Ma et al.
JOCNote
5.09. Found: C, 65.21; H, 6.40; N, 4.97. The same reaction of
3-ethoxy-2-cyclohexenone (1b) and 2 as above produced the
corresponding Michael adducts 3b as a separable mixture (ca.
1:1) of diastereomers in 76%. 3-Ethoxy-6-(2-nitro-1-phenylethyl)-
2-cyclohexenone (3b): (less polar component) Rf = 0.43, hexane/
ethyl acetate 2:1; mp 86.5-88.0 °C (from hexane/ethyl acetate); 1H
NMR (600 MHz) δ 1.33 (t, J=7.1 Hz, 3H), 1.66 (m, 1H), 1.97 (m,
1H), 2.28 (m, 1H), 2.40 (m, 1H), 2.62 (m, 1H), 3.85 (m, 2H), 4.08
(m, 1H), 4.94 (dd, J=13.4, 5.4 Hz, 1H), 5.09 (dd, J=13.4, 10.0 Hz,
1H), 5.33 (d, J=1.5 Hz, 1H), 7.25 (m, 3H), 7.29 (m, 2H); 13CNMR
(150.8 MHz) δ 14.0, 24.4, 28.9, 44.3, 48.7, 64.5, 76.9, 102.9, 127.5,
128.5 (2C), 128.6 (2C), 137.7, 177.3, 198.2. Anal. Calcd for
C16H19NO4: C, 66.42; H, 6.62; N, 4.84. Found: C, 66.47; H, 6.54;
N, 4.87. 3b: (polar component) Rf = 0.42, hexane/ethyl acetate
acetic anhydride (61 mg, 0.6 mmol) at 0 °C. After being stirred at
0 °C for 40 min, the reaction was quenched with aqueous
saturated NaHCO3 and the products were extracted with
EtOAc (10 mL ꢀ 3). The combined extracts were dried
(MgSO4) and concentrated in vacuo. The crude products were
purified by column chromatography (SiO2, hexane/EtOAc, by
increasing the gradient from 10:1 to 2:1 v/v) to afford 38 mg
(75% yield) of 5aa (Rf = 0.37, hexane/ethyl acetate 2:1) as a
light-blue gum: 1H NMR (600 MHz) δ 2.21 (s, 3H), 3.82 (s, 3H),
3.94 (dd, J = 10.3, 6.4 Hz, 1H), 4.47 (t, J = 10.3 Hz, 1H), 4.55
(dd, J=10.0, 6.6 Hz, 1H), 6.57 (dd, J=8.3, 2.4 Hz, 1H), 6.85 (d,
J=7.9 Hz, 1H), 7.18 (m, 2H), 7.26 (m, 1H), 7.32 (m, 2H), 7.96
(d, J = 2.4 Hz, 1H); 13C NMR (150.8 MHz) δ 24.2, 45.8, 55.5,
58.8, 102.6, 110.4, 125.2, 126.4, 127.2, 127.6 (2C), 128.9 (2C),
143.4, 144.0, 159.8, 168.7; HRMS (ESI) calcd for C17H18NO2
(MHþ) 268.1338, found 268.1334 (MHþ).
1
2:1; mp 101.0-102.5 °C (from hexane/ethyl acetate); H NMR
(600 MHz) δ 1.37 (t, J=7.1 Hz, 3H), 1.50 (m, 1H), 1.82 (m, 1H),
2.28 (m, 1H), 2.42 (m, 1H), 2.50 (m, 1H), 3.84 (m, 1H), 3.92 (m,
2H), 4.70 (dd, J= 12.9, 10.2 Hz, 1H), 5.05 (dd, J= 12.9, 5.1 Hz,
1H), 5.34 (s, 1H), 7.21 (m, 2H), 7.28 (m, 1H), 7.33 (m, 2H); 13C
NMR (150.8 MHz) δ 14.1, 24.2, 26.8, 43.4, 47.2, 64.6, 79.5, 102.0,
127.9, 128.0 (2C), 129.0 (2C), 137.8, 177.2, 199.3. Anal. Calcd for
C16H19NO4: C, 66.42; H, 6.62; N, 4.84. Found: C, 66.43; H, 6.70;
N, 4.81.
