Supporting Information for the Paper Investigation of the Passerini and

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MHz, CDCl3, 25°C) δ 7.35-7.24 (m, 7H), 7.12-6.95 (m, 3H), 5.91-5.62 (m, 2H), ..... 4.6781. 4.6610. 3.7894. 3.5898. 1.9868. 1.2876. (ppm). 1.5. 2.0. 2.5. 3.0. 3.5.
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is © The Royal Society of Chemistry 2014

Supporting Information for the Paper

Investigation of the Passerini and Ugi Reactions in -Lactam Aldehydes. Synthetic Applications Benito Alcaide,*, a Pedro Almendros,b Cristina Aragoncillo,a Ricardo Callejo,a M. Pilar Ruiza and M. Rosario Torresc a

Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgánica I,

Unidad Asociada al CSIC, Facultad de Química, Universidad Complutense de Madrid, 28040-Madrid, Spain b

Instituto de Química Orgánica General, IQOG-CSIC, Juan de la Cierva 3, 28006Madrid, Spain

c

CAI Difracción de Rayos X, Facultad de Química, Universidad Complutense de Madrid, 28040-Madrid, Spain Email: [email protected]

Table of Contents Preparation and Characterization of P-3CR Adducts 2b-h

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Preparation and Characterization of U-4CR Adducts 3a-h and 3j-m

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Figure S1. Observed NOE for compounds 5

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Table S1. Representative chemical shifts and vicinal coupling constants of 1H and 13

C NMR of compounds 2

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Table S2. Representative chemical shifts and vicinal coupling constants of 1H and 13

C NMR of compounds 3

21

1

1

H NMR in (CDCl2)2 of compound syn-(+)-3a at different temperatures

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1H NMR in (CDCl2)2 of compound anti-(+)-3b at different temperatures

23

1

24

H and 13C NMR spectra for all new compounds

X-Ray data for compound anti-(+)-2d

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PREPARATION AND CHARACTERIZATION OF COMPOUNDS 2b-h Passerini adduct 2b. Method A. From 37 mg (0.10 mmol) of aldehyde (+)-1b, compound 2b was obtained as a mixture of isomers in a syn/anti ratio (65:35). After flash chromatography using n-hexane/ethyl acetate (3:1) as eluent, the less polar compound syn-(+)-2b (31 mg, 56%) and the more polar compound anti-(+)-2b (17 mg, 32%) were obtained. syn-(+)-2b. White solid; mp 148149°C (n-hexane/ethyl acetate); []D +110.2 (c 0.9, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.97-7.95 (m, 2H), 7.57 (tt, J = 7.4, 1.5 Hz, 1H), 7.50 (AA'XX', 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.28-7.22 (m, 5H), 7.03-6.92 (m, 5H), 6.84 (AA'XX', 2H), 6.37 (t, J = 5.7 Hz, 1H), 5.95 (d, J = 2.0 Hz, 1H), 5.52 (d, J = 5.3 Hz, 1H), 5.40 (dd, J = 5.3, 2.2 Hz, 1H), 4.37 (dd, J = 14.9, 5.7 Hz, 1H), 4.26 (dd, J = 14.9, 5.8 Hz, 1H), 3.78 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  168.1, 165.0, 163.2, 157.1, 156.9, 136.7, 133.8, 130.0, 129.6, 128.65, 128.61, 127.6, 122.6, 119.8, 115.5, 114.5, 79.5, 69.8, 58.0, 55.4, 43.5; IR (KBr, cm–1)  3369, 1749, 1668; HRMS (ESI) calcd for C32H29N2O6+ [M+H]+: 537.2020; found: 537.2000. anti(+)-2b. White solid; mp 147148°C (n-hexane/ethyl acetate); []D +91.3 (c 0.3, CHCl3); 1

H NMR (300 MHz, CDCl3, 25°C)  8.03-8.00 (m, 2H), 7.59 (tt, J = 7.5, 1.4 Hz, 1H),

7.44 (t, J = 7.7 Hz, 2H), 7.35 (AA'XX', 2H), 7.35-7.30 (m, 2H), 7.24-7.22 (m, 3H), 7.097.00 (m, 5H), 6.85 (AA'XX', 2H), 6.47 (t, J = 5.7 Hz, 1H), 6.29 (d, J = 3.2 Hz, 1H), 5.54 (d, J = 5.1 Hz, 1H), 5.27 (dd, J = 5.0, 3.3 Hz, 1H), 4.36 (dd, J = 14.8, 6.4 Hz, 1H), 3.88 (dd, J = 14.8, 5.0 Hz, 1H), 3.78 (s, 3H);

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C NMR (75 MHz, CDCl3, 25°C)  166.9,

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164.8, 162.8, 157.7, 156.9, 136.9, 133.9, 130.0, 129.8, 129.5, 128.74, 128.69, 128.3, 127.7, 127.6, 122.8, 118.9, 115.7, 114.6, 80.1, 68.7, 58.6, 55.4, 43.3; IR (KBr, cm–1)  3375, 1756, 1666; HRMS (ESI) calcd for C32H29N2O6+ [M+H]+: 537.2020; found: 537.2022. Passerini adduct 2c. Method A. From 60 mg (0.26 mmol) of aldehyde (+)-1c, compound 2c was obtained as a mixture of isomers in a syn/anti ratio (72:28). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, an inseparable mixture of isomers (80 mg, 65%) was obtained as a colorless oil. syn-2c. 1H NMR (300 MHz, CDCl3, 25°C)  8.11-8.08 (m, 2H); 7.64-7.59 (m, 1H), 7.50-7.43 (m, 2H), 7.337.20 (m, 7H), 7.05-6.94 (m, 1H), 6.94-6.87 (m, 2H), 6.69 (t, J = 5.4 Hz, 1H), 5.81 (d, J = 5.1 Hz, 1H), 5.41 (d, J = 5.1 Hz, 1H), 4.91 (t, J = 5.0 Hz, 1H), 4.51-4.40 (m, 2H), 4.32 (dd, J =17.8, 2.6 Hz, 1H), 3.92 (dd, J = 17.7, 2.4 Hz, 1H), 2.30 (t, J = 2.5 Hz, 1H); 13C NMR (75 MHz, CDCl3, 25°C)  166.9, 165.7, 165.2, 157.0, 137.2, 133.9, 130.0, 129.6, 128.74, 128.68, 128.6, 127.8, 127.7, 122.6, 115.6, 80.5, 76.3, 73.2, 71.6, 57.5, 43.6, 31.1; HRMS (ESI) calcd for C28H25N2O5+ [M+H]+: 469.1758; found: 469.1776. anti-2c. 1

H NMR (300 MHz, CDCl3, 25°C)  8.07-8.04 (m, 2H), 7.64-7.59 (m, 1H), 7.50-7.43

(m, 2H), 7.33-7.20 (m, 7H), 7.14-7.11 (m, 2H), 7.05-6.94 (m, 1H), 6.53 (t, J = 5.4 Hz, 1H), 6.09 (d, J = 4.0 Hz, 1H), 5.43 (d, J = 5.0 Hz, 1H), 4.93 (dd, J = 4.9, 3.9 Hz, 1H), 4.45-4.40 (m, 1H), 4.29 (dd, J = 17.8, 2.6 Hz, 1H), 4.02 (dd, J = 14.8, 5.3 Hz, 1H), 3.86 (dd, J = 17.8, 2.5 Hz, 1H), 2.31 (t, J = 2.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, 25°C) : 166.7, 165.3, 165.2, 157.4, 137.0, 134.0, 130.0, 129.7, 128.74, 128.7, 128.68, 127.7, 127.6, 122.6, 115.5, 80.8, 75.8, 73.6, 69.7, 58.1, 43.3, 30.4. Passerini adduct 2d. Method A. From 52 mg (0.22 mmol) of aldehyde (+)-1a, compound 2d was obtained as a mixture of isomers in a syn/anti ratio (60:40). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar

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compound syn-(+)-2d (46 mg, 51%) and the more polar compound anti-(+)-2d (30 mg, 33%) were obtained. syn-(+)-2d. Colorless oil; []D +106.1 (c 0.7, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.39 (AA'XX', 2H), 7.30-7.26 (m, 3H), 7.08-7.05 (m, 2H), 6.82 (AA'XX', 2H), 6.45 (bs, 1H), 5.56 (d, J = 4.5 Hz, 1H), 4.97 (t, J = 4.8 Hz, 1H), 4.66 (d, J = 5.3 Hz, 1H), 4.43 (dd, J = 14.8, 5.8 Hz, 1H), 4.25 (dd, J = 14.9, 5.6 Hz, 1H), 3.77 (s, 3H), 3.52 (s, 3H), 1.99 (s, 3H);

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C NMR (75 MHz, CDCl3, 25°C)  169.6, 167.7,

164.4, 156.7, 137.0, 130.1, 128.6, 127.62, 127.56, 119.7, 114.1, 82.7, 70.5, 59.8, 57.3, 55.4, 43.4, 20.7; IR (CHCl3, cm–1)  3347, 1750, 1668; HRMS (ESI) calcd for C22H25N2O6+ [M+H]+: 413.1707; found: 413.1713. anti-(+)-2d. White solid; mp 179181°C (n-hexane/ethyl acetate); []D +31.3 (c 0.2, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.37 (AA'XX', 2H), 7.34-7.27 (m, 3H), 7.20-7.18 (m, 2H), 6.87 (AA'XX', 2H), 6.61 (t, J = 5.3 Hz, 1H), 5.78 (d, J = 3.7 Hz, 1H), 4.80 (dd, J = 5.1, 3.8 Hz, 1H), 4.67 (d, J = 5.1 Hz, 1H), 4.64 (dd, J = 14.7, 5.9 Hz, 1H), 4.27 (dd, J = 14.8, 5.4 Hz, 1H), 3.78 (s, 3H), 3.48 (s, 3H), 2.10 (s, 3H);

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C NMR (75 MHz, CDCl3, 25°C) : 169.2,

166.9, 164.4, 156.6, 137.3, 130.0, 128.7, 127.8, 127.6, 118.6, 114.4, 83.0, 69.0, 60.0, 58.1, 55.4, 43.4, 20.6. IR (KBr, cm–1)  3330, 1752, 1666; HRMS (ESI) calcd for C22H25N2O6+ [M+H]+: 413.1707; found: 413.1709. Passerini adduct 2e. Method A. From 59 mg (0.25 mmol) of aldehyde (+)-1a, compound 2e was obtained as a mixture of isomers in a syn/anti ratio (60:40). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound syn-(+)-2e (50 mg, 53%) and the more polar compound anti-(+)-2e (33 mg, 35%) were obtained. syn-(+)-2e. Colorless oil; []D +77.9 (c 0.7, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.42 (AA'XX', 2H), 6.85 (AA'XX', 2H), 5.94 (bs, 1H), 5.39 (d, J = 5.1 Hz, 1H), 4.92 (t, J = 5.1 Hz, 1H), 4.67 (d, J = 5.1 Hz, 1H), 3.79 (s, 3H), 3.59 (s, 3H), 1.99 (s, 3H), 1.29 (s, 9H,);

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C NMR (75 MHz, CDCl3, 25°C)  169.6, 166.5, 164.5, 4

156.7, 130.3, 119.9, 114.1, 82.7, 71.3, 59.8, 57.2, 55.4, 51.5, 28.4, 20.6. IR (CHCl3, cm– 1

)  3360, 1753, 1677; HRMS (ESI) calcd for C19H27N2O6+ [M+H]+: 379.1864; found:

379.1875. anti-(+)-2e. Colorless oil; []D +86.3 (c 0.3, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.41 (AA'XX', 2H), 6.86 (AA'XX', 2H), 6.23 (bs, 1H), 5.55 (d, J = 2.3 Hz, 1H), 4.71 (d, J = 5.4 Hz, 1H), 4.66 (dd, J = 5.4, 2.3 Hz, 1H), 3.78 (s, 3H), 3.69 (s, 3H), 2.17 (s, 3H), 1.27 (s, 9H);

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C NMR (75 MHz, CDCl3, 25°C)  169.4, 164.8, 164.2,

156.6, 130.3, 118.7, 114.3, 82.6, 69.8, 60.0, 58.7, 55.4, 51.4, 28.4, 20.7; IR (CHCl3, cm– 1

)  = 3355, 1752, 1695; HRMS (ESI) calcd for C19H27N2O6+ [M+H]+: 379.1864; found:

379.1868. Passerini adduct 2f. Method A. From 46 mg (0.20 mmol) of aldehyde ()-1d, compound 2f was obtained as a mixture of isomers in a syn/anti ratio (73:27). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, an inseparable mixture of isomers (68 mg, 61%) was obtained as a colorless oil. syn-2f. 1H NMR (300 MHz, CDCl3, 25°C)  7.98 (dd, J = 7.9, 0.9 Hz, 1H), 7.77 (dd, J = 7.8, 1.7 Hz, 1H), 7.41 (td, J = 7.6, 1.1 Hz, 1H), 7.29-7.23 (m, 2H), 7.19 (td, J = 7.7, 1.6 Hz, 1H), 7.08-6.97 (m, 3H), 6.23 (bs, 1H), 5.85-5.70 (m, 1H), 5.70 (d, J = 3.2 Hz, 1H), 5.39 (d, J = 5.1 Hz, 1H), 5.235.16 (m, 2H), 4.78 (dd, J = 5.0, 3.2 Hz, 1H), 4.21-4.11 (m, 1H), 3.68 (dd, J = 15.7, 6.5 Hz, 1H), 1.36 (s, 9H); 13C NMR (75 MHz, CDCl3, 25°C)  166.0, 165.8, 165.7, 157.1, 140.9, 134.7, 133.1, 130.9, 130.8, 129.6, 128.4, 122.6, 118.9, 115.5, 93.8, 80.1, 71.5, 57.3, 51.9, 44.0, 28.5; HRMS (ESI) calcd for C25H28IN2O5+ [M+H]+: 563.1037; found: 563.1017. anti-2f. 1H NMR (300 MHz, CDCl3, 25°C)  8.00 (dd, J = 7.9, 0.9 Hz, 1H), 7.87 (dd, J = 7.8, 1.7 Hz, 1H), 7.40 (td, J = 7.6, 1.1 Hz, 1H), 7.29-7.23 (m, 3H), 7.086.97 (m, 3H), 6.30 (bs, 1H), 5.85-5.70 (m, 1H), 5.73 (d, J = 3.9 Hz, 1H), 5.42 (d, J = 5.0 Hz, 1H), 5.34-5.25 (m, 2H), 4.66 (dd, J = 4.8, 4.1 Hz, 1H), 4.21-4.11 (m, 1H), 3.68 (dd, J = 15.7, 6.5 Hz, 1H), 1.28 (s, 9H); 13C NMR (75 MHz, CDCl3, 25°C) : 166.0, 165.7,

