General. Column chromatography (CC): Merck silica-gel (63-200 mesh). TLC: Merck
silica-gel 60 F 254 plates. M.p.: uncorrected; Laboratory Devices. IR Spectra: Bio-Rad FTS 3100; ν in cm-1. 1H- and 13C-NMR Spectra: Varian Unity-300; CDCl3 unless otherwise indicated; δ in ppm, J in Hz (reference peak: δH 7.24, δC 77). EI-MS: Trio-2000 and Jeol SX-102A; ionization potential 70 eV. EA: Heraeus CHN-O Rapid. THF and ether were distilled from sodium-benzophenone, and DMF from Mg2SO4, while dicholomethane and toluene from calcium hydride.
4,7-dimethylindene11 (39)
Sodium (5 g, 0.22 mol) was dissolved in dry methanol (60 ml). The NaOMe solution was cooled at 0o and freshly distilled cyclopentadiene (6.5 g, 0.10 mol) and 2,5-hexandione (11.41 g, 0.10 mol) were added dropwise. The ice bath was removed, and the mixture was stirred at room temperature for 2 hr. After quenching with water, the mixture was evaporated. The residue was extracted with hexane, and the extracts were washed with brine and dried over Na2SO4. Solvent was removed in vacuo and the product was isolated by fractional distillation (b.p. 45oC, 0.05 torr) to afford 39 as a pale yellow oil, 12.18 g (84 %).
1H NMR: δ 2.43 (s, 3H); 2.53 (s, 3H); 3.37-3.38 (m, 2H); 6.63-6.67 (m, 1H); 7.01-7.03 (m, 1H); 7.08-7.12 (m, 2H)
13C NMR: δ 18.24 (q); 18.39 (q); 38.22 (t); 125.77 (d); 127.53 (d); 127.66 (s); 130.10 (s);
130.48 (d); 130.18 (d); 142.12 (s); 143.18 (s)
4,7-dimethylindane34 (40)
A mixture of 4,7-dimethylindene (1 g, 6.9 mmol) and 10 % Pd/C (20 mg) in methanol (2 ml) was stirred under H2. After absorption of hydrogen ceased, the catalyst was removed by filtration and the solvent was evaporated to provide indane 40 (0.96 g, 94.7 %).
1H NMR: δ 2.20 (quintet, 2H, J=7.5 Hz); 2.36 (s, 6H); 2.98 (t, 4H, J=7.5 Hz); 7.02 (s, 2H)
13C NMR: δ 18.88 (q); 24.16 (t); 31.61 (t); 126.98 (d); 130.85 (s); 142.54 (s)
O2N
4,7-dimethyl-5-nitroindane (41)
A mixture of conc. HNO3 (1 ml), conc. H2SO4 (1 ml) and 4,7-dimethylindane (1 g, 6.85 mmol) was stirred at 0o for 10 min. and at room temperature for 30 min. The reaction product was poured into 20 ml of ice water and extracted with CH2Cl2. The combined organic extracts were washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography to afford 41 (0.40 g, 30.4 %), m.p. 61-62oC
1H NMR: δ 2.10 (tt, 2H, J1=7.5 Hz, J2=7.5 Hz); 2.21 (s, 3H); 2.35 (s, 3H); 2.85 (t, 2H, J=7.5 Hz); 2.88 (t, 2H, J=7.5 Hz); 7.51 (s, 1H)
13C NMR: δ 16.14 (q); 18.53 (q); 23.93 (t); 31.88 (t); 32.08 (t); 123.46 (d); 126.24 (s); 131.61 (s); 145.27 (s); 148.03 (s); 148.38 (s)
IR (neat): ν 3441; 3433; 2958; 2918; 1645; 1514; 1458; 1433; 1378; 1333; 1265; 1212; 1004;
898
EI-MS: 192 (M++1, 27.35); 191 (M+, 22.06); 175 (61.18); 174 (55.59); 147 (32.06); 146 (43.53); 128 (100); 115 (47.65); 91 (20.59)
EA: Anal. calcd. for C11H13O2N: C: 69.09; H: 6.85; N: 7.32; Found: C: 69.25; H: 7.03; N:
7.28
NH
N-phenyl-4,7-dimethyl-5-indanamine (42)
TFA (3.42 g, 30 mmol) and TFAA (1.05 g, 5mmol) were mixed, stirred and warmed to 60o. 4,7-Dimethylindane (3.65 g, 25 mmol) and N-phenylhydroxyamine (0.55 g, 5 mmol) were added slowly. After 3 hr the reaction mixture was basified with aqueous Na2CO3 to pH>7, and extracted with CH2Cl2. The combined extracts were washed with 30% HCl and water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography (CH2Cl2/Hex=1/20) to afford 44 (0.74 g, 62 % based on N-phenylhydroxyamnie). Approximately 80 % of indene 42 was recovered.
1H NMR: δ 2.23 (s ,3H); 2.24 (tt, 2H, J1=7.5 Hz, J2=7.5 Hz); 2.31 (s, 3H); 2.96 (t, 2H, J=7.5 Hz); 3.00 (t, 2H, J=7.5 Hz); 5.32 (br, 1H); 6.90-6.94 (m, 3H); 7.01 (s, 1H); 7.28-7.34 (m, 2H)
13C NMR: δ 14.08 (q); 18.91 (q); 24.47 (t); 31.37 (t); 32.23 (t); 115.61 (d); 118.97 (d); 121.05 (d); 124.03 (s); 129.12 (d); 131.26 (s); 137.78 (s); 138.63 (s); 144.07 (s); 145.66 (s)
IR (neat): ν 3389; 3046; 2939; 2841; 1652; 1599; 1496; 1479; 1405; 1323; 1308; 1247; 1175;
748; 693
EI-MS: 237 (M+, 100); 222 (14.18); 220 (3.77); 145 (2.97); 144 (2.13); 91 (2.72); 77 (2.72) HR-MS: Anal. calcd. for C17H19N: 237.1519; Found: 237.1523
I
5-iodo-4,7-dimethylindane (43)
Fe(NO3)3.9H2O (4 g, 10 mmol) was grinded with silica gel (8 g) in an agate mortar to furnish a pale yellow powder “silfen”. It was used directly.
To a stirred solution of 4,7-dimethyindane (4.38 g, 30 mmol) in CH2Cl2 (45 ml), iodine (4.20 g, 16.5 mmol) and silfen (18 g) were added. After 12 hr at room temperature, the reaction mixture was filtered, and the filter cake was washed with CH2Cl2. The combined organic solution was washed with aqueous sodium thiosulfate and water, dried over Na2SO4
and evaporated. The residue was purified by column chromatography to give 43 (5.83 g, 70.9
%).
1H NMR: δ 2.08 (tt, 2H, J1=7.5 Hz, J2=7.5 Hz); 2.19 (s, 3H); 2.34 (s, 3H); 2.82 (t, 2H, J=7.5 Hz); 2.91 (t, 2H, J=7.5 Hz); 7.47 (s, 1H)
13C NMR: δ 18.29 (q); 24.26 (t); 24.42 (q); 31.61 (t); 33.31 (t); 98.57 (s); 133.05 (s); 133.98 (s); 137.30 (d); 142.98 (s); 143.50 (s)
IR (neat): ν 2941; 2916; 2842; 2360; 2342; 1710; 1637; 1593; 1570; 1459; 1377; 1174; 949;
859; 746
EI-MS: 272 (M+, 100); 145 (18.82); 130 (9.48); 115 (4.16) HR-MS: Anal. calcd. for C11H13I: 272.0063; Found: 272.0069
NH
4,10-dimethyl-1,2,3,5-tetrahydrocyclopentano[2,3-b]carbazole (44)
A mixture of 45 (70 mg, 0.26 mmol) and triethyl phosphite (0.5 ml) was heated at 150oC under nitrogen for 5 hr. Excess (EtO)3P and (EtO)3P=O were distilled at reduced pressure to leave a brown residue which was purified by column chromatography over silica gel to give product 44 (40 mg, 64.9 %).
