9432 J . Org. Chem., Vol. 63, No. 25, 1998
Kuehne and Xu
extracted with dichloromethane. The residue, obtained on
drying and concentration, was purified on a silica gel column,
eluting with EtOAc/Hex (2:3), to give 1.95 g (82% yield) of the
1.97 mmol) in 4 mL of THF, at 0 °C, was added (EtO)2P(O)-
CH2COOMe (388 uL, 2.03 mmol), dropwise. The solution was
stirred at room temperature for another 30 min. A solution of
the ketone 15 (180 mg, 0.58 mmol) in 2 mL of THF was then
cannulated into the above solution. The reaction mixture was
stirred at room temperature for 8 h, and the reaction was then
quenched with water. The aqueous phase was extracted with
dichloromethane. The residue, obtained on drying and con-
centration, was chromatographed on a silica gel column,
eluting with Hex/CH2Cl2/Et3N (60:40:5), to afford 135 mg of
the title (E)-ester (19, 64% yield) and 10 mg of the (Z)-ester
20, contaminated with (EtO)2P(O)CH2COOEt.
title product 18: Rf ) 0.25 (EtOAc/Hex, 2:3, CAS blue); [R]25
D
-200 (c ) 1.0, CHCl3); UV λmax (EtOH) 206, 228, 296, 324 nm;
1
IR (KBr) νmax 3473, 3362, 1706, 1683, 1608 cm-1; H NMR δ
9.20 (s, 1 H), 7.34 (m, 2 H), 7.29 (m, 3 H), 7.16 (t, J ) 7.7 Hz,
1 H), 7.06 (d, J ) 7.3 Hz, 1 H), 6.87 (m, 2 H), 4.68 (d, J ) 18.0
Hz, 1 H), 4.39 (d, J ) 18.0 Hz, 1 H), 4.14 (d, J ) 13.2 Hz, 1 H),
3.81 (d, J ) 4.1 Hz, 1 H), 3.75 (s, 3 H), 3.51 (d, J ) 13.2 Hz,
1 H), 3.26 (d, J ) 3.5 Hz, 1 H), 2.78 (dd, J 6.8, 8.7 Hz, 1 H),
2.54 (d, J ) 14.3 Hz, 1 H), 2.45 (ddd, J ) 8.7, 12.2, 13.6 Hz, 1
H), 2.12 (ddd, J ) 6.8, 12.2, 12.2 Hz, 1 H), 1.60 (m, 2 H); 13C
NMR δ 210.6, 167.9, 142.6, 137.8, 137.2, 128.8, 128.4, 128.0,
127.2, 121.3, 120.9, 109.6, 91.7, 66.7, 65.3, 58.2, 56.0, 51.2, 50.9,
44.1, 43.7, 30.5; MS m/z 419 (2), 418 (M+, 6), 359 (21), 159
(12), 146 (39), 134 (15), 112 (14), 91 (100).
For the (E)-ester 19: Rf ) 0.19 (Hex/CH2Cl2/Et3N, 60:40:5,
CAS blue); [R]26D -403 (c ) 0.45, CHCl3); UV λmax (EtOH) 206,
234, 298, 326 nm; IR (KBr) νmax 3368, 1723, 1676, 1607 cm-1
;
1H NMR δ 8.78 (s, 1 H), 7.18 (d, J ) 7.5 Hz, 1 H), 7.12 (t, J )
7.6 Hz, 1 H), 6.88 (t, J ) 7.5 Hz, 1 H), 6.79 (d, J ) 7.7 Hz, 1
H), 5.75 (s, 1 H), 4.79 (s, 1 H), 3.98 (s, 1 H), 3.75 (s, 3 H), 3.69
(s, 3 H), 3.63 (d, J ) 14.5 Hz, 1 H), 3.16 (m, 2 H), 2.91 (dd, J
) 7.0, 12.2 Hz, 1 H), 2.66 (ddd, J ) 7.0, 12.4 Hz, 1 H), 2.26 (d,
J ) 13.5 Hz, 1 H), 1.87 (dd, J ) 5.9, 12.4 Hz, 1 H), 1.46 (d, J
) 13.5 Hz, 1 H); 13C NMR δ 168.5, 168.2, 165.9, 158.1, 144.0,
135.8, 127.7, 127.6, 120.9, 120.2, 114.9, 109.5, 101.2, 61.3, 57.1,
55.6, 55.0, 51.1, 51.0, 44.6, 30.6, 30.6; MS m/z 367 (15), 366
(M+, 38), 334 (12), 307 (11), 216 (21), 202 (15), 180 (10), 169
(12), 165 (100), 156 (26), 152 (10), 137 (22), 133 (16), 123 (17),
115 (10), 109 (18), 106 (18); HRMS calcd or C21H22N2O4
366.1580, found 366.1572.
