4040
C. Ramesh et al. / Tetrahedron Letters 50 (2009) 4037–4041
J. Bioorg. Med. Chem. 2006, 14, 4600; (s) Madapa, S.; Singh, V.; Batra, S.
(8), 305 (15), 229 (19), 217 (68), 206 (100), 192 (72), 178 (18), 151 (8). HRMS
calcd for C25H20N2O3 (M+) 396.1468, found 396.1466. Anal. Calcd for
C25H20N2O3: C, 75.74; H, 5.08; N, 7.07. Found: C, 75.63; H, 5.36; N, 7.09.
Tetrahedron 2006, 62, 8740; (t) Pathak, R.; Madapa, S.; Batra, S. Tetrahedron
2007, 63, 451; (u) Colacino, E.; André, C.; Martinez, J.; Lamaty, F. Tetrahedron
Lett. 2008, 49, 4953; (v) Gowrisankar, S.; Lee, H. S.; Kim, J. M.; Kim, J. N.
Tetrahedron Lett. 2008, 49, 1670.
3-((5-Methoxy-1H-indol-3-yl)methyl)-4-(3-nitrophenyl)but-3-en-2-one
(5a):
Yellow solid; mp: 133–134 °C. 1H NMR (400 MHz, CDCl3)
d
8.27 (s, 1H),
11. (a) Chu, C. M.; Gao, S.; Sastry, M. N. V.; Yao, C.-F. Tetrahedron Lett. 2005, 46,
4971; (b) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett. 2005, 46,
5771; (c) Shivaji, V. M.; Sastry, M. N. V.; Wang, C. C.; Yao, C.-F. Tetrahedron Lett.
2005, 46, 6345; (d) Lin, C.; Hsu, J.; Sastry, M. N. V.; Fang, H.; Tu, Z.; Liu, J. T.; Yao,
C.-F. Tetrahedron 2005, 61, 11751; (e) Ko, S.; Lin, C.; Tu, Z.; Wang, Y. F.; Wang, C.
C.; Yao, C. F. Tetrahedron Lett. 2006, 47, 487; (f) Gao, S.; Tzeng, T.; Sastry, M. N.
V.; Chu, C. M.; Liu, J. T.; Lin, C.; Yao, C.-F. Tetrahedron Lett. 2006, 47, 1889; (g)
Chu, C. M.; Huang, W. J.; Liu, J. J.; Yao, C.-F. Tetrahedron Lett. 2007, 48, 6881.
12. (a) Basavaih, D.; Gowriswari, V. V. L. Tetrahedron Lett. 1986, 27, 2031; (b) Shi,
M.; Jiang, J.-K.; Li, C.-Q. Tetrahedron Lett. 2002, 43, 127; (c) Shi, M.; Liu, Y.-H.
Org. Biomol. Chem. 2006, 1468.
13. Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V.; Prabhakar, A.;
Jagadeesh, B. Tetrahedron Lett. 2005, 46, 639.
14. Das, B.; Holla, H.; Srinivas, Y.; Chowdhury, N.; Bandgar, B. P. Tetrahedron Lett.
2007, 48, 3201.
15. (a) Madapa, S.; Sridhar, D.; Yadav, G. P.; Maulik, P. R.; Batra, S. Eur. J. Org. Chem.
2007, 4343; (b) Basavaiah, D.; Reddy, R. J.; Rao, J. S. Tetrahedron Lett. 2006, 47,
73; (c) Basavaiah, D.; Reddy, M. R.; Kumaragurubaran, N.; Sharada, D.
Tetrahedron 2002, 58, 3693.
16. Di Santo, R.; Costi, R.; Forte, M.; Galeffi, C. Arkivoc 2004, 5, 181.
17. Parvatkar, P. T.; Parameswaran, P. S.; Tilve, S. G. Tetrahedron Lett. 2007, 48,
7870.
