structural and mechanistic studies of the base-induced ... · s4 2. preparation and crystal data of...

Structural and mechanistic studies of the base-induced

Sommelet–Hauser rearrangement of N--branched benzylic

azetidine-2-carboxylic acid-derived ammonium salts

Eiji Tayama,* Kazutoshi Watanabe and Sho Sotome

Department of Chemistry, Faculty of Science, Niigata University 950-2181, Japan

E-mail: [email protected]

Electronic Supplementary Information

Contents:

1. HPLC chromatogram of 3a and 4a for determination of ee S1–3

2. Preparation and crystal data of (1S,2S,1’S)-2a-BPh4 and (1R*,2R*,1’S*)-2e-BPh4 S4–7

3. Preparation of substrates S8–16

4. Copies of NMR spectra of substrates and rearrangement products (2–4, 7, 9–14, 16) S17–44

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2017

S1

1. HPLC chromatogram of 3a and 4a for determination of ee The ee were determined by HPLC analysis using chiral column in comparison with the racemic compounds. (R)-3a (99% ee): Daicel Chiralcel OD-RH column (15 cm), H2O/MeCN = 30/70 as the eluent, flow rate = 0.50 mL/min, tR = 8.6 min for (R)-3a (99.5%) and 9.6 min for (S)-3a (0.5%).

S2

(S)-3a (66% ee): Daicel Chiralcel OD-RH column (15 cm), H2O/MeCN = 40/60 as the eluent, flow rate = 0.50 mL/min, tR = 13.4 min for (R)-3a (16.9%) and 15.0 min for (S)-3a (83.1%).

S3

4a (89% ee): Daicel Chiralcel OJ-H column (25 cm), n-hexane/2-PrOH = 95/5 as the eluent, flow rate = 0.50 mL/min, tR = 9.0 min (94.3%) and 11.8 min (5.7%).

S4

2. Preparation and crystal data of (1S,2S,1’S)-2a-BPh4 and (1R*,2R*,1’S*)-2e-BPh4 (1S,2S,1´S)-2-(tert-Butoxycarbonyl)-1-methyl-1-(1´-phenylethyl)azetidin-1-ium tetraphenylborate [(1S,2S,1´S)-2a-BPh4]

A mixture of (1S,2S,1´S)-2a (193 mg, 0.454 mmol) and sodium tetraphenylborate (233 mg, 0.681 mmol) in THF (4.5 mL) was stirred for 2 days at room temperature. The resulting mixture was concentrated and the residue was crystallized from EtOH–THF to obtain (1S,2S,1´S)-2a-BPh4 (221 mg, 82% yield) as colourless crystals. Recrystallization from EtOH–THF gave a single crystal suitable for X-ray crystallographic analysis. CCDC-1553028 contains the supplementary crystallographic data for this paper. These data are provided free of charge by the CCDC. Colourless crystals; mp 181–182 °C; []26589 –24.5 (c 1.0 in acetone); IR (KBr) max/cm-1 3034, 3004, 2981, 1735, 1579, 1477, 1458, 1424, 1395, 1370, 1355, 1250, 1147, 1065, 1032, 1011, 866, 836, 773, 747, 737, 707; 1H NMR (400 MHz, acetone-d6) 7.67-7.61 (2H, m, Ph), 7.59-7.49 (3H, m, Ph), 7.38-7.30 (8H, m, Ph), 6.93 (8H, dd, J = 8.0, 7.2 Hz, Ph), 6.79 (4H, tt, J = 7.2, 1.2 Hz, Ph), 5.49 (1H, dd, J = 9.8, 9.8 Hz, 2-H), 5.03 (1H, q, J = 6.8 Hz, 1´-H), 4.70 (1H, ddd, J = 10.0, 9.8, 9.8 Hz, 4-H), 3.52 (1H, dddd, J = 10.0, 9.8, 3.4, 0.8 Hz, 4-H), 3.18 (3H, s, NCH3), 3.01 (1H, dddd, J = 12.2, 10.0, 10.0, 9.8 Hz, 3-H), 2.63-2.48 (1H, m, 3-H), 1.86 (3H, d, J = 6.8 Hz, 1´-CH3), 1.58 (9H, s, tBu); 13C NMR (100 MHz, acetone-d6) 165.0 (q, J = 49 Hz), 164.6, 137.1 (q, J = 2 Hz), 132.8, 131.7, 131.3, 130.3, 126.1 (q, J = 3 Hz), 122.4, 86.2, 74.6, 72.5, 62.0, 41.1, 28.0, 18.4, 14.6; HRMS (ESI): calcd. for C17H26NO2 [M–BPh4]+ 276.1958, found 276.2951.

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Empirical Formula C41H46BNO2 Formula Weight 595.60 Crystal System orthorhombic Lattice Parameters a = 13.4025(10) Å

b = 15.8388(12) Å c = 16.5989(13) Å V = 3523.6(5) Å3

Space Group P212121 (#19) Z value 4 Temperature 293 K No. of Reflections Measured Total: 36211

Unique: 8075 (Rint = 0.0360) Residuals: R1 (I > 2.00(I)) 0.0442 Residuals: wR2 (All reflections) 0.1085 Goodness of Fit Indicator 1.014 Flack parameter (Parsons' quotients = 1927) 0.2(4)

(1R*,2R*,1´S*)-2-(tert-Butoxycarbonyl)-1-(2´,3´-dihydro-1´H-inden-1´-yl)-1-methylazetidin-1-ium tetraphenylborate [(1R*,2R*,1´S*)-2e-BPh4]

(1R*,2R*,1'S*)-2e

N

BPh4NaBPh4THF

rt

recryst.

EtOH–THFsingle crystal

X-ray diffraction

N

OTf

(1R*,2R*,1'S*)-2e-BPh4(1S*,2R*,1'S*)-2e

N

OTf+

9/1 mixture

N

BPh4

(1S*,2R*,1'S*)-2e-BPh4

+

9/1 mixture

N

BPh4

(1R*,2R*,1'S*)-2e-BPh4pure

O

O

O

O

O

O O

O

O

O

A 9/1 mixture of (1R*,2R*,1´S*)-2e and (1S*,2R*,1´S*)-2e (127 mg, 0.290 mmol) and sodium tetraphenylborate (0.12 g, 0.35 mmol) in THF (2.9 mL) was stirred for 24 h at room temperature. The resulting mixture was concentrated and the residue was purified by chromatography on silica gel (CH2Cl2/MeOH = 50/1 to 10/1 as the eluent) to obtain a 9/1 mixture of (1R*,2R*,1´S*)-2e-BPh4 and (1S*,2R*,1´S*)-2e-BPh4 (146 mg, 83% yield) as a white solid. Recrystallization from EtOH–THF of the

