Total Synthesis of (+) Vicenin-2

Supporting Information Total Synthesis of (+) Vicenin-2 Thanh C. Ho, Haruki Kamimura, Ken Ohmori,* and Keisuke Suzuki* Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, Japan * *kohmori@chem.titech.ac.jp *ksuzuki@chem.titech.ac.jp Table of Contents General Information and Experimental Procedures...S1 1 H-NMR, 13 C-NMR, and 19 F-NMR spectra......s13

General information All reactions utilizing air- or moisture-sensitive reagents were performed in dried glassware under an atmosphere of dry argon. Ethereal solvents and dichloromethane (anhydrous; Kanto Chemical Co., Inc.) were purified under argon, using an Organic Solvent Pure Unit (Wako Pure Chemical Industries, Ltd.). For thin-layer chromatography (TLC) analysis, Merck pre-coated plates (TLC silica gel 60 F254, Art 5715, 0.25 mm) were used. Silica-gel preparative thin-layer chromatography (PTLC) was performed using plates prepared from Merck Silica gel 60 PF254 (Art 7747). For flash column chromatography, silica gel 60N (Spherical, neutral, 63-210 μm) from Kanto Chemical was used. Melting point (mp) determinations were performed by using a Mettler Toledo MP-70 melting point system, and are uncorrected. 1 H-, 13 C- and 19 F-NMR were measured on a Bruker DRX-500 (500MHz), a Bruker Advance-600 (600 MHz) or a JEOL JNM ECX-400 (400 MHz) spectrometer in the solvent indicated; Chemical shifts (δ) are expressed in parts per million (ppm) and are referenced to internal standard (hexafluorobenzene 162.2 for 19 F-NMR), (tetramethylsilane 0.00 for 1 H-NMR) or to the solvent, i.e. 7.26/77.0 for CHCl 3 /CDCl 3 and coupling constants are reported as hertz (Hz). Splitting patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. Infrared (IR) spectra were recorded on a Thermo Fisher Scientific Nicolet is5 FT-IR spectropolarimeter. High-resolution mass spectra (HRMS) were obtained with Bruker Daltonics microtof-q II. High-performance liquid chromatography (HPLC) analyses were performed on a JASCO CO-2060 plus for column thermostat, UV-2077 plus for UV/VIS detector, PU-1580 for HPLC pump. Gelpermeation chromatography preparative isolations were performed on a LC-918 recycling preparative HPLC (Japan Analytical Industry Co., Ltd.), YRU-880 midget plus for RI/UV monitor (SHIMAMURATECH Ltd.). Optical rotations ([α]d) were measured on a JASCO P-3000 polarimeter. S-1

Experimental Procedures F OBn OBn BnO BnO O BnO O 4 BnO F n-buli F Et 2 O 78 C 78 C 15 min F 1 h 98% 3 OBn OBn F 6 O OH F (3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-((benzyloxy)methyl)-2-(2,4,6-trifluorophenyl)tetrahydro-2H-pyran-2-ol (6) To a solution of 1,3,5-trifluorobenzene (3.86 g, 29.2 mmol) in Et 2 O (50 ml) under argon atmosphere at 78 o C was added a 1.54 M solution of n-buli/hexane (18.0 ml, 27.7 mmol) over 20 min. The mixture was stirred at 78 o C for an additional 1 h. Aryllithium was introduced to a solution of lactone 4 (10.0 g, 18.6 mmol) in Et 2 O (50 ml) at 78 o C via a cannula, and the reaction mixture was stirred at 78 o C for 15 min. Glacial acetic acid (1.8 ml, 32 mmol) was added slowly at 78 o C, and the mixture was stirred for an additional 10 min at this temperature. Saturated aqueous NaHCO 3 (ca. 15 ml) was added slowly, and the mixture was warmed to room temperature. The organic material was extracted with Et 2 O. The combined organic extracts were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (3/7) as eluent to afford ketal 6 (12.0 g, 98% yield) as a white solid. R f 0.57 (EtOAc/hexane = 3/7); mp 84 87 o C; 1 H NMR (500 MHz, acetone-d 6, 300 K) δ 7.38 7.17 (m, 18H), 7.07 7.05 (m, 2H), 6.78 (dd, 3 J H,F = 9.9, 9.9 Hz, 2H), 5.66 (s, 1H), 4.92 (s, 2H), 4.90 (d, J = 11.2 Hz, 1H), 4.72 (d, J = 11.1 Hz, 1H), 4.68 (d, J = 11.2 Hz, 1H), 4.62 (d, J = 12.2 Hz, 1H), 4.52 (d, J = 12.2 Hz, 1H), 4.26 (d, J = 11.2 Hz, 1H), 4.21 4.15 (m, 2H), 3.88 3.79 (m, 3H), 3.69 (d, J = 11.2 Hz, 1H); 13 C NMR (126 MHz, acetone-d 6, 300 K) δ 163.6 (dt, 1 J C,F = 248 Hz, 3 J C,F = 17 Hz), 162.8 (ddd, 1 J C,F = 253 Hz, 3 J C,F = 15 Hz, 3 J C,F = 9 Hz), 140.4, 140.3, 140.2, 139.3, 129.5 128.5 (12C), 116.6 (td, 2 J C,F = 13 Hz, 4 J C,F = 5 Hz), 102.3 (ddd, 2 J C,F = 29 Hz, 2 J C,F = 25 Hz, 4 J C,F = 4 Hz), 99.2 (t, 3 J C,F = 4 Hz), 84.5, 84.2, 79.8, 76.4, 76.1, 75.8, 74.0, 73.2, 70.3; 19 F NMR (565 MHz, acetone-d 6, 300 K) δ 103.7 (br), 107.9; IR (thin film, cm -1 ): 3550 (br, OH), 3030, 2928, 2867, 1624, 1600, 1496, 1453, 1439, 1362, 1209, 1123, 1090, 843, 737, 698; HRMS (ESI-TOF) m/z Calcd for C 40 H 37 F 3 NaO 6 : [M+Na] + 693.2434, found 693.2430; [α] 23 D 9.0 o (c 1.0, CHCl 3 ). S-2

(2R,3R,4R,5S,6S)-3,4,5-Tris(benzyloxy)-2-((benzyloxy)methyl)-6-(2,4,6-trifluorophenyl)tetrahydro-2H-pyran (7) To a solution of ketal 6 (12.0 g, 17.9 mmol) in CH 2 Cl 2 (180 ml) under nitrogen atmosphere at 78 o C was added Et 3 SiH (8.55 ml, 53.7 mmol) followed by addition of BF 3 OEt 2 (6.63 ml, 53.7 mmol) over 5 min. After completion of addition, the reaction mixture was stirred at 0 o C for 35 min. Saturated aqueous NaHCO 3 (ca. 30 ml) was added slowly to the reaction mixture under ice-cooling, and the organic material was extracted with CH 2 Cl 2. The combined organic extracts were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (1/9 1/4) as eluent to afford glycoside 7 (9.68 g, 83% yield) as a colorless oil. R f 0.59 (EtOAc/hexane = 1/4); 1 H NMR (600 MHz, acetone-d 6, 300 K) δ 7.46 7.21 (m, 18H, H-Ar), 7.04 7.03 (m, 2H, H- Ar), 6.86 (dd, 3 J H,F = 8.9, 8.9 Hz, 2H, H-4), 5.01 (s, 2H, CH 2 Ph), 4.96 (d, J = 10.9 Hz, 1H, CHPh), 4.78 (d, J = 9.4 Hz, 1H, H-1'), 4.77 (d, J = 10.9 Hz, 1H, CHPh), 4.73 (d, J = 11.2 Hz, 1H, CHPh), 4.67 (d, J = 12.2 Hz, 1H, CHPh), 4.56 (d, J = 12.2 Hz, 1H, CHPh), 4.32 (d, J = 11.2 Hz, 1H, CHPh), 4.04 (dd, J = 8.7, 9.4 Hz, 1H, H-2'), 3.89 3.83 (m, 3H, H-3',4',6'), 3.79 (d, J = 11.2 Hz, 1H, H-6'), 3.71 3.69 (m, 1H, H-5'); 13 C NMR (151 MHz, acetone-d 6, 300 K) δ 163.8 (dt, 1 J C,F = 248.7 Hz, 3 J C,F = 15.8 Hz, C-5), 163.1 (brd, 1 J C,F = 250 Hz, C-1), 140.2 (C-Ar), 140.0 (C-Ar), 139.9 (C-Ar), 139.2 (C-Ar), 129.4 (C-Ar), 129.4 (C-Ar), 129.4 (C-Ar), 129.3 (C-Ar), 129.0 (C-Ar), 128.9 (C-Ar), 128.9 (C-Ar), 128.8 (C-Ar), 128.7 (C-Ar), 128.7 (C-Ar), 128.6 (C-Ar), 128.5 (C-Ar), 112.9 (t, 2 J C,F = 17.1 Hz, C-2), 101.7 (brs, C-4), 88.2 (C-3'), 81.3 (C-2'), 80.9 (C-5'), 79.5 (C-4'), 76.3 (CH 2 Ph), 75.8 (CH 2 Ph), 75.5 (CH 2 Ph), 74.1 (CH 2 Ph), 73.0 (C-1'), 70.2 (C-6'); 19 F NMR (565 MHz, acetone-d 6, 300 K) δ 106.1 (br), 107.1, 110.1 (br); IR (thin film, cm -1 ): 3030, 2900, 2865, 1635, 1605, 1497, 1451, 1360, 1208, 1119, 1072, 842, 736, 697; HRMS (ESI-TOF) m/z Calcd for C 40 H 37 F 3 NaO 5 : [M+Na] + 677.2485, found 677.2503; [α] 23 D 16.9 o (c 1.0, CHCl 3 ). S-3