8.16–8.14 (m, 1H), 7.93 (br s, 1H), 7.72 (d, J = 7.4 Hz, 1H), 7.67 (s, 1H), 7.47 (t,
J = 8.0 Hz, 1H), 7.24 (d, J = 2.4 Hz, 1H), 6.90–6.82 (m, 3H), 3.93 (s, 2H), 3.81 (s,
3H), 2.47 (s, 3H). 13C NMR (100 MHz, CDCl3) d 199.7, 154.0, 148.3, 142.3, 137.1,
136.5, 134.8, 131.6, 129.6, 127.2, 124.3, 123.2, 122.6, 112.7, 112.5, 111.9, 100.5,
55.8, 26.4, 23.0. MS (m/z) (relative intensity) 349 (M+, 100), 333 (26), 306 (33),
290 (16), 260 (18), 228 (21), 189 (11), 160 (35), 147 (24), 116 (12). HRMS calcd
for C20H18N2O4 (M+) 350.1261, found 350.1264. Anal. Calcd for C20H18N2O4: C,
68.56; H, 5.18; N, 8.00. Found: C, 67.80; H, 4.93; N, 7.66. 3-((5-Bromo-1H-indol-
3-yl)methyl)-4-(3-nitrophenyl) but-3-en-2-one (6a): Yellow solid; mp: 122–
123 °C. 1H NMR (400 MHz, CDCl3) d 8.23 (br s, 1H), 8.18–8.16 (m, 2H), 7.67 (d,
J = 6.2 Hz, 2H), 7.50 (t, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.25–7.17 (m, 2H), 6.84 (s,
1H), 3.88 (s, 2H), 2.47 (s, 3H). 13C NMR (100 MHz, CDCl3) d 199.5, 148.3, 142.2,
137.1, 136.9, 134.9, 134.6, 129.7, 128.5, 125.1, 124.1, 123.4, 123.2, 121.3, 112.8,
112.7, 112.6, 26.3, 22.6. MS (m/z) (relative intensity) 400 (M+2, 69), 399 (M+,
55), 382 (53), 381 (37), 301 (19), 275 (75), 274 (58), 208 (70), 207 (51), 195
(39), 153 (18), 128 (38), 114 (22), 101 (14). HRMS calcd for C19H15BrN2O3 (M+)
398.0261, found 398.0248 and HRMS calcd for C19H1581BrN2O3 (M+) 400.0240,
found 400.0240. Anal. Calcd for C19H15BrN2O3: C, 57.16; H, 3.79; N, 7.02.
Found: C, 56.96; H, 3.89; N, 6.69. 3-((7-Ethyl-1H-indol-3-yl)methyl)-4-(3-nitro
phenyl) but-3-en-2-one (7a): Brown gummy liquid, 1H NMR (400 MHz, CDCl3) d
8.26 (s, 1H), 8.14 (dd, J = 8.2, 1.4 Hz, 1H), 7.99 (br s, 1H), 7.72 (d, J = 1.8 Hz, 1H),
7.67 (s, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.34–7.32 (m, 1H), 7.10–7.05 (m, 2H), 6.85
(s, 1H), 3.97 (s, 2H), 2.84 (q, J = 7.5 Hz, 2H), 2.46 (s, 3H), 1.35 (t, J = 7.6 Hz, 3H).
13C NMR (100 MHz, CDCl3) d 200.0, 147.8, 141.9, 136.7, 136.6, 135.0, 134.6,
129.3, 126.5, 126.3, 123.9, 122.8, 121.5, 120.3, 119.3, 115.9, 112.7, 26.1, 23.5,
22.8, 13.5. MS (m/z) (relative intensity) 348 (M+, 100), 304 (51), 275 (23), 258
(36), 228 (32), 227 (23), 202 (14), 157 (48), 144 (38), 129 (24), 114 (9). HRMS
calcd for C21H20N2O3 (M+) 348.1468, found 348.1472. Anal. Calcd for
C21H20N2O3: C, 72.40; H, 5.79; N, 8.04. Found: C, 67.58; H, 5.70; N, 7.16. 3-
((1H-Indol-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one (8a): Yellow solid;
mp: 135–136 °C. 1H NMR (400 MHz, CDCl3) d 8.12 (d, J = 9.6 Hz, 1H,), 7.98
(br s, 1H), 7.93 (s, 1H), 7.54–7.44 (m, 2H), 7.39 (d, J = 7.6 Hz, 1H,), 7.33–7.25 (m,
2H), 7.16 (t, J = 7.3 Hz, 1H), 7.03 (t, J = 7.3 Hz, 1H), 6.7 (s, 1H), 3.7 (s, 2H), 2.4 (s,
3H). 13C NMR (100 MHz, CDCl3) d 199.8, 147.4, 141.1, 136.4, 136.2, 133.6,
131.7, 130.8, 129.2, 126.8, 124.9, 122.1, 121.9, 119.2, 118.5, 113.7, 111.0, 26.5,
22.4. MS (m/z) (relative intensity): 320 (M+, 18), 276 (31), 261 (50), 260 (100),
230 (33), 202 (16). HRMS calcd for C19H16N2O3 (M+) 320.1155, found 320.1153.