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165.1, 157.1, 141.4, 134.7, 133.3, 131.5, 130.6, 129.7, 128.2, 122.6, 119.7, 115.5, 94.4, 80.2, 71.3, 57.7, 51.8, 43.6, 28.4. Passerini adduct 2g. Method A. From 35 mg (0.15 mmol) of aldehyde ()-1d, compound 2g was obtained as a mixture of isomers in a syn/anti ratio (77:23). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound anti-()-2g (14 mg, 17%) and the more polar compound syn-()-2g (46 mg, 55%) were obtained. syn-()-2g. White solid; mp 165166°C (n-hexane/ethyl acetate); []D 4.6 (c 1.5, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.92 (AA'BB', 2H), 7.78 (AA'BB', 2H), 7.33-7.28 (m, 2H), 7.10 (t, J = 5.5 Hz, 1H), 7.06-7.01 (m, 3H), 5.74-5.61 (m, 1H), 5.64 (d, J = 2.3 Hz, 1H), 5.28 (d, J = 5.0 Hz, 1H), 5.18-5.12 (m, 2H), 4.66 (dd, J = 5.0, 2.3 Hz, 1H), 4.60 (d, J = 17.4 Hz, 1H), 4.54 (d, J = 17.2 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 4.23 (dd, J = 18.0, 6.4 Hz, 1H), 3.91 (dd, J = 17.8, 4.9 Hz, 1H), 3.94-3.87 (m, 1H), 3.63 (dd, J = 15.6, 6.9 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  168.9, 167.4, 167.2, 165.9, 165.3, 157.1, 134.4, 131.8, 130.8, 129.6, 123.8, 122.6, 119.0, 115.5, 80.2, 70.3, 61.6, 57.2, 43.3, 41.2, 39.2, 14.1; IR (KBr, cm–1)  3372, 1760, 1721, 1684; HRMS (ESI) calcd for C28H28N3O9+ [M+H]+: 550.1820; found: 550.1810. anti-()-2g. White solid; mp 159161°C (n-hexane/ethyl acetate); []D 16.2 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.69 (AA'BB', 2H), 7.54 (AA'BB', 2H), 7.19-7.14 (m, 2H), 6.98-6.93 (m, 2H ), 6.76-6.73 (m, 2H), 5.79 (d, J = 3.5 Hz, 1H), 5.82-5.68 (m, 1H), 5.31-5.25 (m, 2H), 5.09 (d, J = 5.0 Hz, 1H), 4.66 (d, J = 17.5 Hz, 1H), 4.53 (dd, J = 4.9, 3.7 Hz, 1H), 4.52 (d, J = 17.7 Hz, 1H), 4.24 (q, J = 7.1 Hz, 2H), 4.08 (ddt, J = 15.4, 5.8, 1.4 Hz, 1H), 4.02 (dd, J = 18.3, 5.8 Hz, 1H), 3.68 (dd, J = 18.1, 4.7 Hz, 1H), 3.58 (dd, J = 15.4, 7.1 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  168.7, 167.5, 166.3, 165.9, 165.2, 157.3, 134.0, 131.5, 130.6, 129.3, 123.6, 122.3, 120.1, 115.6, 80.7, 69.7, 61.6, 57.3, 43.4, 41.2, 38.9, 14.1; IR (KBr,

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cm–1)  3384, 1760, 1721, 1682; HRMS (ESI) calcd for C28H28N3O9+ [M+H]+: 550.1820; found: 550.1845. Passerini adduct 2h. Method A. From 56 mg (0.24 mmol) of aldehyde ()-1a, compound 2h was obtained as a mixture of isomers in a syn/anti ratio (68:32). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound syn-()-2h (69 mg, 58%) and the more polar compound anti-()-2h (32 mg, 28%) were obtained. Method B. From 30 mg (0.13 mmol) of aldehyde ()-1a, compound 2h was obtained as a mixture of isomers in a syn/anti ratio (63:37). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound syn-()-2h (36 mg, 56%) and the more polar compound anti-()-2h (21 mg, 33%) were obtained. syn-(+)-2h. Colorless oil; []D 65.6 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.71 (AA'BB', 2H,), 7.36 (AA'BB', 2H), 7.29 (AA'XX', 2H), 7.16 (dd, J = 8.2, 5.1 Hz, 1H), 6.82 (AA'XX', 2H), 5.41 (d, J = 5.0 Hz, 1H), 4.88 (dd, J = 14.0, 8.5 Hz, 1H), 4.65 (d, J = 5.1 Hz, 1H), 4.62 (t, J = 5.1 Hz, 1H), 4.17 (dd, J = 14.0, 5.1 Hz, 1H), 3.77 (s, 3H), 3.61 (s, 3H), 2.45 (s, 3H), 1.94 (s, 3H);

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C NMR (75 MHz, CDCl3,

25°C)  169.3, 167.5, 164.0, 156.8, 145.6, 133.6, 130.0, 129.9, 128.7, 119.8, 114.1, 82.3, 70.3, 59.8, 59.7, 56.8, 55.4, 21.7, 20.4; IR (CHCl3, cm–1)  3333, 1752, 1696; HRMS (ESI) calcd for C23H26N2NaO8S+ [M+Na]+: 513.1302; found: 513.1306. anti-()-2h. Colorless oil; []D 31.3 (c 3.1, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C) : 7.73 (AA'BB', 2H), 7.39 (bs, 1H), 7.32 (AA'BB', 2H), 7.28 (AA'XX', 2H), 6.84 (AA'XX', 2H), 5.66 (d, J = 3.2 Hz, 1H), 4.66 (d, J = 5.3 Hz, 1H), 4.62-4.48 (m, 2H), 4.60 (dd, J = 5.3, 3.4 Hz, 1H), 3.77 (s, 3H), 3.62 (s, 3H), 2.43 (s, 3H), 2.11 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C) : 169.0, 166.9, 164.1, 156.8, 145.4, 133.8, 129.9, 129.7, 128.7, 118.7, 114.4, 82.8, 68.7, 60.1, 59.8, 57.9, 55.4, 21.7, 20.5; IR (CHCl3, cm–1)  3331, 1753, 1700; HRMS (ESI) calcd for C23H27N2O8S+ [M+H]+: 419.1483; found: 491.1467. 7

PREPARATION AND CHARACTERIZATION OF COMPOUNDS 3a-h and 3j-m Ugi adduct 3a. Method A. From 100 mg (0.43 mmol) of aldehyde ()-1a, compound 3a was obtained as a mixture of isomers in a syn/anti ratio (65:35). After flash chromatography using n-hexane/ethyl acetate (2:1) as eluent, the less polar compound syn-()-3a (110 mg, 50%) and the more polar compound anti-()-3a (60 mg, 28%) were obtained. Compounds 3a and 3b are a mixture of the corresponding rotamers, as shown in Scheme S1. Thus, the 1H and

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C NMR characterization has been achieved as is

explained bellow. R

O O

N MeO

N O

H N

H H

N Ph

MeO

O PMP

H H N

O 3a R = Ph 3b R = H

I

R H N

Ph

O PMP II

Scheme S1. Rotamers of compounds 3a and 3b 1

H NMR spectra of both syn-(+)-3a and anti-(+)-3a at room temperature using

CDCl3 showed a collection of broad signals. In addition, some signals of the 13C NMR spectra (CDCl3, 25°C) for both isomers were missed. Then, the multiplicity of the corresponding signals of

1

H NMR was achieved at 100°C using 1,1,2,2-

tetrachloroethane as deuterated solvent. See: 1H NMR in (CDCl2)2 of compound syn-(+)3a at different temperatures in page 22. syn-()-3a. White solid; mp 7779°C (n-hexane/ethyl acetate); []D 125.0 (c 0.3, CHCl3). 1H NMR (300 MHz, C2D2Cl4, 100°C)  7.41-7.24 (m, 10H), 7.06-7.04 (m, 2H,), 6.85-6.82 (m, 1H), 6.83 (AA'XX', 2H), 5.88-5.75 (m, 1H), 5.19 (dd, J = 9.1, 5.3 Hz, 1H), 5.13-5.04 (m, 2H), 4.83 (d, J = 8.8 Hz, 1H), 4.68 (d, J = 5.1 Hz, 1H), 4.19 (dd, J =

8

15.0, 5.7 Hz, 1H), 4.18-4.02 (m, 3H), 3.78 (s, 3H), 3.67 (s, 3H);

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C NMR (75 MHz,

C2D2Cl4, 100°C)  174.6, 170.2, 166.5, 159.0, 139.2, 137.7, 135.7, 131.5, 131.1, 130.1, 129.9, 129.1, 129.0, 128.2, 123.0, 119.4, 116.0, 85.7, 62.6, 60.8, 58.1, 57.2, 45.2; IR (KBr, cm–1)  3305, 1752, 1675, 1632; HRMS (ESI) calcd for C30H32N3O5+ [M+H]+: 514.2337; found: 514.2345. anti-()-3a. Colorless oil; []D 6.2 (c 1.4, CHCl3); 1H NMR (300 MHz, C2D2Cl4, 100°C)  7.35-7.18 (m, 10H), 6.89 (AA'XX', 2H), 6.75 (d, J = 7.1 Hz, 2H), 6.44 (t, J = 5.5 Hz, 1H), 5.58-5.45 (m, 1H), 5.26 (dd, J = 9.4, 5.2 Hz, 1H), 4.89 (d, J = 9.3 Hz, 1H), 5.02-4.87 (m, 2H), 4.72 (d, J = 5.1 Hz, 1H), 4.47 (dd, J = 14.7, 5.5 Hz, 1H), 4.40 (dd, J = 14.7, 5.6 Hz, 1H), 3.85-3.66 (m, 2H), 3.79 (s, 3H), 3.54 (s, 3H);

13

C NMR (75 MHz, C2D2Cl4, 100°C) : 174.5, 169.6, 166.9, 159.4, 139.7, 137.0,

134.1, 131.5, 131.4, 130.2, 129.6, 129.2, 129.0, 128.2, 123.8, 120.8, 116.5, 85.8, 61.6, 61.0, 58.0, 57.3, 53.5, 45.1; IR (CHCl3, cm–1)  3327, 1751, 1674, 1630; HRMS (ESI) calcd for C30H32N3O5+ [M+H]+: 514.2337; found: 514.2337. Ugi adduct 3b. Method A. From 71 mg (0.30 mmol) of aldehyde ()-1a, compound 3b was obtained as a mixture of isomers in a syn/anti ratio (55:45). After flash chromatography using n-hexane/ethyl acetate (2:1) as eluent, the less polar compound syn-()-3b (50 mg, 38%) and the more polar compound anti-()-3b (41 mg, 31%) were obtained.1 syn-()-3b. Colorless oil; []D 27.0 (c 0.3, CHCl3). 1H NMR2 (300 MHz, C2D2Cl4, 25°C)  7.97 (s, 0.3H), 7.65 (s, 0.7H), 7.31-7.09 (m, 7H), 6.81 (AA'XX', 2H), 6.22 (bs, 0.3H), 6.17 (t, J = 5.9 Hz, 0.7H), 5.65-5.43 (m, 1H), 5.17-5.04 (m, 2H), 5.06 (dd, J = 9.7, 5.2 Hz, 0.7H), 4.94 (dd, J = 8.6, 5.2 Hz, 0.3H), 4.69-4.13 (m, 4H), 3.833.55 (m, 2H), 3.74 (s, 2.1H), 3.72 (s, 0.9H), 3.45 (s, 2.1H), 3.44 (s, 0.9H); 13C NMR (75 11

H NMR spectra of both isomers of compound 3b at room temperature in CDCl3 and (CDCl2)2 showed two collections of well resolved signals of the corresponding rotamers I and II. However, it was not possible to achieve the coalescence temperature. Then, syn-(+)-3b and anti-(+)-3b are described as a mixture of rotamers at room temperature. 2 Compound syn-(+)-3b is observed as a mixture of rotamers 37:63 in CDCl3 and 30:70 in C2D2Cl4 at 25°C.

9

MHz, CDCl3, 25°C) (m, rotamer)  167.33, 165.1, 162.8, 157.1, 137.4, 132.0, 129.3, 128.63, 127.8, 127.6, 120.3, 118.7, 114.5, 83.3, 60.9, 57.0, 56.1, 55.4, 45.7, 43.5; (M, rotamer)  167.27, 165.2, 163.7, 157.4, 137.7, 132.5, 128.8, 128.57, 127.7, 127.5, 122.0, 119.9, 114.1, 83.6, 60.1, 55.5, 55.3, 55.4, 49.6, 43.4; IR (KBr, cm–1)  3307, 1752, 1662; HRMS (ESI) calcd for C24H28N3O5+ [M+H]+: 438.2024; found: 438.2034. anti-()-3b. White solid; mp 130132°C (n-hexane/ethyl acetate); []D 70.3 (c 0.5, CHCl3); 1H NMR3 (300 MHz, C2D2Cl4, 25°C)  8.30 (s, 0.5H), 8.00 (s, 0.5H), 7.27-7.14 (m, 5H), 6.86-6.76 (m, 4H), 6.76 (bs, 0.5H), 6.33 (bs, 0.5H), 5.84-5.64 (m, 1H), 5.28-5.08 (m, 2H), 5.07 (dd, J = 9.4, 5.1 Hz, 0.5H), 4.80 (dd, J = 9.2, 5.1 Hz, 0.5H), 4.74 (d, J = 9.5 Hz, 0.5H), 4.58 (d, J = 4.9 Hz, 0.5H), 4.56 (d, J = 4.9 Hz, 0.5H), 4.43 (dd, J = 15.8, 4.2 Hz, 0.5H), 4.16-3.98 (m, 2.5H), 3.83 (dd, J = 15.7, 7.8 Hz, 0.5H), 3.74 (s, 1.5H), 3.72 (s, 1.5H), 3.73-3.65 (m, 0.5H), 3.48-3.42 (m, 0.5H), 3.52 (s, 1.5H), 3.46 (s, 1.5H);

13

C

NMR (75 MHz, CDCl3, 25°C): (m, rotamer)  168.11, 164.9, 163.8, 157.10, 137.0, 133.3, 129.0, 128.47, 127.6, 127.4, 120.9, 118.0, 114.1, 83.6, 60.3, 56.8, 55.6, 55.37, 46.1, 43.8; (M, rotamer)  168.09, 165.1, 163.5, 157.13, 136.7, 134.0, 129.1, 128.49, 127.8, 127.5, 120.2, 118.6, 114.2, 84.0, 60.0, 59.4, 57.0, 55.43, 49.8, 43.5; IR (CHCl3, cm–1)  3308, 1752, 1663; HRMS (ESI) calcd for C24H28N3O5+ [M+H]+: 438.2024; found: 438.2034. Ugi adduct 3c. Method A. From 82 mg (0.35 mmol) of aldehyde ()-1a, compound 3c was obtained as a mixture of isomers in a syn/anti ratio (57:43). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, an inseparable mixture of isomers (85 mg, 54%) was obtained as a colorless oil. syn-3c 1H NMR (300 MHz, CDCl3, 25°C)  7.35-7.18 (m, 5H), 6.91-6.80 (m, 4H), 6.76 (t, J = 5.6 Hz, 1H), 5.91-5.78

3

Compound anti-(+)-3b is observed as a mixture of rotamers 47:53 in CDCl3 and 50:50 in C2D2Cl4 at 25°C.

