1. General information 1 H NMR spectra were recorded at 400 MHz with JEOL ECS-400 instruments. Coupling constants (J) are reported in Hz. 13 C NMR spe

Stereoselective Synthesis of Tabtoxinine-β-lactam by using the Vinylogous Mukaiyama Aldol Reaction with Acetate-type Vinylketene Silyl N,O-Acetal and α-keto-β-lactam Hirotaka Ejima, Fumihiro Wakita, Ryo Imamura, Takuya Kato, and Seijiro Hosokawa* Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University 3-4-1 Ohkubo, Shunjuku-ku, Tokyo 169-8555, Japan Supporting Information Table of Contents 1. General information 2. Experimental details 3. References 4. 1 H NMR and 13 C NMR spectra of new compounds S2 S3-S16 S17 S18-S48 S1

1. General information 1 H NMR spectra were recorded at 400 MHz with JEOL ECS-400 instruments. Coupling constants (J) are reported in Hz. 13 C NMR spectra were recorded at 100 MHz with JEOL ECS-400 instruments. Chemical shifts (δ) are quoted in parts per million (ppm) and referenced to the residual solvent peak (CDCl 3 7.26 ppm for 1 H, 77.00 ppm for 13 C; C 6 D 6 7.16 ppm for 1 H, D 2 O 4.72 ppm for 1 H, 49.50 ppm (MeOH as internal standard) for 13 C). The following abbreviations were used for multiplicities (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet). Melting point (mp) determinations were performed by using a Yanako MP-S3 instrument. FT-IR spectra were recorded with ThermoFisher SCIENTIFIC NICOLET 6700 FT-IR. HR-MS and MS were obtained with a ThermoFisher EXACTIVE PLUS and JEOL JMS-GCMATEII, respectively. Optical rotations were measured with a JASCO P-2200. X-ray crystallographic analysis was performed with Rigaku RAXIS-RAPID. All reactions were monitored by TLC (silica gel 60 F 254, Merck). THF was distilled from Na before use. CH 2 Cl 2 was distilled from P 2 O 5 immediately before use. Molecular sieves 4A was activated by heating at 250 C in vacuo before use. All moisture sensitive reactions were performed under a static argon atmosphere in glassware with magnetic stirring. S2

2. Experimental details -Keto- -lactam 6 was prepared from S1 according to the Paquette s procedure. S1 Synthesis of compound S2 To a solution of methyl 3-hydroxy-2-methylene butyrate S1 (9.38 ml, 77.3 mmol) in MeOH (100 ml) was added p-methoxybenzylamine (10.0 ml, 77.3 mmol). After stirring for 2 d at room temperature, the resulting mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:4) to give compound S2 as a colorless oil (16.1 g, 60.3 mmol, 78%). R f value: 0.27 (n-hexane/ethyl acetate = 1:4); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.21-7.16 (2H, m), 6.86-6.81 (2H, m), 4.19 (1H, dq, J = 6.8, 6.5 Hz), 3.77 (3H, s), 3.70 (2H, s), 3.68 (3H, s), 3.07 (1H, dd, J = 12.2, 7.0 Hz), 2.98 (1H, dd, J = 12.2, 4.0 Hz), 2.45 (1H, ddd, J = 7.0, 6.8, 4.0 Hz), 1.16 (3H, d, J = 6.5 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 173.5, 158.8, 131.0, 129.4, 113.8, 70.1, 55.2, 53.1, 51.7, 50.8, 48.4, 21.8; HRMS (ESI) m/z calcd for C 14 H 22 O 4 N [M+H] +, 268.1543; found 268.1540; IR (thin film, KBr) 3317, 2952, 2837, 1731, 1513, 1247, 1174, 1034, 818 cm -1. S3

Synthesis of compound S3 To a solution of compound S2 (6.77 g, 25.3 mmol) in THF (33.9 ml) was added t-bumgcl solution (101 ml, 101 mmol, 1.0 M in THF) at 0 C and warmed to room temperature. After stirring for 3 h, saturated aqueous solution of NH 4 Cl (67.7 ml) was added at 0 C. The resulting mixture was filtered through a pad of celite and concentrated under reduced pressure to a volume of 70 ml. Ethyl acetate (100 ml) was added to the mixture and phases were separated. The aqueous layer was extracted with ethyl acetate (100 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/acetone = 3:2) to give the compound S3 as a white solid (5.73 g, 24.4 mmol, 96%). R f value: 0.28 (n-hexane/acetone = 3:2); mp 69-70 C; 1 H NMR (C 6 D 6, 400 MHz): δ (ppm) 7.02-6.97 (2H, m), 6.76-6.71 (2H, m), 4.16 (1H, d, J = 15.0 Hz), 3.95 (1H, d, J = 15.0 Hz), 3.82 (1H, qd, J = 6.5, 5.5 Hz), 3.27 (3H, s), 2.80 (1H, dd, J = 5.5, 2.5 Hz), 2.76 (1H, ddd, J = 5.5, 5.5, 2.5 Hz), 2.58 (1H, dd, J = 5.5, 5.5 Hz), 1.34-1.26 (1H, brs), 1.01 (3H, d, J = 6.5 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 168.2, 159.1, 129.4, 127.5, 114.1, 65.0, 56.8, 55.2, 45.3, 40.9, 21.3; HRMS (ESI) m/z calcd for C 13 H 17 O 3 NNa [M+Na] +, 258.1101; found 258.1101; IR (thin film, KBr) 3406, 2966, 1727, 1514, 1247 cm -1. Synthesis of compound S4 To a solution of compound S3 (7.21 g, 30.6 mmol) in dichlorormethane (72.1 ml) was added triethylamine (6.42 ml, 46.0 mmol) and methanesulfonyl chloride (2.84 ml, 36.7 mmol) at 0 C. S4

