4. ExperimentalInfrared spectra were recorded on a Perkin Elmer-1600 model 1605 spectrophotometer (KBr). NMR spectra were recorded on a Varian Gemini-200 (1H: 200 MHz and 13C: 50.3 MHz) spectrometer, using CDCl3 as the solvent and TMS as internal standard. Coupling constants (J) are reported in Hertz (Hz), and multiplicities are indicated as singlet (s), broad singlet (bs), doublet (d), broad doublet (bd), double doublet (dd), triplet (t), and multiplet (m). Low-resolution mass spectra (LRMS) were obtained by electron impact (70 eV) on a Varian GC-MS Saturn 2000 spectrometer. Thin-layer chromatography was performed on aluminium sheets coated with 60 F254 silica and visualization by UV light and/or for contact of the plates with 7% ethanolic solution of phosphomolybdic acid and posterior heating. The purifications by column chromatography were performed on silica gel (230–400 mesh). The solvents and reagents were dried and purified by usual procedures [19].
4.1. 2-Pyrrolidinone(1)It is used as starting material to obtain some compounds. Rf 0.18 (EtOAc). 1H NMR (200 MHz, CDCl3): δ 6.61 (bs, 1H), 3.40 (m, 2H), 2.36–2.22 (m, 2H), 2.22–2.03 (m, 2H).
4.2. N-(tert-butoxycarbonyl)-2-pyrrolidinone(2)2-Pyrrolidinone(1) (2.000 g, 23.500 mmol) was added to a stirred suspension of NaH (0.677 g, 28.200 mmol) in THF (47 mL), at room temperature and nitrogen atmosphere. After 15 minutes, (Boc)2O (6.154 g, 28.200 mmol) was added and the mixture was stirred at room temperature and nitrogen atmosphere for 40 minutes. Saturated solution of NH4Cl (60 mL) was added and then extracted with EtOAc (2 × 200 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with 30% EtOAc/hexane and crescent gradient of EtOAc (50 and 100%). A colourless oil was obtained (3.043 g, 70%), characterized as the pyrrolidinone 2. Rf 0.33 (50% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 3.75 (m, 2H), 2.51 (m, 2H), 2.00 (m, 2H), 1.53 (s, 9H).
4.3. N-(tert-butoxycarbonyl)-3-thiophenoxy-2-pyrrolidinone(3)n-BuLi 1.85 mol L−1 (3.0 mL, 5.520 mmol) was added dropwise to a stirred solution of diisopropylamine (0.55 mL, 3.940 mmol) in THF (26 mL) at 0°C and stirred for 20 minutes under nitrogen atmosphere. The stirred solution was put on a bath at −78°C, and the pyrrolidinone 2 (0.552 g, 2.820 mmol) in THF (2.8 mL) was added. After 30 minutes (PhS)2 (0.860 g, 3.94 mmol) in THF (39 mL) was added and left under magnetic stirring, −78°C and nitrogen atmosphere for 15 minutes, and then at room temperature for 2 h. The mixture was concentrated in vacuum, diluted with EtOAc (50 mL), and then washed with saturated solution of NH4Cl (1 × 50 mL) and H2O (1 × 50 mL). The organic layer was separated, and the aqueous phases were extracted with EtOAc (2 × 50 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with 20% EtOAc/hexane. Pyrrolidinone 3 (0.070 g, 16%) was obtained as a colourless oil, and substrate 2 (0.247 g, 47%) was recovered without reacting. Pyrrolidinone 3: Rf 0.61 (50% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 7.60–7.45 (m, 2H), 7.40–7.30 (m, 3H), 3.90–3.80 (m, 1H), 3.70–3.45 (m, 2H), 2.55–2.25 (m, 1H), 2.15–1.90 (m, 1H), 1.52 (s, 9H). Minor isomer: δ 1.43 (s, 9H).
4.4. 3-iodine-2-pyrrolidinone(4a): Kinetic ProductTo a solution of 2-pyrrolidinone(1) (0.569 g, 6.686 mmol) in CH2Cl2 (15 mL) at −15°C and magnetic stirring, Et3N (4.7 mL, 33.430 mmol) and then TMSCl (2.5 mL, 20.058 mmol) were added. After 10 minutes, I2 (3.394 g, 13.372 mmol) in CH2Cl2 (20 mL) was added, and the mixture was transferred to a bath at 0°C. After 2 h, the mixture was washed with aqueous solution of 10% Na2SO3 (2 × 100 mL) and then saturated solution of NaCl (1 × 100 mL). The organic layer was separated, and the aqueous phases were extracted with CH2Cl2 (3 × 100 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with EtOAc. A yellowish crystalline residue was obtained (0.352 g, 25%) characterized as 3-iodine-2-pyrrolidinone (4a + 4b/5 : 1). Major product (4a): Rf 0.23 (EtOAc). 1H NMR (200 MHz, CDCl3): Table 2.
