Double Diastereoselection in Photocycloadditions
J. Am. Chem. Soc., Vol. 120, No. 8, 1998 1753
2H,), 1.84 (dd, J ) 9.3, 13.1 Hz, 1H), 2.02 (m, J ) 3.7, 5.6, 13.1 Hz,
2H), 2.25 (t, J ) 9.3 Hz, 1H), 2.46 (m, J ) 4.8 Hz, 1H), 2.54 (m, 1H),
2.79 (m, J ) 9.3, 11.2, 16.8 Hz, 1H), 3.14 (dd, J ) 5.6, 13.1 Hz, 1H),
3.72 (s, 3H), 4.34 (dd, J ) 3.7, 5.6 Hz, 1H). 13C NMR (250 MHz,
CDCl3): δ 214.96, 169.82, 97.87, 71.12, 66.78, 58.78, 55.80, 51.87,
48.36, 43.25, 37.15, 33.93, 33.73, 31.76, 30.36, 30.18, 24.39, 21.51.
IR (film): 2980, 2940, 1750, 1730, 1430, 1370, 1285, 1250, 1200,
1190 cm-1. Anal. Calcd for C18H26O5: C, 67.06; H, 8.13. Found:
C, 66.98; H, 8.10. Spectral data for the minor syn photoadduct 20 are
as follows. 1H NMR (250 MHz, CDCl3): δ 1.13 (s, 3H), 1.23 (s, 3H),
1.44 (s, 6H), 1.59 (m, J ) 12.1, 18.7 Hz, 1H), 1.92-2.10 (band, 5H),
2.25 (t, J ) 9.3 Hz, 1H), 2.31 (dd, J ) 7.5, 14.9 Hz, 1H), 2.47-2.63
(band, J ) 3.7, 6.3 Hz, 2H), 2.78 (m, J ) 9.3, 10.3, 18.7 Hz, 1H),
3.62 (s, 3H), 4.14 (d, J ) 1.9 Hz, 1H). 13C NMR (400 MHz, CDCl3):
δ 215.83, 170.03, 97.42, 73.54, 71.00, 58.46, 57.77, 52.01, 44.76, 44.03,
38.20, 32.62, 32.00, 31.63, 30.02, 29.93, 24.33, 23.71. IR (film): 2990,
Thiocarbonylimidazole Derivative 36. To a solution of the tricyclic
diol 35 (0.945 g, 3.35 mmol) in 50 mL of freshly distilled CHCl3 under
nitrogen were added thiocarbonyldiimidazole (0.995 g, 90% technical
grade, 5.03 mmol) and 4-(dimethylamino)pyridine all at once (0.082
g, 0.67 mmol). The reaction mixture was heated at reflux for 1 h and
cooled to room temperature, and the solvent was removed in vacuo.
Chromatography with 50% ethyl acetate/hexanes, then 75% ethyl
acetate/hexanes, and then 100% ethyl acetate afforded the pure
thiocarbonylimidazole derivative 36 (1.122 g, 2.86 mmol, 85%) as a
pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 1.228 (s, 3H), 1.26
(s, 3H), 1.93 (dd, J ) 8.0, 14.0 Hz, 1H), 2.09 (m, 4H), 2.37 (m, 2H),
2.60 (m, 3H), 2.74 (m, 1H), 3.67 (s, 3H), 5.41 (d, J ) 8.4 Hz, 1H),
6.99 (s, 1H), 7.56 (s, 1H), 8.25 (s, 1H). 13C NMR (400 MHz, CDCl3):
δ 214.5, 183.4, 169.7, 136.5, 130.8, 118.1, 91.23, 69.82, 57.42, 57.2,
56.23, 52.27, 45.06, 38.04, 32.36, 32.27, 29.69, 29.18, 29.04. IR
(film): 3330 (br), 2970, 1745, 1730, 1465, 1385, 1335, 1285, 1240,
1210, 1145, 1090, 980 cm-1. HRMS (MH+) (m/e) for C19H24O5N2S:
calcd 393.1484, found 393.1479.