After stirring for 5 min, the resulting mixture was diluted with water (70.0 ml) and layers were separated. The aqueous layer was extracted with dichloromethane (70.0 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel (ethyl acetate) to give the mesylated compound, which was immediately used to the next reaction. To a solution of the resulting mesylated compound in toluene (72.1 ml) was added DBU (4.86 ml, 32.2 mmol) and warmed to 70 C. After stirring for 2 h, the reaction mixture cooled to room temperature, and acidified to ph 2 with 1 M HCl. The layers were separated and the aqueous layer was extracted with toluene (70.0 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel (n-hexane/ethyl acetate = 3:2) to give E/Z mixture of compound S4 (E/Z 5:1) as a pale yellow solid (5.79 g, 26.7 mmol, 87% in 2 steps). [(E)-isomer]: white solid; R f value: 0.38 (n-hexane/ethyl acetate = 1:1); mp 64-65 C; 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.20-7.15 (2H, m), 6.90-6.85 (2H, m), 6.16 (1H, qt, J = 7.0, 1.5 Hz), 4.43 (2H, s), 3.80 (3H, s), 3.60 (2H, d. J = 1.5 Hz), 1.70 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 163.8, 159.1, 138.1, 129.4, 127.7, 121.3, 114.1, 55.3, 46.3, 45.3, 14.2; HRMS (ESI) m/z calcd for C 13 H 15 O 2 NNa [M+Na] +, 240.0995; found 240.0995; IR (thin film, KBr) 2944, 1744, 1513, 1386, 1246, 1032, 772 cm -1. [(Z)-isomer]: pale yellow oil; R f value: 0.55 (n-hexane/ethyl acetate = 1:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.20-7.15 (2H, m), 6.89-6.84 (2H, m), 5.59 (1H, qt, J = 7.0, 1.0 Hz), 4.42 (2H, s), 3.80 (3H, s), 3.51 (2H, d. J = 1.0 Hz), 2.04 (3H, d, J = 7.0 Hz) ; 13 C NMR (CDCl 3, 400MHz): δ (ppm) 164.3, 159.0, 136.7, 129.4, 127.8, 124.8, 114.0, 55.2, 46.9, 45.1, 14.6; HRMS (ESI) m/z calcd for C 13 H 15 O 2 NNa [M+Na] +, 240.0995; found 240.0996; IR (thin film, KBr) 2942, 1733, 1513, 1390, 1246, 1033, 795 cm -1. Synthesis of compound 6 To a solution of compound S4 (5.92 g, 27.3 mmol) in 1,4-dioxane (118 ml) and water (39.4 ml) were added 2,6-lutidine (6.31 ml, 54.5 mmol), 4% osmium tetroxide in water (3.46 ml, 0.545 mmol) and sodium periodate (23.3 g, 109 mmol) at 0 C. After strirring 2.5 h at room temperature, S5

the resulting mixture was diluted with water (195 ml) and dichloromethane (390 ml). Layers were separated and the aqueous layer was extracted with dichloromethane (390 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 2:3) to give compound 6 as a pale yellow solid (4.32 g, 22.6 mmol, 83%). R f value: 0.27 (n-hexane/ethyl acetate = 2:3); mp 68-70 C; 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.23-7.18 (2H, m), 6.92-6.87 (2H, m), 4.70 (2H, s), 3.81 (3H, s), 3.76 (2H, s); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 192.9, 163.3, 159.7, 129.8, 125.4, 114.5, 58.8, 55.3, 46.4; HRMS (ESI) m/z calcd for C 11 H 11 O 3 NNa [M+Na] +, 228.0631; found 228.0632; IR (thin film, KBr) 1821, 1764, 1514, 1247, 1219, 772 cm -1. S6

Synthesis of compound 12 A solution of compound 6 in dichloromethane (5.0 w/v%) was dried over molecular sieves 4A (500 wt%)for 4 h at room temperature. The supernatant solution was transferred by syringe to another flask and concentrated under reduced pressure. To a solution of compound 6 (25.5 mg, 0.124 mmol) and compound 3 (87.7mg, 0.1491 mmol) in dichloromethane (1.02 ml) was added tin(iv) chloride (43.6 μl, 0.373 mmol) at -78 C. After stirring for 12 h, pyridine (120 μl, 1.49 mmol) was added to the reaction mixture and the resulting mixture was warmed to room temperature. Then, a mixture of sat. NaHCO 3 aq. and sat. Rochelle salt aq. (1:1, 2.04 ml) was added to the solution. The resulting two-phase mixture was stirred vigorously for 1 h. After the layers were separated, the aqueous layer was extracted with dichloromethane (1.2 ml 3). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:1) to give compound 12 as colorless oil (66.8 mg, 97%). R f value: 0.20 (n-hexane / ethyl acetate = 1:1); Optical rotation: [α] 24 D 164.4 (c 1.02, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.49-7.44 (2H, m), 7.42-7.23 (9H, m), 7.16-7.10 (2H, m), 7.07 (1H, ddd, J = 15.5, 7.0, 7.0 Hz), 6.90-6.84 (2H, m), 5.45 (1H, d, J = 3.0 Hz), 4.33 (1H, d, J = 15.0 Hz), 4.26 (1H, d, J = 15.0 Hz), 3.80 (3H, s), 3.18 (1H, s), 3.18 (1H, d, J = 6.0 Hz), 3.16 (1H, J = 6.0 Hz), 2.78 (1H, ddd, J = 15.5, 7.0, 1.0 Hz), 2.67 (1H, ddd, J = 15.5, 7.0, 1.0 Hz), 1.98 (1H, qqd, J = 7.0, 7.0, 3.0 Hz), 0.89 (3H, d, J = 7.0 Hz), 0.76 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 169.7, 164.2, 159.2, 152.9, 143.6, 142.2, 138.2, 129.5, 128.9, 128.6, 128.3, 127.9, 126.7, 125.9, 125.6, 124.0, 114.3, 89.4, 83.1, 64.3, 55.3, 53.3, 45.0, 37.8, 30.1, 21.8, 16.3; HRMS (ESI) m/z calcd for C 33 H 34 O 6 N 2 Na [M+Na] +, 577.2309; found 577.2309; IR (thin film, KBr) 3355, 2965, 1778, 1734, 1514, 1351, 1247, 1176, 760 cm -1. S7

Synthesis of compound 15 To a solution of 12 (2.35g, 4.23 mmol) in ethyl acetate (71.0 ml) was added 10% Pd/C (235 mg, 0.221 mmol) and stirred for 2 h at room temperature. The mixture was filtered through a pad of celite. The filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 2:3) to give the compound 15 as white solid (2.36 g, 4.23 mmol, quant.). R f value: 0.40 (n-hexane/ethyl acetate = 2:3); mp 174-176 C; Optical rotation: [α] 23 D 150.0 (c 1.03, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.48-7.43 (2H, m), 7.41-7.24 (8H, m), 7.17-7.12 (2H, m), 6.90-6.85 (2H, m), 5.36 (1H, d, J = 3.0 Hz), 4.31 (2H, s), 3.80 (3H, s), 3.21-3.16 (1H, m), 3.11 (2H, s), 3.00-2.90 (1H, m), 2.84-2.74 (1H, m), 1.96 (1H, qqd, J = 7.0, 7.0, 3.0 Hz), 1.87-1.67 (4H, m), 0.86 (3H, d, J = 7.0 Hz), 0.74 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 172.7, 170.3, 159.2, 153.0, 142.2, 138.0, 129.5, 128.9, 128.6, 128.4, 127.9, 127.0, 125.9, 125.6, 114.2, 89.5, 84.4, 64.4, 55.3, 53.8, 44.9, 34.9, 33.6, 29.8, 21.8, 18.6, 16.4; HRMS (ESI) m/z calcd for C 33 H 36 O 6 N 2 Na [M+Na] +, 579.2466; found 579.2465; IR (thin film, KBr) 3368, 2964, 1782, 1732, 1514, 1247, 1176, 759 cm -1. The absolute configuration of 15 was determined by X-ray crystallography. Fig. S1. ORTEP drawing of 15 S8