4.5. 3-iodine-2-pyrrolidinone(4b): Thermodynamic Product (Experiment 1, Table 1)A mixture of 3-iodine-2-pyrrolidinone (4a + 4b/5 : 1) (0.060 g, 0.284 mmol), LiCl (0.060 g, 1.415 mmol), and DMF (1.4 mL) was heated at 100°C, under magnetic stirring and nitrogen atmosphere for 5 h. The mixture was concentrated in vacuum, diluted with CH2Cl2 (20 mL), and then washed with H2O (1 × 20 mL). The organic layer was separated, and the aqueous phase was extracted with CH2Cl2 (1 × 30 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with EtOAc. A colourless crystalline residue (0.024 g, 40%) was obtained characterized as 3-iodine-2-pyrrolidinone (4a + 4b/1 : 10). Major product (4b): Rf 0.30 (EtOAc). 1H NMR (200 MHz, CDCl3): Table 2.
4.6. Elimination Reaction Performed with Lactam 4 : (Experiment 2, Table 1)A mixture of 3-iodine-2-pyrrolidinone (4a + 4b/5 : 1) (0.037 g, 0.175 mmol), Et3N (0.12 mL, 0.875 mmol), and CH3CN (0.5 mL) was stirred at 25°C for 72 h. The mixture was concentrated in vacuum, diluted with EtOAc (20 mL), and then washed with saturated solution of NH4Cl (1 × 30 mL) and H2O (1 × 30 mL). The organic layer was separated, and the aqueous phases were extracted with EtOAc (1 × 30 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with EtOAc and 10% MeOH/EtOAc. A brownish oil (0.014 g, 41%) was obtained characterized by 1H NMR as a mixture of 3-iodine-2-pyrrolidinone (4a + 4b) and 3-pyrrolin-2-one(5), previously described [1], in a respective proportion of (1 : 5 : 1).
4.7. Elimination Reaction Performed with Lactam 4: (Experiment 3, Table 1)A mixture of 3-iodine-2-pyrrolidinone (4a + 4b/5 : 1) (0.046 g, 0.218 mmol), Et3N (0.15 mL, 1.09 mmol), and CH3CN (0.6 mL) under magnetic stirring and nitrogen atmosphere was heated at 85°C for 3 h. The mixture was concentrated in vacuum, diluted with EtOAc (20 mL), and then washed with saturated solution of NH4Cl (1 × 20 mL) and H2O (1 × 20 mL). The organic layer was separated, and the aqueous phases were extracted with EtOAc (1 × 30 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with 50% EtOAc/hexane and EtOAc. A colourless crystalline residue was obtained (0.012 g, 27%) characterized as 3-iodine-2-pyrrolidinone (4b) (Rf 0.30, EtOAc) and a brownish oil (0.003 g, 13%) characterized as 3-pyrrolin-2-one(5), previously described [1].
4.8. N-(tert-butoxycarbonyl)-2-hydroxy-pyrrolidine(6)NaBH4 (0.012 g, 0.317 mmol) was added to a solution of the pyrrolidinone 2 (0.053 g, 0.286 mmol) in MeOH (1.0 mL). The mixture was left under magnetic stirring, room temperature, and nitrogen atmosphere for 5 h. H2O (30 mL) was added and then extracted with CH2Cl2 (2 × 50 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with 50% EtOAc/hexane and EtOAc. A colourless oil (0.040 g, 75%) was obtained characterized as the hemiaminal 6. Rf 0.22 (60% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 4.66 (bs, 1H), 3.67 (m, 2H), 3.15 (m, 2H), 1.58 (m, 3H), 1.44 (s, 9H).