10

(m, 1H), 5.29-5.09 (m, 3H), 5.01-4.96 (m, 1H), 4.60 (d, J = 5.0 Hz, 1H), 4.36-4.27 (m, 1H), 4.14 (dd, J = 14.6 Hz, 6.3 Hz, 1H), 4.02 (dd, J = 14.8, 5.1 Hz, 1H), 3.78 (s, 3H), 3.60 (s, 3H), 3.56-3.48 (m, 1H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  172.1, 168.7, 165.1, 157.1, 137.2, 134.0, 128.9, 128.4, 127.6, 127.2, 121.3, 116.9, 114.0, 83.7, 59.2, 56.1, 55.43, 55.35, 49.5, 43.4, 21.7; HRMS (ESI) calcd for C25H30N3O5+ [M+H]+: 452.2180; found: 452.2199. anti-3c 1H NMR (300 MHz, CDCl3, 25°C)  7.35-7.18 (m, 5H), 6.91-6.80 (m, 4H), 6.25 (t, J = 5.5 Hz, 1H), 5.66-5.53 (1H, m), 5.29-5.09 (m, 3H), 5.01-4.96 (m, 1H), 4.73 (d, J = 5.0 Hz, 1H), 4.50 (dd, J = 14.9, 6.2 Hz, 1H), 4.36-4.27 (m, 1H), 4.13-4.06 (m, 1H), 3.84-3.78 (m, 1H), 3.78 (s, 3H), 3.59 (s, 3H), 1.59 (s, 3H); 13

C NMR (75 MHz, CDCl3, 25°C)  172.0, 168.0, 165.2, 157.1, 137.8, 132.5, 129.0,

128.5, 127.7, 127.4, 121.7, 118.2, 114.2, 83.6, 60.1, 57.3, 55.7, 55.4, 49.5, 43.3, 21.2. Ugi adduct 3d. Method A. From 56 mg (0.24 mmol) of aldehyde ()-1a, compound 3d was obtained as a mixture of isomers in a syn/anti ratio (60:40). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound syn-()-3d (56 mg, 44%) and the more polar compound anti-()-3d (37 mg, 30%) were obtained. syn-()-3d. Colorless oil; []D 85.3 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C) 7.31 (AA'XX', 2H), 7.22-7.19 (m, 3H), 6.92-6.88 (m, 2H), 6.84 (AA'XX', 2H), 6.64 (t, J = 5.4 Hz, 1H), 5.96-5.81 (m, 1H), 5.31-5.21 (m, 2H), 5.16 (d, J = 9.2 Hz, 1H), 4.98 (dd, J = 9.1, 5.1 Hz, 1H), 4.61 (d, J = 5.0 Hz, 1H), 4.46-4.33 (m, 2H), 4.17 (dd, J = 14.8, 5.9 Hz, 1H), 4.06 (dd, J = 14.8, 5.4 Hz, 1H), 3.85 (s, 2H), 3.78 (s, 3H), 3.62 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  168.2, 167.9, 165.0, 157.2, 137.0, 133.8, 128.8, 128.4, 127.5, 127.3, 121.4, 117.3, 114.0, 83.6, 59.2, 57.9, 55.8, 55.4, 49.3, 43.4, 26.2; IR (CHCl3, cm–1)  3313, 1752, 1659; HRMS (ESI) calcd for C25H28BrN3NaO5+ [M+Na]+: 552.1105; found: 552.1127. anti-()-3d. Colorless oil; []D 16.1 (c 1.3, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.36-7.26 (m, 5H), 7.19 (AA'XX', 2H), 6.85 (AA'XX', 11

2H), 6.17 (t, J = 5.0 Hz, 1H), 5.73-5.60 (m, 1H), 5.27-5.17 (m, 3H), 4.80 (d, J = 9.2 Hz, 1H), 4.75 (d, J = 5.1 Hz, 1H), 4.42 (d, J = 5.7 Hz, 2H), 3.91 (dd, J = 16.3, 4.9 Hz, 1H), 3.78 (s, 3H), 3.62-3.54 (m, 1H), 3.56 (s, 3H), 3.50 (d, J = 11.7 Hz, 1H), 3.32 (d, J = 11.7 Hz, 1H); 13C NMR (75 MHz, CDCl3, 25°C)  167.7, 167.5, 165.3, 157.4, 137.6, 131.7, 129.0, 128.6, 127.7, 127.5, 121.8, 120.0, 114.4, 83.8, 60.2, 58.5, 55.8, 55.5, 51.3, 43.5, 26.5; IR (CHCl3, cm–1)  3307, 1751, 1654; HRMS (ESI) calcd for C25H29BrN3O5+ [M+H]+: 530.1285; found: 530.1271. Ugi adduct 3e. Method A. From 66 mg (0.28 mmol) of aldehyde ()-1a, compound 3e was obtained as a mixture of isomers in a syn/anti ratio (57:43). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound syn-()-3e (88 mg, 52%) and the more polar compound anti-()-3e (66 mg, 39%) were obtained. syn-()-3e. Colorless oil; []D 89.9 (c 1.6, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.88 (AA'BB', 2H), 7.74 (AA'BB', 2H), 7.29 (AA'XX', 2H), 7.21-7.19 (m, 3H), 6.89-6.86 (m, 2H), 6.81 (AA'XX', 2H), 6.62 (t, J = 5.7 Hz, 1H), 6.00-5.87 (m, 1H), 5.46-5.36 (m, 2H), 5.12 (d, J = 9.1 Hz, 1H), 5.01 (dd, J = 9.1, 5.0 Hz, 1H), 4.64 (d, J = 5.0 Hz, 1H), 4.60-4.42 (m, 1H), 4.57 (d, J = 16.5 Hz, 1H), 4.45 (d, J = 16.5 Hz, 1H), 4.23-4.16 (m, 1H), 4.20 (dd, J = 14.9, 6.3 Hz, 1H), 4.02 (dd, J = 14.8, 4.8 Hz, 1H), 3.77 (s, 3H), 3.67 (s, 3H);

C NMR (75 MHz, CDCl3, 25°C)  168.1, 167.8, 167.6, 165.0,

13

157.1, 137.0, 134.1, 133.1, 132.1, 128.9, 128.5, 127.6, 127.3, 123.5, 121.2, 118.0, 114.0, 83.8, 59.5, 58.3, 55.7, 55.4, 48.5, 43.5, 39.5; IR (CHCl3, cm–1)  3336, 1752, 1718, 1667; HRMS (ESI) calcd for C33H33N4O7+ [M+H]+: 597.2344; found: 597.2339. anti()-3e. White solid; mp 157158°C (n-hexane/ethyl acetate); []D 15.2 (c 1.6, CHCl3); 1

H NMR (300 MHz, CDCl3, 25°C)  7.84 (AA'BB', 2H), 7.75 (AA'BB', 2H), 7.33-7.22

(m, 7H), 7.06 (AA'XX', 2H), 6.24 (t, J = 5.3 Hz, 1H), 5.84-5.71 (m, 1H), 5.38-5.28 (m, 2H), 5.21 (dd, J = 9.5, 5.0 Hz, 1H), 4.74 (d, J = 5.0 Hz, 1H), 4.66-4.52 (m, 1H), 4.46

12

(dd, J = 15.0, 6.1 Hz, 1H), 4.34 (dd, J = 14.9, 5.6 Hz, 1H), 4.00 (AB, J = 16.3 Hz, 2H), 3.88 (s, 3H), 3.83-3.74 (m, 1H), 3.54 (s, 3H), 3.50 (dd, J = 11.8, 6.9 Hz, 1H); 13C NMR (75 MHz, CDCl3, 25°C)  167.6, 167.5, 167.4, 165.3, 157.3, 137.8, 134.1, 132.1, 131.3, 129.0, 128.5, 127.6, 127.2, 123.4, 121.4, 120.1, 114.8, 83.9, 60.3, 59.8, 55.6, 55.5, 50.7, 43.4, 39.3; IR (KBr, cm–1)  3329, 1751, 1719, 1664; HRMS (ESI) calcd for C33H33N4O7+ [M+H]+: 597.2344; found: 597.2362. Ugi adduct 3f. Method A. From 53 mg (0.23 mmol) of aldehyde ()-1a, compound 3f was obtained as a mixture of isomers in a syn/anti ratio (60:40). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound anti-()-3f (31 mg, 36%) and the more polar compound syn-()-3f (46 mg, 54%) were obtained. syn-()-3f. White solid; mp 17678°C (n-hexane/ethyl acetate); []D 79.6 (c 1.5, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.30 (AA'XX', 2H), 6.82 (AA'XX', 2H), 6.22 (bs, 1H), 5.90-5.78 (m, 1H), 5.27-5.21 (m, 2H), 5.11 (d, J = 8.6 Hz, 1H), 4.89 (dd, J = 8.6, 5.1 Hz, 1H), 4.60 (d, J = 5.0 Hz, 1H), 4.24 (dd, J = 18.2, 5.6 Hz, 1H), 4.134.04 (m, 1H), 3.76 (s, 3H), 3.62 (s, 3H), 2.10 (s, 3H), 1.07 (s, 9H); 13C NMR (75 MHz, CDCl3, 25°C)  172.1, 167.6, 165.3, 157.4, 134.2, 128.9, 122.2, 116.7, 114.0, 83.6, 59.3, 57.9, 56.5, 55.5, 51.3, 49.3, 28.2, 21.8; IR (KBr, cm–1)  3310, 1753, 1675, 1634; HRMS (ESI) calcd for C22H32N3O5+ [M+H]+: 418.2337; found: 418.2358; anti-()-3f. White solid; mp 134135°C (n-hexane/ethyl acetate); []D 10.8 (c 0.3, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.19 (AA'XX', 2H), 6.87 (AA'XX', 2H), 5.77-5.63 (m, 1H), 5.63 (bs, 1H), 5.22-5.15 (m, 2H), 5.00 (dd, J = 9.5, 4.8 Hz, 1H), 4.93 (d, J = 8.8 Hz, 1H), 4.71 (d, J = 4.7 Hz, 1H), 3.91 (dd, J = 16.7, 4.7 Hz, 1H), 3.79 (s, 3H), 3.58 (s, 3H), 3.52 (dd, J = 17.0, 6.9 Hz, 1H), 1.60 (s, 3H), 1.32 (s, 9H); 13C NMR (75 MHz, CDCl3, 25°C)  171.9, 167.5, 165.3, 157.3, 132.9, 129.4, 122.0, 118.3, 114.3, 83.8, 60.3, 58.0,

13

56.1, 55.5, 51.4, 50.0, 28.6, 21.4; IR (KBr, cm–1)  3312, 1753, 1642; HRMS (ESI) calcd for C22H32N3O5+ [M+H]+: 418.2337; found: 418.2334. Ugi adduct 3g. Method A. From 66 mg (0.23 mmol) of aldehyde ()-1b, compound 3g was obtained as a mixture of isomers in a syn/anti ratio (65:35). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound anti-(+)-3g (22 mg, 20%) and the more polar compound syn-()-3g (42 mg, 37%) were obtained. syn-()-3g. White solid; mp 137138°C (n-hexane/ethyl acetate); []D 28.5 (c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.31-7.25 (m, 5H), 7.24 (AA'XX', 2H), 7.17-7.14 (m, 2H), 7.05-7.01 (m, 3H), 6.90 (AA'XX', 2H), 6.26 (t, J = 5.5 Hz, 1H), 5.65-5.52 (m, 1H), 5.49 (d, J = 4.8 Hz, 1H), 5.34 (d, J = 9.9 Hz, 1H), 5.27 (dd, J = 9.4, 5.1 Hz, 1H), 5.18-5.09 (m, 2H), 4.30 (dd, J = 14.6, 6.0 Hz, 1H), 4.20 (dd, J = 14.6, 5.3 Hz, 1H), 4.02-3.94 (m, 1H), 3.80 (s, 3H), 3.56 (dd, J = 17.0, 6.3 Hz, 1H), 1.60 (s, 3H); 13

C NMR (75 MHz, CDCl3, 25°C)  172.2, 167.6, 163.8, 157.7, 157.5, 137.4, 132.6,

129.5, 128.9, 128.6, 128.0, 127.5, 122.6, 122.1, 118.0, 116.4, 114.3, 80.8, 57.1, 55.7, 55.5, 49.8, 43.5, 21.4; IR (KBr, cm–1)  3324, 1756, 1641; HRMS (ESI) calcd for C30H32N3O5+ [M+H]+: 514.2336; found: 514.2317. anti-()-3g. White solid; mp 158159°C (n-hexane/ethyl acetate); []D 95.5 (c 0.8, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.39 (AA'XX', 2H), 7.30 (t, J = 8.0 Hz, 1H), 7.22-7.19 (m, 3H), 7.067.02 (m, 3H), 6.89-6.84 (m, 3H), 6.85 (AA'XX', 2H), 5.77-5.64 (m, 1H), 5.44 (d, J = 4.5 Hz, 1H), 5.30 (dd, J = 9.9, 4.4 Hz, 1H), 5.23 (d, J = 9.8 Hz, 1H), 5.18-5.10 (m, 2H), 4.22-4.10 (m, 1H), 4.19 (dd, J = 15.0, 6.6 Hz, 1H), 4.01-3.95 (m, 1H), 4.00 (dd, J = 14.7, 4.9 Hz, 1H), 3.79 (s, 3H), 1.94 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  172.2, 168.6, 164.4, 157.3, 157.2, 137.1, 133.6, 129.6, 128.8, 128.5, 127.6, 127.3, 122.3, 121.5, 117.3, 115.3, 114.0, 80.1, 58.5, 56.1, 55.4, 50.0, 43.4, 21.8; IR (KBr, cm–1)  3286, 1757, 1642; HRMS (ESI) calcd for C30H32N3O5+ [M+H]+: 514.2336; found: 514.2355. 14