2970, 2950, 2925, 1745, 1725, 1370, 1145 cm-1
.
Anti Photoadduct 22. A solution of photosubstrate 9a (4.412 g,
13.7 mmol) in hexanes and CH2Cl2 (550 mL, 10:1) was placed in a
Pyrex immersion well reactor and irradiated with a 450-W medium-
pressure mercury vapor lamp, through a uranium glass filter for 15 h
at room temperature. The solvent was removed, and flash chroma-
tography (15% ethyl acetate/hexanes) afforded as the sole product anti
photoadduct 22 (4.30 g, 13.4 mmol, 98%, mp 100-103 °C) as a white
crystalline solid. 1H NMR (250 MHz, CDCl3): δ 1.24 (s, 3H), 1.27
(s, 3H), 1.38 (s, 3H), 1.46 (s, 3H), 1.58-1.72 (band, 2H), 2.02 (m, J
) 7.5, 13.1 Hz, 1H), 2.15-2.34 (band, 3H), 2.47-2.65 (band, 2H),
2.78 (ddd, J ) 9.3, 13.1, 17.5 Hz, 1H), 3.71 (s, 3H), 3.77-3.87 (m,
1H). 13C NMR (250 MHz, CDCl3): δ 214.01, 170.13, 100.32, 79.58,
75.79, 57.81, 54.71, 52.16, 50.35, 42.49, 37.21, 34.06, 32.64, 31.76,
31.67, 30.24, 24.78, 22.35. IR (film): 2970, 2940, 2870, 1745, 1725,
1445, 1435, 1370, 1250, 1185 cm-1. Anal. Calcd for C18H26O5: C,
67.06; H, 8.13. Found: C, 66.92; H, 8.07.
Spiroketones 37a,b. In a three-neck 3-L round-bottom flask
equipped with a reflux condenser, a mechanical stirrer, and an addition
funnel, the thiocarbamate 36 (1.451 g, 3.702 mmol) was dissolved in
1000 mL of benzene (freshly distilled and subsequently degassed with
N2 for 1 h prior to use) under N2 and heated to a gentle reflux. A
solution of tributyltin hydride (1.19 mL, 4.442 mmol) and AIBN (0.121
g, 0.740 mmol) in 500 mL of degassed benzene was added to the
reaction mixture very slowly over a 6-h period. The reflux was
continued for 1 h after the addition was complete, and the solvent was
then removed in vacuo. Purification by flash chromatography (25-
50% ethyl acetate/hexanes) gave the spiroketones 37a (0.552 g, 2.075
mmol, 56%, Rf 50% ) 0.15) as the higher Rf diastereomer and 37b (0.406
g, 1.526 mmol, 41%, Rf 50% ) 0.13) as the lower Rf diastereomer.