(3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-((benzyloxy)methyl)-2-(2,4,6-trifluoro-3-((2S,3S,4R,5R,6R)-3,4,5- tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2h-pyran-2-yl)phenyl)tetrahydro-2h-pyran-2-ol (8) To a solution of mono-glycoside 7 (8.0 g, 0.012 mol) in Et 2 O (25 ml) under argon atmosphere at 78 o C was added a 1.65 M solution of t-buli/pentane (8.1 ml, 0.013 mol) over 20 min. The mixture was stirred at 78 o C for an additional 1 h. Aryllithium was introduced to a solution of lactone 4 (6.6 g, 0.012 mol) in Et 2 O (25 ml) at 78 o C via a cannula, and the reaction mixture was stirred at 78 o C for 30 min. Glacial acetic acid (0.80 ml, 0.014 mol) was added slowly at 78 o C, and the mixture was stirred for an additional 10 min at this temperature. Saturated aqueous NaHCO 3 (ca. 7.0 ml) was added slowly, and the mixture was warmed to room temperature. The organic material was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (1/4 3/7) as eluent to afford ketal 8 (12.1 g, 83% yield) as a white foam. R f 0.51 (EtOAc/hexane = 3/7); 1 H NMR (500 MHz, toluene-d 8, 333 K) δ 7.33 6.97 (m, 40H), 6.15 (dd, 3 J H,F = 10.9, 11.0 Hz, 1H), 4.88 4.83 (m, 5H), 4.78 4.71 (m, 3H), 4.66 (d, J = 11.4 Hz, 1H), 4.59 4.53 (m, 3H), 4.51 4.49 (m, 1H), 4.41 (d, J = 12.2 Hz, 2H), 4.33 4.31 (m, 1H), 4.21 (d, J = 11.4 Hz, 1H), 4.15 4.13 (m, 1H), 4.09 4.05 (m, 2H), 4.02 3.98 (m, 2H), 3.88 3.81 (m, 3H), 3.78 3.75 (m, 1H), 3.69 3.63 (m, 3H), 3.46 3.43 (m, 1H); 13 C NMR (126 MHz, toluene-d 8, 333 K) δ 161.7 (brd, 1 J C,F = 251.3 Hz), 161.3 (brd, 1 J C,F = 253.1 Hz), 160.6 (brd, 1 J C,F = 259.5 Hz), 139.5, 139.5, 139.4, 139.4, 139.3, 139.2, 138.6, 138.0, 128.5 127.5 (24C), 115.8 (brs), 112.9 (dd, 2 J C,F = 16.1 Hz), 101.4 (brs), 98.6, 87.6, 84.0, 81.1, 80.7, 78.8, 78.8, 75.7, 75.6, 75.5, 75.0, 75.0, 74.8, 73.7, 73.6, 73.6, 73.1, 72.9, 69.7, 69.4; 19 F NMR (376 MHz, toluene-d 8, 333 K) δ 103.2 (br), 107.0 (br), 109.8 (br); IR (thin film, cm -1 ): 3545 (br, OH), 3030, 2911, 2865, 1624, 1603, 1496, 1454, 1361, 1208, 1137, 1092, 736, 697; HRMS (ESI-TOF) m/z Calcd for C 74 H 71 F 3 NaO 11 : [M+Na] + 1215.4841, found 1215.4787; [α] 23 D 7.3 o (c 1.0, CHCl 3 ). S-4

(2R,2'R,3R,3'R,4R,4'R,5S,5'S,6S,6'S)-6,6'-(2,4,6-Trifluoro-1,3-phenylene)bis(3,4,5-tris(benzyloxy)-2- ((benzyloxy)methyl)tetrahydro-2h-pyran) (9) To a solution of ketal 8 (6.60 g, 5.53 mmol) in CH 2 Cl 2 (200 ml) under nitrogen atmosphere at 78 o C was added Et 3 SiH (4.4 ml, 28 mmol) followed by addition of BF 3 OEt 2 (3.4 ml, 28 mmol) over 6 min. After completion of addition, the reaction mixture was stirred at 0 o C for 30 min. Saturated aqueous NaHCO 3 (ca. 15 ml) was added slowly to the reaction mixture under ice-cooling, and the organic material was extracted with CH 2 Cl 2. The combined organic extracts were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (3/17 1/4) as eluent to afford bis-c-glycoside 9 (5.31 g, 82% yield) as a white foam. R f 0.40 (EtOAc/hexane = 1/4); 1 H NMR (500 MHz, toluene-d 8, 373 K) δ 7.27 6.94 (m, 40H, H-Ar), 6.23 (t, 3 J H,F = 10.1 Hz, 1H, H-6), 4.84 (d, J = 11.4 Hz, 2H, CHPh), 4.83 (s, 4H, CH 2 Ph), 4.76 (d, J = 9.8 Hz, 2H, H-1'), 4.67 (d, J = 11.4 Hz, 2H, CHPh), 4.55 (d, J = 11.4 Hz, 2H, CHPh), 4.53 (d, J = 12.2, 2H, CHPh), 4.41 (d, J = 12.2 Hz, 2H, CHPh), 4.22 (d, J = 11.4 Hz, 2H), 4.10 (dd, J = 9.2, 9.8 Hz, 2H, H-2'), 3.84 (dd, J = 9.3, 9.4 Hz, 2H, H-4'), 3.77 (dd, J = 11.4, 4.2 Hz, 2H, H- 6'), 3.69 (dd, J = 9.2, 9.3 Hz, 2H, H-3'), 3.65 (dd, J = 11.4 Hz, 1.8 Hz, 2H, H-6'), 3.46 (ddd, J = 9.4, 4.2, 1.8 Hz, 2H, H-5'); 13 C NMR (126 MHz, toluene-d 8, 373 K) δ 162.1 (ddd, 1 J C,F = 253 Hz, 3 J C,F = 16 Hz, 3 J C,F = 11 Hz, C-1), 161.6 (brd, 1 J C,F = 253 Hz, C-3), 139.8 (C-Ar), 139.6 (C-Ar), 139.5 (C-Ar), 138.9 (C-Ar), 128.6 127.6 (12C, C-Ar), 112.9 (ddd, 2 J C,F = 18 Hz, 2 J C,F = 18 Hz, 4 J C,F = 4 Hz, C-2), 100.9 (td, 2 J C,F = 28 Hz, 4 J C,F = 2 Hz, C-6), 87.9 (C-3'), 81.6 (C-2'), 81.0 (C-5'), 79.2 (C-4'), 75.7 (CH 2 Ph), 75.2 (CH 2 Ph), 75.0 (CH 2 Ph), 74.0 (CH 2 Ph), 73.2 (C-1'), 70.1 (C-6'); 19 F NMR (376 MHz, toluene-d 8, 373 K) δ 108.3 (br, 3F); IR (thin film, cm -1 ): 3030, 2908, 2864, 1637, 1609, 1496, 1453, 1360, 1208, 1134, 1095, 735, 697; HRMS (ESI-TOF) m/z Calcd for C 74 H 71 F 3 NaO 10 : [M+Na] + 1199.4892, found 1199.4844; [α] 23 D 14.4 o (c 1.0, CHCl 3 ). S-5

(E)-3-(4-(Benzyloxy)phenyl)-1-(2,4,6-trifluoro-3,5-bis((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6- ((benzyloxy)methyl)tetrahydro-2h-pyran-2-yl)phenyl)prop-2-en-1-one (2) To a solution of bis-glycoside 9 (4.30 g, 3.65 mmol) in Et 2 O (30 ml) under argon atmosphere at 78 o C was added a 1.65 M solution of t-buli/pentane (2.6 ml, 4.3 mmol) over 10 min. The mixture was stirred at 78 o C for an additional 1h. Aryllithium was introduced to a solution of amide 5 (1.09 g, 3.65 mmol) in THF (50 ml) at 50 o C via a cannula, and the reaction mixture was stirred at 50 o C for 2 h. The reaction was quenched with saturated aqueous NH 4 Cl, and the organic material was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (1/4) as eluent to afford 2 (4.12 g, 80%) as a pale yellow amorphous solid. Bis-glycoside 9 was recovered in 0.68 g (15%). R f 0.28 (EtOAc/hexane = 1/4); mp 46 49 o C; 1 H NMR (500 MHz, toluene-d 8, 363 K) δ 7.44 (d, J = 16.0 Hz, 1H), 7.27 6.97 (m, 47H), 6.82 (d, J = 16.0 Hz, 1H), 6.66 (d, J = 8.8 Hz, 2H), 4.86 4.82 (m, 8H), 4.72 (s, 2H), 4.67 (d, J = 11.4 Hz, 2H), 4.59 (d, J = 11.3 Hz, 2H), 4.53 (d, J = 12.3 Hz, 2H), 4.42 (d, J = 12.3 Hz, 2H), 4.28 (d, J = 11.3 Hz, 2H), 4.12 (dd, J = 9.1, 9.2 Hz, 2H), 3.85 (dd, J = 9.3, 9.4 Hz, 2H), 3.77 (dd, J = 11.3, 4.1 Hz, 2H), 3.70 (dd, J = 9.1, 9.3 Hz, 2H), 3.66 (dd, J = 11.3, 1.8 Hz, 2H), 3.46 (ddd, J = 9.4, 4.1, 1.8 Hz, 2H); 13 C NMR (126 MHz, toluene-d 8, 363 K) δ 185.1, 161.8 (brd, 1 J C,F = 259 Hz), 161.7, 159.2 (brd, 1 J C,F = 256 Hz), 146.0, 139.6, 139.5, 139.4, 138.7, 137.3, 130.8, 128.8 127.6 (16C), 126.0, 116.1 (brs), 115.9, 113.4 (t, 2 J C,F = 17 Hz), 87.7, 81.4, 81.0, 79.0, 75.6, 75.1, 75.1, 73.9, 73.2, 70.5, 69.9; 19 F NMR (376 MHz, toluene-d 8, 373 K) δ 106.4 (br), 110.5; IR (thin film, cm -1 ): 3031, 2914, 2866, 1651 (CO), 1597, 1510, 1497, 1453, 1360, 1265, 1172, 829, 744, 697; HRMS (ESI-TOF) m/z Calcd for C 90 H 84 F 3 O 12 : [M+H] + 1413.5909, found 1413.5850; [α] 23 D 24.2 o (c 1.0, CHCl 3 ). S-6

