,
, , vol.16, pp.1585-1591, 2010.
, Tetrahedron Lett, vol.16, pp.1742-1744, 2010.
, Chem. Eur. J, vol.18, pp.13959-13963, 2012.
, Chem. Eur. J, vol.16, pp.13930-13934, 2010.
, , vol.17, pp.13958-13962, 2011.
, Following the typical procedure II-F, starting from 233 (65 mg), compound 248 was obtained as a white solid (100 mg, 1:1 dr, 90% yield) after flash column chromatography
, 300 MHz, CDCl3) 248a-b ? 7.56 -7.36 (m, 4H), 7.25 -7.07 (m, 4H), 5.95 -5.77 (m, 1H), 5.77 -5.59 (m, 1H)
, 75 MHz, CDCl3) 248a-b ? 158, vol.9, p.39
, Following the typical procedure II-F, starting from 234 (85 mg), compound 249 was obtained as a white solid (76 mg, 1:2.3 dr, 57% yield) after flash column chromatography
, 300 MHz, CDCl3) 249a-b ? 8.03 -7.81 (m, 4H), 7.83 -7.59 (m, 2H), 7.59 -7.43 (m, 3H), 7.41 -7.28 (m, 3H), 6.03 -5.81 (m, 1H), 5.81 -5.65 (m, 1H), 5.55 -5.39 (m, 4H)
, 75 MHz, CDCl3) 249a-b ? 157.3 (2C), 157.0 (2C), 134.1 (2C), 130.9, 130.9, 129.9, 129.7, 129.5 (2C)
,
,
, , vol.128
, 282 MHz, CDCl3) ? -112.8 ppm. mp (°C), pp.108-112
,
, Following the typical procedure III-C, starting from 300 (50 mg, p.76
, 300 MHz, CDCl3) ? 7.51 -7.42 (m, 2H), 7.14 (ddd, J = 8.7, 5.9
, 42 (s, 1H) ppm, vol.1
, 75 MHz, CDCl3) ? 163.2 (d, JC-F = 252 Hz), 136.1, 130.3 (d, JC-F = 8 Hz, vol.7, p.41
, 282 MHz, CDCl3) ? -113, vol.2
, MS (CI-NH3) m/z = 271 (M+H + )
, Enantiomeric ratio (er) determined by chiral phase SFC analysis in comparison with authentic racemic material after reduction to the alcohol (AD-H column, 150 bar, 3 mL/min, 10% MeOH) : t (major isomer) = 18.04 min, t (minor isomer) = 2
, 5:8:2.5 dr, 54% overall yield) after flash column chromatography (cyclohexane / ethyl (dd, J, vol.89
,
, MS (CI-NH3) m/z = 283 (M+H + )
, Enantiomeric ratio (er) determined by chiral phase SFC analysis in comparison with authentic racemic material after reduction to the alcohol (AD-H column, 150 bar, 3 mL/min, 10% MeOH) : t (major diastereomer) = 4.06 min, t (minor diastereomer) = 2.28 min, 99.6/0.4 er, Methyl, vol.3, issue.2, p.304
, 79% overall yield) after flash column chromatography (cyclohexane / ethyl acetate 9:1). A fraction containing isomers a and c was obtained after a second flash column chromatography (cyclohexane / tert-butyl methyl ether 10:1) as a clear oil, vol.121, p.9
, 300 MHz, CDCl3) ? 9.68 (d, J = 1.0 Hz, 1H), 8.18 -8.01 (m, 2H), 7.71 -7.61 (m, 1H), 7.51 (t, J = 7.7 Hz, 1H), 5.72 (ddd, J = 16, vol.9
,
, Methyl, vol.3, issue.2
, Following the typical procedure III-C, starting from 304 (51 mg, p.75
, 92 (s, 3H), 3.81 (d, J = 10.9 Hz, 1H), 3.71 (dd, 300 MHz, CDCl3) ? 8.17 -8.03 (m, 2H), 7.69 (d, J = 7.8 Hz, 1H), 7.52 (dd, J = 9.6, 5.9 Hz, 1H), 6.14 -5.96 (m, 1H), 5.34 -5.22 (m, 2H), vol.3
,
, MS (CI-NH3) m/z = 311 (M+H + )
, Enantiomeric ratio (er) determined by chiral phase SFC analysis in comparison with authentic racemic material after reduction to the alcohol, p.10
, MeOH) : t (major enantiomer) = 2.27 min, t (minor enantiomer) = 1.71 min, 99.6/0.4 er. 3-formyl-2-(naphthalen-2-yl)-4-vinylcyclopentane-1,1-dicarbonitrile
