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M.G. Banwell et al. / Tetrahedron 66 (2010) 9252e9262
4. 2. 3. 6. 2-(2-Oxoindoli n-3-yl)-N-phenylacetamide
4.2.3.10. 3-(2-Hydroxypropyl)indolin-2-one (5g). Reductive cy-
clization of cross-coupling product 3g under the conditions speci-
fied in the general procedure gave oxindole 5g24 (141 mg, 74%) as
a clear, colorless oil that slowly crystallized on standing. For the
purposes of spectroscopic characterization, a sample of this mate-
(5b). Reductive cyclization of cross-coupling product 3b under the
conditions specified in the general procedure gave oxindole 5b22
(264 mg, 99%) as a pale-pink, crystalline solid. For the purposes
of spectroscopic characterization, a sample of this material was
recrystallized (acetone) to give a white, crystalline solid, no mp
rial was recrystallized (ethyl acetate/hexane) to give colorless
ꢂ
ꢂ
(decomposition above 184 ꢀC) (lit.22 mp¼202e203 ꢀC) (Found: Mþ
,
,
needles, mp¼99e101 ꢀC (lit.24 mp¼105e105.5) (Found: Mþ
,
ꢂ
ꢂ
266.1055. C, 71.98; H, 5.49; N, 10.30. Calculated for C16H14N2O2 Mþ
191.0946. Calculated for C11H13NO2 Mþ , 199.0946). 1H NMR
266.1055. C, 72.17; H, 5.30, N, 10.52%). 1H NMR (300 MHz, acetone-
(300 MHz, CDCl3) d 8.69 (broad s, 1H), 7.28e7.14 (m, 2H), 7.03 (t,
d6)
d
9.47 (s, 1H), 9.42 (s, 1H), 7.66 (d, J¼7.5 Hz, 2H), 7.35e7.26 (m,
J¼7.8 Hz, 1H), 6.89 (d, J¼7.8 Hz, 1H), 3.68e3.58 (m, 2H), 3.54e3.46
3H), 7.20e7.14 (m, 1H), 7.09e7.02 (m, 1H), 6.96e6.88 (m, 2H),
3.92e3.83 (m, 1H), 3.12 (dd, J¼15.9 and 4.5 Hz, 1H), 2.72 (dd, J¼15.9
(m, 1H), 2.16e1.96 (m, 2H), 1.70e1.50 (m, 2H) (signal due to OH
group proton not observed); 13C NMR (75 MHz, CDCl3)
d 180.7,
and 8.7 Hz, 1H); 13C NMR (75 MHz, acetone-d6)
d
179.1, 179.0, 169.5,
141.6, 129.6, 128.1, 124.2, 122.6, 109.9, 62.5, 45.7, 28.9, 26.7; IR nmax
169.4, 143.6, 143.4, 140.2, 140.1, 130.6, 129.5, 128.7, 125.1, 124.2,
122.4, 120.0, 119.9, 110.1(3), 110.0(8), 43.0, 38.3, 38.2 (additional
signals due to the presence of amide rotamers); IR nmax (KBr) 3315,
(KBr) 3233, 1701, 1621, 1471, 1338, 1221, 1057, 751 cmꢃ1; MS (EI,
ꢂ
70 eV) m/z 191 (Mþ , 64%),173 (66),146 (100),145 (83),133 (40),132
(53), 117 (39), 77 (30).
3213, 3092, 2875, 1702, 1679, 1623, 1600, 1551, 1498, 1472, 1446,
ꢂ
1346, 1317, 1184, 961, 7841, 692 cmꢃ1; MS (EI, 70 eV) m/z 266 (Mþ
,
4.2.3.11. N-[3-(2-Oxoindolin-3-yl)propyl]acetamide
(5k). Reductive cyclization of cross-coupling product 3k (92 mg,
0.35 mmol) under the conditions specified in the general procedure
gave a colorless and unstable resin. Subjection of this material to
rapid flash chromatography (silica, 8:92 v/v methanol/ethyl acetate)
gave oxindole 5k (59 mg, 72%) as a clear, colorless resin, Rf¼0.3
43), 173 (30), 146 (45), 145 (100), 132 (24), 117 (28), 93 (58), 77 (27).
