoro-α-D-mannopyranoside (198 mg, 0.57 mmol) in dry CH 2 Cl 2 (8.2 ml) at room temperature. The reaction mixture was stirred at the same temperature for 48 h before solid Na 2 CO 3 was added and stirring continued for 10 min. The crude was then diluted with CH 2 Cl 2 and washed with saturated aqueous NaHCO 3 and brine. The combined organic layers were dried over MgSO 4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (from petroleum ether to 1:1 EtOAc/petroleum ether) to afford the product (170 mg, 75%) as a colorless syrup. R f (1:1 EtOAc/petroleum ether): H NMR (CDCl 3, 400 MHz): δ = (m, 5H, Ar), 5.67 (dd, J = 14.5 Hz, J = 1.4 Hz, H1), 5.46 (appt, J = 10.1 Hz, H4), 5.22 (ddd, J = 28.7 Hz, J = 10 Hz, J = 2.3 Hz, 1H, H3), 5.10 (ddd, J = 50.7 Hz, J = 2.3 Hz, J = 1.4 Hz, 1H, H2), (m, 1H, H5), 4.33 (dd, J = 12.1 Hz, J = 5.3 Hz, 1H, H6a), 4.12 (dd, J = 12.1 Hz, J = 2.3 Hz, 1H, H6b), 2.12, 2.08, 2.06 (s, 9H, 3 CH 3 OAc) ppm. 19 F NMR (CDCl 3, S7

8 376.5 MHz): δ = (ddd, J F,2 = 50.7 Hz, J F,3 = 28.7 Hz, J F,1 = 14.5 Hz, F-2). LRMS-TOF ES + for [M+Na + ] C 18 H 21 FNaO 7 S + (m/z): calc ; found Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-1-thio-β-D-mannopyranose (5b) 4 To a solution of 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-mannopyranosyl bromide 7 (98.7 mg, 0.26 mmol) in CHCl 3 (2.6 ml), was added a solution of tetrabutylammonium bromide (15.9 mg, mmol) in H 2 O (340 µl) followed by the addition of thiophenol (41 µl, 0.39 mmol). The mixture was cooled in an ice water bath and a solution of KOH (25 mg, 0.51 mmol) in H 2 O (340 µl) was added. After the addition was complete, the mixture was stirred overnight at room temperature. The organic phase was separated, washed with H 2 O, dried over MgSO 4 and concentrated. The residue was purified by column chromatography (from 4:1 to 1:1 hexane/etoac) to afford (76 mg, 73%) as a white solid. R f (1:1 EtOAc/hexane): H NMR (CDCl 3, 400 MHz): δ = 7.52 (m, 2H, Ar), 7.32 (m, 3H, Ar), 5.37 (appt, J = 10.0 Hz, 1H, H4), 5.06 (dd, J = 49.9 Hz, J = 2.7 Hz, 1H, H2), 4.98 (ddd, J = 26.8 Hz, J = 10.0 Hz, J = 2.7 Hz, 1H, H3), 4.86 (d, J = 26.8 Hz, 1H, H1), 4.27 (dd, J = 12.2 Hz, J = 6.0 Hz, 1H, H6a), 4.16 (dd, J = 12.2 Hz, J = 2.4 Hz, 1H, H6b), 3.69 (ddd, J = 10.0 Hz, J = 6.0 Hz, J = 2.4 Hz, 1H, H5), 2.11, 208, 2.04 (s, 9H, CH 3 OAc) ppm. 13 C NMR(CDCl 3, 400 MHz): δ = 170.8, 170.4, (3 C=O, Ac), (C, Ar), 132.2, 129.2, (3CH, Ac), (d, J 2,F = Hz, C2), 85.4 (d, J 1,F =18.2 Hz, C1), 76.4 (C5), 72.5 (d, J 3,F = 17.8 Hz, C3), 65.7 (C4), 62.7 (C6), 20.9, 20.8 (3 CH 3 OAc) ppm. 19 F NMR (CDCl 3, MHz): δ = (dt, J F,2 = 49.9 Hz, J F,1 = J F,3 =26.8 Hz, F-2). HRMS-TOF ES + for [M+Na + ] C 18 H 21 FNaO 8 S + (m/z): calc ; found Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-1-thio-α-D-glucopyranose (6a) BF 3 Et 2 O (160 µl, 1.3 mmol) and thiophenol (66 µl, mmol) were added to a solution of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-fluoro-α/β-D-glucopyranoside (151.8 mg, mmol) in dry CH 2 Cl 2 (5.2 ml) at room temperature. The reaction mixture was stirred at the same temperature for 48 h before solid Na 2 CO 3 was added and stirring continued for 10 min. The crude was then S8

9 diluted with CH 2 Cl 2 and washed with saturated aqueous NaHCO 3 and brine. The combined organic layers were dried over MgSO 4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (from hexane to 1:1 EtOAc/hexane) and recrystallized from EtOH to afford 6a (97 mg, 56%) as white needles. R f (1:1 EtOAc/hexane): H NMR (CDCl 3, 400 MHz): δ = 7.51 (m, 2H, Ar), 7.32 (m, 3H, Ar), 5.76 (dd, J = 5.9 Hz, J = 1.4 Hz, 1H, H1), 5.46 (dt, J = 12.3 Hz, J = 9.6 Hz, 1H, H3), 5.05 (appt, J = 9.6 Hz, 1H, H4), 4.83 (ddd, J = 50.0 Hz, J = 9.6 Hz, J = 5.9 Hz, 1H, H2), 4.61 (ddd, J = 10.2 Hz, J = 5.2 Hz, J = 2.2 Hz, 1H, H5), 4.30 (dd, J = 12.4 Hz, J = 5.2 Hz, 1H, H6a), 4.07 (dd, J = 12.4 Hz, J = 2.2 Hz, 1H, H6b), 2.09, 2.06, 2.05 (s, 9H, CH 3 OAc) ppm. 13 C NMR(CDCl 3, 400 MHz): δ = 170.7, 170.1, (3 C=O, Ac), (C, Ar), 132.4, 129.4, (3 CH, Ar), 87.0 (d, J 2,F = Hz, C2), 86.0 (d, J 1,F = 16.3 Hz, C1), 71.4 (d, J 3,F = 19.2 Hz, C3), 68.4 (C5), 68.2 (d, J 4,F =6.7 Hz, C4), 62.0 (C6), 20.9, 20.8, (3 CH 3 OAc) ppm. 19 F NMR (CDCl 3, MHz): δ = (dd, J F,2 =50.0 Hz, J F,3 =12.3 Hz, F- 2) ppm. HRMS-TOF ES + for [M+Na + ] C 18 H 21 FNaO 8 S + (m/z): calc ; found Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-1-thio-β-D-glucopyranose (6b) To a solution of 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide 7 (99.0 mg, 0.26 mmol) in CHCl 3 (2.6 ml), was added a solution of tetrabutylammonium bromide (16 mg, mmol) in H 2 O (338 µl) followed by the addition of thiophenol (40 µl, 0.39 mmol). The mixture was cooled in an ice water bath and a solution of KOH (26 mg, 0.52 mmol) in H 2 O (338 µl) was added. After the addition was complete, the mixture was stirred overnight at room temperature. The organic phase was separated, washed with H 2 O, dried over MgSO 4 and concentrated. The residue was purified by column chromatography (from 4:1 to 1:1 hexane/etoac) to afford (77.9 mg, 75%) as a white solid. 1 H NMR (CDCl 3, 400 MHz): δ = 7.57 (m, 2H, Ar), 7.34 (m, 3H, Ar), 5.32 (dt, J = 14.1 Hz, J = 9.2 Hz, 1H, H3), 4.95 (t, J = 9.8 Hz, 1H, H4), 4.69 (dd, J = 9.8 Hz, J = 1.5 Hz, 1H, H1), 4.19 (m, 2H, H6), 4.16 (dt, J = 49.5 Hz, J = 9.4 Hz, 1H, H2), 3.74 (ddd, J = 10.1 Hz, J = 4.5 Hz, J = 2.9 Hz, 1H, H5), 2.08, 2.06, 2.02 (s, 9H, 3 CH 3 OAc) ppm. 13 C NMR (CDCl 3, 100 MHz): δ = 170.7, 170.1, (3 CO, Ac), 134.4, 130.2, 129.2, (4C, Ar), 87.1, (d, J 2,F = Hz, C2), 84.3 (d, J 1,F =23.9Hz, C1), 75.9 (C5), 74.0 (d, J 4,F = 20.4 Hz, C4), 68.1 (d, J 3,F = 7.6 Hz, C3), 62.1 (C6), 20.9, 20.8, 20.7 (3 CH 3 OAc) ppm. 19 F NMR (CDCl 3, S9