(-)-Meth yl (2S,3aS,5R,11bR)-3-Ben zyl-2,3,3a,4,5,7-h exa-
h yd r o-3,5-et h a n o-12-oxo-1H -p yr r olo[2,3-d ]ca r b a zole-6-
ca r boxyla te (15). To a solution of the keto alcohol 18 (200
mg, 0.478 mmol) in 4 mL of 1,2-dichloroethane, at 0 °C, were
added Et3N (133 µL, 0.956 mmol), Ts2O (187 mg, 0.573 mmol),
and DMAP (5.9 mg, 0.048 mmol). The reaction was carefully
monitored by TLC. As soon as the starting material had
disappeared (ca. 20 min.), 4 mL of MeOH was introduced. The
reaction solution was stirred at 0 °C for another 30 min and
then heated in a 60 °C oil bath for 1 h. The solvent was
evaporated under vacuum, and the residual solid was tritu-
rated with ethyl ether.
For the (Z)-ester 20: Rf ) 0.28 (Hex/CH2Cl2/Et3N, 60:40:5,
CAS blue); UV λmax (EtOH) 208, 234, 298, 328 nm; selected
1H NMR data δ 8.86 (s, 1 H), 7.24 (d, J ) 7.7 Hz, 1 H), 7.16 (t,
J ) 7.6 Hz, 1 H), 6.92 (t, J ) 7.3 Hz, 1 H), 6.85 (d, J ) 7.7 Hz,
1 H), 6.02 (s, 1 H), 4.65 (d, J ) 17.4 Hz, 1 H), 3.88 (apparent
s, 1 H), 3.84 (s, 3 H), 3.68 (3, 3 H), 2.40 (m, 1 H), 2.18 (m, 1
H), 1.89 (m, 1 H).
The resulting quaternary salt was dissolved in 6 mL of
MeOH, and PdCl2 (25 mg, 0.143 mmol) was added. Hydro-
genolysis was carried out under 1 atm of hydrogen for 3 h.
The solid was removed by filtration, and the solvent was
evaporated under vacuum. The residue was dissolved in
dichloromethane and washed with 5% sodium carbonate. The
residue, obtained on drying and concentration, was purified
on a silica gel column, eluting with CH2Cl2/MeOH (95:5), to
afford 135 mg (91% yield) of the title product as a white foam:
Rf ) 0.4 (CH2Cl2/MeOH, 95:5, CAS blue); [R]26D -327 (c ) 0.95,
CHCl3); UV λmax (EtOH) 204, 226, 296, 326 nm; IR (KBr) νmax
3364, 1717, 1673, 1608 cm-1; 1H NMR δ 8.90 (s, 1 H), 7.27 (d,
J ) 8.0 Hz, 1 H), 7.19 (ddd, J ) 1.0, 7.7, 7.7 Hz, 1 H), 6.94
(ddd, J ) 0.6, 7.5, 7.5 Hz, 1 H), 6.86 (d, J ) 7.8 Hz, 1 H), 4.19
(s, 1 H), 3.87 (d, J ) 17.3 Hz, 1 H), 3.82 (s, 3 H), 3.72 (dd, J )
1.6, 1.6 Hz, 1 H), 3.30 (ddd, J ) 5.6, 12.0, 12.0 Hz, 1H), 3.02
(d, J ) 17.3 Hz, 1 H), 2.93 (ddd, J ) 5.6, 7.8, 12.0 Hz, 1 H),
2.61 (ddd, J ) 1.6, 3.6, 13.7 Hz, 1 H), 1.95 (m, 2 H), 1.65 (ddd,
J ) 1.6, 1.6, 13.7 Hz, 1 H); 13C NMR δ 212.2, 167.7, 166.9,
143.3, 135.1, 128.4, 121.4, 120.9, 109.9, 97.3, 60.6, 60.2, 57.5,
55.9,. 51.5, 46.7, 40.7, 29.1; MS m/z 311 (2), 310 (M+, 11), 215
(10), 183 (11), 156 (40), 154 (11), 115 (11), 109 (100), 95 (32);
HRMS calcd for C18H18N2O3 310.1317, found 310.1317.