4.2.3.7. 2-(4-Methoxy-2-oxoindolin-3-yl)-N-methylacetamide
(5c). Reductive cyclization of cross-coupling product 3c under the
conditions specified in the general procedure gave oxindole 5c
(181 mg, 77%) as a pale-pink, crystalline solid. For the purposes of
spectroscopic characterization, a sample of this material was
recrystallized (ethanol) to give a white, crystalline solid, no mp
ꢂ
ꢂ
(Found: Mþ , 232.1218. Calculated for C13H16N2O2 Mþ , 232.1212). 1H
NMR (300 MHz, CDCl3)
d 8.58 (s, 1H), 7.25e7.17 (m, 2H), 7.00 (t,
J¼7.5 Hz,1H), 6.88 (d, J¼8.4 Hz,1H), 5.83 (broad s,1H), 3.30e3.15 (m,
ꢂ
(decomposition above 145 ꢀC) (Found: Mþ , 234.1004. C, 61.61; H,
2H), 2.06e1.92 (m, 3H), 1.95 (s, 3H), 1.62e1.50 (m, 2H); 13C NMR
ꢂ
6.11; N, 11.68. Calculated for C12H14N2O3 Mþ , 234.1004. C, 61.53; H,
(75 MHz, CDCl3) d 180.5,170.5,141.8,129.3,128.2,124.2,122.6,110.0,
6.02, N, 11.96%). 1H NMR (300 MHz, CDCl3)
d
7.05 (t, J¼8.1 Hz, 1H),
45.6, 39.4, 27.6, 25.6, 23.4; IR nmax (KBr) 3268, 2937, 2465,1704,1622,
6.44e6.32 (m, 2H), 4.08e3.98 (m, 1H), 3.67 (s, 3H), 3.65 (broad s,
2H), 3.06 (s, 3H), 3.06e2.96 (m, 1H), 2.73 (dd, J¼18.0 and 5.1 Hz,
1554,1471,1370,1336,1295,1222,1104 cmꢃ1; MS (EI, 70 eV) m/z 232
ꢂ
(Mþ , 85%), 228 (52), 185 (36), 157 (57), 145 (78), 133 (50), 173 (100).
1H); 13C NMR (75 MHz, CDCl3)
d 179.3, 177.2, 158.0, 145.8, 129.0,
111.7, 110.8, 102.4, 55.6, 37.4, 35.5, 24.9; IR nmax (KBr) 1692, 1599,
4.2.3.12. 1-Acetyl-7-methoxy-2,3,4,9-tetrahydro-1H-pyrido[2,3-
b]indole (5l). In a variation of the general procedure for reductive
cyclization specified above, a magnetically stirred solution of the
cross-coupling product 3i (65 mg, 0.22 mmol) in methanol (25 mL)
was cooled to 10 ꢀC then treated with 10% Pd on C (15 mg). The
resulting mixture was deoxygenated then charged with dihydrogen
(1 atm) and stirred at 10 ꢀC for 3 h. The reaction mixture was then
filtered through a pad of CeliteÔ and the solids thus retained
washed with methanol (25 mL). The combined filtrates were con-
centrated under reduced pressure to give a mauve-colored solid.
Recrystallization (9:1 v/v i-propanol/methanol) of this material
gave the title indole 5l (51 mg, 93%) as white needles, no mp (de-
composition above 129 ꢀC), Rf¼0.3 (8:92 v/v methanol/ethyl ace-
1472,1439,1384, 1283, 1121, 1092, 951, 776 cmꢃ1; MS (EI, 70 eV) m/z
ꢂ
234 (Mþ , 100%), 176 (48), 175 (68), 149 (18), 134 (19).
4.2.3.8. 2-(5-Methoxy-2-oxoindolin-3-yl)-N-methylacetamide
(5d). Reductive cyclization of cross-coupling product 3d under the
conditions specified in the general procedure gave oxindole 5d
(127 mg, 54%) as an off-white, crystalline solid, no mp (de-
ꢂ
composition above 145 ꢀC) (Found: Mþ , 234.1004. Calculated for
ꢂ
C12H14N2O3 Mþ , 234.1004). 1H NMR (300 MHz, CDCl3)
d 10.67
(broad d, J¼4.2 Hz,1H), 7.30 (broad s,1H), 7.21 (d, J¼2.7 Hz,1H), 7.02
(d, J¼8.4 Hz, 1H), 6.85 (dd, J¼8.4 and 2.7 Hz, 1H), 4.10e4.00 (m, 1H),
3.71 (s, 3/2H), 3.67 (s, 3/2H), 3.18 (dd, J¼15.0 and 4.2 Hz,1H), 2.89 (s,
3/2H), 2.87 (s, 3/2H), 2.76e2.55 (m,1H); 13C NMR (75 MHz, toluene-
ꢂ
ꢂ
tate) (Found: Mþ
,
244.1212. Calculated for C14H16N2O2 Mþ
10.39 (s, 1H), 7.30 (d,
,
d8/DMSO-d6)
d
179.1, 170.8, 155.5, 136.9, 131.8, 112.6, 112.1, 110.0,
244.1212). 1H NMR (300 MHz, CDCl3)
d
ꢂ
55.4, 43.6, 37.0, 26.0; MS (EI, 70 eV) m/z 234 (Mþ , 98%),176 (88),175
J¼8.7 Hz, 1H), 6.86 (d, J¼2.1 Hz, 1H), 6.76 (dd, J¼8.7 and 2.1 Hz, 1H),
(100), 160 (61).
