J.-ka Kobayashi et al. / Tetrahedron 66 (2010) 3917–3922
3921
Anal. Calcd for C13H12N2O: C, 73.56; H, 5.70; N, 13.20. Found: C,
73.38; H, 5.67; N, 13.19.
J¼7.1), 3.03 (2H, t, J¼5.8), 7.29–7.34 (2H, m), 7.80 (1H, s), 9.05 (1H, br
s); 13C NMR (125 MHz,
, CDCl3) 13.82, 17.73, 19.06, 22.35, 23.50,
d
30.27, 31.25, 42.47, 42.85, 43.89, 101.81, 110.96, 111.41, 121.03, 123.41,
124.25, 127.61, 136.98, 137.72, 207.99, 212.95. Anal. Calcd for
C21H26N2O2: C, 74.52; H, 7.74; N, 8.28. Found: C, 74.39; H, 7.77; N, 8.29.
4.1.5. 4-(7-Methyl-1H-indol-3-yl)butan-2-one (3f). Mp 140–141 ꢀC
(recrystallized from hexane/dichloromethane); Rf 0.52 (ether/
hexane¼6/1); IR (neat, cmꢁ1) 3336, 1710, 1409, 1382, 1163, 792, 742,
597; 1H NMR (500 MHz,
d
, CDCl3, J¼Hz) 2.14 (3H, s), 2.47 (3H, s),
4.1.10. 2,3-Bis(3-oxybutenyl) 1H-indol (4a)9. Bp 145 ꢀC, 6 Torr/
2.84 (2H, t, J¼7.6), 3.04 (2H, t, 7.6), 6.98–7.00 (2H, m), 7.05 (1H, t,
Kugelrohr; Rf 0.2 (ether/hexane: ether¼2/1); 1H NMR (400 MHz,
d,
J¼7.4), 7.44 (1H, d, J¼7.7), 7.91 (1H, br s); 13C NMR (125 MHz,
d
,
CDCl3, J¼Hz) 2.09 (3H, s), 2.16 (3H, s), 2.76–2.83 (4H, m), 2.93–3.00
(4H, m) 7.03–7.13 (2H, m), 7.26 (1H, d, J¼8.1), 7.45 (1H, d, J¼7.7),
CDCl3) 16.53, 19.47, 30.01, 44.10, 115.66, 116.35, 119.52, 120.33,
121.17, 122.55, 125.67, 135.86, 208.77. Anal. Calcd for C13H15NO: C,
77.58; H, 7.51; N, 6.96. Found: C, 77.23; H, 7.50; N, 7.00.
8.48 (1H, br s, NH); 13C NMR (125 MHz,
d, CDCl3, J¼Hz) 18.16, 19.10,
30.04, 30.25, 43.85, 44.24, 109.96, 110.64, 117.88, 118.94, 121.20,
127.66, 134.90, 135.25, 208.80, 209.76; IR (neat, cmꢁ1) 3398, 2924,
1715, 1701, 1365, 1159, 808. Anal. Calcd for C16H19NO2: C, 74.68; H,
7.44; N, 5.44. Found: C, 74.34; H, 7.42; N, 5.49.
