Oxidative Rearrangement via in situ generated N-Chloroamine: Synthesis of Fused Tetrahydroisoquinolines

Oxidative Rearrangement via in situ generated N-Chloroamine: Synthesis of Fused Tetrahydroisoquinolines Kenichi Murai*, Kei Matsuura, Hiroshi Aoyama, Hiromichi Fujioka* Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka, 565-0871 (Japan) Tel: (+81) 6-6879-8225, Fax: (+81) 6-6879-8229 E-mail: murai@phs.osaka-u.ac.jp, fujioka@phs.osaka-u.ac.jp Supporting Information Table of Contents 1. Page S2 General 2. Page S2 Preparation of compound 1 3. Page S9 Reaction in Table 2 (Oxidative rearrangement reaction with NaBH4) 4. Page S13 Reactions in Table 3 (Reaction with carbon nucleophiles) 5. Page S16 Reactions in Scheme 3 (Synthesis of crispine A and analogues) 6. Page S18 Reactions in Scheme 4 (Reaction with the norcamphor derivative) 7. Page S20 X-ray crystallographic analysis of 6a TsOH 8. Page S22 NMR study 9. Page S24 1 H and 13 C NMR Data 10. Page S90 2D NMR data for 1f-CHO, 1g, 2f, 2g, and 5-CHO S1

1. General Melting points were measured by BÜCHI B-545 and all melting points were uncorrected. 1 H-NMR and 13 C-NMR spectra were measured by JEOL JNM-ECS 400, JEOL ECS 300 or JEOL JNM-LA 500 spectrometers with tetramethylsilane as an internal standard. IR spectra were recorded by Shimadzu FTIR 8400 using a diffuse reflectance measurement of samples dispersed in KBr powder. High resolution mass spectra and elemental analysis were performed by the Elemental Analysis Section of Osaka University. Column chromatography was performed with SiO 2 (Merck Silica Gel 60 (230-400 mesh) or Kanto Chemical Silicagel 60 (spherical, 63-210 m). Microwave irradiations were performed in Biotage Initiator+. Unless otherwise noted, materials were purchased from Aldrich Inc., Kanto Kagaku, Wako Chemicals, and other commercial suppliers and were used without purification. 2-(3,4-Methylenedioxyphenyl)ethylamine, cyclobutanone 7a, 7b, and 7c were prepared according to the literature. 1 2. Preparation of compound 1 General Method A A 20 ml or 5 ml microwave vial was charged with arylethylamine (1.0 equiv), cyclobutanone (1.1 equiv), trifluoroacetic acid (8 equiv), and toluene (0.3 M) at rt. The reaction vial was placed in the microwave reactor and heated to 140 o C for 4 h. The reaction mixture was poured into sat. NaHCO 3 aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography to give compound 1. 1 For 2-(3,4-Methylenedioxyphenyl)ethylamine ; F. Crestey, A. A. Jensen, M. Borch, J. T. Andreasen, J. Andersen, T. Balle, J. L. Kristensen, J. Med. Chem. 2013, 56, 9673.; for 7a: H.-J. Xu, F.-F. Zhu, Y.-Y. Shen, X. Wan, Y.-S. Feng, Tetrahedron, 2012, 68, 4145.; for 7b: Y. L. Bennani, B. Huck, M. J. Robarge, PCT Int. Appl. (2006), WO 2006025601.; for 7b: A. Rioz-Martínez1, G. Gonzalo1, D. E. Torres Pazmiño, M. W. Fraaije, V. Gotor, Eur. J. Org. Chem. 2009, 2526. ; for 7c: B. M. Trost, J. Xie, J. Am. Chem. Soc. 2008, 130, 6231. S2

General Method B (2 step preparation) 2 X NH 2 R O Ti(OiPr) 4 HCOOH R' Ac 2 O X R 1-CHO NCHO R' NaOH 1st step: Under N 2, the mixture of ketone (1.0 equiv), arylethylamine (1.5 equiv), and Ti(OiPr) 4 was heated at 80 o C for 3 h. After the reaction mixture was cooled to 0 o C, the mixture of HCOOH (100 equiv) and Ac 2 O (100 equiv) was added to the reaction mixture and the resulting solution was heated at 70 o C for 2 h. After trifluoroacetic acid (200 equiv) was added to the reaction mixture, the resulting solution was heated at 70 o C overnight. After the completion of the reaction, the solution was diluted with AcOEt and the reaction was quenched with NaHCO 3 aq.. The organic layer was washed with NaHCO 3 aq. and brine, dried over Na 2 SO 4, and evaporated in vacuo. The residue was roughly purified by SiO 2 column chromatography to give 1-CHO. 2nd step: The solution of 1-CHO and NaOH in EtOH/H 2 O (1/1) was heated under reflux. After the completion of the reaction, the solution was diluted with H 2 O. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography to give compound 1. X R 1 NH R' Compound 1a Reaction was carried out according to the general method A with 2-(3-methoxyphenyl)-ethylamine (0.29 ml, 1.98 mmol), cyclobutanone (0.17 ml, 2.18 mmol), and trifluoroacetic acid (1.2 ml, 15.9 mmol) in toluene (6.6 ml) to give 1a (332.5 mg, 82%) as pale yellow oil. Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 1 H NMR (500 MHz, CDCl 3 ): δ= 7.41 (d, J = 8.6 Hz, 1H), 6.79 (dd, J = 8.6, 2.9 Hz, 1H), 6.57 (d, J = 2.9 Hz, 1H), 3.78 (s, 3H), 3.06 (t, J = 5.8 Hz, 2H), 2.76 (t, J = 5.8 Hz, 2H), 2.50-2.41 (m, 2H), 2.18-2.11 (m, 3H), 2.05-1.96 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.5, 135.6, 135.3, 126.5, 113.1, 112.5, 59.1, 55.2, 39.5, 37.3, 30.5, 14.5 ppm; IR (KBr): 3280, 2930, 1609 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 18 NO [M+H] + : 204.1383, found 204.1383. 2 Y. Horiguchi, H. Kodama, M. Nakamura, T. Yoshimura, K. Hanezi, H. Hamada, T. Saitoh, T. Sano, Chem. Pharm. Bull. 2002, 50, 253. S3

Compound 1b Reaction was carried out according to the general method A with 2-(3,4-methylenedioxyphenyl)ethylamine (170.8 mg, 1.03 mmol), cyclobutanone (0.10 ml, 1.30 mmol), and trifluoroacetic acid (0.64 ml, 8.36 mmol) in toluene (3.5 ml) to give 1b (42.8 mg, 19 %) as pale yellow oil. Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 1 H NMR (300 MHz, CDCl 3 ): δ= 6.98 (s, 1H), 6.50 (s, 1H), 5.91 (s, 2H), 3.03 (t, J = 5.8 Hz, 2H), 2.68 (t, J = 5.8 Hz, 2H), 2.47-2.36 (m, 2H), 2.20-1.92 ppm (m, 4H); 13 C NMR (100.5 MHz, CDCl 3 ): δ= 146.1, 145.6, 136.4, 127.3, 108.3, 105.5, 100.6, 59.5, 39.5, 37.3, 30.3, 14.5 ppm; IR (KBr): 3283, 2933, 1503, 1484 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 16 NO 2 [M+H] + : 218.1176, found 218.1176 Compound 1c Title compound was prepared according to the general method B. 1st reaction was carried out with 2-(3-methylphenyl)ethylamine (0.24 ml, 1.61 mmol), cyclobutanone (0.08 ml, 1.08 mmol), Ti(OiPr) 4 (0.51 ml, 1.62 mmol), HCOOH (4.6 ml, 110 mmol), Ac 2 O (10.4 ml, 110 mmol) and trifluoroacetic acid (16.8 ml, 220 mmol) to give 1c-CHO (181.9 mg, 78%) as pale yellow oil. Column chromatography: SiO 2, AcOEt/triethylamine = 20/1. 2nd reaction was carried out with 1c-CHO (181.9, 0.845 mmol) and NaOH (2.1 g, 53 mmol) in EtOH/H 2 O (1/1, 4.2 ml) to give 1c (45.5 mg, 29%) as pale yellow oil. Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 1 H NMR (500 MHz, CDCl 3 ): δ= 7.39 (d, J = 8.1 Hz, 1H), 7.04 (d, J = 8.1 Hz, 1H), 6.86 (s, 1H), 3.05 (t, J = 5.8 Hz, 2H), 2.74 (t, J = 5.8 Hz, 2H), 2.49-2.44 (m, 2H), 2.29 (s, 3H), 2.18-2.11 (m, 3H), 2.05-1.99 ppm (m, 2H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 140.2, 135.4, 133.8, 129.3, 127.0, 125.3, 59.1, 39.5, 37.2, 30.1, 20.9, 14.5 ppm; IR (KBr): 3285, 2930, 1662 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 18 N [M+H] + : 188.1434, found 188.1436. Synthesis of 1d 1d was prepared from 1e as following scheme. S4