Ugi adduct 3h. Method A. From 77 mg (0.35 mmol) of aldehyde ()-1e, compound 3h was obtained as a mixture of isomers in a syn/anti ratio (76:24). After flash chromatography using n-hexane/ethyl acetate (1:1) as an eluent, the less polar compound syn-()-3h (20 mg) and an inseparable mixture of isomers (68 mg) in a syn/anti ratio (69:31), (62% yield considering both fractions). syn-()-3h. Colorless oil; []D 29.0 (c 1.4, CHCl3);1H NMR (300 MHz, CDCl3, 25°C)  7.38-7.13 (m, 10H), 6.45 (t, J = 5.6 Hz, 1H), 5.50-5.38 (m, 1H), 5.25 (d, J = 10.0 Hz, 1H), 4.98-5.04 (m, 2H), 4.66 (d, J = 5.0 Hz, 1H), 4.60 (d, J = 15.9 Hz, 1H), 4.47 (dd, J = 10.0, 4.9 Hz, 1H), 4.46 (dd, J = 14.9, 5.1 Hz, 1H), 4.18 (dd, J = 14.9, 5.3 Hz, 1H), 4.16 (d, J = 16.2 Hz, 1H), 3.71 (dd, J = 17.1, 4.8 Hz, 1H), 3.48 (s, 3H), 3.47 (dd, J = 16.9, 6.9 Hz, 1H), 1.87 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  172.6, 168.6, 168.3, 137.8, 135.7, 132.7, 128.8, 128.5, 127.8, 127.7, 127.4, 127.1, 117.8, 84.4, 59.8, 56.5, 55.4, 48.3, 44.8, 43.1, 21.9; IR (CHCl3, cm–1)  3318, 1755, 1645; HRMS (ESI) calcd for C25H30N3O4+ [M+H]+: 436.2231; found: 436.2229. Ugi adduct 3j. Method A. From 78 mg (0.34 mmol) of aldehyde ()-1d, compound 3j was obtained as a mixture of isomers in a syn/anti ratio (68:32). After flash chromatography using n-hexane/ethyl acetate (2:1) as eluent, the less polar compound anti-(+)-3j (49 mg, 28%) and the more polar compound syn-()-3j (103 mg, 58%) were obtained. syn-()-3j. Colorless oil; []D 39.0 (c 1.2, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.28-7.23 (m, 5H), 7.18-7.15 (m, 2H), 7.07-6.92 (m, 3H), 6.37 (t, J = 5.6 Hz, 1H), 5.85-5.62 (m, 2H), 5.42 (d, J = 10.2 Hz, 1H), 5.40 (d, J = 5.0 Hz, 1H), 5.315.11 (m, 4H), 4.73 (dd, J = 9.9, 4.9 Hz, 1H), 4.26-4.04 (m, 5H), 3.99 (d, J = 10.8 Hz, 1H), 3.85 (d, J = 11.0 Hz, 1H), 3.64 (dd, J = 16.2, 6.7 Hz, 1H);

13

C NMR (75 MHz,

CDCl3, 25°C)  168.7, 167.4, 166.1, 157.4, 137.2, 132.8, 131.8, 129.4, 128.7, 128.1, 127.6, 122.6, 118.35, 118.27, 116.2, 81.4, 57.5, 54.6, 48.3, 43.6, 43.5, 26.2; IR (CHCl3, 15

cm–1)  3323, 1760, 1660; HRMS (ESI) calcd for C26H29BrN3O4+ [M+H]+: 526.1336; found: 526.1357. anti-()-3j. Colorless oil; []D 105.3 (c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.35-7.24 (m, 7H), 7.12-6.95 (m, 3H), 5.91-5.62 (m, 2H), 5.29 (d, J = 10.4 Hz, 1H), 5.26 (d, J = 5.0 Hz, 1H), 5.32-5.12 (m, 4H), 4.61 (dd, J = 9.9, 4.8 Hz, 1H), 4.44 (dd, J = 14.7, 6.1 Hz, 1H), 4.36 (dd, J = 14.9, 6.0 Hz, 1H), 4.16-3.87 (m, 3H), 3.71 (d, J = 11.1 Hz, 1H), 3.64 (d, J = 11.0 Hz, 1H), 3.65-3.58 (m, 1H);

13

C NMR (75

MHz, CDCl3, 25°C)  168.3, 168.2, 166.0, 157.0, 137.4, 132.9, 131.6, 129.6, 128.6, 127.7, 127.6, 122.3, 118.4, 117.9, 115.4, 80.6, 58.0, 55.4, 48.8, 43.8, 43.6, 26.1; IR (CHCl3, cm–1)  3321, 1759, 1652; HRMS (ESI) calcd for C26H29BrN3O4+ [M+H]+: 526.1336; found: 526.1356. Ugi adduct 3k. Method B. From 76 mg (0.32 mmol) of aldehyde ()-1a, compound 3k was obtained as a mixture of isomers in a syn/anti ratio (60:40). After flash chromatography using n-hexane/ethyl acetate (2:1) as eluent, the less polar compound syn-()-3k (58 mg, 34%), and the more polar compound anti-(+)-3k (38 mg, 23%) were obtained. syn-()-3k. Colorless oil; []D 35.4 (c 0.8, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.23-7.19 (m, 5H), 7.22 (AA'XX', 2H), 6.94 (AA'XX', 2H), 6.86-6.83 (m, 2H), 6.82 (AA'XX', 2H), 6.50 (t, J = 5.5 Hz, 1H), 5.21 (d, J = 9.8 Hz, 1H), 4.39 (dd, J = 9.8, 5.1 Hz, 1H), 4.34 (d, J = 5.0 Hz, 1H), 4.13 (dd, J = 14.6, 5.1 Hz, 1H), 3.98 (dd, J = 14.6, 6.1 Hz, 1H), 3.87 (s, 3H), 3.76 (s, 3H), 3.71 (s, 3H), 1.81 (s, 3H);

13

C NMR (75

MHz, CDCl3, 25°C)  171.5, 169.2, 165.0, 159.6, 157.0, 137.1, 132.1, 128.9, 128.4, 127.6, 127.2, 121.2, 114.5, 113.8, 82.6, 58.8, 58.1, 56.1, 55.4, 55.3, 43.6, 22.7; IR (CHCl3, cm–1)  3301, 1751, 1654; HRMS (ESI) calcd for C29H32N3O6+ [M+H]+: 518.2286; found: 518.2293. anti-()-3j. Colorless oil; []D 29.1 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.38-7.19 (m, 7H), 6.91 (AA'XX', 2H), 6.71-6.67 (m, 1H), 6.69 (AA'XX', 2H), 6.51 (AA'XX', 2H), 5.12 (dd, J = 9.3, 5.2 Hz, 1H), 4.95 (d, J = 16

9.2 Hz, 1H), 4.68 (d, J = 5.0 Hz, 1H), 4.51 (d, J = 5.7 Hz, 2H), 3.82 (s, 3H), 3.76 (s, 3H), 3.50 (s, 3H), 1.61 (s, 3H);

13

C NMR (75 MHz, CDCl3, 25°C)  173.0, 168.2, 166.0,

159.0, 158.0, 138.1, 129.1, 128.7, 128.6, 127.7, 127.5, 123.7, 114.6, 114.2, 83.6, 60.0, 56.8, 55.5, 55.4, 43.5, 23.1; IR (CHCl3, cm–1)  3366, 1751, 1660; HRMS (ESI) calcd for C29H32N3O6+ [M+H]+: 518.2286; found: 518.2295. Ugi adduct 3l. Method B. From 112 mg (0.48 mmol) of aldehyde ()-1d, compound 3l was obtained as a mixture of isomers in a syn/anti ratio (70:30). After flash chromatography using n-hexane/ethyl acetate (1:1), the less polar compound anti-(+)-3l (34 mg, 19%) and the more polar compound syn-()-3l (80 mg, 46%) were obtained. syn-()-3l. Colorless oil; []D 36.7 (c 1.7, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)

 7.33-7.21 (m, 7H), 7.02-6.97 (m, 5H), 6.84 (AA'BB', 2H), 6.74 (t, J = 5.9 Hz, 1H), 5.89-5.76 (m, 1H), 5.71 (d, J = 8.9 Hz, 1H), 5.31 (d, J = 4.4 Hz, 1H), 5.26-5.19 (m, 2H), 4.46 (dd, J = 8.9, 5.0 Hz, 1H), 4.41 (dd, J = 14.5, 5.8 Hz, 1H), 4.32 (dd, J = 14.7, 5.9 Hz, 1H), 3.96 (ddt, J = 16.7, 5.3, 1.5 Hz, 1H), 3.82 (s, 3H), 3.81 (ddt, J = 16.5, 5.4, 1.5 Hz, 1H), 1.86 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  172.7, 168.2, 166.5, 159.5, 157.6, 137.8, 132.2, 131.7, 130.0, 129.3, 128.6, 128.1, 127.4, 122.3, 117.5, 116.2, 114.7, 81.9, 58.9, 56.4, 55.4, 43.5, 43.3, 23.1; IR (CHCl3, cm–1)  3336, 1758, 1653; HRMS (ESI) calcd for C30H32N3O5+ [M+H]+: 514.2336; found: 514.2339. anti-()-3l. Colorless oil; []D 50.7 (c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.40-7.29 (m, 7H), 7.15-7.12 (m, 2H), 7.05 (t, J = 7.3 Hz, 1H), 6.83 (AA'BB', 2H), 6.79 (AA'BB', 2H), 5.765.63 (m, 1H), 5.62 (d, J = 10.8 Hz, 1H), 5.17-5.05 (m, 2H), 5.11 (d, J = 4.8 Hz, 1H), 4.51 (dd, J = 14.6, 6.0 Hz, 1H), 4.44 (dd, J = 14.4, 5.6 Hz, 1H), 4.00 (dd, J = 10.4, 4.8 Hz, 1H), 3.84 (ddt, J = 15.6, 6.2, 1.2 Hz, 1H), 3.78 (s, 3H), 3.63 (ddt, J = 15.6, 5.6, 1.4 Hz, 1H), 1.84 (s, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  171.9, 169.4, 165.9, 159.7, 157.3, 137.9, 131.9, 131.3, 129.9, 129.7, 128.6, 127.8, 127.5, 122.3, 117.8, 115.7, 114.9, 80.5, 17

57.1, 55.6, 55.4, 43.9, 43.6, 22.5; IR (CHCl3, cm–1)  3345, 1760, 1676, 1651; HRMS (ESI) calcd for C30H32N3O5+ [M]+: 514.2336; found: 514.2358. Ugi adduct 3m. Method B. From 76 mg (0.33 mmol) of aldehyde ()-1d, compound 3m was obtained as a mixture of isomers in a syn/anti ratio (70:30). After flash chromatography using n-hexane/ethyl acetate (1:1) as eluent, the less polar compound anti-(+)-3m (44 mg, 20%) and the more polar compound syn-()-3m (103 mg, 48%) were obtained. syn-()-3m. Colorless oil; []D 26.4 (c 0.7, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.87 (AA'BB', 2H), 7.74 (AA'BB', 2H), 7.44 (AA'XX', 2H), 7.24-7.21 (m, 2H), 7.02-6.96 (m, 5H), 6.76 (t, J = 5.6 Hz, 1H), 5.97-5.84 (m, 1H), 5.64 (d, J = 8.6 Hz, 1H), 5.37-5.31 (m, 2H), 5.32 (d, J = 5.1 Hz, 1H), 4.59 (dd, J = 8.6, 5.0 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 4.22 (d, J = 17.2 Hz, 1H), 4.14-4.03 (m, 2H), 4.13 (d, J = 17.1 Hz, 1H), 3.84 (s, 3H), 3.82-3.75 (m, 2H), 1.30 (t, J = 7.2 Hz, 3H);

13

C NMR (75

MHz, CDCl3, 25°C)  169.3, 168.3, 167.8, 167.7, 166.4, 160.1, 157.3, 134.1, 132.1, 132.0, 130.4, 129.8, 129.3, 123.5, 122.3, 118.0, 115.9, 115.2, 81.4, 61.4, 59.8, 56.0, 55.5, 43.4, 40.9, 40.3, 14.1; IR (CHCl3, cm–1)  3340, 1759, 1718, 1669; HRMS (ESI) calcd for C35H34N4NaO9+ [M+Na]+: 677.2218; found: 677.2237. anti-()-3m. Colorless oil; []D 134.7 (c 0.3, CHCl3); 1H NMR (300 MHz, CDCl3, 25°C)  7.93 (AA'BB', 2H), 7.75 (AA'BB', 2H), 7.47-7.41 (m, 2H), 7.38-7.35 (m, 2H), 7.20 (t, J = 6.1 Hz, 1H), 7.11 (tt, J = 7.1, 1.2 Hz, 1H), 7.04-6.82 (m, 4H), 5.78-5.65 (m, 1H), 5.59 (d, J = 10.2 Hz, 1H), 5.18-5.07 (m, 2H), 5.15 (d, J = 5.0 Hz, 1H), 4.31 (d, J = 16.8 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 4.16 (dd, J = 17.8, 6.6 Hz, 1H), 4.06 (d, J = 16.8 Hz, 1H), 4.04 (dd, J = 10.4, 4.8 Hz, 1H), 3.93-3.86 (m, 1H), 3.91 (dd, J = 17.8, 5.5 Hz, 1H), 3.82 (s, 3H), 3.68 (ddt, J = 15.6, 5.7, 1.3 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3, 25°C)  169.6, 169.0, 167.7, 167.6, 166.0, 160.2, 157.3, 134.0, 132.1, 131.8, 130.8, 129.8, 129.0, 123.5, 122.4, 117.9, 116.1, 115.3, 80.6, 61.5, 57.5, 55.5, 54.9, 43.8, 41.3, 40.0, 14.2; IR

18

(CHCl3, cm–1):  3364, 1760, 1721, 1682; HRMS (ES): calcd for C35H34N4O9+ [M+H]+: 655.2399; found: 655.2410.