1H NMR: δ 2.20 (tt, 2H, J1=7.8 Hz, J2=7.8 Hz); 2.43 (s, 3H); 2.79 (s, 3H); 3.05 (t, 2H, J=7.8 Hz); 3.08 (t, 2H, J=7.8 Hz); 7.21-7.27 (m, 1H); 7.36-7.46 (m, 2H); 7.80 (br, 1H); 8.18-8.21 (m, 1H)
13C NMR: δ 13.51 (q); 16.97 (q); 25.25 (t); 31.22 (t); 31.81 (t); 110.29 (d); 112.04 (s); 118.95 (d); 120.42 (s); 122.19 (d); 124.17 (d); 124.69 (s); 125.34 (s); 134.44 (s); 138.41 (s); 139.70 (s); 140.79 (s)
IR (neat): ν 3476; 3413; 2947; 2841; 1609; 1511; 1455; 1386; 1344; 1305; 1251; 1225; 1145;
1114; 744; 730
EI-MS: 235 (M+, 100); 220 (90.98); 204 (42.29); 117 (7.85); 108 (12.22); 102 (14.10) HR-MS: Anal. calcd. for C17H17N: 235.1362; Found: 235.1362
NO2
4,7-dimethyl-5-(2-nitrophenyl)indane (45)
5-Iodo-4,7-dimethylindane (0.27 g, 1 mmol) and o-chloronitrobenzene (0.16 g, 1.1 mmol) were dissolved in dry DMF (6 ml). The mixture was heated in a N2 atmosphere, then Cu powder (0.64 g, 10 mmol) and CuI (0.76 g, 40 mmol) were added at reflux. After 20 hr the cooled reaction mixture was filtered, washed with CH2Cl2, and the organic solutions were combined, washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography over silica gel to give product 45 (0.05 g, 18.7 %).
1H NMR: δ 1.99 (s, 3H); 2.13 (tt, 2H, J1=7.5 Hz, J2=7.5 Hz); 2.24 (s, 3H); 2.88-2.93 (m, 4H);
6.76 (s, 1H); 7.34 (d, 1H, J=7.5 Hz); 7.45-7.50 (m, 1H); 7.57-7.62 (m, 1H); 7.94 (d, 1H, J=8.1 Hz)
13C NMR: δ 16.36 (q); 18.81 (q); 24.02 (t); 31.08 (t); 32.09 (t); 123.76 (d); 127.37 (d); 127.77 (d); 128.53 (s); 130.66 (s); 132.15 (d); 132.54 (d); 135.19 (s); 136.95 (s); 142.70 (s); 143.15 (s); 149.49 (s)
IR (neat): ν 3392; 3062; 2940; 2921; 2867; 2845; 1704; 1608; 1571; 1526; 1487; 1467; 1437;
1349; 1292; 1194; 1119; 959; 871; 854; 786; 757; 722; 695
EI-MS: 267 (M+, 90.20); 250 (93.14); 236 (94.12); 205 (43.87); 189 (28.92); 178 (29.41);
165 (26.23); 152 (9.99)
HR-MS: Anal. calcd. for C17H17O2N: 267.1260; Found: 267.1255
O
4,7-dimethyl-2-indanone19 (46)
To an ice-cooled solution of 30 % H2O2 (5.5 g) in 98 % formic acid (24 ml), 4,7-dimethylindene (4.8 g, 33 mmol) was added dropwise. After addition was completed, the reaction mixture was stirred overnight at room temperature. The excess formic acid was removed in vacuo, and the remaining brown oil was mixed with 140 ml of 7% H2SO4. Steam distillation gave an off-white solid. The product was collected by dissolving in CH2Cl2 and dried over Na2SO4. On evaporation, 46 (2.55 g, 47.8 %) was obtained.
1H NMR: δ 2.22 (s, 6H); 3.42 (s, 4H); 7.01 (s, 2H)
13C NMR: δ 18.87 (q); 43.15 (t); 128.03 (d); 131.19 (s); 136.47 (s); 215.21 (s)
O I
5-iodo-4,7-dimethyl-2-indanone (47)
To an ice-cooled, stirred solution of 5-iodo-4,7-dimethyl-2-indanol (8 g. 27.8 mmol) in acetone (50 ml) was added slowly Jones’ reagent (16 ml). After 1 hr, excess oxidant was destroyed by isopropanol. Addition of water (100 ml) was followed by evaporation of acetone under reduced pressure. The residue was filtered and redissolvd with CH2Cl2. The organic phase was washed with water, dried over Na2SO4, and evaporated to afford product 47 (7.48 g, 94.2 %), m.p. 124-125oC.
1H NMR: δ 2.15 (s, 3H); 2.28 (s, 3H); 3.37 (s, 2H); 3.46 (s, 2H); 7.56 (s, 1H)
13C NMR: δ 18.43 (q); 24.68 (q); 43.26 (t); 44.46 (t); 99.47 (s); 133.45 (s); 134.57 (s); 136.79 (s); 137.01 (s); 138.44 (d); 213.84 (s)
IR (neat): ν 2912; 2859; 1749; 1577; 1462; 1376; 1182; 1147; 938; 863; 796; 761; 729; 576 EI-MS: 286 (M+, 100); 272 (5.10); 258 (83.67); 131 (15.43); 115 (10.84); 91 (21.30); 77 (20.28)
HR-MS: Anal. calcd. for C11H11OI: 285.9855; Found: 285.9855
O O
4,7-dimethyl-2-(1,3-dioxolan-2-yl)indane (48)
A mixture of 4,7-dimethyl-2-indanone (0.20 g, 1.25 mmol), ethlylene glycol (0.62 g, 10 mmol), and p-toluenesufonic acid (10 mg) in benzene (10 ml) was heated under a Dean-Stark apparatus at reflux overnight. Benzene was distilled as much as possible. The residue was basified with sat. K2CO3 and extracted with CH2Cl2. The organic phase was washed with water and brine, dried over Na2SO4 and evaporated. The residue was purified by short column chromatography over silica gel to afford product 48 (0.25 g, 98 %), m.p. 65-66oC.
1H NMR: δ 2.31 (s, 6H); 3.22 (s, 4H); 4.09 (d, 4H, J=1.2 Hz); 7.01 (s, 2H)
13C NMR: δ 18.56 (q); 42.09 (t); 64.17 (t); 116.91 (s); 127.39 (d); 130.50 (s); 138.03 (s) IR (neat): ν 2979; 2938; 2892; 1496; 1442; 1333; 1290; 1274; 1203; 1188; 1175; 1164; 1139;
1108; 1051; 1012; 947; 836; 806; 735; 578; 540
EI-MS: 204 (M+, 100); 159 (8.2); 145 (22.95); 132 (59.77); 117 (25.00); 91 (14.36) HR-MS: Anal. calcd. for C13H16O2: 204.1151; Found: 204.1149
EA: Anal. calcd. for C13H16O2: C: 76.44; H: 7.89; Found: C: 76.62; H: 7.77
O O I
5-iodo-4,7-dimethyl-2-(1,3-dioxolan-2-yl)indane (49)
A mixture of 5-iodo-4,7-dimethyl-2-indanone (0.50 g, 1.75 mmol), ethlylene glycol (0.86 g, 8 eq.), and p-toluenesufonic acid (50 mg) in benzene (30 ml) was heated under a Dean-Stark apparatus at reflux overnight. Benzene was distilled as much as possible. The residue was basified with sat. K2CO3 and extracted with CH2Cl2. The organic phase was washed with water and brine, dried over Na2SO4 and evaporated. The residue was purified by short column chromatography over silica gel to afford product 49 (0.55 g, 95.3 %), m.p.