4.1.6. 1-(3-(3-Oxobutyl)-1H-indol-2-yl)octan-3-one (4b)
(Scheme 2). To a mixture of 3a (187 mg, 1.0 mmol) and 1-buten-3-
one (2a) (140 mg, 2.0 mmol) was added Fe(ClO4)3$nH2O (21 mg,
0.06 equiv) in one portion, and the mixture was stirred at 40 ꢀC for
72 h. The residue was diluted with ether and the organic layer was
filtered through a florisil short column, evaporated to dryness and
purified by silica gel flash column chromatography to give 4b
(197 mg, 0.63 mmol) in 63% yield and 3a (28 mg, 0.15 mmol) was
recovered in 15% yield. Compound4b: bp 132–135 ꢀC (3 Torr,
Kugelrohr); Rf 0.82 (ether/hexane¼6/1); IR (neat, cmꢁ1) 3386, 2929,
2860, 1713, 1710, 1461, 1406, 1363, 1161, 740, 551; 1H NMR
4.1.11. 1-(7-Methyl-3-(3-oxobutyl)-1H-indol-2-yl)octan-3-one (4f)
(Scheme 3). To a mixture of indol 1f (131 mg, 1.0 mmol) and
1-buten-3-one (2a) (77 mg, 1.1 mmol) was added Fe(ClO4)3$nH2O
(11 mg, 0.03 equiv) in one portion, and the mixture was stirred at
60 ꢀC for 20 min. Then the reaction flask was moved to an oil bath at
40 ꢀC, a mixture of 1-octene-3-one (2b) (252 mg, 2.0 equiv) and
Fe(ClO4)3$nH2O (17 mg, 0.05 equiv) was added to the reaction mix-
ture and stirred at 40 ꢀC for 5 h. The residue was diluted with ether
and the organic layer was filtered through a florisil short column,
evaporated to dryness and purified by silica gel flash column chro-
matography to give 4f (229 mg, 0.70 mmol) in 70% yield: 123–125 ꢀC
(1 Torr, Kugelrohr); Rf 0.67 (ether/hexane: ether¼6/1); IR (neat,
cmꢁ1) 3377, 3117, 3053, 2957, 2861, 1717, 1701, 1541,1448,1364,1080,
(500 MHz,
d
, CDCl3, J¼Hz) 0.78–0.82 (3H, m), 1.14–1.26 (4H, m),
1.47–1.53 (2H, m), 2.01(3H, s), 2.30–2.35 (2H, m), 2.69–2.73 (4H, m),
2.88 (2H, t, J¼7.4), 2.93 (2H, t, J¼6.6), 6.98 (1H, t, J¼8.2), 7.04 (1H, t,
J¼7.8), 7.20 (1H, d, J¼7.8), 7.38 (1H, d, J¼7.8), 8.43 (1H, br s); 13C
NMR (125 MHz, d, CDCl3) 13.79, 18.17, 19.13, 22.33, 23.17, 23.45,
30.20, 31.24, 42.80, 44.25, 109.87, 110.61, 117.82, 118.86, 121.10,
127.66, 134.98, 135.24, 208.76, 209.44; HRMS (MALDI-TOF MS,
matrix: SA) found 313.2045 (C20H27NO2, Calcd: 313.20418).
2,3-Dialkylated-indoles, 4c, 4d, and 4e were prepared by the
same method in the yields described in Table 1. Compound 4a9 was
also obtained in 70% yield from 3a.9
1061, 779, 746; 1H NMR (500 MHz,
d
, CDCl3, J¼Hz) 0.86 (3H, t, J¼7.4),
1.20–1.33 (4H, m), 1.56 (2H, quin, J¼7.4), 2.08 (3H, s), 2.39 (2H, t,
J¼7.6), 2.44 (3H, s), 2.75–2.80 (4H, m), 2.94 (2H, t, J¼7.3), 3.01 (2H, t,
J¼6.2), 6.91 (1H, d, J¼7.3), 6.97 (1H, t, J¼7.3), 7.31 (1H, d, J¼7.8), 8.50
(1H, br s); 13C NMR (125 MHz,
d, CDCl3) 13.78, 16.44, 18.28, 19.20,
22.31, 23.48, 30.16, 31.23, 42.84, 42.88, 44.26, 110.33, 115.55, 119.13,
119.82, 121.72, 127.15, 134.68, 134.73, 208.84, 212.42; HRMS (MALDI-
TOF MS, matrix: SA) found 327.2198 (C21H29NO2, Calcd: 327.2198).