Anal. Calcd for C19H16N2O3: C, 71.24; H, 5.02; N, 8.74. Found: C, 71.31; H, 5.26;
N, 8.53. 3-((2-Methyl-1H-indol-3-yl) methyl)-4-(2-nitrophenyl)but-3-en-2-one
(9a): Brown gummy liquid. 1H NMR (400 MHz, CDCl3) d 8.12 (d, J = 7.4 Hz,
1H), 7.8 (s, 1H), 7.59 (br s, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.38–7.31 (m, 2H), 7.12–
7.07 (m, 2H), 7.02–6.99 (m, 1H), 6.92 (m, 1H) 3.76 (s, 2H), 2.44 (s, 3H), 2.11 (s,
3H). 13C NMR (100 MHz, CDCl3) d 200.3, 146.8, 141.8, 135.9, 134.9, 133.1,
131.7, 131.6, 130.8, 128.7, 128.1, 124.6, 120.6, 118.9, 117.8, 109.9, 107.9, 26.4,
21.6, 11.5. MS (m/z) (relative intensity) 335 (M+1, 15), 333 (81), 290 (33), 275
(72), 274 (80), 244 (20), 183 (15), 158 (46), 143 (100), 129 (79), 126 (15). HRMS
calcd for C20H18N2O3 (M+) 334.1312, found 334.1317. Anal. Calcd for
C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 70.99; H, 5.55; N, 7.99.
Methyl 3-(2-(2-nitrobenzylidene)-3-oxobutyl)-1H-indole-2-carboxylate (10a):
Yellow solid; mp: 149–150 °C 1H NMR (400 MHz, CDCl3) d 8.45 (br s, 1H),
7.88 (s, 1H), 7.82 (dd, J = 8.2, 1.0 Hz, 1H), 7.36–7.30 (m, 2H), 7.22–7.14 (m, 4H),
7.00–6.97 (m, 1H), 4.22 (s, 2H), 3.83 (s, 3H), 2.56 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 199.5, 161.8, 146.0, 141.3, 137.5, 135.5, 132.8, 131.7, 130.3, 128.4,
127.2, 125.5, 124.0, 122.9, 121.1, 121.0, 120.0, 111.4, 51.6, 26.1, 22.1. MS (m/z)
(relative intensity) 378 (M+, 60), 361 (27), 318 (59), 286 (57), 258 (62), 228
(32), 188 (100), 187 (80), 155 (53), 127 (40), 101 (15). HRMS calcd for
C21H18N2O5 (M+) 378.1210, found 378.1210. Anal. Calcd for C21H18N2O5: C,
72.40; H, 5.79; N, 8.04. Found: C, 66.30; H, 4.95; N, 7.22. 4-(2-Nitrophenyl)-3-
((2-phenyl-1H-indol-3-yl)methyl)but-3-en-2-one (11a): Red solid; mp: 134–
135 °C. 1H NMR (400 MHz, CDCl3) d 7.87 (dd, J = 8.0, 1.1 Hz, 2H), 7.76 (s, 1H),
7.42–7.38 (m, 4H), 7.36–7.28 (m, 3H), 7.26–7.20 (m, 2H), 7.15–7.08 (m, 2H),
6.99 (t, J = 7.5 Hz, 1H) 4.06 (s, 2H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) d
200.2, 146.3, 141.9, 136.5, 135.6, 134.6, 132.8, 132.7, 131.5, 130.3, 128.6, 128.5,
128.1, 127.6, 124.4, 122.1, 119.5, 119.3, 110.5, 110.4, 109.6, 26.2, 22.2. MS (m/z)
(relative intensity) 396 (M+, 23), 362 (10), 353 (30), 336 (51), 318 (42), 305
(12), 229 (13), 216 (22), 203 (100), 193 (85), 178 (22), 151 (7). HRMS calcd for
C25H20N2O3 (M+) 396.1468, found 396.1461. Anal. Calcd for C25H20N2O3: C,
75.74; H, 5.08; N, 7.07. Found: C, 75.84; H, 5.14; N, 6.98. 3-((5-Methoxy-1H-
indol-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one (12a): Yellow solid; mp:
133–134 °C. 1H NMR (400 MHz, CDCl3) d 8.13 (dd, J = 8.1, 1.2 Hz, 1H), 7.93 (s,