89-90oC.
1H NMR: δ 2.13 (s, 3H); 2.27 (s, 3H); 3.05 (s, 2H); 3.14 (s, 2H); 4.01 (s, 4H); 7.48 (s, 1H)
13C NMR: δ 18.21 (q); 24.39 (q); 42.25 (t); 43.71 (t); 64.45 (t); 99.18 (s); 116.66 (s); 133.03 (s); 133.97 (s); 137.91 (d); 138.62 (s); 138.94 (s)
IR (neat): ν 2946; 2883; 1576; 1462; 1417; 1378; 1328; 1280; 1220; 1114; 1061; 1012; 948;
859; 798; 742; 579; 504; 464; 451
EI-MS: 330 (M+, 87.30); 258 (100); 131 (48.36); 115 (50.82); 91 (23.26) HR-MS: Anal. calcd. for C13H15O2I: 330.0118; Found: 330.0113
EA: Anal. calcd. for C13H15O2I: C: 47.29; H: 4.58; Found: C: 47.17; H: 4.70
OH
4,7-dimethyl-2-indanol (50)
Sodium borohydride (0.2 g, 5.28 mmol) was added slowly to a stirred solution of 4,7-dimethyl-2-indanone (0.60 g, 3.75 mmol) in CH2Cl2 (10 ml) and methanol (10 ml) in an ice bath. After 3 hr, water was added and the solvents were evaporated. The residue was extracted with CH2Cl2, the organic layer was washed with brine, dried over Na2SO4 and evaporated to furnish product 50 (0.6 g, 98.8 %), m.p. 58-59oC.
1H NMR: δ 2.32 (s, 6H); 2.87 (dd, 2H, J1=16.5 Hz; J2=3.3 Hz); 3.16 (dd, 2H, J1=16.5 Hz, J2=6.6 Hz); 3.19 (br, 1H); 4.69 (tt, 1H, J1=3.3 Hz, J2=6.6 Hz); 7.00 (s, 2H)
13C NMR: δ 18.64 (q); 41.08 (t); 71.97 (d); 131.03 (s); 139.21 (s)
IR (neat): ν 3321; 3036; 3009; 2918; 1867; 1743; 1607; 1497; 1417; 1328; 1295; 1266; 1219;
1200; 1020; 948; 832; 805
EI-MS: 162 (M+, 43.93); 144 (20.27); 133 (100); 129 (11.61); 119 (16.61); 91 (19.20); 77 (19.29); 65 (14.02); 51 (20.80)
HR-MS: Anal. calcd. for C11H14O: 162.1045; Found: 162.1051
EA: Anal. calcd. for C11H14O: C: 81.44; H: 8.70; Found: C: 81.80; H: 8.73
OH I
5-iodo-4,7-dimethyl-2-indanol (51)
To a stirred solution of 4,7-dimethyl-2-indanol (6.26 g, 38.6 mmol) in CH2Cl2 (60 ml), iodine (5.60 g, 22 mmol) and then silfen (24 g) were added. The reaction mixture was allowed to proceed for 12 hr at room temperature, filtered, and washed with CH2Cl2. The organic solution was washed with aqueous sodium thiosulfate and water. The extracts were dried over Na2SO4 and evaporated. The residue dissolved in methanol (20 ml) was cooled in an ice bath and conc. HCl(10 ml) was added slowly. The mixture was stirred for 2 hr and water (200 ml) was added. Solids that appeared were filtered and redissolved in CH2Cl2. The organic solution was washed with water, dried over Na2SO4, and evaporated to afford product 51 (8.97 g, 81.6
%), m.p. 85-86oC.
1H NMR: δ 2.15 (s, 3H); 2.94 (s, 3H); 2.67-2.83 (m, 2H); 2.89 (br, 1H); 2.96-3.14 (m, 2H);
4.52-4.58 (m, 1H); 7.47 (s, 1H)
13C NMR: δ 18.25 (q); 24.36 (q); 41.16 (t); 42.75 (t); 71.80 (d); 99.06 (s); 133.37 (s); 134.28 (s); 137.77 (d); 139.65 (s); 140.09 (s)
IR (neat): ν 3305; 2917; 1573; 1459; 1417; 1331; 1299; 1263; 1201; 1177; 1017; 955; 934;
859; 797; 743
EI-MS: 288 (M+, 100); 270 (15.67); 259 (96.48); 245 (9.02); 161 (11.14); 143 (38.73); 128 (22.71); 115 (28.17); 91 (12.15)
HR-MS: Anal. calcd. for C11H13OI: 288.0012; Found: 288.0013
EA: Anal. calcd. for C11H13OI: C: 45.86; H: 4.55; Found: C: 45.82; H: 4.78
O NO2
4,7-dimethyl-5-(2-nitrophenyl)-2-indanone (52)
5-Iodo-4,7-dimethyl-2-indanone (0.57 g, 2 mmol), 2-nitrophenylboronic acid (0.40 g, 2.4 mmol), NaHCO3 (0.50 g, 6 mmol), and Pd(PPh3)2Cl2 (30 mg, 2 mol %) were placed in a two-necked round-bottomed flask filled with N2. A mixture of DME and water (1:1 v/v, 16 ml) was added through syringe. The reaction was heated at 80oC for 18 hr, solvents were evaporated and the residue was extracted with CH2Cl2. The extracts were combined, washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography over silica gel to give product 52 (0.26 g, 46 %).
1H NMR: δ 1.95 (s, 3H); 2.22 (s, 3H); 3.49 (s, 2H); 3.50 (s, 2H); 6.87 (s, 1H); 7.29-7.32 (m, 1H); 7.53-7.48 (m, 1H); 7.60-7.65 (m, 1H); 7.95-7.98 (m, 1H)
13C NMR: δ 16.58 (q); 18.87 (q); 43.40 (t); 43.67 (t); 124.00 (d); 128.24 (d); 128.26 (d);
129.12 (s); 131.30 (s); 132.25 (d); 132.48 (d); 136.19 (s); 136.56 (s); 136.59 (s); 137.10 (s);
149.15 (s); 214.78 (s)
IR (neat): ν 3447; 2920; 1748; 1647; 1608; 1524; 1470; 1388; 1351; 1287; 1199; 1165; 1141;
950; 876; 854; 786; 758
EI-MS: 281 (M+, 44.13); 253 (100); 206 (16.90); 191 (15.34); 115 (5.65); 89 (11.38) HR-MS: Anal. calcd. for C17H15O3N: 281.1053; Found: 281.1054
O NO2 O
4,7-dimethyl-5-(2-nitrophenyl)-2-(1,3-dioxolan-2-yl)indane (53)
49 (2.90 g, 8.8 mmol), 2-nitrophenylboronic acid (2.50 g, 15 mmol), NaHCO3 (2.58 g, 30.7 mmol), and Pd(PPh3)2Cl2 (0.25 g, 4 mol %) were placed in a two-necked round-bottomed flask filled with N2. A mixture of DME and water (1:1 v/v, 40 ml) was added through syringe. The reaction was heated at 80oC for 18 hr, solvents were evaporated and the residue was extracted with CH2Cl2. The extracts were combined, washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography over silica gel to give product 53 (2.53 g, 88.6 %), m.p. 155-156oC.