Synthesis of compound 16 PMBN OH O O N Ph O O Ph BOMCl TBAI i-pr 2 NEt THF 65 C, 12 h quant. BOMO PMBN O O Ph Ph N O O 19 20 To a solution of compound 15 (1.98 g, 3.56 mmol) and tetrabutylammonium iodide (1.31 g, 3.56 mmol) in THF (19.8 ml) were added N,N-diisopropylethylamine (1.81 ml, 10.7 mmol) and benzyl chloromethyl ether (1.47 ml, 10.7 mmol). After strirring for 12 h at 65 C, the resulting mixture was added sat. NaHCO 3 aq. (19.8 ml) at 0 C and concentrated under reduced pressure to a volume of 20 ml. Chloroform (20 ml) was added to the mixture and phases were separated. The aqueous layer was extracted with chloroform (20 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/acetone = 4:1) to give the compound 16 as a colorless oil (2.41 g, 3.56 mmol, quant.). R f value: 0.30 (n-hexane/acetone = 3:1); Optical rotation: [α] 23 D 97.2 (c 1.00, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.48-7.43 (2H, m), 7.41-7.23 (13H, m), 7.16-7.10 (2H, m), 6.84-6.79 (2H, m), 5.36 (1H, d, J = 3.0 Hz), 4.98 (1H, d, J = 7.0 Hz), 4.90 (1H, d, J = 7.0 Hz), 4.64 (1H, d, J = 12.0 Hz), 4.58 (1H, d, J = 12.0 Hz), 4.36 (1H, d, J = 15.0 Hz), 4.27 (1H, d, J = 15.0 Hz), 3.78 (3H, s), 3.45 (1H, d, J = 6.0 Hz), 2.99 (1H, d, J = 6.0 Hz), 2.96 (1H, ddd, J = 17.0, 6.5, 6.5 Hz), 2.75 (1H, d, J = 17.0, 7.5, 6.0 Hz), 1.96 (1H, qqd, J = 7.0, 7.0, 3.0 Hz),1.92-1.68 (4H, m), 0.86 (3H, d, J = 7.0 Hz), 0.74 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 172.4, 168.5, 159.1, 153.0, 142.2, 138.1, 137.5, 129.4, 128.9, 128.6, 128.3, 128.3, 127.9, 127.8, 127.6, 127.1, 125.9, 125.5, 114.1, 91.7, 89.3, 88.9, 70.0, 64.3, 55.2, 51.0, 44.9, 35.0, 33.4, 29.8, 21.8, 18.7, 16.4; HRMS (ESI) m/z calcd for C 41 H 44 O 7 N 2 Na [M+Na] +, 699.3041; found 699.3035; IR (thin film, KBr) 2963, 1782, 1751, 1704, 1514, 1247, 1176, 1035, 751, 699 cm -1. S9

Synthesis of compound 17 To a mixture of KHMDS solution (10.1 ml, 5.07 mmol, 0.5 M in toluene) and THF (26.4 ml) was added via cannula a precooled solution of compound 16 (2.64 g, 3.90 mmol) in THF (20.0 ml) at -78 C. Residual 16 was rinsed in with two 3.2 ml of THF, and stirring was continued at -78 C for 30 min. A precooled solution of trisyl azide S2 (1.57g, 5.07 mmol) in THF (26.4 ml) was added via cannula to the solution of potassium enolate at -78 C. After 20 min, the reaction was quenched with glacial acetic acid (1.03 ml, 17.9 mmol). The reaction mixture was immediately warmed to 30 C and stirred for 1 h. Dichloromethane (100 ml) and dilute brine (100 ml) was added to the mixture and layers were separated. The aqueous layer was extracted with dichloromethane (100 ml 2). The combined organic layer was washed with sat. NaHCO 3 aq (100 ml 3) and dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (toluene/ethyl acetate = 12:1) to give the compound 17 as a colorless oil (2.22 g, 3.09 mmol, 82%). The diastereomer of 17 can be separated by column chromatography on silica gel (n-hexane/acetone = 3:1). R f value: 0.27 (toluene/ethyl acetate = 12:1); Optical rotation: [α] 23 D 82.0 (c 1.08, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.47-7.43 (2H, m), 7.41-7.19 (13H, m), 7.15-7.08 (2H, m), 6.84-6.78 (2H, m), 5.35 (1H, d, J = 3.5 Hz), 5.02, (1H, dd, J = 8.0, 4.0 Hz), 4.90 (1H, d, J = 7.0 Hz), 4.80 (1H, d, J = 7.0 Hz), 4.57 (1H, d, J = 12.0 Hz), 4.53 (1H, d, J = 12.0 Hz), 4.37 (1H, d, J = 15.0 Hz), 4.21 (1H, d, J = 15.0 Hz), 3.78 (3H, s), 3.40 (1H, d, J = 6.0 Hz), 2.80 (1H, d, J = 6.0 Hz), 2.02 (1H, qqd, J = 7.0, 7.0, 3.5 Hz),1.85-1.62 (4H, m), 0.90 (3H, d, J = 7.0 Hz), 0.80 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 169.9, 168.1, 159.2, 152.4, 141.9, 137.5, 137.4, 129.4, 129.0, 128.7, 128.5, 128.4, 128.1, 127.9, 127.7, 127.0, 125.7, 125.4, 114.2, 91.7, 90.0, 88.2, 70.1, 65.1, 59.8, 55.2, 50.8, 44.9, 30.6, 29.7, 25.3, 21.6, 16.2; HRMS (ESI) m/z calcd for C 41 H 43 O 7 N 5 Na [M+Na] +, 740.3055; found 740.3048; IR (thin film, KBr) 2965, 2105, 1783, 1751, 1708, 1514, 1248, 1209, 1177, 1035, 760, 699 cm -1. S10

