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A. Harrison-Marchand et al. / Tetrahedron 60 (2004) 1827–1839
1H, m), 6.16 (1H, d, J¼6.0 Hz), 7.34 and 7.50 (5H, 2m); dH
(400 MHz; C6D6): 2.21 (6H, s), 2.71 (1H, ddd, J¼3.4, 5.0,
13.1 Hz), 2.80 (1H, dd, J¼3.4, 13.1 Hz), 3.41 (1H, m and
3H, s), 3.62 (1H, dd, J¼5.0, 6.0 Hz), 6.01 (1H, d,
J¼6.0 Hz), 7.12 and 7.55 (5H, 2m); dC (50 MHz; CDCl3):
24.3, 44.7, 46.0, 51.8, 58.3, 116.8, 126.7, 128.5, 137.6,
139.7 (2C), 173.4; m/z (EI): 277 (Mþz, 1), 233 (6), 191 (50),
158 (100), 121 (13), 115 (18), 77 (8); Anal. calcd for
C15H19NO2S: C, 64.95; H, 6.90; N, 5.05; found: C, 65.15;
H, 6.67; N, 5.05.
53.3, 56.8, 123.0, 142.1, 166.0, 166.3, 172.0; m/z (EI): 317
(Mþz, 11), 286 (7), 270 (7), 258 (17), 231 (50), 213 (20), 199
(100), 184 (19), 172 (61), 141 (40), 129 (13), 113 (13), 72 (24),
42 (32), 15 (22); Anal. calcd for C13H19NO6S: C, 49.20; H,
6.03; N, 4.41; found: C, 49.34; H, 6.26; N, 4.51.
4.2.8. cis-Dimethyl 4-(dimethylamino)-3-[(2-oxo-1,3-oxa-
zolidin-3-yl)carbonyl]-3,4-dihydro-2H-thiopyran-5,6-
dicarboxylate: 11c. The title compound was prepared
according to the same procedure as compound 11b starting
from 0.2 g of diene 10. White crystals (0.216 g, 75%); Rf
0.25 (petroleum ether/ethyl acetate 3:7; mp 114 8C
(petroleum ether/ethyl acetate); nmax/cm21 1776, 1739,
1710, 1693, 1447, 1333, 1262, 1242, 719; dH (200 MHz;
CDCl3): 2.32 (6H, s), 2.89 (1H, dd, J¼3.0, 13.0 Hz), 3.47
(1H, dd, J¼2.1, 13.0 Hz), 3.72 (1H, ddd, J¼3.0, 3.0,
13.0 Hz), 3.77 (3H, s), 3.84 (3H, s), 4.09 (2H, m), 4.40 (1H,
d, J¼3.0 Hz), 4.46 (1H, m); dC (100 MHz; CDCl3): 22.9,
42.8, 44.5, 44.6, 52.4, 53.2, 57.0, 62.4, 123.5, 141.7, 153.1,
165.7, 166.1, 172.1; m/z (EI): 372 (Mþz, 6), 231 (50), 199
(100), 172 (65), 141 (37), 113 (28), 55 (39); calcd for
C14H20N2O6S: C, 48.83; H, 5.85; N, 8.13; found: C, 49.03;
H, 6.47; N, 8.25. HRMS (LSIMS): m/z¼373 [MþH]þ, calcd
for C15H21N2O7S: 373.1070; found: 373.1066.
Compound 9b. Pale yellow solid; Rf 0.21 (petroleum ether/
ethyl acetate 3:2); mp 60–61 8C (diethyl ether/petroleum
ether); nmax/cm21 1740, 1347; dH (400 MHz; CDCl3): 2.36
(6H, s), 2.99 (1H, dd, J¼2.8, 12.4 Hz), 3.03 (1H, ddd,
J¼2.8, 9.3, 10.5 Hz), 3.30 (1H, dd, J¼10.5, 12.4 Hz), 3.75
(3H, s), 3.82 (1H, dd, J¼2.9, 9.3 Hz), 6.04 (1H, d,
J¼2.9 Hz), 7.33 and 7.48 (5H, 2m); dC (50 MHz; CDCl3):
29.4, 41.0, 42.6, 52.4, 61.9, 118.4, 126.6, 128.6, 137.1,
139.4 (2C), 174.6; m/z (EI): 277 (Mþz, 6), 262 (14), 246 (2),
233 (9), 191 (34), 158 (100); Anal. calcd for C15H19NO2S:
C, 64.95; H, 6.90; N, 5.05; found: C, 65.18; H, 6.89; N, 4.83.
4.2.6. cis and trans 3-{[4-(Dimethylamino)-6-phenyl-3,4-
dihydro-2H-thiopyran-3-yl]carbonyl}-1,3-oxazolin-2-
one: 8c and 9c. Compound 8c. dH (400 MHz; C6D6): 2.19
(6H, s), 2.76 (1H, dd, J¼3.2, 13.2 Hz), 3.18 (4H, m), 3.60
(1H, dd, J¼13.2, 13.2 Hz), 4.16 (1H, ddd, J¼3.2, 6.9,
13.2 Hz), 4.36 (1H, dd, J¼5.0, 6.9 Hz), 6.14 (1H, d,
J¼5.0 Hz), 7.11 and 7.57 (5H, 2m).