1H NMR: δ 1.91 (s, 3H); 2.18 (s, 3H); 3.07-3.21 (m, 4H); 4.03 (s, 4H); 6.74 (s, 1H);
7.26-7.29 (m, 1H); 7.43-7.48 (m, 1H); 7.54-7.60 (m, 1H); 7.90-7.93 (m, 1H)
13C NMR: δ 16.32 (q); 18.67 (q); 42.34 (t); 42.69 (t); 64.25 (t); 64.56 (t); 117.02 (s); 123.76 (d); 127.83 (d); 127.87 (d); 128.50 (s); 130.67 (s); 132.20 (d); 132.44 (d); 135.75 (s); 136.62 (s); 138.31 (s); 138.78 (s); 149.29 (s)
IR (neat): ν 2946; 2890; 2361; 2341; 2252; 1526; 1454; 1417; 1350; 1284; 1209; 1115; 1059;
1013; 948; 911; 854; 786; 758; 730; 709
EI-MS: 325 (M+, 100); 308 (27.30); 294 (19.14); 278 (32.43); 234 (25.90); 222 (26.58); 207 (34.91); 189 (36.26); 178 (49.55); 165 (35.14); 152 (24.10); 88 (20.05)
HR-MS: Anal. calcd. for C19H19O4N: 325.1315; Found: 325.1308
EA: Anal. calcd. for C19H19O4N: C: 70.14; H: 5.89; N: 4.31; Found: C: 69.85; H: 5.87; N:
4.55
O N O
H
4,10-dimethyl-2-(1,3-dioxolan-2-yl)-
1,2,3,5-tetrahydrocyclopentano[2,3-b]carbazole (54)
A mixture of 53 (80 mg, 0.25 mmol) and triethyl phosphite (2 ml) was heated at 150oC under nitrogen for 5 hr. Excess (EtO)3P and (EtO)3P=O were distilled at reduced pressure to leave a brown residue which was purified by column chromatography over silica gel to give product 54 (50 mg, 69.3 %), m.p. 219-220oC.
1H NMR (CDCl3+CD3OD): δ 2.31 (s, 3H); 2.55 (s, 3H); 2.90 (br, 1H); 3.24 (s, 4H); 4.05 (s, 4H); 7.11-7.16 (m, 1H); 7.27-7.39 (m, 2H); 8.04-8.07 (m, 1H)
13C NMR (CDCl3+CD3OD): δ 13.31 (q); 16.64 (q); 41.58 (t); 42.03 (t); 64.36 (t); 110.23 (d);
112.39 (s); 117.42 (s); 118.59 (d); 120.40 (s); 122.04 (d); 124.11 (d); 124.29 (s); 125.47 (s);
129.19 (s); 135.46 (s); 138.42 (s); 139.58 (s)
IR (neat): ν 3359; 2936; 2904; 2882; 2359; 2337; 1296; 1136; 1120; 1050; 1008; 952; 738 EI-MS: 293 (M+, 100); 265 (7.88); 248 (20.28); 221 (56.12); 204 (26.66); 102 (19.52) HR-MS: Anal. calcd. for C19H19O2N: 293.1417; Found: 293.1415
EA: Anal. calcd. for C19H19O2N: C: 77.79; H: 6.53; N: 4.77; Found: C: 77.50; H: 6.67; N:
5.11
OAc I
5-iodo-4,7-dimethyl-2,3-dihydro-1H-2-indentyl acetate (59)
5-Iodo-4,7-dimethyl-2-indanol (0.36 g, 1.25 mmol), acetic anhydride (0.64 g, 6.27 mmol), pyridine (0.50 g, 6.33 mmol) and DMAP (20 mg) were dissolved in CH2Cl2 (10 ml).
The reaction mixture was stirred at room temperature overnight and then evaporated in vacuo.
The residue was purified by column chromatography over silica gel to afford 59 (0.41 g, 99.4
%), m.p. 63-64oC.
1H NMR: δ 2.02 (s, 3H); 2.16 (s, 3H); 2.29 (s, 3H); 2.85-3.00 (m, 2H); 3.14-3.31 (m, 2H);
5.46-5.50 (m, 1H); 7.48 (s, 1H)
13C NMR: δ 18.22 (q); 21.21 (q); 24.34 (q); 38.52 (t); 40.05 (t); 74.41 (d); 99.30 (s); 133.24 (s); 134.25 (s); 138.08 (d); 139.32 (s); 139.70 (s); 170.79 (s)
IR (neat): ν 2942; 2916; 2860; 1732; 1574; 1462; 1373; 1312; 1242; 1199; 1015; 973; 860;
744
EI-MS: 330 (M+); 286; 270; 259; 244; 210; 195; 178; 160; 143; 128; 115; 105; 91; 77; 65; 51 HR-MS: Anal. calcd. for C13H15O2I: 330.0118; Found: 330.0115
OAc NO2
5-(2-nitrophenyl)-4,7-dimethyl-2,3-dihydro-1H-2-indentyl acetate (60)
59 (0.41 g, 1.24 mmol), 2-nitrophenylboronic acid (0.33 g, 1.98 mmol), NaHCO3 (0.42 g, 5 mmol), and Pd(PPh3)2Cl2 (20 mg, 2 mol %) were placed in a two-necked round-bottomed flask filled with N2. A mixture of DME and water (1:1 v/v, 8 ml) was added through syringe.
The reaction was heated at 80oC for 18 hr, solvents were evaporated and the residue was extracted with CH2Cl2. The extracts were combined, washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography over silica gel to give product 60 (0.32 g, 79.2 %).
1H NMR: δ 1.95 (s, 3H); 2.04 (d, 3H, J=6.9 Hz); 2.20 (s, 3H); 2.95-3.02 (m, 2H); 3.24-3.35 (m, 2H); 5.54-5.58 (m, 1H); 6.78 (s, 1H); 7.27-7.32 (m, 1H); 7.43-7.49 (m, 1H); 7.56-7.61 (m, 1H); 7.90-7.31 (m, 1H) (conformation isomer)
13C NMR: δ 16.18 (q); 16.19 (q); 18.53 (q); 21.12 (q); 38.50 (t); 38.61 (t); 38.84 (t); 38.98 (t);
74.48 (d); 74.62 (d); 123.69 (d); 123.72 (d); 127.88 (d); 127.99 (d); 128.70 (s); 130.77 (s);
132.15 (d); 132.17 (s); 132.29 (s); 135.93 (s); 136.41 (s); 138.89 (s); 139.39 (s); 139.42 (s);
149.25 (s); 170.83 (s); 170.99 (s) (conformation isomer)
IR (neat): ν 2943; 2920; 1734; 1609; 1571; 1527; 1469; 1437; 1350; 1244; 1194; 1021; 977;
873; 854; 786; 758; 708
EI-MS: 325 (M+); 295; 282; 265; 248; 234; 218; 203; 178; 165; 152; 146; 115; 101; 91; 77 HR-MS: Anal. calcd. for C19H19O4N: 325.1315; Found: 325.1316
OAc NH
4,10-dimethyl-1,2,3,5-tetrahydrocyclopentano[2,3-b]carbazol-2-yl acetate (61) A mixture of 60 (0.32 g, 0.98 mmol) and triethyl phosphite (5 ml) was heated at 150oC under nitrogen for 5 hr. Excess (EtO)3P and (EtO)3P=O were distilled at reduced pressure to leave a brown residue which was purified by column chromatography over silica gel to give product 61 (0.21 g, 72.8 %).
