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A. Salomone et al.
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 3.29 (d, 2JH,H = 17.3 Hz, 1 H, CH2), 3.36
(d, 2JH,H = 17.3 Hz, 1 H, CH2), 3.45–3.55 (br s, 1 H, OH, D2O exch.), 5.38
(dd, JH,H = 0.7 Hz, JH,H = 10.6 Hz, 1 H, =CH2), 5.67 (dd, JH,H = 0.7 Hz,
3JH,H = 17.2 Hz, 1 H, =CH2), 6.15 (dd, 3JH,H = 10.6 Hz, 3JH,H = 17.2 Hz, 1 H,
=CH2), 7.33–7.39 (m, 2 Harom), 7.53–7.60 (m, 2 Harom).
13C NMR (75 MHz, CDCl3): δ = 46.2, 99.6, 106.8, 118.0, 121.3, 122.4,
128.2, 129.2, 136.2, 136.5, 156.9.
13C NMR (75 MHz, CDCl3): δ = 45.9, 106.4, 108.9, 114.3, 118.4, 135.9,
139.4, 144.1, 149.2.
GC-MS (70 eV): m/z (%) = 213 (M+, 22), 197 (12), 196 (14), 195 (23),
162 (11), 143 (6), 127 (10), 104 (11), 73 (11), 55 (100).
2
3
2
Anal. Calcd for C9H8ClNO3: C, 50.60; H, 3.71; N, 6.56. Found: C, 50.91;
H, 4.04; N, 6.57.
GC-MS (70 eV): m/z (%) = 223 (M+, 41), 222 (28), 208 (18), 207 (24),
206 (50), 205 (48), 195 (10), 180 (23), 179 (13), 178 (50), 177 (13),
153 (34), 152 (13), 151 (74), 150 (16), 139 (12), 138 (10), 137 (10),
125 (10), 111 (30), 102 (17), 75 (29), 55 (100).
3-(2,4,6-Trimethoxyphenyl)-5-hydroxy-5-vinyl-2-isoxazoline (1h)
Yield: 24 mg (14%, 0.086 mmol); white solid; mp 103–105 °C (EtOAc–
hexane).
FT-IR (KBr): 3189, 3014, 2941, 2839, 1730, 1607, 1497, 1454, 1329,
Anal. Calcd for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C,
59.09; H, 5.02; N, 6.27.
1234, 1206, 1157, 1123, 1063, 1036, 991, 944, 905, 845, 807 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 3.20 (d, 2JH,H = 17.6 Hz, 1 H, CH2), 3.37
(d, 2JH,H = 17.6 Hz, 1 H, CH2), 3.70–3.90 (br s, 1 H, OH, D2O exch.), 3.80
(s, 6 H), 3.82 (s, 3 H), 5.35 (dd, 2JH,H = 1.0 Hz, 3JH,H = 10.6 Hz, 1 H, CH2),
5.67 (dd, 2JH,H = 1.0 Hz, 3JH,H = 17.2 Hz, 1 H, CH2), 6.13 (s, 2 H), 6.17 (dd,
3JH,H = 10.6 Hz, 3JH,H = 17.2 Hz, 1 H, CH).
3-(3-Chlorophenyl)-5-hydroxy-5-vinyl-2-isoxazoline (1e)
Yield: 0.550 g (93%, 2.47 mmol); white crystals; mp 73–74 °C (hex-
ane).
FT-IR (KBr): 3375, 2927, 1596, 1562, 1430, 1360, 1343, 1238, 1105,
13C NMR (75 MHz, CDCl3): δ = 49.9, 55.6, 56.2, 91.0, 100.4, 105.5,
117.5, 136.7, 153.9, 159.8, 162.7.
LC-MS (ESI+): m/z = 302 (100, [M + Na]+).
GC-MS (70 eV): m/z (%) = 279 (M+, 23), 261 (100), 248 (48), 232 (86),
218 (36), 206 (83), 193 (66), 176 (22), 168 (87), 149 (18), 136 (18),
121 (23), 109 (14), 69 (46), 55 (82).
985, 910, 861, 787, 752, 684, 484 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 3.28 (d, 2JH,H = 17.6 Hz, 1 H, CH2), 3.35
(d, 2JH,H = 17.6 Hz, 1 H, CH2), 3.70–3.95 (br s, 1 H, OH, D2O exch.), 5.37
2
3
2
(dd, JH,H = 0.8 Hz, JH,H = 10.6 Hz, 1 H, =CH2), 5.66 (dd, JH,H = 0.8 Hz,
3JH,H = 17.2 Hz, 1 H, =CH2), 6.14 (dd, 3JH,H = 17.2 Hz, 3JH,H = 10.6 Hz, 1 H,
=CH), 7.30–7.40 (m, 2 Harom), 7.49–7.53 (m, 1 Harom), 7.60–7.62 (m, 1
Anal. Calcd for C14H17NO5: C, 60.21; H, 6.14; N, 5.02. Found: C, 60.12;
H, 6.34; N, 5. 20.
H
arom).
13C NMR (75 MHz, CDCl3): δ = 46.2, 106.7, 118.2, 125.1, 127.0, 130.3,
130.6, 131.2, 135.0, 136.2, 156.7.