Compound 1e-Tf To a solution of 1e (83.4 mg, 0.441 mmol) in CH 2 Cl 2 (4.4 ml) was added Et 3 N (0.14 ml, 0.97 mmol) at rt and the reaction mixture was cooled to -78 o C. Tf 2 O (0.16 ml, 0.97 mmol) was added to the resulting solution at -78 o C and the resulting mixture was stirred for 1 h. The reaction was quenched with sat. NaHCO 3 aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/Hexane = 1/8) to give compound 1e-Tf (189.3 mg, 95%) as colorless solid. Mp: 126-127 o C; 1 H NMR (300 MHz, CDCl 3 ): δ= 7.60 (d, J = 8.8 Hz, 1H), 7.18 (dd, J = 8.8, 2.4 Hz, 1H), 7.08 (d, J = 2.4 Hz, 1H), 3.82-3.76 (m, 2H), 3.17-3.05 (m, 2H), 2.91-2.74 (m, 2H), 2.59-2.42 (m, 2H), 2.09-1.95 ppm (m, 2H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 148.6, 140.8, 135.3, 124.7, 122.4, 119.4, 119.3 (q, J = 321 Hz), 118.7 (q, J = 320 Hz), 62.7, 42.3, 34.9, 28.6, 13.7 ppm; IR (KBr): 2966, 1490, 1424, 1381 cm -1 ; HRMS (MALDI-TOF): calcd for C 14 H 13 NO 5 F 6 NaS 2 [M+H] + : 476.0032, found 476.0025. Compound 1d-Tf To a solution of 1e-Tf (168.6 mg, 0.372 mmol) in MeOH (3.7 ml) were added 10% Pd/C (17.5 mg, 10 wt%), Mg (48.4 mg, 1.99 mmol) and NH 4 OAc (307.0 mg, 3.98 mmol) at rt 3 and the resulting solution was stirred at rt for 17 h. The reaction mixture was filtered through a celite (eluent: AcOEt) and the filtrate was evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/Hexane = 1/12) to give compound 1d-Tf (97.1 mg, 86%) as colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ= 7.55-7.50 (m, 1H), 7.29-7.22 (m, 2H), 7.16-7.13 (m, 1H), 3.81-3.77 (m, 2H), 3.11-3.00 (m, 2H), 2.85-2.76 (m, 2H), 2.58-2.44 (m, 2H), 2.09-1.93 ppm (m, 2H); 13 C NMR (100.5 MHz, CDCl 3 ): δ= 140.3, 132.1, 129.8, 127.6, 126.6, 122.6, 119.4 (q, J = 322 Hz), 63.2, 42.8, 34.9, 28.4, 13.8 ppm; IR (KBr): 2970, 1382 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 14 NO 2 F 3 NaS [M+H] + : 328.0590, found 328.0584. 3 H. Sajiki, A. Mori, T. Mizusaki, T. Ikawa, T. Maegawa, K. Hirota, Org. Lett., 2006, 8, 987. S5

Compound 1d To a solution of 1d-Tf (97.1 mg, 0.318 mmol) in toluene (3.7 ml) was added Red-Al (0.9 ml, 3.18 mmol) and the resulting solution was heated to 50 o C. After being stirred for 15 h, the solution was cooled to rt and the reaction was quenched with sat. Rochell's salt aq.. The mixture was extracted with AcOEt. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 1d (39.8 mg, 72%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.50 (d, J = 8.3 Hz, 1H), 7.23 (t, J = 7.4 Hz, 1H), 7.12 (td, J = 7.4, 1.1 Hz, 1H), 7.03 (d, J = 8.3 Hz, 1H), 3.07 (t, J = 6.0 Hz, 2H), 2.78 (t, J = 6.0 Hz, 2H), 2.53-2.46 (m, 2H), 2.20-2.12 (m, 3H), 2.09-1.99 ppm (m, 2H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 143.1, 134.0, 128.8, 126.2, 125.9, 125.3, 59.3, 39.5, 37.3, 30.1, 14.6 ppm; IR (KBr): 3276, 2931 cm -1 ; HRMS (MALDI-TOF): calcd for C 12 H 16 N [M+H] + : 174.1277, found 174.1275. Compound 1e To a solution of 1a (128.3 mg, 0.631 mmol) in CH 2 Cl 2 was added BBr 3 (1.0 M in CH 2 Cl 2, 3.2 mmol), at -20 o C and the resulting solution was stirred at the same temperature for 18 h. The reaction was quenched with MeOH and the resulting solution was concentrated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/MeOH/trimethylamine = 15/1/0.8) to give compound 1e (107.9 mg, 90%) as colorless solid. Mp: 138-140 o C; 1 H NMR (500 MHz, CD 3 OD): δ= 7.34 (d, J = 8.8. Hz, 1H), 6.65 (dd, J = 8.8, 2.8 Hz, 1H), 6.45 (d, J = 2.8 Hz, 1H), 2.97 (t, J = 6.0 Hz, 2H), 2.73 (t, J = 6.0 Hz, 2H), 2.45-2.39 (m, 2H), 2.24-2.18 (m, 2H), 2.15-1.96 ppm (m, 2H); 13 C NMR (125.8 MHz, CD 3 OD): δ= 157.0, 135.3, 133.4, 127.3, 115.6, 115.2, 60.4, 39.8, 37.2, 29.5, 14.6 ppm; IR (KBr): 3269, 2940, 1612 cm -1 ; HRMS (MALDI-TOF): calcd for C 12 H 16 NO [M+H] + : 190.1226, found 190.1229. Compound 1f Title compound was prepared according to the general method B. 1st reaction was carried out with 2-(3-methoxyphenyl)ethylamine (0.43 ml, 2.93 mmol), cyclobutanone 7a (242.6 mg, 1.95 mmol), Ti(OiPr) 4 (0.92 ml, 2.93 mmol), HCOOH (8.2 ml, 195 mmol), Ac 2 O (18.7 ml, 195 mmol) and trifluoroacetic acid (29.9 ml, 391 mmol) to give 1f-CHO (408.6 mg, 73%) as S6

yellow solid. Column chromatography: SiO 2, Hexane/AcOEt = 2/1. 2nd reaction was carried out with 1f-CHO (258.6 mg, 0.906 mmol) and NaOH (3.2 g, 54.4 mmol) in EtOH/H 2 O (1/1, 7.7 ml) to give 1f (182.5 mg, 78%) as pale yellow oil. Column chromatography: SiO 2, Hexane/AcOEt = 1/1 to AcOEt/triethylamine = 20/1. 1f-CHO: Mp: 127-128 o C; 1 H NMR (500 MHz, CDCl 3 ): δ= 8.25 (s, 1H), 7.39 (d, J = 8.6 Hz, 1H), 6.78 (dd, J = 8.6, 2.3 Hz, 1H), 6.75 (d, J = 2.3 Hz, 1H), 3.88-3.82 (m, 1H), 3.81 (s, 3H), 3.34-3.29 (m, 1H), 2.93-2.88 (m, 1H), 2.84-2.76 (m, 1H), 2.74-2.71 (m, 1H), 2.61-2.54 (m, 2H), 2.17-2.10 (m, 1H), 1.83-1.77 (m, 1H), 1.71-1.65 (m, 1H), 1.63-1.52 (m, 3H), 1.46-1.31 (m, 2H), 1.09-1.00 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 161.2, 158.7, 136.7, 134.3, 123.0, 114.1, 111.2, 59.8, 55.3, 45.0, 39.3, 29.5, 27.4, 25.7, 25.5, 23.9, 22.4, 21.1 ppm; IR (KBr): 2930, 1652, 1612 cm -1 ; HRMS (MALDI-TOF): calcd for C 18 H 24 NO 2 [M+H] + : 286.1802, found 286.1798. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.47 (d, J = 8.6 Hz, 1H), 6.77 (dd, J = 8.6, 2.9 Hz, 1H), 6.58 (d, J = 2.9 Hz, 1H), 3.78 (s, 3H), 3.05-2.99 (m, 1H), 2.96-2.91 (m, 1H), 2.85-2.78 (m, 1H), 2.69 (td, J = 16.1, 5.1 Hz,1H), 2.53-2.46 (m, 2H), 2.46-2.41 (m, 1H), 1.95-1.90 (m, 2H), 1.74-1.59 (m, 4H), 1.55-1.39 (m, 3H), 1.27-1.18 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.4, 136.8, 135.7, 125.5, 113.3, 112.1, 58.2, 55.2, 44.8, 41.2, 40.2, 30.1, 27.0, 25.5, 21.5, 21.2, 20.8 ppm; IR (KBr): 3320, 2928 1609 cm -1 ; HRMS (MALDI-TOF): calcd for C 17 H 24 NO [M+H] + : 258.1852, found 258.1852. Stereochemistry was determined by NOESY of 1f-CHO. Compound 1g Title compound was prepared according to the general method B. 1st reaction was carried out with 2-(3-methoxyphenyl)ethylamine (0.32 ml, 2.20 mmol), cyclobutanone 7b (222.2 mg, 1.40 mmol), Ti(OiPr) 4 (0.65 ml, 2.07 mmol), HCOOH (5.8 ml, 138 mmol), Ac 2 O (13.2 ml, 138 mmol) and trifluoroacetic acid (21.2 ml, 276 mmol) to give 1g-CHO (367.5 mg, 83%) as pale yellow oil. Column chromatography: SiO 2, Hexane/AcOEt = 5/4. 2nd reaction was carried out with 1g-CHO (367.5, 1.15 mmol) and NaOH (4 g, 100 mmol) in EtOH/H 2 O (1/1, 6.5 ml) to give 1g (298.1 mg, 89%) as pale yellow solid. Column chromatography: SiO 2, Hexane/AcOEt = 1/1 to 1/3. Mp: 73-75 o C; 1 H NMR (500 MHz, CDCl 3 ): δ= 7.53 (d, J = 8.6 Hz, 1H), 7.30-7.28 (m, 1H), 7.23-7.18 (m, 3H), 6.87 (dd, J = 8.6, 2.9 Hz, 1H), 6.57 (d, J = 2.9 Hz, 1H), 3.89-3.84 (m, 1H), 3.80 (s, 3H), 3.45-3.41 (m, 1H), 3.37-3.33 (m, 1H), 3.12 (dd, J = 17.8, 9.7 Hz, 1H), 3.02-2.94 (m, 2H), 2.89-2.83 (m, S7