10 376.5 MHz): δ = (dd, J F,2 = 49.9 Hz, J F,3 = 14.1 Hz, F-2) ppm. HRMS-TOF ES + for [M+Na + ] C 18 H 21 FNaO 8 S + (m/z): calc ; found ,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-1-O-sulfonylmesityl-α-D-mannopyranose (7) Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-1-thio-β-D-mannopyranose 5b (15 mg, mmol) was dissolved in dry CH 2 Cl 2 (2 ml). MSH (40.4 mg, mmol) and K 2 CO 3 (10.3 mg, mmol) were added and the reaction was stirred at room temperature for 16 h. The reaction mixture was diluted with CH 2 Cl 2 and washed with saturated aqueous Na 2 CO 3 and NaCl solutions. The organic layer was dried over MgSO 4, filtrated and concentrated. The crude was purified by column chromatography (2:1 petroleum ether/etoac) to afford 7 (8.1 mg, 44%) as a yellowish solid. 1 H NMR (500 MHz, CDCl 3 ): δ = 7.01 (s, 2H, H-Mes), 5.91 (dd, J = 6.3 Hz, J = 1.9 Hz, 1H, H1), 5.35 (t, J = 10.1 Hz, 1H, H4), (m, 1H, H3), (m, 1H, H2), 4.07 (dd, J = 12.6 Hz, J = 3.9 Hz, 1H, H6), (m, 1H, H5), 3.64 (dd, J = 12.6 Hz, J = 2.3 Hz, 1H, H6), 2.65 (s, 6H, CH 3 -Mes), 2.33 (s, 3H, CH 3 -Mes), 2.10, , 2.03 (3 s, 9H CH 3 CO) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 170.6, 169.9, (3 CH 3 CO), 144.4, (2 C4 -Mes), 132.1, (CH-Mes), 96.1 (d, J 1,F = 32.2 Hz, C1), 86.1 (d, J 2,F = Hz, C2), 71.3 (C5), 69.3 (d, J 3,F = 25.0 Hz, C3), 64.8 (C4), 60.8 (C6), 22.8, 21.3 (CH 3 -Mes), 20.77, (CH 3 CO) ppm. 19 F NMR (376 MHz, CDCl 3 ) δ (bs, F-2) ppm. HRMS-ESI + for [M + Na + ] C 21 H 27 FNaO 10 S + (m/z): calc ; found ,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-1-O-sulfonylmesityl-α/β-D-glucopyranose (8a,b) Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-1-thio-β-D-glucopyranose 6b (20 mg, 0.05 mmol) was dissolved in dry CH 2 Cl 2 (2 ml). MSH (53.8 mg, 0.25 mmol) and K 2 CO 3 (13.8 mg, 0.1 mmol) were added and the reaction was stirred at room temperature for 16 h. The reaction mixture was diluted with CH 2 Cl 2 and washed with saturated aqueous Na 2 CO 3 and NaCl solutions. The organic layer S10

11 was dried over MgSO 4, filtrated and concentrated. The crude was purified by column chromatography (from 3:1 to 2:1 petroleum ether/etoac) to afford 8a,b (18.6 mg, 76%) as an inseparable 7:1 α/β mixture as a yellowish solid. Data for 8a: 1 H NMR (400 MHz, CDCl 3 ): δ = 6.99 (s, 2H, H-Mes), 5.99 (d, J = 3.9 Hz, 1H, H1), (m, 1H, H3), 5.04 (dd, J = 19.9 Hz, J = 9.9 Hz, 1H, H4), (m, 2H, H2), 4.19 (dd, J = 12.6 Hz, J = 4.0 Hz, 1H, H6), (m, 1H, H5), 3.82 (dd, J = 12.6 Hz, J = 2.2 Hz, 1H, H6 ), 2.65 (s, 6H, 2 CH 3 -Mes), 2.31 (s, 3H, CH 3 -Mes), 2.05 (s, 6H, 2 CH 3 O), 2.03 (s, 3H, CH 3 O) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = 170.6, 169.9, (3 CH 3 CO), (p-c-mes), (C1-Mes), 132.0, (C4 -CH 3 Mes), 94.9 (d, J 1,F = 22.0 Hz, C1), 86.0 (d, J 2,F = Hz, C2), 70.2 (d, J 3,F = 20.0 Hz, C3), 69.9 (C5), 67.1 (C4) 60.7 (C6), 22.8 (2 CH 3 -Mes), 21.2 (CH 3 -Mes), 20.7, 20.6 (3 CH 3 O) ppm. 19 F NMR (376 MHz, CDCl 3 ) δ (ddd, J = 50.3, 14.7, 3.2 Hz, F-2). Data for 8b: 1 H NMR (400 MHz, CDCl 3 ): δ = 6.96 (s, 2H, H-Mes), 5.42 (dd, J = 7.6 Hz, J = 3.2 Hz, 1H, H1), (m, 1H, H3), 5.05 (t, J = 10.0 Hz, 1H, H3), (m, 1H, H4), (m, 2H, H2), 4.08 (dd, J = 12.4 Hz, J = 4.9 Hz, 1H, H6), 3.97 (dd, J = 12.4 Hz, J = 2.4 Hz, 1H, H6 ), 3.76 (ddd, J = 10.1 Hz, J = 4.9 Hz, J = 2.4 Hz, 1H, H5), 2.63 (s, 6H, 2 CH 3 -Mes), 2.32 (s, 3H, CH 3 -Mes), 2.04 (s, 6H, 2 CH 3 O), 2.01 (s, 3H, CH 3 O) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = 169.9, 169.6, (3 CH 3 CO), (p-c-mes), (C1-Mes), 132.0, (C4 -CH 3 Mes), (d, J 1,F = 25.1 Hz, C1), 88.1 (d, J 2,F = Hz, C2), 72.5 (d, J 3,F = 20.0 Hz, C3), 69.9 (C5), 67.6 (d, J 4,F = 10.0 Hz, C4), 61.4 (C6), 22.8 (2 CH 3 -Mes), 21.2 (CH 3 -Mes), , 20.6 (3 CH 3 O) ppm. 19 F NMR (376 MHz, CDCl 3 ) δ (dd, J = 48.3, 11.8 Hz, F-2). HRMS-ESI + for [M + Na + ] C 21 H 27 FNaO 10 S + (m/z): calc ; found Ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyranoside (14) 2, 6 To a solution of ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside (2.50 g, 6.37 mmol) in dry MeOH (30 ml), a NaOMe solution (30%, 3.13 ml) was added at room temperature and the reaction was stirred until the complete consumption of the starting material as monitored by TLC. The mixture was neutralized with Dowex 50W (H + form). The resin was removed by filtration and the reaction was concentrated. Ethyl thiogalactopyranoside was used without further purification. S11