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mixture afforded pure (1R*,2R*,1´S*)-2e-BPh4 (105 mg, 60% yield) as colourless crystals. The 2nd recrystallization from EtOH–THF gave a single crystal suitable for X-ray crystallographic analysis. CCDC-1553029 contains the supplementary crystallographic data for this paper. These data are provided free of charge by the CCDC. Colourless crystals; mp 146–147 °C; IR (KBr) max/cm-1 3052, 2996, 2980, 1738, 1579, 1478, 1462, 1426, 1394, 1370, 1352, 1254, 1233, 1149, 1031, 1000, 896, 842, 753, 734, 707; 1H NMR (400 MHz, CDCl3) 7.47-7.38 (8H, m, ArH), 7.39 (1H, ddd, J = 7.4, 7.4, 1.2 Hz, ArH), 7.26 (1H, d, J = 7.4 Hz, ArH), 7.20 (1H, dd, J = 7.4, 7.4 Hz, ArH), 7.02 (9H, dd, J = 7.4, 7.4 Hz, ArH), 6.91 (4H, tt, J = 7.4, 1.2 Hz, ArH), 4.06 (1H, dd, J = 9.6, 9.6 Hz, 2-H), 3.86 (1H, d, J = 8.4 Hz, 1´-H), 2.78 (1H, ddd, J = 10.2, 10.0, 9.6 Hz, 4-H), 2.71 (1H, ddd, J = 17.4, 9.0, 8.8 Hz, 3´-H), 2.62 (1H, ddd, J = 17.4, 8.8, 8.4 Hz, 3´-H), 2.39 (1H, ddd, J = 10.2, 10.0, 4.0 Hz, 4-H), 2.04 (1H, dddd, J = 12.5, 10.0, 10.0, 9.6 Hz, 3-H), 1.90 (1H, dddd, J = 16.0, 9.0, 8.8, 8.4 Hz, 2´-H), 1.77 (3H, s, NCH3), 1.61 (1H, dddd, J = 12.5, 9.6, 9.6, 4.0 Hz, 3-H), 1.47-1.31 (1H, m, 2´-H), 1.37 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 163.9 (q, J = 49 Hz), 162.6, 146.4, 136.0, 132.3, 131.3, 127.1, 127.0, 125.82 (q, J = 2 Hz), 125.76, 122.1, 85.8, 79.5, 70.4, 61.6, 39.6, 30.4, 27.7, 26.2, 17.6; HRMS (ESI): calcd. for C18H26NO2 [M–BPh4]+ 288.1958, found 288.1953.

(1:1 mixture of conformational isomers)

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Empirical Formula C84H92B2N2O4 Formula Weight 1215.21 Crystal System triclinic Lattice Parameters a = 10.1389(13) Å

b = 10.2830(13) Å c = 19.617(3) Å = 79.125(6)° = 89.681(6)° g = 62.353(4)° V = 1771.3(4) Å3

Space Group P1 (#1) Z value 1 Temperature 293 K No. of Reflections Measured Total: 18195

Unique: 15384 (Rint = 0.0233) Residuals: R1 (I > 2.00(I)) 0.0552 Residuals: wR2 (All reflections) 0.1265 Goodness of Fit Indicator 1.063 Flack parameter (Parsons' quotients = 4314) -0.1(8)

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3. Preparation of substrates tert-Butyl 1-((S)-1´-phenylethyl)azetidine-2-carboxylate [(2S,1´S)-1a and (2R,1´S)-1a]

A mixture of (S)-1-phenylethylamine (400 L, 3.10 mmol), tert-butyl 2,4-dibromobutanoate (937 mg, 3.10 mmol), and K2CO3 (1.29 g, 9.3 mmol) in MeCN (16 mL) was refluxed for 6 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel [n-hexane/EtOAc = 7/1 to 4/1 as the eluent, Rf: (2S,1´S) > (2R,1´S)] to obtain (2S,1´S)-1a (261 mg, 32% yield) as a colourless oil and (2R,1´S)-1a (270 mg, 33% yield) as a colourless oil. The stereochemistry of each diastereomers were clarified in our previous work.1 (2S,1´S)-1a: []22589 –111.1 (c 1.0 in EtOH); IR (film) max/cm-1 3061, 3025, 3003, 2973, 2930, 2869, 2837, 2779, 1742, 1718, 1493, 1478, 1453, 1391, 1366, 1319, 1284, 1232, 1213, 1152, 1101, 1071, 1042, 1031, 975, 945, 847, 763, 701; 1H NMR (400 MHz, CDCl3) 7.36-7.27 (4H, m, Ph), 7.22 (1H, dddd, J = 7.4, 6.6, 1.6, 1.6 Hz, Ph), 3.62 (1H, dd, J = 8.6, 8.2 Hz, 2-H), 3.43 (1H, q, J = 6.6 Hz, 1´-H), 3.08 (1H, dddd, J = 8.4, 7.0, 2.8, 0.8 Hz, 4-H), 2.73 (1H, ddd, J = 8.9, 8.2, 7.0 Hz, 4-H), 2.21 (1H, dddd, J = 10.6, 8.9, 8.6, 8.4 Hz, 3-H), 2.12 (1H, dddd, J = 10.6, 8.2, 8.2, 2.8 Hz, 3-H), 1.48 (9H, s, tBu), 1.23 (3H, d, J = 6.6 Hz, 1´-CH3); 13C NMR (100 MHz, CDCl3) 172.5, 142.9, 128.2, 127.4, 127.0, 80.6, 67.3, 64.8, 49.5, 28.0, 21.2, 20.7; HRMS (ESI): calcd. for C16H24NO2 [M+H]+ 262.1802, found 262.1794. (2R,1´S)-1a: []22589 +56.8 (c 1.0 in EtOH); IR (film) max/cm-1 3062, 3026, 3003, 2973, 2930, 2870, 2827, 2784, 1735, 1493, 1477, 1453, 1391, 1366, 1302, 1276, 1233, 1208, 1153, 1114, 1081, 1057, 1030, 1012, 975, 947, 846, 762, 700; 1H NMR (400 MHz, CDCl3) 7.34-7.29 (2H, m, Ph), 7.26 (2H, dddd, J = 7.2, 7.2, 1.6, 1.6 Hz, Ph), 7.20 (1H, tt, J = 7.2, 1.6 Hz, Ph), 3.54 (1H, dddd, J = 8.2, 6.6, 2.6, 0.6 Hz, 4-H), 3.50 (1H, dd, J = 8.2, 8.2 Hz, 2-H), 3.36 (1H, q, J = 6.6 Hz, 1´-H), 2.96 (1H, ddd, J = 9.2, 8.2, 6.6 Hz, 4-H), 2.22 (1H, dddd, J = 10.5, 9.2, 8.2, 8.2 Hz, 3-H), 2.11 (1H, dddd, J = 10.5, 8.2, 8.2, 2.6 Hz, 3-H), 1.26 (3H, d, J = 6.6 Hz, 1´-CH3), 1.17 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 171.6, 142.2, 128.2, 128.1, 127.3, 80.1, 68.0, 65.4, 50.7, 27.7, 20.8, 20.0; HRMS (ESI): calcd. for C16H24NO2 [M+H]+ 262.1802, found 262.1792. (rac)-tert-Butyl 1-(1´-phenylethyl)azetidine-2-carboxylate [(2S*,1´S*)-1a and (2R*,1´S*)-1a] Prepared by the same procedure with (2S,1´S)-1a and (2R,1´S)-1a using (rac)-1-phenylethylamine instead of (S)-1-phenylethylamine. (2S*,1´S*)-1a: 31% yield; colourless oil. (2R*,1´S*)-1a: 28% yield; colourless oil.

