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Can. J. Chem. Vol. 83, 2005
NMR (CDCl3, 200 MHz) δ: 7.48 (dd, 1H, J = 1.7 and
7.7 Hz, arom.-H), 7.21 (ddd, 1H, arom.-H, J = 8.8, 7.3, and
1.7 Hz), 7.24–6.89 (m, 2H, arom.-Hs), 4.34 (unresolved dd,
pressure and the products were isolated by similar column
chromatographic separations of the concentrate. From the re-
action of 2a were obtained 1a (84 mg, 42%), 2a (30 mg,
15%), and 5a (66 mg, 33%), eluted with hexane – ethyl ace-
tate 9:1, 7:1, and 3:1, respectively.
From the reaction of 2b were obtained 1b (80 mg, 40%),
2b (32 mg, 16%), and 5b (70 mg, 35%), eluted, respectively,
with hexane – ethyl acetate 9:1, 7:1, and 3:1.
2
2
1H, J ≅ 3J ~ 8.3 Hz, C3-H), 4.21 (dd, 1H, J = 11.6 and J =
2
4.6 Hz, C4-H), 3.78 (dd, 1H, J = 11.6 and J = 8.1 Hz, C4-
2
H), 3.73 (dd, 1H, J = 8.1 and 5.1 Hz, C3-H), 2.78–2.69 (m,
1H, C3a-H), 1.56 (s, 3H, C9b-CH3). 13C NMR (CDCl3,
75 MHz) δ: 154.69 (C5a), 128.92 (CH), 128.69 (CH),
124.67 (C9a), 121.89 (CH), 117.15 (CH), 72.50 (C3), 65.41
(C9b), 61.13 (C4), 47.66 (C3a), 26.29 (CH3). MS (EI) m/z:
192 (M+ + 1), 191 (M+). Anal. calcd. for C11H13NO2: C
69.09, H 6.85, N 7.32; found: C 68.97, H 6.99, N 7.20. Fur-
ther elution with hexane – ethyl acetate (1:1) afforded 3a as
a reddish oil (20 mg, 10%) (5). Rf 0.16 (CHCl3).
From the reaction of 3c were isolated 1c (86 mg, 43%), 2c
(28 mg, 14%) and 3c (68 mg, 34%), eluted with hexane –
ethyl acetate 9:1, 7:1, and 1:1, respectively.
General procedure for the reactions of ketones 1a–1c
with N-methylhydroxylamine hydrochloride under
microwave irradiation
(3S,3aS,9bR)-9b-Dimethyl-1,3a,4,9b-tetrahydro-3H-
chromeno[4,3-c]isoxazole (5b)
Ketones 1a–1c (200 mg) were mixed with N-methyl-
hydroxylamine hydrochloride (equimolar) and sodium bicar-
bonate (1.0 g), and adsorbed on silica gel (G, 3.0 g) as
described earlier. The reaction mixture was exposed to mi-
crowave radiation (500 W) for 15 min (five cycles, 3 min
each); exposure time optimization is based on TLC (CHCl3
solvent) monitoring. The adsorbed material was then ex-
tracted with ethyl acetate (25 mL), and dried over anhydr.
Na2SO4. The solvent was then distilled off under reduced
pressure. The products were isolated by column chromato-
graphic separation over silica gel (60–120 mesh, 30 g). The
column was packed in hexane and hexane – ethyl acetate
gradients were used for elution.
Elution of the column initially with hexane – ethyl acetate
(9:1) afforded 1b (20 mg, 10%) and unreacted oxime 2b
(30 mg, 15%) with hexane – ethyl acetate (7:1). Further elu-
tion with hexane – ethyl acetate (3:1) afforded cycloadduct
5b (122 mg, 61%) as a yellow oil. Rf 0.37 (CHCl3). IR
(CHCl3, cm–1): 3270, 1615, 1585, 1490, 1450, 1380, 1298,
1
1235, 1125. H NMR (CDCl3, 300 MHz) δ: 7.43 (dd, 1H,
J = 1.2 and 7.9 Hz, arom.-H), 7.22–7.16 (m, 1H, arom.-H),
2
7.00–6.83 (m, 2H, arom.-Hs), 4.17 (dd, 1H, J = 11.7 and
J = 4.3 Hz, C4-H), 3.95 (dd, 1H, J = 4.2 and 6.0 Hz, C3-H),
3.88 (dd, 1H, J = 6.1 and 11.7 Hz, C4-H), 2.19–2.14 (m, 1H,
C3a-H), 1.60 (s, 3H, C9b-CH3), 1.45 (d, 3H, J = 6.0 Hz, C3-
CH3). 13C NMR (CDCl3, 75 MHz) δ: 154.37 (C5a), 128.86
(CH), 128.13 (CH), 125.86 (C9a), 122.08 (CH), 117.29
(CH), 81.37 (C3), 65.52 (C9b), 61.96 (C4), 56.12 (C3a),
27.98 (C9b-CH3), 18.84 (C3-CH3). MS (ESI) m/z: 228 (M +
Na)+. Anal. calcd. for C12H15NO2: C 70.22, H 7.37, N 6.82;
found: C 70.15, H 7.49, N 6.73.