3-(3-Chloro-2,4,6-trimethoxyphenyl)-5-hydroxy-5-vinyl-2-isox-
azoline (1i)
GC-MS (70 eV): m/z (%) = 223 (M+, 22), 208 (12), 207 (19), 206 (33),
205 (40), 180 (18), 179 (11), 178 (44), 177 (16), 153 (15), 152 (7), 151
(35), 150 (8), 137 (11), 113 (10), 111 (26), 102 (11), 75 (24), 55 (100).
Yield: 15 mg (9%, 0.048 mmol); white solid; mp 101 °C (dec.).
1H NMR (300 MHz, CDCl3): δ = 3.10–3.40 (s, 1 H, OH, D2O exch.), 3.23
(d, J = 17.6 Hz, 1 H), 3.34 (d, J = 17.6 Hz, 1 H), 3.85 (s, 3 H), 3.87 (s, 3 H),
3.93 (s, 3 H), 5.37 (d, 3JH,H = 10.6 Hz, 1 H, CH2), 5.67 (d, 3JH,H = 17.2 Hz, 1
H, CH2), 6.18 (dd, 3JH,H = 10.6 Hz, 3JH,H = 17.2 Hz, 1 H, CH), 6.34 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 49.6, 56.6, 60.6, 62.5, 92.8, 105.9, 107.2,
117.6, 136.6, 153.3, 156.4, 157.7, 157.8.
Anal. Calcd for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C,
58.76; H, 4.55; N, 6.11.
3-(2-Chlorophenyl)-5-hydroxy-5-vinyl-2-isoxazoline (1f)
Partial characterization of isoxazoline 1f was due to the spontaneous
dehydration/aromatization observed in solution or during its purifi-
cation; yield: 80 mg (44%, 0.359 mmol).
GC-MS (70 eV): m/z (%) = 313 (M+, 18), 295 (75), 282 (84), 266 (76),
252 (27), 240 (58), 227 (61), 202 (72), 55 (100).
LC-MS (ESI+): m/z = 336 (100, [M + Na]+).
1H NMR (300 MHz, CDCl3): δ = 3.00–3.10 (br s, 1 H, OH, D2O exch.),
3.49 (d, 2JH,H = 17.7 Hz, 1 H, CH2), 3.59 (d, 2JH,H = 17.7 Hz, 1 H, CH2), 5.41
3
3
(d, JH,H = 10.6 Hz, 1 H, =CH2), 5.70 (d, JH,H = 17.2 Hz, 1 H, =CH), 6.20
Anal. Calcd for C14H16ClNO5: C, 53.60; H, 5.14; N, 4.46; Found: C,
53.62; H, 5.24; N, 4.46.
3
3
(dd, JH,H = 17.2 Hz, JH,H = 10.6 Hz, 1 H, =CH), 7.29–7.43 (m, 3 Harom),
7.70–7.72 (m, 1 Harom).
13C NMR (75 MHz, CDCl3): δ = 48.8, 106.9, 118.0, 127.3, 129.5, 129.9,
3-Aryl-5-vinylisoxazoles 3b–g; General Procedure
130.8, 130.9, 131.3, 136.4, 157.5.
To a solution of isoxazoline 1b–g (3.862 g, 20.43 mmol) in anhydrous
CH2Cl2 (100 mL) at r.t. was added Et2O·BF3 (2.6 mL, 20.43 mmol). The
reaction mixture was stirred for 1 h and then quenched with H2O (15
mL). The products were extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic layers were dried (Na2SO4) and then evaporated under
vacuum. The reaction afforded crude isoxazoles 3b–g in quantitative
yields. The products were isolated by silica gel column and then puri-
fied by crystallization in 44–93% yields as reported in Scheme 6.
GC-MS (70 eV): m/z (%) = 223 (M+, 5), 222 (5), 208 (6), 207 (10), 206
(16), 205 (26), 188 (60), 180 (19), 178 (39), 177 (14), 170 (11), 153
(19), 152 (12), 151 (36), 150 (13), 139 (10), 138 (9), 137 (17), 123 (7),
111 (18), 102 (16), 90 (9), 75 (29), 55 (100).
3-(5-Chlorofuran-2-yl)-5-hydroxy-5-vinyl-2-isoxazoline (1g)
Yield: 0.215 g (90%, 1.009 mmol); yellow solid; mp 86–88 °C (EtOAc–
hexane).
3-(4-Nitrophenyl)-5-vinylisoxazole (3b)
FT-IR (KBr): 3423, 3151, 3116, 3096, 1619, 1495, 1412, 1381, 1246,
Yield: 0.252 g (52%, 1.17 mmol); yellow solid; mp 137–139 °C
(MeOH).
1110, 1019, 987, 942, 883, 841, 790 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 3.29 (s, 2 H), 3.35 (s, 1 H, OH, D2O
FT-IR (KBr): 3090, 2922, 1605, 1563, 1526, 1435, 1351, 1110, 990,
3
3
exch.), 5.39 (d, JH,H = 10.6 Hz, 1 H, CH2), 5.67 (d, JH,H = 17.1 Hz, 1 H,
932, 861, 852, 807, 758, 697 cm–1
.
CH2), 6.13 (dd, 3JH,H = 17.1 Hz, 3JH,H = 10.6 Hz, 1 H, =CH), 6.27 (d, 3JH,H
3.3 Hz, 1 Hfuryl), 6.73 (d, 3JH,H = 3.3 Hz, 1 Hfuryl).
=
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 807–816