12 Ethyl thiogalactopyranoside (1.44 g, 6.42 mmol) was dissolved in dry DMF (24 ml) and cooled to 10 ºC. Sodium hydride (60% in mineral oil, 2.15 g, 64.2 mmol) was added and the reaction was stirred for 1 h, while warming up to room temperature. Benzyl bromide (7.63 ml, 64.2 mmol) was added and the mixture was stirred overnight. H 2 O (30 ml) was added carefully at 0 ºC and the aqueous layer was extracted with EtOAc (3 50 ml). The combined organic layers were washed with NaCl solution (3 30 ml) and dried over MgSO 4. After column chromatography (10:1 petroleum ether/etoac), ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyranoside 14 was obtained (3.8 g, 60% over two steps) as a yellowish oil. 1 H NMR (400 MHz, CDCl 3 ): δ = (m, 20H, H-Benzyl), 4.95 (d, J = 11.7 Hz, 1H, CH 2 Benzyl), 4.88 (d, J = 10.2 Hz, 1H, CH 2 Benzyl), 4.80 (d, J = 10.1 Hz, 1H, CH 2 Benzyl), 4.73 (s, 2H, CH 2 Benzyl), (m, 1H, CH 2 Benzyl), 4.43 (d, J = 9.1 Hz, 3H, CH 2 Benzyl, H1), 3.96 (d, J = 2.8 Hz, 1H, H4), 3.83 (t, J = 9.4 Hz, 1H, H2), 3.58 (dtd, J = 12.2 Hz, J = 7.4 Hz, J = 6.8 Hz, J = 4.5 Hz, 4H, H3, H5, H6a/b), (m, 2H, SCH 2 CH 3 ), 1.30 (t, J = 7.4 Hz, 3H, SCH 2 CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = 138.9, 138.5, 138.4, 138.0, 128.6, 128.5, 128.3, 128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, (C-Benzyl), 85.5 (C1), 84.3 (C5), 78.6 (C2), 75.9 (CH 2 Benzyl), 74.6 (CH 2 Benzyl, C3), 73.7 (C4, CH 2 Benzyl), 72.8 (CH 2 Benzyl), 68.9 (C6), 24.9 (SCH 2 CH 3 ), 15.2 (SCH 2 CH 3 ) ppm. HRMS-ESI + for [M + Na + ] C 36 H 40 NaO 5 S + (m/z): calc ; found ,3,4,6-Tetra-O-benzyl-D-glucopyranosyl-(1 6)-1,2:3,4-di-O-isopropylidene-Dgalactopyranoside (15) 12 1,2:3,4-Di-O-isopropylidene-α-D-galactopyranose 9 (11.5 mg, mmol) was dissolved in dry CH 3 CN (2 ml) and stirred over 3 Å molecular sieves for 30 min. Cu(OTf) 2 (18.4 mg, mmol) was added for 10 min, followed by the addition of 4 (20 mg, mmol). MSH (36.6 mg, 0.17 mmol) was added and the reaction was stirred at room temperature. TLC monitoring showed a completion of the reaction after 15 min. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (5:1 petroleum ether/etoac) to afford 15 (24.5 mg, 71%) as an S12

