5206
P. Kahnberg et al. / Tetrahedron 58 22002) 5203±5208
m/z 3% rel int) 320.1264 3M1, 2 , CH20O6 requires
320.1260), 305 326%), 291 315%), 267 311%), 266 357%),
259 314%), 252 314%), 251 3100%), 221 313%), 207 317%),
191 334%), 147 316%).
J11.7 Hz), 6.99 3d, 1H, J8.4 Hz), 7.73 3dd, 1H, J8.4,
2.3 Hz), 7.82 3d, 1H, J2.3 Hz). 13C NMR 3CDCl3) 26.6,
34.1, 69.9, 120.3, 126.5, 128.6, 131.6, 131.9, 133.9, 134.0,
163.0, 197.0. MS m/z 3% rel int) 188.0839 3M1, 67,
C12H12O2 requires 188.0837), 173 3100%), 167 317%), 149
332%), 145 314%), 115 313%).
17
4.1.5. 5-Hydroxy-7-(2-methyl-[1,3]dioxolan-2-yl)-2,3,4,
5-tetrahydro-benzo[b]oxepin-4-carboxylic acid ethyl
ester (8). NaBH4 314.5 mg, 0.382mmol) was added to a
solution of 7 3123 mg, 0.382 mmol) in MeOH 325 mL) at
08C. After the addition, the reaction was kept at room
temperature for 4 h, before it was neutralized with 1 M
HCl3aq) extracted with THF 33£40 mL) and washed with
brine 32£40 mL). The organic phase was dried, evaporated
and the product was puri®ed by chromatography 3heptane±
ethyl acetate 3:1). 8 was obtained as 2:1 epimeric mixture,
as a white solid in 85% yield, 105 mg: mp 58±608C; nmax
3KBr) 3467, 2985, 2891, 1729, 1498, 1373, 1245, 1198,
4.1.8.7-(2-Methyl-[1,3]dioxolan-2-yl)-2,3-dihydro-benzo[b]-
oxepin (2). Compound 2 was prepared from 10 according to
the procedure for transforming 4 to 5. The product was
puri®ed by chromatography 3heptane±ethyl acetate 10:1)
and obtained as a yellow oil in 99% yield; nmax 3liquid
®lm) 2987, 2889, 1610, 1496, 1373, 1240, 1200, 1123,
1
1039, 949, 871, 842, 706; H NMR 3CDCl3) 1.65 3s, 3H),
2.68 3m, 2H), 3.79 3m, 2H), 4.04 3m, 2H), 4.23 3t, 2H,
J4.8 Hz), 5.99 3dt, 1H, J11.7, 4.5 Hz), 6.34 3d, 1H,
J11.7 Hz), 6.93 3d, 1H, J8.3 Hz), 7.23 3dd, 1H, J8.3,
2.3 Hz), 7.29 3d, 1H, J2.3 Hz). 13C NMR 3CDCl3) 27.8,
34.4, 64.6, 69.6, 108.8, 119.9, 125.2, 126.5, 129.0, 129.8,
130.7, 137.4, 158.7. MS m/z 3% rel int) 232.1103 3M1, 15,
C14H16O3 requires 232.1099), 218 313%), 217 3100%), 173
321%).
1
1039, 987, 869, 837, 736; H NMR 3CDCl3) of the major
epimer 1.24 3t, 3H, J7.1 Hz), 1.61 3s, 3H), 2.22 3m, 1H),
2.49 3m, 1H), 2.97 3ddd, 1H, J9.5, 4.5, 1.8 Hz), 3.34 3d,
1H, J6.8 Hz), 3.76 3m, 2H), 4.01 3m, 1H), 4.03 3m, 2H),
4.15 3m, 2H, J7.1 Hz), 4.22 3m, 1H), 5.17 3d, 1H,
J6.8 Hz), 6.94 3d, 1H, J8.2Hz), 7.31 3dd, 1H, J8.2,
2.3 Hz), 7.42 3d, 1H, J2.3 Hz). It was not possible to
assign which carbon signals belong to this isomer. MS m/z
3% rel int) 322.1412 3M1, 3, C17H20O6 requires 322.1416),
308 317%), 307 3100%).
4.1.9. 5-Acetyl-2-hydroxy-benzaldehyde (11). Acetic acid
anhydride 31.51 mL, 16.0 mmol) was added to a stirred
suspension of AlCl3 35.24 g, 39.3 mmol) in freshly distilled
CH2Cl2 330 mL). Salicylic aldehyde 31.5 g, 12.3 mmol) was
added and the reaction was re¯uxed under nitrogen for 24 h.
