9136 J . Org. Chem., Vol. 62, No. 26, 1997
Carren˜o et al.
mixture from 1.14 g of 3e11a,17 following method A and purified
by flash chromatography (AcOEt/hexane, 5:1) in 79% yield as
[4R,4a S,8R,8a R,(S)R]-10a : white solid; mp 175 °C dec; [R]20
D
) +315 (c 1.05, CHCl3); 13C NMR δ 199.2, 146.8, 142.2, 140.1,
131.3, 130.2 (2C), 129.3, 123.8 (3C), 74.3, 64.8, 48.7, 47.1, 33.6,
23.2, 21.3, 18.5. Anal. Calcd for C19H22O3S: C, 69.06; H, 6.71;
S, 9.70. Found: C, 69.12; H, 6.64; S, 9.53.
a
60:40 mixture of diastereoisomers. Anal. Calcd for
C15H16O4S: C, 61.63; H, 5.52; S, 10.97. Found: C, 61.44; H,
5.65; S, 11.23.
Meth od B. Diels-Ald er Rea ction in Th er m a l Con d i-
tion s. Diene (10 equiv) was added at room temperature to a
solution of 5a or a mixture of 5 and 6d ,e (0.1 M) in the solvent
indicated in each case (see Table 2 for conditions). A portion
of 5 equiv of diene was added every 4 days. The reaction was
TLC monitored, and after completion (see Table 1 for reaction
times), the solvent was evaporated at reduced pressure.
Meth od C. Ca ta lyzed Diels-Ald er Rea ction . A solu-
tion of 5 or a mixture of 5 and 6d ,e (0.1 M) in dry CH2Cl2 was
added to the appropriate Lewis acid under argon at the desired
temperature (see Tables 2 and 3 for conditions). After 30 min
the diene (2 equiv) was added. The reaction was TLC
monitored, and after completion (see Tables 2 and 3 for
reaction times) water was added. The aqueous layer was
extracted with CH2Cl2. The organic layer was dried with Na2-
SO4 and evaporated at reduced pressure.
4a ,5,8,8a -Tetr a h yd r o-4-h yd r oxy-2,8,8a -tr im eth yl-4-[(p-
tolylsu lfin yl)m eth yl]n aph th alen -1-on e (9b an d 10b). Com-
pounds 9b and 10b were obtained from 5b under the experi-
mental conditions and in the ratios shown in Table 3.
Purification and separation were achieved by flash chroma-
tography (AcOEt/hexane, 2:3). [4S,4aR,8S,8aS,(S)R]-9b: white
solid; mp 158 °C dec; [R]20 ) +342 (c 1.0, CHCl3); 13C NMR δ
D
(75 MHz) 202.9, 142.0, 141.7, 141.0, 135.9, 131.9, 130.0 (2C),
123.9 (2C), 123.8, 70.8, 68.7, 45.6, 42.6, 37.7, 25.2, 22.0, 21.3,
17.9, 16.3. [4R,4aS,8R,8aR,(S)R]-10b: white solid; mp 144.0-
144.9 °C; [R]20 ) -44 (c 1.0, CHCl3); 13C NMR δ (75 MHz)
D
203.5, 142.2, 141.5, 140.1, 136.0, 130.7, 130.2 (2C), 123.9 (2C),
122.7, 70.7, 67.3, 45.7, 43.8, 38.0, 25.5, 21.9, 21.4, 17.5, 16.4.
4a ,5,8,8a -Tetr a h yd r o-4-h yd r oxy-3,4a ,8-tr im eth yl-4-[(p-
tolylsu lfin yl)m eth yl]n aph th alen -1-on e (9c an d 10c). Com-
pounds 9c and 10c were obtained from 5c under the experi-
mental conditions and in the ratios shown in Table 3.
Purification and separation were achieved by flash chroma-
tography (AcOEt/hexane, 1:3). [4S,4aR,8S,8aS,(S)R]-9c: pale
4a,5,8,8a-Tetr ah ydr o-4-h ydr oxy-5,8-m eth an o-4-[(p-tolyl-
su lfin yl)m eth yl]n a p h th a len -1-on e (7a a n d 8a ). Com-
pounds 7a and 8a were obtained from 5a under the experi-
mental conditions and in the ratios shown in Table 2.