13 inseparable 1:5 α/β mixture as a yellowish solid. 1 H NMR (500 MHz, CDCl 3 ): δ = (m, 2H, H-Aryl), (m, 20H, H-Aryl), (m, 3H, H-Aryl), 5.57 (d, J = 5.0 Hz, 1H, H1 Glc ), 5.52 (d, J = 5.0 Hz, H1α Glc ), 5.05 (d, J = 11.1 Hz, 1H, OCH 2 -Benzyl), 4.96 (d, J = 11.0 Hz, 1H, OCH 2 -Benzyl), (m, 4H, OCH 2 -Benzyl), (m, 2H, OCH 2 -Benzyl), (m, 1H, H3 Glc ), 4.46 (dd, J = 7.5 Hz, J = 2.4 Hz, 1H, H1 Gal ), 4.32 (dd, J = 5.0 Hz, J = 2.4 Hz, 1H, H2 Glc ), 4.25 (dd, J = 7.9, 1.9 Hz, 1H, H4 Glc ), 4.16 (dd, J = 10.7, J = 3.7 Hz, 1H, H6 Glc ), 4.09 (ddd, J = 7.5, J = 3.6 Hz, J = 1.8 Hz, 2H, H5), (m, 3H, H4 Gal, H6a/b Gal ), (m, 1H, H5 Gal ), (m, 2H, H2 Gal, H3 Gal ), 1.50, 1.45, 1.32, 1.26 (4 s, 4 CH 3 ) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 143.3, 140.7, 138.9, 138.3, 128.8, 128.4, 128.1, 128.0, 127.9, 127.8, 127.7, (12 C-Aryl), (C(CH 3 ) 2 ), (C(CH 3 ) 2 ), (C1 Gal ), 96.5 (C1 Glc ), 84.8 (C2 Gal ), 81.6 (C2/3 Gal ), 77.1, 76.5, 75.7, 75.1 (4 CH 2 -Aryl), 74.4 (C2/3 Gal ), 73.5, 71.5 (C4 Glc ), 70.8 (C3 Glc ), 70.5 (C2 Glc ), 69.7 (C5 Glc ), 68.7 (C6 Gal ), 67.4 (C6 Glc ), 29.9, 26.2, 25.2, 24.6 (4 CH 3 ) ppm. HRMS- ESI + for [M + Na + ] C 46 H 54 NaO + 11 (m/z): calc ; found ,3,4,6-Tetra-O-benzyl-D-glucopyranosyl-(1 3)-1-O-methyl-2,4,6-tri-O-benzyl-α-Dmannopyranoside (16) 10 A solution of methyl 2,4,6-tri-O-benzyl-α-D-mannopyranoside 10 (20.4 mg, mmol), Cu(OTf) 2 (18.4 mg, mmol), and 4 (20 mg, mmol) in dry toluene (1.5 ml) was stirred over 3 Å molecular sieves for 10 min. A solution of MSH (36.6mg, 0.17 mmol) in dry toluene (0.5 ml) was added and the reaction was stirred overnight at room temperature. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (19:1 toluene/etoac) to afford 16 (13.4 mg, 40%) as a colorless oil. 1 H NMR (500 MHz, CDCl 3 ): δ = (m, 35H), 5.18 (d, J = 3.5 Hz, 1H, H1 ), 5.08 (d, J = 11.5 Hz, 1H, OCH 2 Bn), 4.92 (d, J = 10.9 Hz, 1H, OCH 2 Bn), 4.83 (d, J = 11.0 Hz, 1H, OCH 2 Bn), (m, 2H, OCH 2 Bn, H1), 4.68 (d, J = 11.9 Hz, 1H, OCH 2 Bn), (m, 9H, OCH 2 Bn), 4.13 (dd, J = 9.2, 3.1 Hz, 1H, H3), 4.09 (t, J = 9.4 Hz, 1H, H3 ), (m, 2H, H5, H4), 3.89 (dd, J = 3.1, 2.0 Hz, 1H, H2), 3.78 (ddd, J = 9.5, 4.9, 2.2 Hz, 1H, H5), (m, 2H, H6), 3.61 (t, J = 9.5 Hz, 1H, H4), (m, 3H, H2, S13

14 H6 ) 3.34 (s, 3H, OCH 3 ) ppm. HRMS-ESI + for [M + Na + ] C 62 H 66 NaO 11 + (m/z): calc ; found Table S1. Solvent optimization for secondary glycosyl acceptors entry solvent t (h) yield (%) a α/β ratio b,c 1 CH 3 CN 1 0 d 2 Et 2 O 3 9 >20:1 3 CH 2 Cl >20:1 4 CH 2 Cl 2 o/n 17 >20:1 5 toluene 1 22 >20:1 6 toluene o/n 40 >20:1 a Isolated yield. b Determined by integration of the anomeric proton signals in the 1 H NMR spectrum of the crude reaction mixture. c Only the α- anomer was detected after purification by SiO 2 flash column chromatography. d Hydrolysis product 4a (75%) was obtained. 2,3,4,6-Tetra-O-benzyl-D-glucopyranosyl-(1 4)-1-O-methyl-2,3,6-tri-O-benzyl-α-Dglucopyranoside (17) 11 A solution of methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside 11 (20.4 mg, mmol), Cu(OTf) 2 (18.4 mg, mmol), and 4 (20 mg, mmol) in dry toluene (1.5 ml) was stirred over 3 Å molecular sieves for 10 min. A solution of MSH (36.6mg, 0.17 mmol) in dry toluene (0.5 ml) was added and the reaction was stirred overnight at room temperature. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (19:1 toluene/etoac) to afford 17 (7.3 mg, 22%) as an inseparable 1.2:1 α/β mixture as a colorless oil. 1 H NMR (500 MHz, CDCl 3 ): δ = 1H NMR (500 MHz, Chloroform-d) δ (m, 77H), 5.69 (d, J = 3.7 Hz, 1H, H1 a), 5.09 (m, 2H), 5.02 (d, J = 11.6 Hz, 1H), 4.91 (d, J = 11.0 Hz, 1H), (m, 2H), (m, 11H), (m, 3H), 4.60 (d, J = 3.9 Hz, 1H, H1a), 4.59 (d, J = 3.5 Hz, 1H, H1b), (m, 2H), (m, 5H), (m, 6H), (m, 2H), 4.38 (d, J = 7.7 Hz, 1H, H1 b), 4.08 (t, J = 9.1 Hz, 1H), 4.04 (t, J = 9.0 Hz, 1H), 3.96 (dd, J = 10.0, 9.0 Hz, 1H), S14

15 3.90 (dd, J = 9.9, 8.8 Hz, 1H), (m, 4H), (m, 2H), (m, 5H), (m, 1H), (m, 4H), 3.37 (s, 4H), 3.36 (s, 3H), 3.29 (ddd, J = 9.9, 4.8, 1.8 Hz, 1H). ppm. HRMS-ESI + for [M + Na + ] C 62 H 66 NaO 11 + (m/z): calc ; found Cholesteryl 2,3,4,6-tetra-O-benzyl-β-D-glucopyranoside (18) 13 Cholesterol 12 (17.2 mg, mmol) was dissolved in dry CH 3 CN (2 ml) and stirred over 3 Å molecular sieves for 30 min. Cu(OTf) 2 (18.4 mg, mmol) was added for 10 min, followed by the addition of 4 (20 mg, mmol). MSH (36.6 mg, 0.17 mmol) was added and the reaction was stirred at room temperature. TLC monitoring showed a completion of the reaction after 15 min. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (5:1 petroleum ether/etoac) to afford 18 (10.2 mg, 35%) as an inseparable 1:3.7 α/β mixture as a yellowish solid. 1 H NMR (500 MHz, CDCl 3 ): δ = (m, 18H, H-Benzyl), (m, 2H, H-Benzyl), 5.34 (dd, J = 4.7 Hz, J = 2.6 Hz, 1H, CH = ), 4.97 (d, J = 10.9 Hz, 1H, CH 2 Benzyl), 4.92 (d, J = 11.0 Hz, 1H, CH 2 Benzyl ), (m, 2H, CH 2 Benzyl), 4.71 (d, J = 10.9 Hz, 1H, CH 2 Benzyl), (m, 2H, CH 2 Benzyl), 4.50 (d, J = 7.8 Hz, 1H, H1), 3.73 (dt, J = 10.7 Hz, J = 2.9 Hz, 1H, H6a), (m, 3H, H3, H5,6b), (m, 1H, H4), (m, 1H, H2), (m, 6H), (m, 1H), (m, 13H), (m, 4H), 1.03 (s, 3H), 0.92 (d, J = 6.5 Hz, 4H), (m, 6H), 0.68 (s, 3H). 13 C NMR (126 MHz, CDCl 3 ): δ = 138.8, 138.7, 138.4, 138.3, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, (C-Benzyl), 121.9, (C1), 84.9 (C3), 82.4 (C2), 79.8 (C4), 75.5, 73.3, 69.2 (C5), 69.0 (C6), 56.9, 56.3, 50.3, 42.5, 39.6, 39.3, 37.4, 36.9, 36.3, 35.9, 32.1, 29.8, 28.4, 28.1, 24.4, 23.9, 22.9, 22.7, 21.2, 19.5, 18.9, 12.0 ppm. S15