(3S,3aS,9bR)-1,3,9b-Trimethyl-1,3a,4,9b-tetrahydro-3H-
chromeno[4,3-c]isoxazole (4b)
Elution with hexane – ethyl acetate (3:1) afforded
cycloadduct 4b (223 mg, 97%) as a colorless oil. Rf 0.35
(CHCl3). IR (CHCl3, cm–1): 1610, 1575, 1490, 1430, 1290,
1
1245, 1235. H NMR (CDCl3, 300 MHz) δ: 7.35 (d, 1H, J =
7.5 Hz, arom.-H), 7.16 (unresolved dd, 1H, J ~ 7.5 Hz,
arom.-H), 6.96 (unresolved dd, 1H, J ~ 7.5 Hz, arom.-H),
6.82 (d, 1H, J = 8.1 Hz, arom.-H), 4.27–4.09 (m, 3H, C3-H
and C4-Hs), 2.89 (s, 3H, N-CH3), 2.27–2.19 (m, 1H, C3a-
H), 1.51 (s, 3H, C9b-CH3), 1.42 (d, 3H, J = 6.3 Hz, C3-
CH3). 13C NMR (CDCl3, 75 MHz) δ: 154.59 (C5a), 128.29
(CH), 128.09 (CH), 126.1 (quat.), 121.16 (CH), 117.03
(CH), 74.89 (C3), 65.0 (C4), 63.64 (C9b), 39.29 (N-CH3),
54.04 (C3a), 20.33 (C3-CH3 and C9b-CH3, hetero-COSY).
MS (EI) m/z: 220 (M+ + 1, 6), 219 (M+, 40). Anal. calcd. for
C13H17NO2: C 71.21, H 7.81, N 6.39; found: C 71.34, H
7.70, N 6.21.
3-Benzyl-5-methyl-2,3-dihydro-benzo[f][1,4]oxazepine-4-
oxide (3c)
Elution of the column initially with hexane – ethyl acetate
(9:1) afforded 1c (20 mg, 10%) and unreacted oxime 2c
(40 mg, 20%) with hexane – ethyl acetate (7:1). Further elu-
tion with hexane – ethyl acetate (1:1) afforded cycloadduct
3c (118 mg, 59%) as a yellow oil. Rf 0.16 (CHCl3). IR
(CHCl3, cm–1): 1600, 1573, 1490, 1447, 1288, 1218. 1H
NMR (CDCl3, 200 MHz) δ: 7.41–6.91 (m, 9H, arom-Hs),
4.65–4.55 (m, 2H, C2-Hs), 4.49–4.41 (m, 1H, C3-H), 3.50
2
3
(dd, 1H, J = 13.8 and J = 4.9 Hz, benzylic-H), 2.87 (dd,
2
3
1H, J = 13.8 and J = 8.2 Hz, benzylic-H), 2.54 (s, 3H,
CH3). 13C NMR (CDCl3, 75 MHz) δ: 154.48 (C9a), 142.97
(quat.), 136.93 (CH), 130.75 (CH), 129.26 (CH), 128.74
(CH), 126.94 (C5a), 124.12 (CH), 123.11 (CH), 121.39
(CH), 75.64 (C3), 71.85 (C2), 32.90 (benzylic-C), 18.89
(CH3). MS (ESI) m/z: 290 (M + Na)+. Anal. calcd. for
C17H17NO2: C 76.48, H 7.29, N 6.94; found: C 76.38, H
6.41, N 5.24.
(3R,3aS,9bR)-1,9b-Dimethyl-3-phenyl-1,3a,4,9b-
tetrahydro-3H-chromeno[4,3-c]isoxazole (4c)
Elution with hexane – ethyl acetate (3:1) afforded cyclo-
adduct 4b (211 mg, 95%) as a colorless solid, mp 43–45 °C
(hexane:chloroform, 2:1). Rf 0.35 (CHCl3). IR (KBr, cm–1):
1610, 1575, 1495, 1430, 1290, 1245, 1235. 1H NMR
(CDCl3, 200 MHz) δ: 7.48–7.16 (m, 7H, arom.-Hs), 7.03–
6.90 (m, 2H, arom.-Hs), 5.05 (d, 1H, J = 7.5 Hz, C3-H),
4.26–4.18 (m, 2H, C4-Hs), 2.78 (s, 3H, N-CH3), 2.67–2.60
(m, 1H, C3a-H), 1.59 (s, 3H, CH3). 13C NMR (CDCl3,
75 MHz) δ: 54.77 (C5a), 140.92 (quat.), 128.56 (CH),
128.14 (CH), 127.71 (CH), 126.29 (quat.), 125.98 (CH),
121.39 (CH), 117.20 (CH), 80.58 (C3), 64.76 (C9b), 64.07
General procedure for thermal transformations of
oximes
Oximes 2a–2c (200 mg) were refluxed in dry toluene
(50 mL) for 72 h. After the completion of the reaction (TLC,
CHCl3 solvent), the solvent was removed under reduced
© 2005 NRC Canada