1H NMR: δ 1.97 (s, 3H); 2.33 (s, 3H); 2.66 (s, 3H) 3.01-3.11 (m, 2H); 3.29-3.38 (m, 2H);
5.51-5.57 (m, 1H); 7.11-7.16 (m, 1H); 7.26-7.37 (m, 2H); 7.88 (br, 1H); 8.06-8.09 (m, 1H)
13C NMR: δ 13.51 (q); 16.93 (q); 21.38 (q); 38.07 (t); 38.57 (t); 75.44 (d); 110.37 (d); 112.48 (s); 119.15 (d); 120.98 (s); 122.27 (d); 124.51 (d); 125.85 (s); 130.52 (s); 136.73 (s); 138.69 (s); 139.66 (s); 171.33 (s) (one Cq peak was not found)
IR (neat): ν 3280; 2740; 1707; 1610; 1517; 1368; 1304; 1263; 1194; 1014; 976; 839; 773;
730
EI-MS: 293 (M+, 15.25); 234 (24.20); 233 (100); 218 (47.80); 117 (5.63) HR-MS: Anal. calcd. for C19H19O2N: 293.1417; Found: 293.1421
OH NH
OH
OH NH
OH
cis-4,10-dimethyl-1,2,3,5-
tetrahydrocyclopentano [2,3-b]carbazole-1,2-diol (62a)
trans-4,10-dimethyl-1,2,3,5-
tetrahydrocyclopentano [2,3-b]carbazole-1,2-diol (62b)
To a mixture of 60 (0.30 g, 1 mmol) and H2O (0.15 g, 8.0 mmol) in THF (5 ml), a solution of DDQ (0.93 g, 4.1 mmol) in THF (10 ml) was added dropwise at 0oC during 10 min. The reaction mixture was stirred at room temperature for 8 hr. 50 % K2CO3 (10 ml) was added and the mixture was stirred for another 1 hr. THF was evaporated. The residue was extracted with CH2Cl2 / MeOH (10 : 1), the organic extracts were combined, washed with sat.
K2CO3, dried over Na2SO4 and evaporated.
The residue (0.26 g) was dissolved in dry THF (10 ml) and added to LAH (0.26 g, 6.8 mmol) in dry THF (5 ml) dropwise. The reaction mixture was stirred at room temperature for 10 hr, excess LAH was destroyed by water. The mixture was filtered, and washed with CH2Cl2. The combined organic extracts were washed with sat. K2CO3, dried over Na2SO4 and evaporated. The residue was purified by column chromatography over silica gel to afford cis-diol 62a (0.06 g, 21.9 %) and trans-diol 62b (0.13 g, 47.6 %).
cis-diol (62a):
1H NMR (CD3OD): δ 2.40 (s, 3H); 2.82 (s, 3H); 2.96 (dd, 1H, J1=15 Hz, J2=8.7 Hz); 3.19 (dd, 1H, J1=15 Hz, J2=7.2 Hz); 4.31 (ddd, 1H, J1=8.7 Hz, J2=7.2 Hz, J3=5.4 Hz); 5.09 (d, 1H, J=5.4 Hz); 7.09-7.14 (m, 1H); 7.27-7.33 (m, 1H); 7.43-7.46 (m, 1H); 8.07-8.10 (m, 1H)
13C NMR (CD3OD): δ 13.53 (q); 16.63 (q); 37.37 (t); 74.39 (d); 74.49 (d); 111.59 (d); 113.99 (s); 119.59 (d); 121.94 (s); 123.00 (d); 125.33 (d); 125.57 (s); 129.05 (s); 132.72 (s); 138.25 (s); 141.58 (s); 141.75 (s)
IR (neat): ν 3419; 2923; 2085; 1645; 1519; 1456; 1338; 1297; 1235; 1118; 1085; 1002; 740 EI-MS: 268 (M+1, 10.20); 267 (M+, 46.84); 249 (74.56); 221 (100); 206 (31.86); 204 (36.55);
191 (14.75); 111 (10.88)
HR-MS: Anal. calcd. for C17H17O2N: 267.1260; Found: 267.1262
trans-diol (62b):
1H NMR (CD3OD): δ 2.43 (s, 3H); 2.82 (m, 1H); 2.86 (s, 3H); 3.44 (dd, 1H, J1=16.8 Hz, J2=5.4 Hz); 4.40-4.42 (m, 1H); 5.16 (s, 1H); 7.09-7.14 (m, 1H); 7.27-7.32 (m, 1H); 7.44-7.46 (m, 1H); 8.09-8.12 (m, 1H)
13C NMR (CD3OD): δ 13.50 (q); 16.72 (q); 38.73 (t); 80.24 (d); 81.84 (d); 111.58 (d); 114.17 (s); 119.54 (d); 122.20 (s); 123.00 (d); 125.25 (d); 125.58 (s); 129.23 (s); 133.13 (s); 139.48 (s); 141.79 (s); 141.87 (s)
IR (neat): ν 3314; 2918; 1685; 1609; 1559; 1518; 1457; 1381; 1340; 1296; 1250; 993; 731 EI-MS: 268 (M+1, 11.66); 267 (M+, 55.19); 249 (77.36); 235 (19.34); 234 (20.80); 221 (100);
218 (13.62); 217 (11.38); 206 (30.86); 204 (35.42); 194 (10.52); 191 (13.30); 165 (10.56); 111 (10.26)
HR-MS: Anal. calcd. for C17H17O2N: 267.1260; Found: 267.1259
NH
N
5,11-dimethyl-6H-pyrido[4,3-b]carbazole; Ellipticine26 (1a)
To a stirred solution of the diol (cis + trans, 0.10 g, 0.37 mmol) and pH=8 phosphate buffer (2 ml) in t-BuOH (6 ml), NaIO4 (0.16 g, 7.5 mmol) was added. At the end of 6 hr, ammonium acetate (0.29 g, 3.6 mmol) was added, stirring was continued for 1 hr and then the solvent was evaporated. The residue was extracted with CH2Cl2 / MeOH (10 : 1), washed with sat. K2CO3, dried over Na2SO4 and evaporated. The residue was purified by column chromatography over silica gel to afford 1a (0.08 g, 86.8 %).
1H NMR (DMSO-d6): δ 2.78 (s, 3H); 3.25 (s, 3H); 7.22-7.27 (m, 1H); 7.49-7.57 (m, 2H);
7.90 (d, 1H, J=6 Hz); 8.37 (d, 1H, J=8.1 Hz); 8.42 (d, 1H, J=6 Hz); 9.68 (s, 1H); 11.37 (s, 1H)
13C NMR (DMSO-d6): δ 11.92 (q); 14.31 (q); 108.00 (s); 110.67 (d); 115.84 (d); 119.15 (d);
121.95 (s); 123.11 (s); 123.37 (s); 123.78 (d); 127.08 (d); 128.01 (s); 132.45 (s); 140.47 (d);
140.53 (s); 142.66 (s); 149.67 (s)
HR-MS: Anal. calcd. for C17H14N2: 246.1158; Found: 246.1152
H H
H H
pentacyclo[8.2.1.14,7.02,9.03,8]tetradeca-5,11-diene27 (76)
Norbornadiene (42.7 g, 50 ml, 463.5 mmol) was added to a stirring solution of nickel bis(cyclooctadiene) (0.65 g, 2.37 mmol) in 1,4-dioxane through syringe. The resulting dark red solution was allowed to stir at room temperature for 22 hr, resulting in formation of a white precipitate. A second portion of norbornadiene (42.7 g, 50 ml, 463.5 mmol) was then added to the reaction mixture, which was heated at 50-55oC for 48 hr and at 40oC for an additional 16 hr. The reaction mixture was then allowed to cool to room temperature and concentrated in vacuo to give a solid residue. The white solid was treated by flash column chromatography (100 % Hex) over silica gel (81.55 g). On evaporation of solvent, the residue was purified by sublimation to afford dimer 76 (46 g, 53.9 %).
