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S.-H. Ahn et al.
PAPER
EIMS: m/z (%) = 378 (2) [M+], 251 (100), 221 (12), 207 (12), 191
(17).
13C NMR (CDCl3): δ = 34.3, 41.0, 51.8, 52.2, 55.6, 59.3, 104.2,
120.6, 126.3, 131.6, 133.0, 133.1, 135.7, 136.9, 137.7, 166.2, 172.1.
Anal. Calcd for C13H15IO5: C, 41.29; H, 4.00. Found: C, 41.17; H,
3.94.
EIMS: m/z (%) = 336 (5), 334 (5), 308 (10), 306 (9), 267 (49), 265
(51), 235 (25), 233 (25), 221 (21), 219 (17), 207 (35), 155 (11), 142
(100), 115 (46).
Methyl 2-Methoxy-1-(methoxycarbonylmethyl)-1,4-dihydro-
2H-3-benzoxocine-5-carboxylates 10; General Procedure
A mixture of the MBH cinnamyl alcohol 5 (1 mmol), 2,5-dimeth-
oxy-2,5-dihydrofuran (6; 0.24 mL, 2 mmol), DIPEA (0.53 mL, 3
mmol), BTEAC (0.23 g, 1 mmol), and Pd(OAc)2 (7 mg, 3 mol%) in
DMF (10 mL) was stirred at 80 °C for 1–24 h under nitrogen atmo-
sphere. Then, the mixture was diluted with H2O (20 mL) and ex-
tracted with Et2O (3 × 30 mL). The combined organic layers were
dried (MgSO4) and the solvent was evaporated under reduced pres-
sure. The resulting mixture was chromatographed on silica gel
(hexane–EtOAc, 3:1) to provide 10.
Anal. Calcd for C17H19BrO6: C, 51.14; H, 4.80. Found: C, 50.92; H,
4.64.
Methyl 9-Chloro-2-methoxy-1-(methoxycarbonylmethyl)-1,4-
dihydro-2H-3-benzoxocine-5-carboxylate (10d)
Reaction time: 24 h; yield: 152 mg (43%); white solid; mp 101–
102 °C (Et2O–PE).
IR (KBr): 1738, 1710, 1645, 1590, 1436, 1251 cm–1.
1H NMR (CDCl3): δ = 2.70 (dd, J = 15.8, 7.6 Hz, 1 H, C1CH2), 2.91
(dd, J = 15.8, 7.0 Hz, 1 H, C1CH2), 3.36 (s, 3 H, OCH3), 3.63 (s, 3
H, OCH3), 3.66–3.75 (m, 1 H, C1H), 3.82 (s, 3 H, OCH3), 4.21 (d,
J = 9.7 Hz, 1 H, C2H), 4.40 (d, J = 19.4 Hz, 1 H, C4H), 4.88 (dd,
J = 19.1, 1.5 Hz, 1 H, C4H), 7.15 (s, 1 Harom), 7.25 (s, 2 Harom), 7.69
(s, 1 H, C6H).
13C NMR (CDCl3): δ = 34.3, 41.2, 51.8, 52.1, 55.5, 59.4, 104.2,
125.1, 127.0, 131.8, 132.1, 134.1, 134.7, 136.2, 140.0, 166.4, 172.0.
EIMS: m/z (%) = 354 (1) [M+], 263 (10), 230 (11), 223 (32), 221
(100), 203 (14), 191 (25), 189 (74), 175 (47), 162 (23), 149 (16),
142 (60), 127 (25), 115 (33).
Methyl 2-Methoxy-1-(methoxycarbonylmethyl)-1,4-dihydro-
2H-3-benzoxocine-5-carboxylate (10a)
Reaction time: 3 h; yield: 131 mg (41%); white solid; mp 94–95 °C
(Et2O–PE).
IR (KBr): 1738, 1706, 1644, 1436, 1251 cm–1.