4.9. N-(tert-butoxycarbonyl)-3-(α-hydroxy-benzyl)-2-pyrrolidinone(7)n-BuLi 1.41 mol L−1 (1.15 mL, 1.621 mmol) was added dropwise to a stirred solution of diisopropylamine (0.21 mL, 1.498 mmol) in THF (5.0 mL) at 0°C and stirred for 10 minutes under nitrogen atmosphere. The stirred solution was put in a bath at −78°C, and pyrrolidinone 2 (0.248 g, 1.339 mmol) in THF (6.0 mL) was added. After 30 minutes, benzaldehyde (0.15 mL, 1.475 mmol) was added dropwise, and the mixture was left at −78°C for 2.5 h and then at room temperature for 1 h. Aqueous solution of 10% HCl (v/v) was added until pH 1, and the mixture was transferred to a separatory funnel, diluted with EtOAc (50 mL), and then washed with H2O (1 × 50 mL). The organic layer was separated, and the aqueous phase was extracted with EtOAc (1 × 50 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with hexane and crescent gradient of EtOAc (70 and 100%). A colourless crystalline residue was obtained (0.114 g, 29%) characterized as a mixture of isomers 7. Rf 0.27 (EtOAc). 1H NMR (200 MHz, CDCl3): δ 7.55–7.28 (m, 5H), 7.23 (bs, 1H, D2O exchange), 3.57 (t, J 6.5 Hz, 2H), 3.28 (m, 1H), 3.22-3.10 (m, 2H), 1.80 (m, 1H), 1.41 (s, 9H). Minor isomers: δ 7.25–7.20 (m, 1H, D2O exchange), 6.80 (bs, 1H, D2O exchange), 6.60 (bs, 1H, D2O exchange), 4.83 (bd, J 7.5 Hz, 1H), 4.72 (d, J 9.6 Hz, 1H), 3.32–3.23 (m, 1H), 2.86 (m, 1H), 2.71 (m, 1H), 1.44 (s, 9H).
4.10. N-benzyl-2-hydroxy-pyrrolidine(9)4.10.1. Preparation of the Grignard ReagentA mixture of magnesium (0.027 g, 1.111 mmol), bromobenzene (0.11 mL, 1.044 mmol), and THF (5.0 mL) was heated at reflux, under magnetic stirring and argon atmosphere for 3 h. It was then allowed to cool at room temperature, and the recently prepared solution of the Grignard reagent was used in the following reaction.
4.10.2. Reaction of PhMgBr-CuBr·SMe2 with N-benzyl-3-pirrolin-2-one(8), TMSCl/THFThe recently prepared solution of the Grignard reagent (5.0 mL) was added to a stirred suspension of CuBr·SMe2 (0.031 g, 0.151 mmol) in THF (0.5 mL) at room temperature and stirred for 10 minutes under argon atmosphere. The stirred mixture was put in a bath at −78°C, and then a solution of lactam 8 (0.116 g, 0.669 mmol) and TMSCl (0.17 mL, 1.339 mmol) in THF (2.0 mL) was added. The mixture was left at −78°C for 3 h and then allowed to reach the room temperature. The mixture was transferred to a separatory funnel, and EtOAc (40 mL) was added and then washed with saturated solution of NH4Cl (1 × 20 mL). The organic layer was separated, and the aqueous phase was extracted with EtOAc (1 × 40 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with EtOAc. A brownish crystalline residue was obtained characterized as compound 9 (0.078 g, 66%). Rf 0.24 (EtOAc). IR (KBr) νmax /cm−1: 3172, 2927, 1643, 1448, 1331, 1259, 1076, 996, 946, 700. 1H NMR (200 MHz, CDCl3): δ 7.38–7.24 (m, 5H), 5.08 (m, 1H), 4.83 (d, J 14.7 Hz, 1H), 4.20 (d, J 14.7 Hz, 1H), 3.21 (bd, J 7.2 Hz, 1H, D2O exchange), 2.72–2.50 (m, 2H), 2.46–2.16 (m, 3H), 2.06–1.80 (m, 1H). m/z (%): 177 (M+., 1%), 173 (100), 91 (100), 65 (30).
4.11. N-benzyl-2-pyrrolidinone(10)A mixture of lactam 8 (0.100 g, 0.577 mmol), 20% Pd(OH)2/C (0.041 g, 0.0577 mmol), and MeOH (6.0 mL), inside a round-bottom flask, was submitted to hydrogen atmosphere (balloon) under magnetic stirring and room temperature for 12 h. The mixture was filtered, concentrated in vacuum, and then purified over column chromatography of silica gel eluted with EtOAc. A brownish oil was obtained characterized as the lactam 10 (0.088 g, 87%). Rf 0.47 (EtOAc). 1H NMR (200 MHz, CDCl3): δ 7.39–7.20 (m, 5H), 4.45 (s, 2H), 3.26 (m, 2H), 2.45 (m, 2H), 1.99 (m, 2H).
