472 J . Org. Chem., Vol. 62, No. 3, 1997
Hanessian et al.
1
1775, 1720, 1650 cm-1; H NMR (CDCl3, 300 Hz) δ 6.79 (d, J
chromatographed on silica gel (hexanes:ether:dichloromethane,
60:8:32 ) to afford 60 mg (60%) of compound 12 and 26 mg of
13.
) 2.1 Hz, 1H), 6.01 (dd, J ) 10.9, 17.6 Hz, 1H), 5.34 (br, d, J
) 10.9 Hz, 1H), 5.14 (br, d, J ) 17.6 Hz, 1H), 4.05 (s, 2H),
3.75 (m, 2H), 3.74 (s, 3H), 3.53 (s, 3H), 2.78 (dd, J ) 5.5, 17.8
Hz, 1H), 2.34 (ddd, J ) 2.9, 8.5, 17.8 Hz, 1H), 0.88 (s, 9H),
0.06 (s, 3H), 0.04 (s, 3H); 13C NMR (CDCl3) δ 169.5, 166.0,
135.6, 135.2, 130.0, 117.8, 87.5, 84.6, 69.0, 61.3, 52.0, 41.2, 34.1,
25.6, 17.9, -4.7, -5.0; MS (EI) m/ e 418, 387, 361, 329, 267,
253, 235, 221, 188, 174, 147, 116, 102, 89, 73; HRMS calcd for
(4S,4a R,6R,7R,7a S)-6-((ter t-Bu tyld im eth ylsilyl)oxy)-7-
m et h oxy-2-oxo-h exa h yd r ob en zofu r a n -4,7a -d ica r b oxy-
lic Acid Dim eth yl Ester (14). A stream of ozone (Wellsbach
generator) was passed through a solution of the olefin 12 (800
mg, 2.08 mmol) in dichloromethane (10 mL) at -78 °C. After
the appearance of a blue coloration the ozone flow was stopped
and replaced by a flow of argon for 30 min. Dimethyl sulfide
(2 mL) was added at -78 °C, and the solution was stirred for
1 h at this temperature, and then the reaction mixture was
allowed to warm to rt whereupon it was stirred for 1 h. After
removal the solvent in vacuo, the residue was dissolved in a
mixture of tert-butyl alcohol (40 mL) and 2-methyl-2-butene
(10 mL) and stirred at rt. A solution of sodium chlorite (1.7
g, 18.9 mmol, 9.2 equiv) and sodium dihydrogen phosphate
(1.7 g, 18.9 mmol, 9.2 equiv) in water (17 mL) was added
dropwise over a period of 10 min. The reaction was stirred at
rt for 2 h, and the volatile components were removed by
evaporation under reduced pressure. Water (15 mL) was
added and the aqueous solution extracted with hexanes. The
aqueous layer was acidified to pH 3 with 10% hydrochloric
acid at 0 °C and extracted with ether. The combined ethereal
extracts were dried (Na2SO4), and the solvent was evaporated
to give the crude acid as a gum. To the solution of the crude
acid in dry ether (40 mL) was added dropwise a freshly
prepared solution of diazomethane in ether at 0 °C until the
yellow color persisted. After stirring the reaction mixture for
5 min at 0 °C, excess diazomethane was destroyed by the
addition of acetic acid and the resulting solution stirred over
a mixture of anhydrous sodium sulfate and sodium carbonate.
The reaction mixture was filtered and then concentrated under
reduced pressure. The crude product was purified by chro-
matography on silica gel (EtOAc:hexanes; 30:70) to afford 789
mg of diester lactone 14 (91%) as a white crystalline solid: mp
131-133° C; [R]D -40.3° (c 4.0, CHCl3); IR (CHCl3) ν 1800,
C
19H31ClO6Si (M+) 35Cl 418.1578; found 418.1592; 37Cl calcd
420.1549; found 420.1554.