1 E. Tayama, K. Watanabe and Y. Matano, Eur. J. Org. Chem., 2016, 3631.

S9

tert-Butyl 1-(1´-(4´´-bromophenyl)ethyl)azetidine-2-carboxylate [(2S*,1´S*)-1b and (2R*,1´S*)-1b]

A mixture of 1-(4-bromophenyl)ethylamine (170 L, 1.18 mmol), tert-butyl 2,4-dibromobutanoate (362 mg, 1.20 mmol), and K2CO3 (835 mg, 6.0 mmol) in MeCN (6 mL) was refluxed for 6 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel [n-hexane/EtOAc = 15/1 to 3/1 as the eluent, Rf: (2S*,1´S*) > (2R*,1´S*)] to obtain (2S*,1´S*)-1b (109 mg, 27% yield) as a colourless oil and (2R*,1´S*)-1b (117 mg, 29% yield) as a colourless oil. The relative stereochemistry of each diastereomers were assigned by analogy with 1a. (2S*,1´S*)-1b: IR (film) max/cm-1 2972, 2930, 2836, 1741, 1589, 1482, 1453, 1392, 1367, 1320, 1288, 1234, 1213, 1154, 1097, 1070, 1043, 1010, 976, 945, 826, 780, 746, 716; 1H NMR (400 MHz, CDCl3) 7.42 (2H, ddd, J = 8.4, 2.0, 2.0 Hz, ArH), 7.23 (2H, ddd, J = 8.4, 2.0, 2.0 Hz, ArH), 3.63 (1H, dd, J = 8.4, 8.4 Hz, 2-H), 3.39 (1H, q, J = 6.8 Hz, 1´-H), 3.11-3.04 (1H, m, 4-H), 2.69 (1H, ddd, J = 8.4, 8.4, 7.2 Hz, 4-H), 2.21 (1H, dddd, J = 10.6, 8.8, 8.4, 8.4 Hz, 3-H), 2.13 (1H, dddd, J = 10.6, 8.4, 8.4, 2.8 Hz, 3-H), 1.48 (9H, s, tBu), 1.19 (3H, d, J = 6.8 Hz, 1´-CH3); 13C NMR (100 MHz, CDCl3) 172.3, 142.0, 131.3, 129.1, 120.6, 80.6, 66.7, 64.6, 49.7, 27.9, 21.2, 20.7; HRMS (ESI): calcd. for C16H23BrNO2 [M+H]+ 340.0907, found 340.0896. (2R*,1´S*)-1b: IR (film) max/cm-1 2972, 2930, 2870, 2830, 1737, 1591, 1486, 1454, 1406, 1391, 1366, 1340, 1297, 1233, 1208, 1153, 1115, 1100, 1071, 1010, 977, 947, 830, 762, 740, 715; 1H NMR (400 MHz, CDCl3) 7.39 (2H, d, J = 8.4 Hz, ArH), 7.21 (2H, d, J = 8.4 Hz, ArH), 3.52 (1H, ddd, J = 8.8, 6.8, 2.6 Hz, 4-H), 3.46 (1H, dd, J = 8.4, 8.4 Hz, 2-H), 3.32 (1H, q, J = 6.6 Hz, 1´-H), 2.95 (1H, ddd, J = 8.8, 8.4, 6.8 Hz, 4-H), 2.22 (1H, dddd, J = 10.6, 8.8, 8.8, 8.4 Hz, 3-H), 2.10 (1H, dddd, J = 10.6, 8.4, 8.4, 2.6 Hz, 3-H), 1.22 (3H, d, J = 6.6 Hz, 1´-CH3), 1.19 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 171.3, 141.2, 131.1, 129.8, 121.0, 80.2, 67.3, 65.3, 50.5, 27.5, 20.6, 19.8; HRMS (ESI): calcd. for C16H23BrNO2 [M+H]+ 340.0907, found 340.0900.

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tert-Butyl 1-(1´-(4´´-(tert-butoxycarbonyl)phenyl)ethyl)azetidine-2-carboxylate [(2S*,1´S*)-1c and (2R*,1´S*)-1c]

A solution of DCC (1.03 g, 5.0 mmol) in CH2Cl2 (10 mL) was added to a solution of 4-acetylbenzoic acid (0.82 g, 5.0 mmol), DMAP (0.18 g, 1.5 mmol), and t-BuOH (1.43 mL, 15 mmol) in CH2Cl2 (15 mL) at 0 °C. The mixture was stirred for 1 h at 0 °C and for 5 h at room temperature. The resulting mixture was filtered and the filtrate was concentrated. The residue was purified by chromatography on silica gel (n-hexane/EtOAc = 9/1 to 6/1 as the eluent) to obtain tert-butyl 4-acetylbenzoate (17) (522 mg, 47% yield) as colourless crystals. A mixture of 17 (514 mg, 2.33 mmol), O-benzylhydroxylamine hydrochloride (409 mg, 2.56 mmol), and AcONa (210 mg, 2.56 mmol) in EtOH (4.7 mL) was refluxed for 15 h. The resulting mixture was cooled to room temperature and filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel (n-hexane/EtOAc = 15/1 to 10/1 as the eluent) to obtain tert-butyl 4-(1-((benzyloxy)imino)ethyl)benzoate (18) (760 mg, quant.) as colourless crystals. 1H NMR analysis of 18 showed a 9/1 mixture of geometric isomers. A mixture of 18 (760 mg, 2.34 mmol) and Pd-C (loading: 10 wt.%, 49 mg) in EtOH (12 mL) was stirred for 15 h at room temperature under a hydrogen atmosphere. The resulting mixture was filtered through a pad of Celite and the filtrate was concentrated. The residue was purified by chromatography on silica gel (CH2Cl2/MeOH = 9/1 to 5/1 as the eluent) to give tert-butyl 4-(1-aminoethyl)benzoate (19) (489 mg, 94% yield) as a colourless oil. A mixture of 19 (482 mg, 2.18 mmol), tert-butyl 2,4-dibromobutanoate (658 mg, 2.18 mmol), and K2CO3 (0.90 g, 6.5 mmol) in MeCN (11 mL) was refluxed for 15 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel [n-hexane/EtOAc = 7/1 to 3/1 as the eluent, Rf: (2S*,1´S*) > (2R*,1´S*)] to obtain (2S*,1´S*)-1c (234 mg, 30% yield) as colourless crystals and (2R*,1´S*)-1c (244 mg, 31% yield) as a colourless oil. The relative stereochemistry of each diastereomers

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were assigned by analogy with 1a. (2S*,1´S*)-1c: mp 54–57 °C; IR (KBr) max/cm-1 2975, 2933, 2860, 1738, 1709, 1609, 1476, 1457, 1417, 1392, 1368, 1295, 1257, 1229, 1211, 1164, 1115, 1103, 1044, 1018, 973, 949, 852, 775, 707; 1H NMR (400 MHz, CDCl3) 7.92 (2H, d, J = 8.4 Hz, ArH), 7.40 (2H, d, J = 8.4 Hz, ArH), 3.65 (1H, dd, J = 8.2, 8.2 Hz, 2-H), 3.48 (1H, q, J = 6.6 Hz, 1´-H), 3.10 (1H, ddd, J = 7.8, 7.3, 1.8 Hz, 4-H), 2.70 (1H, ddd, J = 8.0, 8.0, 7.8 Hz, 4-H), 2.30-2.08 (2H, m, 3-H), 1.59 (9H, s, tBu), 1.49 (9H, s, tBu), 1.21 (3H, d, J = 6.6 Hz, 1´-CH3); 13C NMR (100 MHz, CDCl3) 172.4, 165.7, 147.9, 130.9, 129.5, 127.2, 80.8, 80.6, 67.1, 64.7, 49.7, 28.2, 28.0, 21.3, 20.8; HRMS (ESI): calcd. for C21H32NO4 [M+H]+ 362.2326, found 362.2310. (2R*,1´S*)-1c: IR (film) max/cm-1 2975, 2931, 2871, 2832, 1735, 1709, 1610, 1577, 1477, 1456, 1416, 1391, 1367, 1346, 1294, 1255, 1208, 1166, 1116, 1057, 1018, 978, 947, 917, 849, 775, 733, 708; 1H NMR (400 MHz, CDCl3) 7.89 (2H, ddd, J = 8.4, 1.8, 1.8 Hz, ArH), 7.37 (2H, ddd, J = 8.4, 1.8, 1.8 Hz, ArH), 3.58-3.51 (1H, m, 4-H), 3.50 (1H, dd, J = 8.4, 8.0 Hz, 2-H), 3.43 (1H, q, J = 6.4 Hz, 1´-H), 2.98 (1H, ddd, J = 8.6, 8.6, 7.0 Hz, 4-H), 2.23 (1H, dddd, J = 10.2, 8.8, 8.6, 8.4 Hz, 3-H), 2.12 (1H, dddd, J = 10.2, 8.6, 8.0, 2.6 Hz, 3-H), 1.57 (9H, s, tBu), 1.25 (3H, d, J = 6.4 Hz, 1´-CH3), 1.17 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 171.5, 165.7, 147.1, 131.1, 129.4, 127.9, 80.7, 80.3, 67.6, 65.3, 50.6, 28.2, 27.6, 20.9, 19.9; HRMS (ESI): calcd. for C21H32NO4 [M+H]+ 362.2326, found 362.2315. tert-Butyl 1-(1´-(4´´-methoxyphenyl)ethyl)azetidine-2-carboxylate [(2S*,1´S*)-1d and (2R*,1´S*)-1d]