Figure S1. Observed NOE for compounds 5 0.3%

5.0% 3.0%

PhO

H

H

R

4%

5.6% 0.4%

Ac N 0.6%

PhO

H

H

4%

N

R

H

Ac

N 4% H

N

O

O ()-5a

R = CONHBn

(+)-5b

19

Table S1. Representative chemical shifts (, ppm) and vicinal coupling constants (3J, Hz) of 1H and 13C NMR of compounds 2a O H H

2

R

N O

O R3 NHR4

O

H H

2

R

O R1

N O

syn-2

R3 NHR4

O

O R1

anti-2 syn

Comp.

1

2

R

R

3

R

b

MeO

Ph

b



4

R

anti 3

H4'

C4'

Bn

5.80

70.4

5.3



J

H3-H4 H4-H4'

3

J

H4'

C4'

H3-H4 H4-H4'

3.2

6.10

69.1

5.3

3.4

2a

PMP

2b

PMP

PhO

Ph

Bn

5.95

69.8

5.3

2.1

6.29

68.7

5.1

3.2

2c

2-propynyl

PhO

Ph

Bn

5.81

71.6

5.1

5.1

6.09

69.7

5.0

4.0

2d

PMP

b

MeO

Me

Bn

5.56

70.5

5.3

4.6

5.78

69.0

5.1

3.8

2e

PMP

b

MeO

Me

t-Bu

5.39

71.3

5.1

5.1

5.55

69.8

5.4

2.3

2f

2-propenyl

PhO

2-IC6H4

t-Bu

5.70

71.5

5.1

3.2

5.73

71.3

5.0

4.0

2g

2-propenyl

PhO CH2Phth CH2CO2Et

5.64

70.3

5.0

2.3

5.79

69.7

5.0

3.6

2h

PMP

MeO

5.41

70.3

5.1

5.0

5.66

68.7

5.3

3.3

b

Me

CH2Ts

a

Chemical shifts and vicinal coupling constants from 1H NMR spectra (300 MHz) and 13C NMR spectra (75 MHz) recorded at c 300 MHz using CDCl3 as solvent. bPMP =- 4-MeO-C6H4. Phth = Phtalimido.

20

Table S2. Representative chemical shifts (, ppm) and vicinal coupling constants (3J, Hz) of 1H and 13C NMR of compounds 3a O

R3 H H

R2

N O

R3

R4 NHR5

N

H H

R2

O R1

N O

syn-3

O R4 NHR5

N

O R1

anti-3 syn

Comp.

1

2

R

R

3

4

R

R

R

anti 3



5

3



J

H4'

C4' H3-H4 H4-H4'

d

56.1

5.0

d

J

H4'

C4' H3-H4 H4-H4'

d

57.3

5.0

d

b

MeO 2-propenyl

Me

Bn

b

MeO 2-propenyl

CH2Br

Bn

5.16 57.9

5.0

9.2

4.80 58.5

5.1

9.2

b

MeO 2-propenyl CH2Phthc

Bn

5.12 58.3

5.0

9.1

4.59 59.8

5.0

9.5

PMP

b

MeO 2-propenyl

Me

t-Bu

5.11 57.9

5.0

8.6

4.93 58.0

4.7

9.2

3g

Bn

MeO 2-propenyl

Me

Bn

5.25 56.5

5.0

10.0







3h

PMP

PhO 2-propenyl

Me

Bn

5.34 57.1

4.8

9.6

5.23 58.5

4.5

9.8

3i

2-propenyl PhO 2-propenyl

Me

Bn

5.53 56.2

4.9

10.0

5.09 58.1

4.7

10.2

3j

2-propenyl PhO 2-propenyl

3c

PMP

3d

PMP

3e

PMP

3f

3k 3l 3m

b

b

PMP

MeO

2-propenyl PhO 2-propenyl PhO



CH2Br

Bn

5.42 57.5

5.0

10.1

5.29 58.0

5.0

10.2

b

Me

Bn

5.21 58.1

5.0

9.8

4.95 56.8

5.0

9.2

PMP

b

Me

Bn

5.71 58.9

4.4

8.9

5.62 57.1

4.8

10.6

PMP

b

CH2CO2Et 5.64 59.8

5.1

8.6

5.59 57.5

5.0

10.3

PMP

c

CH2Phth

a

Chemical shifts and vicinal coupling constants from 1H NMR spectra (300 MHz) and 13C NMR spectra (75 MHz) recorded at 300 c MHz using CDCl3 as solvent. bPMP =- 4-MeO-C6H4.. Phth = Phtalimido. d It could not be measured because the corresponding signals are observed as a complex multiplet.

21

1

O

H NMR in (CDCl2)2 of compound syn-(+)-3a at different temperatures MeO

100 ºC

O

H H N

N

Ph NHBn

O PMP

syn-(+)-3a

80 ºC

60 ºC

40 ºC

25 ºC

22

1

H NMR in (CDCl2)2 of compound anti-(+)-3b at different temperatures

CHO MeO O

H H N

N NHBn O PMP

anti-(+)-3b

100 ºC

80 ºC

60 ºC

40 ºC

25 ºC

23

160 7.6 7.4

150 7.2 7.0

140 6.8 6.6

130

75 MHz (CDCl3, 25ºC) 6.0

120

N

5.8 5.6 (ppm)

110

H N

5.4

100 5.2

90 5.0 4.8

80 4.6 4.4

70

4.2 4.0

60

3.8

43.4457

O

O

59.6556 57.6630 55.4231

H H

70.4040

MeO

77.0000

82.7451

6.2

114.3431

6.4

119.7828

133.6874 130.1603 129.9931 128.7568 128.6332 128.5386 127.5351

7.8

136.9454

8.0

156.7842

168.1798 165.2927 164.6019

3.4651

3.7495

4.4590 4.4390 4.4093 4.3893 4.2939 4.2749 4.2442 4.2252

4.7311 4.7136

5.1616 5.1509 5.1441 5.1338

5.8034 5.7927

6.4383 6.4198 6.4013

6.8147 6.7845

7.0533 7.0222

7.5967 7.5719 7.5471 7.4507 7.4214 7.3990 7.2700 7.2515 7.2291

7.9337 7.9054

1

H and 13C NMR spectra for all new compounds

300 MHz (CDCl3, 25ºC)

O Ph

Ph

O PMP

syn-(+)-2a

3.6 3.4

(ppm)

50

24

160

150

140 6.6

130 6.4 6.2

120 6.0 5.8 5.6 (ppm)

110

100 5.4 5.2

90 5.0 4.8

80 4.6 4.4

70

4.2 4.0

60 43.3512

N

H N

55.3577

O

O

60.1138 58.2448

6.8

H H

69.1168

MeO

77.0000

7.0

83.2760

7.2

114.4086

7.4

118.7501

7.6

133.8038 130.0004 129.8040 128.6550 128.5023 127.6660 127.5714

7.8

137.4181

8.0

156.6751

167.1617 164.9800 164.4637

3.8

3.5216

3.7544

4.9887 4.9775 4.9717 4.9600 4.7531 4.7355 4.5734 4.5524 4.5237 4.5028 4.3659 4.3479 4.3168 4.2983

6.1048 6.0936

6.8284 6.7982 6.6798 6.6608 6.6414

7.6211 7.5967 7.5719 7.4794 7.4536 7.4253 7.3260 7.2958 7.2700 7.2379 7.2116

8.0286 8.0004

300 MHz (CDCl3, 25ºC)

O Ph

Ph

O PMP

anti-(+)-2a

3.6

75 MHz (CDCl3, 25ºC)

(ppm)

50

25

160

150

140

130 6.8 6.6

120 6.4 6.2 6.0 (ppm)

110 5.8

100 5.6 5.4

90 5.2 5.0

80

4.8 4.6

70

4.4 4.2

60 43.5039

N

H N

55.4450

O

O

57.9612

7.0

H H

69.7932

PhO

77.0000

7.2

79.5162

7.4

115.5431 114.4668

7.6

119.7537

7.8

122.6408

8.0

136.7490 133.8256 130.0294 129.6149 128.6477 128.6113 127.5714

8.2

157.1405 156.9441

8.4

165.0527 163.1910

168.1435

4.0

3.7763

4.4093 4.3903 4.3596 4.3406 4.2983 4.2788 4.2486 4.2291

5.5253 5.5078 5.4143 5.4070 5.3968 5.3895

5.9499 5.9431

6.3852 6.3663 6.3473

7.9746 7.9463 7.5914 7.5665 7.5422 7.5135 7.4833 7.4487 7.4229 7.3981 7.2788 7.2700 7.2539 7.2505 7.2383 7.2281 7.2174 7.0304 7.0061 6.9822 6.9501 6.9467 6.9209 6.9184 6.8546 6.8245

300 MHz (CDCl3, 25ºC)

O Ph

Ph

O PMP

syn-(+)-2b

3.8

75 MHz (CDCl3, 25ºC)

(ppm)

50

26

8.0 7.8 7.6 7.4 7.2 7.0 6.8 6.6 6.4 6.2

PhO O

H H N

O

6.0 5.8 (ppm) 5.6

H N

5.4 5.2 5.0 4.8 4.6 4.4 4.2

3.9189 3.9024 3.8698 3.8527 3.7792

4.3922 4.3713 4.3431 4.3216

5.2809 5.2697 5.2638 5.2531

5.5502 5.5331

6.2932 6.2825

6.4875 6.4685 6.4495

6.8654 6.8352

7.0012

7.0928

7.6167 7.5919 7.5670 7.4653 7.4390 7.4141 7.3674 7.3372 7.2978 7.2700 7.2393 7.2179

8.0311 8.0028

300 MHz (CDCl3, 25ºC)

O Ph

Ph

O PMP

anti-(+)-2b

4.0 3.8

75 MHz (CDCl3, 25ºC)

27

170

160

150 6.8

140 6.4

130 6.0

120 80.8107 80.5416 77.0000 76.2873 75.8219 73.5820 73.2475 71.6403 69.6841

7.2

115.5722 115.4922

7.6

122.6554 122.6044

8.0

137.1999 137.0326 133.9856 133.9056 130.0222 129.9931 129.6658 129.5786 128.7350 128.6841 128.6477 127.7605 127.6878 127.6660 127.6150

8.4

157.3878 157.0460

166.8926 166.6963 165.7072 165.3218 165.2491 165.1836

5.6

110

75 MHz (CDCl3, 25ºC) 5.2 (ppm) 4.8

100 (ppm)

90

H N

4.4

80 4.0

70

3.6

60

3.2

50

2.8

40

31.1265 30.4501

N

O

43.5984 43.2857

H H

58.1139 57.4667

PhO

2.3233 2.3145 2.3082 2.2999 2.2916

4.4541 4.4341 4.3966 4.3538 4.3236 4.2861 4.2554 4.0494 3.9822 3.9564 3.8892 3.8245

4.9493 4.9201 4.9089

5.4411 5.4245 5.4182 5.4012

5.8146 5.7975

6.1014 6.0882

6.5294

8.1139 8.0929 8.0817 8.0403 7.6454 7.6410 7.5870 7.4993 7.4331 7.3012 7.2700 7.2101 7.1439 7.1117 7.0460 6.9403 6.9092 6.8770 6.7134 6.6949 6.6774

300 MHz (CDCl3, 25ºC)

O Ph

Ph

O O

2c (mixture of diastereoisomers syn/anti 72:28)

2.4

30

28

170

160

150

140

130

120

110 5.2 4.8 (ppm)

100

90 4.4

80 4.0

70 3.6 3.2

60

50 20.6908

5.6

43.4094

N

H N

59.7865 57.3212 55.4086

O

O

70.5277

6.0

H H

77.0000

6.4

82.6651

MeO

114.1177

6.8

119.6883

7.2

130.1385 128.6550 127.6151 127.5642

7.6

137.0036

156.6678

164.4201

169.5834 167.6708

1.9902

3.5192

4.4594 4.4400 4.4103 4.3908 4.2822 4.2637 4.2325 4.2140 3.7724

4.6664 4.6489

4.9892 4.9732 4.9576

5.5657 5.5506

6.4481

6.8396 6.8099

7.4015 7.3713 7.2992 7.2856 7.2802 7.2700 7.2632 7.0786 7.0679 7.0543 7.0480

300 MHz (CDCl3, 25ºC)

O Ph

O PMP

syn-(+)-2d

2.8

40

2.4

30

2.0

75 MHz (CDCl3, 25ºC)

(ppm)

20

29

170

160

150

140

130

120 5.2

110 4.8 (ppm)

100 4.4

90 4.0

80 3.6

70 3.2

60

50 20.5671

5.6

43.4166

6.0

59.9683 58.0630 55.3650

N

H N

69.0587

O

O

77.0000

6.4

H H

82.9633

MeO

114.3577

6.8

118.5829

7.2

130.0585 128.6623 127.7678 127.6005

7.6

137.2872

156.6387

169.2561 166.8854 164.4055

2.1037

3.4851

4.8188 4.8061 4.8018 4.7891 4.6771 4.6601 4.4867 4.4667 4.4375 4.4180 4.3056 4.2876 4.2564 4.2384 3.7811

5.7858 5.7737

6.8809 6.8512 6.6253 6.6073 6.5898

7.3815 7.3513 7.3172 7.2934 7.2700 7.2038 7.1979 7.1775

300 MHz (CDCl3, 25ºC)

O Ph

O PMP

anti-(+)-2d

2.8

40

2.4

30

2.0

75 MHz (CDCl3, 25ºC)

(ppm)

20

30

170

160 6.5

150 6.0

140 5.5

75 MHz (CDCl3, 25ºC)

130

120 5.0 4.5 (ppm)

110

100 (ppm)

90

80

70 2.5

60

50

2.0

40 20.6544

3.0

28.4285

3.5

51.4816

4.0

59.7938 57.2485 55.4450

N

71.2622

O

O

77.0000

H H

82.6869

MeO

114.1177

7.0

119.8846

7.5

130.2767

156.6969

166.4999 164.4855

169.6052

1.2876

1.9868

3.5898

3.7894

4.9337 4.9167 4.8991 4.6781 4.6610

5.3997 5.3827

5.9412

6.8629 6.8327

7.2700

7.4321 7.4020

300 MHz (CDCl3, 25ºC)

O H N

O PMP

syn-(+)-2e

1.5

30

31

170

160

150

140

130

120

110 4.5 (ppm)