Synthesis of compound 18 To a solution of compound 17 (669 mg, 0.933 mmol) in MeCN (13.7 ml) was added celium (IV) ammonium nitrate (1.12 g, 2.05 mmol) at room temperature. After stirring for 30 min, H 2 O (4.55 ml) was added dropwise and stirred for 12 h. Na 2 S 2 O 3 (324 mg, 2.05 mmol) and sat. NaHCO 3 aq. (20 ml) were added to the resulting mixture at 0 C. Ethyl acetate (20 ml) was added to the mixture and layers were separated. The aqueous layer was extracted with ethyl acetate (20 ml 2). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 2:1) to give the compound 18 as a colorless oil (394 mg, 0.659 mmol, 71%). R f value: 0.23 (n-hexane/ethyl acetate = 2:1); Optical rotation: [α] 23 D 87.6 (c 2.54, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.50-7.45 (2H, m), 7.41-7.22 (13H, m), 5.57 (1H, s), 5.37 (1H, d, J = 3.5 Hz), 5.04 (1H, dd, J = 8.0, 4.5 Hz), 4.90 (1H, d, J = 7.0 Hz), 4.85 (1H, d, J = 7.0 Hz), 4.59 (2H, s), 3.58 (1H, d, J = 6.0 Hz), 2.93 (1H, d, J = 6.0 Hz), 2.02 (1H, qqd, J = 7.0, 7.0, 3.5 Hz),1.89-1.66 (4H, m), 0.91 (3H, d, J = 7.0 Hz), 0.81 (3H, d, J = 7.0 Hz); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 169.9, 169.2, 152.5, 142.0, 137.5, 137.3, 129.0, 128.7, 128.5, 128.4, 128.2, 128.0, 127.8, 125.7, 125.4, 91.6, 90.0, 89.9, 70.2, 65.1, 59.8, 47.5, 30.7, 29.7, 25.3, 21.6, 16.3; HRMS (ESI) m/z calcd for C 33 H 35 O 6 N 5 Na [M+Na] +, 620.2480; found 620.2476; IR (thin film, KBr) 3306, 2966, 2104, 1779, 1709, 1368, 1211, 1178, 1051, 761, 699 cm -1. S11

Synthesis of compound 19 A mixture of titanium tetraisopropoxide (365 μl, 1.23 mmol) and benzyl alcohol (2.56 ml) was stirred under the vacuum (10 mmhg) for 30 min in order to remove the 2-propanol and then transferred via cannula to the compound 18 (364 mg, 0.615 mmol) in a dried flask. The mixture was heated to 80 C for 12 h and was subsequently quenched by the addition of 1 M HCl aq. (10 ml). The solution was extracted with ethyl acetate (10 ml 3). The combined organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/ethyl acetate = 10:1) to give the compound 19 as a colorless oil (229 mg, 0.540 mmol, 88%). R f value: 0.27 (chloroform/ethyl acetate = 10:1); Optical rotation: [α] 24 D 24.8 (c 2.08, CHCl 3 ); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.39-7.26 (10H, m), 5.68 (1H, s), 5.23 (2H, s), 4.98 (1H, d, J = 7.0 Hz), 4.95 (1H, d, J = 7.0 Hz), 4.67 (1H, d, J = 12.0 Hz), 4.63 (1H, d, J = 12.0 Hz), 4.04 (1H, dd, J = 7.5, 4.5 Hz), 3.70 (1H, d, J = 6.0 Hz), 3.16 (1H, d, J = 6.0 Hz), 2.28-2.18 (1H, m), 2.04-1.97 (2H, m), 1.96-1.84 (1H, m); 13 C NMR (CDCl 3, 100 MHz): δ (ppm) 170.1, 169.3, 137.2, 135.0, 128.7, 128.6, 128.5, 128.5, 127.95, 127.87, 91.8, 90.1, 70.4, 67.5, 61.8, 48.0, 31.0, 25.8; HRMS (ESI) m/z calcd for C 22 H 24 O 5 N 4 Na [M+Na] +, 447.1639; found 447.1636; IR (thin film, KBr) 3284, 2900, 2106, 1759, 1188, 1044, 1027, 739, 698 cm -1. S12

The absolute configuration of the C2 position was determined by derivatization to (S)- and (R)- MTPA amides. S3 Synthesis of compound S5 To a solution of compound 19 (11.7 mg, 0.0285 mmol) in THF (292 μl) and H 2 O (59 μl) was added triphenylphosphine (9.7 mg, 0.037 mmol). After stirring for 12 h at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/methanol = 15:1) to give the compound S5 as a white solid (9.0 mg, 0.0226 mmol, 80%). R f value: 0.23 (chloroform/methanol = 15:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.38-7.27 (10H, m), 5.65 (1H, s), 5.16 (2H, s), 4.98 (1H, d, J = 7.0 Hz), 4.94 (1H, d, J = 7.0 Hz), 4.67 (1H, d, J = 11.5 Hz), 4.63 (1H, d, J =11.5 Hz), 3.67 (1H, d, J = 6.0 Hz), 3.54 (1H, dd, J = 8.0, 5.0 Hz), 3.15 (1H, d, J = 6.0 Hz), 2.16-2.06 (1H, m), 2.03-1.97 (2H, m), 1.76-1.65 (1H, m); HRMS (ESI) m/z calcd for C 22 H 27 O 5 N 2 [M+H] +, 339.1914; found 339.1914. Synthesis of compound (S)-MTPA amide S6 To a solution of compound S5 (4.3 mg, 0.012 mmol) in pyridine (215 μl) was added (R)-MTPACl (3.3 μl, 0.0176 mmol). After stirring for 2 h at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:1) to give the compound S6 as a colorless oil (6.3 mg, 0.012 mmol, 95%). R f value: 0.33 (n-hexane/ethyl acetate = 1:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.57-7.53 (2H, m), 7.38-7.26 (14H, m), 5.63 (1H, s), 5.24 (1H, d, J = 12.0 Hz), 5.14 (1H, d, J = 12.0 S13