Br

BrO

O NH2

+N

O

O

NO

O

+K2CO3MeCNrefluxOMe

OMe OMe(2S*,1'S*)-1d (2R*,1'S*)-1d

A mixture of 1-(4-methoxyphenyl)ethylamine (1.01 g, 6.68 mmol), tert-butyl 2,4-dibromobutanoate (2.02 g, 6.69 mmol), and K2CO3 (2.76 g, 20 mmol) in MeCN (33 mL) was refluxed for 6 h. The resulting mixture was cooled to room temperature followed by filtered. Evaporation of the volatiles and purification of the residue by chromatography on silica gel [n-hexane/EtOAc = 6/1 to 2/1 as the eluent, Rf: (2S*,1´S*) > (2R*,1´S*)] gave (2S*,1´S*)-1d (415 mg, 21% yield) as colourless crystals and (2R*,1´S*)-1d (486 mg) as a colourless oil with small amounts of impurities. Re-purification of (2R*,1´S*)-1d by chromatography on aminopropyl-modified silica gel (Chromatorex NH–DM10202) (n-hexane/EtOAc = 20/1 to 10/1 as the eluent) gave pure (2R*,1´S*)-1d (446 mg, 23% yield) as a colourless oil. The relative stereochemistry of each diastereomers were assigned by analogy with 1a. (2S*,1´S*)-1d: mp 65–68 °C; IR (KBr) max/cm-1 2979, 2932, 2863, 2836, 2798, 1749, 1610, 1583, 1511, 1456, 1391, 1367, 1317, 1289, 1249, 1231, 1210, 1158, 1101, 1030, 976, 941, 848, 824, 759, 734; 1H NMR (400 MHz, CDCl3) 7.25 (2H, d, J = 8.8 Hz, ArH), 6.84 (2H, d, J = 8.8 Hz, ArH), 3.77 (3H, s, OCH3), 3.59 (1H, dd, J = 8.4, 8.4 Hz, 2-H), 3.37 (1H, q, J = 6.4 Hz, 1´-H), 3.05 (1H, ddd, J = 8.8, 7.0, 2.4 Hz, 4-H), 2.71 (1H, ddd, J = 8.4, 8.4, 7.0 Hz, 4-H), 2.19 (1H, dddd, J = 10.4, 8.8, 8.4, 8.4 Hz, 3-H), 2.10 (1H, dddd, J = 10.4, 8.4, 8.4, 2.4 Hz, 3-H), 1.48 (9H, s, tBu), 1.20 (3H, d, J = 6.4 Hz, 1´-CH3); 13C NMR (100 MHz, CDCl3) 172.4, 158.5, 134.8, 128.3, 113.4, 80.3, 66.4, 64.6, 55.0, 49.2, 27.9, 21.1, 20.5; HRMS (ESI): calcd. for C17H26NO3 [M+H]+ 292.1907, found 292.1900. (2R*,1´S*)-1d: IR (film) 2 Commercially available from Fuji Silysia Chemical Ltd., Japan.

S12

max/cm-1 2969, 2931, 2869, 2834, 1737, 1612, 1585, 1512, 1456, 1390, 1366, 1297, 1245, 1208, 1153, 1105, 1058, 1036, 977, 946, 834, 764, 734; 1H NMR (400 MHz, CDCl3) 7.23 (2H, d, J = 8.6 Hz, ArH), 6.81 (2H, d, J = 8.6 Hz, ArH), 3.77 (3H, s, OCH3), 3.52 (1H, ddd, J = 8.6, 6.4, 2.4 Hz, 4-H), 3.47 (1H, dd, J = 8.4, 8.4 Hz, 2-H), 3.30 (1H, q, J = 6.6 Hz, 1´-H), 2.93 (1H, ddd, J = 8.6, 8.2, 6.4 Hz, 4-H), 2.20 (1H, dddd, J = 10.2, 8.6, 8.6, 8.4 Hz, 3-H), 2.09 (1H, dddd, J = 10.2, 8.4, 8.2, 2.4 Hz, 3-H), 1.24 (3H, d, J = 6.6 Hz, 1´-CH3), 1.19 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 171.6, 158.8, 134.2, 129.1, 113.5, 80.0, 67.3, 65.2, 55.2. 50.6, 27.7, 20.7, 19.9; HRMS (ESI): calcd. for C17H26NO3 [M+H]+ 292.1907, found 292.1903. tert-Butyl 1-(2´,3´-dihydro-1´H-inden-1´-yl)azetidine-2-carboxylate [(2S*,1´S*)-1e and (2R*,1´S*)-1e]

A mixture of 2,3-dihydro-1H-inden-1-amine (128 L, 1.00 mmol), tert-butyl 2,4-dibromobutanoate (302 mg, 1.00 mmol), and K2CO3 (0.41 g, 3.0 mmol) in MeCN (5 mL) was refluxed for 15 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel (n-hexane/EtOAc = 4/1 to 2/1 as the eluent, Rf: (2S*,1´S*) > (2R*,1´S*)] to obtain (2S*,1´S*)-1e (68.4 mg, 25% yield) as a yellow oil and (2R*,1´S*)-1e (57.6 mg, 21% yield) as a yellow oil. The relative stereochemistry of each diastereomers were assigned by analogy with 1a. (2S*,1´S*)-1e: IR (film) max/cm-1 3069, 3003, 2973, 2934, 2846, 1739, 1477, 1458, 1391, 1366, 1323, 1298, 1237, 1212, 1154, 1097, 1061, 1043, 1024, 994, 942, 847, 753, 738; 1H NMR (400 MHz, CDCl3) 7.27 (1H, d, J = 7.6 Hz, ArH), 7.25 (1H, d, J = 7.6 Hz, ArH), 7.20 (1H, ddd, J = 7.6, 7.6, 1.0 Hz, ArH), 7.12 (1H, ddd, J = 7.6, 7.6, 1.0 Hz, ArH), 3.94 (1H, dd, J = 6.6, 2.6 Hz, 1´-H), 3.78 (1H, dd, J = 8.4, 8.2 Hz, 2-H), 3.32-3.26 (1H, m, 4-H), 3.12 (1H, ddd, J = 15.8, 8.4, 8.4 Hz, 3´-H), 3.07 (1H, ddd, J = 9.0, 8.6, 6.8 Hz, 4-H), 2.77 (1H, ddd, J = 15.8, 8.2, 3.4 Hz, 3´-H), 2.27 (1H, dddd, J = 10.6, 8.6, 8.6, 8.4 Hz, 3-H), 2.18 (1H, dddd, J = 10.6, 8.4, 8.2, 2.6 Hz, 3-H), 2.14-1.98 (2H, m, 2´-H), 1.47 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 172.4, 144.8, 142.4, 127.7, 125.7, 125.0, 124.8, 80.8, 70.5, 64.0, 49.1, 30.8, 29.9, 28.0, 21.4; HRMS (ESI): calcd. for C17H24NO2 [M+H]+ 274.1802, found 274.1796. (2R*,1´S*)-1e: IR (film) max/cm-1 3068, 2972, 2932, 2852, 1735, 1477, 1458, 1391, 1366, 1334, 1316, 1294, 1232, 1208, 1154, 1097, 1055, 1018, 990, 947, 845, 753; 1H NMR (400 MHz, CDCl3) 7.30 (1H, d, J = 7.2 Hz, ArH), 7.23 (1H, dd, J = 7.4, 1.0 Hz, ArH), 7.20 (1H, ddd, J = 7.4, 7.2, 1.0 Hz, ArH), 7.15-7.09 (1H, m, ArH), 4.06 (1H, t, J = 5.0 Hz, 1´-H), 3.79 (1H, ddd, J = 8.2, 8.2, 0.6 Hz, 2-H), 3.35 (1H, dddd, J = 8.2, 6.5, 3.1, 0.6 Hz, 4-H), 3.080 (1H, ddd, J = 8.6, 8.2, 6.8 Hz, 4-H), 3.079 (1H, ddd, J = 16.0, 8.0, 8.0 Hz, 3´-H), 2.77 (1H, ddd, J = 16.0, 6.5, 6.5 Hz, 3´-H), 2.29-2.14 (2H, m, 3-H), 2.06 (2H, ddd, J = 8.0, 6.5, 5.0 Hz, 2´-H), 1.34 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 172.2, 144.7, 142.2, 127.6, 125.8, 125.1, 124.7, 80.4, 68.9, 62.8, 48.2, 30.7, 28.6, 27.9, 21.5; HRMS (ESI): calcd. for C17H24NO2 [M+H]+ 274.1802, found 274.1791.