16 2,3,4,6-Tetra-O-benzyl-glucopyranosyl-(1)-Boc-L-serine methyl ester (19) Boc-L-serine methyl ester 13 (9.65 mg, mmol) was dissolved in dry CH 3 CN (2 ml) and stirred over 3 Å molecular sieves for 30 min. Cu(OTf) 2 (18.4 mg, mmol) was added for 10 min, followed by the addition of 4 (20 mg, mmol). MSH (36.6 mg, 0.17 mmol) was added and the reaction was stirred at room temperature. TLC monitoring showed a completion of the reaction after 15 min. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (5:1 petroleum ether/etoac) to afford 19 (12.6 mg, 50%) as an inseparable 1:2.2 α/β mixture as a colorless oil. 1 H NMR (500 MHz, CDCl 3 ): δ = (m, 2H, H-Benzyl), (m, 15H, H-Benzyl), 7.14 (ddd, J = 8.9 Hz, J = 4.8 Hz, J = 2.8 Hz, 2H, H-Benzyl), 5.64 (d, J = 8.7 Hz, NHα), 5.45 (d, J = 8.6 Hz, 1H, NHβ), 4.93 (d, J = 11.3 Hz, 1H, CH 2 Benzyl), 4.86 (d, J = 10.9 Hz, 1H, CH 2 Benzyl), (m, 2H, CH 2 OCNH,), 4.76 (d, J = 3.7 Hz, H1α), 4.69 (dd, J = 11.4 Hz, J = 4.2 Hz, 1H, CH 2 Benzyl), (m, 2H, CH 2 Benzyl), (m, 2H, CH 2 Benzyl)) 4.48 (s, 1H, CHNH α) 4.37 (d, J = 7.8 Hz, 1H, H1), 3.90 (t, J = 9.3 Hz, 1H, H3α), 3.73 (s, 3H, CH 3 ), (m, 5H, H2, H4, H5, H6ab), 1.43 (s, 9H, (CH 3 ) 3 C) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 170.9, 138.2, 131.8, 128.6, 128.1, 127.9, 127.7, (C-Benzyl), (C1β), 98.5 (C1α), 84.5 (C5, C6), 81.9 (C2), 77.3 (C3), 77.0 (C5, C6), 75.7 (CH 2 Benzyl), 75.2 (CH 2 CN), 75.0 (CH 2 Benzyl), 74.9 (CH 2 Benzyl), 74.8 (C4), 69.8 (C4α, C5α), 68.45, 52.7 (CH 3 O), 29.8, 28.5 (CH 3 ) ppm. HRMS-ESI+ for [M + Na + ] C 43 H 51 NaNO + 10 (m/z): calc ; found ,3,4,6-Tetra-O-benzyl-D-galactopyranosyl-(1 6)-1,2:3,4-di-O-isopropylidene-Dgalactopyranoside (20) 1,2:3,4-Di-O-isopropylidene-α-D-galactopyranose 9 (11.5 mg, mmol) was dissolved in dry CH 3 CN (2 ml) and stirred over 3 Å molecular sieves for 30 min. Cu(OTf) 2 (18.4 mg, mmol) S16

17 was added for 10 min, followed by the addition of 14 (20 mg, mmol). MSH (36.6 mg, 0.17 mmol) was added and the reaction was stirred at room temperature. TLC monitoring showed a completion of the reaction after 15 min. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (5:1 petroleum ether/etoac) to afford 20 (17.2 mg, 50%) as an inseparable 1:2.9 α/β mixture as a white solid. 1 H-NMR (500 MHz, CDCl 3 ): δ = (m, 3H, H-Phenyl), (m, 17H, H-Phenyl), 5.55 (d, J = 5.0 Hz, 1H, H1β), 5.51 (d, J = 5.0 Hz, H1α), 5.04 (d, J = 11.0 Hz, 1H, CH 2 Benzyl), 5.00 (d, J = 3.7 Hz, H1 α), (m, 5H, CH 2 Benzyl), (m, 3H, CH 2 Benzyl, H3), (m, 1H, H1 β), (m, 1H, H2), 4.21 (dd, J H4/H3 = 7.9 Hz, J = 1.9 Hz, 1H, H4), 4.12 (dd, J = 10.6 Hz, J = 3.7 Hz, 1H, H6), (m, 1H, H6), 3.82 (dd, J H2 /H1 = 9.8 Hz, J = 7.7 Hz, 1H, H2 ), 3.68 (dd, J = 10.6 Hz, J = 7.5 Hz, 1H, H5), , (m, 4H, H3, H4, H5, H6 ), 1.49, 1.43, 1.30 (3 s, 12H, CH 3 ) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 128.7, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.6, 127.5, (C-Benzyl), 109.5, ((CH 3 ) 2 C), (C1 ), 96.5 (C1), 74.9, 74.6, 73.4 (CH 2 ), 73.4 (C2 ), 73.2 (C3, C4, C5,C6 ), 71.6 (C4), 70.7 (C3, C2), 69.6 (C6), 68.9 (C5), 26.1, 26.0, 24.7 (CH 3 ) ppm. HRMS-ESI + for [M + Na + ] C 46 H 54 NaO + 11 (m/z): calc ; found Control experiment for the activation of thioglycosides with MSH vs. Cu(OTf) 2 Ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucose 4 (33.3 mg, mmol) and 1,2:3,4-di-Oisopropylidene-α-D-galactopyranose 9 (10 mg, mmol) were dissolved in Et 2 O (2.5 ml) and stirred over 3 Å molecular sieves and Cu(OTf) 2 (30.9 mg, 0.086) for 16 h from 20 ºC to room temperature. The reaction was monitored by TLC (5:1 petroleum ether/etoac) and no disaccharide 15 was detected during the whole reaction time. After 16 h, MSH (41 mg, 0.19 mmol) was added and disaccharide 15 was detected instantaneously. S17