1H), 2.80-2.67 (m, 2H), 2.05-2.00 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.4, 148.2, 144.4, 136.8, 135.3, 126.83, 126.81, 126.6, 124.8, 124.3, 112.9, 57.7, 55.2, 50.2, 47.2, 39.9, 39.0, 32.8, 30.3 ppm; IR (KBr): 3335, 2925, 1610 cm -1 ; HRMS (MALDI-TOF): calcd for C 20 H 22 NO [M+H] + : 292.1696, found 292.1699. Stereochemistry was determined by NOESY. MeO NH H H 1g Compound 1h Title compound was prepared according to the general method B. 1st reaction was carried out with 2-(3-methoxyphenyl)ethylamine (0.32 ml, 2.16 mmol), cyclobutanone 7c (320.5 mg, 1.44 mmol), Ti(OiPr) 4 (0.68 ml, 2.16 mmol), HCOOH (5.7 ml, 144 mmol), Ac 2 O (13.6 ml, 144 mmol) and trifluoroacetic acid (22.1 ml, 288 mmol) to give 1h-CHO (401.6 mg, 73%) as pale yellow solid. Column chromatography: SiO 2, Hexane/AcOEt = 5/4. 2nd reaction was carried out with 1h-CHO (401.6 mg, 1.05 mmol) and NaOH (4.0 g, 100 mmol) in EtOH/H 2 O (1/1, 6.5 ml) to give 1h (307.9 mg, 83%) as colorless solid. Column chromatography: SiO 2, Hexane/AcOEt = 1/3 Mp: 157-159 o C; 1 H NMR (400 MHz, CDCl 3 ): δ= 7.50-7.47 (m, 2H), 7.37-7.27 (m, 6H), 7.17-7.10 (m, 2H), 7.02 (d, J = 8.7 Hz, 1H), 6.64 (dd, J = 8.7, 2.7 Hz, 1H), 6.54 (d, J = 2.7 Hz, 1H), 3.74 (s, 3H), 3.34-3.30 (m, 2H), 3.24-3.20 (m, 2H), 2.97 (t, J = 6.0 Hz, 2H), 2.76 (t, J = 6.0 Hz, 2H); 13 C NMR (100.5 MHz, CDCl 3 ): δ= 157.5, 150.6, 150.0, 136.0, 134.8, 128.6, 128.4, 127.2, 126.3, 125.9, 125.6, 125.5, 113.0, 112.4, 55.1, 55.0, 51.0, 44.4, 39.4, 30.5 ppm; IR (KBr): 3331, 2935, 1609 cm -1 ; HRMS (MALDI-TOF): calcd for C 25 H 26 NO [M+H] + : 356.2009, found 356.2005. S8

3. Reaction in Table 2 (Oxidative rearrangement reaction with NaBH4) General Procedure A To a solution of 1 (1.0 equiv) in MeOH (0.05-0.1 M) was added NCS (1.1 equiv) at 0 o C and the reaction mixture was stirred at rt. After the disappearance of N-chloroamine (checked by TLC), NaBH 4 was added to the resulting solution at 0 o C and stirred for 1 h. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography to give compound 2. General Procedure B To a solution of 1 (1.0 equiv) in CF 3 CH 2 OH (0.025-0.1 M) was added NCS (1.1 equiv) at 0 o C and the reaction mixture was stirred at rt. After the disappearance of N-chloroamine (checked by TLC), CF 3 CH 2 OH was evaporated in vacuo and to the residue was added MeOH (0.05-0.1 M). NaBH 4 was added to the resulting solution at 0 o C and stirred for 1 h. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The misxture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography to give compound 2. Compound 2a Reaction was carried out according to the general procedure A with 1a (21.5 mg, 0.106 mmol), NCS (15.7 mg, 0.118 mmol), and NaBH 4 (12.3 mg, 0.325 mmol) in MeOH (1.1 ml) to give 2a (21.0 mg, 98%) as colorless oil. Reaction time for rearrangement: 10.5 h; Column chromatography: SiO 2, AcOEt/triethylamine = 25/1 1 H NMR (500 MHz, CDCl 3 ): δ= 6.99 (d, J = 8.3 Hz, 1H), 6.71 (dd, J = 8.3, 2.3 Hz, 1H), 6.65 (d, J = 2.3 Hz, 1H), 3.77 (s, 3H), 3.38-3.34 (m, 1H), 3.20-3.16 (m, 1H), 3.12-3.04 (m, 2H), 2.84-2.78 (m, 1H), 2.62 (ddd, J = 10.8, 10.8, 4.6 Hz, 1H), 2.52 (q, J = 8.4 Hz, 1H), 2.36-2.29 (m, 1H), 1.98-1.81 (m, 2H), 1.74-1,65 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.7, 135.5, 131.3, 126.5, 113.2, 111.8, 63.0, 55.2, 53.3, 48.4, 30.3, 28.9, 22.1 ppm; IR (KBr): 2939, 1611 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 18 NO [M+H] + : 204.1383, found 204.1387. Compound 2b O O N Reaction was carried out according to the general procedure A with 1b (22.2 mg, 0.102 mmol), NCS (15.2 mg, 0.114 mmol), and NaBH 4 (12.0 mg, 0.317 mmol) in MeOH (1.0 ml) to give 2b (21.4 mg, 96%) as pale yellow oil. Reaction time for rearrangement: 24 h; Column chromatography: SiO 2, S9