S13

tert-Butyl 1-(2,6-dimethylbenzyl)azetidine-2-carboxylate (20)

A mixture of 2,6-dimethylbenzylamine (268 mg, 1.98 mmol), tert-butyl 2,4-dibromobutanoate (600 mg, 1.99 mmol), and K2CO3 (1.39 g, 10 mmol) in MeCN (10 mL) was refluxed for 6 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel (n-hexane/EtOAc = 20/1 to 10/1 as the eluent) to obtain 20 (353 mg, 65% yield) as a colourless oil. IR (film) max/cm-1 3065, 3004, 2974, 2930, 2844, 1735, 1588, 1470, 1390, 1366, 1296, 1236, 1158, 1094, 1067, 1040, 1018, 976, 940, 847, 769; 1H NMR (400 MHz, CDCl3) 7.07-6.95 (3H, m, Ar), 3.83 (1H, d, J = 12.4 Hz, CH2Ar), 3.65 (1H, dd, J = 9.2, 8.0 Hz, 2-H), 3.63 (1H, d, J = 12.4 Hz, CH2Ar), 3.17 (1H, ddd, J = 8.4, 6.4, 2.4 Hz, 4-H), 2.95 (1H, ddd, J = 9.2, 7.8, 6.4 Hz, 4-H), 2.44 (6H, s, ArCH3), 2.27 (1H, dddd, J = 10.0, 9.2, 9.2, 8.4 Hz, 3-H), 2.10 (1H, dddd, J = 10.0, 8.0, 7.8, 2.4 Hz, 3-H), 1.39 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 171.9, 137.8, 134.1, 128.1, 126.9, 80.6, 65.9, 55.4, 50.9, 27.9, 21.4, 20.4; HRMS (ESI): calcd. for C17H26NO2 [M+H]+ 276.1958, found 276.1953. (1S*,2S*)-2-(tert-Butoxycarbonyl)-1-(2,6-dimethylbenzyl)-1-methylazetidin-1-ium trifluoromethanesulfonate [(1S*,2S*)-7]

A mixture of 20 (353 mg, 1.28 mmol) and NaHCO3 (0.30 g, 3.6 mmol) in CH2Cl2 (6 mL) was treated with MeOTf (160 L, 1.41 mmol) at 0 °C and stirred for 1 h at room temperature. The resulting mixture was evaporated to ca. 1/2 to 1/3 volume and purified by chromatography on silica gel (CH2Cl2/MeOH = 50/1 to 20/1 as the eluent) to obtain (1S*,2S*)-7 (500 mg, 89% yield) as a colourless gum. The relative stereochemistry was determined by analogy with 1a and analogous derivatives reported previously.3 IR (film) max/cm-1 2982, 1737, 1594, 1467, 1396, 1371, 1329, 1261, 1224, 1153, 1055, 1030, 978, 912, 888, 835, 783, 755, 730; 1H NMR (400 MHz, CDCl3) 7.27 (1H, t, J = 7.8 Hz, ArH), 7.15 (2H, d, J = 7.8 Hz, ArH), 5.34 (1H, dd, J = 9.6, 9.6 Hz, 2-H), 4.88 (1H, d, J = 14.4 Hz, CH2Ar), 4.71 (1H, d, J = 14.4 Hz, CH2Ar), 4.60 (1H, ddd, J = 10.0, 10.0, 9.2 Hz, 4-H), 4.00 (1H, ddd, J = 9.6, 9.2, 2.0 Hz, 4-H), 3.13 (3H, s, NCH3), 3.00 (1H, dddd, J = 10.8, 10.0, 9.6, 9.6 Hz, 3-H), 2.64-2.51 (1H, m, 3-H), 2.43 (6H, s, ArCH3), 1.51 (9H, s, tBu); 13C

3 (a) F. Couty, O. David, F. Durrat, G. Evano, S. Lakhdar, J. Marrot and M. Vargas-Sanchez, Eur. J. Org. Chem., 2006, 3479; (b) F. Couty, F. Durrat, G. Evano and D. Prim, Tetrahedron Lett., 2004, 45, 7525; see also, ref 1.

S14

NMR (100 MHz, CDCl3) 163.3, 139.4, 130.2, 129.3, 124.8, 120.3 (q, J = 319 Hz), 85.8, 69.1, 62.0, 61.3, 44.0, 27.3, 20.4, 19.2; HRMS (ESI): calcd. for C18H28NO2 [M–OTf]+ 290.2115, found 290.2106. tert-Butyl 1-benzhydrylazetidine-2-carboxylate (22)

A mixture of benzylamine (546 L, 5.00 mmol), tert-butyl 2,4-dibromobutanoate (1.51 g, 5.00 mmol), and K2CO3 (2.07 g, 15 mmol) in MeCN (25 mL) was refluxed for 12 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel (n-hexane/EtOAc = 6/1 to 4/1 as the eluent) to obtain tert-butyl 1-benzylazetidine-2-carboxylate (21) (651 mg, 53% yield) as a colourless oil. A solution of 21 (646 mg, 2.61 mmol) in MeOH (13 mL) was treated with ca. 4 M hydrogen chloride in cyclopentyl methyl ether (CPME) (0.78 mL, 3.1 mmol) at 0 °C. After stirring for 30 min at room temperature, the solution was evaporated. A mixture of the residue and palladium on activated carbon (loading: 10 wt.%, 0.14 g) in MeOH (13 mL) was stirred at room temperature for 2 days under a hydrogen atmosphere. The resulting mixture was filtered through a pad of Celite and the filtrate was concentrated. A mixture of the residual oil, -bromodiphenylmethane (645 mg, 2.61 mmol), and potassium hydrogen carbonate (1.30 g, 13.0 mmol) in MeCN (13 mL) was stirred for 1 h at room temperature and refluxed for 7 h. The resulting mixture was cooled to room temperature and filtered. The filtrate was concentrated and the residue was purified by chromatography on silica gel (n-hexane/EtOAc = 20/1 to 10/1 as the eluent) to obtain 22 (623 mg, 74% yield) as colourless crystals. Mp 91–92 °C; IR (KBr) max/cm-1 3066, 3002, 2984, 2960, 2933, 2876, 2843, 2813, 1738, 1599, 1491, 1453, 1392, 1364, 1345, 1309, 1290, 1224, 1209, 1159, 1152, 1094, 1078, 1053, 1029, 950, 845, 780, 744, 706; 1H NMR (400 MHz, CDCl3) 7.49-7.44 (2H, m, Ph), 7.43-7.38 (2H, m, Ph), 7.30-7.24 (2H, m, Ph), 7.24-7.17 (3H, m, Ph), 7.14 (1H, tt, J = 7.2, 1.2 Hz, Ph), 4.48 (1H, s, CHPh2), 3.66 (1H, dd, J = 8.4, 8.4 Hz, 2-H), 3.41 (1H, dddd, J = 8.1, 7.2, 3.4, 0.8 Hz, 4-H), 2.87 (1H, ddd, J = 8.5, 8.5, 7.2 Hz, 4-H), 2.29-2.13 (2H, m, 3-H), 1.20 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 171.8, 141.7, 141.4, 128.4, 128.3, 128.2, 127.5, 127.2, 127.0, 80.1, 77.3, 65.3, 51.3, 27.7, 21.0; HRMS (ESI): calcd. for C21H26NO2 [M+H]+ 324.1958, found 324.1955.