100 4.0

90 3.5

80 3.0

70 2.5

60

50

2.0

40

30

20.6835

5.0

28.4503

5.5

51.3943

6.0

59.9974 58.6957 55.3577

6.5

69.7641

N

O

77.0000

7.0

H H

82.5633

O

114.2632

MeO

118.6992

7.5

130.3131

156.6169

164.7764 164.2164

169.4161

1.2730

2.1723

3.7846 3.6862

4.7161 4.6980 4.6751 4.6674 4.6571 4.6493

5.5555 5.5477

6.2265

6.8727 6.8430

7.4234 7.3932 7.2700

300 MHz (CDCl3, 25ºC)

O H N

O PMP

anti-(+)-2e

1.5

75 MHz (CDCl3, 25ºC)

(ppm)

20

32

170

160

150

140

130

120

110 5.0 (ppm)

100 (ppm) 4.5

90 4.0

80 3.5

70

3.0

60

2.5 2.0

50

40

28.5594 28.4430

N

44.0057 43.5839

5.5

H H O

51.9470 51.7579

O

57.6776 57.2776

PhO

71.4731 71.2694

6.0

80.2434 80.1489 77.0000

6.5

94.4026 93.7553

7.0

119.6665 118.9174 115.5285 115.4922

7.5

122.6408 122.5972

8.0

141.4324 140.8651 134.7128 133.3456 133.1056 131.4766 130.8803 130.8439 130.6112 129.6731 129.6295 128.4005 128.2405

8.5

157.1405 157.0750

165.9981 165.7945 165.7072 165.6709 165.0891

1.3635 1.2793

3.7256 3.6516

5.8511 5.7444 5.7313 5.7065 5.6958 5.4304 5.4138 5.4046 5.3875 5.3457 5.2531 5.2307 5.1689 4.8003 4.7730 4.6747 4.6450 4.2131 4.1215

6.3030 6.2338

8.0243 7.9687 7.8894 7.8577 7.7900 7.7584 7.4424 7.4068 7.3878 7.3776 7.2924 7.2388 7.2184 7.1614 7.0816 7.0114 6.9842

300 MHz (CDCl3, 25ºC)

I H N

O O

2f (mixture of diastereoisomers syn/anti 73:27)

1.5

75 MHz (CDCl3, 25ºC)

30

33

170

160

150

140

130

120

110

100

90 4.0

80

70

H H

3.5

60

O

N

3.0

50

H N

2.5

40 14.1021

Pht

43.3003 41.1840 39.1769

PhO

57.2340

4.5 (ppm)

61.5900

5.0

70.3095

5.5

80.2289 77.0000

6.0

115.5213

6.5

118.9610

7.0

123.8117 122.6481

7.5

134.4437 131.7821 130.8294 129.6440

8.0

157.1114

168.9361 167.4380 167.2490 165.9254 165.3218

1.3285 1.3051 1.2812

4.6727 4.6649 4.6562 4.6484 4.5758 4.5661 4.2793 4.2671 4.2554 4.2462 4.2316 4.2077 4.1858 3.9472 3.9311 3.8883 3.8717 3.6682 3.6453 3.6161 3.5932

5.2940 5.2775 5.1816 5.1192

5.7381 5.6471 5.6393 5.6066

7.9293 7.9011 7.7978 7.7696 7.3299 7.3007 7.2763 7.2700 7.1229 7.1044 7.0864 7.0616 7.0119

300 MHz (CDCl3, 25ºC)

O

CO2 Et

O O

sy n-()-2g

2.0

30

1.5

75 MHz (CDCl3, 25ºC)

(ppm)

20

34

170

160

150

140

130

120

110

100

90 (ppm) 4.0

80

70

H H

3.5

60

O

N

H N

3.0 2.5

50

40 14.1239

Phth

43.3875 41.1622 38.8787

4.5 (ppm)

57.3067

PhO

61.6046

5.0

69.6841

5.5

77.0000

6.0

80.6725

6.5

115.6013

7.0

123.6371 122.2699 120.0664

7.5

133.9783 131.5057 130.5603 129.3459

157.2787

168.6816 167.5399 166.3108 165.9472 165.1909

1.3221 1.2983 1.2744

4.2793 4.2559 4.2320 4.2082 4.1127 4.0938 4.0616 4.0553 4.0421 4.0358 3.9939 3.9749 3.7159 3.7003 3.6555 3.6399 3.6141 3.5908 3.5630 3.5391

5.3096 5.2473 5.1012 5.0847 4.6849 4.6265 4.5505 4.5432 4.5305 4.5266 4.5145 4.4916

5.8155 5.8004 5.7888 5.6826

7.2700 7.1901 7.1366 6.9856 6.9330 6.7651 6.7329

7.7043 7.6761 7.5505 7.5217

300 MHz (CDCl3, 25ºC)

O

CO2Et

O O

anti-()-2g

2.0

30

1.5

75 MHz (CDCl3, 25ºC)

20

35

170

160

150

140

130

120

110 5.0 (ppm)

100 90 (ppm) 4.5 4.0

80 3.5

70

60 21.7089 20.4508

5.5

59.8156 59.7211 56.8267 55.4377

6.0

70.3459

6.5

H N

77.0000

7.0

82.3451

O

O

114.0668

MeO H H

119.8192

133.6001 130.0004 129.8695 128.7059

7.5

145.6430

8.0

156.7987

164.0492

169.3434 167.5471

3.0

50

40

1.9435

2.4494

3.6122

3.7724

4.9142 4.8860 4.8675 4.8392 4.6571 4.6401 4.6230 4.6060 4.2038 4.1868 4.1571 4.1400

5.4167 5.4002

6.8357 6.8055

7.7258 7.6985 7.3742 7.3469 7.3060 7.2758 7.2700 7.1853 7.1682 7.1580 7.1410

300 MHz (CDCl3, 25ºC)

O

O N PMP

Ts

syn-(+)-2h

2.5 2.0

75 MHz (CDCl3, 25ºC)

30

20

36

170

160

150

140

130 6.0 5.6

120

110 5.2 4.8 (ppm)

100

90 4.4

80 4.0

70 60.1429 59.8301 57.9103 55.3722

6.4 3.6

75 MHz (CDCl3, 25ºC)

60

3.2 2.8 2.4

50

40

30 21.7016 20.4653

H N

68.7241

N

O

77.0000

O

82.7669

6.8

H H

114.3940

MeO

118.6774

7.2

133.7892 129.9422 129.7386 128.7277

7.6

145.4103

156.7551

168.9507 166.9072 164.1437

2.1081

2.4304

3.6258

4.6722 4.6547 4.6157 4.6045 4.5982 4.5870 4.5748 4.5524 4.5300 4.5057 4.4833 3.7743

5.6626 5.6519

6.8517 6.8215

7.3874 7.3314 7.3017 7.2783 7.2700

7.7428 7.7151

300 MHz (CDCl3, 25ºC)

O Ts

O PMP

anti-(+)-2h

2.0

(ppm)

20

37

170

160

150

140

130

O N

5.8

120 5.6 5.4 (ppm)

110 (ppm)

H N

5.2

100 5.0 4.8

90 4.6

80

4.4 4.2

70 4.0

60 45.1601

6.0

H H

58.0987 57.2077

MeO

62.5766 60.7641

N

75.5000

6.2

85.6666

6.4

116.0294

6.6

119.3954

6.8

122.9975

7.0

139.2184 137.7410 135.6924 131.4811 131.1156 130.1332 129.9199 129.0746 128.9680 128.2598

7.2

159.0414

7.4

166.4969

170.2132

174.5693

3.8

3.6746

3.7774

4.2282 4.2095 4.1784 4.1592 4.1217 4.0755 4.0248

4.6877 4.6708

4.8436 4.8144

5.1276 5.0969 5.0425

5.2149

5.9400 5.8755 5.8211 5.8019 5.7466

6.8462 6.8160

7.0597 7.0519 7.0359

7.4149 7.3573 7.2956 7.2650 7.2412

300 MHz (C2D2Cl4, 100ºC)

Bz Ph

O PMP

syn-(+)-3a

3.6

75 MHz (C2D2Cl4, 100ºC)

50

38

170

160

150

140

O N

130 6.0 5.8

120 5.6 5.4 (ppm)

110 (ppm) 5.2

100

H N

5.0 4.8

90 4.6

80

4.4 4.2

70

4.0 3.8

60 45.1296

6.2

H H

53.4761

MeO

61.6551 61.0230 58.0302 57.3143

N

75.5000

6.4

85.8037

6.6

116.4787

6.8

120.8423

7.0

123.7819

7.2

139.6829 136.9795 134.1160 131.4659 131.3973 130.1789 129.6153 129.1508 129.0137 128.2445

7.4

159.3993

166.9005

7.6

169.6573

174.5464

3.8533 3.7998 3.7884 3.7377 3.7153 3.6705 3.6627 3.5424

5.0233 4.9895 4.9401 4.9374 4.9017 4.8834 4.8802 4.8706 4.7339 4.7170 4.5003 4.4811 4.4504 4.4331 4.4152 4.3851 4.3654

5.5816 5.5258 5.5038 5.4481 5.2844 5.2675 5.2533 5.2359

5.9400

6.4598 6.4415 6.4251

6.9047 6.8750 6.7607 6.7323

7.3537 7.3239 7.3070 7.2901 7.2599 7.2320 7.2060 7.1813

300 MHz (C2D2Cl4, 100ºC)

Bz Ph

O PMP

anti-(+)-3a

3.6

75 MHz (C2D2Cl4, 100ºC)

50

39

170

160

N

O N

7.2

150 7.0 6.8

140 6.6 6.4

130 6.2

120 6.0 5.8 5.6 (ppm)

110 (ppm) 5.4

100 5.2

H N

5.0

90 4.8 4.6

80 60.9283 60.0920 56.9940 56.0631 55.4959 55.3868 55.3359 49.6126 45.7001 43.5475 43.4021

MeO H H

77.0000

7.4

83.6178 83.3342

7.6

121.9645 120.2919 119.9064 118.7356 114.5104 114.1468

7.8

137.6799 137.3890 132.5093 132.0439 129.2295 128.8004 128.6332 128.5750 127.7678 127.6805 127.6223 127.4842

8.0

157.4459 157.1187

167.3290 167.2708 165.2491 165.0891 163.7437 162.8347

4.4

70

4.2 4.0

60

3.8

3.5479 3.4533 3.4377

3.8300 3.7358 3.7240

4.1345

4.2717

4.4011

4.4975

4.6909 4.6274

5.0375 4.9652 4.9191

5.1705

5.4284

5.6460

5.9400

6.2175 6.1905 6.1709 6.1512

6.8283 6.7991

7.0894

7.3134

7.6527

7.9713

300 MHz (C2D2Cl4, 25ºC)

CHO Ph

O PMP

syn-(+)-3b (mixture of rotamers 30:70)

3.6 3.4

75 MHz (CDCl3, 25ºC)

50

40

170

160 7.2

150 6.8

140 6.4

130

120 6.0 (ppm)

110 (ppm)

H H

O N

5.6

100

H N

5.2

90 4.8

80 60.2810 60.0120 59.3865 56.9503 56.8194 55.6559 55.4304 55.3722 49.7944 46.0783 43.8093 43.5330

N

77.0000

MeO

83.9959 83.6469

7.6

120.8955 120.2191 118.5538 118.0011 114.2050 114.0668

8.0

137.0327 136.7054 134.0219 133.2729 129.1204 129.0113 128.4950 128.4732 127.7678 127.5714 127.5060 127.3532

157.1332 157.1041

168.1144 168.0925 165.0891 164.9218 163.8383 163.5474

5.2784 5.0992 5.0818 5.0507 4.8249 4.7773 4.7554 4.7238 4.5913 4.5748 4.5638 4.5474 4.4610 4.4468 4.4079 4.3951 4.1587 3.9763 3.8666 3.8405 3.8140 3.7884 3.7368 3.7203 3.6540 3.5178 3.4771 3.4227

5.6360

5.8367

5.9400

6.3346

6.8649 6.7671 6.7556

7.1415

7.2673

7.9992

8.2950

300 MHz (C2D2Cl4, 25ºC)

CHO Ph

O PMP

anti-(+)-3b (mixture of rotamers 50:50)

4.4

70

4.0

60

3.6

75 MHz (CDCl3, 25ºC)

50

41

170

160

N

150 6.0

140 5.6

130 5.2

120 4.8

110 4.4 (ppm)

100 (ppm) 4.0

90 3.6

80 3.2

70 2.8

60

2.4

50

40

21.7234 21.2435

O

H N

60.0774 59.2338 57.2703 56.0777 55.7286 55.4304 55.3504 49.5181 43.3730 43.2639

6.4

H H

77.0000

N

83.6905 83.5669

MeO

121.6736 121.3245 118.1756 116.8812 114.1541 113.9504

6.8

137.8326 137.1781 133.9638 132.5166 129.0113 128.9095 128.5095 128.4077 127.7169 127.5642 127.3823 127.2369

7.2

157.1187 157.0969

172.1068 171.9832 168.7252 168.0126 165.1618 165.0746

1.5870

2.0998

4.7360 4.7195 4.6060 4.5894 4.5198 4.4497 4.3630 4.2661 4.1790 4.1093 4.0553 3.9891 3.8406 3.8001 3.7841 3.7763 3.6054 3.5562 3.5333 3.4788

5.2877 5.2332 5.1660 5.0934 5.0077 4.9605

5.5331

5.6617

5.7858

5.9124

6.2460

7.3226 7.2924 7.2700 7.2189 7.2091 7.1794 6.9082 6.8775 6.8454 6.8147 6.7563

300 MHz (CDCl3, 25ºC)

Ac Ph

O PMP

3c (mixture of diastereoisomers syn/anti 57:43)

2.0 1.6

75 MHz (CDCl3, 25ºC)

30

42

170

160

150

140

130 6.2 6.0

120 5.8

110 5.6 5.4 (ppm)