AcOEt/triethylamine = 20/1 1 H NMR (500 MHz, CDCl 3 ): δ= 6.58 (s, 1H), 6.55 (s, 1H), 5.88 (s, 2H), 3.36-3.32 (m, 1H), 3.16 (ddd, J = 11.2, 6.3, 3.2 Hz, 1H), 3.10-3.05 (m, 1H), 3.04-2.96 (m, 1H), 2.75-2.69 (m, 1H), 2.62-2.56 (m, 1H), 2.51 (q, J = 8.6 Hz, 1H), 2.32-2.25 (m, 1H), 1.98-1.80 (m, 2H), 1.73-1.64 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 145.7, 145.6, 131.9, 127.2, 108.3, 105.8, 100.5, 63.4, 53.2, 48.4, 30.4, 28.7, 22.0 ppm; IR (KBr): 2904 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 16 NO 2 [M+H] + : 218.1176, found 218.1177. Compound 2c Reaction was carried out according to the general procedure A with 1d (23.7 mg, 0.127 mmol), NCS (18.5 mg, 0.139 mmol), and NaBH 4 (14.7 mg, 0.389 mmol) in MeOH (1.3 ml) to give 2d (21.6 mg, 91%) as pale yellow oil. Reaction time for rearrangement: 12 h; Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 1 H NMR (400 MHz, CDCl 3 ): δ= 6.89-6.86 (m, 3H), 3.35-3.31 (m, 1H), 3.10 (ddd, J = 11.0, 6.0, 2.7 Hz, 1H), 3.04-2.94 (m, 2H), 2.75-2.68 (m, 1H), 2.59-2.52 (m, 1H), 2.45 (q, J = 8.7 Hz, 1H), 2.31-2.23 (m, 1H), 2.22 (s, 3H), 1.92-1.73 (m, 2H), 1.69-1.58 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 135.8, 135.4, 134.0, 129.0, 126.5, 125.5, 63.0, 53.2, 48.3, 30.4, 28.4, 22.2, 21.0 ppm; IR (KBr): 2966 cm -1 ; HRMS (MALDI-TOF): calcd for C 13 H 18 N [M+H] + : 188.1434, found 188.1432. Compound 2d Reaction was carried out according to the general procedure A with 1d (20.0 mg, 0.115 mmol), NCS (17.1 mg, 0.118 mmol), and NaBH 4 (14.4 mg, 0.381 mmol) in MeOH (2.0 ml) to give 2d (11.7 mg, 59%) as colorless oil. Reaction time for rearrangement: 24 h; Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 1 H NMR (300 MHz, CDCl 3 ): δ= 7.17-7.05 (m, 4H), 3.47-3.39 (m, 1H), 3.24-3.15 (m, 1H) 3.14-3.04 (m, 2H), 2.88-2.77 (m, 1H), 2.69-2.60 (m, 1H), 2.58-2.49 (m, 1H), 2.41-2.28 (m, 1H), 2.03-1.83 (m, 2H), 1.81-1.67 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 138.8, 134.1, 128.4, 126.0, 125.7, 125.6, 63.4, 53.4, 48.5, 30.2, 28.6, 22.2 ppm; IR (KBr): 2952 cm -1 ; HRMS (MALDI-TOF): calcd for C 12 H 16 N [M+H] + : 174.1277, found 174.1279. S10

Compound 2e To a solution of 1e (20.6 mg, 0.109 mmol) in MeOH (1.1 ml) was added NCS (16.4 mg, 0.123 mmol) at 0 o C and the reaction mixture was stirred at rt for 7 h. NaBH 4 (12.4 mg, 0.330 mmol) was added to the resulting solution at 0 o C and stirred for 1 h. The solution was concentrated in vacuo and the residue was purified by SiO 2 column chromatography to give compound 2e (11.7 mg, 57%) as colorless solid. Mp: 138-140 o C; 1 H NMR (500 MHz, CD 3 OD): δ= 6.91 (d, J = 8.0 Hz, 1H), 6.59 (dd, J = 8.0, 2.3 Hz, 1H), 6.55 (d, J = 2.3 Hz, 1H), 3.50-3.45 (m, 1H), 3.15-3.10 (m, 1H), 3.07-3.02 (m, 1H), 3.01-2.93 (m, 1H), 2.80 (td, J = 16.6, 4.6 Hz, 1H), 2.68-2.60 (m, 2H), 2.39-2.31 (m, 1H), 1.99-1.85 (m, 2H), 1.73-1.64 ppm (m, 1H); 13 C NMR (125.8 MHz, CD 3 OD): δ= 156.9, 136.0, 130.0, 127.8, 115.6, 114.4, 64.3, 54.3, 49.2, 31.3, 29.4, 22.9 ppm; IR (KBr): 2935 cm -1 ; HRMS (MALDI-TOF): calcd for C 12 H 16 NO [M+H] + : 190.1226, found 190.1226. Compound 2f Reaction was carried out according to the general procedure A with 1f (29.1 mg, 0.113 mmol), NCS (17.0 mg, 0.127 mmol), and NaBH 4 (13.8 mg, 0.365 mmol) in MeOH (1.1 ml) at -78 o C to give 2f (22.5 mg, 77%) as pale yellow oil. Reaction time for rearrangement: 1 h; Column chromatography: SiO 2, Hexane/AcOEt = 1/2 1 H NMR (400 MHz, CDCl 3 ): δ= 6.95 (d, J = 8.3 Hz, 1H), 6.69 (dd, J = 8.3, 2.3 Hz, 1H), 6.66 (d, J = 2.3 Hz, 1H), 3.77 (s, 3H), 3.31-3.24 (m, 1H), 3.18-3.05 (m, 2H), 2.83 (dd, J = 16.7, 4.8 Hz, 1H), 2.49-2.41 (m, 1H), 2.35-2.30 (m, 1H), 2.22 (ddd, J = 11.0, 11.0, 5.0 Hz, 1H), 2.17-2.09 (m, 1H), 1.82-1.75 (m, 1H), 1.65-1.44 (m, 4H), 1.39-1.17 ppm (m, 4H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.8, 135.9, 132.7, 125.7, 113.4, 111.3, 64.5, 63.1, 55.2, 47.4, 36.0, 30.7, 30.0, 29.7, 25.0, 24.0, 20.2 ppm; IR (KBr): 2927, 1610 cm -1 ; HRMS (MALDI-TOF): calcd for C 17 H 24 NO [M+H] + : 258.1852, found 258.1853. Stereochemistry was determined by NOESY. MeO H N H S11

Compound 2g Reaction was carried out according to the general procedure A with 1g (29.4 mg, 0.101 mmol), NCS (15.2 mg, 0.114 mmol), and NaBH 4 (12.2 mg, 0.323 mmol) in MeOH (2.0 ml) to give 2g (21.9 mg, 75%) as colorless solid. Reaction time for rearrangement: 22 h; Column chromatography: SiO 2, Hexane/AcOEt = 1/3 Mp: 138-140 o C; 1 H NMR (500 MHz, CDCl 3 ): δ= 7.18-7.08 (m, 4H), 6.96 (d, J = 8.6 Hz, 1H), 6.66 (dd, J = 8.6, 2.9 Hz, 1H), 6.60 (d, J = 2.9 Hz, 1H), 3.87-3.81 (m, 1H), 3.73 (s, 3H), 3.38-3.33 (m, 2H), 3.21 (t, J = 6.9 Hz, 1H), 3.13-3.00 (m, 3H), 2.97-2.91 (m, 1H), 2.82 (dd, J = 17.2, 4.6 Hz, 1H), 2.46 (ddd, J = 11.4, 11.4, 4.6 Hz, 1H), 1.68 ppm (ddd, J = 11.4, 11.4, 6.3 Hz, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.9, 147.2, 141.8, 135.7, 131.1, 126.7, 126.5, 125.8, 125.2, 124.4, 113.3, 111.5, 68.2, 65.0, 55.2, 48.3, 48.0, 37.2, 36.6, 30.0 ppm; IR (KBr): 2904, 1611 cm -1 ; HRMS (MALDI-TOF): calcd for C 20 H 22 NO [M+H] + : 292.1696, found 292.1690. Stereochemistry was determined by NOESY. Compound 2h MeO N Ph Ph Reaction was carried out according to the general procedure B with 1h (16.2 mg, 0.046 mmol), NCS (7.2 mg, 0.054 mmol), and NaBH 4 (5.7 mg, 0.151 mmol) in CF 3 CH 2 OH (1.8 ml) and MeOH (1.0 ml) to give 2h (16.2 mg, 100%) as colorless solid. Reaction time for rearrangement: 22 h; Column chromatography: SiO 2, Hexane/AcOEt= 1/2 Mp: 107-108 o C; 1 H NMR (500 MHz, CDCl 3 ): δ= 7.45-7.42 (m, 2H), 7.34-7.30 (m, 2H), 7.23-7.18 (m, 5H), 7.15-7,12 (m, 1H), 6.99 (d, J = 8.3 Hz, 1H), 6.73 (dd, J = 8.3, 2.3 Hz, 1H), 6.66 (d, J = 2.3 Hz, 1H), 4.13-4.09 (m, 1H), 3.78 (s, 3H), 3.72-3.66 (m, 1H), 3.47 (d, J = 9.1 Hz, 1H), 3.14-3.06 (m, 2H), 2.98-2.93 (m, 2H), 2.73-2.67 (m, 1H), 2.32 ppm (dd, J = 12.0, 10.3 Hz, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.6, 136.3, 128.3, 128.1, 127.3, 126.94, 126.87, 126.0, 125.9, 113.2, 112.2, 65.1, 59.9, 55.2, 53.3, 48.2, 47.0, 27.2 ppm; IR (KBr): 2931, 1611 cm -1 ; HRMS (MALDI-TOF): calcd for C 25 H 26 NO [M+H] + : 356.2009, found 356.2005. S12