, 90:8:2 dr, 67% overall yield) after flash column chromatography (cyclohexane / ethyl acetate 15:1). A fraction containing isomers a and c was obtained after a second flash column chromatography (cyclohexane / tert-butyl methyl ether 15:1) as an off-white solid, Following the typical procedure III-B, compound 305 was obtained as a yellow solid, vol.101
, 300 MHz, CDCl3) ? 9.73 (d, J = 1.3 Hz, 1H), 8.06 -7.76 (m, 4H), 7.65 -7.47 (m, 3H), 5.77 (ddd, J = 16.9, 10.1, 8.7 Hz, 1H)
, , pp.148-152
, 98% overall yield) after flash column chromatography (cyclohexane / ethyl acetate 20:1). A fraction containing isomers a and c was obtained after a second flash column chromatography (cyclohexane / tert-butyl methyl ether 40:1) as a white solid
, 300 MHz, CDCl3) ? 9.66 (d, J = 2.3 Hz, 1H), 7.93 -7.79 (m, 1H), 7.79 -7.60 (m, 3H), 7.09 -6.87 (m, 2H), 6.80 -6.61 (m, 2H), 5.94 -5.90 (m, 1H), 5.36 -5.10 (m, 2H)
,
, 282 MHz, CDCl3) ? -115.63. mp (°C), pp.123-127
, , vol.307
, Following the typical procedure III-C, starting from 307 (50 mg, p.72
, 300 MHz, CDCl3) ? 7.85 -7.77 (m, 1H), 7.71 -7.48 (m, 4H), 7.37 -7.30 (m, 2H), vol.7
, Partie expérimentale 3-(hydroxymethyl)-2-(naphthalen-2-yl)-4-vinylspiro, vol.308, p.3
, Following the typical procedure III-C, starting from 308 (131 mg
, 18 (dd, J = 8.6, 1.7 Hz, 1H), 6.17 (dt, J = 17.1, 9.8 Hz, 1H), 5.30 -5.08 (m, 2H), 3.78 (d, J = 11.6 Hz, 1H), 3.52 (dd, 300 MHz, CDCl3) ? 7.85 -7.74 (m, 1H), 7.73 -7.41 (m, 7H), 7.41 -7.27 (m, 2H), vol.7
,
, MS (CI-NH3) m/z = 383 (M+H + )
, Enantiomeric ratio (er) determined by chiral phase SFC analysis in comparison with authentic racemic material after reduction to the alcohol (IA column, 150 bar, 3 mL/min
, 56 min, t (minor enantiomer) = 20.36 min, 99.2/0.8 er, vol.15, pp.9-15
, Following the typical procedure III-B, compound 309 was obtained as an orange oil (228 mg, 81:19 dr, 67% overall yield) after flash column chromatography (cyclohexane, vol.12
, Partie expérimentale (tert-butoxycarbonyl)glycine (327)
, A solution of glycine (15.0 g, 200 mmol, 1.0 equiv) and NaHCO3 (16.8 g, 200 mmol, 1.0 equiv) in water (200 mL) was slowly added and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was partitioned with water (300 mL), AcOEt (100 mL) and petroleum ether (100 mL). The organic layer was discarded and the aqueous phase, a round-bottomed flask, di-tert-butyl dicarbonate (43.6 g, 200 mmol, 1.0 equiv) was dissolved in THF (150 mL
, × 150 mL), the combined organic extracts were washed with an aqueous saturated solution of sodium chloride (2 × 150 mL), dried over anhydrous magnesium sulphate
, MHz, CDCl3) ? 11.96 (s, 1H), 6.81 (s, 1H), 3.90 (m, 2H), 1.43 (s, 9H) ppm. tert-butyl (2-(methoxy(methyl)amino
, mmol, 1.0 equiv) and Nmethylmorpholine (24.8 mL, 226 mmol, 2.2 equiv) were dissolved in CH2Cl2 (350 mL) and cooled to ?15 °C. Isobutyl chloroformate (1.06 mL, 123 mmol, 1.2 equiv) was added dropwise, p.103
, 300 MHz, CDCl3)
,
, N-tosyl-4-vinyl-1,4-dihydro-2H-benzo
, 300 MHz, CDCl3) ? 8.09 (d, J = 8.2 Hz, 2H), 7.61 (d, J = 8.2 Hz, 1H), 7.40 (dd, J = 16.4, 7.2 Hz, 3H), 7.25 (t, J = 7.2 Hz, 1H), 7.19 (d, J = 7.2 Hz, 1H)
,
, N-benzyl-4-vinyl-1,4-dihydro-2H-benzo
, 300 MHz, CDCl3) ? 7.43 -7.16 (m, 1H), 7.16 -6.98 (m, 1H), 6.83 (d, J = 8.1 Hz, 1H), vol.6
, Nat. Commun, vol.5, pp.5500-5510, 2014.