4.12. Mixture of the Probable Isomers 11–13A solution of lactam 8 (0.102 g, 0.589 mmol) in S-α-methylbenzylamine (0.5 mL, 3.878 mmol) was left under magnetic stirring, room temperature, and nitrogen atmosphere for 72 h. The mixture was transferred to a separatory funnel, diluted with EtOAc (30 mL), and then washed with aqueous 10% HCl (v/v) (1 × 20 mL) and H2O (1 × 20 mL). The organic layer was separated, and the aqueous phases were extracted with EtOAc (1 × 30 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with hexane and 50% EtOAc/hexane. A colourless oil was obtained characterized as a mixture of the probable isomers 11–13 (0.079 g, 48%). Rf 0.30 (50% EtOAc/hexane). IR (KBr) νmax /cm−1: 3418, 2924, 1743, 1689, 1613, 1496, 1429, 1396, 1339, 1292, 1254, 1188, 1129, 1061, 1014, 930, 871, 823, 696, 626, 522, 458, 433, 408. 1H NMR (200 MHz, CDCl3): δ 7.44–7.20 (m), 7.10–7.00 (m), 4.93 (s), 4.63 (s), 3.50 (dd, J 1.7 and 3.5 Hz), 3.46 (m), 3.45 (dd, J 1.7 and 3.5 Hz), 3.43 (t, J 1.7 Hz), 3.26 (t, J 1.7 Hz), 3.24 (d, J 7.7 Hz), 2.80–2.60 (m). 13C NMR (50 MHz, CDCl3): δ 177.67 (C=O), 173.38 (C=O), 170.56 (C=O), 152.27 (C), 135.97 (C), 135.73 (C), 129.19 (CH), 128.69 (CH), 128.45 (CH), 127.75 (CH), 127.69 (CH), 125.05 (CH), 96.12 (C), 44.36 (CH2), 41.94 (CH2), 32.93 (CH2), 27.45 (CH2), 25.40 (CH2). m/z (%) (TR 2.1 min, GC): 281 (M + 1, 15%), 264 (5), 247 (3), 225 (3), 209 (18), 191 (5), 179 (5), 167 (8), 147 (35), 132 (100), 105 (85), 91 (22), 77 (90), 55 (63). m/z (%) (TR 7.4 min, GC): 281 (M + 1, 8%), 267 (3), 243 (1), 209 (5), 189 (100), 173 (10), 160 (45), 149 (10), 132 (35), 119 (25), 104 (38), 91 (28), 77 (20), 65 (15), 51 (18). m/z (%) (TR 8.4 min, GC): 281 (M + 1, 13%), 264 (3), 249 (1), 225 (2), 209 (10), 189 (15), 173 (85), 160 (8), 146 (20), 132 (5), 118 (8), 104 (28), 91 (100), 77 (15), 65 (28), 55 (15), 44 (18).
4.13. N-(tert-butoxycarbonyl)-3-pyrrolin-2-one(18) and N,2-O-[bis (tert-butoxycarbonyl)]-pyrrole(19)This reaction was performed by previously described procedure [1], starting from 3-pyrrolin-2-one(5) (0.654 g, 7.876 mmol). After purification of crude product over column chromatography of silica gel eluted with 30% EtOAc/hexane and crescent gradient of EtOAc (50 and 100%), lactam 18 (0.802 g, 55.5%), previously described [1] [Rf 0.29 (50% EtOAc/hexane)], was obtained. A colourless oil was also isolated and characterized as compound 19 (0.124 g, 5.5%). Compound 19: Rf 0.66 (50% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 6.94 (dd, J 2.0 and 3.7 Hz, 1H), 6.04 (dd, J 3.6 and 3.7 Hz, 1H), 5.84 (dd, J 2.0 and 3.6 Hz, 1H), 1.57 (s, 9H), 1.55 (s, 9H). 13C NMR (50 MHz, CDCl3): δ 150.88 (C=O), 147.43 (C=O), 136.88 (C), 116.33 (CH), 107.95 (CH), 100.23 (CH), 84.03 (C), 83.74 (C), 27.68 (3 CH3), 27.34 (3 CH3).
