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R. Schobert et al. / Tetrahedron Letters 45 (2004) 1121–1124
7.24–7.40 (4H, m, Ph); 13C NMR (125.7 MHz, CDCl3): d
(75.5 MHz, CDCl3): d 11.6, 21.8, 22.0, 24.6, 32.7, 32.9,
33.3, 57.4, 81.9, 84.3, 102.8, 126.6, 127.8, 129.2, 130.2,
133.3, 135.1, 173.0, 179.3; m=z (EI) 352 (Mþ, 0.2%), 351
(0.1), 350 (0.9), 320 (0.1), 318 (0.7), 302 (0.1), 300 (0.3), 265
(0.7), 157 (39), 155 (100).
11.4, 21.0, 21.1, 32.2, 32.4, 37.8, 38.0, 47.3, 89.2, 126.8,
129.3, 129.6, 130.6, 131.4, 135.4, 171.3, 208.4; m=z (EI) 321
(Mþ+1, 4%), 320 (38), 319 (14), 318 (91), 305 (6), 303 (32),
302 (6), 300 (19), 287 (6), 285 (18), 283 (66), 265 (23), 219
(18), 178 (17), 152 (85), 129 (100).
Acid-catalyzed methanolysis (ii) of 3d: 3d (520 mg,
1.46 mmol) was placed in a round-bottomed flask with a
side arm. Under a constant stream of nitrogen dry
chloroform (20 mL) was added followed by the slow
addition of HBF4 in diethyl ether (7.5 M, 0.2 mL). The
solution was stirred for 1 h, then methanol (10 mL) was
added and the solution was refluxed for 16 h. The solvent
was removed in vacuo and the residue was purified by
column chromatography (silica gel 60; diethyl ether/
hexane, 1:1, v/v) to give 4-hydroxy-3-[syn-20-methoxy-10-
methyl-20-(m-nitrophenyl)ethyl]-1-oxaspiro[4.5]dec-3-en-2-
one 4d (485 mg, 92%) as a white solid of mp 163 °C;
(found: C, 63.11; H, 6.46. C19H23NO6 requires C, 63.15;
H, 6.41%); mmax (KBr)/cmꢀ1 3433, 2937, 1701, 1660, 1602,
1536, 1353; 1H NMR (300 MHz, CDCl3): d 0.96 (3H, d, 3J
6. (a) Royles, B. J. L. Chem. Rev. 1995, 95, 1981–2001; (b)
Fischer, R.; Dumas, J.; Bretschneider, T.; Erdelen, C.;
Wachendorff-Neumann, U.; Santel, H.-J.; Dollinger, M.;
Mencke, N.; Turberg, A.; DE Patent 19518962, 1996;
Chem. Abstr. 1996, 124, 231916g.
7. 6a: mp 166 °C; mmax (KBr)/cmꢀ1 3191, 3081, 1745, 1686; 1H
NMR (300 MHz, CDCl3): d 1.37–1.67 (10H, m), 2.52 (2H,
dd, 3J 6.9, 5.5 Hz, 10-H), 2.94 (1H, t, 3J 5.5 Hz, 3-H), 4.94–
4.98 (1H, m, @CHcis), 5.03 (1H, ddt, 3J 17.1, 2J ¼ 4J
1.5 Hz, @CHtrans), 5.57–5.71 (1H, m, 20-H), 8.78 (1H, s,
NH); 13C NMR (75.5 MHz, CDCl3): d 21.2, 21.3, 24.8,
30.3, 32.7, 49.0 (C-3), 66.8, 118.6, 133.0, 173.4, 212.2. 7a:
mp 156 °C, Rf ¼ 0:75 (ethyl acetate); mmax (KBr)/cmꢀ1
3185, 1748, 1683; 1H NMR (300 MHz, CDCl3): d 1.23–
1.67 (10H, m), 1.34 (3H, d, 3J 6.2 Hz, CH3), 1.45 (1H, dd,
3J 8.3, 2J 3.4 Hz, 1-H) 1.73 (1H, dd, 3J 8.8, 2J 3.4 Hz,
1-H0), 1.85–1.95 (1H, m, 2-H), 8.45 (1H, s, NH); 13C NMR
(75.5 MHz, CDCl3): d 12.0, 21.4, 21.5, 24.8, 26.3, 32.7,
33.2, 34.1, 34.7, 65.9, 173.5, 212.4. 7a0 (diastereomer): mp
156 °C, Rf ¼ 0:66 (ethyl acetate); 1H NMR (300 MHz,
3
7.3 Hz, 10-CH3), 1.13–1.84 (10H, m), 2.83 (1H, dq, J 7.3,
3
2.8 Hz, 10-H), 3.41 (3H, s, OCH3), 4.66 (1H, d, J 2.8 Hz,
20-H), 7.43–7.61 and 8.10–8.17 (4H, m, Ph), 10.00 (1H, s,
OH); 13C NMR (75.5 MHz, CDCl3): d 14.6, 21.6, 21.8,
24.4, 32.6, 33.1, 35.5, 57.6, 82.1, 86.4, 102.0, 121.4, 123.0,
129.6, 132.9, 140.6, 148.4, 173.0, 179.7; m=z (EI) 361 (Mþ,
0.5%), 344 (1), 331 (2), 329 (17), 311 (3), 299 (8), 167 (47),
166 (100).