Spectral data for 37a are as follows. 1H NMR (400 MHz, CDCl3): δ
1.11 (s, 3H), 1.16 (s, 3H), 1.22 (m, 1H), 1.75 (m, 1H), 1.89 (m, 3H),
2.32 (m, 1H), 2.45 (m, 2H), 2.59 (m, 1H), 2.88 (m, 2H), 3.58 (s, 3H),
5.72 (dd, J ) 1.2, 6.0 Hz, 1H), 5.75 (dd, J ) 2.4, 6.0 Hz, 1H). 1H
NMR (300 MHz, benzene-d6): δ 1.18 (s, 3H), 1.21 (s, 3H), 1.39 (m,
2H), 1.60 (m, 1H), 1.74 (dd, J ) 7.8, 13.2 Hz, 1H), 1.88 (dd, J ) 7.8,
13.2 Hz, 1H), 2.17 (m, 3H), 2.40 (dd, J ) 3.6, 14.4 Hz, 1H), 2.57 (dd,
J ) 10.8, 14.1 Hz, 1H), 2.65 (dd, J ) 3.9, 11.1 Hz, 1H), 2.79 (tt, J )
1.8, 8.1 Hz, 1H), 3.38 (s, 3H), 5.58 (dd, J ) 2.7, 5.7 Hz, 1H), 5.73
(dd, J ) 1.5, 5.7 Hz, 1H). 13C NMR (400 MHz, CDCl3): δ 209.1,
172.9, 138.2, 131.1, 71.67, 55.76, 51.69, 50.89, 50.11, 40.66, 38.18,
35.66, 30.76, 28.06, 27.07. IR (film): 3480 (br), 2975, 2865, 1760,
1440, 1370, 1280, 1230, 1195, 1175, 1135 cm-1. HRMS (MH+) (m/
e) for C15H22O4: calcd 267.1596, found 267.1584. Spectral data for
37b are as follows. 1H NMR (400 MHz, CDCl3): δ 1.12 (s, 3H),
1.19 (s, 3H), 1.28 (m, 1H), 1.50 (br, 1H), 1.65 (m, 1H), 1.78 (dd, J )
8.0, 12.8 Hz, 1H), 1.99 (m, 2H), 2.37 (m, 2H), 2.47 (dd, J ) 5.2, 15.6
Hz, 1H), 2.60 (dd, J ) 7.2, 15.6 Hz, 1H), 2.86 (m, 2H), 3.62 (s, 3H),
5.77 (dd, J ) 2.0, 5.6 Hz, 1H), 5.88 (dd, J ) 2.4, 5.6 Hz, 1H). 13C
NMR (400 MHz, CDCl3): δ 208.7, 173.2, 136.7, 131.7, 71.4, 55.61,
51.75, 51.49, 50.32, 40.79, 38.02, 36.35, 35.16, 28.32, 27.11. IR
(film): 3450 (br), 1970, 2870, 1730, 1440, 1365, 1280, 1195, 1170
Syn Photoadduct Diol 21. The syn photoadduct 19 (438.0 mg,
1.360 mmol) was dissolved in 15 mL of 4:1 THF/H2O at room
temperature. To the solution was added pyridinium p-toluenesulfonate
(85.4 mg, 0.340 mmol). After 2 days of stirring, the mixture was diluted
with ether, washed with brine, dried over magnesium sulfate, filtered,
concentrated, and chromatographed with 30% ethyl acetate/hexanes to
afford syn diol 21 (341.5 mg, 1.211 mmol, 89%, mp 142-144 °C) as
a white crystalline solid. 1H NMR (400 MHz, CDCl3): δ 1.22 (s, 3H),
1.44 (s, 3H), 1.65 (dd, J ) 6.0, 13.5 Hz, 1H), 1.73 (m, J ) 5.8, 13.5
Hz, 1H), 1.86 (dd, J ) 9.0, 13.5 Hz, 1H), 2.02 (m, J ) 5.4 Hz, 2H),
2.25 (t, J ) 13.5 Hz, 1H), 2.44 (m, J ) 7.5, 12.0 Hz, 1H), 2.53 (m, J
) 3.6, 4.5, 6.0, 18.0 Hz, 1H), 2.74 (dt, J ) 10.5, 12.0, 18.0 Hz, 1H),
3.01 (dd, J ) 6.0, 13.5 Hz, 1H), 3.28 (br s, 1H), 3.68 (s, 3H), 4.46 (br
t, 1H). 13C NMR (250 MHz, CDCl3): δ 215.31, 170.34, 73.40, 71.52,
57.63, 56.07, 54.74, 52.13, 43.58, 37.49, 33.03, 32.48, 29.97, 29.60,
21.50. IR (film): 3460 (br), 3200 (br), 2970, 2940, 2920, 2860, 1745,
1720, 1430, 1410, 1380, 1290, 1240, 1190, 1150, 1130 cm-1. Anal.