S15

(1S*,2S*)-1-Benzhydryl-2-(tert-butoxycarbonyl)-1-methylazetidin-1-ium trifluoromethanesulfonate [(1S*,2S*)-11]

A mixture of 22 (381 mg, 1.18 mmol) and NaHCO3 (0.29 g, 3.5 mmol) in CH2Cl2 (6 mL) was treated with MeOTf (256 L, 2.26 mmol) at 0 °C and stirred for 1 h at room temperature. The resulting mixture was evaporated to ca. 1/2 to 1/3 volume and purified by chromatography on silica gel (CH2Cl2/MeOH = 20/1 to 10/1 as the eluent) to obtain (1S*,2S*)-11 (528 mg, 92% yield) as a white amorphous. The relative stereochemistry was determined by analogy with 1a and analogous derivatives reported previously.3 IR (KBr) max/cm-1 3064, 2982, 2935, 1733, 1499, 1456, 1396, 1372, 1259, 1224, 1153, 1030, 1000, 933, 909, 890, 835, 793, 776, 754, 721; 1H NMR (400 MHz, CDCl3) 7.76-7.70 (4H, m, Ph), 7.52-7.42 (6H, m, Ph), 6.08 (1H, s, CHPh2), 5.47 (1H, dd, J = 9.8, 9.4 Hz, 2-H), 5.02 (1H, ddd, J = 9.8, 9.8, 9.4 Hz, 4-H), 3.89 (1H, ddd, J = 9.8, 9.8, 3.4 Hz, 4-H), 3.34 (3H, s, NCH3), 2.95 (1H, dddd, J = 12.0, 9.8, 9.8, 9.8 Hz, 3-H), 2.65 (1H, dddd, J = 12.0, 9.4, 9.4, 3.4 Hz, 3-H), 1.35 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 163.3, 131.4, 131.0, 130.8, 130.5, 130.4, 129.8, 129.7, 120.8 (q, J = 319 Hz), 85.7, 80.7, 69.8, 62.0, 43.6, 27.6, 18.8; HRMS (ESI): calcd. for C22H28NO2 [M–OTf]+ 338.2115, found 338.2111. tert-Butyl 1-(2´-phenylpropan-2´-yl)azetidine-2-carboxylate (23)

A mixture of cumylamine (0.72 mL, 5.0 mmol), tert-butyl 2,4-dibromobutanoate (1.51 g, 5.00 mmol), and K2CO3 (2.07 g, 15 mmol) in MeCN (25 mL) was refluxed for 15 h. The resulting mixture was cooled to room temperature followed by filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel (n-hexane/EtOAc = 8/1 to 6/1 as the eluent) to obtain 23 (471 mg, 34% yield) as a colourless oil. IR (film) max/cm-1 3058, 2974, 2930, 2865, 1741, 1717, 1600, 1493, 1477, 1446, 1391, 1381, 1366, 1296, 1255, 1233, 1207, 1152, 1110, 1072, 1052, 1030, 1002, 944, 919, 899, 846, 766, 700; 1H NMR (400 MHz, CDCl3) 7.50 (2H, ddd, J = 7.8, 1.6, 1.6 Hz, Ph), 7.33 (2H, dddd, J = 7.8, 7.2, 1.6, 1.6 Hz, Ph), 7.23 (1H, tt, J = 7.2, 1.6 Hz, Ph), 3.76 (1H, dd, J = 8.4, 8.4 Hz, 2-H), 3.04 (1H, ddd, J = 8.4, 6.4, 2.6 Hz, 4-H), 2.96 (1H, ddd, J = 8.4, 8.4, 6.4 Hz, 4-H), 2.14 (1H, dddd, J = 10.2, 8.4, 8.4, 8.4 Hz, 3-H), 1.92 (1H, dddd, J = 10.2, 8.4, 8.4, 2.6 Hz, 3-H), 1.41 (9H, s, tBu), 1.39 (3H, s, 2´-CH3), 1.33 (3H, s, 2´-CH3); 13C NMR (100 MHz, CDCl3) 173.0, 144.3, 127.9, 126.8, 126.5, 80.2, 59.3, 57.8, 43.8, 27.9, 25.7, 22.3, 20.2; HRMS (ESI): calcd. for C17H26NO2 [M+H]+ 276.1958, found 276.1957.

S16

(1R*,2S*)-2-(tert-Butoxycarbonyl)-1-methyl-1-(2´-phenylpropan-2´-yl)azetidin-1-ium trifluoromethanesulfonate [(1R*,2S*)-14]

NO

O

NO

OMeOTf

NaHCO3CH2Cl2

0 °C to rtOTf

23 (1R*,2S*)-14 A mixture of 23 (432 mg, 1.57 mmol) and NaHCO3 (0.40 g, 4.8 mmol) in CH2Cl2 (8 mL) was treated with MeOTf (355 L, 3.14 mmol) at 0 °C and stirred for 1 h at room temperature. The resulting mixture was evaporated to ca. 1/2 to 1/3 volume and purified by chromatography on silica gel (CH2Cl2/MeOH = 20/1 to 10/1 as the eluent) to obtain (1R*,2S*)-14 (630 mg, 91% yield) as a colourless gum. The relative stereochemistry was determined by analogy with 1a and analogous derivatives reported previously.3 IR (film) max/cm-1 3065, 2984, 2938, 1735, 1634, 1503, 1471, 1452, 1424, 1397, 1372, 1263, 1225, 1155, 1102, 1083, 1050, 1031, 1001, 977, 918, 878, 837, 773, 755, 734, 705; 1H NMR (400 MHz, CDCl3) 7.66-7.61 (2H, m, Ph), 7.57-7.47 (3H, m, Ph), 5.25 (1H, dd, J = 9.6, 9.4 Hz, 2-H), 4.76 (1H, ddd, J = 10.0, 9.6, 9.6 Hz, 4-H), 3.74 (1H, ddd, J = 10.0, 10.0, 3.6 Hz, 4-H), 3.16 (3H, s, NCH3), 2.90 (1H, dddd, J = 12.4, 10.0, 9.6, 9.6 Hz, 3-H), 2.45 (1H, dddd, J = 12.4, 9.6, 9.4, 3.6 Hz, 3-H), 2.04 (3H, s, 2´-CH3), 1.93 (3H, s, 2´-CH3), 1.51 (9H, s, tBu); 13C NMR (100 MHz, CDCl3) 163.5, 135.0, 130.5, 129.5, 128.3, 120.7 (q, J = 319 Hz), 86.1, 73.2, 67.3, 58.1, 42.5, 27.7, 23.8, 22.5, 17.5; HRMS (ESI): calcd. for C18H28NO2 [M–OTf]+ 290.2115, found 290.2111.