Purification and separation were achieved by flash chroma-
tography (AcOEt/hexane, 1:1). [4S,4a R,5S,8R,8a S,(S)R]-7a :
yellow solid; mp 70-71.5 °C; [R]20 ) -89 (c 0.98, CHCl3); 13
C
D
NMR δ 198.6, 159.5, 142.6, 140.3, 131.0, 130.4 (2C), 126.5,
123.9 (3C), 78.5, 61.0, 52.6, 46.2, 31.1, 29.4, 21.4, 20.5, 19.0,
18.2. [4R,4aS,8R,8aR,(S)R]-10c: pale yellow solid; mp 139.4-
white solid; mp 129-130 °C; [R]20 ) +104 (c 1, CHCl3); IR
D
140.6 °C; [R]20 ) +308 (c 0.25, CHCl3); 13C NMR δ (75 MHz)
-1
(KBr) 3315, 1665, 1025, 805 cm
;
13C NMR δ 200.2, 151.3,
D
198.9, 162.1, 142.7, 140.0, 130.9, 130.4 (2C), 127.3, 124.4, 123.9
(2C), 79.0, 62.5, 52.3, 46.8, 30.7, 29.6, 21.6, 21.5, 20.3, 19.3.
1,4,4a ,9a -Tetr a h yd r o-10-h yd r oxy-1-m eth yl-10-[(p-tolyl-
su lfin yl)m eth yl]a n th r a cen -9-on e (9d a n d 10d ). Com-
pounds 9d and 10d were obtained from a mixture of 5d and
6d under the experimental conditions and in the ratios shown
in Table 3. Purification and separation were achieved by flash
chromatography (AcOEt/hexane, 1:5). [1S,4a R,9a S,10R,
142.4, 139.4, 136.1, 134.2, 130.3 (2C), 129.8, 124.0 (2C), 71.8,
67.6, 51.3, 48.7, 47.8, 47.2, 45.3, 21.4. Anal. Calcd for
C19H20O3S: C, 69.49; H, 6.14. Found: C, 69.18; H,5.79.
[4R,4a S,5R,8S,8a R,(S)R]-8a : white solid; mp 147-148 °C;
[R]20D ) +109 (c 1, CHCl3); IR (CHCl3) 3390, 1665, 1600, 1040
-1
cm
;
13C NMR δ 200.2, 151.4, 142.3, 139.9, 135.8, 133.9, 130.7
(2C), 130.2, 123.8 (2C), 72.0, 71.7, 51.1, 48.6, 47.5 (2C), 46.1,
21.3. Anal. Calcd for C19H20O3S: C, 69.49; H, 6.14. Found:
C, 69.19; H, 5.90.
(S)R]-9d : white solid; mp 161.4-161.9 °C; [R]20 ) -133 (c
D
1.00, CHCl3); 13C NMR δ 197.1, 144.1, 142.6, 139.4, 134.1,
131.5, 130.8, 130.3 (2C), 128.3, 126.9, 126.4, 124.6, 123.9 (2C),
75.8, 64.4, 49.6, 45.4, 34.7, 24.6, 21.4, 19.3. Anal. Calcd for
C23H26O3S: C, 72.22; H, 6.85; S, 8.38. Found: C, 72.17; H,
6.25; S, 8.08. [1R,4a S,9a R,10S,(S)R]-10d : white solid; mp
64.2-65.5 °C; [R]20D ) +233 (c 1.00, CHCl3); 13C NMR δ 197.6,
143.8, 142.1, 140.0, 134.0, 131.8, 131.3, 130.3 (2C), 128.5,
127.0, 126.8, 124.0 (3C), 76.1, 65.8, 49.2, 47.0, 34.2, 23.9, 21.4,
19.1.
4a ,5,8,8a -Tetr a h yd r o-4-h yd r oxy-2-m eth oxy-8-m eth yl-
4-[(p-tolylsu lfin yl)m eth yl]n a p h th a len -1-on e (9e a n d 10e).
Compounds 9e and 10e were obtained from 5e and 6e under
the experimental conditions and in the ratios shown in Table
3. Purification and separation were achieved by flash chro-
matography (AcOEt/hexane, from 1: to 3:1). [4S,4a R,8S,8a S,
(S)R]-9e: oil; [R]20D ) -71.5 (c 1.00, CHCl3); 13C NMR δ 193.4,
149.8, 142.2, 139.8, 131.1, 130.1 (2C), 123.9 (3C), 114.0, 74.2,
64.3, 55.0, 49.0, 47.6, 33.8, 23.8, 21.3, 18.4. [4R,4a S,8R,8a R,
(S)R]-10e: oil; [R]20D ) +205 (c 1.00, CHCl3); 13C NMR δ 193.4,
150.3, 142.4, 140.0, 131.1, 130.2 (2C), 123.9 (3C), 112.8, 74.3,
65.4, 55.3, 48.7, 47.6, 33.7, 23.1, 21.4, 18.5.