100 (ppm) 5.2

90 5.0

80 4.8

70

4.6 4.4

60

4.2

50 26.1886

6.4

43.4384

N

H N

49.2781

N

59.2484 57.9030 55.8304 55.3795

6.6

H H

77.0000

O

83.5669

6.8

114.0232

MeO

117.2811

7.0

121.3682

7.2

137.0472 133.8256 128.8441 128.4586 127.5496 127.3169

7.4

157.1841

164.9946

168.1653 167.9471

4.6221 4.6055 4.4590 4.4395 4.3986 4.3791 4.3338 4.2262 4.2194 4.2121 4.1760 4.1648 4.1571 4.1274 4.1069 4.0976 4.0796 4.0485 4.0309 4.0085 3.8537 3.7816 3.6205

5.3101 5.2565 5.2069 5.1708 5.1402 5.0072 4.9902 4.9770 4.9600

5.8087

5.9626

6.6443

6.9179 6.8537 6.8240

7.2700 7.2359 7.2228 7.2125 7.2009 7.1872

300 MHz (CDCl3, 25ºC)

O Br Ph

O PMP

syn-(+)-3d

4.0

40

3.8 3.6

75 MHz (CDCl3, 25ºC)

30

43

160

150 6.6

140 6.4

130 6.2 6.0

120 5.8

110 5.6 5.4 5.2 (ppm)

100

90 5.0 4.8

80 4.6

70 4.4 4.2

60

4.0

50 26.4795

N

H N

43.4966

N

60.2229 58.5066 55.7940 55.4959 51.2852

6.8

H H

77.0000

O

83.7705

MeO

114.3504

7.0

121.8263 120.0301

7.2

137.6290 131.7239 128.9604 128.6041 127.7096 127.4987

7.4

157.3805

167.6780 167.5180 165.2636

3.8

40

3.6195 3.5567 3.5396 3.5163 3.4773 3.3444 3.3054

3.9482 3.9321 3.8941 3.8776 3.7811

4.4254 4.4064

4.8115 4.7808 4.7623 4.7453

5.2668 5.2103 5.1704

5.5998

5.7318

6.1885 6.1715 6.1549

6.8697 6.8400

7.3606 7.2700 7.2525 7.2052 7.1755

300 MHz (CDCl3, 25ºC)

O Br Ph

O PMP

anti-(+)-3d

3.6 3.4

75 MHz (CDCl3, 25ºC)

(ppm)

30

44

170

160

150

140

130 6.4 6.2

120 6.0 5.8 5.6 (ppm)

110

100 5.4 5.2

90 5.0

80 4.8 4.6

70

4.4 4.2

60

4.0

50

3.8

39.4823

6.6

43.4966

6.8

H N

48.4636

N

59.5320 58.3321 55.7286 55.3577

7.0

H H

77.0000

O

83.7632

MeO

114.0304

7.2

118.0011

7.4

123.4844 121.2155

7.6

136.9890 134.0874 133.0765 132.1384 128.8877 128.4805 127.5569 127.2878

7.8

157.1332

168.1362 167.7580 167.5835 165.0237

3.6716

3.7665

4.0553 4.0392 4.0061 3.9900

4.2340 4.1634

4.6454 4.6289 4.5968 4.5417 4.4760 4.4210

5.1348 5.1046 5.0330 4.9863

5.3607

5.4640

5.8725

5.9981

6.8887 6.8581 6.8264 6.7967 6.6399 6.6199 6.6019

7.3031 7.2700 7.2150 7.1940

7.8952 7.8665 7.7589 7.7306

300 MHz (CDCl3, 25ºC)

O Phth Ph

N

O PMP syn-(+)-3e

3.6

75 MHz (CDCl3, 25ºC)

(ppm)

40

45

170

160

150

140 6.6

130 6.4 6.2

120 6.0 5.8 5.6 (ppm)

110

100 5.4 5.2

90 5.0

Phth Ph

N

O PMP anti-()-3e

80

4.7535 4.7370

5.3822 5.2819 5.2322 5.1840

5.7138

5.8438

6.2582 6.2411 6.2226

7.0777 7.0475

7.3323 7.2700 7.2198

7.8597 7.8314 7.7569 7.7287

4.6 4.4

70 4.2

60

4.0 3.8

50

3.5406 3.4685

4.0665 4.0124 3.9969 3.9423 3.8839 3.8347 3.7402

4.4916 4.4215 4.3742 4.3061

O

4.5914

4.8

39.3223

6.8

43.4239

7.0

H N

55.5831 55.5031

N

60.3247 59.8083

7.2

H H

77.0000

O

83.9450

MeO

114.8449

7.4

123.4553 121.4554 120.0737

7.6

137.8399 134.0656 132.0802 131.3166 129.0259 128.4659 127.5641 127.2369

7.8

157.3296

167.5835 167.4671 167.4017 165.3145

300 MHz (CDCl3, 25ºC)

3.6

75 MHz (CDCl3, 25ºC)

(ppm)

40

46

170

160

150

140

130

120 4.5

110 4.0

100 (ppm) 3.5

90

80 3.0

70 2.5

60

2.0

50

1.5

40

30 21.7961

5.0

28.2103

5.5

51.2634 49.3290

6.0

59.3065 57.9103 56.4994 55.4741

6.5

77.0000

N

83.6396

O

116.7430 114.0232

N

122.1681

MeO H H

128.8732

7.0

134.1965

157.3732

167.6126 165.2927

172.0632

1.0733

2.0969

4.2783 4.2593 4.2174 4.1989 4.1313 4.1201 4.1069 4.0592 4.0451 3.7578 3.6175

4.6104 4.5938

5.2663 5.2122 5.1124 5.0837 4.9094 4.8923 4.8806 4.8636

5.9056 5.8530 5.8321 5.7800

6.2231

6.8342 6.8045

7.3177 7.2880 7.2700

300 MHz (CDCl3, 25ºC)

Ac

H N

O PMP

syn-(+)-3f

(ppm) 1.0

75 MHz (CDCl3, 25ºC)

20

47

170

160

150 6.0

140 5.6

130 5.2

120 4.8

75 MHz (CDCl3, 25ºC)

110 4.4 (ppm) 4.0

100 (ppm)

90 3.6

80

70 2.4

60

50

2.0

40

1.6

21.4325

28.5885

2.8

51.4234 50.0344

3.2

60.2956 58.0485 56.1286 55.5032

77.0000

N

83.8505

O

114.2704

6.4

H H

118.2920

N

122.0300

MeO

129.0404

6.8

132.9238

7.2

157.2860

167.4817 165.3073

171.9032

1.3158

1.6022

3.9438 3.9273 3.8873 3.8727 3.7895 3.5859 3.5557 3.5328 3.4992 3.4764

5.7683 5.7128 5.6963 5.6335 5.2210 5.2079 5.1874 5.1504 5.0209 5.0043 4.9888 4.9732 4.9449 4.9157 4.7161 4.7005

6.8868 6.8571

7.2700 7.2072 7.1775

300 MHz (CDCl3, 25ºC)

Ac H N

O PMP

anti-(+)-3f

1.2

30

48

170

160

150

140

130 5.6 5.2

120

110 4.8 4.4

100 (ppm)

90 4.0

80 3.6

70 3.2 2.8

60

50 21.3525

6.0

43.5403

N

H N

49.7944

6.4

H H

57.0885 55.7140 55.5177

N

77.0000

O

80.7961

PhO

118.0156 116.3576 114.3431

6.8

122.6263 122.1390

7.2

137.4326 132.6111 129.4840 128.8732 128.6550 128.0078 127.5496

7.6

157.6641 157.4968

163.8383

167.6053

172.1796

1.6036

4.3353 4.3153 4.2866 4.2666 4.2281 4.2101 4.1790 4.1619 4.0256 3.9428 3.8006 3.6029 3.5820 3.5464 3.5255

5.6480 5.5200 5.4981 5.4820 5.3534 5.3203 5.2974 5.2804 5.2663 5.2492 5.1781 5.0905

6.2757 6.2577 6.2392

7.3099 7.2700 7.2559 7.2267 7.1692 7.1376 7.0519 7.0129 6.9121 6.8824

300 MHz (CDCl3, 25ºC)

Ac Ph

O PMP

syn-(+)-3g

(ppm) 2.4 2.0

40 1.6

75 MHz (CDCl3, 25ºC)

30

20

49

170

160

150

140 6.0

130 5.6

120 5.2

110 4.8 (ppm)

100 (ppm) 4.4

90 4.0

80 3.6

70 3.2

60

50 21.7671

6.4

43.4457

N

H N

49.9617

6.8

H H

58.4848 56.0704 55.3941

N

77.0000

O

80.1125

PhO

117.3102 115.2740 114.0304

7.2

122.3354 121.4700

7.6

137.1199 133.5710 129.6295 128.8004 128.4805 127.5569 127.3314

157.3005 157.1696

163.4383

168.5652

172.2232

1.9352

4.2233 4.2014 4.1731 4.1512 4.0952 4.0309 4.0144 3.9818 3.9657 3.7899

5.6422 5.4508 5.4357 5.3276 5.3057 5.2945 5.2799 5.2619 5.2293 5.1796 5.1275 5.0954

5.7703

7.4020 7.3718 7.3513 7.3255 7.2978 7.2700 7.2160 7.1940 7.0640 7.0178 6.8936 6.8634 6.8405 6.8337

300 MHz (CDCl3, 25ºC)

Ac Ph

O PMP

anti-(+)-3g

2.8 2.4

40 2.0

75 MHz (CDCl3, 25ºC)

30

50

170 7.2 6.8

160 6.4

150

140 6.0 5.6

130 5.2

120

110 4.8 4.4

100 (ppm)

90 4.0

(ppm)

75 MHz (CDCl3, 25ºC)

80 3.6 3.2

70

60

50

2.8

21.9052

44.8420 43.1257

48.2745

N

56.5431 55.4522

O H N

59.8447

H H

77.0000

MeO

84.3523

N

117.7902

137.7526 135.6946 132.7057 128.8586 128.5459 127.7823 127.6878 127.4260 127.0696

172.5650 168.5871 168.2671

1.8695

4.6683 4.6518 4.6216 4.5685 4.4960 4.4789 4.4619 4.4507 4.4463 4.4292 4.2194 4.2019 4.1683 4.1522 4.1142 3.7451 3.7290 3.6881 3.6721 3.5055 3.4822 3.4491 3.4262

5.0399 4.9839

5.5054 5.4513 5.4289 5.3758 5.2716 5.2380

6.4709 6.4520 6.4335

7.3864 7.3333 7.2700 7.2121 7.1332

300 MHz (CDCl3, 25ºC)

Ac Ph

O Ph

syn-()-3h

2.4

40

2.0

30

51

170

160

150 6.0

140

130 5.6

120

75 MHz (CDCl3, 25ºC) 5.2 4.8 (ppm)

110

100 (ppm)

90

80

N

3.6

70

60

H N

N

3.2 2.8

50

40 22.1307

4.0

H H

43.7075 43.3075

PhO

48.3618

56.2304 55.0741

4.4

77.0000

81.3997

6.4

117.8847 116.1830

6.8

122.4008

7.2

137.4472 132.7638 131.8912 129.3459 128.5677 128.0005 127.4405

157.5332

168.0780 166.2236

172.4777

2.1384

4.3247 4.3041 4.2758 4.2557 4.2209 4.2026 4.1725 4.1533 4.0627 3.9818 3.9594 3.9251 3.9023 3.6357 3.6142 3.5818 3.5603

4.7175 4.7005 4.6841 4.6672

5.1294

5.2574

5.5692 5.5427 5.5093 5.3941 5.3777

5.8111

6.5147 6.4960 6.4772

7.0291 6.9486

7.2782 7.2700 7.2215 7.1790 7.1475

300 MHz (CDCl3, 25ºC)

Ac Ph

O O

syn-()-3i

2.4

30

52

170

160 6.4

150 6.0

140 5.6

130

120 80.5271

6.8

122.1899 118.3065 117.4920 115.2376

7.2

137.6144 133.0620 131.6293 129.5786 128.6623 127.6950 127.5569

157.2350

165.9836

169.2852

172.4268

5.2

110

75 MHz (CDCl3, 25ºC) 4.8 (ppm) 4.4

100 (ppm)

90

80

N

3.6

70

60

H H

3.2

50

H N

2.8

40 21.5416

N

43.8020 43.5184

PhO

49.3217

4.0

58.0630 55.6122

77.0000

1.8928

4.4614 4.4414 4.4122 4.3922 4.3757 4.3557 4.3260 4.3065 4.0485 3.9701 3.9019 3.8045 3.6453 3.6248 3.5932 3.5727

4.7029 4.6873 4.6693 4.6537

5.5414 5.3184 5.2858 5.2702 5.2215 5.1635 5.1299 5.1061 5.0715

5.8297

7.2700 7.2281 7.1478 7.1293 7.1098 7.0489 6.9545

300 MHz (CDCl3, 25ºC)

Ac Ph

O O

anti-(+)-3i

2.4 2.0

30

53

170

160

150

140

130 6.0

120 5.8

110 5.6 5.4 (ppm)

100 (ppm) 5.2

90 5.0

80 4.8

70

4.6 4.4

60 4.2

50

4.0

40

26.2177

6.2

43.5693 43.4821

6.4

48.2890

6.6

54.5723

6.8

57.5103

N

H N

77.0000

7.0

H H

81.4070

N

118.3502 118.2702 116.1830

PhO

122.5608

7.2

137.2217 132.8075 131.8112 129.4331 128.6623 128.0805 127.6005

7.4

157.4532

168.6889 167.4162 166.1363

4.2608 4.2355 4.2038 4.1342 4.0767 4.0382 4.0090 3.9730 3.8693 3.8328 3.6769 3.6545 3.6229 3.6005

4.7506 4.7346 4.7180 4.7014

5.1114

5.1971

5.4406 5.4065 5.3900 5.3091 5.2916

5.6213

5.7347

5.8487

6.3891 6.3706 6.3516

6.9759 6.9189

7.0689

7.2841 7.2700 7.2306 7.1838 7.1526

300 MHz (CDCl3, 25ºC)

O Br Ph

O O

syn-()-3j

3.8 3.6

75 MHz (CDCl3, 25ºC)

30

54

170

160

150

140

130 6.2 6.0

120 5.8

110 5.6 5.4 (ppm)