1H), 7.86 (br s, 1H), 7.54–7.52 (m, 1H), 7.49–7.47 (m, 1H), 7.41 (d, J = 7.5 Hz,
1H), 7.18 (d, J = 8.6 Hz, 1H), 6.83–6.78 (m, 2H), 6.73 (s, 1H), 3.79 (s, 3H), 3.74 (s,
2H), 2.49 (s, 3H). 13C NMR (100 MHz, CDCl3) d 199.8, 153.8, 147.4, 141.1, 136.4,
133.6, 131.7, 131.3, 130.9, 129.2, 127.1, 124.9, 122.6, 113.4, 112.4, 111.8, 100.4,
55.8, 26.5, 22.6. MS (m/z) (relative intensity) 350 (M+, 47), 315 (8), 306 (33),
290 (100), 248 (23), 247 (29), 217 (25), 188 (19), 159 (48), 147 (35), 132 (22),
117 (11), 89 (6). HRMS calcd for C20H18N2O4 (M+) 350.1261, found 350.1254.
Anal. Calcd for C20H18N2O4: C, 68.56; H, 5.18; N, 8.00. Found: C, 68.78; H, 5.15;
N, 7.83. 3-((5-Bromo-1H-indol-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one
(13a): Yellow solid; mp: 122–123 °C. 1H NMR (400 MHz, CDCl3) d 8.14 (dd,
J = 8.1, 1.0 Hz, 1H), 8.0 (br s, 1H), 7.93 (s, 1H), 7.61–7.57 (m, 1H), 7.54–7.50 (m,
18. (a) Lee, K. Y.; Lee, Y. J.; Kim, J. N. Bull. Korean Chem. Soc. 2007, 28, 143; (b)
Basavaiah, D.; Rao, J. S. Tetrahedron Lett. 2004, 45, 1621; (c) Lee, M. J.; Lee, K. Y.;
Park, D. Y.; Kim, J. N. Bull. Korean Chem. Soc. 2005, 26, 1281.
19. CCDC numbers of 12a, 12b are 714386, 714387, respectively. These data can be
obtained free of charge from Cambridge Crystallographic Data Center via
20. Experimental procedures: The C-alkylation of indoles with Baylis–Hillman adducts:
To a stirred solution of Baylis–Hillman adduct (8) (2 mmol) in acetonitrile were
added indole (2.8 mmol) and iodine (30 mol %) and the mixture was stirred to
completion, as monitored by TLC. After completion of the reaction, the reaction
mixture was quenched with saturated solution of sodium thiosulfate and
extracted with ethyl acetate (2 ꢀ 10 mL). The organic layer was separated,
dried over anhydrous magnesium sulfate and concentrated to give the crude
product. The crude product obtained 8a was purified by passing through a
short silica gel column.
21. Reductive cyclization: To a stirred solution of 8a (1 mmol) in acetic acid (5 mL),
powdered Fe (6 mmol) was added and the reaction mixture was then refluxed
for 2 h. The mixture was cooled to room temperature and the acetic acid was
removed under reduced pressure, EtOAc (10 mL) was added, then the mixture
was stirred for 2 min and then filtered to remove any iron impurities. The
insoluble iron residue was washed with EtOAc (10 mL). The filtrate and
washings were combined and dried over anhydrous MgSO4. The solvent was
removed under reduced pressure and the crude product thus obtained was
purified by column chromatography (silica gel).