1H NMR: δ 1.23 (d, 2H, J=9 Hz); 1.34 (s, 4H); 1.69 (d, 2H, J=9 Hz); 2.62 (s, 4H); 6.01 (s, 4H)
13C NMR: δ 39.76 (d); 42.20 (t); 44.17 (d); 136.13 (d)
OMe OMe
O O
dimethyl (2R,3S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate35 (79)
Freshly distilled cyclopentadiene (10.2 g, 153 mmol) was added slowly to an ice-cooled solution of dimethyl maleate (21.6 g, 150 mmol) and lithium perchlorate (6 g) in dry ether (30 ml). The mixture was stirred at room temperature for 10 hr and water was added. The aqueous layer was extracted with CH2Cl2, and the organic extracts were combined, washed with water and brine, dried over Na2SO4, and evaporated. The resulting oil was purified by column chromatography over silica gel to afford 79 (30.5 g, 96.8 %).
1H NMR: δ 1.23-1.26 (m, 1H); 1.35-1.39 (m, 1H); 3.06-3.07 (m, 2H); 3.19-3.20 (m, 2H); 3.51 (s, 6H); 6.15-6.16 (m, 2H)
13C NMR: δ 46.01 (d); 47.79 (d); 48.42 (t); 51.23 (q); 134.65 (d); 172.66 (s)
TMSO OTMS
endo-3,4-bis(trimethylsiloxy)tricyclo[4.2.1.02.5]nona-3,7-diene36 (80)
To a vigorously stirred suspension of sodium (1.84 g, 80 mmol) in dry toluene (40 ml) at reflux was added a solution of diester 79 (3.74 g, 17.8 mmol) and freshly distilled chlorotrimethylsilane (9.12 g, 84 mmol) in dry toluene (10 ml) during 2 hr. The resulting mixture was heated at reflux for an additional 10 hr, cooled, filtered through Celite, and washed with dry ether. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography over silica gel (Hex : EA = 10 :1) to provide 80 (4.43 g, 96.4 %).
1H NMR: δ 0.19 (s, 18 H); 1.56 (d, 1H, J=8.1 Hz); 1.94 (d, 1H, J=8.1 Hz); 2.57 (s, 2H);
2.72-2.73 (m, 2H); 5.90-5.91 (m, 2H)
13C NMR: δ 0.40 (q); 41.11 (d); 42.27 (d); 54.22 (t); 125.97 (s); 131.54 (d)
O O
bicyclo[4.2.1]non-7-ene-3,4-dione (82)
A mixture of 3,4-bis(trimethylsiloxy)bicycle[4.2.1]nona-3,7-diene (6.18 g, 20.9 mmol) and Cu(OAc)2.H2O (8.34 g, 2 eq.) in methanol (10 ml) and 50 % aqueous acetic acid was heated at 75oC for 12 hr. The reaction mixture was cooled, filtered though Celite, and washed with CH2Cl2. The solution was separated on addition of water, the organic layer was separated.
The aqueous layer was extracted with CH2Cl2, and the organic extracts were combined, washed with water and 10 % K2CO3, dried over Na2SO4, and evaporated. The residue was purified by column chromatography over silica gel to afford 82 (1.97 g, 62 %).
1H NMR: δ 1.42-1.46 (d, 1H, J=13.8 Hz); 2.20-2.29 (m, 1H); 2.25-2.32 (m, 2H); 2.47 (dd, 2H, J1=14.4 Hz, J2=5.4 Hz); 2.92-2.97 (m, 2H); 5.72 (s, 2H)
13C NMR: δ 35.47 (t); 37.14 (d); 42.26 (t); 134.53 (d); 207.49 (s)
IR (neat): ν 3410; 2938; 1698; 1653; 1541; 1457; 1380; 1215; 1139; 1103; 1049; 991; 871;
812; 739
EI-MS: 150 (M+, 14.89); 122 (8.78); 107 (10.45); 91 (11.07); 79 (100); 66 (26.72) HR-MS: Anal. calcd. for C9H10O2: 150.0681; Found: 150.0681
MeOOC COOMe
cis-1,3-dicarbomethoxycyclopent-4-ene37 (83)
88 (8.86 g, 60 mmol) was hydrolyzed with KOH (13.6 g, 24.3 mmol) in 70 % ethanol (50 ml) by heating the solution at reflux for 10 hr. After addition of water (30 ml), ethanol was evaporated. The solution was then acidified, and extracted with EA. The combined extracts were dried over Na2SO4 and evaporated. The residue was dissolved in methanol (30 ml) and several drops of conc. H2SO4 were added. The solution was heated at reflux overnight and the methanol was evaporated after addition of water (20 ml). The residue was extracted with CH2Cl2, and the organic extracts were washed with water, dried over Na2SO4, and evaporated.
The residue was purified by column chromatography over silica gel to afford 83 (9.2 g, 71.5
%).
1H NMR: δ 0.97 (dt, 1H, J1=7.5 Hz, J2=13.2 Hz); 2.19-2.41 (m, 5H); 2.95-3.05 (m, 2H); 3.59 (s, 6H); 5.60 (s, 2H)
13C NMR: δ 36.71 (t); 40.54 (t); 41.85 (d); 51.29 (q); 134.24 (d); 172.83 (s)
TMSO OTMS
3,4-bis(trimethylsiloxy)bicyclo[4.2.1]nona-3,7-diene (84)
A dispersion of sodium (0.30 g, 13 mmol) was placed in dry toluene (15 ml) at reflux and with rapidly stirring for 1 hr. After cooling to room temperature, diester 83 (0.50 g, 2.4 mmol) was added followed by freshly distilled chlorotrimethylsilane (1.36 g, 12.6 mmol) in dry toluene (4 ml) in a dropwise manner at temperature below 50oC during 0.5 hr. The resulting mixture was heated at reflux for 1 d, cooled, filtered through Celite, and washed with dry ether. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography over silica gel (Hex : EA = 10 :1) to provide 84 (0.30 g, 43 %).
1H NMR: δ 0.10 (s, 18H); 1.442 (d, 1H, J=11.7 Hz); 1.99-2.09 (m, 1H); 2.13-2.14 (m, 2H);
2.41-2.51 (m, 2H); 2.72-2.76 (m, 2H); 5.68 (s, 2H)
13C NMR: δ 0.99 (q); 37.26 (t); 38.33 (t); 39.43 (d); 133.48 (d); 133.72 (s)
IR (neat): ν 3052; 2956; 2907; 2832; 2360; 1718; 1667;1558; 1507; 1448; 1435; 1410; 1340;
1250; 1178; 1082; 1025; 972; 888; 842; 757; 718; 687; 650
EI-MS: 296 (M+, 51.11); 281 (10.56); 230 (99.11); 215 (31.56); 147 (39.56); 73 (100); 45 (27.33)
HR-MS: Anal. calcd. for C15H28O2Si2: 296.1628; Found: 296.1627
O O O O
3,4-bis(1,3-dioxolan-2-yl)-bicyclo[4.2.1]non-7-ene (85)
A mixture of bicyclo[4.2.1]non-7-ene-3,4-dione (0.25 g, 1.67 mmol), ethlylene glycol (1.60 g, 25.8 mmol), and p-toluenesufonic acid (30 mg) in benzene (20 ml) was heated under a Dean-Stark apparatus at reflux overnight. Benzene was distilled as much as possible. The residue was basified with sat. K2CO3 and extracted with CH2Cl2. The organic phase was washed with water and brine, dried over Na2SO4 and evaporated. The residue was purified by short column chromatography over silica gel to afford bisketal product 85 (0.21 g, 53 %).