100 (ppm) 5.2

90 5.0

80 4.8

70

4.6 4.4

60 4.2

50

4.0

40

26.0868

6.4

43.8457 43.5548

6.6

48.7617

6.8

58.0121 55.4304

N

H N

77.0000

7.0

H H

80.5780

N

118.3502 117.9066 115.3540

PhO

122.2917

7.2

137.3744 132.9093 131.5712 129.5858 128.6477 127.6587 127.5641

7.4

156.9878

168.3471 168.1944 165.9763

4.6333 4.6172 4.6002 4.5841 4.4706 4.4507 4.4219 4.4015 4.3961 4.3757 4.3460 4.3265 4.1571 4.0962 4.0378 3.9925 3.9409 3.8995 3.8707 3.7305 3.6935 3.6536 3.6170 3.5839

5.6222 5.3203 5.3038 5.2692 5.2526 5.2234 5.2030 5.1772 5.1445 5.1178

5.9124

6.9491

7.0353

7.1181

7.3513 7.2982 7.2700 7.2427

300 MHz (CDCl3, 25ºC)

O Br Ph

O O

anti-(+)-3j

3.8 3.6

75 MHz (CDCl3, 25ºC)

30

55

170 6.8

160 6.4

150 6.0

140

130 5.6 5.2

120 4.8

110 4.4

100 (ppm)

90 4.0

(ppm)

75 MHz (CDCl3, 25ºC)

80 3.6 3.2

70

60

50

2.8

22.6868

43.5683

58.7991 58.0909 56.0957 55.4331 55.3494

H N

77.0000

O

N

82.6583

MeO H H

114.4679 113.8358

PMP

121.2380

7.2

137.1314 132.1281 128.9448 128.4041 127.6197 127.2390

159.5588 157.0077

164.9734

171.4922 169.1543

1.8120

4.4185 4.4015 4.3859 4.3689 4.3494 4.3328 4.1653 4.1483 4.1166 4.0996 4.0149 3.9944 3.9662 3.9457 3.8707 3.7646 3.7144

5.2278 5.1952

6.5226 6.5041 6.4860

7.2700 7.2369 7.2072 7.1887 6.9603 6.9306 6.8576 6.8313 6.8016

300 MHz (CDCl3, 25ºC)

Ac Ph

N

O PMP syn-(+)-3k

2.4

40

2.0

30

56

170

160

150

140

130 5.2

120 4.8

110 4.4 (ppm)

100 (ppm) 4.0

90 3.6

80 3.2

70 2.8

60

50 23.1056

5.6

43.5302

6.0

56.8572 55.5017 55.3950

6.4

59.9643

6.8

H N

77.0000

O

N

83.6330

MeO H H

114.5593 114.2318

PMP

123.7206

7.2

138.0833 129.1276 128.7087 128.6554 127.6730 127.4750

159.0257 157.9596

168.1642 165.9786

172.9772

1.6089

3.5055

3.8206 3.7636

5.1436 5.1260 5.1124 5.0954 4.9639 4.9332 4.6898 4.6732 4.5174 4.4984

6.7081 6.6789 6.5265 6.4987

6.9272 6.8975

7.3883 7.3299 7.2700 7.1882

300 MHz (CDCl3, 25ºC)

Ac Ph

N

O PMP anti-(+)-3k

2.4 2.0

40 1.6

75 MHz (CDCl3, 25ºC)

30

57

170

160

150

140 5.6

130 5.2

120 4.8

110 4.4

100 (ppm)

90 4.0

80 3.6

70 3.2

60

2.8

50

2.4

40 23.1197

6.0

43.5402 43.3075

6.4

58.9284 56.4631 55.3868

N

H N

77.0000

6.8

N

81.8651

PhO H H

117.4775 116.2485 114.7358

PMP

122.3499

7.2

137.8108 132.2257 131.7384 129.9785 129.3168 128.5895 128.0877 127.4478

159.5185 157.5623

168.2525 166.5435

172.6741

1.8592

3.9973 3.9243 3.8464 3.8211 3.7734

4.4833 4.4370 4.3733 4.3509 4.2822

5.3208 5.3062 5.2624 5.1850

5.8930 5.7659 5.7201 5.6904

7.3279 7.2700 7.2145 7.0207 6.9978 6.9691 6.8595 6.8293 6.7422

300 MHz (CDCl3, 25ºC)

Ac Ph

O O

syn-(+)-3l

(ppm) 2.0

75 MHz (CDCl3, 25ºC)

30

58

170

160 6.8

150 6.4

140

130 6.0 5.6

75 MHz (CDCl3, 25ºC)

120 5.2 4.8 (ppm)

110

100 (ppm)

90

80 3.6

70 3.2

60

2.8

50

40 22.5161

4.0

43.9257 43.5548

4.4

57.1176 55.5541 55.4086

N

H N

77.0000

N

80.5416

PhO H H

117.8193 115.7103 114.9031

PMP

122.3427

7.2

137.9126 131.8766 131.3385 129.8985 129.7313 128.6477 127.8041 127.5060

7.6

159.6858 157.2932

165.9254

171.8814 169.4452

1.8422

4.0217 3.9710 3.8746 3.8021 3.7841 3.6653 3.5947

4.5412 4.4916 4.4726 4.4551 4.4059

5.1733 5.1207 5.1046 5.0506

5.7566 5.6305 5.5959

6.8473 6.7699

7.4015 7.3377 7.2700 7.1536 7.1220 7.0777 7.0533 7.0290

300 MHz (CDCl3, 25ºC)

Ac Ph

O O

anti-(+)-3l

2.4 2.0

30

59

170

160

150

140

130

120

110

100

PMP

N

90 (ppm) 4.0

80 3.5

70 3.0

60

50

N

H H H N

2.5

40 14.1042

4.5 (ppm)

43.3550 40.9181 40.3470

PhO

55.9586 55.4712

5.0

61.4417 59.8501

5.5

77.0000

6.0

81.3560

6.5

117.9938 115.8996 115.2294

7.0

123.4769 122.3118

7.5

134.0928 132.1357 132.0291 130.4450 129.8587 129.3027

8.0

160.1071 157.3351

169.2761 168.3394 167.7530 167.6921 166.3670

1.3236 1.2997 1.2759

4.6089 4.5924 4.5807 4.5636 4.2768 4.2530 4.2291 4.2053 4.1955 4.1624 4.1351 4.1254 4.1054 4.0650 4.0446 4.0319 3.8420 3.8250 3.7480

5.3705 5.3072

5.9728 5.8452 5.6495 5.6208

7.8884 7.8602 7.7579 7.7292 7.4594 7.4297 7.2700 7.2427 7.2379 7.2135 7.0256 6.9939 6.9637 6.7826 6.7646 6.7456

300 MHz (CDCl3, 25ºC)

O Phth CO2Et

O O

syn-(+)-3m

2.0

30

1.5

75 MHz (CDCl3, 25ºC)

20

60

170

160

150

140

130

120

110

PMP

N

100

90 (ppm) 4.5 4.0

80 3.5

70 3.0

60

50

N

H H H N

2.5

40 14.1804

PhO

43.8501 41.2913 40.0500

5.0 (ppm)

57.5121 55.4864 54.9457

5.5

61.4950

6.0

77.0000

6.5

80.6554

7.0

117.8872 116.0824 115.3132

7.5

123.5302 122.4489

8.0

134.0548 132.1281 131.8463 130.7649 129.8282 129.0438

8.5

160.2518 157.3275

169.5960 168.9639 167.6845 167.6388 165.9786

1.3450 1.3212 1.2978

4.3406 4.3090 4.2846 4.2613 4.2393 4.2062 4.1473 4.1249 4.0884 4.0670 4.0324 4.0163 3.9491 3.8625 3.8186 3.7164 3.6453

5.1806 5.1606 5.1441 5.0696

5.7810 5.6514 5.6105 5.5765

6.8240

7.9171 7.8889 7.7633 7.7350 7.4687 7.4156 7.3839 7.3508 7.2700 7.2198 7.1999 7.1794 7.1337 7.1098 7.0864 7.0392

300 MHz (CDCl3, 25ºC)

O Phth CO2Et

O O

anti-(+)-3m

2.0

30

1.5

75 MHz (CDCl3, 25ºC)

20

61

160

150 6.6 6.4

140 6.2

130 6.0

O PMP

syn-(+)-4a

5.8 5.6

120 5.4 5.2 (ppm)

110 (ppm) 5.0

100 4.8 4.6

90 4.4

80

4.2 4.0

70

3.8 3.6

60

3.4

49.9729 49.7216 47.5055

6.8

59.9186 59.3322 55.7758 55.5321

N

Ph

77.0000

O N

82.8410

7.0

H H

114.8867

MeO

118.8011 118.4888

7.2

134.8163 131.1457 129.8587 128.8534 128.5640 128.2290

7.4

156.9848

164.5393 164.1433 163.3361

3.2494 3.1715

3.3414

3.8922 3.8352 3.8240 3.7782 3.7217

4.2647 4.2169

4.7677 4.7589 4.6537 4.6352 4.5778 4.4930 4.4356

5.0189 4.9824 4.9371 4.9322 4.9040 4.8899

5.5477 5.4873 5.4761 5.4163

6.9632 6.9330

7.4097 7.3796 7.3654 7.2700 7.2525

300 MHz (CDCl3, 25ºC)

O

N

3.2

75 MHz (CDCl3, 25ºC)

50

62

165

160

155

150

145

140

135 6.2

130 6.0

125

120 5.8

115 5.6

110 5.4

105 100 (ppm) 5.2

95 5.0

90 4.8

85

80 4.6

75

4.4

70

4.2

65

60

4.0

55

50

43.8093

6.4

49.5326 49.3508 47.3946

6.6

56.7176 55.9686

N

77.0000

6.8

N

81.8433

7.0

H H

120.2846 119.4628 116.7066

PhO

123.2517

7.2

134.5455 131.2512 130.7203 129.7095 128.8077 128.6404 128.1096

157.2423

165.2709 163.9473 163.1474

3.9562 3.8977 3.8424 3.7839 3.7427 3.7162 3.6915 3.6650

4.6164 4.5995 4.5844 4.5487 4.4376 4.4221 4.3773 4.3645 4.3490 4.3288

4.8267 4.7792

5.2990 5.2757 5.2281 5.2131

5.8499 5.7759 5.7539 5.6963

7.0752 7.0501 7.0249 6.9971

7.2951 7.2700 7.2321

300 MHz (CDCl3, 25ºC)

O

N Ph

O O

syn-(+)-4b

(ppm) 3.8

75 MHz (CDCl3, 25ºC)

45

63

165

160

155

150

145

140

135 6.2

130 6.0

125 5.8

120

115 5.6

110 5.4 (ppm)

105 (ppm) 5.2

100 5.0

95 4.8

90 4.6

85

80

4.4

75

4.2

70

4.0

65

3.8

60

55

3.6

50

43.6421

6.4

49.9035 49.3581 47.6273

6.6

59.1611 57.7212

6.8

77.0000

N

N

80.9707

7.0

H H

120.0010 117.9938 115.9431

PhO

123.0408

7.2

134.5892 131.6803 130.4949 129.8040 129.0550 128.5750 128.4005

7.4

156.8787

165.2855 164.5073 163.7801

3.4866 3.4082

4.3504 4.3328 4.3148 4.2720 4.1921 4.1439 4.0105 3.9525 3.8761 3.8182 3.7660 3.6911

4.8164 4.7686 4.6717 4.6557 4.6367 4.6036

5.1036

5.3359 5.3189 5.2716

5.6373

5.8321

7.0893 7.0275

7.3435 7.3202 7.2700 7.2296

300 MHz (CDCl3, 25ºC)

O

N Ph

O O

anti-(+)-4b

3.4

75 MHz (CDCl3, 25ºC)

45

64

170

160

150

140

130

120

110

100 (ppm) 4.4

90 4.0

80 3.6

70 3.2

60

50

2.8

40 21.4988

4.8 (ppm)

36.0747

5.2

43.2256

5.6

46.5307

6.0

55.6235 53.8643

6.4

O

79.6806 77.0000

6.8

HN H H

115.9453

PhO

122.4793 121.1619

7.2

137.4665 130.8944 129.4398 128.6478 127.6807 127.4903

7.6

157.3275

164.2499

167.7149

171.9110

2.1489

4.4386 4.3645 4.3375 4.3160 4.2539 4.2164 4.1985 4.1505 4.1341 4.0870 3.8072 3.7523

4.6873 4.6365

5.2826 5.2670

5.8824 5.7823 5.7370 5.5980 5.5628

6.6574

7.2782 7.2700 7.2252 7.1246 7.0926 7.0323 7.0080 6.9833 6.9646 6.9330

300 MHz (CDCl3, 25ºC)

Ph

N Ac

O N

()-5a

2.4

75 MHz (CDCl3, 25ºC)

30

65

170

160

150

140

130

120

110

100 (ppm) 4.4

90 4.0

80 3.6

70 3.2

60

50

40 21.4543

4.8 (ppm)

37.1043

5.2

43.3803 41.5549

5.6

52.6670

6.0

58.8775

6.4

O

78.5854 77.0000

6.8

HN H H

115.7394

PhO

122.6335

7.2

137.6872 131.7457 129.6077 128.6041 127.9205 127.4478 126.8951

157.0460

163.7801

167.1035

170.6597

2.2424

4.0470 4.0251 3.9754 3.9024

4.2958 4.2320 4.2067

4.7126 4.6255 4.5729 4.5028

5.1674 5.1499

5.5039

6.4807 6.4627 6.4451 6.2431 6.2090 6.1871 6.1535 6.0089 5.9826 5.9499 5.9232

7.2700 7.2262 7.2116 7.0338 7.0090 6.9847 6.9238 6.8946

300 MHz (CDCl3, 25ºC)

Ph

N Ac

O N

(+)-5b

2.8 2.4

75 MHz (CDCl3, 25ºC)

30

66

X-Ray data for compound anti-(+)-2d

Table 1. Crystal data and structure refinement for C22H24N2O6. Empirical formula

C22 H24 N2 O6

Formula weight

412.43

Temperature

296(2) K

Wavelength

0.71073 Å

Crystal system

Orthorhombic

Space group

P2(1)2(1)2(1)

Unit cell dimensions

a = 9.4466(14) Å

= 90°.

b = 12.1860(18) Å

= 90°.

c = 18.704(3) Å

 = 90°.

Volume

2153.2(6) Å3

Z

4

Density (calculated)

1.272 Mg/m3

Absorption coefficient

0.093 mm-1

F(000)

872

Crystal size

0.56 x 0.18 x 0.09 mm3

Theta range for data collection

1.99 to 26.00°.

Index ranges

-11