(3S,4S,5R)-5-((ter t-Bu tyld im eth ylsilyl)oxy)-3-(iod oa c-
etoxy)-4-m eth oxy-3-vin ylcycloh ex-1-en eca r boxylic Acid
Meth yl Ester (11). To a solution of 372 mg of the chloro ester
10 (0.89 mmol) in 5 mL dry acetonitrile were added activated
powdered molecular sieves 3 Å and 536 mg of NaI (3.6 mmol,
4 equiv). The reaction mixture was stirred at rt for 18 h. After
concentration in vacuo and filtration of the residue, the crude
product was purified by chromatography on silica gel (EtOAc:
hexanes, 10:90) to afford 441 mg (97%) of the iodo ester 11 as
a colorless oil: [R]D -24.4° (c 2.25, CCl4); IR (neat) ν 2980-
1
2880, 1740, 1625 cm-1; H NMR (CDCl3, 300 Hz) δ 6.72 (d, J
) 2.8 Hz, 1H), 6.02 (dd, J ) 10.8, 17.6 Hz, 1H), 5.32 (d, J )
10.8 Hz, 1H), 5.13 (d, J ) 17.1 Hz, 1H), 3.75 (s, 5H), 3.72-
3.68 (m, 2H), 3.58 (s, 3H), 2.77 (dd, J ) 5.2, 17.6 Hz, 1H), 2.31
(dddd, J ) 1.3, 2.9, 7.8, 17.7 Hz, 1H), 0.89 (s, 9H), 0.05 (s,
3H), 0.04 (s, 3H); 13C NMR (CDCl3) δ 167.0, 166.0, 135.5, 135.3,
129.7, 117.5, 86.9, 84.5, 69.1, 61.5, 51.9, 34.0, 26.3, 25.6, 17.8,
-4.5, -4.7; MS (EI) m/ e 510, 479, 469, 453, 327, 295, 267,
253, 235, 169, 128, 89, 73; HRMS calcd for C19H31IO6Si (M+)
510.0936; found 510.0949.
(4S,4a R,6R,7R,7a S)-6-((ter t-Bu tyld im eth ylsilyl)oxy)-7-
m eth oxy-2-oxo-7a -vin yl-octa h yd r oben zofu r a n -4-ca r box-
ylic Acid Meth yl Ester (12) a n d (4S,4a R,6R,7R,7a S)-6-
((ter t -Bu t yld im et h ylsilyl)oxy)-7-m et h oxy-2-oxo-7a -vi-
n ylocta h yd r oben zofu r a n -4-ca r boxylic Acid Meth yl Es-
ter (13). A solution of the iodo ester 11 (324 mg, 0.635 mmol)
in dry benzene (33 mL) was stirred at reflux under an
1740 cm-1 1H NMR (CDCl3, 300 Hz) δ 4.00 (ddd, J ) 13.8,
;
9.2, 4.6 Hz, 1H), 3.85 (s, 3H), 3.70 (s, 3H), 3.55 (s, 3H), 3.24
(dt, J ) 13.8, 4.2 Hz, 1H), 3.10 (d, J ) 9.2 Hz, 1H), 3.15-3.00
(m, 1H), 2.70-2.45 (m, 2H), 2.17 (dt, J ) 13.8, 4.4 Hz, 1H),
1.70 (dt, J ) 11.4, 13.6 Hz, 1H), 0.9 (s, 9H), 0.1 (2 × s, 6H);
13C NMR (CDCl3) δ 172.8, 172.1, 169.0, 89.5 (q), 87.9, 70.1,
61.5, 52.7, 52.2, 40.8, 38.2, 30.1 (2CH2), 25.6, 17.9, -4.7, -5.0;
MS (EI) m/ z 385, 359, 327, 313, 299, 285, 281, 267, 253, 239,
atmosphere of argon with
a catalytic amount of azobis-
(isobutyronitrile) (4 mg). A solution of triphenyltin hydride
(401 mg, 1.143 mmol) in dry benzene (24 mL) was added over
5.5 h using a syringe pump. Upon completion of the addition,
the reaction was allowed to cool to rt, and the benzene was
evaporated under reduced pressure. The crude residue was
purified by chromatography (hexanes:ether:dichloromethane,
60:8:32) to give the lactone 12 (124 mg, 51%, Rf ) 0.14,
hexanes-ether-CH2Cl2, 60:8:32) as a white crystalline solid,
and the isomeric 13 (53 mg, 22%, Rf ) 0.23) as an oil after
two chromatographic separations. For lactone 12: mp 98 °C
(recrystallized from hexanes) [R]D -20° (c 1.1, CCl4); IR (neat)
ν 3080, 1790, 1740 cm-1; 1H NMR (CDCl3, 300 Hz) δ 6.04 (dd,
J ) 11.1, 17.3 Hz, 1H), 5.53 (br, d, J ) 17.3 Hz, 1H), 5.37 (br,
d, J ) 11.1 Hz, 1H), 3.70 (s, 3H), 3.55 (ddd, J ) 4.6, 9.3, 11.2
Hz, 1H), 3.48 (s, 3H), 3.08 (d, J ) 9.3 Hz, 1H), 2.89 (ddd, J )
4.8, 10.1, 12.1 Hz, 1H), 2.77 (ddd, J ) 4.4, 4.4, 13.6 Hz, 1H),
2.61 (d, J ) 12.1 Hz, 1H), 2.60 (d, J ) 9.7 Hz, 1H), 2.12 (ddd,
J ) 4.1, 4.1, 13.8 Hz, 1H), 1.80 (m, 1H), 0.90 (s, 9H), 0.10 (s,
3H), 0.09 (s, 3H); 13C NMR (CDCl3) δ 174.0, 172.1, 133.2, 116.9,
89.5, 87.6, 70.5, 60.7, 52.1, 43.9, 38.3, 30.9, 30.7, 25.6, 17.9,
-4.7, -5.1; MS (EI) m/ e 369, 353, 337, 327, 295, 267, 253,
235, 207, 185, 140, 98, 89, 73; HRMS calcd for C15H23O6Si (M+
- t-Bu) 327.1263; found 327.1251. For 13: [R]D -2.7° (c 1.4,
225, 207, 193, 179, 165; HRMS calcd for C18H29O7Si (M+
OCH3) 385.1682; found 385.1700.