(E)-3-(4-(Benzyloxy)phenyl)-1-(2,4-difluoro-6-hydroxy-3,5-bis((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6- ((benzyloxy)methyl)tetrahydro-2h-pyran-2-yl)phenyl)prop-2-en-1-one (10) To a solution of 2 (1.04 g, 0.740 mmol) and benzaldoxime (182 mg, 1.50 mmol) in THF (25 ml) under nitrogen flush at room temperature was added t-buok (185 mg, 1.65 mmol) in one portion. The reaction mixture was stirred at room temperature for 10 h, quenched with 1 M aqueous HCl until ph ~ 3, and the organic material was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (1/4) as eluent to afford 10 (0.93 g, 90% yield) as a yellow amorphous solid. R f 0.31 (EtOAc/hexane = 1/4); mp 96 99 o C; 1 H NMR (500 MHz, toluene-d 8, 363 K) δ 14.26 (brs, OH), 7.89 (d, J = 15.5 Hz, 1H), 7.32 6.89 (m, 48H), 6.75 (d, J = 8.7 Hz, 2H), 5.14 (brs, 1H), 4.91 4.56 (m, 15H), 4.47 4.41 (m, 4H), 4.34 (d, J = 10.9 Hz, 1H), 4.16 (dd, J = 9.3, 9.2 Hz, 1H), 3.95 3.69 (m, 8H), 3.61 3.53 (m, 2H); 13 C NMR (126 MHz, toluene-d 8, 363 K) δ 192.0, 165.3 (brd, 1 J C,F = 253 Hz), 165.2, 162.6 (brd, 1 J C,F = 257 Hz), 161.9, 145.9, 139.8, 139.6, 139.6, 139.4, 139.4, 139.3, 139.2, 138.7, 137.1, 130.9, 128.8 127.3 (28C), 123.8, 116.0, 112.6 (brs), 108.3 (brs), 107.3 (dd, 2 J C,F = 19.3, 19.3 Hz), 87.9, 87.6, 81.1, 80.8, 80.7, 79.2, 79.1, 78.9, 75.6, 75.6, 75.1, 75.5, 75.5, 74.8, 73.9, 73.9, 73.3, 73.0, 70.5, 70.1, 70.0 ; 19 F NMR (376 MHz, toluene-d 8, 373 K) δ 97.9 (br), 103.6 (br); IR (thin film, cm -1 ): 3350 (br, OH), 3030, 2897, 2865, 1633 (CO), 1555, 1510, 1497, 1453, 1358, 1255, 1163, 829, 743, 697; HRMS (ESI-TOF) m/z Calcd for C 90 H 85 F 2 O 13 : [M+H] + 1411.5953, found 1411.5910; [α] 23 D 1.2 o (c 1.0, CHCl 3 ). S-7

2H-pyran-2-yl)-4H-chromen-4-one (11) To a solution of 10 (1.42 g, 1.01 mmol) in DMSO (85 ml) under nitrogen atmosphere at room temperature was added I 2 (25 mg, 0.10 mmol) in DMSO (15 ml). The reaction mixture was warmed to 140 o C and stirred for 3 h. After cooled to room temperature, water (50 ml) was added, and the organic material was extracted with EtOAc (3 150 ml). Brine (ca. 3 ml) was added to give a phase separation in extraction. The combined organic extracts were washed with aqueous Na 2 S 2 O 3, brine, dried over MgSO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (3/7) as eluent to afford 11 (1.27 g, 90% yield) as a pale yellow amorphous solid. R f 0.23 (EtOAc/hexane = 3/7); mp 59 62 o C; 1 H NMR (500 MHz, toluene-d 8, 373 K) δ 7.75 (brs, 2H), 7.33 6.84 (m, 45H), 6.74 (d, J = 6.7 Hz, 2H), 6.35 (s, 1H), 5.02 (brs, 1H), 4.94 4.86 (m, 7H), 4.78 4.75 (m, 3H), 4.70 (d, J = 11.4 Hz, 1H), 4.61 4.56 (m, 2H), 4.49 4.19 (m, 8H), 4.01 (brs, 1H), 3.89 3.79 (m, 4H), 3.76 3.68 (m, 3H), 3.53 3.52 (m, 2H). 13 C NMR (126 MHz, toluene-d 8, 373 K) δ 174.4, 162.1 (brd, 1 J C,F = 249.7 Hz), 162.1, 161.9, 160.6 (brd, 1 J C,F = 272.8 Hz), 156.2 (brs), 139.6 139.3 (7C), 138.6, 137.1, 128.8 127.4 (29C), 124.6, 116.0, 112.6 (brs), 111.5 (brs), 107.8, 88.5, 87.7, 81.1, 80.9, 80.7, 79.1, 79.0, 78.2, 75.5, 75.5, 75.0, 75.0, 74.9, 74.2, 74.0, 73.9, 73.8, 73.1, 70.6, 70.1, 69.9 ; 19 F NMR (376 MHz, toluene-d 8, 373 K) δ 100.8, 105.9, 107.1; IR (thin film, cm -1 ): 3030, 2932, 2866, 1656 (CO), 1620, 1510, 1453, 1353, 1264, 1178, 1095, 836, 748, 698. HRMS (ESI-TOF) m/z Calcd for C 90 H 83 F 2 O 13 : [M+H] + 1409.5796, found 1409.5742. [α] 23 D 6.0 o (c 1.0, CHCl 3 ). BnO OBn OBn BnO OBn OBn BnO BnO O BnO H F O H O F O OBn OBn 11 OBn BnOH KOH 1,4-dioxane 88 o C, 2 h 89% BnO BnO O BnO H BnO O H O OBn O OBn OBn 12 OBn 5,7-Difluoro-2-(4-hydroxyphenyl)-6,8-bis((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro- 5,7-Bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-6,8-bis((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6- ((benzyloxy)methyl)tetrahydro-2h-pyran-2-yl)-4h-chromen-4-one (12) To a solution of 11 (400 mg, 0.280 mmol) and benzyl alcohol (600 mg, 5.55 mmol, excess) in 1,4-dioxane (20 ml) under nitrogen flush at room temperature was added KOH (320 mg, 5.70 mmol, excess) in one portion. The heterogeneous reaction mixture was stirred in a preheated oil bath at 88 o C. Upon completion (LC-MS analysis, ca. 2 h), the reaction mixture was cooled to room temperature, quenched with 1M aqueous HCl until ph ~ 3, and the organic material was S-8

extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (1/3 3/7) as eluent to afford 12 (401 mg, 89%) as a pale yellow amorphous solid. HPLC (4.6 250 mm Ph-3, 30% EtOAc in hexane, 1 ml/min, UV detection at 254 nm) 5.81 min and 99.0% pure; R f 0.39 (EtOAc/hexane = 3/7); mp 95 96 o C; IR (thin film, cm -1 ): 3030, 2932, 2866, 1646 (CO), 1605, 1510, 1497, 1454, 1343, 1263, 1178, 1097, 836, 749, 697; HRMS (ESI-TOF) m/z Calcd for C 104 H 97 O 15 : [M+H] + 1585.6822, found 1585.6818; [α] 23 D +17.0 o (c 1.0, CHCl 3 ). NMR spectral data of 12 is complicated by the mixture of rotamers (see the NMR spectra below). 5,7-Dihydroxy-2-(4-hydroxyphenyl)-6,8-bis((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2Hpyran-2-yl)-4H-chromen-4-one (1) A mixture of 12 (155 mg, 0.0980 mmol) and ASCA-2 (77 mg, 52% H 2 O, 10% Pd(OH) 2 /C, 2.4 wt%) in EtOH/EtOAc (66 ml, 1/1) was stirred under H 2 atmosphere (balloon) at room temperature. Upon completion (LC-MS analysis, ca. 12 h), the catalyst was removed via filtration (Celite pad), and the filtrate was concentrated under reduced pressure. The residue was dissolved in MeOH (5 ml), neutralized with Amberlite IR-120 (H + ), and filtered, and concentrated under reduced pressure. The residue was absorbed onto Celite, and purified by Cosmosil column chromatography (Cosmosil 75C 18 OPN, Nacalai Tesque, Inc., 150 ml) with MeOH/H 2 O (1/9 3/7) as eluent to afford 1 (54 mg, 92 % yield) as a pale yellow powder. Note: yellow color intensity, solubility in an organic solvent (MeOH or DMSO), and 1 H NMR chemical shifts of hydroxy groups of vicenin-2 vary depending on the ph of the solution. Vicenin-2 in DMSO-d 6 decomposes slowly at 100 o C. HPLC (4.6 250 mm ODS-3, 85% H 2 O (ph 2.2, H 3 PO 4 ) in CH 3 CN (90% in H 2 O), 0.8 ml/min, UV detection at 200 nm) 14.66 min and 98.1 % pure; mp 150 o C (decomp); 1 H NMR (500 MHz, DMSO-d 6, 363 K) δ 13.64 (br, ArOH), 9.96 (br, ArOH), 9.19 (br, ArOH), 7.96 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 6.69 (s, 1H), 4.91 (d, J = 8.6 Hz, 1H), 4.82 (d, J = 9.7 Hz, 1H), 3.85 3.84 (m, 2H), 3.79 3.77 (m, 2H), 3.74 3.71 (m, 2H), 3.64 3.34 (m, 6H); 13 C NMR (126 MHz, DMSO-d 6, 363 K) 182.0, 163.9, 160.9, 160.7, 159.0, 154.5, 128.4, 121.4, 115.8, 107.8, 104.2, 103.6, 102.5, 81.4, 80.9, S-9