18 MSH addition product Figure S1. TLC (5:1 petroleum ether/etoac) pictures of the control experiment Control experiment for the glycosylation of intermediate (8a,b) with MeOH 3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-1-O-sulfonylmesityl-α/β-D-glucopyranose 8a,b (7:1 α/β) (10 mg, 0.02 mmol) was dissolved in dry CH 3 CN (0.5 ml) and stirred over 3 Å molecular sieves for 10 min. Anhydrous MeOH (10 µl, 0.24 mmol) was added for 5 min, followed by the addition of Cu(OTf) 2 (10.9 mg, 0.03 mmol). After 16 h stirring at room temperature, the solvent was evaporated and the residue redissolved in EtOAc. The organic layer was washed with water (3x), dried with MgSO 4, filtered, and concentrated. The crude was purified by column chromatography (2:1 petroleum ether/etoac) to afford (6.5 mg, 99%) as an inseparable 1:1 mixture of S1 24 /S2 as a yellowish syrup. 1 H NMR (CDCl 3, 400 MHz): δ = 5.37 (dt, J = 14.5, 9.3 Hz, 1H, H3-S2), 5.32 (dt, J = 14.6, 9.3 Hz, 2H, H3-S1), 5.04 (t, J = 9.8 Hz, 1H, H4-S1), 5.00 (t, J = 9.7 Hz, 2H, H4-S2), 4.53 (dd, J = 7.7, 2.7 Hz, 1H, H1-S2), 4.50 (dd, J = 7.7, 2.7 Hz, 1H, H1-S1), (m, 3H, H2, H6a-S1), 4.14 (dd, J = 12.4, 2.4 Hz, 1H, H6b-S2), 3.78 (d, J = 12.6 Hz, 1H, H6a-S2), 3.72 (ddd, J = 10.2, 4.7, 2.4 Hz, 1H, H5-S1), 3.59 (t, J = 3.8 Hz, 7H, OMe, H6b-S2), 3.54 (ddd, J = 9.9, 4.4, 2.3 Hz, 1H, H5-S2), 2.09 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.03 (s, 3H, OAc) ppm. 13 C NMR (CDCl 3, 126 MHz): δ = 170.8, 170.4, 170.2, 170.2, 169.7, (d, J 1,F = 22.8 Hz, C1), 89.7 (d, J 2,F = Hz, C2-S2), 89.5 (d, J 2,F = Hz, C1-S1), 74.1 (C5- S2), 73.0 (d, J 3,F = 19.8 Hz, C3-S2), 72.8 (d, J 3,F = 20.0 Hz C3-S1), 71.9 (C5-S1), 68.6 (d, J 4,F = 7.3 Hz, C4-S2), 68.3 (d, J 4,F = 7.5 Hz, C4-S1), 61.9 (C6-S1), 61.2 (C6-S2), 57.5 (OMe), 20.9, 20.8, 20.8, 20.7 (5 x CH 3 OAc) ppm. 19 F NMR (CDCl 3, MHz): δ = (ddd, J 2,F = 50.5, J 3,F = 14.7, J 1,F = 2.6 Hz, F2-S1), (ddd, J 2,F = 50.5, J 3,F = 14.5, J 1,F = 2.5 Hz, F2-S2) ppm. S18

19 HRMS-TOF ES + for S1 [M+Na + ] C 13 H 19 FNaO 8 + (m/z): calc ; found HRMS-TOF ES + for S2 [M+Na + ] C 11 H 17 FNaO 8 + (m/z): calc ; found Phenyl 2,3,4-tri-O-benzyl-1-thio-β-D-glucose (21) 7 To a solution of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose 1 (170 mg, mmol) in dry MeOH (1.2 ml), a NaOMe solution (30%, 230 µl) was added at room temperature and the reaction was stirred for 1 h, until all starting material was consumed as monitored by TLC (2:1 petroleum ether/etoac). After neutralization with Dowex 5W (H + -form) for 10 min, the resin was removed by filtration and the solvent evaporated. The obtained phenyl thioglucopyranoside was used in the next step without further purification. Phenyl thioglucopyranoside (106 mg, mmol) and trityl chloride (109 mg, mmol) were dissolved in pyridine (1 ml) and stirred at room temperature. After 16 h, trityl chloride (70 mg, 0.25 mmol) was added. After 22 h, the reaction mixture was poured into water and extracted with CH 2 Cl 2. The organic layers were washed with water, dried over MgSO 4, filtrated and concentrated. The crude phenyl-6-o-tritylthioglucopyranose was dissolved in anhydrous DMF (2 ml) and cooled to 0 C. NaH (60% in mineral oil, 62.6 mg, 1.87 mmol) was added and the mixture was stirred for 30 min. Benzyl bromide (0.22 ml, 1.87 mmol) was added and the reaction was stirred overnight from 0 ºC to room temperature. The reaction mixture was cooled again and H 2 O (2 ml) were added carefully. The reaction was extracted with CH 2 Cl 2 (3 x 10 ml), the combined organic layers were washed with saturated NaCl (3 x 10 ml), and dried over MgSO 4. After filtration and concentration, the crude product was directly used for the next step without further purification. Phenyl tri-o-benzyl-6-otrityl-1-thio-β-d-glucopyranose was dissolved in 4:1 MeOH/CH 2 Cl 2 and p-tsoh (37.1 mg, mmol) was added. After 24 h, TLC showed complete consumption of the starting material. The mixture was neutralized with Et 3 N and the solvent evaporated. The final compound was purified by column chromatography (from 6:1 petroleum ether/etoac to EtOAc) to afford 21 (63.1 mg, 51% overall) as a white solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 7.51 (dt, J = 4.4 Hz, J = 2.4 Hz, 2H, Bn/SPh), (m, 18H, Bn/SPh), (m, 4H, 2 CH 2 Ph), 4.77 (d, J = 10.3 Hz, 1H, CH 2 Ph), 4.72 (d, J = 9.8 Hz, 1H, H1), 4.65 (d, J = 11.0 Hz, 1H, CH 2 Ph), 3.88 (dd, J = 12.0 Hz, J = 2.6 Hz, 1H, H6), (m, 2H, H6, H3), 3.58 (t, J = 9.4 Hz, 1H, H4), (m, 1H, S19