1H NMR (CDCl3): δ = 2.75 (dd, J = 15.9, 7.6 Hz, 1 H, C1CH2), 2.92
(dd, J = 15.9, 7.6 Hz, 1 H, C1CH2), 3.35 (s, 3 H, OCH3), 3.61 (s, 3
H, OCH3), 3.71–3.76 (m, 1 H, C1H), 3.82 (s, 3 H, OCH3), 4.21 (d,
J = 9.4 Hz, 1 H, C2H), 4.41 (d, J = 19.0 Hz, 1 H, C4H), 4.90 (dd,
J = 19.0, 1.8 Hz, 1 H, C4H), 7.18–7.32 (m, 4 Harom), 7.76 (s, 1 H,
C6H).
Anal. Calcd for C17H19ClO6: C, 57.55; H, 5.40. Found: C, 57.69; H,
5.57.
13C NMR (CDCl3): δ = 34.6, 41.2, 51.7, 52.0, 55.5, 59.4, 104.6,
124.7, 126.8, 128.9, 130.6, 131.5, 135.5, 137.4, 138.0, 166.6, 172.4.
EIMS: m/z (%) = 320 (1) [M+], 187 (100), 155 (80), 143 (38), 141
(64), 128 (58), 115 (42).
Methyl 2-Methoxy-1-(methoxycarbonylmethyl)-8-methyl-1,4-
dihydro-2H-3-benzoxocine-5-carboxylate (10e)
Reaction time: 2 h; yield: 144 mg (43%); white solid; mp 119–
121 °C (Et2O–PE).
IR (KBr): 1739, 1705, 1643, 1506, 1435, 1254 cm–1.
Anal. Calcd for C17H20O6: C, 63.74; H, 6.29. Found: C, 63.45; H,
6.11.
1H NMR (CDCl3): δ = 2.32 (s, 3 H, CH3), 2.72 (dd, J = 15.8, 7.9 Hz,
1 H, C1CH2), 2.91 (dd, J = 15.8, 7.0 Hz, 1 H, C1CH2), 3.35 (s, 3 H,
OCH3), 3.60 (s, 3 H, OCH3), 3.64–3.72 (m, 1 H, C1H), 3.81 (s, 3 H,
OCH3), 4.18 (d, J = 9.4 Hz, 1 H, C2H), 4.39 (d, J = 18.8 Hz, 1 H,
C4H), 4.88 (dd, J = 18.8, 1.6 Hz, 1 H, C4H), 7.05–7.13 (m, 3 Harom),
7.73 (s, 1 H, C6H).
Methyl 7-Fluoro-2-methoxy-1-(methoxycarbonylmethyl)-1,4-
dihydro-2H-3-benzoxocine-5-carboxylate (10b)
Reaction time: 6 h; yield: 199 mg (59%); colorless oil.
IR (CH2Cl2): 1738, 1710, 1649, 1611, 1573, 1454, 1436, 1257 cm–1.
1H NMR (CDCl3): δ = 2.74 (dd, J = 15.8, 7.6 Hz, 1 H, C1CH2), 2.93
(dd, J = 15.8, 7.6 Hz, 1 H, C1CH2), 3.36 (s, 3 H, OCH3), 3.61 (s, 3
H, OCH3), 3.62–3.71 (m, 1 H, C1H), 3.83 (s, 3 H, OCH3), 4.18 (d,
J = 9.7 Hz, 1 H, C2H), 4.43 (d, J = 19.1 Hz, 1 H, C4H), 4.91 (dd,
J = 19.1, 2.3 Hz, 1 H, C4H), 6.96–7.03 (m, 2 Harom), 7.26–7.33 (m,
1 Harom), 7.81 (d, J = 2.1 Hz, 1 H, C6H).
13C NMR (CDCl3): δ = 34.6, 41.3, 51.8, 52.1, 55.5, 59.4, 104.2,
113.9 (d, J = 22.0 Hz), 120.1, 123.8, 129.5, 130.0 (d, J = 8.8 Hz),
133.3, 140.4, 160.6 (d, J = 249.3 Hz), 166.1, 172.2.