4.14. N-benzyl-4-amino(tert-butoxycarbonyl)-2-butenamide(21) and N-benzyl-3-aminobenzyl-4-amino(tert-butoxycarbonyl)-butanamide(22) (Experiment 1, Table 3)H2O (0.03 mL, 1.665 mmol) was added to a solution of lactam 18 (0.059 g, 0.322 mmol) in benzylamine (0.06 mL, 0.549 mmol), under magnetic stirring, at room temperature and nitrogen atmosphere. After 1 h the mixture was concentrated in vacuum, diluted with CH2Cl2 (1.0 mL), transferred with a pipette to the top of a column chromatography of silica gel, and then eluted with hexane and crescent gradient of EtOAc (10, 50, and 100%). Butenamide 21 (0.009 g, 10%) was obtained as a colourless oil. Rf 0.46 (70% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 7.54–7.40 (m, 1H), 7.40–7.14 (m, 5H), 6.66 (m, 1H), 6.02 (m, 1H), 4.66 (m, 1H), 4.43 (d, J 5.7 Hz, 2H), 2.93 (m, 2H), 1.47 (s, 9H). Minor isomers: δ 1.52 (s, 9H), 1.51 (s, 9H), 1.43 (s, 9H). Butanamide 22 (0.019 g, 15%) was obtained as a colourless oil. Rf 0.23 (70% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 7.83 (m, 1H), 7.40–7.12 (m, 10H), 4.92 (m, 1H), 4.41 (m, 2H), 3.85 (m, 1H), 3.79 (m, 2H), 3.26 (m, 2H), 3.06 (m, 1H), 2.34 (m, 2H), 1.43 (s, 9H). Minor isomer: δ 1.52 (s, 9H).
4.15. N-(tert-butoxycarbonyl), 4[N(R)-α-methylbenzylamine]-2-pyrrolidinone(24) (Experiment 2, Table 3)R-α-methylbenzylamine (0.05 mL, 0.388 mmol) was added to a solution of lactam 18 (0.056 g, 0.306 mmol) in THF (0.5 mL), under magnetic stirring, at room temperature and nitrogen atmosphere. After 120 h, the mixture was concentrated in vacuum, diluted with CH2Cl2 (1.5 mL), transferred with a pipette to the top of a column chromatography of silica gel, and then eluted with hexane and crescent gradient of EtOAc (50 and 100%). A colourless oil was obtained characterized as a mixture (1 : 1) of isomers 24 (0.031 g, 33%). Rf 0.36 (70% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ 7.40–7.20 (m, 10H), 3.90–3.50 (m, 6H), 3.42–3.15 (m, 4H), 2.74–2.14 (m, 4H), 1.52 (s, 9H), 1.48 (s, 9H), 1.36 (d, J 6.6 Hz, 6H).
4.16. N-(tert-butoxycarbonyl)-4-(dimethyl malonyl)-2-pyrrolidinone(26) (Experiment 3, Table 3)Dimethyl malonate (0.04 mL, 0.35 mmol) was added to a stirred solution of MeONa [Na (0.003 g, 0.130 mmol), MeOH (0.2 mL)] at room temperature and nitrogen atmosphere. After 10 minutes, lactam 18 (0.053 g, 0.289 mmol) in MeOH (0.5 mL) was added and the mixture was left under magnetic stirring, at room temperature and nitrogen atmosphere for 1.5 h. The mixture was concentrated in vacuum, diluted with EtOAc (20 mL), and then washed with saturated solution of NH4Cl (1 × 30 mL). The organic layer was separated, and the aqueous phase was extracted with EtOAc (1 × 30 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with hexane and crescent gradient of EtOAc (20 and 30%). A colourless oil was obtained characterized as a mixture of isomers 26 (0.026 g, 28%). Rf 0.35 (50% EtOAc/hexane). 1H NMR (200 MHz, CDCl3): δ4.07 (d, J 8.0 Hz, 1H), 3.80 (s, 3H), 3.70 (s, 3H), 3.38 (m, 2H), 3.11 (m, 1H), 2.54 (m, 2H), 1.52 (s, 9H). Minor isomers: δ4.12 (d, J 8.0 Hz, 1H), 3.76 (d, J 3.9 Hz, 1H), 3.68 (d, J 4.4 Hz, 1H), 1.45 (s, 9H). 13C NMR (50 MHz, CDCl3): δ170.93 (C=O), 168.17 (C=O), 167.38 (C=O), 149.45 (C=O), 83.59 (C), 55.42 (CH), 52.80 (CH3), 51.84 (CH3), 49.51 (CH2), 36.52 (CH2), 31.10 (CH), 27.82 (3 CH3).