3.84 (s, 3H), 3.83e3.78 (m, 2H), 2.75 (t, J¼6.3 Hz, 2H), 2.31 (s, 3H),
2.18e2.06 (m, 2H); 13C NMR (75 MHz, CDCl3)
d 169.1, 155.7, 132.9,
4.2.3.9. 3-(2-Hydroxyethyl)indolin-2-one (5f). Reductive cycli-
zation of cross-coupling product 3f under the conditions specified in
the general procedure gave oxindole 5f23 (170 mg, 96%) as a pale-
yellow oil that crystallized on standing. For the purposes of spectro-
scopic characterization, a sample of this material was recrystallized
(chloroform)togive awhite, crystallinesolid,mp¼109.5e111 ꢀC(lit.23
132.7, 120.2, 117.9, 109.2, 96.5, 95.1, 55.9, 47.0, 23.3, 23.2, 19.2; IR
nmax (KBr) 3350, 2935, 2846, 1647, 1621, 1585, 1573, 1486, 1394,
1344, 1242, 1206, 1146, 1118, 1027 cmꢃ1; MS (EI, 70 eV) m/z 244
ꢂ
(Mþ , 100%), 229 (14), 201 (85), 187 (67), 173 (24).
4.2.3.13. N-[3-(6-Methyl-2-oxoindolin-3-yl)propyl]acetamide
(5m). Reductive cyclization of cross-coupling product 3j (105 mg,
0.38 mmol) under the conditions specified in the general procedure
gave a colorless and unstable resin. Subjection of this material to
rapid flash chromatography (silica, 6:94 v/v methanol/ethyl ace-
tate) gave oxindole 5m (57 mg, 60%) as a clear, colorless resin, Rf¼0.3
ꢂ
mp¼109e111 ꢀC) (Found: Mþ , 177.0786. C, 67.77; H, 6.23; N, 7.78.
ꢂ
Calculated for C10H11NO2 Mþ ,177.0790. C, 67.78; H, 6.26, N, 7.90%).1H
NMR (300 MHz, CDCl3)
d 9.14 (broad s, 1H), 7.28e7.18 (m, 2H),
7.07e6.99 (m, 1H), 6.93e6.87 (m, 1H), 3.94e3.84 (m, 2H), 3.66e3.58
(m, 1H), 3.47 (t, J¼6.0 Hz, 1H), 2.31e2.19 (m, 1H), 2.14e2.05 (m, 1H);
ꢂ
ꢂ
13CNMR(75MHz,CDCl3)
d
181.5,141.3,129.4,128.1,123.9,122.6,110.0,
(Found: Mþ , 246.1369. Calculated for C14H18N2O2 Mþ , 246.1368).
60.7, 44.8, 33.1; IR nmax (KBr) 3353, 3157, 2953, 2884,1688,1618,1472,
1H NMR (300 MHz, CDCl3)
d
8.27 (s, 1H), 7.08 (d, J¼7.5 Hz, 1H), 6.84
1348, 1298, 1213, 1183, 1108, 1037, 805, 761, 661 cmꢃ1; MS (EI, 70 eV)
(d, J¼7.5 Hz, 1H), 6.72 (s, 1H), 5.76 (broad s, 1H), 3.46 (t, J¼5.7 Hz,
ꢂ
m/z 178 [(MþH)þ, 35%],177 (Mþ , 81),159(56),146(100),144 (56),133
1H), 3.30e3.15 (m, 2H), 2.33 (s, 3H), 2.01e1.88 (m, 2H), 1.94 (s, 3H),
(56), 130 (48), 77 (38).
1.60e1.48 (m, 2H); 13C NMR (75 MHz, CDCl3)
d 180.5, 170.3, 141.5,