78.5, 78.2, 73.7 (2C), 71.3 (2C), 70.1, 69.7, 61.0, 60.5; IR (ATR, cm -1 ): 3270 (br), 2923, 1645, 1621, 1610, 1573, 1442, 1356, 1214, 1178, 1077, 1007, 832; HRMS (ESI-TOF) m/z Calcd for C 27 H 31 O 15 : [M+H] + 595.1658, found 595.1648; [α] 23 D + 49.0 o (c 0.1, MeOH). Sample of Vicenin-2 from Kanto Chemical Co., Inc., Japan, purchasing from PhytoLab GmbH & Co. KG, Germany on June 17, 2016: HPLC (4.6 250 mm ODS-3, 85% H 2 O (ph 2.2, H 3 PO 4 ) in CH 3 CN (90% in H 2 O), 0.8 ml/min, UV detection at 200 nm) 14.24 min and 98.3 % pure; [α] 23 D + 46.9 o (c 0.1, MeOH). * Preparation of lactone 4 (1) (3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (4) To a stirred suspension of NaH (25.0 g, 63 % in oil, 0.656 mol) in DMF (400 ml) at 0 o C under nitrogen atmosphere was added portion wise methyl-α-d-glucopyranoside 13 (19.4 g, 0.0999 mol). The mixture was vigorously stirred at room temperature for 2 h. TBAI (3.69 g, 0.010 mol) was added to the mixture, followed by dropwise addition of BnBr (72 ml, 0.60 mol) over 45 min. The reaction mixture was stirred for 18 h. Ice cold water was added, and the organic material was extracted with Et 2 O. The combined organic extracts were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure to give crude methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside as a pale yellow oil. To a stirred solution of crude methyl glycoside in glacial acetic acid (585 ml) at 85 o C was added 2 M aqueous HCl (225 ml) dropwise over 45 min. The reaction mixture was stirred at this temperature for an additional 2 h 45 min, cooled to room temperature, and left over night for crystallization of product. The crystals were filtered, washed consecutively with water (3 100 ml), methanol (2 100 ml) and air dried to afford 14 (24.7 g) as a white powder. The filtrated solution was heated again at 85 o C for 3.5 h, and the second crop of crystallization gave additional 6.6 g of 14 (58% overall yield from 13). Note: Acidic hydrolysis of methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside in 7 h continuously gave 14 in 45% yield. The major anomer of 14 can be obtained in pure form (see the NMR spectra below) by recrystallization after further purification of the mixture of anomers 14 by silica gel column chromatography with EtOAc/hexane (1/1) as eluent. R f 0.52 and 0.60 (EtOAc/hexane = 2/3); 1 H NMR (500 MHz, CDCl 3, 300 K) δ 7.33 7.10 (m, 20H), 5.20 (t, J = 3.3 Hz, 1H), 4.96 4.90 (m, 1H), 4.83 4.63 (m, 4H), 4.55 4.42 (m, 3H), 4.07 3.39 (m, 7H); 13 C NMR (126 MHz, CDCl 3, 300 K) δ 138.6, 138.5 (anomer), 138.3 (anomer), 138.2, 137.9 (anomer), 137.8, 137.8, 137.7 (anomer), 128.4 127.5 (24C), 97.4 (anomer), 91.1, 84.5 (anomer), 83.0 (anomer), 81.7, 79.9, 77.8 (anomer), 77.7, 75.6, 75.6 (anomer), 74.9, 74.9 (anomer), S-10

74.6 (anomer), 74.5 (anomer), 73.4 (anomer), 73.4, 73.0, 70.0, 68.9 (anomer), 68.6; IR (thin film, cm -1 ): 3350 (br, OH), 3029, 2916, 2860, 1496, 1451, 1357, 1212, 1147, 1087, 745, 695; HRMS (ESI-TOF) m/z Calcd for C 34 H 36 NaO 6 : [M+Na] + 563.2404, found 563.2395. A solution of hemiacetals 14 (22.4 g, 41.4 mmol) in DMSO (112 ml) was stirred under nitrogen atmosphere at room temperature for 30 min. Acetic acid anhydride (67 ml) was added over 15 min, and the reaction mixture was stirred for 22 h at room temperature. Water (900 ml) was added to dilute, and the organic material was extracted with EtOAc (4 300 ml). The combined organic extracts were washed with ph 7 phosphate buffer, brine, dried over Na 2 SO 4, filtered, and concentrated under reduced pressure at room temperature. The residue was carefully purified by silica gel column chromatography with EtOAc/hexane (3/20 1/4) as eluent to afford gluconolactone 4 (19.9 g, 89% yield) as a colorless oil. R f 0.37 (EtOAc/hexane = 1/4); 1 H NMR (500 MHz, CDCl 3, 300 K) δ 7.37 7.16 (m, 20H), 4.97 (d, J = 11.4 Hz, 1H), 4.72 4.44 (m, 8H), 4.12 (d, J = 6.6 Hz, 1H), 3.96 3.88 (m, 2H), 3.71 3.63 (m, 2H); 13 C NMR (126 MHz, CDCl 3, 300 K) δ 169.2, 137.5, 137.4, 137.4, 136.9, 128.4 127.7 (12C), 80.8, 78.1, 77.3, 76.0, 73.8, 73.6, 73.6, 73.4, 68.2; IR (thin film, cm -1 ): 3030, 2910, 2868, 1756 (CO), 1496, 1453, 1362, 1210, 1164, 1097, 738, 698; HRMS (ESI-TOF) m/z Calcd for C 34 H 35 O 6 : [M+H] + 539.2428, found 539.2428; [α] 23 D +62.1 o (c 1.0, CHCl 3 ). * Preparation of amide 5 (2) (E)-3-(4-(Benzyloxy)phenyl)-N-methoxy-N-methylacrylamide (5) To a suspension of ester 15 (2.01 g, 7.49 mmol) and N,O-dimethylhydroxylamine hydrochloride (1.73g, 17.7 mmol) in THF (20 ml) under argon atmosphere at 20 o C was added a 1.78 M solution of i-prmgcl/thf (20 ml, 36 mmol) dropwise. The reaction mixture was stirred at 0 o C for 1 h. Saturated aqueous NH 4 Cl was added, and the organic material was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO 4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with EtOAc/hexane (3/2) as eluent to afford amide 5 (1.96 g, 93% yield) as a white solid. R f 0.53 (EtOAc/hexane = 3/2); mp 93 94 o C; 1 H NMR (600 MHz, CDCl 3, 300 K) δ 7.69 (d, J = 15.8 Hz, 1H), 7.51 (d, J = 8.7 Hz, 2H), 7.43 7.37 (m, 4H), 7.32 (t, J = 7.2 Hz, 1H), 6.97 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 15.8 Hz, 1H), 5.08 (s, 2H), S-11

3.74 (s, 3H), 3.29 (s, 3H); 13 C NMR (151 MHz, CDCl 3, 300 K) δ 167.3, 160.1, 143.0, 136.5, 129.6, 128.6, 128.1, 128.0, 127.4, 115.1, 113.4, 70.0, 61.7, 32.5; IR (thin film, cm -1 ): 3035, 2964, 2936, 2871, 1650 (CO), 1612, 1511, 1455, 1423, 1383, 1303, 1241, 1176, 1097, 1004, 829, 739, 698; HRMS (ESI-TOF) m/z Calcd for C 18 H 20 NO 3 : [M+H] + 298.1438, found 298.1437. * Preparation of benzaldehyde oxime (3) To a solution of hydroxylamine hydrochloride (4.20 g, 60.0 mmol) and sodium acetate (4.92 g, 60.0 mmol) in MeOH (165 ml) and water (15 ml) under nitrogen atmosphere at room temperature was added dropwise benzaldehyde (3.0 ml, 0.03 mol) over 10 min, and the reaction mixture was stirred at ambient temperature for 4 h. Solvent was removed under reduced pressure. The organic material was diluted with EtOAc, washed with water (4 times), dried over Na 2 SO 4, filtered, and concentrated under reduced pressure. Benzaldoxime (3.45 g, 95% yield) as a white semisolid at room temperature was used for the next step without further purification. 1 H NMR (600 MHz, CDCl 3, 300 K) δ 9.84 (brs, OH), 8.18 (s, 1H, CH=N), 7.57 7.55 (m, 2H, Ar), 7.35 7.34 (m, 3H, Ar); 13 C NMR (151 MHz, CDCl 3, 300 K) δ 150.4 (C=N), 131.7 (C), 130.0 (CHp), 128.7 (CHo), 127.0 (CHm) in good agreement with the literature data; 3b IR (thin film, cm -1 ): 3314 (br, OH), 3028, 2986, 2898, 1700 (C=N), 1633, 1494, 1451, 1304, 1211, 951, 870, 742, 691. References (1) For the preparation of hemiacetals 14, see: (a) Dasari, B.; Jogula, S.; Borhade, R.; Balasubramanian, S.; Chandrasekar, G.; Kitambi, S. S.; Arya, P. Org. Lett. 2013, 15, 432 435. For the oxidation of 14, see: (b) Li, L.-T.; Zhou, L.-F.; Li, Y.-J.; Huang, J.; Liu, R.-H.; Wang, B.; Wang, P. Bioorg. Med. Chem. Lett. 2012, 22, 642 644. (c) Zhang, F.; Vasella, A. Carbohydr. Res. 2007, 342, 2546 2556. (2) For the preparation of Weinreb amide from the corresponding ester, see: (a) Cusso, O.; Garcia-Bosch, I.; Ribas, X.; Lloret-Fillol, J.; Costas, M. J. Am. Chem. Soc. 2013, 135, 14871 14878. Ester 15 was prepared from 4- hydroxybenzaldehyde, see: (b) Nanda, S.; Tetrahedron Lett. 2005, 46, 3661 3663. (3) (a) Tamilselvan, P.; Basavaraju, Y. B.; Sampathkumar, E.; Murugesan, R. Catal. Commun. 2009, 10, 716 719. (b) Sanders, B. C.; Friscourt, F.; Ledin, P. A.; Mbua, N. E.; Arumugam, S.; Gou, J.; Boltje, T. J.; Popik, V. V.; Boons, G. J. J. Am. Chem. Soc. 2011, 133, 949 957. S-12

1 H NMR (500 MHz, acetone d 6, 300 K) 7.38 7.36 7.35 7.31 7.29 7.29 7.28 7.26 7.25 7.24 7.23 7.18 7.18 7.17 7.07 7.07 7.06 7.05 6.80 6.78 6.76 5.66 4.92 4.91 4.89 4.73 4.70 4.69 4.67 4.63 4.61 4.53 4.50 4.27 4.25 4.21 4.21 4.19 4.18 4.17 4.15 3.88 3.86 3.85 3.84 3.83 3.81 3.79 3.70 3.68 0.00 NAME nmr EXPNO 42 Date_ 20160204 Time 19.47 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Acetone NS 32 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 18 DW 71.400 use DE 6.00 use TE 300.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300250 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 18.37 2.02 2.00 0.84 1.94 1.02 1.01 1.10 1.10 1.14 0.99 2.09 3.11 1.12 S-13