Hz), 4.88 (1H, d, J = 7.5 Hz), 4.81 (1H, d, J = 7.5 Hz), 4.71 (1H, ddd, J = 7.5, 7.5, 5.5 Hz), 4.59 (1H, d, J = 11.5 Hz), 4.54 (1H, d, J = 11.5 Hz), 3.55 (1H, d, J = 6.0 Hz), 3.48 (3H, s), 2.93 (1H, d, J = 6.0 Hz), 2.27-2.13 (1H, m), 1.93-1.81 (2H, m),1.71-1.60 (1H, m); HRMS (ESI) m/z calcd for C 32 H 33 O 7 N 2 F 3 Na [M+Na] +, 637.2132; found 637.2129. Synthesis of compound (R)-MTPA amide S7 To a solution of compound S5 (4.2 mg, 0.011 mmol) in pyridine (210 μl) was added (S)-MTPACl (3.2 μl, 0.0171 mmol). After stirring for 12 h at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 1:1) to give the compound S7 as a colorless oil (5.6 mg, 0.0091 mmol, 86%). R f value: 0.33 (n-hexane/ethyl acetate = 1:1); 1 H NMR (CDCl 3, 400 MHz): δ (ppm) 7.56 (1H, d, J = 7.5 Hz), 7.54-7.49 (2H, m), 7.41-7.26 (13H, m), 5.66 (1H, s), 5.22 (1H, d, J = 12.0 Hz), 5.15 (1H, d, J = 12.0 Hz), 4.98 (1H, d, J = 7.5 Hz), 4.92 (1H, d, J = 7.5 Hz), 4.69 (1H, ddd, J = 7.5, 7.5, 5.5 Hz), 4.67 (1H, d, J = 11.5 Hz), 4.63 (1H, d, J = 11.5 Hz), 3.67 (1H, d, J = 6.0 Hz), 3.33 (3H, s), 3.09 (1H, d, J = 6.0 Hz), 2.35-2.22 (1H, m), 2.05-1.82 (3H, m) ; HRMS (ESI) m/z calcd for C 32 H 33 O 7 N 2 F 3 Na [M+Na] +, 637.2132; found 637.2128. Ph 0.08 0.09 O 0.12 0.16 0.03 0.10 0.11 HN O 0.14 0.21 O 0.09 0.11 = S R NHMTPA H 0.02 O O 0.005 0.025 Fig. S2. Δδ values (ppm) obtained for (R) and (S)-MTPA amides Ph S14

Synthesis of tabtoxinine-β-lactam (2) To a solution of compound 19 (6.4 mg, 0.015 mmol) in methanol (256 μl) was added 10% Pd/C (19.2 mg, 0.0180 mmol) and benzylaminehydrochloride (10.8 mg, 0.0754 mmol). After stirring for 12 h at room temperature, the mixture was filtered through a pad of celite. The filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/methanol/water = 4:4:1) to give the mixture of tabtoxinine-β-lactam (2) and N-methyltabtoxinine-β-lactam (20) (2/20 =95:5) as white solid (2.4 mg, 0.013 mmol, 85%). The mixture of 2 and 20 was separated by HPLC (COSMOSIL HILIC Packed Column 4.6mmI.D. 150 mm, MeCN/H 2 O = 4:1, flow rate = 1.0 ml/min, UV = 210 nm, retention time = 20: 8.33 min, 2: 10.67 min) [tabtoxinine-β-lactam (2)]: R f value: 0.27 (chloroform/methanol/water = 4:4:1); mp 175-177 C (decomposition); Optical rotation: [α] 24 D 27.1 (c 0.34, H 2 O); 1 H NMR (D 2 O, 400 MHz): δ (ppm) 3.67 (1H, t, J = 5.5 Hz), 3.36 (1H, d, J = 6.5 Hz), 3.24 (1H, d, J = 6.5 Hz), 2.02-1.72 (4H, m); 13 C NMR (D 2 O, 100 MHz, MeOH standard): δ (ppm) 174.8, 174.2, 84.6, 55.1, 51.5, 29.9, 25.5; HRMS (ESI) m/z calcd for C 7 H 12 O 4 N 2 Na [M+Na] +, 211.0689; found 211.0690; IR (thin film, KBr) 3120, 1735, 1617, 1406, 1205 cm -1. [N-methyltabtoxinine-β-lactam (20)]: R f value: 0.27 (chloroform/methanol/water = 4:4:1); 1 H NMR (D 2 O, 400 MHz): δ (ppm) 3.55 (1H, dd, J = 6.0, 5.0 Hz), 3.35 (1H, d, J = 6.5 Hz), 3.23 (1H, d, J = 6.5 Hz), 2.60 (3H, s), 2.02-1.69 (4H, m); 13 C NMR (D 2 O, 100 MHz, MeOH standard): δ (ppm) 174.1, 173.3, 84.5, 63.2, 51.6, 32.3, 29.6, 24.2; HRMS (ESI) m/z calcd for C 8 H 14 O 4 N 2 Na [M+Na] +, 225.0846; found 225.0847. S15

[N,N-dimethyltabtoxinine-β-lactam (21)]: R f value: 0.27 (chloroform/methanol /water = 4:4:1); 1 H NMR (D 2 O, 400 MHz): δ (ppm) 3.54 (1H, t, J = 6.0 Hz), 3.36 (1H, d, J = 6.5 Hz), 3.24 (1H, d, J = 6.5 Hz), 2.81 (3H, s), 2.78 (3H, s), 2.01-1.91 (2H, m), 1.88-1.72 (2H, m); 13 C NMR (D 2 O, 100 MHz, MeOH standard): δ (ppm) 174.1, 172.9, 84.5, 70.8, 51.7, 43.8, 40.4, 30.1. 22.7; HRMS (ESI) m/z calcd for C 9 H 16 O 4 N 2 Na [M+Na] +, 239.1002; found 239.1003 HPLC trace COSMOSIL HILIC Packed Column 4.6mmI.D. 150 mm, MeCN/H 2 O = 4:1, flow rate = 1.0 ml/min, UV = 210 nm, retention time = 21: 7.44 min, 20: 8.33 min, 2: 10.67 min 140 mv 90 40 1 7.44 2 8.33 3 10.67-10 -- 0 2 4 6 8 10 12 14 -- Time(min) -- -- -- peak# Ret. Time Area Height Area % Height % 1 7.44 651379 47483 27.224 33.461 2 8.33 460078 31251 19.228 22.022 3 10.67 1281242 63172 53.548 44.517 S16

References (S1) (a) Behrens, C.; Paquette, L. A. Org. Synth., 1998, 75, 106. (b) Paquette, L. A.; Brand, S.; Behrens, C. J. Org. Chem. 1999, 64, 2010. (S2) Harmon, R. E; Wellman, G.; Gupta, S. K. J. Org. Chem., 1973, 38, 11. (S3) (a) Kusumi, T.; Fukushima, T.; Ohtani, I; Kakisawa, H. Tetrahedron Lett. 1991, 32, 2939. (b) Seco, J. M.; Quiñoá, E.; Riguera, R. Chem. Rev. 2004, 104, 17. S17

9HE_1150_michaeladdition_TM2_P_CDCl3_20161002 3.jdf 3 3.12 3.09 2.02 2.02 2.02 1.02 1.02 1.01 1.06 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1150_michaeladdit Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 2 OCT 2016 11:37:36 Revision_time = 2 OCT 2016 11:44:44 Current_time = 2 OCT 2016 11:45:11 Comment = single_pulse Dim_size = 13107 Dim_title = 1H X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 26 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21.7[dC] S18 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_1150_michaeladdition_TM2_13C_CDCl3_20161002 4.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.7[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1150_michaeladdit Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 2 OCT 2016 12:29:54 Revision_time = 2 OCT 2016 12:30:00 Current_time = 2 OCT 2016 12:31:26 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S19 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 21.7982 55.1665 53.1450 51.7175 50.8266 48.3549 70.1022 77.3257 77.2012 77.0000 76.6743 113.7980 130.9803 129.3564 158.7632 173.4929 X : parts per Million : 13C : parts per Million