13C NMR (CDCl3): δ = 20.8, 34.6, 40.9, 51.7, 52.0, 55.4, 55.5, 59.4,
104.8, 124.6, 129.7, 131.3, 135.0, 135.3, 136.4, 137.6, 166.7, 172.5.
EIMS: m/z (%) = 334 (1) [M+], 201 (100), 183 (10), 169 (96), 155
(41), 142 (54), 128 (21), 115 (23).
Anal. Calcd for C18H22O6: C, 64.66; H, 6.63. Found: C, 64.47; H,
6.48.
Methyl 2,8-Dimethoxy-1-(methoxycarbonylmethyl)-1,4-di-
hydro-2H-3-benzoxocine-5-carboxylate (10f)
Reaction time: 1 h; yield: 147 mg (42%); white solid; mp 38–40 °C
(Et2O–PE).
EIMS: m/z (%) = 338 (1) [M+], 278 (10), 247 (10), 215 (10), 205
(100), 187 (15), 173 (80), 161 (41), 159 (64), 146 (64), 133 (39).
IR (KBr): 1737, 1706, 1646, 1605, 1574, 1506, 1436, 1238 cm–1.
Anal. Calcd for C17H19FO6: C, 60.35; H, 5.66. Found: C, 60.12; H,
5.38.
1H NMR (CDCl3): δ = 2.71 (dd, J = 15.8, 8.1 Hz, 1 H, C1CH2), 2.90
(dd, J = 15.8, 7.6 Hz, 1 H, C1CH2), 3.35 (s, 3 H, OCH3), 3.60–3.69
(m, 1 H, C1H), 3.61 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3), 3.82 (s, 3
H, OCH3), 4.16 (d, J = 9.4 Hz, 1 H, C2H), 4.39 (d, J = 19.0 Hz, 1 H,
C4H), 4.89 (d, J = 19.0 Hz, 1 H, C4H), 6.84–6.86 (m, 2 Harom), 7.08–
7.11 (m, 1 Harom), 7.71 (s, 1 H, C6H).
13C NMR (CDCl3): δ = 34.7, 40.6, 51.7, 52.1, 55.3, 55.5, 59.3,
104.8, 114.8, 115.2, 125.8, 130.1, 131.8, 136.6, 137.2, 158.0, 166.6,
172.4.
Methyl 8-Bromo-2-methoxy-1-(methoxycarbonylmethyl)-1,4-
dihydro-2H-3-benzoxocine-5-carboxylate (10c)
Reaction time: 23 h; yield: 148 mg (37%); white solid; mp 124–
125 °C (Et2O–PE).
IR (KBr): 1737, 1707, 1646, 1488, 1435, 1251 cm–1.
1H NMR (CDCl3): δ = 2.71 (dd, J = 15.8, 8.4 Hz, 1 H, C1CH2), 2.92
(dd, J = 15.8, 6.7 Hz, 1 H, C1CH2), 3.56 (s, 3 H, OCH3), 3.61 (s, 3
H, OCH3), 3.63–3.70 (m, 1 H, C1H), 3.82 (s, 3 H, OCH3), 4.17 (d,
J = 9.4 Hz, 1 H, C2H), 4.40 (d, J = 19.1 Hz, 1 H, C4H), 4.89 (dd,
J = 19.1, 2.1 Hz, 1 H, C4H), 7.04–7.07 (m, 1 Harom), 7.41–7.46 (m,
2 Harom), 7.66 (s, 1 H, C6H).
EIMS: m/z (%) = 350 (1) [M+], 259 (15), 227 (11), 216 (100), 199
(12), 185 (51), 171 (35), 158 (56), 141 (11), 128 (28), 115 (25).
Anal. Calcd for C18H22O7: C, 61.71; H, 6.33. Found: C, 61.42; H,
6.21.
Synthesis 2012, 44, 3613–3622
© Georg Thieme Verlag Stuttgart · New York