Meth od D. Red u ction of Ca r bon yl Gr ou p . To a solu-
tion of DIBALH (1.8 mL, 1 M in hexane, 2.4 equiv) in THF
(10 mL) cooled at -78 °C was added a solution of the
corresponding adduct 7a or 8a (0.75 mmol, 1 equiv) in THF
(15 mL). The reaction was monitored by TLC (1:3 hexanes/
ethyl acetate). Excess organoaluminum reagent was destroyed
with methanol, and the mixture was poured into an Erlenm-
eyer containing ethyl acetate and sodium potassium tartrate
and stirred vigorously for 30 min. The organic layer was
washed with brine, dried over Na2SO4, filtered, and concen-
trated in vacuo.
Meth od E. P r ep a r a tion of MTP A Ester s of Diols 11
a n d 12. A mixture of 8 mg of diol 11 or 12, 7 mg of DMPA,
and 8 µL of MTPA-Cl in 2 mL of CH2Cl2 was stirred at 30 °C
overnight. Then H2O (1 mL) and ether (2 mL) were added
and stirred for 15 min. The mixture was diluted with ether
and washed with 10% HCl (3 mL), 1 N NaOH (3 mL), and
1,4,4a ,9a -Tet r a h yd r o-10-h yd r oxy-1,4-m et h a n o-10-[(p -
tolylsu lfin yl)m eth yl]a n th r a cen -9-on e (7d a n d 8d ). Com-
pounds 7d and 8d were obtained from a mixture of 5d and 6d
under the experimental conditions and in the ratios shown in
Table 2. Purification and separation were achieved by flash
chromatography (AcOEt/hexane, 1:3). [1R,4S,4a R,9a S,
10R,(S)R]-7d : white solid; mp 112-112.5 °C; [R]20 ) -11 (c
D
1, CHCl3); 13C NMR δ 200.9, 145.8, 142.5, 139.1, 135.5, 134.4,
133.6, 133.4, 130.3 (2C), 127.7, 125.6, 125.1, 124.0 (2C), 73.6,
69.1, 51.8, 49.8, 49.6, 47.0, 46.0, 21.4. Anal. Calcd for
C23H24O3S: C, 72.60; H, 6.36; S, 8.43. Found: C, 72.72; H,
5.79; S, 8.14. [1S,4R,4a S,9a R,10S,(S)R]-8d : oil; [R]20
)
D
+116 (c 1.16, CHCl3); 13C NMR δ 200.8, 143.9, 142.0, 139.3,
134.9, 133.8, 133.6, 133.0, 129.9 (2C), 127.8, 126.0, 125.6, 123.7
(2C), 73.8, 71.5, 51.1, 49.5, 49.3, 49.0, 45.7, 21.2.
4a ,5,8,8a -Tetr a h yd r o-4-h yd r oxy-5,8-m eth a n o-2-m eth -
oxy-4-[(p-tolylsu lfin yl)m eth yl]n a p h th a len -1-on e (7e a n d
8e). Compounds 7e and 8e were obtained from 5e and 6e
under the experimental conditions and in the ratios shown in
Table 2. Purification and separation were achieved by flash
chromatography (AcOEt/hexane, 3:2). [4S,4a R,5S,8R,8a S,
(S)R]-7e: white solid; mp 74.5-75.5 °C; [R]20 ) +91 (c 1,
D
CHCl3); 13C NMR δ 195.0, 151.5, 142.4, 139.5, 136.7, 132.9,
130.3 (2C), 124.0 (2C), 118.8, 72.5, 68.7, 55.1, 52.3, 48.8 (2C),
47.2, 45.0, 21.1. [4R,4a S,5R,8S,8a R,(S)R]-8e: oil; [R]20
)
D
+26 (c 1.2, CHCl3); 13C NMR δ 195.0, 151.6, 142.1, 139.7, 136.4,
132.3, 130.1 (2C), 123.7 (2C), 117.6, 72.8, 72.0, 55.2, 52.2, 48.7,
48.0, 47.0, 46.0, 21.2.
4a ,5,8,8a -Tet r a h yd r o-4-h yd r oxy-8-m et h yl-4-[(p -t olyl-
su lfin yl)m eth yl]n a p h th a len -1-on e (9a a n d 10a ). Com-
pounds 9a and 10a were obtained from 5a under the experi-
mental conditions and in the ratios shown in Table 3.
Purification and separation were achieved by flash chroma-
tography (AcOEt/hexane, 1:2). [4S,4aR,8S,8aS,(S)R]-9a: white
solid; mp 90-91 °C; [R]20D ) -109 (c 1.01, CHCl3); 13C NMR δ
199.0, 147.3, 142.2, 139.8, 131.2, 130.1 (2C), 128.5, 123.9 (3C),
74.2, 64.5, 48.9, 47.2, 33.9, 23.7, 21.2, 18.4. Anal. Calcd for
C19H20O3S: C, 69.49; H, 6.14. Found: C, 69.18; H, 5.79.