22. Spectral data: 3-((1H-indol-3-yl)methyl)-4-phenylbut-3-en-2-one (1a): Gummy
liquid, 1H NMR (400 MHz, CDCl3) d 8.0 (br s, 1H), 7.70 (s, 1H), 7.52 (d, J = 7.8 Hz,
1H), 7.43–7.41 (m, 2H), 7.31–7.29 (m, 4H), 7.22–7.15 (m, 1H), 7.11–7.07 (m,
1H), 6.78 (s, 1H), 3.99 (s, 2H), 2.43 (s, 3H). 13C NMR (100 MHz, CDCl3) d 200.5,
140.1, 139.4, 136.2, 134.1, 129.3, 128.6, 128.3, 126.7, 121.7, 121.6, 118.8, 118.4,
112.9, 111.1, 26.0, 22.7.MS (m/z) (relative intensity) 275 (M+, 66), 274 (100),
232 (30), 201 (7), 153 (6), 114 (24), 102 (5). HRMS calcd for C19H17NO (M+)
275.1305, found 275.1307. Anal. Calcd for C19H17NO: C, 80.60; H, 6.94; N,
4.72. Found: C, 80.21; H, 6.78; N, 4.79. 3-((1H-Indol-3-yl)methyl)-4-(3-nitro-
phenyl)but-3-en-2-one (2a): Brown gummy liquid, 1H NMR (400 MHz, CDCl3) d
8.25 (br s, 1H), 8.20 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.65 (d, J = 4.8 Hz, 2H), 7.44
(d, J = 7.8 Hz, 1H), 7.38–7.33 (m, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.16–7.12 (m, 1H),
7.10–7.04 (m, 1H), 6.74 (s, 1H), 3.93 (s, 2H), 2.44 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 199.9, 148.0, 142.0, 136.9, 136.8, 136.4, 134.7, 129.5, 126.6, 124.1,
123.1, 122.1, 121.8, 119.3, 118.4, 112.7, 111.2, 26.3, 22.9. MS (m/z) (relative
intensity) 319 (M+, 100), 302 (36), 277 (28), 260 (14), 230 (47), 202 (18), 200
(14), 159 (8), 129 (31), 116 (18), 76 (8). HRMS calcd for C19H16N2O3 (M+)
320.1155, found 320.1162. Anal. Calcd for C19H16N2O3: C, 71.24; H, 5.03; N,
8.74. Found: C, 69.45; H, 4.70; N, 8.37. 3-((2-Methyl-1H-indol-3-yl)methyl)-4-
(3-nitrophenyl)but-3-en-2-one (3a): Red solid, mp: 110–111 °C. 1H NMR
(400 MHz, CDCl3) d 8.22 (s, 1H), 8.12 (dd, J = 8.1, 1.6 Hz, 1H), 7.74 (br s, 1H),
7.68 (d, J = 7.6 Hz, 1H), 7.55 (s, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.16 (m, 2H), 7.03 (t,
J = 7.0 Hz, 1H), 6.95–6.92 (m, 1H), 3.95 (s, 2H), 2.38 (s, 3H), 2.27 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 200.1, 148.0, 143.5, 137.4, 135.4, 135.0, 134.8, 131.8,
129.3, 128.1, 123.9, 122.8, 120.8, 119.1, 117.9, 110.2, 107.5, 26.6, 22.4, 11.9. MS
(m/z) (relative intensity) 335 (M+1, 16), 333 (100), 318 (36), 290 (10), 244 (18),
201 (10), 183 (15), 143 (80), 130 (70), 126 (7). HRMS calcd for C20H18N2O3 (M+)
334.1312, found 334.1320. Anal. Calcd for C20H18N2O3: C, 71.84; H, 5.43; N,
8.38. Found: C, 72.11; H, 5.12; N, 8.39. 4-(3-Nitrophenyl)-3-((2-phenyl-1H-indol-
3-yl)methyl)but-3-en-2-one (4a): Red solid; mp: 109–110 °C. 1H NMR
(400 MHz, CDCl3) d 7.96–7.93 (m, 3H), 7.43–7.33 (m, 8H), 7.27–7.23 (m, 2H),
7.14–7.10 (m, 1H), 7.05–7.01 (m, 1H), 4.19 (s, 2H), 2.29 (s, 3H).13C NMR
(100 MHz, CDCl3) d 199.9, 147.7, 143.5, 137.0, 136.3, 135.7, 134.9, 134.2, 132.8,
128.8, 128.6, 128.4, 128.2, 127.8, 123.4, 122.5, 122.1, 119.6, 119.1, 110.8, 109.1,
26.3, 22.4. MS (m/z) (relative intensity) 396 (M+, 56), 394 (46), 353 (18), 318