13 C NMR (126 MHz, acetone d 6, 300 K) 206.60 164.74 164.61 164.47 163.92 163.84 163.80 163.72 162.76 162.63 162.50 161.90 161.83 161.79 161.71 140.42 140.25 140.16 139.30 129.48 129.46 129.43 129.33 129.18 128.99 128.85 128.71 128.67 128.60 128.50 116.72 116.68 116.62 116.58 116.52 116.48 102.54 102.51 102.34 102.31 102.28 102.11 102.08 99.25 99.22 99.19 84.47 84.23 79.80 76.35 76.06 75.83 73.98 73.19 70.31 30.76 30.60 30.45 30.30 30.14 29.99 29.84 NAME nmr EXPNO 46 Date_ 20160204 Time 23.09 PROBHD 5 mm Multinucl PULPROG zgpg TD 65536 SOLVENT Acetone NS 1029 DS 8 SWH 28985.508 Hz FIDRES 0.442284 Hz AQ 1.1304960 sec RG 32768 DW 17.250 use DE 6.00 use TE 300.0 K D1 2.00000000 sec d11 0.03000000 sec DELTA 1.89999998 sec TD0 1 SFO1 125.7715724 MHz NUC1 13C P1 4.30 use PLW1 1.00000000 W SFO2 500.1320005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 90.00 use PLW2 1.00000000 W PLW12 1.00000000 W PLW13 1.00000000 W SI 65536 SF 125.7576336 MHz LB 1.00 Hz PC 1.40 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-14

19 F NMR (565 MHz, acetone-d 6, 300 K, C 6 F 6 internal standard) 103.65 107.87 162.20 NAME th01.04.no5 EXPNO 11 Date_ 20160215 Time 16.34 PROBHD 5 mm CPPBBO BB PULPROG zgflqn TD 131072 SOLVENT Acetone NS 128 DS 4 SWH 133928.578 Hz FIDRES 1.021794 Hz AQ 0.4893355 sec RG 17.5 DW 3.733 use DE 18.00 use TE 300.0 K D1 1.00000000 sec TD0 1 ======== CHANNEL f1 ======= SFO1 564.6299196 MHz NUC1 19F P1 15.00 use PLW1 15.50000000 W SI 65536 SF 564.6850739 MHz LB 0.30 Hz PC 1.00 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 ppm S-15

1 H NMR (600 MHz, acetone d 6, 300 K) 7.46 7.44 7.41 7.40 7.37 7.36 7.34 7.33 7.32 7.31 7.29 7.28 7.22 7.21 7.04 7.03 6.87 6.85 6.84 5.01 4.97 4.95 4.79 4.78 4.78 4.77 4.74 4.72 4.68 4.66 4.57 4.55 4.33 4.31 4.06 4.04 4.03 3.89 3.88 3.86 3.85 3.83 3.80 3.78 3.71 3.71 3.70 3.69 2.05 NAME th01.05.no7 EXPNO 20 Date_ 20160215 Time 19.04 PROBHD 5 mm CPPBBO BB PULPROG zg30 TD 65536 SOLVENT Acetone NS 16 DS 2 SWH 12019.230 Hz FIDRES 0.183399 Hz AQ 2.7262976 sec RG 5.45 DW 41.600 use DE 10.00 use TE 300.0 K D1 1.00000000 sec TD0 1 ======== CHANNEL f1 ======= SFO1 600.1337060 MHz NUC1 1H P1 12.00 use PLW1 23.00000000 W SI 65536 SF 600.1300124 MHz LB 0.30 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 17.87 2.00 2.02 1.99 1.01 0.95 0.97 1.02 1.02 1.01 0.99 1.00 2.98 1.00 1.03 S-16

13 C NMR (151 MHz, acetone d 6, 300 K) 206.40 164.68 164.57 164.47 163.87 163.03 162.92 162.82 162.21 140.21 139.95 139.92 139.23 129.43 129.41 129.38 129.25 128.96 128.90 128.89 128.77 128.72 128.66 128.58 128.49 113.02 112.90 112.79 101.67 88.19 81.31 80.93 79.45 76.32 75.80 75.52 74.11 73.00 70.23 30.68 30.56 30.43 30.30 30.17 30.04 29.92 NAME th01.05.no7 EXPNO 11 Date_ 20160207 Time 14.56 PROBHD 5 mm CPPBBO BB PULPROG zgpg30 TD 65536 SOLVENT Acetone NS 1024 DS 4 SWH 36057.691 Hz FIDRES 0.550197 Hz AQ 0.9087659 sec RG 175.56 DW 13.867 use DE 18.00 use TE 300.0 K D1 2.00000000 sec D11 0.03000000 sec TD0 1 ======== CHANNEL f1 ======= SFO1 150.9178981 MHz NUC1 13C P1 10.00 use PLW1 70.00000000 W ======== CHANNEL f2 ======= SFO2 600.1324005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 70.00 use PLW2 26.00000000 W PLW12 0.76407999 W PLW13 0.37439999 W SI 32768 SF 150.9026507 MHz LB 1.00 Hz PC 1.40 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-17

19 F NMR (565 MHz, acetone d 6, 300 K, C 6 F 6 internal standard) 106.05 107.08 110.12 162.20 NAME th01.05.no7 EXPNO 22 Date_ 20160215 Time 20.01 PROBHD 5 mm CPPBBO BB PULPROG zgflqn TD 131072 SOLVENT Acetone NS 16 DS 4 SWH 133928.578 Hz FIDRES 1.021794 Hz AQ 0.4893355 sec RG 175.56 DW 3.733 use DE 18.00 use TE 300.0 K D1 1.00000000 sec TD0 1 ======== CHANNEL f1 ======= SFO1 564.6299196 MHz NUC1 19F P1 15.00 use PLW1 15.50000000 W SI 65536 SF 564.6855968 MHz LB 0.30 Hz PC 1.00 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 ppm S-18

COSYGPSW (acetone d 6, 300 K) ppm 3.5 4.0 4.5 5.0 5.5 6.0 6.5 NAME th01.05.no7 EXPNO 15 Date_ 20160207 Time 15.30 PROBHD 5 mm CPPBBO BB PULPROG cosygpppqf TD 2048 SOLVENT Acetone NS 1 DS 8 SWH 2958.580 Hz FIDRES 1.444619 Hz AQ 0.3461120 sec RG 4.46 DW 169.000 usec DE 10.00 usec TE 300.0 K D0 0.00000300 sec D1 1.78168297 sec D11 0.03000000 sec D12 0.00002000 sec D13 0.00000400 sec D16 0.00020000 sec IN0 0.00033800 sec ======== CHANNEL f1 ======== SFO1 600.1333570 MHz NUC1 1H P0 12.00 usec P1 12.00 usec P17 2500.00 usec PLW1 23.00000000 W PLW10 4.89940023 W ====== GRADIENT CHANNEL ===== GPNAM[1] SMSQ10.100 GPZ1 10.00 % P16 1000.00 usec F1 Acquisition parameters TD 128 SFO1 600.1334 MHz FIDRES 23.113905 Hz SW 4.930 ppm FnMODE QF SI 1024 SF 600.1300124 MHz WDW QSINE LB 0 Hz PC 1.40 7.0 7.5 8.0 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm S-19

HMBCGP (acetone d 6, 300 K) ppm 60 70 80 90 100 110 120 130 140 NAME th01.05.no7 EXPNO 16 Date_ 20160207 Time 15.37 PROBHD 5 mm CPPBBO BB PULPROG hmbcgplpndqf TD 2048 SOLVENT Acetone NS 4 DS 16 SWH 2958.580 Hz FIDRES 1.444619 Hz AQ 0.3461120 sec RG 175.56 DW 169.000 usec DE 10.00 usec TE 300.0 K CNST2 145.0000000 CNST13 10.0000000 D0 0.00000300 sec D1 1.28496003 sec D2 0.00344828 sec D6 0.05000000 sec D16 0.00020000 sec IN0 0.00001490 sec ======== CHANNEL f1 ======== SFO1 600.1333570 MHz NUC1 1H P1 12.00 usec P2 24.00 usec PLW1 23.00000000 W ======== CHANNEL f2 ======== SFO2 150.9178741 MHz NUC2 13C P3 10.00 usec PLW2 70.00000000 W ====== GRADIENT CHANNEL ===== GPNAM[1] SMSQ10.100 GPNAM[2] SMSQ10.100 GPNAM[3] SMSQ10.100 GPZ1 50.00 % GPZ2 30.00 % GPZ3 40.10 % P16 1000.00 usec F1 Acquisition parameters TD 128 SFO1 150.9179 MHz FIDRES 262.164429 Hz SW 222.353 ppm FnMODE QF 150 160 170 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm S-20

HSQCEDETGPSISP (acetone d 6, 300 K) ppm 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 NAME th01.05.no7 EXPNO 17 Date_ 20160207 Time 15.53 PROBHD 5 mm CPPBBO BB PULPROG hsqcedetgpsisp2.3 TD 2048 SOLVENT Acetone NS 4 DS 32 SWH 7211.539 Hz FIDRES 3.521259 Hz AQ 0.1419947 sec RG 175.56 DW 69.333 usec DE 10.00 usec TE 300.0 K CNST2 145.0000000 CNST17 0.5000000 D0 0.00000300 sec D1 2.00000000 sec D4 0.00172414 sec D11 0.03000000 sec D16 0.00020000 sec D21 0.00360000 sec D24 0.00089000 sec IN0 0.00002000 sec ======== CHANNEL f1 ======== SFO1 600.1328224 MHz NUC1 1H P1 12.00 usec P2 24.00 usec P28 0 usec PLW1 23.00000000 W ======== CHANNEL f2 ======== SFO2 150.9133710 MHz NUC2 13C CPDPRG[2 garp P3 10.00 usec P14 500.00 usec P24 2000.00 usec P31 1730.00 usec PCPD2 60.00 usec PLW0 0 W PLW2 70.00000000 W PLW12 1.94439995 W SPNAM[3] Crp60,0.5,20.1 SPOAL3 0.500 SPOFFS3 0 Hz SPW3 10.69499969 W SPNAM[7] Crp60comp.4 SPOAL7 0.500 SPOFFS7 0 Hz SPW7 10.69499969 W SPNAM[18 Crp60_xfilt.2 SPOAL18 0.500 SPOFFS18 0 Hz SPW18 3.09109998 W 135 140 145 150 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm S-21