-
(2RS,4S,4a S,6R,7R,7a S)-6-((ter t-Bu t yld im et h ylsilyl)-
oxy)-2-h yd r oxy-7-m et h oxyh exa h yd r ob en zofu r a n -4,7a -
d ica r boxylic Acid Dim eth yl Ester (15). To a solution of
14 (300 mg, 0.72 mmol) in 20 mL of dry THF was added 5 mL
of disiamylborane (0.5 mmol/mL in THF) at 0 °C under argon.
The solution was allowed to warm to rt and stirred for 4 h.
Upon completion of the reaction, the solution was quenched
with 10 mL of saturated NaCl and extracted with EtOAc. The
organic layer was dried (Na2SO4) and concentrated in vacuo.
The residue was chromatographed on silica gel (EtOAc:
hexanes, 50:50) to give 295 mg of lactol 15 (98%) as a syrup
which was used as such in the next step: IR (CHCl3) ν 3700,
3610 (OH), 1740 (CdO, ester) cm-1
.
La cta m 16 a n d 17. A mixture of the lactol 15 (80 mg, 0.19
mmol), 6-methoxytryptamine (54 mg, 0.28 mmol), and pivalic
acid (58 mg, 0.57 mmol) in 10 mL of toluene, under argon,
was refluxed with azeotropic removal of water, and the solution
was concentrated to half its original volume. After 50 min,
the solution was cooled to rt, and the toluene was evaporated
in vacuo. The residue was purified by chromatography
(EtOAc:hexanes, 60:40) to give 56 mg of the 3-â lactam 16 and
40 mg of 3-R lactam 17, both as white crystalline solids (total
yield, 90%). For 16: mp 223 °C dec; [R]D +36.83° (c 0.6, CH2-
CCl4); IR (neat, CHCl3) ν 3020, 2975-2296, 1780, 1730 cm-1
;
1H NMR (CDCl3, 300 Hz) δ 6.02 (dd, J ) 10.9, 7.3 Hz, 1H),
5.42 (d, J ) 17.3 Hz, 1H), 5.29 (d, J ) 10.9 Hz, 1H), 4.05 (m,
1H), 3.70 (s, 3H), 3.40 (s, 3H), 3.20 (d, J ) 4.6 Hz, 1H), 2.81-
2.62 (m, 3H), 2.32-2.21 (m, 1H), 2.00 (ddd, J ) 3.0, 11.0, 13.5
Hz, 1H), 1.82 (ddd, J ) 4.0, 4.2, 13.5 Hz, 1H), 0.90 (s, 9H),
0.10 (s, 3H), 0.09 (s, 3H); 13C NMR (CDCl3) δ 175.0, 174.0,
135.0, 115.3, 86.0, 81.6, 66.5, 59.6, 51.8, 50.1, 39.3, 38.2, 34.8,
29.8, 25.4, -5.0, -5.3; MS (EI) m/ z 353, 341, 309, 295, 267,
235, 207, 193, 161, 133, 116, 89, 71; HRMS calcd for C18H29O5-
Si (M+ - OCH3) 353.1813; found 353.1784.
1
Cl2); IR (CH2Cl2) ν 3480, (1740, 1640 cm-1; H NMR (CDCl3,
300 Hz) δ 7.78 (s, 1H), 7.32 (d, J ) 8.6 Hz, 1H), 6.84 (d, J )
2.0 Hz, 1H), 6.78 (dd, J ) 8.6, 2.3 Hz, 1H), 5.05 (m, 1H), 4.95
(dd, J ) 11.8, 7.8, 1H), 4.12-4.00 (m, 2H), 3.81 (s, 3H), 3.75
(s, 3H), 3.55 (s, 3H), 3.26 (d, J ) 8.4 Hz, 1H), 3.10-2.85 (m,
3H), 2.60 (m, 2H), 2.40 (m, 1H), 2.20 (m, 2H), 2.15-1.90 (m,
A solution of lactone 13 (100 mg, 0.26 mmol) in 1 mL of
DBU was stirred for 16 h at rt. The mixture was directly