4. Reactions in Table 3 (Reaction with carbon nucleophiles) Compound 3a To a solution of 1a (21.4 mg, 0.105 mmol) in MeOH (1.1 ml) was added NCS (15.6 mg, 0.117 mmol) at 0 o C and the reaction mixture was stirred at rt for 28 h. MeOH was removed in vacuo and to the residue were added CH 2 Cl 2 (0.6 ml) and THF (0.6 ml). AllylMgBr solution (0.7 M in THF, 1.5 ml, 1.05 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 3 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 3a (21.9 mg, 86%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.05 (d, J = 8.6 Hz, 1H), 6.74 (dd, J = 8.6, 2.9 Hz, 1H), 6.59 (d, J = 2.9 Hz, 1H), 5.80-5.72 (m, 1H), 5.03-4.99 (m, 2H), 3.78 (s, 3H), 3.27-3.21 (m, 1H), 3.08-3.04 (m, 1H), 3.01-2.93 (m, 2H), 2.85-2.80 (m, 1H), 2.58-2.52 (m, 1H), 2.51-2.47 (m, 1H), 2.42-2.38 (m, 1H), 2.20-2.15 (m, 1H), 2.00-1.95 (m, 1H), 1.84-1.75 (m, 1H), 1.70-1.63 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.2, 135.68, 135.66, 135.2, 128.2, 116.6, 112.8, 112.4, 64.8, 55.1, 51.2, 46.8, 43.6, 37.8, 24.7, 22.6 ppm; IR (KBr): 2932, 1609 cm -1 ; HRMS (MALDI-TOF): calcd for C 16 H 22 NO [M+H] + : 244.1696, found 244.1701. Compound 3b To a solution of 1a (20.9 mg, 0.103 mmol) in MeOH (1.0 ml) was added NCS (15.1 mg, 0.113 mmol) at 0 o C and the reaction mixture was stirred at rt for 9 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (0.5 ml). MeMgBr solution (0.91 M in THF, 1.1 ml, 1.03 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 2.5 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 3b (12.2 mg, 55%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.10 (d, J = 8.6 Hz, 1H), 6.75 (dd, J = 8.6, 2.3 Hz, 1H), 6.58 (d, J = 2.3 Hz, 1H), 3.78 (s, 3H), 3.26-3.20 (m, 1H), 3.09-2.99 (m, 3H), 2.89-2.84 (m, 1H), 2.58-2.53 (m, 1H), 2.14-2.05 (m, 2H), 1.90-1.81 (m, 1H), 1.71-1.63 (m, 1H), 1.41 ppm (s, 3H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.2, 136.1, 135.0, 127.8, 112.8, 112.7, 62.4, 55.1, 50.6, 43.1, 40.2, 30.1, 24.5, 22.3 ppm; IR (KBr): 2963, 1609, 1500 cm -1 ; HRMS (MALDI-TOF): calcd for C 14 H 20 NO [M+H] + : 218.1539, found 218.1540. S13

Compound 3c To a solution of 1a (22.6 mg, 0.111 mmol) in MeOH (1.1 ml) was added NCS (16.5 mg, 0.124 mmol) at 0 o C and the reaction mixture was stirred at rt for 11 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (1.1 ml). EtMgBr solution (1.0 M in THF, 1.1 ml, 1.11 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 2 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 3c (22.3 mg, 87%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.06 (d, J = 8.6 Hz, 1H), 6.74 (dd, J = 8.6, 2.8 Hz, 1H), 6.59 (d, J = 2.8 Hz, 1H), 3.78 (s, 3H), 3.19-3.13 (m, 1H), 3.09-3.05 (m, 1H), 2.98-2.87 (m, 2H), 2.84-2.79 (m, 1H), 2.58 (td, J = 16.2, 4.7 Hz, 1H), 2.11-2.05 (m, 1H), 1.98-1.92 (m, 1H), 1.84-1.75 (m, 1H), 1.73-1.65 (m, 3H), 0.80 ppm (t, J = 7.4 Hz, 3H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.0, 136.0, 135.5, 128.1, 112.7, 112.3, 65.5, 55.1, 51.8, 44.6, 38.0, 35.0, 25.5, 22.8, 9.3 ppm; IR (KBr): 2959, 1609 cm -1 ; HRMS (MALDI-TOF): calcd for C 15 H 22 NO [M+H] + : 232.1696, found 232.1697. Compound 3d To a solution of 1a (22.4 mg, 0.110 mmol) in MeOH (1.1 ml) was added NCS (16.7 mg, 0.125 mmol) at 0 o C and the reaction mixture was stirred at rt for 8 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (1.1 ml). iprmgbr solution (1.0 M in THF, 1.1 ml, 1.10 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 6 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 3d (22.7 mg, 84%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.09 (d, J = 8.6 Hz, 1H), 6.73 (dd, J = 8.6, 2.9 Hz, 1H), 6.59 (d, J = 2.9 Hz, 1H), 3.78 (s, 3H), 3.27-3.21 (m, 1H), 3.04-3.00 (m, 1H), 2.97-2.88 (m, 2H), 2.76 (ddd, J = 16.6, 7.4, 7.4 Hz, 1H), 2.55 (td, J = 17.2, 5.6 Hz, 1H), 2.15 (ddd, J = 12.6, 8.6, 4.6 Hz, 1H), 1.96-1.86 (m, 2H), 1.81-1.72 (m, 1H), 1.63-1.56 (m, 1H), 0.93 (d, J = 6.9 Hz, 3H), 0.84 ppm (d, J = 6.9 Hz, 3H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.0, 136.2, 135.1, 128.7, 112.7, 111.8, 67.4, 55.1, 52.3, 44.7, 37.9, 35.9, 24.8, 22.9, 18.7, 18.4 ppm; IR (KBr): 2954, 1608 cm -1 ; HRMS (MALDI-TOF): calcd for C 16 H 24 NO [M+H] + : 246.1852, found 246.1852. S14

Compound 3e MeO N To a solution of 1a (21.0 mg, 0.103 mmol) in MeOH (1.0 ml) was added NCS (15.2 mg, 0.114 mmol) at 0 o C and the reaction mixture was stirred at rt for 17 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (1.0 ml). VinylMgBr solution (1.0 M in THF, 1.0 ml, 1.03 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 4 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 3e (19.0 mg, 80%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.03 (d, J = 8.6 Hz, 1H), 6.74 (dd, J = 8.6, 2.9 Hz, 1H), 6.60 (d, J = 2.9 Hz, 1H), 5.94 (dd, J = 17.2, 10.3 Hz, 1H), 5.05 (dd, 10.3, 1.4 Hz, 1H), 4.70 (dd, J = 17.2, 1.4 Hz, 1H), 3.78 (s, 3H), 3.21-3.14 (m, 1H), 3.07-2.96 (m, 3H), 2.90-2.84 (m, 1H), 2.55-2.48 (m, 1H), 2.21 (ddd, J = 12.6, 9.2, 5.7 Hz, 1H), 2.13 (ddd, J = 12.6, 8.6, 6.3 Hz, 1H), 1.90-1.81 (m, 1H), 1.74-1,66 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.5, 145.7, 136.3, 131.4, 129.3, 114.3, 112.8, 112.3, 66.9, 55.1, 49.8, 42.5, 38.5, 24.4, 22.6 ppm; IR (KBr): 2933, 1608 cm -1 ; HRMS (MALDI-TOF): calcd for C 15 H 20 NO [M+H] + : 230.1539, found 230.1539. Compound 3f To a solution of 1a (18.7 mg, 0.092 mmol) in MeOH (1.0 ml) was added NCS (13.9 mg, 0.104 mmol) at 0 o C and the reaction mixture was stirred at rt for 11 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (1.0 ml). PhenylethynylMgBr solution (1.0 M in THF, 0.9 ml, 0.920 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 3.5 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 3f (24.1 mg, 86%) as pale yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ= 7.30-7.27 (m, 2H), 7.19-7.16 (m, 4H), 6.68 (dd, J = 8.2, 2.7 Hz, 1H), 6.57 (d, J = 2.7 Hz, 1H), 3.71 (s, 3H), 3.17-2.97 (m, 4H), 2.89-2.83 (m, 1H), 2.75-2.69 (m, 1H), 2.60-2.53 (m, 1H), 2.06-1.81 ppm (m, 3H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 158.1, 135.0, 132.4, 131.8, 131.7, 128.0, 127.7, 127.1, 123.4, 113.3, 112.3, 91.0, 85.7, 61.6, 55.2, 50.1, 43.8, 39.1, 27.6, 21.4 ppm; IR (KBr): 2938, 1608 cm -1 ; HRMS (MALDI-TOF): calcd for C 21 H 22 NO [M+H] + : 304.1696, found 304.1696. S15