9HE_1152_lactamization_TM2_P_C6D6_20161206 3.jdf 3 2.99 2. sexp : 0.2[Hz] : 0.0[s] 1.95 1.94 Filename = 9HE_1152_lactamizatio Experiment = single_pulse.ex2 Solvent = BENZENE D6 Creation_time = 6 DEC 2016 11:23:16 Revision_time = 6 DEC 2016 11:26:31 Current_time = 6 DEC 2016 11:27:06 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 0.98 0.99 0.95 0.99 0.99 1.0 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 20.2[dC] S20 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 X : parts per Million : 1H

9HE_1152_lactamization_TM_13 C_CDCl3_20160928 3.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.7[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1152_lactamizatio Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 2 OCT 2016 18:51:40 Revision_time = 2 OCT 2016 18:51:18 Current_time = 2 OCT 2016 18:51:58 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S21 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 21.3288 40.9397 45.2987 56.8334 55.2479 65.0342 77.3162 77.2012 77.0000 76.6743 114.1046 129.3804 127.4787 159.0746 168.2046 X : parts per Million : 13C : parts per Million

9HE_xx_E1cb(datedori)_P_CDCl3_20161005 3.jdf 3 3.11 2. sexp : 0.2[Hz] : 0.0[s] 2.07 2.07 2.03 2.02 Filename = 9HE_xx_E1cb(datedori) Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 5 OCT 2016 11:24:29 Revision_time = 5 OCT 2016 11:25:08 Current_time = 5 OCT 2016 11:25:49 0.98 Comment = single_pulse Dim_size = 13107 Dim_title = 1H X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21.1[dC] S22 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_xx_E1cb(datedori)_13C_CDCl3_20161005 3.jdf Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.6[dC] Filename = 9HE_xx_E1cb(datedori) Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 5 OCT 2016 13:07:24 Revision_time = 5 OCT 2016 13:07:02 Current_time = 5 OCT 2016 13:07:35 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 500 Total_scans = 500 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ S23 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 14.1819 46.2663 45.3179 55.2575 77.3257 77.0000 76.6839 114.1046 121.2706 129.4474 127.7086 138.0985 159.1081 163.8264 X : parts per Million : 13C : parts per Million

9HE_xx_E1cb_Z product_p_cdcl3_20170212 4.jdf 3 2.98 2. sexp : 0.2[Hz] : 0.0[s] 1.99 1.99 1.96 1.94 Filename = 9HE_xx_E1cb_Z product Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 12 FEB 2017 12:39:05 Revision_time = 13 MAR 2017 15:49:51 Current_time = 13 MAR 2017 15:50:32 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 0.96 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 36 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 18.9[dC] S24 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 X : parts per Million : 1H

9HE_xx_E1cb_Z product_13c_cdcl3_20170212 3.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 19.2[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_xx_E1cb_Z product Experiment = single_pulse_dec Sample_id = S#457031 Solvent = CHLOROFORM D Creation_time = 12 FEB 2017 13:32:10 Revision_time = 12 FEB 2017 13:44:01 Current_time = 12 FEB 2017 13:45:16 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S25 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 14.5555 46.8699 45.1359 55.2335 77.3161 77.0000 76.6743 114.0471 124.8154 129.3947 127.8236 136.7141 159.0267 164.2767 X : parts per Million : 13C : parts per Million

9HE_ensyu_sample_P_CDCl3_20150115 3.jdf 3 2.11 2.1 1.98 2.0 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_ensyu_sample_P_CD Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 15 JAN 2015 17:25:46 Revision_time = 5 OCT 2016 21:17:24 Current_time = 5 OCT 2016 21:18:05 Comment = single_pulse Dim_size = 13107 Dim_title = 1H X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Clipped = TRUE Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 23.1[dC] S26 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 X : parts per Million : 1H

9HE_ensyu_sample_13C_CDCl3_20150115 5.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 23.4[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_ensyu_sample_13C_ Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 15 JAN 2015 18:54:19 Revision_time = 5 OCT 2016 21:22:01 Current_time = 5 OCT 2016 21:22:43 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S27 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 46.4196 55.3102 58.8453 77.3161 77.0000 76.6743 114.5165 125.4189 129.8163 159.7117 163.2899 192.9410 X : parts per Million : 13C : parts per Million

9.06 3.12 3 9HE_1160_VMAR_TM_2ndcolumn_FC20_kyoufutsu_P_CDCl3_20161020 3.jdf 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1160_VMAR_TM_2ndc Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 20 OCT 2016 17:43:35 Revision_time = 20 OCT 2016 17:54:06 Current_time = 20 OCT 2016 17:54:25 2.95 3.02 2.04 2.03 2.0 1.96 2.05 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 1.08 0.99 1.03 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21[dC] S28 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 X : parts per Million : 1H

9HE_1160_VMAR_TM_13C_CDCl3_20161019 8.jdf Total_scans = 600 9HE_1160_VMAR_TM_13C_CDCl3_20161019 8.jdf X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 50 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.6[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1160_VMAR_TM_13C_ Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 19 OCT 2016 15:10:02 Revision_time = 19 OCT 2016 15:51:11 Current_time = 19 OCT 2016 15:54:33 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C 134.0 132.0 130.0 128.0 126.0 124.0 122.0 120.0 118.0 116.0 X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 600 123.9819 126.6644 125.8979 125.6297 129.4810 128.9061 128.5804 128.3409 127.9194 X : parts per Million : 13C S29 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 16.3183 21.7503 30.0852 37.7782 45.0496 53.3175 55.2623 64.3252 77.3161 77.0000 76.6743 83.1410 89.3778 114.2770 129.4810 128.9061 128.5804 128.3409 125.8979 125.6297 123.9819 138.1703 143.5832 142.1845 152.9048 159.2470 164.2384 169.7470 X : parts per Million : 13C : parts per Million