N-Acetyl-6-methoxy-3-phenylindole (6aa):. To a solution of
indoline 5aa (32 mg, 0.12 mmol) in dichloromethane (2 mL) was
added 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ, 41 mg,
0.18 mmol). The mixture was stirred at 0 °C for 2 h before being
quenched with aqueous saturated NaHCO3. Products were
extracted with EtOAc (10 mL ꢀ 3), and extracts were dried
(MgSO4) and concentrated in vacuo. The crude product was
purified by column chromatography (SiO2, hexane/ethyl acet-
ate, by increasing the gradient from 10:1 to 3:1 v/v) to afford
28 mg (88% yield) of 6aa (Rf=0.48, hexane/ethyl acetate 5:1) as
3-Methoxy-7-phenyl-9-azabicyclo[4.3.0]nona-2,9-diene N-Oxide
(4a): To a solution of 3a (275 mg, 1.0 mmol) in methanol (8 mL)
containing water (0.7 mL) were added zinc powder (262 mg, 4.0
mmol) and ammonium chloride (107 mg, 2.0 mmol). After heating
at reflux for 6 h, the mixture was filtered and the filtrate was
concentrated in vacuo. The crude products were purified by
column chromatography (SiO2, EtOAc/ethanol, by increasing
the gradient from 5:1 to 2:1 v/v) to afford 159 mg (combined
amount of two diastereoisomers, 67% yield) of 4a as pale-yellow
solids. 4a: (less polar component) Rf =0.41, ethyl acetate/ethanol
1
a light-blue gum: H NMR (300 MHz) δ 2.67 (s, 3H), 3.91 (s,
3H), 6.97 (dd, J=8.6, 2.3 Hz, 1H), 7.39 (m, 2H), 7.44-7.51 (m,
2H), 7.60-7.69 (m, 3H), 8.14 (d, J = 2.1 Hz, 1H); 13C NMR
(75.5 MHz) δ 24.1, 55.7, 100.9, 113.1, 120.3, 120.6, 122.6, 124.0,
127.5, 127.8 (2C), 128.9 (2C), 133.4, 137.3, 158.6, 168.8.
Acknowledgment. The Electric Technology Research
Foundation of Chugoku, Sumitomo Chemical, and Promo-
tion of Graduate Course Students by Okayama University,
which are sincerely acknowledged, supported this work. We
are grateful to Advanced Science Research Center for NMR
experiments and EA. We are indebted to Professor Junzo
Nokami, Okayama University of Science, for HRMS ana-
lyses. We are thankful to Japan Student Services Organiza-
tion (JASSO) for a scholarship to L.-J.M.
1
1:1; mp 168.0-169.5 °C (from EtOAc/CH2Cl2); H NMR (300
MHz) δ 1.50-1.65 (m, 1H), 2.00 (m, 1H), 2.12-2.42 (m, 2H), 2.99
(m, 1H), 3.27 (q, J=9.7 Hz, 1H), 3.70 (s, 3H), 4.27 (d, J=9.7 Hz,
2H), 5.96 (s, 1H), 7.21-7.34 (m, 5H); 13C NMR (75.5 MHz) δ
26.2, 28.9, 46.1, 47.6, 56.1, 67.6, 88.3, 127.4 (2C), 127.5, 128.9 (2C),
138.2, 147.0, 170.1. Anal. Calcd for C15H17NO2: C, 74.05; H, 7.04;
N, 5.76. Found: C, 73.64; H, 6.80; N, 5.76; EI-MS m/z 225 (Mþ -
H2O). 4a: (polar component) Rf =0.33, ethyl acetate/ethanol 1:1;
mp 185.0-187.0 °C (from EtOAc/CH2Cl2); 1H NMR (600 MHz)
δ 0.95 (m, 1H), 1.52 (m, 1H), 2.20 (m, 1H), 2.42 (m, 1H), 3.35 (m,
1H), 3.64 (t, J=7.6Hz, 1H), 3.72(s, 3H), 4.13 (d, J=13.9 Hz, 1H),
4.59 (m, 1H), 5.93 (d, J=1.7 Hz, 1H), 7.12 (m, 2H), 7.25 (m, 1H),
7.30 (m, 2H); 13C NMR (150.8 MHz) δ 23.1, 29.1, 40.9, 44.2, 55.9,
68.4, 88.6, 127.32 (2C), 127.33, 128.8 (2C), 139.7, 145.9, 170.2.
N-Acetyl-6-methoxy-3-phenylindoline (5aa):. To a solution of
4a (49 mg, 0.2 mmol) in dry DMF (1 mL) was added dropwise
Supporting Information Available: Spectral data including
IR, 1H NMR, and 13C NMR spectra of 3a,b, 7a-c, 11, 14,
18a-d, 4a, 8a-c, 15, 19a-d, 12, 5aa-ac, 9a-c, 20a-d, 13,
6aa-ac, 10a-c, 16, and 21a-d, and products in the conversion
of 15 to 16 are provided. This material is available free of charge
J. Org. Chem. Vol. 74, No. 23, 2009 9221