Comparison of solvent 5. Reactions in Scheme 3 (Synthesis of crispine A and analogues) Compound 1i Reaction was carried out according to the general method A with 2-(3,4-dimethoxyphenyl)ethylamine (0.52 ml, 3.0 mmol), cyclobutanone (0.254 ml, 3.3 mmol), and trifluoroacetic acid (1.84 ml, 24 mmol) in toluene (10 ml) to give 1i (551.3 mg, 79%) as pale yellow oil. Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 1 H NMR (500 MHz, CDCl 3 ): δ= 6.98 (s, 1H), 6.52 (s, 1H), 3.92 (s, 3H), 3.85 (s, 3H), 3.06 (t, J = 6.3 Hz, 2H), 2.70 (t, J = 6.3 Hz, 2H), 2.49-2.44 (m, 2H), 2.22-2.11 (m, 3H), 2.05-1.97 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 147.5, 147.4, 135.1, 126.4, 111.3, 108.6, 59.2, 56.1, 55.8, 39.7, 37.1, 29.8, 14.8 ppm; IR (KBr): 3304, 2934 cm -1 ; HRMS (MALDI-TOF): calcd for C 14 H 20 NO 2 [M+H] + : 234.1489, found 234.1489. Compound 4a (crispine A) 4 MeO MeO N Reaction was carried out according to the general procedure A with 1i (24.2 mg, 0.104 mmol), NCS (15.4 mg, 0.115 mmol), and NaBH 4 (12.2 mg, 0.323 mmol) in MeOH (1.0 ml) to give 4a (22.3 mg, 92%) as pale yellow solid. Reaction time for rearrangement: 15.5 h; Column chromatography: SiO 2, 4 Q. Zhang, G. Tu, Y. Zhao, T. Cheng, Tetrahedron 2002, 58, 6795. S16

AcOEt/triethylamine = 20/1 Mp: 88-90 o C (lit 87-89 o C); 1 H NMR (500 MHz, CDCl 3 ): δ= 6.61 (s, 1H), 6.57 (s, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 3.46-3.41 (m, 1H), 3.20-3.15 (m, 1H), 3.10-3.05 (m, 1H), 3.05-2.98 (m, 1H), 2.76-2.71 (m, 1H), 2.67-2.62 (m, 1H), 2.60-2.54 (m, 1H), 2.36-2.29 (m, 1H), 1.99-1.82 (m, 2H), 1.77-1.68 (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 147.3, 147.2, 130.9, 126.2, 111.3, 108.8, 62.9, 56.0, 55.8, 53.1, 48.3, 30.5, 28.0, 22.2 ppm; IR (KBr): 2936, 1507 cm -1 ; HRMS (MALDI-TOF): calcd for C 14 H 20 NO 2 [M+H] + : 234.1489, found 234.1489. Compound 4b MeO MeO N To a solution of 1i (27.0 mg, 0.116 mmol) in MeOH (1.2 ml) was added NCS (17.4 mg, 0.130 mmol) at 0 o C and the reaction mixture was stirred at rt for 15.5 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (1.2 ml). AllylMgCl solution (1.0 M in THF, 1.1 ml, 1.16 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 3 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 4b (24.7 mg, 78%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 6.61 (s, 1H), 6.54 (s, 1H), 5.85-5.76 (m, 1H), 5.04-5.00 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H), 3.22 (ddd, J = 13.2, 10.3, 4.6 Hz, 1H), 3.05-2.99 (m, 2H), 2.96-2.89 (m, 1H), 2.86-2.81 (m, 1H), 2.53-2.39 (m, 3H), 2.20-2.14 (m, 1H), 1.98 (ddd, J = 16.6, 12.6, 8.0 Hz, 1H), 1.84-1.75 (m, 1H), 1.70-1.62 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 147.2, 146.9, 135.7, 134.9, 126.3, 116.6, 110.9, 110.1, 64.9, 56.0, 55.7, 50.8, 46.6, 43.3, 37.7, 23.4, 22.5 ppm; IR (KBr): 2928, 1512 cm -1 ; HRMS (MALDI-TOF): calcd for C 17 H 24 NO 2 [M+H] + : 274.1802, found 274.1807. Compound 4c To a solution of 1i (24.8 mg, 0.106 mmol) in MeOH (1.1 ml) was added NCS (15.7 mg, 0.118 mmol) at 0 o C and the reaction mixture was stirred at rt for 17 h. MeOH was removed in vacuo and to the residue was added CH 2 Cl 2 (1.1 ml). BnMgCl solution (0.96 M in THF, 1.1 ml, 1.06 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 4 h at rt. The reaction was quenched S17

with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (AcOEt/triethylamine = 20/1) to give compound 4c (25.7 mg, 75%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.18-7.15 (m, 3H), 6.95-6.93 (m, 2H), 6.53 (s, 1H), 6.17 (s, 1H), 3.85 (s, 3H), 3.62 (s, 3H), 3.20 (ddd, J = 12.6, 9.7, 4.6 Hz, 1H), 3.11-3.06 (m, 1H), 3.02-2.79 (m, 5H), 2.38 (td, J = 16.0, 4.3 Hz, 1H), 2.25 (ddd, J = 12.6, 8.0, 4.6 Hz, 1H), 1.93 (ddd, J = 16.0, 12.6, 8.0 Hz, 1H) 1.76-1.66 (m, 1H), 1.65-1.58 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 146.9, 146.5, 138.8, 133.6, 131.0, 127.4, 127.0, 125.9, 110.8, 110.7, 65.9, 55.70, 55.65, 51.4, 48.5, 43.9, 38.1, 24.1, 22.5 ppm; IR (KBr): 2935, 1609, 1512 cm -1 ; HRMS (MALDI-TOF): calcd for C 21 H 26 NO 2 [M+H] + : 324.1958, found 324.1958 6. Reactions in Scheme 4 (Reaction with the norcamphor derivative) Compound 5 Title compound was prepared according to the general method B. 1st reaction was carried out with 2-(3-methoxyphenyl)ethylamine (0.44 ml, 2.96 mmol), norcamphor (233.1 mg, 1.40 mmol), Ti(OiPr) 4 (0.95 ml, 3.03 mmol), HCOOH (8.4 ml, 0.2 mol), Ac 2 O (19.1 ml, 0.2 mol) and trifluoroacetic acid (30.6 ml, 0.4 mol) to give 5-CHO (333.4 mg, 59%) as pale yellow oil. Column chromatography: SiO 2, Hexane/AcOEt = 1/1. 2nd reaction was carried out with 5-CHO (195.5 mg, 0.72 mmol) and NaOH (2.32 g, 58 mmol) in EtOH/H 2 O (3.6 ml) to give 5 (112.5 mg, 64%) as pale yellow oil. Column chromatography: SiO 2, AcOEt/triethylamine = 20/1 5-CHO: 1 H NMR (500 MHz, CDCl 3 ): δ= 8.44 (s, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.69 (dd, J = 8.6, 2.9 Hz, 1H), 6.64 (d, J = 8.6 Hz, 1H), 4.53-4.43 (m, 1H), 3.77 (s, 3H), 3.45-3.35 (m, 1H), 3.17-3.07 (m, 1H), 2.83 (ddd, J = 16.9, 7.5, 2.3 Hz, 1H), 2.55-2.46 (m, 2H), 2.40-2.31 (m, 1H), 2.01 (dd, J = 14.0, 2.3 Hz, 1H), 1.83-1.78 (m, 1H), 1.65-1.57 (m, 2H), 1.53 (td, J = 12.6, 4.5 Hz, 1H), 1.35-1.29 (m, 1H), 1.27-1.21 ppm (m, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 163.3, 158.3, 136.1, 135.6, 125.9, 114.5, 110.7, 66.9, 55.2, 47.9, 37.5, 37.1, 36.3, 35.0, 29.8, 27.3, 22.8 ppm; IR (KBr): 2960, 1657, 1608 cm -1 ; HRMS (MALDI-TOF): calcd for C 17 H 22 NO 2 [M+H] + : 272.1645, found 272.1647. 5: 1 H NMR (500 MHz, CDCl 3 ): δ= 7.19 (d, J = 8.6 Hz, 1H), 6.68 (dd, J = 8.6, 2.9 Hz, 1H), 6.61 (d, J = 2.9 Hz, 1H), 3.77 (s, 3H), 3.12-3.03 (m, 2H), 2.99-2.92 (m, 1H), 2.77-2.71 (m, 1H), 2.37-2.29 (m, 3H), 1.96-1.92 (m, 1H), 1.88-1.82 (m, 1H), 1.66-1.59 (m, 1H), 1.42-1.30 (m, 2H), 1.28-1.23 (m, 1H), 1.18 ppm (dd, J = 13.2, 2.8 Hz, 1H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.5, 137.8, 135.7, 127.2, 114.1, 110.7, 62.1, 55.1, 46.9, 46.4, 40.0, 37.0, 36.5, 29.3, 29.1, 23.5 ppm; IR (KBr): 3324, 2947 1607 cm -1 ; HRMS (MALDI-TOF): calcd for C 16 H 22 NO [M+H] + : 244.1696, found 244.1697. Stereochemistry was determined by NOESY of 5f-CHO. S18