4.3. Cycloaddition of diene 2 with methyl acrylate
catalysed by alumina: obtention of the cis- and -trans
methyl 4-(dimethylamino)-2-phenyl-5,6-dihydro-4H-
1,3-thiazine-5-carboxylates 12 and 6b
A solution of 4-dimethylamino-2-phenyl-1-thia-3-aza-buta-
1,3-diene 2 (0.5 g, 2.6£1023 mol) and methyl acrylate
(2.3 mL, 26£1023 mol) in dry dichloromethane (5 mL) was
added to 1.5 g of basic alumina (Merck, type E). The
reaction mixture was vigorously stirred for 1 h at 20 8C (or
0 8C). After addition of dichloromethane (40 mL) the
resulting slurry was filtered on a pad of celite and the
solvent concentrated (no heating!) under reduced pressure.
NMR analysis of the crude mixture revealed, next to
unreacted material, the presence of two diastereomeric
adducts, 6b and 12, in a ratio depending on the reaction
temperature (see text). Flash chromatography on silica
(petroleum ether/ethyl acetate 80:20) gave 6b (0.477 g,
66%). Due to its extremely facile conversion into trans-6b,
the cis adduct 12 could not be isolated. Main NMR
characteristic values for 12 (cf. 6b): dH (200 MHz;
CDCl3): 2.52 (3H, s); 3.75 (3H, s); 4.62 (1H, d, J¼4.0 Hz).
Compound 9c. Rf 0.36 (ethyl acetate/acetone 1:1); mp 131–
132 8C (ethyl acetate/petroleum ether); nmax/cm21 1770,
1693, 694; dH (400 MHz; CDCl3): 2.35 (6H, s), 2.98 (1H,
dd, J¼2.8, 12.7 Hz), 3.25 (1H, dd, J¼11.0, 12.7 Hz), 4.07
(3H, m), 4.44 (2H, ddd, J¼2.5, 7.7, 8.6 Hz), 4.47 (1H, ddd,
J¼2.8, 10.1, 11.0 Hz), 6.07 (1H, d, J¼2.7 Hz), 7.33, 7.48
(5H, 2m); dH (400 MHz; C6D6): 2.25 (6H, s), 2.78 (1H, dd,
J¼2.8, 12.6 Hz), 3.00 (4H, m), 3.24 (1H, dd, J¼11.2,
12.6 Hz), 4.10 (1H, dd, J¼2.6, 10.4 Hz), 4.82 (1H, ddd,
J¼2.8, 10.4, 11.2 Hz), 6.04 (1H, d, J¼2.6 Hz), 7.12 and
7.60 (5H, 2m); dC (100 MHz; CDCl3): 29.9, 40.3, 41.2,
43.1, 62.1, 62.2, 117.8, 126.7, 128.6, 137.2, 139.5, 131.9,
153.5, 174.5; m/z (EI: 332 (Mþz, 1), 191 (49), 158 (100), 143
(21), 121 (26), 115 (34), 55 (98); Anal. calcd for
C17H20N2O3S: C, 61.43; H, 6.06; N, 8.43; found: C,
61.00; H, 6.09; N, 8.22.
4.2.7. cis-Trimethyl-4-(dimethylamino)-3,4-dihydro-2H-
thiopyran-3,5,6-tricarboxylate: 11b. To a solution of 4-
dimethylamino-2,3-dimethoxycarbonyl-1-thia-buta-1,3-diene
10 (0.1 g, 4.33£1024 mol) in dry dichloromethane (5 mL) was
added methyl acrylate (0.06 mL, 6.66£1024 mol). The reac-
tion mixture was stirred for 4 h at room temperature then
concentrated under reduced pressure. Purification by flash
chromatography on silica (petroleum ether/ethyl acetate 1:1)
gave 11b as white crystals (0.124 g, 91%); Rf 0.66 (petroleum
ether/ethyl acetate 1:1; mp 76 8C (diethyl ether); nmax/cm21
1735, 1725, 1440, 1314, 1247, 729; dH (400 MHz; CDCl3):
2.34 (6H, s), 2.59 (1H, ddd, J¼3.2, 3.6, 13.2 Hz), 3.08 (1H,
ddd,J¼1.6,3.2,13.2 Hz),3.31(1H,dd,J¼13.2,13.2 Hz), 3.77
(3H, 3s), 3.79 (3H, 3s), 3.84 (3H, 3s), 4.33 (1H, dd, J¼1.6,
3.3 Hz); dC (100 MHz; CDCl3): 22.8, 44.7, 44.9, 52.1, 52.5,
4.4. Synthesis of chiral non-racemic heterocycles
Thermal activation. To a solution of 4-dimethylamino-2-
phenyl-1-thia-3-aza-buta-1,3-diene
1024 mol) in dry toluene (2 mL) was added a solution of
(4S)-4-benzyl-3-(prop-2-enoyl)-oxazolidin-2-one 13
2
(0.05 g, 2.6£
(0.09 g, 3.9£1024 mol) in dry toluene (10 mL). The reaction
mixture was stirred for 20 h at 110 8C then, after cooling at
room temperature, concentrated under reduced pressure.
Purification by flash chromatography on silica (petroleum
ether/ethyl acetate 1:1 then 1:4) gave 14 and 15 (ratio:
85:15) as white needles (0.082 g, 75%).
Magnesium bromide activation. Magnesium turnings
(0.021 g, 8.6£1024 mol) in dry diethyl ether (4 mL) were