, Following the typical procedure IV-A starting from 2-hydroxyacetophenone (5.45 g
, 343 was obtained as an off-white solid (3.17 g, 43% yield) after trituration in heptane and filtration
, 300 MHz, CDCl3) ? 7.81 (dd, J = 1.3, 7.9 Hz, 1H), 7.70 -7.75 (m, 1H), vol.7
, 1H), 7.30 (d, J = 8.3 Hz, 1H), 2.74 (s, 3H) ppm
, MHz, issue.75
, MS (CI-NH3) m/z = 215 (M+NH4 + )
, 400 MHz, CDCl3) ? 8.68 (s, 1H), vol.7
, 100 MHz, CDCl3) ? 167.9
, MS (CI-NH3) m/z = 201 (M+NH4 + )
, Following the typical procedure IV-A starting from 4-methyl-2-hydroxybenzaldehyde (1.36 g, 10 mmol) compound 346 was obtained as a white solid (382 mg, 19% yield) after flash column chromatography
, 08 (s, 1H), 2.49 (s, 3H) ppm
,
, Following the typical procedure IV-A starting from 5-methyl-2-hydroxybenzaldehyde (1.36 g, 10 mmol) compound 347 was obtained as a white solid (668 mg, 34% yield) after flash column chromatography
, 300 MHz, CDCl3) ? 8.61 (s, 1H), vol.7
,
, Following the typical procedure IV-A starting from 4-fluoro-2-hydroxybenzaldehyde (1.40 g, 10 mmol) compound 348 was obtained as a white solid (400 mg
, 300 MHz, d6 DMSO) ? 9.17 (s, 1H), 7.91 (dd, J = 7.7, 3.1 Hz, 1H), vol.7
,
, 120.4 (d, JC-F = 8 Hz), 117.7 (d, JC-F = 25 Hz), 115.9 (d, JC-F= 9 Hz) ppm
, 376 MHz, d6 DMSO) ? -114.5 (m) ppm
, Following the typical procedure IV-A starting from 4-bromo-2-hydroxybenzaldehyde (2.01 g, 10 mmol) compound 351 was obtained as a white solid (540 mg
, 400 MHz, CDCl3) ? 8.62 (s, 1H), 7.87 -7.81 (m, 2H), 7.21 (d, J = 9.6 Hz, 1H) ppm. mp (°C) =151-153. 5-methylbenzo
, Imine 351 was prepared from N-tosyl-tert-butylamine (1.13 g, 5 mmol) according to the procedure described by Zhang et al. 158 to afford the desired compound as an off-white solid (480 mg, 53% yield)
, 300 MHz, CDCl3) ? 8.73 (s, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H), vol.7
,
, 300 MHz, CDCl3) ? 8.95 (s, 1H), 7.86 -7.80 (m, 4H), 7.43 -7.38 (m, 2H), 7.28 -7.25 (m, 2H), vol.2
,
, Following the typical procedure IV-B, compound 345 was obtained as an orange solid (55 mg, > 20:1 dr, 91% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, 300 MHz, CDCl3) ? 7.59 -7.45 (m, 2H), 7.45 -7.35 (m, 1H), 7.25 -7.19 (m, 1H), 5.91
,
, , p.41
, MS (CI-NH3) m/z = 319 (M+NH4 + )
, Following the typical procedure IV-B, compound 354 was obtained as a white solid (44 mg, > 20:1 dr, 70% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, 03 (s, 1H), 5.90 (ddd, J = 17.1, 10.2, 6.9 Hz, 1H), 5.53 (d, J = 17.1 Hz, 1H), 5.46 -5.37 (m, 2H), vol.7
, MHz, CDCl3) ? 150.7, 143.2, 133.9, vol.127