Compound 6a Reaction was carried out according to the general procedure B with 5 (29.8 mg, 0.122 mmol), NCS (18.4 mg, 0.138 mmol), and NaBH 4 (13.9 mg, 0.367 mmol) in CF 3 CH 2 OH (1.2 ml) and MeOH (1.2 ml) to give 6a (18.5 mg, 62%) as colorless oil. Reaction time for rearrangement: 8 h; Column chromatography: SiO 2, Hexane/AcOEt= 4/1 1 H NMR (500 MHz, CDCl 3 ): δ= 7.11 (d, J = 8.6 Hz, 1H), 6.70 (dd, J = 8.6, 2.3 Hz, 1H), 6.61 (d, J = 2.3 Hz, 1H), 3.77 (s, 3H), 3.17-3.08 (m, 1H), 3.06 (s, 1H), 2.80 (dd, J = 11.8, 6.3 Hz, 1H), 2.71-2.65 (m, 2H), 2.64-2.58 (m, 1H), 2.49 (ddd, J = 11.8, 11.8, 4.1 Hz, 1H), 2.36 (d, J = 10.3 Hz, 1H), 2.20-2.16 (m, 1H), 1.71-1.53 (m, 4H), 1.44-1.30 ppm (m, 2H); 13 C NMR (125.8 MHz, CDCl 3 ): δ= 157.4, 137.5, 130.5, 125.4, 113.5, 111.4, 66.9, 62.3, 55.1, 51.8, 38.41, 38.38, 35.6, 30.1, 29.0, 25.6 ppm; IR (KBr): 2935, 1502 cm -1 ; HRMS (MALDI-TOF): calcd for C 16 H 22 NO [M+H] + : 244.1696, found 244.1699. Compound 6b MeO N To a solution of 5 (26.4 mg, 0.108 mmol) in CF 3 CH 2 OH (1.1 ml) was added NCS (16.1 mg, 0.121 mmol) at 0 o C and the reaction mixture was stirred at rt for 10 h. CF 3 CH 2 OH was removed in vacuo and to the residue was added CH 2 Cl 2 (0.6 ml) and THF (0.6 ml). AllylMgBr solution (1.0 M in Et 2 O, 1.1 ml, 1.1 mmol) was added to the resulting solution at 0 o C and the reaction mixture was stirred for 0.5 h at rt. The reaction was quenched with sat. NH 4 Cl aq. and the solution was basified with 10% NaOH aq.. The mixture was extracted with CH 2 Cl 2. The organic layer was dried over Na 2 SO 4 and evaporated in vacuo. The residue was purified by SiO 2 column chromatography (Hexane/AcOEt = 4/1) to give compound 6b (18.5 mg, 60%) as pale yellow oil. 1 H NMR (500 MHz, CDCl 3 ): δ= 7.01 (d, J = 8.6 Hz, 1H), 6.65-6.61 (m, 2H), 5.78-5.69 (m, 1H), 5.00-4.97 (m, 1H), 4.92-4.88 (m, 1H), 3.77 (s, 3H), 3.13-3.05 (m, 2H), 2.84 (d, J = 10.3 Hz, 1H), 2.65-2.61 (m, 2H), 2.57-2.53 (m, 2H), 2.48-2.44 (m, 1H), 2.29 (dd, J = 14.1, 7.4 Hz, 1H), 2.15-2.12 (m, 1H), 1.90 (d, J = 11.5 Hz, 1H), 1.56-1.45 (m, 2H), 1.42-1.25 ppm (m, 3H); 13 C NMR (125.8 MHz, S19

CDCl 3 ): δ= 157.2, 136.8, 135.6, 134.7, 126.1, 117.0, 113.7, 110.2, 61.6, 57.4, 55.0, 45.0, 40.4, 35.6, 34.8, 32.2, 29.3, 28.8, 26.4 ppm; IR (KBr): 2933, 1609, 1502 cm -1 ; HRMS (MALDI-TOF): calcd for C 19 H 26 NO [M+H] + : 284.2009, found 284.2005 7. X-ray crystallographic analysis of 6a TsOH 6a TsOH was prepared 6a and TsOH H 2 O (1.0 equiv). Crystallization Method:Re-crystallization from AcOEt and Hexane. Single crystal X-ray diffraction data were collected under nitrogen gas flow on Rigaku AFC-7R diffractometer and Mercury CCD detector equipped with graphite-monochoromatic Mo K radiation ( Å), installed at the institute of scientific and industrial research, Osaka University. A transparent block of crystal was mounted on LithoLoops (Moleclular Deimensions, USA) with vacuum grease under an optical microscope. The intensity data sets were integrated by CrystalClear software. 5 The absorption corrections were carried out by the empirical method. The structures were solved by direct methods using SIR2004 program 6 and refined by full-matrix least squares on F 2 using SHELXL-97 program 7, implemented in program package WinGX. 8 The final models include anisotropic refinement for the non-hydrogen atoms and an isotropic riding model for H atoms. Further details of the refinements are given table S1. Crystallographic data for the structures reported in this paper have been deposited at the Cambridge Crystallographic Data Centre (CCDC-1413456 ). Table S2. Crystallographic data and structure refinement for 6a TsOH: Compound 6a TsOH Moiety formula C 16 H 22 NO, C 7 H 7 O 3 S Sum formula C 23 H 29 NO 4 S Formula weight 415.53 Temperature (K) 123(2) Crystal system triclinic Space group P-1 a (A ) 9.5230 (1) b (A ) 9.6405 (17) c (A ) 11.7824 (3) ( ) 83.18 (4) ( ) 76.85 (3) 5 CrystalClear Rigaku Corporation, The Woodlands, Texas, USA, 1999 6 M. C. Burla, R. Caliandro, M. Camalli, B. Carrozzini, G. L. Cascarano, L. De Caro, C. Giacovazzo, G. Polidori, R. Spagna, J. Appl. Crystallogr. 2005, 38, 381-338 7 G. M. Sheldrick. Acta Cryst. 2008, A64, 112-122 8 L. J. Farrugia J. Appl. Crystallogr. 1999, 32, 837-838 S20

( ) 71.05 (4) V (A 3 ) 995.1 (3) Z 2 D calcd (g/cm 3 ) 1.387 Data completeness 0.979 Data / parameters 4,504 / 263 R 1 0.0555 wr 2 0.1397 Goodness-of-fit c 1.037 Full structure 6a TsOH S21

8. NMR Study 8 6 4 2 0 S22

13 C NMR of the intermediate single pulse decoupled gated NOE 200 175 150 125 100 75 50 25 DFILE 140179 carbon_carbon-1-1 COMNT single pulse decoupled gate DATIM 2014-11-13 11:32:06 OBNUC 13C EXMOD carbon.jxp OBFRQ 125.77 MHz OBSET 7.87 KHz OBFIN 4.21 Hz POINT 26214 FREQU 31446.54 Hz SCANS 439 ACQTM 0.8336 sec PD 2.5000 sec PW1 3.20 usec CTEMP 20.5 c SLVNT CD3OD EXREF 49.00 ppm RGAIN 60 181.5563 168.4218 141.2848 134.6651 117.4291 115.1208 114.9586 60.1791 56.7166 49.5055 49.3338 49.1717 49.0000 48.8283 48.6566 48.4849 46.0526 30.5716 26.9852 19.7741 S23

9. 1 H and 13 C NMR Data of 2a 1 H NMR chart of 1a single_pulse 8 6 4 2 0 DFILE 140171_proton-1-1.als COMNT single_pulse DATIM 2014-11-15 19:16:42 OBNUC 1H EXMOD proton.jxp OBFRQ 500.16 MHz OBSET 2.41 KHz OBFIN 6.01 Hz POINT 13107 FREQU 7507.51 Hz SCANS 16 ACQTM 1.7459 sec PD 2.0000 sec PW1 5.80 usec CTEMP 20.0 c EXREF 0.00 ppm RGAIN 36 1.00 0.93 0.93 1.09 1.09 2.01 2.01 2.04 3.02 3.02 7.4198 7.4026 7.2606 6.8048 6.7991 6.7876 6.7819 6.5700 6.5643 3.7803 3.0726 3.0611 3.0497 2.7748 2.7634 2.7519 2.4805 2.4771 2.4691 2.4645 2.4576 2.4496 2.4393 2.4336 2.4278 2.4244 2.1816 2.1736 2.1713 2.1679 2.1644 2.1587 2.1564 2.1507 2.1427 2.1370 2.1289 2.1255 2.1198 2.1152 2.0396 2.0339 2.0213 2.0087 2.0018 1.9949 1.9835 1.9331 0.0000 S24