9HE_1161_H2add_TM_P_CDCl3_20161020 3.jdf 8.01 2. sexp : 0.2[Hz] : 0.0[s] 4.02 3 2.98 2.98 Filename = 9HE_1161_H2add_TM_P_C Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 20 OCT 2016 21:12:00 Revision_time = 20 OCT 2016 21:15:45 Current_time = 20 OCT 2016 21:16:14 1.99 1.98 1.96 1.97 2.01 1.09 1.01 1.0 0.99 1.03 Comment = single_pulse Dim_size = 13107 Dim_title = 1H X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 46 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21.2[dC] S30 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_xx_H2add(datedori)_13C_P_CDCl3_20161002 6.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.6[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_xx_H2add(datedori Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 2 OCT 2016 17:30:12 Revision_time = 4 OCT 2016 14:17:28 Current_time = 4 OCT 2016 14:18:32 139.0 137.0 135.0 133.0 131.0 129.0 127.0 125.0 123.0 121.0 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C 129.4666 128.9157 128.6092 128.3601 127.9481 127.0380 125.8692 125.5530 138.0410 X : parts per Million : 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S31 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 16.3853 18.5601 21.7695 29.8217 34.8897 33.6347 44.9443 55.2623 53.7725 64.4450 77.3161 77.0000 76.6743 84.3625 89.4544 114.2147 129.4666 128.9157 128.3601 125.8692 125.5530 138.0410 142.2276 152.9958 159.1847 170.3458 172.6690 X : parts per Million : 13C : parts per Million

9HE_1201_protection(BOM)_TM_kyoufutsu2_P_CDCl3_20161022 3.jdf 12.99 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1201_protection(B Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 22 OCT 2016 21:30:22 Revision_time = 23 OCT 2016 12:42:16 Current_time = 23 OCT 2016 12:43:02 4.07 3 2.97 2.94 1.97 2.06 1.99 1.99 1.94 1.97 2.01 1.07 1.03 0.99 1.0 Comment = single_pulse Dim_size = 13107 Dim_title = 1H X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21.3[dC] S32 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_1201_protection(BOM)_TM_13C_CDCl3_20161023 3.jdf 9HE_1201_protection(BOM)_TM_13C_CDCl3_20161023 3.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.3[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1201_protection(B Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 23 OCT 2016 13:37:01 Revision_time = 23 OCT 2016 13:38:28 Current_time = 23 OCT 2016 13:41:34 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C 129.0 128.0 127.0 126.0 125.0 125.5339 125.8500 127.0571 127.9098 127.8236 127.6415 128.5517 128.3313 128.8678 129.4139 X : parts per Million : 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S33 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 16.3566 18.6846 21.7791 29.8265 34.9616 33.4096 44.8580 50.9990 55.2048 64.3348 70.0447 77.3161 77.0000 76.6743 89.3299 88.8509 91.7154 114.1237 129.4139 128.8678 128.3313 127.8236 125.5339 138.0649 137.4614 142.2419 152.9623 159.0937 168.5399 172.4104 X : parts per Million : 13C : parts per Million

9HE_1202_azidation_column3_FC18_kyoufutsu_P_CDCl3_20161027 3.jdf 12.18 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1202_azidation_co Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 27 OCT 2016 14:05:46 Revision_time = 27 OCT 2016 14:10:34 Current_time = 27 OCT 2016 14:11:15 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 4.02 3.15 3 3.07 2.1 2.08 2.05 2.1 1.09 0.98 1.01 0.99 1.03 1.07 1.05 1.03 1.02 1.11 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21[dC] S34 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_1202_azidation_column2_FC5_13C_CDCl3_20161026 3.jdf Total_scans = 500 9HE_1202_azidation_column2_FC5_13C_CDCl3_20161026 3.jdf X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.2[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1202_azidation_co Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 26 OCT 2016 14:52:33 Revision_time = 26 OCT 2016 14:53:08 Current_time = 26 OCT 2016 14:54:07 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C 129.0 128.0 127.0 126.0 125.0 125.4093 125.7447 126.9709 127.8906 127.6990 128.4750 128.3601 128.1493 128.7433 128.9828 129.4139 X : parts per Million : 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Clipped = TRUE Scans = 500 S35 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 16.2416 21.6449 25.3238 30.6313 29.7307 44.8868 50.8266 55.2335 59.8417 65.0821 70.1405 77.3257 77.0000 76.6839 91.7441 89.9622 88.2473 114.1620 129.4139 128.9828 128.3601 127.8906 125.4093 137.4997 137.4230 141.9162 152.4450 159.1512 169.9195 168.0801 X : parts per Million : 13C : parts per Million

9HE_1203_dePMB_TM_P_CDCl3_20161029 3.jdf 12.49 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_1203_dePMB_TM_P_C Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 29 OCT 2016 14:59:41 Revision_time = 29 OCT 2016 15:03:41 Current_time = 29 OCT 2016 15:04:07 4.03 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 3.05 3 2.01 2.1 2.02 1.06 0.99 1.03 0.98 1.02 1.02 0.68 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 21.2[dC] S36 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_1203_dePMB_TM_13C_CDCl3_20161029 3.jdf 9HE_1203_dePMB_TM_13C_CDCl3_20161029 3.jdf Total_scans = 500 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.2[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1203_dePMB_TM_13C Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 29 OCT 2016 16:16:06 Revision_time = 22 JAN 2017 10:54:49 Current_time = 22 JAN 2017 10:57:17 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C 129.0 128.0 127.0 126.0 125.0 125.4285 125.7255 127.8044 128.1685 128.0248 128.4846 128.4176 128.7146 129.0020 X : parts per Million : 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 500 S37 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 16.2800 21.6354 25.2950 30.6696 29.7020 47.5310 59.8417 65.0725 70.2459 77.3162 77.0000 76.6743 91.5908 90.0388 89.9239 129.0020 128.4176 128.0248 125.7255 125.4285 137.4518 137.2985 141.9641 152.4929 169.9195 169.2201 X : parts per Million : 13C : parts per Million

9HE_1204_deXN_TM_column3_hexEA53_FC16 18_kyofutsu_P_CDCl3_20161102 3.jdf 10.23 Filename = 9HE_1204_deXN_TM_colu Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 3 NOV 2016 09:14:07 Revision_time = 3 NOV 2016 09:17:10 Current_time = 3 NOV 2016 09:17:31 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 2.08 2.13 2.15 2.07 1.05 1.05 1.04 1.03 1 1.07 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 20.7[dC] S38 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_1204_deXN_TM_column4_hexEA53_kyoufutsu_13C_CDCl3_20161103 7.jdf 9HE_1204_deXN_TM_column4_hexEA53_kyoufutsu_13C_CDCl3_20161103 7.jdf Total_scans = 1000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 21.1[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1204_deXN_TM_colu Experiment = single_pulse_dec Solvent = CHLOROFORM D Creation_time = 3 NOV 2016 19:48:28 Revision_time = 14 FEB 2017 16:50:44 Current_time = 14 FEB 2017 16:52:35 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C 129.0 128.0 127.9481 127.8715 128.4655 128.6762 128.6092 X : parts per Million : 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 1000 S39 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 25.7549 31.0336 48.0100 61.7960 67.5442 70.3513 77.3257 77.0000 76.6838 91.7633 90.0867 128.6762 128.6092 128.4655 127.9481 127.8715 134.9801 137.2314 170.0824 169.2968 X : parts per Million : 13C : parts per Million