13 C DEPT135 (acetone d 6, 300 K) 129.42 129.40 129.37 129.26 128.96 128.89 128.78 128.71 101.67 88.19 81.29 80.93 79.44 76.32 75.79 75.52 74.10 72.99 70.21 NAME th01.05.no7 EXPNO 12 Date_ 20160207 Time 15.12 PROBHD 5 mm CPPBBO BB PULPROG deptsp135 TD 65536 SOLVENT Acetone NS 256 DS 4 SWH 24038.461 Hz FIDRES 0.366798 Hz AQ 1.3631488 sec RG 175.56 DW 20.800 use DE 18.00 use TE 300.0 K CNST2 145.0000000 D1 2.00000000 sec D2 0.00344828 sec D12 0.00002000 sec TD0 1 ======== CHANNEL f1 ======= SFO1 150.9148800 MHz NUC1 13C P1 10.00 use P13 2000.00 use PLW0 0 W PLW1 70.00000000 W SPNAM[5] Crp60comp.4 SPOAL5 0.500 SPOFFS5 0 Hz SPW5 10.69499969 W ======== CHANNEL f2 ======= SFO2 600.1319193 MHz NUC2 1H CPDPRG[2 waltz16 P3 12.00 use P4 24.00 use PCPD2 70.00 use PLW2 26.00000000 W PLW12 0.76407999 W 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 ppm S-22

1 H NMR (500 MHz, toluene d 8, 333 K) 7.33 7.32 7.32 7.27 7.25 7.24 7.16 7.15 7.13 7.12 7.09 7.01 6.98 6.97 6.17 6.15 6.13 4.88 4.83 4.78 4.71 4.67 4.65 4.59 4.53 4.51 4.49 4.42 4.39 4.33 4.31 4.22 4.20 4.15 4.13 4.09 4.05 4.02 3.98 3.88 3.81 3.78 3.77 3.76 3.75 3.69 3.63 3.46 3.45 3.44 3.43 2.11 2.10 2.10 2.10 2.09 0.48 NAME nmr EXPNO 163 Date_ 20160531 Time 21.04 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Tol NS 32 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 128 DW 71.400 use DE 6.00 use TE 333.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300132 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 53.89 1.00 5.18 3.23 1.14 3.28 1.05 2.13 1.11 1.11 0.97 2.28 2.20 3.27 1.08 3.11 1.02 S-23

13 C NMR (126 MHz, toluene d 8, 333 K) 162.66 162.27 161.63 160.66 160.25 159.57 139.53 139.50 139.37 139.36 139.33 139.20 138.60 138.05 128.52 128.46 128.45 127.94 127.93 127.87 127.86 127.81 127.72 127.70 127.64 127.61 127.54 115.80 113.09 112.96 112.80 101.36 98.64 87.61 83.95 81.12 80.70 78.79 78.76 75.66 75.58 75.46 75.07 75.03 74.79 73.74 73.62 73.60 73.12 72.87 69.66 69.43 20.86 20.71 20.55 20.40 20.25 20.09 19.94 NAME nmr EXPNO 165 Date_ 20160531 Time 22.33 PROBHD 5 mm Multinucl PULPROG zgpg TD 65536 SOLVENT Tol NS 11455 DS 8 SWH 26455.027 Hz FIDRES 0.403672 Hz AQ 1.2386304 sec RG 32768 DW 18.900 use DE 6.00 use TE 333.0 K D1 2.00000000 sec d11 0.03000000 sec DELTA 1.89999998 sec TD0 1 SFO1 125.7696860 MHz NUC1 13C P1 4.30 use PLW1 1.00000000 W SFO2 500.1320005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 90.00 use PLW2 1.00000000 W PLW12 1.00000000 W PLW13 1.00000000 W SI 65536 SF 125.7577426 MHz LB 1.00 Hz PC 1.40 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-24

0 1.0 2.0 3.0 4.0 5.0 abundance 19 F NMR (376 MHz, toluene-d 8, 333 K, C 6 F 6 internal standard) Filename = th01.06.te60oc_fluorine-3- Author = suzuki Experiment = proton.jxp Sample_Id = th01.06 Solvent = TOLUENE-D8 Creation_Time = 1-JUN-2016 22:41:47 Revision_Time = 1-JUN-2016 22:45:57 Current_Time = 1-JUN-2016 22:50:27 Comment = single_pulse Data_Format = 1D COMPLEX Dim_Size = 13107 Dim_Title = Fluorine19 Dim_Units = [ppm] Dimensions = X Site = JNM-ECS400 Spectrometer = DELTA2_NMR Field_Strength = 9.389766[T] (400[MHz]) X_Acq_Duration = 86.50752[ms] X_Domain = 19F X_Freq = 376.17105393[MHz] X_Offset = 0[ppm] X_Points = 16384 X_Prescans = 1 X_Resolution = 11.55968868[Hz] X_Sweep = 189.39393939[kHz] X_Sweep_Clipped = 151.51515152[kHz] Irr_Domain = Fluorine19 Irr_Freq = 376.17105393[MHz] Irr_Offset = 5[ppm] Tri_Domain = Fluorine19 Tri_Freq = 376.17105393[MHz] Tri_Offset = 5[ppm] Clipped = FALSE Scans = 32 Total_Scans = 32 Relaxation_Delay = 5[s] Recvr_Gain = 44 Temp_Get = 60[dC] X_90_Width = 7.12[us] X_Acq_Time = 86.50752[ms] X_Angle = 45[deg] X_Atn = 2.3[dB] X_Pulse = 3.56[us] Irr_Mode = Off Tri_Mode = Off Dante_Presat = FALSE Initial_Wait = 1[s] Repetition_Time = 5.08650752[s] -40.0-50.0-60.0-70.0-80.0-90.0-100.0-110.0-120.0-130.0-140.0-150.0-160.0-170.0-180.0 X : parts per Million : Fluorine19-103.199-107.040-109.775 S-25-162.200

1 H NMR (500 MHz, toluene d 8, 373 K) 7.27 7.26 7.26 7.26 7.26 7.25 7.25 7.25 7.23 7.23 7.21 7.21 7.14 7.14 7.13 7.13 7.12 7.12 7.11 7.11 7.11 7.08 7.08 7.07 7.05 7.05 7.04 7.03 7.02 7.01 7.01 7.00 6.98 6.97 6.96 6.96 6.96 6.94 6.25 6.23 6.21 4.85 4.83 4.77 4.75 4.68 4.65 4.56 4.54 4.51 4.42 4.40 4.23 4.21 4.12 4.10 4.08 3.86 3.84 3.82 3.78 3.77 3.75 3.75 3.71 3.69 3.68 3.66 3.66 3.64 3.64 3.47 3.47 3.46 3.46 3.45 3.45 3.45 3.44 2.11 2.10 2.10 2.10 2.09 NAME nmr EXPNO 80 Date_ 20160213 Time 14.24 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT CDCl3 NS 16 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 22.6 DW 71.400 use DE 6.00 use TE 300.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300120 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 35.96 1.00 6.11 2.11 2.11 4.03 2.06 2.02 2.04 2.06 2.05 2.06 2.03 2.03 S-26

13 C NMR (126 MHz, toluene d 8, 373 K) 163.19 163.10 163.07 162.98 162.64 161.18 161.09 161.06 160.97 160.62 139.78 139.62 139.50 138.90 128.60 128.55 128.54 128.49 128.04 127.99 127.92 127.70 127.66 127.62 113.09 112.94 112.77 101.08 100.86 100.63 87.89 81.56 81.01 79.23 75.69 75.17 75.00 74.04 73.24 70.11 20.86 20.71 20.55 20.40 20.25 20.09 19.94 NAME nmr EXPNO 78 Date_ 20160213 Time 12.58 PROBHD 5 mm Multinucl PULPROG zgpg TD 65536 SOLVENT Tol NS 2175 DS 8 SWH 28985.508 Hz FIDRES 0.442284 Hz AQ 1.1304960 sec RG 32768 DW 17.250 use DE 6.00 use TE 373.0 K D1 2.00000000 sec d11 0.03000000 sec DELTA 1.89999998 sec TD0 1 SFO1 125.7715724 MHz NUC1 13C P1 4.30 use PLW1 1.00000000 W SFO2 500.1320005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 90.00 use PLW2 1.00000000 W PLW12 1.00000000 W PLW13 1.00000000 W SI 65536 SF 125.7577154 MHz LB 1.00 Hz PC 1.40 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-27

abundance -2.0-1.0 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 19 F NMR (376 MHz, toluene-d 8, 373 K, C 6 F 6 internal standard) Filename = th01.07.te100oc_fluorine-1 Author = suzuki Experiment = proton.jxp Sample_Id = th01.07.te100oc Solvent = TOLUENE-D8 Creation_Time = 19-FEB-2016 16:28:15 Revision_Time = 19-FEB-2016 16:36:43 Current_Time = 19-FEB-2016 16:36:50 Comment = single_pulse Data_Format = 1D COMPLEX Dim_Size = 13107 Dim_Title = Fluorine19 Dim_Units = [ppm] Dimensions = X Site = JNM-ECS400 Spectrometer = DELTA2_NMR Field_Strength = 9.389766[T] (400[MHz]) X_Acq_Duration = 86.50752[ms] X_Domain = 19F X_Freq = 376.17105393[MHz] X_Offset = 0[ppm] X_Points = 16384 X_Prescans = 1 X_Resolution = 11.55968868[Hz] X_Sweep = 189.39393939[kHz] X_Sweep_Clipped = 151.51515152[kHz] Irr_Domain = Fluorine19 Irr_Freq = 376.17105393[MHz] Irr_Offset = 5[ppm] Tri_Domain = Fluorine19 Tri_Freq = 376.17105393[MHz] Tri_Offset = 5[ppm] Clipped = FALSE Scans = 128 Total_Scans = 128 Relaxation_Delay = 5[s] Recvr_Gain = 46 Temp_Get = 100[dC] X_90_Width = 7.12[us] X_Acq_Time = 86.50752[ms] X_Angle = 45[deg] X_Atn = 2.3[dB] X_Pulse = 3.56[us] Irr_Mode = Off Tri_Mode = Off Dante_Presat = FALSE Initial_Wait = 1[s] Repetition_Time = 5.08650752[s] -40.0-50.0-60.0-70.0-80.0-90.0-100.0-110.0-120.0-130.0-140.0-150.0-160.0-170.0-180.0 X : parts per Million : Fluorine19-108.330 S-28-162.200