S17

4. Copies of NMR spectra of substrates and rearrangement products (2–4, 7, 9–14, 16) 1S,2S,1'S-2a_1H.esp

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

9.233.062.013.000.980.991.010.994.97

0.00

0

1.53

7

1.75

7

2.86

0

3.01

0

3.27

7

4.90

3

5.30

4

5.60

5

7.28

0

7.46

67.

555

1S,2S,1'S-2a_13C.esp

200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)

13.9

95

17.9

41

27.7

74

39.5

34

61.4

69

71.3

4772

.850

76.6

8177.0

0077

.319

85.9

98

115.

938

119.

117

122.

303

125.

482

129.

420

130.

012

130.

839

131.

021

163.

791

S18

1R,2R,1'S-2a_1H.esp


8.963.021.923.000.960.980.990.975.29

0.00

0

1.18

3

1.69

1

2.88

0

3.14

8

4.03

1

4.81

8

5.25

9

5.57

7

7.27

9

7.46

67.

568

1R,2R,1'S-2a_13C.esp


13.4

87

18.0

70

27.4

40

39.3

07

62.5

92

69.9

4472

.918

76.6

8177

.000

77.3

1184

.944

115.

976

119.

15512

2.34

112

5.52

0

129.

352

130.

058

131.

492

163.

092

S19

1S,2S,1'S-2b_1H.esp


9.323.155.000.970.970.980.984.00

0.00

0

1.53

6

1.74

5

2.90

03.

008

3.29

8

4.87

3

5.29

3

5.58

0

7.28

4

7.50

47.

588

1S,2S,1'S-2b_13C.esp


14.0

03

17.8

73

27.7

51

39.5

11

61.5

22

71.5

8372

.099

76.6

8977

.000

77.3

19

86.1

81

115.

892

119.

071

122.

2581

25.4

52

130.

027

131.

666

132.

652

163.

608

S20

1R,2R,1'S-2b_1H.esp


8.853.012.033.000.950.970.980.944.07

0.00

0

1.20

7

1.65

5

2.90

8

3.13

0

4.05

7

4.75

1

5.25

2

5.55

9

7.29

9

7.52

77.

579

1R,2R,1'S-2b_13C.esp


13.3

35

17.7

74

27.3

64

39.0

79

62.7

5170.

171

72.1

3776

.681

77.0

0077

.319

85.2

09

115.

885

119.

071

122.

250

125.

278

125.

437

130.

482

131.

712

132.

448

162.

910

S21

1S,2S,1'S-2c_1H.esp

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

18.523.162.020.980.990.990.992.012.00

0.00

0

1.54

11.

592

1.78

4

2.86

63.

011

3.26

2

4.97

3

5.42

7

5.66

17.2

77

7.67

1

8.05

0

1S,2S,1'S-2c_13C.esp


13.9

96

18.1

23

27.7

9728

.055

39.6

94

61.7

34

71.6

0572

.190

76.6

8177.0

0077

.319

81.8

41

86.1

88

115.

923

119.

102

122.

288

125.

467

129.

982

130.

331

134.

344

134.

997

163.

715

164.

504

S22

1R,2R,1'S-2c_1H.esp


9.1013.071.943.000.980.981.010.972.052.05

0.00

0

1.18

3

1.58

71.

717

2.88

0

3.15

5

4.07

0

4.83

7

5.34

6

5.60

5

7.28

47.67

6

8.04

1

1R,2R,1'S-2c_13C.esp


13.4

19

18.1

15

27.3

9528

.047

39.3

52

62.8

73

70.1

7172

.266

76.6

8177

.000

77.3

1981

.689

85.1

64

115.

953

119.

140

122.

319

125.

498

129.

989

130.

217

134.

200

135.

498

162.

971

164.

602

S23

1S,2S,1'S-2d_1H.esp


9.173.370.994.060.993.000.950.960.961.951.96

0.00

0

1.53

6

1.72

8

2.74

9

2.92

43.

006

3.29

4

3.81

5

4.77

1

5.16

8

5.49

8

6.93

5

7.35

07.

489

1S,2S,1'S-2d_13C.esp


13.8

9717

.425

27.5

01

39.1

55

55.1

34

60.8

3970.

938

72.5

0176

.681

77.0

0077

.319

85.6

80

114.

435

115.

763

118.

950

122.

129

122.

706

125.

316

131.

196

161.

021

163.

548

S24

1R,2R,1'S-2d_1H.esp


9.323.092.022.973.000.980.980.970.971.981.98

0.00

0

1.20

3

1.66

1

2.77

82.

902

3.13

1

3.81

2

4.05

4

4.73

0

5.15

6

5.52

7

6.96

3

7.36

8

7.52

0

1R,2R,1'S-2d_13C.esp


13.3

43

17.5

46

27.1

82

38.8

51

55.1

03

62.0

2369.

564

72.5

0876.6

8177

.000

77.3

1984.5

72

114.

337

115.

794

118.

973

122.

159

123.

176

125.

346

131.

188

161.

029

162.

948

S25

1S,2S,1'S-2e_1H.esp


9.211.013.984.030.980.992.004.21

0.00

0

1.52

4

2.51

3

2.74

4

2.99

0

3.84

3

5.07

6

5.65

2

7.28

07.

288

7.36

07.

419

7.46

7

1S,2S,1'S-2e_13C.esp


18.7

98

25.7

7827

.766

30.9

00

39.4

13

62.7

28

71.4

1676

.68177.0

0077

.319

79.4

43

86.0

14

115.

885

119.

071

122.

250

125.

437

125.

9071

27.8

7213

1.15

013

3.62

4

146.

1731

64.0

41

S26

1R,2R,1'S-2e_1H.esp


8.310.892.147.070.101.000.910.181.944.20

0.00

0

1.40

8

1.57

8

2.37

02.

510

2.85

62.

981

3.08

7

3.31

6

4.14

14.

221

4.74

1

4.93

85.

034

5.56

15.67

4

7.26

27.

281

7.33

77.

416

7.58

1

1R,2R,1'S-2e_13C.esp


18.1

53

26.3

5527

.668

30.7

71

40.1

41

62.6

1571.2

2676

.681

77.0

0077

.319

79.4

43

85.5

81

115.

907

119.

094

122.

273

125.

346

125.

520

127.

144

127.

630

131.

173

133.

168

146.

552

163.

502

N

O

O OTf

(1R*,2R*,1'S*)-2e

N

O

O OTf

(1S*,2R*,1'S*)-2e9/1 mixture

1H: CDCl3, 13C: CDCl3

S27

3a_1H.esp


2.968.972.983.000.981.962.840.94

0.00

0

1.19

1

1.41

8

2.20

22.

345

2.48

8

2.93

2

3.34

63.

4767

.189

7.25

9

7.49

5

3a_13C.esp


14.4

67

24.2

77

28.1

2429

.808

39.8

99

52.1

60

75.6

8776

.681

77.0

0077

.319

81.5

67

125.

1021

26.7

0312

7.63

6

139.

297

141.

953

170.

837

S28

4a_1H.esp


3.269.291.023.991.000.991.035.08

0.00

0

1.31

3

1.48

2

2.04

8

2.33

3

2.90

8

3.12

4

3.29

67.2

317.

267

4a_13C.esp


14.1

85

24.9

8928

.275

39.9

97

45.3

00

51.4

3976.6

8177

.000

77.3

1981

.385

126.

279

127.

569

129.

049

142.

023

170.

930

S29

3b_1H.esp


3.109.171.002.083.071.001.960.980.970.92

0.00

0

1.16

6

1.42

6

2.15

02.2

79

2.45

7

2.90

7

3.33

63.

466

7.04

8

7.26

57.