1H NMR: δ 1.49-1.60 (m, 3H); 1.62-1.77 (m, 2H); 2.18 (d, 1H, J=11.7 Hz); 2.46-2.51 (m, 2H);
3.71-3.82 (m, 8H); 5.62 (s, 2H)
13C NMR: δ 35.47 (t); 37.14 (d); 42.26 (t); 134.53 (d); 207.49 (s)
IR (neat): ν 3481; 2952; 2895; 1724; 1427; 1404; 1367; 1314; 1156; 1070; 1030; 1002; 953;
867; 849; 830; 717
EI-MS: 238 (M+, 5.47); 165 (37.34); 150 (18.67); 137 (25.31); 86 (100); 79 (34.02); 41 (28.63)
HR-MS: Anal. calcd. for C13H18O4: 238.1205; Found: 238.1206
HO OH
cis-1,3-bis-hydroxymethyl-cyclopent-4-ene8 (86)
Ozone was bubbled into a solution of norbornadiene (20.00 g, 217.1 mmol) in a mixture of methanol (280.0 ml) and CH2Cl2 (160 ml) at -78oC. When all starting material had been consumed, the solution was purged with N2, and NaBH4 (8.20 g, 216.6 mmol) was added very slowly to the reaction mixture while keeping the temperature below -60oC. After 1 hr, the reaction mixture was warmed to room temperature, and sat. K2CO3 was added. Solvents were evaporated under reduced pressure, and the residue was extracted with EA. The product was isolated by distillation to give the product 86 (15.70 g, 56.4%) as a clear oil.
1H NMR: δ 1.32 (dt, 1H, J1=5.4 Hz, J2=13.5 Hz); 2.13 (dt, 1H, J1=9.3 Hz, J2=13.5 Hz);
2.79-2.87 (m, 2H); 3.49 (d, 4H, J=4.8 Hz); 3.94 (s, 2H); 5.64 (s, 2H)
13C NMR: δ 28.80 (t); 47.93 (d); 65.92 (t); 133.31 (d)
TsO OTs
cis-1,3-bis(toluenesulfonyloxymethyl)-cyclopent-4-ene8 (87)
To a solution of diol 86 (6.40 g, 50.0 mmol), p-toluenesulfonyl chloride (28.6 g, 150 mmol) in dry ether (50 ml), pyridine (25.0 ml) was added dropwise at 0oC. The reaction mixture was stirred for another 2 hr after removal of the ice bath. The mixture was poured into ice water and ether was evaporated carefully. The residue was added more ice water and excess p-toluenesulfonyl chloride was consumed after 3 hr. The white solid was filtered and washed with water and methanol. The solid was dried under reduced pressure to give the product 87 (18.7 g, 86%) without further purification.
1H NMR: δ 1.09 (dt, 1H, J1=6.3 Hz, J2=13.5 Hz); 2.13 (dt, 1H, J1=8.7 Hz, J2=13.5 Hz); 2.42 (s, 6H); 2.93-3.02 (m, 2H); 3.84 (d, 4H, J=4.5 Hz); 5.57 (s, 2H); 7.31-7.34 (m, 4H); 7.72-7.76 (m, 4H)
13C NMR: δ 21.60 (q); 29.11 (t); 44.96 (d); 72.91 (t); 127.83 (d); 129.86 (d); 132.46 (d);
132.76 (s); 144.86 (s)
NC CN
cis-1,3-bis(cyanomethyl)-cyclopent-4-ene8 (88)
A solution of ditosylate 87 (10.0 g, 22.9 mmol) and NaCN (4.5 g, 91.8 mmol) in DMF (50.0 ml) was heated at 60oC for 30 hr. The reaction mixture was evaporated under reduced pressure and the residue was triturated with EA, washed with water and 0.5N HCl. The organic solutions were dried over Na2SO4 and evaporated. The residue was purified by column chromatography over silica gel to give the product 88 (3.1 g, 93%) as a colorless oil.
1H NMR (CDCl3): δ 1.19 (dt, 1H, J1=6.9 Hz, J2=13.5 Hz); 2.42 (d, 4H, J=6.6 Hz); 2.50 (dt, 1H, J1=8.4 Hz, J2=13.5 Hz); 3.00-3.09 (m, 2H); 5.73 (s, 2H)
13C NMR (CDCl3): δ 23.19 (t); 32.73 (t); 41.93 (d); 118.34 (s); 133.82 (t)
O O O O OH OH
O O
(12RS,14SR)-1,4,7,10-tetraoxadispiro[4.0.4.5]pentadecane- 12,14-dicarboxylic acid (89)
A mixture of 85 (0.21, 0.88 mmol), ether (20 mL), and water (20 mL) was cooled in an ice bath. Solid KMnO4 (0.50 g, 3.16 mmol) was added in small portions with efficient stirring and cooling within 30 min. The mixture was then stirred at room temperature for 6 h. Solid Na2SO3 (0.30 g, 2.38 mmol) was added, MnO2 was filtered off, and the cake was washed several times with 5% NaHCO3. The clear filtrate was adjusted to pH 7 with conc. HCl and the insoluble solid was extracted with EA. The solution was cooled in an ice bath then acidified with conc. HCl to ~pH 3 and extracted immediately with EA. The extracts were combined, dried over Na2SO4, and evaporated to furnish diacid 89 (0.20 g, 75 %).
1H NMR (CD3OD): δ 1.87-2.00 (m, 2H); 2.09-2.11 (m, 3H); 2.25 (dt, 1H, J1=11.4 Hz, J2=3.3 Hz); 2.58-2.67 (m, 2H); 3.88-4.02 (m, 8H); 5.00 (br)
13C NMR (CD3OD): δ 32.33 (t); 37.97 (t); 40.5 (d); 66.79 (t); 66.91 (t); 112.01 (s); 179.15 (s) IR (neat): ν 3369; 2969; 2889; 2362; 2337; 1695; 1456; 1431; 1363; 1295; 1165; 1117; 1064;
1036; 955; 900; 654
EI-MS: 302 (M+); 284; 256; 240; 216; 212; 198; 185; 157; 143; 112; 99; 86 HR-MS: Anal. calcd. for C13H18O8: 302.1001; Found: 302.1002
NH
N
O O O
O
O O
3,4-bis(1,3-dioxolan-2-yl)-8-[2-(1H-indol-3-yl)ethyl]- 8-azabicyclo[4.3.1]decane-7,9-dione (90)
To an ice-cooled solution of diacid 89 (0.30 g, 1 mmol) in dry THF (10 ml) was added triethylamine (0.25 g, 2.5 mmol), and a solution of ethyl chloroformate (0.27 g, 2.4 mmol) in dry THF (5 ml) dropwise. The reaction mixture was stirred overnight at room temperature, and then evaporated in vacuo below 20oC. The residue (0.28 g) and tryptamine (0.16 g , 1 mmol) were dissolved in THF (10 ml) and the mixture was heated at reflux for 8 hr. On cooling, acetyl chloride (1 ml) was added, and then the mixture was heated at reflux for 10 hr.
Volatile materials were evaporated and the residue was purified by column chromatography over silica gel to afford 90 (0.40 g, 95 %).