COSY fg (toluene d 8, 373 K) ppm 3.5 4.0 4.5 5.0 5.5 6.0 6.5 NAME nmr EXPNO 81 Date_ 20160213 Time 14.38 INSTRUM PROBHD PULPROG TD SOLVENT NS DS spect 5 mm Multinucl cosygs 2048 Tol 4 2 SWH 2500.000 Hz FIDRES 1.220703 Hz AQ 0.4096000 sec RG 90.5 DW 200.000 usec DE TE 6.00 usec 373.0 K D0 0.00000300 sec D1 1.48689198 sec D13 0.00000300 sec D16 0.00010000 sec IN0 0.00040000 sec ======== CHANNEL f1 ======== NUC1 1H P0 9.00 usec P1 9.00 usec PL1 2.10 db SFO1 500.1327507 MHz ====== GRADIENT CHANNEL ===== P16 1000.00 usec F1 Acquisition parameters TD 256 SFO1 500.1328 MHz FIDRES 9.765625 Hz SW 4.999 ppm FnMODE undefined SI 1024 SF 500.1300120 MHz WDW SINE LB 0 Hz PC 1.00 F1 Processing parameters SI 1024 MC2 QF SF 500.1300120 MHz WDW SINE LB 0 Hz 7.0 7.5 8.0 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm S-29

HMBC FG (toluene d 8, 373 K) ppm 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 NAME nmr EXPNO 170 Date_ 20160602 Time 17.23 PROBHD 5 mm Multinucl PULPROG inv4gslplrnd TD 2048 SOLVENT Tol NS 2 DS 4 SWH 2500.000 Hz FIDRES 1.220703 Hz AQ 0.4096000 sec RG 11585.2 DW 200.000 usec DE 6.00usec TE 373.0K D0 0.00000300sec D1 2.00000000sec D2 0.00345000sec D6 0.06500000sec D13 0.00000300sec D16 0.00010000sec IN0 0.00002485sec ======== CHANNEL f1 ======== NUC1 1H P1 9.00 usec P2 20.40 usec PL1 2.10 db SFO1 500.1327507 MHz ======== CHANNEL f2 ======== NUC2 13C P3 8.00 usec PL2 5.00 db SFO2 125.7690572 MHz ====== GRADIENT CHANNEL ===== P16 1000.00 usec F1 Acquisition parameters TD 1024 SFO1 125.7691 MHz FIDRES 19.649145 Hz SW 159.982 ppm FnMODE undefined 130 135 140 145 150 155 160 165 170 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm S-30

HMQC (toluene d 8, 373 K) ppm 55 60 65 70 75 80 85 NAME nmr EXPNO 174 F1 Acquisition parameters TD 128 SFO1 125.7697 MHz FIDRES 196.540878 Hz SW 200.026 ppm FnMODE undefined SI 1024 SF 500.1300122 MHz WDW QSINE SSB 2 LB 0 Hz PC 1.40 F1 Processing parameters SI 512 MC2 TPPI SF 125.7577154 MHz WDW QSINE SSB 2 LB 0 Hz 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm S-31

13 C DEPT135 (toluene d 8, 373 K) 128.04 127.99 127.93 127.62 101.06 87.89 81.61 81.01 79.25 75.71 75.19 75.00 74.09 73.23 70.11 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 ppm S-32

1 H NMR (500 MHz, toluene d 8, 363 K) 7.45 7.42 7.27 7.27 7.25 7.23 7.23 7.22 7.20 7.19 7.18 7.16 7.15 7.15 7.14 7.14 7.13 7.13 7.12 7.12 7.09 7.09 7.08 7.08 7.08 7.07 7.06 7.06 7.05 7.03 7.03 7.02 7.01 7.00 7.00 6.98 6.98 6.98 6.97 6.97 6.84 6.80 6.67 6.65 4.86 4.84 4.83 4.82 4.72 4.68 4.66 4.60 4.57 4.54 4.51 4.43 4.41 4.29 4.27 4.14 4.12 4.10 3.87 3.85 3.83 3.79 3.78 3.76 3.75 3.71 3.70 3.68 3.67 3.67 3.65 3.65 3.47 3.47 3.47 3.46 3.46 3.45 3.45 3.44 2.11 2.10 2.10 2.10 2.09 NAME nmr EXPNO 11 Date_ 20160129 Time 14.56 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Tol NS 16 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 32 DW 71.400 use DE 6.00 use TE 300.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300123 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 1.05 45.04 1.05 2.00 8.13 2.14 2.12 2.00 2.15 2.09 2.03 2.11 2.14 2.06 2.01 2.02 2.08 S-33

13 C NMR (126 MHz, toluene d 8, 363 K) 185.06 162.87 161.74 160.82 160.22 158.19 145.98 139.64 139.47 139.35 138.67 137.26 130.81 128.82 128.63 128.59 128.51 127.93 127.88 127.84 127.79 127.69 127.63 127.58 125.96 116.12 115.86 113.57 113.45 113.28 87.73 81.43 80.97 79.03 75.64 75.14 75.10 73.93 73.16 70.51 69.90 20.86 20.71 20.55 20.40 20.25 20.09 19.94 NAME nmr EXPNO 48 Date_ 20160205 Time 22.03 PROBHD 5 mm Multinucl PULPROG zgpg TD 65536 SOLVENT Tol NS 4096 DS 8 SWH 28985.508 Hz FIDRES 0.442284 Hz AQ 1.1304960 sec RG 32768 DW 17.250 usec DE 6.00 usec TE 363.0 K D1 2.00000000 sec d11 0.03000000 sec DELTA 1.89999998 sec TD0 1 SFO1 125.7715724 MHz NUC1 13C P1 4.30 usec PLW1 1.00000000 W SFO2 500.1320005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 90.00 usec PLW2 1.00000000 W PLW12 1.00000000 W PLW13 1.00000000 W SI 65536 SF 125.7577264 MHz LB 1.00 Hz PC 1.40 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-34

abundance -1.0 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 19 F NMR (376 MHz, toluene-d 8, 373 K, C 6 F 6 internal standard) Filename = th01.10.te100oc_19f-1-7.jd Author = suzuki Experiment = proton.jxp Sample_Id = th01.10.te100oc Solvent = TOLUENE-D8 Creation_Time = 18-FEB-2016 18:14:39 Revision_Time = 19-FEB-2016 00:09:20 Current_Time = 19-FEB-2016 00:09:33 Comment = single_pulse Data_Format = 1D COMPLEX Dim_Size = 13107 Dim_Title = Fluorine19 Dim_Units = [ppm] Dimensions = X Site = JNM-ECS400 Spectrometer = DELTA2_NMR Field_Strength = 9.389766[T] (400[MHz]) X_Acq_Duration = 86.50752[ms] X_Domain = 19F X_Freq = 376.17105393[MHz] X_Offset = 0[ppm] X_Points = 16384 X_Prescans = 1 X_Resolution = 11.55968868[Hz] X_Sweep = 189.39393939[kHz] X_Sweep_Clipped = 151.51515152[kHz] Irr_Domain = Fluorine19 Irr_Freq = 376.17105393[MHz] Irr_Offset = 5[ppm] Tri_Domain = Fluorine19 Tri_Freq = 376.17105393[MHz] Tri_Offset = 5[ppm] Clipped = FALSE Scans = 32 Total_Scans = 32 Relaxation_Delay = 5[s] Recvr_Gain = 46 Temp_Get = 100[dC] X_90_Width = 7.12[us] X_Acq_Time = 86.50752[ms] X_Angle = 45[deg] X_Atn = 2.3[dB] X_Pulse = 3.56[us] Irr_Mode = Off Tri_Mode = Off Dante_Presat = FALSE Initial_Wait = 1[s] Repetition_Time = 5.08650752[s] -40.0-50.0-60.0-70.0-80.0-90.0-100.0-110.0-120.0-130.0-140.0-150.0-160.0-170.0-180.0 X : parts per Million : Fluorine19-106.425-110.482 S-35-162.200

1 H NMR (500 MHz, toluene d 8, 363 K) 14.26 7.90 7.87 7.32 7.29 7.25 7.16 7.15 7.09 6.98 6.92 6.89 6.75 6.74 5.14 4.91 4.89 4.82 4.80 4.76 4.67 4.58 4.56 4.47 4.45 4.42 4.41 4.35 4.33 4.18 4.16 4.14 3.95 3.93 3.90 3.83 3.77 3.72 3.69 3.61 3.58 3.55 3.53 2.11 2.10 2.10 2.10 2.09 NAME nmr EXPNO 35 Date_ 20160204 Time 10.52 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Tol NS 16 DS 2 SWH 8012.820 Hz FIDRES 0.244532 Hz AQ 2.0447233 sec RG 12.7 DW 62.400 use DE 6.00 use TE 300.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1337510 MHz SI 32768 SF 500.1300123 MHz LB 0.20 Hz PC 1.00 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm 0.88 0.97 47.95 2.00 0.93 15.12 4.01 1.06 1.02 8.02 2.04 S-36

13 C NMR (126 MHz, toluene d 8, 363 K) 192.00 166.25 165.17 164.24 163.61 161.85 161.57 145.94 139.81 139.59 139.56 139.43 139.38 139.29 139.16 138.67 137.10 130.94 128.80 128.48 128.41 127.97 127.79 127.52 127.33 123.80 115.97 112.62 108.23 107.45 107.30 107.15 87.94 87.62 81.10 80.84 80.71 79.15 79.06 78.93 75.61 75.55 75.09 75.03 75.02 74.76 73.91 73.88 73.26 72.97 70.49 70.07 69.99 20.86 20.70 20.55 20.40 20.25 20.09 19.94 NAME nmr EXPNO 124 Date_ 20160322 Time 22.14 PROBHD 5 mm Multinucl PULPROG zgpg TD 65536 SOLVENT Tol NS 2252 DS 8 SWH 26455.027 Hz FIDRES 0.403672 Hz AQ 1.2386304 sec RG 32768 DW 18.900 use DE 6.00 use TE 363.0 K D1 2.00000000 sec d11 0.03000000 sec DELTA 1.89999998 sec TD0 1 SFO1 125.7696860 MHz NUC1 13C P1 4.30 use PLW1 1.00000000 W SFO2 500.1320005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 90.00 use PLW2 1.00000000 W PLW12 1.00000000 W PLW13 1.00000000 W SI 65536 SF 125.7577400 MHz LB 1.00 Hz PC 1.40 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-37