3057.65

3

3b_13C.esp


14.2

69

23.8

59

28.0

8529

.580

39.5

87

51.9

77

75.1

3477

.000

77.3

1981

.924

119.

489

128.

305

129.

420

129.

716

138.

358

144.

200

170.

270

S30

4b_1H.esp


3.2010.170.974.051.001.982.011.94

0.00

0

1.24

6

1.50

1

1.94

2

2.30

0

2.90

6

3.07

8

3.23

1

7.10

3

7.26

37.

396

4b_13C.esp


14.0

0324.

041

28.3

05

39.7

39

44.0

5651.3

93

76.5

6876

.681

77.0

0077

.319

81.6

05

120.

171

130.

551

130.

922

141.

104

170.

824

S31

3c_1H.esp


3.0118.360.975.010.961.990.980.940.91

0.00

0

1.19

9

1.42

4

1.59

3

2.16

72.37

92.

513

2.91

8

3.36

73.

488

7.22

47.

272

7.81

68.16

3

3c_13C.esp


14.2

76

24.4

8128

.115

28.1

6829

.747

39.6

33

52.1

14

75.3

3176

.681

77.0

0077

.319

80.3

6181

.810

126.

621

127.

652

127.

804

129.

170

142.

212

144.

451

166.

067

170.

619

S32

4c_1H.esp


3.3619.470.994.042.031.002.562.00

0.00

0

1.26

2

1.50

91.

589

1.97

7

2.30

6

2.90

63.

058

3.35

2

7.26

4

7.90

5

4c_13C.esp


14.0

33

24.0

49

28.2

0628

.328

39.6

78

44.5

5751.3

93

76.6

8177

.000

77.3

1980

.657

81.6

36

128.

639

129.

071

130.

005

147.

152

165.

907

170.

824

4c1H: CDCl3, 13C: CDCl3

N

OO

O

O

S33

3d_1H.esp


2.989.023.033.000.991.993.000.961.92

0.00

0

1.16

0

1.42

6

2.18

02.27

7

2.46

8

2.91

3

3.32

43.

464

3.81

9

6.76

6

7.07

37.

135

7.26

3

3d_13C.esp


14.6

10

23.4

42

28.0

4029

.62539

.648

51.9

3255

.035

75.4

3777

.000

77.3

1981

.469

111.

196

111.

643

128.

525

131.

378

143.

244

157.

372

170.

558

S34

4d1_1H.esp


12.035.161.951.183.001.941.95

0.00

0

1.27

61.

377

1.49

4

2.26

72.

391

3.05

6

3.32

9

3.76

4

6.78

8

7.03

4

7.26

3

4d1_13C.esp


17.6

07

22.4

86

28.0

32

39.1

7842

.433

52.0

3855

.187

76.6

8177.

000

77.3

1980

.930

113.

373

129.

041

135.

9601

57.9

26

170.

983

S35

4d2_1H.esp


3.009.231.043.890.941.883.151.961.89

0.00

0

1.27

8

1.49

2

2.01

8

2.32

9

2.90

3

3.12

83.

239

3.79

3

6.84

3

7.13

37.

263

4d2_13C.esp


14.3

90

24.8

2328

.297

40.0

12

44.4

43

51.4

1655

.126

76.6

8177

.000

77.3

1981

.34011

2.97

1

129.

906

134.

049

157.

979

171.

029

S36

3e_1H.esp


9.293.065.113.062.043.11

0.00

0

1.42

2

2.00

0

2.15

9

2.49

52.

585

2.86

5

3.31

3

3.46

9

7.15

57.

278

3e_13C.esp


25.3

3828

.138

28.7

00

32.4

78

40.0

88

52.1

82

75.4

4576

.681

77.0

0077

.319

81.4

39

122.

121

122.

675

126.

029

139.

299

140.

1181

44.0

94

170.

490

S37

1S,2S-7_1H.esp


9.117.094.000.981.991.001.213.01

0.00

0

1.51

4

2.42

8

2.58

3

3.00

23.

130

3.99

5

4.58

94.7

264.

865

5.31

0

7.15

67.

266

1S,2S-7_13C.esp


19.2

0020

.376

27.3

04

43.9

50

61.2

6461

.97769

.087

76.6

8177.0

0077

.319

85.7

94

115.

513

118.

700

121.

879

124.

845

125.

065

129.

344

130.

232

139.

405

163.

320

S38

9_1H.esp


9.220.9510.051.002.972.99

0.00

0

1.46

9

1.88

2

2.27

72.

352

2.87

83.0

50

7.01

0

7.21

9

9_13C.esp


20.9

68

26.0

8228

.153

34.1

17

38.0

70

51.7

80

74.0

7177

.000

77.3

1981.0

29

125.

953

127.

789

135.

369

138.

039

172.

470

S39

10_1H.esp


9.043.0010.110.941.921.92

0.00

0

1.46

9

2.15

22.

281

2.30

02.

396

2.80

8

3.28

2

6.94

6

7.26

1

10_13C.esp


15.1

56

20.7

71

28.1

3829

.345

39.6

33

51.3

25

74.4

6676

.681

77.0

0077

.319

81.2

34

124.

807

133.

912

136.

074

137.

569

172.

448

S40

1S,2S-11_1H.esp


9.100.980.993.000.981.000.981.006.404.11

0.00

0

1.35

2

2.64

0

2.94

8

3.34

2

3.89

8

5.00

4

5.46

96.08

4

7.27

4

7.46

4

7.72

1

1S,2S-11_13C.esp


18.8

44

27.6

07

43.5

63

62.0

30

69.7

92

76.6

8177

.000

77.3

1980

.733

85.7

41

116.

014

119.

200

122.

379

125.

566

129.

731

129.

800

130.

354

130.

786

131.

036

131.

401

163.

335

S41

12_1H.esp


9.051.023.000.992.042.000.977.050.98

0.00

0

1.43

6

2.18

6

2.51

4

2.88

6

3.34

13.

4733.

726

6.86

77.10

17.2

52

7.58

9

12_13C.esp


28.1

6829

.777

37.6

4539

.944

52.1

82

75.6

7276

.681

77.0

0077

.319

81.8

63

125.

354

125.

938

126.

68112

8.31

312

9.36

012

9.76

9

136.

272

140.

34614

2.46

3

170.

657

S42

13_1H.esp


9.081.023.041.002.001.0010.16

0.00

0

1.16

2

2.13

8

2.35

0

2.62

4

3.01

8

4.32

8

7.12

67.24

2

13_13C.esp


23.4

49

27.6

98

38.4

72

52.6

3054

.800

76.6

8176.

810

77.0

0077

.319

81.0

97

126.

059

127.

273

128.

935

130.

907

140.

983

141.

689

170.

422

N


OO

S43

1R,2S-14_1H.esp


9.206.701.001.023.001.001.001.025.03

0.00

0

1.50

9

1.93

42.

036

2.46

5

2.89

5

3.16

2

3.73

1

4.75

1

5.25

1

7.28

07.51

47.

627

1R,2S-14_13C.esp


17.5

22

22.4

6923

.835

27.7

04

42.5

38

58.0

6267.

296

73.1

9176

.681

77.0

0077

.311

86.1

28

115.

946

119.

133

122.

320

125.

506

128.

306

129.

543

130.

499

134.

960

163.

466

S44

16_1H.esp


9.246.183.002.001.021.015.34

0.00

0

1.18

2

1.41

01.

505

2.32

3

2.48

82.

577

2.87

5

3.32

4

7.26

1

16_13C.esp


22.7

04

27.8

0327

.849

42.2

6543

.228

51.7

87

76.6

8177

.000

77.3

1179

.686

81.0

37

125.

689

126.

751

127.

593

147.

616

170.

196

N


OO

structural and mechanistic studies of the base-induced ... · s4 2. preparation and crystal data of...

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