The solution was poured on a mixture of 1 M HCl3aq) and ice
350 g) and extracted with CH2Cl2 33£40 mL). The organic
phase was washed with brine 32£40 mL), dried and
evaporated, and the crude product was puri®ed by
chromatography 3heptane±ethyl acetate 6:1). 11 was
obtained as a yellowish oil in 69% yield, 1.39 g. The product
has previously been reported, produced by other
methods.21,22
4.1.6. 7-Acetyl-5-hydroxy-2,3,4,5-tetrahydro-benzo[b]-
oxepin-4-carboxylic acid (9). LiOH 30.305 g, 12.7 mmol)
was added to a solution of 8 31.60 g, 5.19 mmol) in THF±
H2O 1:1 350 mL). After 16 h at room temperature, the solu-
tion was acidi®ed 3which caused removal of the protective
group) with a few drops of 1 M HCl3aq), extracted with THF
33£30 mL) and washed with brine 32£30 mL). The organic
phase was dried and evaporated, the product was puri®ed by
chromatography 3heptane±ethyl acetate 1:1!0:1) and
obtained as a white solid in 98% yield, 1.50 g: mp 139±
1418C; nmax 3KBr) 3422, 3054, 2987, 1696, 1663, 1599,
1265, 985, 738, 705; 1H NMR 3MeOD) 2.25 3m, 1H),
2.44 3m, 1H), 2.56 3s, 3H), 2.95 3ddd, 1H, J1.5, 5.6,
9.2Hz), 4.11 3ddd, 1H, J3.9, 5.6, 12.3 Hz), 4.33 3ddd,
1H, J3.1, 9.2, 12.3 Hz), 5.27 3d, 1H, J1.5 Hz), 6.99 3d,
1H, J8.4 Hz), 7.823dd, 1H, J8.4, 2.3 Hz), 8.02 3d, 1H,
J2.3 Hz). 13C NMR 3CD3OD) 25.9, 28.4, 63.4, 71.6, 73.0,
121.5, 129.8, 132.1, 132.2, 133.4, 164.0, 175.7, 198.6. MS
m/z 3% rel int) 250.0841 3M1, 81, C13H14O5 requires
250.0841), 235 364%), 333 324%), 204 354%), 189
331%), 179 333%), 173 339%), 163 334%), 161 333%), 149
3100%).
4.1.10. 5-Acetyl-2-but-3-enyloxy-benzaldehyde (12).
K2CO3 321.2 mg, 0.154 mmol) was added to a solution of
11 321.0 mg, 0.128 mmol) and 4-brombut-1-en 316 mL,
0.154 mmol) in DMF 32mL). The solution was re¯uxed
for 6 h, cooled to room temperature and extracted with
ether 33£10 mL). The organic phase was washed with
brine 32£10 mL), dried and evaporated, and the crude
product was puri®ed by chromatography 3heptane±ethyl
acetate 6:1). 12 was obtained as white crystals in 81%
yield, 22.6 mg: mp 71±738C; nmax 3KBr) 2926, 1675,
1
1603, 1497, 1359, 1266, 1190, 986, 919, 821; H NMR
3CDCl3) 2.58 3s, 3H), 2.62 3m, 2H), 4.21 3t, 2H,
J6.5 Hz), 5.14 3dd, 1H, J10.2, 1.6 Hz), 5.19 3dd, 1H,
J17.1, 1.6 Hz), 5.88 3m, 1H), 7.05 3d, 1H, J8.8 Hz),
8.19 3dd, 1H, J8.8, 2.4 Hz), 8.37 3d, 1H, J2.4 Hz),
10.47 3s, 1H). 13C NMR 3CDCl3) 26.8, 33.7, 68.6, 113.1,
118.4, 124.6, 129.8, 130.4, 133.9, 136.1, 162.9, 189.4,
196.6; MS m/z 3% rel int) 218.0934 3M1, 2 2 , 1C3H14O3
requires 218.0943), 203 383%), 177 335%), 149 3100%),
55 375%).
4.1.7. 1-(2,3-Dihydro-benzo[b]oxepin-7-yl)-ethanone (10).
Compound 9 31.97 g, 6.69 mmol) was dissolved in toluene
370 mL) and re¯uxed with a Dean Stark trap for 16 h, before
DMF±DMA 32mL, 15.1 mmol) was added. 10 min after
the addition, the mixture was washed with brine
32£40 mL), dried and evaporated. The product was puri®ed
by chromatography 3heptane±ethyl acetate 10:1) and
obtained as a yellow oil in 81% yield, 1.02g; nmax 3liquid
®lm) 2965, 2929, 2893, 1678, 1597, 1497, 1360, 1277,
1245, 1129, 1117, 1037, 1000, 835, 774, 736, 705; 1H
NMR 3CDCl3) 2.56 3s, 3H), 2.69 3m, 2H), 4.28 3t, 2H,
J4.8 Hz), 6.05 3dt, 1H, J11.7, 4.6 Hz), 6.38 3d, 1H,
4.1.11.
1-(4-But-3-enyloxy-3-vinyl-phenyl)-ethanone
(13). KOtBu 339 mg, 0.344 mmol) was added to a stirred
suspension of Ph3PCH3Br in freshly distilled THF 35 mL)
under N2. After stirring for 1 h at room temperature, the
mixture was cooled to 2788C and slowly transferred to