, Following the typical procedure IV-B, compound 355 was obtained as a white solid (47 mg, > 20:1 dr, 75% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, 400 MHz, CDCl3) ? 7.31 (d, J = 8.4 Hz, 1H), 7.26 (s, 1H), 7.10 (d, J = 8.4 Hz, 1H), 5.90 (ddd, J = 17.1, 10.2, 7.1 Hz, 1H), 5.53 (d, J = 17.1 Hz, 1H), 5.46 -5.39 (m, 2H)
, , vol.5, p.5
, Following the typical procedure IV-B, compound 356 was obtained as a white solid (40 mg, 15:1 dr, 53% yield) after flash column chromatography (cyclohexane / ethyl acetate 95:5 to, vol.9
, 400 MHz, CDCl3) ? 7.67 -7.59 (m, 2H), 7.11 (d, J = 8.7 Hz, 1H), 5.90 (ddd, J = 17.0, 10.4, 7.1 Hz, 1H), 5.54 (d, J = 17.0 Hz, 1H), 5.43 (d, J = 10.4 Hz, 1H), vol.5
, MHz, issue.101, p.41
, Following the typical procedure IV-B, compound 357 was obtained as a white solid (69 mg, 1.4:1 dr, 94% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, 300 MHz, CDCl3) 357a-b ? 7.46 (brd, J = 7.7 Hz, 1H), 7.39 (brd, J = 7.9 Hz, 1H), 7.35 -7.26 (m, 2H)
, 36 (d, J = 5.3 Hz, 1H), 5.30 (s, 1H), Hz, 1H), 5.93 (s, 1H), 5.86 (ddd, J = 17.1, 10.3, 7.0 Hz, 1H), 5.45 (d, J = 13.3 Hz, 1H), vol.5
, , pp.151-153
, MS (CI-NH3) m/z = 381 (M+NH4 + )
, Following the typical procedure IV-B, compound 358 was obtained as a white solid (70 mg, 1.3:1 dr, 83% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.95
, 300 MHz, CDCl3) 358a-b ? 7.63 -7.54 (m, 1H), 7.54 -7.45 (m, 1H), 7.34 -7.24 (m, 2H), 7.20 -7.10 (m, 2H), vol.7
, Partie expérimentale
,
, , vol.21
, Following the typical procedure IV-B, compound 359 was obtained as a colourless oil (63 mg, > 20:1 dr, 63% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.95
, 300 MHz, CDCl3) ? 7.43 (d, J = 8.0 Hz, 1H), 7.34 (td, J = 7.7, 1.0 Hz, 1H), 7.20 (td, J = 7.7, 1.0 Hz, 1H)
, Hz, 1H), 5.43 (d, J = 17.0 Hz, 1H), 5.29 (d, J = 10.2 Hz, 1H)
,
, , vol.120
, 7 Hz), 39.6 ppm. 3-vinyl-2,3-dihydro-10bH-spiro, vol.5, p.5
, Following the typical procedure IV-B, compound 360 was obtained as a white solid (50 mg, > 20:1 dr, 66% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, Partie expérimentale
, Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.02 (d, J = 8.2 Hz, 2H), 6.75 (t, J = 7.5 Hz, 1H), vol.6
,
, , pp.176-178
, Following the typical procedure IV-B, compound 361 was obtained as a white solid (42 mg, > 20:1 dr, 70% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, 44 (s, 1H), 5.93 (ddd, 300 MHz, CDCl3) ? 7.76 (d, J = 8.1 Hz, 1H), 7.55 (d, J = 8.1 Hz, 1H), vol.7
, 55 (s, 3H) ppm, vol.2
, , p.22
, MS (CI-NH3) m/z = 317 (M+NH4 + )
, Following the typical procedure IV-B, compound 362 was obtained as an orange solid (37 mg, > 20:1 dr, 49% yield) after flash column chromatography (cyclohexane / ethyl acetate, vol.9
, 300 MHz, CDCl3) ? 7.63 -7.56 (m, 2H), 7.48 -7.35 (m, 5H), vol.7
, 43 (s, 3H) ppm, vol.2
, 75 MHz, CDCl3) ? 144.9