20 H2), 3.39 (ddd, J = 9.6 Hz, J = 4.9 Hz, J = 2.7 Hz, 1H, H5) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ =139.2, 138.4, 138.0, (4 C4 in Ph), 132.0, 129.2, 128.7, 128.6, 128.5, 128.4, 128.2, 128.1, 128.0, (CH in Ph), 87.4 (C1), 86.7 (C3) 81.2 (C2), 79.4 (C5), 77.8 (C4), 75.9, 75.7, 75.2 (4 PhCH 2 ), 62.5 (C6). HRMS-ESI + (m/z) C 33 H 34 O 5 S: calc. [M + Na + ] = ; found [M + Na + ] = Phenyl 6-O-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2,3,4-tri-O-benzyl-β-Dthioglucopyranoside (22) 14 Phenyl 2,3,4-tri-O-benzyl-1-thio-β-D-glucose 21 (23.8 mg, mmol) was dissolved in dry CH 3 CN (2 ml) and stirred over 3 Å molecular sieves for 30 min. Cu(OTf) 2 (18.4 mg, mmol) was added for 10 min, followed by the addition of 4 (20 mg, mmol). MSH (36.6 mg, 0.17 mmol) was added and the reaction was stirred at room temperature. TLC monitoring showed a completion of the reaction after 15 min. The reaction mixture was filtered through Celite and the organic layer was washed with saturated solutions of Na 2 CO 3 and NaCl. The crude was purified by column chromatography (3:1 petroleum ether/etoac) to afford 22 (18.1 mg, 50%) as a yellowish solid. 1 H NMR (500 MHz, CDCl 3 ): δ = 7.54 (d, J = 7.5 Hz, 2H), (m, 38H, H-Phenyl,), (m, 20H), 4.40 (d, J = 7.7 Hz, 1H, H1 ), 4.17 (d, J = 11.1 Hz, 1H), (m, 8H), (m, 4H) ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 139.1, 138.9, 138.8, 138.7, 138.6, 138.6, 138.4, 138.3, 138.2, 135.4, 134.2, 132.3, 131.6, 129.1, 128.7, 128.6, 128.5, 128.4, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.8, 127.6, 127.6, 127.5, 127.4, (C1 ), 97.6 (C1), 88.3, 87.5, 86.9, 84.9, 82.5, 81.9, 81.3, 81.0, 80.3, 79.1, 78.2, 75.9, 75.6, 75.2, 75.1, 74.9, 73.7, 69.1, 68.8 ppm. HRMS-ESI + for [M + Na + ] C 67 H 68 NaO 10 S + (m/z): calc ; found S20

21 2,3,4,6-Tetra-O-benzyl-β-D-glucopyranosyl-(1 6)-2,3,4-tri-O-benzyl-β-D-glucopyranosyl- 15, 16 (1 6)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranoside (23) 1,2:3,4-Di-O-isopropylidene-α-D-galactopyranose 9 (4.7 mg, mmol) and 22 (6.4 mg, mmol) were dissolved in dry CH 3 CN (2 ml) and stirred over 3 Å molecular sieves for 10 min. NBS (3.2 mg, mmol) was added. After 5 min, Cu(OTf) 2 (1.63 mg, mmol) was added. The reaction was stirred at room temperature for 16 h before being filtered through Celite. The concentrated crude was purified by column chromatography (from 3:1 petroleum ether/etoac to EtOAc) to afford 23 (4 mg, 50%) as an inseparable 1:1 α/β mixture as a yellowish solid. 1 H NMR (500 MHz, CDCl 3 ): δ = , 5.54 (d, J = 4.8 Hz, 1H, H1 c ), 5.52 (d, J = 5.0 Hz, 1H, H1 c ), 5.12, 5.05, 4.94, , , 4.42 (d, J = 7.8 Hz, 1H, H1 b ), 4.40 (d, J = 7.8 Hz, 1H, H1 a ), , , , 4.24, , , , , 1.53, 1.37 ppm. 13 C NMR (126 MHz, CDCl 3 ): δ = 138.8, 138.5, 138.3, 138.2, 128.7, 128.5, 128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.4, 109.6, 109.3, 108.9, 108.5, (C1 b ), (C1 a ), 96.4 (C1 c ), 96.3 (C1 c ), 84.8, 84.5, 81.8, 81.5, 75.7, 75.6, 71.3, 70.8, 70.7, 70.6, 70.5, 70.4, 70.3, 68.1, 67.4, 67.3, 66.9, 26.0, 25.9, 24.9, 24.3 ppm. HRMS-ESI + for [M + Na + ] C 73 H 82 NaO + 16 (m/z): calc ; found S-acetyl-2,3,4,6-tetra-O-benzyl-β-D-glucopyranose (S3) 17 The reaction was performed under dry conditions with 3 Å molecular sieves and argon atmosphere. Ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranose 4 (10 mg, mmol) was dissolved in dry CH 2 Cl 2 (2 ml) and MSH (11.8 mg, mmol) was added at room temperature. After 10 min, a solution of potassium thioacetate (2.97 mg, mmol) and 18-crown-6 (5.6 µl, mmol) was added to the mixture and the reaction was stirred for 24 h. The reaction was filtered through Celite and the organic layer was washed with saturated Na 2 CO 3 solution (3 3 ml) and saturated S21

22 NaCl solution (3 ml). The crude was purified by column chromatography (from 3:1 petroleum ether/etoac to EtOAc) to afford S3 (3.56 mg, 35%) as a yellowish solid. 1 H NMR (400 MHz, CDCl 3 ): δ = (m, 17H, H-Phenyl), (m, 3H, H-Phenyl), 5.16 (d, J 1,2 = 10.2 Hz, 1H, H1), 4.87, , 4.77, 4.62, , 4.48 (8H, CH 2 Benzyl), (m, 5H, H2, H3, H4, H5, H6a,b), 2.37 (s, 3H, CH 3, SAc) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = (C=O), 128.4, , 127.8, (C-Phenyl), 86.82, 81.7, 80.3, 75.7, 75.3, 74.9, 73.5, 70.40, (C1/2/3/4/5/6, 4 CH 2 Benzyl), 29.7 (CH 3, SAc) ppm. HRMS-ESI + (m/z) for [M + H + ] C 36 H 41 O 5 S + : calc ; found ; for [M + Na + ] C 36 H 38 NaO 6 S + : calc ; found S22

23 2.2. Kinetic studies by 1 H NMR All reactions were performed directly in the NMR tube. The NMR of the pure starting material was measured directly before the addition of MSH and K 2 CO 3. All reaction were performed at room temperature and the mixtures were slightly shaken between the measurements. For the kinetic calculations the peak of the anomeric proton H1 of the starting material was used as internal reference with the value 1. The reaction progress was measured, calculating the ratio of the anomeric proton H1 of the intermediate to the starting material. Table S2. 1 H NMR kinetic studies Ac 4 Glc-SPh 1 Bn 4 Glc-SPh 2 Ac 4 Glc-SEt 3 Bn 4 Glc-SEt 4 M [g/mol] n compound [mmol} m compound [mg] m K2CO3 [mg] n K2CO3 [mmol] m MSH [mg] n MSH [mmol] V CDCl3 [ml] S23

24 Figure S2. Progress of the reaction of thioglycoside 1 with MSH by 1 H NMR (CDCl 3, 400 MHz) Figure S3. Progress of the reaction of thioglycoside 2 with MSH by 1 H NMR (CDCl 3, 400 MHz) S24

25 Figure S4. Progress of the reaction of thioglycoside 3 with MSH by 1 H NMR (CDCl 3, 400 MHz) Figure S5. Progress of the reaction of thioglycoside 4 with MSH by 1 H NMR (CDCl 3, 400 MHz) S25