13 C NMR chart of 1a single pulse decoupled gated NOE 200 175 150 125 100 75 50 25 0 DFILE 140171 carbon_carbon-1-1 COMNT single pulse decoupled gate DATIM 2014-11-15 19:19:57 OBNUC 13C EXMOD carbon.jxp OBFRQ 125.77 MHz OBSET 7.87 KHz OBFIN 4.21 Hz POINT 26214 FREQU 31446.54 Hz SCANS 500 ACQTM 0.8336 sec PD 2.5000 sec PW1 3.20 usec CTEMP 20.5 c EXREF 77.00 ppm RGAIN 60 157.5428 135.6139 135.3468 126.4665 113.0936 112.5022 77.2575 77.0000 76.7520 59.0581 55.1664 39.4852 37.3009 30.5381 14.5039-0.0327 S25

1 H NMR chart of 1b single_pulse F:\NMR\140275_proton-1-1.als 8 6 4 2 0 DFILE 140275_proton-1-1.als COMNT single_pulse DATIM 2015-02-02 11:56:09 OBNUC 1H EXMOD proton.jxp OBFRQ 300.53 MHz OBSET 1.15 KHz OBFIN 8.57 Hz POINT 13107 FREQU 4508.57 Hz SCANS 16 ACQTM 2.9072 sec PD 2.0000 sec PW1 5.60 usec CTEMP 17.9 c EXREF 0.00 ppm RGAIN 44 0.95 0.92 2.24 2.00 2.04 1.95 2.82 4.07 7.2635 6.9820 6.4978 5.9061 3.0457 3.0263 3.0068 2.7024 2.6818 2.6623 2.4414 2.1427 2.1312 1.7203 0.0000 S26

13 C NMR chart of 1b single pulse decoupled gated NOE F:\NMR\140275 for data_carbon-1-1.als 200 175 150 125 100 75 50 25 0 DFILE 140275 for data_carbon-1- COMNT single pulse decoupled gate DATIM 2015-07-03 12:12:29 OBNUC 13C EXMOD carbon.jxp OBFRQ 100.53 MHz OBSET 5.35 KHz OBFIN 5.86 Hz POINT 26214 FREQU 25125.63 Hz SCANS 1000 ACQTM 1.0433 sec PD 2.0000 sec PW1 3.05 usec CTEMP 20.7 c EXREF 77.00 ppm RGAIN 60 146.0886 145.6024 136.3823 127.2671 108.2930 105.4612 100.5889 77.3146 77.0000 76.6758 59.4752 39.4999 37.2688 30.2894 14.4713-0.0311 S27

1 H NMR chart of 1c single_pulse 8 6 4 2 0 DFILE 140254 for data_proton-1-1 COMNT single_pulse DATIM 2015-04-20 22:19:52 OBNUC 1H EXMOD proton.jxp OBFRQ 500.16 MHz OBSET 2.41 KHz OBFIN 6.01 Hz POINT 13107 FREQU 7507.51 Hz SCANS 16 ACQTM 1.7459 sec PD 2.0000 sec PW1 5.80 usec CTEMP 17.3 c EXREF 0.00 ppm RGAIN 32 0.95 0.99 0.90 1.90 2.13 1.92 2.25 3.00 3.01 7.4015 7.3854 7.2549 7.0522 7.0361 6.8586 3.0657 3.0543 3.0417 2.7531 2.7416 2.7290 2.4840 2.4794 2.4725 2.4656 2.4588 2.4530 2.4439 2.2927 2.1690 2.1633 2.1507 2.1415 2.1312 2.0373 2.0339 2.0247 2.0224 2.0144 2.0075 1.9949 0.0000 S28

13 C NMR chart of 1c single pulse decoupled gated NOE 200 175 150 125 100 75 50 25 0 DFILE 140254 for data_carbon-1- COMNT single pulse decoupled gate DATIM 2015-04-20 22:23:09 OBNUC 13C EXMOD carbon.jxp OBFRQ 125.77 MHz OBSET 7.87 KHz OBFIN 4.21 Hz POINT 26214 FREQU 31446.54 Hz SCANS 512 ACQTM 0.8336 sec PD 2.0000 sec PW1 3.20 usec CTEMP 18.0 c EXREF 77.00 ppm RGAIN 60 140.2496 135.4327 133.8493 129.3090 127.0293 125.2551 77.2480 77.0000 76.7425 59.1344 39.4947 37.2341 30.1089 20.8566 14.5326-0.0422 S29

1 H NMR chart of 1e-Tf single_pulse 8 6 4 2 0 DFILE 140507-2_proton-1-1.als COMNT single_pulse DATIM 2015-12-09 23:42:11 OBNUC 1H EXMOD proton.jxp OBFRQ 300.53 MHz OBSET 1.15 KHz OBFIN 8.57 Hz POINT 13107 FREQU 4508.57 Hz SCANS 16 ACQTM 2.9072 sec PD 2.0000 sec PW1 5.50 usec CTEMP 19.5 c EXREF 0.00 ppm RGAIN 40 1.06 1.07 0.99 2.00 1.99 2.08 1.87 2.12 7.6184 7.5886 7.2624 7.2006 7.1926 7.1720 7.1628 7.0827 7.0747 3.8126 3.7909 3.7691 3.1293 3.1075 3.0847 2.8775 2.8420 2.8042 2.7676 2.5055 2.0511 2.0477 2.0374 2.0213 2.0156 1.9904 0.0000 S30

13 C NMR chart of 1e-Tf single pulse decoupled gated NOE 200 175 150 125 100 75 50 25 0 DFILE 140507-500_Carbon-1-1.al COMNT single pulse decoupled gate DATIM 2015-12-10 00:08:24 OBNUC 13C EXMOD carbon.jxp OBFRQ 125.77 MHz OBSET 7.87 KHz OBFIN 4.21 Hz POINT 26214 FREQU 31446.54 Hz SCANS 7500 ACQTM 0.8336 sec PD 3.0000 sec PW1 3.20 usec CTEMP 21.2 c EXREF 77.00 ppm RGAIN 60 148.5671 140.8124 135.2705 124.7305 122.3554 120.5813 119.9613 119.4367 118.0250 117.4145 77.2575 77.0000 76.7520 62.7495 42.2895 34.8686 28.5636 13.6836-0.0232 S31

1 H NMR chart of 1d-Tf single_pulse 8 6 4 2 0 DFILE 140524 d.p._proton-1-1.als COMNT single_pulse DATIM 2015-11-17 01:04:22 OBNUC 1H EXMOD proton.jxp OBFRQ 399.78 MHz OBSET 4.19 KHz OBFIN 7.29 Hz POINT 13107 FREQU 6002.40 Hz SCANS 16 ACQTM 2.1837 sec PD 2.0000 sec PW1 5.64 usec CTEMP 20.1 c EXREF 0.00 ppm RGAIN 40 1.02 0.93 2.00 1.83 1.89 1.75 2.16 2.08 7.5352 7.5248 7.5122 7.2705 7.2602 7.2568 7.2488 7.1560 7.1422 7.1331 3.8042 3.7882 3.7710 3.0631 2.8260 2.7973 2.5132 2.0413 2.0356 2.0241 2.0161 2.0069 1.9989 1.9909 1.9737 1.5567 0.0000 S32

13 C NMR chart of 1d-Tf single pulse decoupled gated NOE 200 175 150 125 100 75 50 25 0 DFILE 140524 d.p._carbon-1-1.als COMNT single pulse decoupled gate DATIM 2015-11-17 01:09:41 OBNUC 13C EXMOD carbon.jxp OBFRQ 100.53 MHz OBSET 5.35 KHz OBFIN 5.86 Hz POINT 26214 FREQU 25125.63 Hz SCANS 9300 ACQTM 1.0433 sec PD 2.0000 sec PW1 3.05 usec CTEMP 19.9 c EXREF 77.00 ppm RGAIN 60 140.3106 132.0916 129.7556 127.6008 126.5710 124.1969 122.5951 120.9932 117.7896 114.5859 77.3146 77.0000 76.6758 63.1651 42.8466 34.9328 28.3824 13.8229-0.0311 S33

1 H NMR chart of 1d single_pulse 8 6 4 2 0 DFILE 140513_proton-1-1.als COMNT single_pulse DATIM 2015-11-11 00:07:51 OBNUC 1H EXMOD proton.jxp OBFRQ 500.16 MHz OBSET 2.41 KHz OBFIN 6.01 Hz POINT 13107 FREQU 7507.51 Hz SCANS 16 ACQTM 1.7459 sec PD 2.0000 sec PW1 5.80 usec CTEMP 19.7 c EXREF 0.00 ppm RGAIN 34 0.97 0.83 0.83 0.84 2.00 1.95 1.95 1.84 2.75 7.5103 7.4942 7.2549 7.2251 7.1243 7.1220 7.0419 7.0247 3.0829 3.0714 3.0588 2.7954 2.7829 2.7714 2.5114 2.5000 2.4920 2.1725 2.1667 2.1587 2.1541 2.1496 2.0350 0.0000 S34