3
CDCl3): d 1.15 (3H, d, J 6.2 Hz, CH3), 1.23–1.67 (10H,
3
2
3
m), 1.37 (1H, dd, J 8.3, J 3.5 Hz, 1-H) 1.77 (1H, dd, J
8.6, J 3.5 Hz, 1-H0), 2.00–2.08 (1H, m, 2-H), 8.61 (1H, s,
9. Typical procedure for the [2,3]-sigmatropic rearrangement
of allyl tetronates 8: a tightly sealed vial charged with a
solution of 8b (500 mg, 2.12 mmol) in dry toluene (6 mL)
was placed in a CEM Discovere single-mode microwave
synthesizer and irradiated at 190 °C and 3.5 bar for 20 min.
The resulting mixture was left overnight in a refrigerator
for crystallization of product 9b. Colorless crystals
(290 mg, 58%) were obtained after washing the crude
three times with toluene; mp 132 °C; mmax (KBr)/cmꢀ1
2
NH); 13C NMR (75.5 MHz, CDCl3): d 11.2, 21.2, 21.3,
24.7, 25.9, 31.5, 33.0, 33.7, 34.5, 66.0, 174.5, 211.0.
8. Typical procedure (i) for the methanolysis of 3: 3a
(400 mg, 1.26 mmol) was dissolved in dry chloroform
(20 mL) and methanol (5 mL). The solution was heated to
reflux for 24 h after which the solvent was removed in
vacuo. The residue was purified by column chromatogra-
phy (silica gel 60; diethyl ether/hexane: 1:1, v/v) to give
3-[syn-20-(o-chlorophenyl)-20-methoxy-10-methylethyl]-4-
hydroxy-1-oxaspiro[4.5]dec-3-en-2-one 4a as a white solid
(278 mg, 63%) mp 180 °C; (found: C, 64.91; H, 6.56.
C19H23ClO4 requires C, 65.05; H, 6.61%); mmax (KBr)/cmꢀ1
3416, 2936, 1705, 1632; 1H NMR (300 MHz, CDCl3):
d 0.92 (3H, d, 3J 7.3 Hz, 10-CH3), 1.16–1.84 (10H, m), 2.98
(1H, dq, 3J 7.3, 1.9 Hz, 10-H), 3.39 (3H, s, OCH3), 4.93
(1H, d, 3J 1.9 Hz, 20-H), 7.23–7.40 (4H, m, Ph); 13C NMR
1
3413, 3072, 2937, 1702, 1643, 1384; H NMR (300 MHz,
3
CDCl3): d 1.20–1.81 (10H, m), 1.27 (3H, d, J 7.0 Hz, 10-
3
CH3), 1.76 (3H, s, 20-CH3), 3.12 (1H, q, J 7.0 Hz, 10-H),
5.05 (2H, d, 2J 2.7 Hz, @CH2), 7.64 (1H, br, OH); 13C
NMR (75.5 MHz, CDCl3): d 16.9, 21.6, 21.7, 22.3, 24.3,
32.6, 32.7, 34.5, 82.4, 101.6, 110.9, 148.4, 173.8, 178.2;
Accurate mass m=z (EI): calculated 236.14123; found
236.14156.