26 2.3. Computational details Full geometry optimizations were carried out with Gaussian using the M06-2X hybrid functional 19 and 6-31G(d,p) basis set. Bulk solvent effects in dichloromethane were considered implicitly through the IEF-PCM polarizable continuum model. 20 The possibility of different conformations was taken into account for all structures. All stationary points were characterized by a frequency analysis performed at the same level used in the geometry optimizations from which thermal corrections were obtained at K. The quasiharmonic approximation reported by Truhlar et al. was used to replace the harmonic oscillator approximation for the calculation of the vibrational contribution to enthalpy and entropy. 21 Scaled frequencies were not considered. Massweighted intrinsic reaction coordinate (IRC) calculations were carried out by using the Gonzalez and Schlegel scheme 22,24 in order to ensure that the TSs indeed connected the appropriate reactants and products. Gibbs free energies (ΔG) were used for the discussion on the relative stabilities of the considered structures. Free energies calculated using the gas phase standard state concentration (1 atm = 1/24.5 M) were converted to reproduce the standard state concentration in solution (1 M) by adding or subtracting 1.89 kcal mol 1 for bimolecular additions and decompositions, respectively. Cartesian coordinates, electronic energies, entropies, enthalpies, Gibbs free energies, and lowest frequencies of the calculated structures are available below. S26

27 Figure S6. Guide to compound numbering of calculated structures (only the lowest energy conformers) S27

28 Figure S7. Guide to compound numbering of calculated structures (only the lowest energy conformer was shown) S28

29 Table S3. Energies, entropies and lowest frequencies of the lowest energy calculated structures a Structure E elec + ZPE Lowest freq. # of imag E elec (Hartree) H (Hartree) S (cal mol -1 K -1 ) G (Hartree) (Hartree) (cm -1 ) freq. α-me 4 Glc-1- OMs α-me 4 Glc OMs_TS hyd 1 α-ac 4 Glc-1-OMs α-ac 4 Glc OMs_TS hyd 1 α-2-f-ac 3 Glc-1- OMs α-2-f-ac 3 Glc-1- OMs_TS hyd α-2-f-ac 3 Man OMs 0 α-2-f-ac 3 Man- 1-OMs_TS hyd a Energy values calculated at the PCM(CH2 Cl 2 )/M06-2X/6-31G(d.p) level. 1 Hartree = kcal mol -1. Thermal corrections at K. S29

30 Table S4. NBO Second Order Perturbation Energies (in kcal mol -1 ) Calculated with PCM(CH 2 Cl 2 )/M06-2X/6-31G(d,p) Structure endo-anomeric effect n Oendo σ* C1 Oexo exo-anomeric effect n Oexo σ* C1 Oendo TOTAL anomeric effect endo-gauche effect σ O,F C2 σ* C1 Oexo exo-gauche effect σ C1 Oexo σ* O,F C2 TOTAL gauche effect α-ac 4 Glc-1-OMes β-ac 4 Glc-1-OMes α-2-f-ac 3 Glc-1-OMes β-2-f-ac 3 Glc-1-OMes α-2-f-ac 3 Man-1-OMes β-2-f-ac 3 Man-1-OMes S30

31 Cartesian coordinates of the lowest energy structures calculated with PCM(CH 2 Cl 2 )/M06-2X/6-31G(d,p) H Structure α-me4glc-1-oms C C C C C O H H H H O S O O H O C H H C H H H O H H O H H O O C H H H C H H H S31

32 C H H O C H H H O H O C H H H C H Structure α-me4glc-1-oms_tshyd C C C C C O H H H H O S O H H O H H O H H O O C H H H S32

33 C H H H C H H O C H H H H O S O O H C H H H O H H Structure α-ac4glc-1-oms C C C C C O H H H O H H O C O C H H H S33

34 O H C O O C O C H H H C H H H C H H O C O C H H Structure α-ac4glc-1-oms_tshyd C C C C C O H H H H O S O O H C H H H O S34

35 H H O H H O C O O C O C H C O C H H H O C O C H H H H H C H H H C H H O Structure α-2-f-ac3glc-1-oms C C C C C O H H S35

36 H H O S O O H C H H H O H H O H H F O O C H H H C H H H C H H O C O C H H H C O O C Structure α-2-f-ac3glc-1-oms_tshyd C C S36

37 C C C O H H H H O S O O H C H H H O H H O H H O C O O C O C H H H C H H H C H H O C O C H H S37

38 H F H H O Structure α-2-f-ac3man-1-oms C C C C C O H H H H O S O O C H H H O H H F H O C O O C O C H H H C H H H C H S38

39 H O C O C H H H O C H H H O H H O Structure α-2-f-ac3man-1-oms_tshyd C C C C C O H H H H O S O H H O C O O C O C H H H C H S39

40 H H C H H O C O C H H H F H S40

41 2.4. NMR spectra Figure S8. 1 H NMR of 3a (CDCl 3, 400 MHz) S41

42 Figure S9. 1 H NMR of 4a (CDCl 3, 400 MHz) S42

43 Figure S10. 1 H NMR of 5b (CDCl MHz) S43

44 Figure S C NMR of 5b (CDCl 3, 100 MHz) S44

45 Figure S F NMR of 5b (CDCl 3, MHz) S45

47 Figure S C NMR of 6a (CDCl 3, 100 MHz) S47

48 Figure S F NMR of 6a (CDCl 3, MHz) S48

49 Figure S16. 1 H NMR of 6b (CDCl 3, 400 MHz) S49

50 Figure S C NMR of 6b (CDCl 3, 100 MHz) S50

51 Figure S F NMR of 6b (CDCl 3, MHz) S51

52 Figure S19. 1 H NMR of 7 (CDCl 3, 400 MHz) S52

53 Figure S C NMR of 7 (CDCl 3, 100 MHz) S53

54 Figure S F NMR of 7 (CDCl 3, MHz) S54

56 Figure S C NMR of 8a (CDCl 3, 100 MHz) S56

57 Figure S F NMR of 8a (CDCl 3, MHz) S57

58 Figure S25. 1 H NMR of 8a/b (CDCl 3, 400 MHz) S58

59 Figure S C NMR of 8a/b (CDCl 3, 100 MHz) S59

60 Figure S F NMR of 8a/b (CDCl 3, MHz) S60

75 Figure S42. 1 H NMR of S1/S2 (CDCl 3, 500 MHz) S75

76 Figure S C NMR of S1/S2 (CDCl 3, 126 MHz) S76

77 Figure S F NMR of S1/S2 (CDCl 3, MHz) S77

78 Figure S45. 1 H NMR of S3 (CDCl 3, 400 MHz) S78

79 Figure S C NMR of S3 (CDCl 3, 100 MHz) S79

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