19 F NMR (376 MHz, toluene-d 8, 373 K, C 6 F 6 internal standard) Filename = th01.26.te100oc_fluorine-2 Author = suzuki Experiment = proton.jxp Sample_Id = th01.26 Solvent = TOLUENE-D8 Creation_Time = 12-MAY-2016 23:32:29 Revision_Time = 13-MAY-2016 15:37:01 Current_Time = 13-MAY-2016 15:38:54 0 1.0 2.0 3.0 4.0 abundance Comment = single_pulse Data_Format = 1D COMPLEX Dim_Size = 13107 Dim_Title = Fluorine19 Dim_Units = [ppm] Dimensions = X Site = JNM-ECS400 Spectrometer = DELTA2_NMR Field_Strength = 9.389766[T] (400[MHz]) X_Acq_Duration = 86.50752[ms] X_Domain = 19F X_Freq = 376.17105393[MHz] X_Offset = 0[ppm] X_Points = 16384 X_Prescans = 1 X_Resolution = 11.55968868[Hz] X_Sweep = 189.39393939[kHz] X_Sweep_Clipped = 151.51515152[kHz] Irr_Domain = Fluorine19 Irr_Freq = 376.17105393[MHz] Irr_Offset = 5[ppm] Tri_Domain = Fluorine19 Tri_Freq = 376.17105393[MHz] Tri_Offset = 5[ppm] Clipped = FALSE Scans = 64 Total_Scans = 64 Relaxation_Delay = 5[s] Recvr_Gain = 46 Temp_Get = 100[dC] X_90_Width = 7.12[us] X_Acq_Time = 86.50752[ms] X_Angle = 45[deg] X_Atn = 2.3[dB] X_Pulse = 3.56[us] Irr_Mode = Off Tri_Mode = Off Dante_Presat = FALSE Initial_Wait = 1[s] Repetition_Time = 5.08650752[s] -40.0-50.0-60.0-70.0-80.0-90.0-100.0-110.0-120.0-130.0-140.0-150.0-160.0-170.0-180.0 X : parts per Million : Fluorine19-97.852-103.567 S-38-162.200

1 H NMR (500 MHz, toluene d 8, 373 K) 7.75 7.33 7.27 7.19 7.17 7.12 7.07 6.99 6.97 6.89 6.88 6.86 6.84 6.74 6.73 6.35 5.02 4.94 4.91 4.88 4.86 4.78 4.77 4.75 4.71 4.68 4.61 4.58 4.56 4.49 4.47 4.44 4.33 4.31 4.28 4.23 4.21 4.19 4.01 3.89 3.87 3.85 3.84 3.82 3.82 3.80 3.79 3.76 3.74 3.73 3.72 3.71 3.68 3.53 3.52 2.10 2.10 2.10 0.50 NAME nmr EXPNO 154 Date_ 20160511 Time 11.16 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Tol NS 32 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 128 DW 71.400 use DE 6.00 use TE 363.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300120 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 2.00 53.86 1.98 1.00 0.98 7.18 3.04 1.12 2.07 8.16 0.98 4.08 3.09 2.04 S-39

13 C NMR (126 MHz, toluene d 8, 373 K) 174.41 163.09 162.10 161.86 161.70 161.11 159.54 156.17 139.59 139.41 139.37 139.29 139.26 138.60 137.09 128.80 128.56 128.48 128.44 128.02 127.96 127.64 127.49 127.44 124.59 115.97 112.64 111.49 107.81 88.50 87.74 81.05 80.86 80.72 79.12 78.97 78.17 75.53 75.51 75.03 75.01 74.86 74.16 73.97 73.85 73.80 73.07 70.59 70.09 69.85 20.86 20.71 20.55 20.40 20.25 20.09 19.94 NAME nmr EXPNO 160 Date_ 20160512 Time 22.44 PROBHD 5 mm Multinucl PULPROG zgpg TD 65536 SOLVENT Tol NS 3637 DS 8 SWH 28985.508 Hz FIDRES 0.442284 Hz AQ 1.1304960 sec RG 32768 DW 17.250 use DE 6.00 use TE 373.0 K D1 2.00000000 sec d11 0.03000000 sec DELTA 1.89999998 sec TD0 1 SFO1 125.7715724 MHz NUC1 13C P1 4.30 use PLW1 1.00000000 W SFO2 500.1320005 MHz NUC2 1H CPDPRG[2 waltz16 PCPD2 90.00 use PLW2 1.00000000 W PLW12 1.00000000 W PLW13 1.00000000 W SI 65536 SF 125.7577472 MHz LB 1.00 Hz PC 1.40 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm S-40

0 1.0 2.0 3.0 4.0 abundance 19 F NMR (376 MHz, toluene-d 8, 373 K, C 6 F 6 internal standard) Filename = th01.36..te100oc.fluorine- Author = suzuki Experiment = proton.jxp Sample_Id = th01.36.no4 Solvent = TOLUENE-D8 Creation_Time = 12-MAY-2016 22:36:02 Revision_Time = 13-MAY-2016 15:16:31 Current_Time = 13-MAY-2016 15:20:48 Comment = single_pulse Data_Format = 1D COMPLEX Dim_Size = 13107 Dim_Title = Fluorine19 Dim_Units = [ppm] Dimensions = X Site = JNM-ECS400 Spectrometer = DELTA2_NMR Field_Strength = 9.389766[T] (400[MHz]) X_Acq_Duration = 86.50752[ms] X_Domain = 19F X_Freq = 376.17105393[MHz] X_Offset = 0[ppm] X_Points = 16384 X_Prescans = 1 X_Resolution = 11.55968868[Hz] X_Sweep = 189.39393939[kHz] X_Sweep_Clipped = 151.51515152[kHz] Irr_Domain = Fluorine19 Irr_Freq = 376.17105393[MHz] Irr_Offset = 5[ppm] Tri_Domain = Fluorine19 Tri_Freq = 376.17105393[MHz] Tri_Offset = 5[ppm] Clipped = FALSE Scans = 64 Total_Scans = 64 Relaxation_Delay = 5[s] Recvr_Gain = 46 Temp_Get = 100[dC] X_90_Width = 7.12[us] X_Acq_Time = 86.50752[ms] X_Angle = 45[deg] X_Atn = 2.3[dB] X_Pulse = 3.56[us] Irr_Mode = Off Tri_Mode = Off Dante_Presat = FALSE Initial_Wait = 1[s] Repetition_Time = 5.08650752[s] -40.0-50.0-60.0-70.0-80.0-90.0-100.0-110.0-120.0-130.0-140.0-150.0-160.0-170.0-180.0 X : parts per Million : Fluorine19-100.802-105.934-107.101 S-41-162.200

1 H NMR (500 MHz, toluene d 8, 300 K) 8.25 8.24 8.00 7.99 7.59 7.57 7.36 7.34 7.33 7.33 7.31 7.30 7.30 7.29 7.25 7.24 7.23 7.23 7.22 7.21 7.21 7.20 7.19 7.19 7.17 7.16 7.14 7.14 7.13 7.13 7.13 7.12 7.11 7.11 7.09 7.08 7.07 7.07 7.06 7.05 7.04 7.04 7.03 7.02 7.01 7.01 7.00 7.00 6.99 6.97 6.96 6.92 6.91 6.90 6.89 6.87 6.85 6.80 6.79 6.78 6.76 6.59 6.52 5.46 5.30 5.28 5.19 5.02 5.00 4.92 4.91 4.89 4.86 4.84 4.82 4.75 4.65 4.64 4.61 4.59 4.57 4.54 4.49 4.40 4.39 4.38 4.37 4.28 4.27 4.26 4.25 4.24 4.23 3.76 3.75 3.75 3.75 3.74 3.58 2.11 2.10 2.10 2.10 2.09 NAME nmr EXPNO 168 Date_ 20160602 Time 14.23 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Tol NS 64 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 64 DW 71.400 use DE 6.00 use TE 300.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300144 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 6.00 63.75 28.01 9.46 S-42

1 H NMR (500 MHz, toluene d 8, 373 K) 8.02 7.97 7.95 7.93 7.89 7.87 7.67 7.52 7.26 7.25 7.21 7.20 7.17 7.14 7.12 7.11 7.09 7.07 7.07 7.07 7.06 7.05 7.01 7.00 6.99 6.98 6.97 6.97 6.97 6.96 6.90 6.89 6.87 6.82 6.81 6.51 5.96 5.80 5.42 5.36 5.26 5.25 5.13 4.92 4.89 4.89 4.84 4.81 4.79 4.77 4.74 4.73 4.72 4.62 4.59 4.57 4.55 4.53 4.52 4.46 4.42 4.38 4.36 4.31 4.29 4.27 4.25 4.13 3.81 3.79 3.76 3.71 3.68 3.61 3.60 3.60 3.58 3.47 2.10 NAME nmr EXPNO 104 Date_ 20160309 Time 21.30 PROBHD 5 mm Multinucl PULPROG zg TD 32768 SOLVENT Tol NS 128 DS 2 SWH 7002.801 Hz FIDRES 0.213709 Hz AQ 2.3396351 sec RG 128 DW 71.400 use DE 6.00 use TE 373.0 K D1 2.00000000 sec MCREST 0 sec MCWRK 0.01500000 sec ======== CHANNEL f1 ======= NUC1 1H P1 4.50 use PL1 2.10 db SFO1 500.1330008 MHz SI 32768 SF 500.1300120 MHz LB 0.20 Hz PC 1.00 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 6.00 54.52 25.69 8.79 S-43

HPLC HPLC (4.6 250 mm Ph-3, 30% EtOAc in hexane, 1 ml/min, UV detection at 254 nm) 5.81 min and 99.0% pure; R f 0.39 (EtOAc/hexane = 3/7). S-44