1H NMR: δ 2.03-2.14 (m, 2H); 2.21-2.28 (m, 4H); 2.90-2.99 (m, 4H); 3.80-4.02 (m, 10H);
7.06 (s, 1H); 7.10-7.24 (m, 2H); 7.32-7.34 (m, 2H); 7.85-7.88 (m, 2H); 8.03 (br, 1H)
13C NMR: δ 22.40 (t); 22.59 (t); 35.40 (d); 37.16 (t); 40.99 (t); 65.54 (t); 65.73 (t); 110.95 (d);
111.53 (s); 113.42 (s); 119.38 (d); 121.94 (d); 121.96 (d); 127.59 (s); 136.19 (s); 176.17 (s) (one CH(Ar) peak was not found)
IR (neat): ν 3406; 3057; 2969; 2895; 1716; 1663; 1456; 1430; 1357; 1278; 1177; 1145; 1117;
1078; 1044; 951; 904; 744
EI-MS: 426 (M+, 4.11); 340 (2.27); 212 (7.43); 143 (100); 130 (17.34) HR-MS: Anal. calcd. for C23H26O6N2: 426.1798; Found: 426.1795
NH
N
O O O
O
O S
(1RS,6SR)-3,4-bis(1,3-dioxolan-2-yl)-8-[2-(1H-indol-3-yl)ethyl]- 9-thioxo-8-azabicyclo[4.3.1]decan-7-one (92)
A mixture of imide 90 (0.50 g, 1.2 mmol) and Lawesson’s reagent (0.95 g, 2.35 mmol) was reflux in dry toluene (15 ml) for 10 hr. Evaporation left a residue which was purified by column chromatography over silica gel to afford 92 (0.35 g, 67.5 %).
1H NMR: δ 2.15-2.58 (m, 6H); 2.95-3.05 (m, 2H); 3.13-3.23 (m, 1H); 3.56-3.58 (m, 1H);
3.77-4.07 (m, 8H); 4.34-4.44 (m, 1H); 4.63-4.73 (m, 1H); 7.06 (s, 1H); 7.10-7.20 (m, 2H);
7.31-7.33 (d, 1H, J=5.4 Hz); 7.90-7.93 (m, 1H); 8.18 (br, 1H) (one CH2 (ketal) peak was not found)
13C NMR: δ 21.18 (t); 23.08 (t); 35.14 (d); 37.95 (t); 40.20 (t); 45.52 (d); 47.44 (t); 65.29 (t);
65.63 (t); 65.75 (t); 110.93 (d); 111.30 (s); 113.43 (s); 119.94 (s); 119.23 (d); 119.42 (d);
121.85 (d); 122.14 (d); 127.51 (s); 136.14 (s); 172.66 (s); 214.59 (s)
IR (neat): ν 3405; 2963; 2932; 2889; 1698; 1456; 1427; 1386; 1362; 1315; 1283; 1231; 1176;
1141; 1095; 1071; 1043; 948; 906; 734
EI-MS: 442 (M+, 2.19); 143 (100); 130 (7.33)
HR-MS: Anal. calcd. for C23H26O5N2S: 442.1564; Found: 442.1565
NH
N
O O O
O O
(1RS,6RS)-3,4-bis(1,3-dioxolan-2-yl)-8-[2-(1H-indol-3-yl)ethyl]- 8-azabicyclo[4.3.1]decan-7-one (93)
A suspension of Raney nickel (ca. 2 g) in absolute t-BuOH (8 ml) added to a hot solution of 92 (0.40 g, 0.9 mmol) in abs. t-BuOH (30 ml). The mixture was stirred for 3 hr at 60oC.
The catalyst was separated by filtration and then washed with CH2Cl2. The filtrate was dried over Na2SO4 and evaporated to afford product 93 (0.35 g, 94 %).
1H NMR: δ 1.88-1.95 (m, 1H); 2.05-2.19 (m, 3H); 2.32-2.37 (m, 1H); 2.43 (dd, 1H, J1=3.3 Hz, J2=14.4 Hz); 2.58-2.60 (m, 1H); 2.88-3.14 (m, 3H); 3.29-3.41 (m, 2H); 3.83-4.14 (m, 10H);
7.00 (s, 1H); 7.04-7.16 (m, 2H); 7.33 (d, 1H, J=7.8 Hz); 7.65 (d, 1H, 7.8 Hz); 8.69 (br, 1H)
13C NMR: δ 22.30 (t); 24.79 (d); 27.64 (t); 34.97 (d); 36.65 (t); 37.75 (t); 48.40 (t); 56.44 (t);
65.20 (t); 65.28 (t); 65.68 (t); 66.05 (t); 111.18 (d); 111.79 (s); 112.13 (s); 113.02 (s); 118.69 (d); 118.97 (d); 121.64 (d); 122.18 (d); 127.41 (s); 136.32 (s); 171.45 (s)
IR (neat): ν 3258; 3053; 2959; 2931; 2893; 2694; 1614; 1494; 1455; 1428; 1340; 1297; 1167;
1169; 1110; 1084; 1046; 1010; 951; 893; 741; 700
EI-MS: 412 (M+, 4.19); 270 (9.88); 210 (14.22); 198 (15.27); 143 (100); 130 (25.9) HR-MS: Anal. calcd. for C23H28O5N2: 412.1999; Found: 412.2008
NH
N
OO O O
Bisketal (91)
Freshly distilled POCl3 (0.6 ml) was added to a boiling solution of lactam 93 (0.15 g, 0.36 mmol) in benzene (5 ml) with vigorous stirring. After refluxing for 3 hr, the excess of POCl3 and benzene were removed in vacuo and the residue was dissolved in CH2Cl2 / MeOH (8 ml, 1:1), then NaBH4 (0.10 g) was added in protions. After stirring for 2 hr at room temperature, solvent was evaporated and water was added to the residue. Extraction with CH2Cl2 followed by standard workup provided a solid which could be purified chromatographically (0.13 g, 90.2 %), dec. ~200oC
1H NMR (CDCl3+CD3OD): δ 1.33-1.41 (m, 1H); 1.56-1.61 (m, 1H); 1.75-1.96 (m, 4H); 2.20 (m, 1H); 2.35-2.49 (m, 3H); 2.62-2.66 (m, 1H); 2.76-2.82 (m, 2H); 3.13 (m, 1H); 3.32-3.39 (m, 1H); 3.77-3.88 (m, 8H); 6.86-6.95 (m, 2H); 7.15 (d, 1H, J=7.5 Hz); 7.30 (d, 1H, J=7.5 Hz)
13C NMR (CDCl3+CD3OD): δ 21.37 (t); 28.58 (d); 29.99 (t); 31.07 (d); 32.88 (t); 39.96 (t);
52.66 (t); 61.20 (t); 63.81 (d); 64.42 (t); 65.14 (t); 65.32 (t); 65.50 (t); 110.00 (s); 110.45 (d);
113.15 (s); 113.45 (s); 117.52 (d); 118.53 (d); 120.50 (d); 127.18 (s); 134.37 (s); 136.18 (s) IR (neat): ν 3419; 2955; 2897; 2796; 2744 (Wenkert-Bohlmann bands); 2529; 2244; 2088;
1645; 1456; 1346; 1266; 1172; 1081; 1045; 952; 852; 737
EI-MS: 396 (M+, 45.20); 251 (23.48); 211 (39.65); 184 (100); 169 (79.8); 156 (32.58); 143 (29.8); 112 (37.63)
HR-MS: Anal. calcd. for C23H28O4N2: 396.2050; Found: 396.2047