4.1.7. 1-(5-Methyl-3-(3-oxobutyl)-1H-indol-2-yl)octan-3-one
(4c). Bp 115 ꢀC (1 Torr, Kugelrohr); Rf 0.69 (ether/hexane¼17/5); IR
(neat, cmꢁ1) 3368, 3013, 2957, 2930, 2860, 1717, 1699, 1449, 1364,
4.1.12. 1-(2-(3-Oxobutyl)-1H-indol-3-yl)octan-3-one (4g). Bp138–
140 ꢀC (0.5 Torr, Kugelrohr); IR (neat, cmꢁ1) 0.53 (Et2O/H¼6/1);
3398, 2956, 292, 2860, 1709, 1460, 1364, 1242, 1163, 910, 739; 1H
1163, 910, 797, 735; 1H NMR (500 MHz,
d
, CDCl3, J¼Hz) 0.86 (3H, t,
J¼7.1), 1.20–1.30 (4H, m), 1.55 (2H, quin, J¼7.5), 2.09 (3H, s), 2.37 (2H,
t, J¼7.6), 2.43 (3H, s), 2.74–2.77 (4H, m), 2.92 (2H, t, J¼7.4), 2.96 (2H, t,
J¼6.2), 6.92 (1H, d, J¼8.3), 7.14 (1H, d, J¼8.3), 7.23 (1H, s), 8.41 (1H, br
NMR (500 MHz,
d
, CDCl3, J¼Hz) 0.85 (3H, J¼7.3), 1.16–1.27 (4H, m),
1.51 (2H, quin, J¼7.8), 2.16 (3H, S), 2.31 (2H, t, 7.8), 2.74 (2H, t, J¼7.3),
s); 13C NMR (125 MHz,
d, CDCl3) 13.78,18.17,19.17, 21.42, 22.31, 23.43,
2.94–3.00 (4H, m), 7.05 (1H, t, J¼6.9), 8.46 (1H, br s); 13C NMR
30.18, 31.22, 42.80, 42.82, 44.30, 109.38,110.27, 117.56,122.56,127.90,
128.01, 133.55, 135.07, 208.84, 212.18; HRMS (MALDI-TOF MS, ma-
trix: SA) found 327.2198 (C21H29NO2, Calcd: 327.2198).
(125 MHz, d, CDCl3) 13.83, 18.26, 19.12, 22.36, 23.44, 30.03, 31.31,
43.21, 43.23, 43.88, 110.15, 110.63, 117.92, 118.93, 121.19, 127.71,
134.85, 135.28, 209.75, 211.29; HRMS (MALDI-TOF MS, matrix: SA)
found 313.2042 (C20H27NO2, Calcd: 313.20418).
4.1.8. 1-(5-Bromo-3-(3-oxobutyl)-1H-indol-2-yl)octan-3-one
(4d). Rf 0.67 (ether/hexane¼6/1); IR (neat, cmꢁ1) 3340, 3057, 2957,
Acknowledgements
2928, 1719, 1638, 1400, 1309, 1076, 1049, 796; 1H NMR (500 MHz,
d,
CDCl3, J¼Hz) 0.86 (3H, t, J¼7.1), 1.19–1.31 (4H, m), 1.57 (2H, quin,
J¼7.5), 2.09 (3H, s), 2.41 (2H, t, J¼7.6), 2.75 (2H, t, J¼7.4), 2.80 (2H, t,
J¼5.9), 2.90 (2H, t, J¼7.1), 2.99 (2H, t, J¼6.0), 7.13 (1H, d, J¼8.7), 1.17–
The work was partly supported by a Grant-in-Aid for Scientific
Research from The Ministry of Education, Culture, Sports, Science
and Technology of Japan.
7.19 (1H, m), 7.56 (1H, s), 8.65 (1H, br s); 13C NMR (125 MHz,
d, CDCl3)
13.83, 17.95, 19.09, 22.36, 23.50, 30.28, 31.26, 42.64, 42.87, 44.04,
109.76, 112.08, 112.15, 120.42, 123.85, 129.54, 133.87, 136.59, 208.42,
212.61; HRMS (MALDI-TOF MS, matrix: SA) found 391.1141
(C20H26BrNO2, Calcd: 391.1147).
Supplementary data
Supplementary data associated with this article can be found
4.1.9. 3-(3-Oxobutyl)-2-(3-oxooctyl)-1H-indole-5-carbonitrile
(4e). Mp 108–110 ꢀC (recrystallized from hexane/ethyl acetate); Rf
0.41 (ether/hexane¼6/1); IR (neat, cmꢁ1) 3337, 2957, 2930, 2862,
References and notes
2218(CN), 1709, 1476, 1364, 1267, 1163, 737; 1H NMR (500 MHz,
d,
1. For nice reviews see: (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev.
2004, 104, 6217–6254; (b) Fu¨ rstner, A.; Martin, R. Chem. Lett. 2005, 34,
624–629; (c) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47,
3317–3321; (d) Bauer, E. B. Curr. Org. Chem. 2008, 12, 1341–1369.
CDCl3, J¼Hz) 0.86 (3H, t, J¼7.2), 1.24–1.29 (4H, m), 1.59 (2H, quin,
J¼7.6), 2.10 (3H, s), 2.44 (2H, t, J¼7.1), 2.85 (2H, t, J¼5.7), 2.95 (2H, t,