Calcd for C15H22O5: C, 63.81; H, 7.85. Found: C, 63.58; H, 7.79.
Anti Photoadduct Diol 35. To a solution of the photoadduct 22
(4.30 g, 13.4 mmol) in 100 mL of THF and 25 mL of H2O at room
temperature was added a catalytic amount of p-toluenesulfonic acid.
After 3 h of stirring, the reaction mixture was diluted with 100 mL of
ether, and the aqueous layer was extracted with ether (50 mL × 3).
The combined organic layers were washed with brine, dried over
magnesium sulfate, concentrated, and chromatographed with 30% ethyl
acetate/hexanes to afford the tricyclic diol 35 (3.283 g, 11.6 mmol,
85% for two steps from the photosubstrate 22) as a white crystalline
solid (mp 108-110 °C). 1H NMR (400 MHz, CDCl3): δ 1.23 (s, 3H),
1.27 (s, 3H), 1.63 (m, J ) 6.0, 10.5 Hz, 2H), 1.98 (dt, J ) 9.0, 12.0
Hz, 1H), 2.08 (m, J ) 1.5, 6.0, 7.5 Hz), 2.21 (m, J ) 9.0, 12.0 Hz,
1H), 2.24-2.33 (m, 2H), 2.51 (m, 1H), 2.55 (m, J ) 9.0, 16.5 Hz,
1H), 2.73 (ddd, J ) 9.0, 12.0, 19.5 Hz, 1H), 3.67 (s, 3H), 4.13 (dd, J
) 3.0, 9.0 Hz, 1H). 13C NMR (400 MHz, CDCl3): δ 215.06, 170.08,
82.69, 72.83, 57.68, 57.25, 56.08, 52.21, 45.42, 37.82, 33.90, 33.12,
31.24, 29.86, 24.18. IR (film): 3420 (br), 2960, 2940, 2870, 1740,
1725, 1440, 1430, 1370, 1280, 1255, 1205, 1135 cm-1. Anal. Calcd
for C15H22O5: C, 63.81; H, 7.85. Found: C, 63.57; H, 7.88.
cm-1
267.1593.
Anti Acetonide Enone 23. To a solution of the anti photoadduct
.
HRMS (MH+) (m/e) for C15H22O4: calcd 267.1596, found
22 (480.3 mg, 1.492 mmol) and ethyl (trimethylsilyl)acetate (0.68 mL,
3.792 mmol) in 8 mL of dry THF at room temperature under nitrogen
was added over 30 min a solution of tetrabutylammonium fluoride (7.5
µL of a 1.0 M solution in THF, 0.075 mmol) in 4 mL of dry THF.
After 40 min of stirring, 20 mL of dry acetonitrile, palladium(II) acetate
(335.0 mg, 1.492 mmol), and benzoquinone (323.0 mg, 2.984 mmol)
were added at once. After being stirred at room temperature for 3
days, the reaction mixture was diluted with 50 mL of 1:1 ether/
petroleum ether and filtered through Celite. Flash chromatography with
15% ethyl acetate/hexanes afforded anti acetonide enone 23 (267.5 mg,
0.8359 mmol, 56%, 66% based on recovered ketone 22). 1H NMR
(250 MHz, CDCl3): δ 1.24 (s, 3H), 1.27 (s, 3H), 1.33 (d, J ) 13.1 Hz,
1H), 1.40 (s, 3H), 1.50 (s, 3H), 1.62 (m, J ) 1.9, 7.5 Hz, 1H), 1.86
(dd, J ) 7.5, 13.1 Hz, 1H), 2.08 (dd, J ) 8.2, 14.2 Hz, 1H), 2.23 (m,
J ) 3.7, 8.2 Hz), 2.83 (dd, J ) 3.7, 14.2 Hz, 1H), 3.73 (s, 3H), 3.99