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
2
Preparation and Characterization of U-4CR Adducts 3a-h and 3j-m
8
Figure S1. Observed NOE for compounds 5
19
Table S1. Representative chemical shifts and vicinal coupling constants of 1H and 13
C NMR of compounds 2
20
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
22
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
67
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 148149°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 147148°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);
13
C NMR (75 MHz, CDCl3, 25°C) 166.9,
2
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
3
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);
13
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 179181°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);
13
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,);
13
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);
13
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,
5
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 165166°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 159161°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,
6
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);
13
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
13
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 7779°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);
13
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 130132°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 157158°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 17678°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 134135°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 137138°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 158159°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