9HE_0813_staudinger_TM_P_CDCl3_20151011 5.jdf 9.99 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_0813_staudinger_T Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 11 OCT 2015 12:08:53 Revision_time = 14 MAR 2017 16:39:16 Current_time = 14 MAR 2017 16:39:44 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 2.05 2.1 2.0 1.98 1.06 1.07 1 1.11 1.06 1.0 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 20.9[dC] S40 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 X : parts per Million : 1H

9HE_0813_Mosher_( )_TM_purified_kyoufutsu_P_CDCl3_20170314 3.jdf 14.23 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_0813_Mosher_( )_T Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 14 MAR 2017 16:29:06 Revision_time = 14 MAR 2017 16:35:12 Current_time = 14 MAR 2017 16:35:57 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 3.12 2.14 2.02 1.98 2.04 2.1 1.15 1.06 1 1.04 1.03 0.92 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 46 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 20.1[dC] S41 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 X : parts per Million : 1H

9HE_0813_Mosher_(+)_TM_purified_P_CDCl3_20151016 7.jdf 12.78 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_0813_Mosher_(+)_T Experiment = single_pulse.ex2 Solvent = CHLOROFORM D Creation_time = 16 OCT 2015 17:54:47 Revision_time = 24 JAN 2017 20:03:32 Current_time = 24 JAN 2017 20:04:08 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 3.0 2.97 2.94 2.09 1.87 1.97 1.13 1.05 1 0.9 0.92 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 20.7[dC] S42 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 X : parts per Million : 1H

9HE_12xx_HPLC_separation_kyoufutsu_MeCN_H2O_4_1_nakarai_mae_P_D2O_20161224 3.jdf 4.02 2. sexp : 0.2[Hz] : 0.0[s] Filename = 9HE_12xx_HPLC_separat Experiment = single_pulse.ex2 Solvent = D2O Creation_time = 24 DEC 2016 15:39:35 Revision_time = 24 DEC 2016 15:40:28 Current_time = 24 DEC 2016 15:40:56 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 1.03 1.06 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 8 Total_scans = 8 1 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 19.7[dC] S43 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 X : parts per Million : 1H

9HE_1208_H2add_TM_MeOHstandard_13C_D2O_20161115 4.jdf Total_scans = 600 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 20.9[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1208_H2add_TM_MeO Experiment = single_pulse_dec Solvent = D2O Creation_time = 16 NOV 2016 13:57:37 Revision_time = 16 NOV 2016 13:58:52 Current_time = 16 NOV 2016 14:00:02 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 600 S44 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 25.5205 29.9370 49.5000 51.5214 55.0949 84.6119 174.8394 174.1783 X : parts per Million : 13C : parts per Million

9HE_1308_H2add_Me_TM_P_D2O_20170312 3.jdf 4.13 2. sexp : 0.2[Hz] : 0.0[s] 2.99 Filename = 9HE_1308_H2add_Me_TM_ Experiment = single_pulse.ex2 Solvent = D2O Creation_time = 12 MAR 2017 15:13:00 Revision_time = 12 MAR 2017 15:18:28 Current_time = 12 MAR 2017 15:19:33 Comment = single_pulse Dim_size = 13107 Dim_title = 1H 1.04 1 1.0 X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 32 Total_scans = 32 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 50 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 19.5[dC] S45 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 X : parts per Million : 1H

9HE_1236_H2add_Me_TM_13C_D2O_20170303 6.jdf Total_scans = 7000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 20.1[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1236_H2add_Me_TM_ Experiment = single_pulse_dec Solvent = D2O Creation_time = 4 MAR 2017 09:13:12 Revision_time = 13 MAR 2017 15:54:12 Current_time = 13 MAR 2017 15:55:47 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 7000 S46 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 24.1600 29.6496 32.2554 49.5000 51.6173 63.2190 84.4873 174.0921 173.3161 X : parts per Million : 13C : parts per Million

9HE_1236_H2add_diMe_TM_kyoufutsu_P_D2O_20170304 4.jdf 4.01 2. sexp : 0.2[Hz] : 0.0[s] 3.05 3.05 Filename = 9HE_1236_H2add_diMe_T Experiment = single_pulse.ex2 Solvent = D2O Creation_time = 4 MAR 2017 13:08:26 Revision_time = 14 MAR 2017 16:49:09 Current_time = 14 MAR 2017 16:49:40 Comment = single_pulse Dim_size = 13107 Dim_title = 1H X_acq_duration = 2.20725248[s] X_domain = 1H X_freq = 395.88430144[MHz] X_offset = 5[ppm] X_points = 16384 X_prescans = 1 X_resolution = 0.45305193[Hz] X_sweep = 7.42280285[kHz] Tri_domain = 1H Tri_freq = 395.88430144[MHz] Tri_offset = 5[ppm] Scans = 16 Total_scans = 16 1.04 1 0.98 X_90_width = 10[us] X_acq_time = 2.20725248[s] X_angle = 45[deg] X_atn = 0.8[dB] X_pulse = 5[us] Irr_mode = Off Tri_mode = Off Dante_presat = FALSE Recvr_gain = 48 Relaxation_delay = 5[s] Repetition_time = 7.20725248[s] Temp_get = 19.9[dC] S47 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 X : parts per Million : 1H

9HE_1236_H2add_diMe_TM_13C_D2O_20170303 5.jdf Total_scans = 5000 X_90_width = 8.9[us] X_acq_time = 1.048576[s] X_angle = 30[deg] X_atn = 4.2[dB] X_pulse = 2.96666667[us] Irr_atn_dec = 22.01396[dB] Irr_atn_noe = 22.01396[dB] Irr_noise = WALTZ Decoupling = TRUE Noe = TRUE Noe_time = 2[s] Recvr_gain = 60 Relaxation_delay = 2[s] Repetition_time = 3.048576[s] Temp_get = 20.1[dC] 2. sexp : 2.0[Hz] : 0.0[s] Filename = 9HE_1236_H2add_diMe_T Experiment = single_pulse_dec Solvent = D2O Creation_time = 4 MAR 2017 03:07:28 Revision_time = 4 MAR 2017 03:11:39 Current_time = 4 MAR 2017 03:13:49 Comment = single pulse decouple Dim_size = 26214 Dim_title = 13C X_acq_duration = 1.048576[s] X_domain = 13C X_freq = 99.54517646[MHz] X_offset = 100[ppm] X_points = 32768 X_prescans = 4 X_resolution = 0.95367432[Hz] X_sweep = 31.25[kHz] Scans = 5000 S48 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 22.6943 30.1094 40.4274 43.8380 49.5000 51.6747 70.8258 84.5161 174.0730 172.9233 X : parts per Million : 13C : parts per Million