4.17. N-(tert-butoxycarbonyl)-4-phenyl-2-pyrrolidinone(28)4-Phenyl-2-pyrrolidinone(27) (0.213 g, 1.321 mmol) in THF (9.5 mL) was added to a stirred suspension of NaH (0.038 g, 1.583 mmol) in THF (1.5 mL), at room temperature and nitrogen atmosphere. After 10 minutes, (Boc)2O (0.407 g, 1.865 mmol) was added and the mixture was left under magnetic stirring, at room temperature and nitrogen atmosphere for 20 minutes. Saturated solution of NH4Cl (50 mL) was added, and then extracted with EtOAc (2 × 50 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with 20% EtOAc/hexane. A yellowish crystalline residue was obtained characterized as pyrrolidinone 28 (0.207 g, 60%). Rf 0.50 (50% EtOAc/hexane). IR (KBr) νmax /cm−1: 2978, 1774, 1694, 1493, 1457, 1366, 1296, 1255, 1155, 1092, 1019, 839, 766, 701. 1H NMR (200 MHz, CDCl3): δ 7.43–7.21 (m, 5H), 4.24–4.10 (m, 1H), 3.76–3.44 (m, 2H), 3.00–2.62 (m, 2H), 1.53 (s, 9H). Minor isomer: δ 1.41 (s, 9H). 13C NMR (50 MHz, CDCl3): δ 172.69 (C=O), 149.53 (C=O), 140.26 (C), 128.63 (2 CH), 127.07 (CH), 126.42 (2 CH), 82.64 (C), 52.80 (CH2), 39.95 (CH2), 36.05 (CH), 27.69 (3 CH3). m/z (%): 263 (M + 2, 1%), 206 (13), 162 (48), 132 (20), 104 (100), 78 (33).
4.18. N-benzyl-4-phenyl-2-pyrrolidinone(29)18-Crown-6 (0.066 g, 0.250 mmol) in THF (0.2 mL) and 4-phenyl-2-pyrrolidinone(27) (0.080 g, 0.496 mmol) in THF (0.7 mL) were added to a stirred suspension of KH (0.030 g, 0.748 mmol) in THF (0.1 mL) at room temperature and nitrogen atmosphere. After 5 minutes, benzyl bromide (0.104 g, 0.608 mmol) was added and the mixture was left under magnetic stirring, at room temperature and nitrogen atmosphere for 10 minutes. Saturated solution of NH4Cl (15 mL) was added, and the mixture was extracted with EtOAc (2 × 20 mL). The organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum. The crude product was purified over column chromatography of silica gel eluted with 30% EtOAc/hexane. A colourless crystalline residue was obtained characterized as pyrrolidinone 29 (0.100 g, 80%). Rf 0.45 (EtOAc). IR (KBr) νmax /cm−1: 3027, 2929, 2848, 1691, 1668, 1492, 1425, 1248, 850, 746, 698, 664, 609, 524. 1H NMR (200 MHz, CDCl3): δ 7.40–7.10 (m, 10H), 4.56 (d, J 14.6 Hz, 1H), 4.44 (d, J 14.6 Hz, 1H), 3.68–3.42 (m, 2H), 3.38–3.16 (m, 1H), 2.95–2.78 (m, 1H), 2.68–2.52 (m, 1H). 13C NMR (50 MHz, CDCl3): δ 173.40 (C=O), 142.00 (C), 136.07 (C), 128.54 (2 CH), 128.47 (2 CH), 127.96 (2 CH), 127.41 (CH), 126.75 (CH), 126.43 (2 CH), 53.49 (CH2), 46.34 (CH2), 38.65 (CH2), 36.90 (CH). m/z (%): 251 (M+., 100%), 160 (35), 146 (20), 120 (13), 104 (48), 91 (45), 78 (15), 65 (15), 51 (10).
See the supplementary material displaying the speculative mechanisms for the reactions presented in the text of the paper. The supplementary material is available online at doi: 10.1155/2011/803120.