Note: If excess Ts2O was used, or if MeOH was not added
as soon as the keto alcohol 18 was consumed, the correspond-
ing enol tosylate could be isolated in variable yields, depending
on reaction conditions: Rf ) 0.41 (EtOAc/Hex, 2:3, CAS gray);
mp 159 °C (EtOAc/Hex) for the racemic compound obtained
from racemic 18 in a parallel series of reactions; UV λmax
(EtOH) 206, 226, 298, 328 nm; IR (KBr) νmax 3366, 1675, 1603
(-)-Meth yl (2S,3aS,5R,11bR)-3-Ben zyl-2,3,3a,4,5,7-h exa-
hydro-3,5-ethano-12-(E)-[(hydroxymethyl)methylene]-1H-pyrrolo-
[2,3-d ]ca r b a zole-6-ca r b oxyla t e (18-H yd r oxya k u a m m i-
cin e, 21). To a solution of the (E)-ester 19 (50 mg, 0.136 mmol)
in 2 mL of CH2Cl2 at -78 °C was added BF3‚Et2O (34 uL, 0.27
mmol), dropwise. The solution was stirred at -78 °C for
15 min. DIBALH (435 uL, 0.435 mmol, 1.0 M in CH2Cl2) was
then added dropwise. After 3 h at -78 °C, the reaction was
quenched with saturated potassium sodium tartrate at -78
°C. The mixture was then allowed to warm to room temper-
ature and stirred until the two phases were clear (ca. 30 min).
The aqueous phase was extracted with dichloromethane. The
residue, obtained on drying and concentration, was dissolved
in a solution of 0.5 mL of Et3N, 4 mL of CH2Cl2, and 1 mL of
MeOH. The solution was heated in a 40 °C oil bath for 1 h.
The residue, obtained on concentration, was purified on a silica
gel column, eluting with CH2Cl2/MeOH/Et3N (95:5:1), to give
42 mg (91% yield) of the title allylic alcohol as a white solid:
Rf ) 0.13 (CH2Cl2/MeOH, 95:5, SiO2 plate, deactivated with
Et3N, CAS blue); mp 146 °C (dec); [R]24D -550 (c ) 0.3, CHCl3);
UV λmax (EtOH) 206, 234, 298, 328 nm; IR (KBr) νmax 3354,
1673, 1605 cm-1; 1H NMR δ 8.91 (s, 1 H), 7.24 (d, J ) 7.3 Hz,
1 H), 7.16 (t, J ) 7.5 Hz, 1 H), 6.91 (t, J ) 7.4 Hz, 1 H), 6.84
(d, J ) 7.7 Hz, 1 H), 5.55 (t, J ) 6.4 Hz, 1 H), 4.22 (d, J ) 6.4
Hz, 1 H), 4.07 (s, 1 H), 3.98 (s, 1 H), 3.88 (d, J ) 15.4 Hz, 1 H),
3.83 (s, 3 H), 3.27 (ddd, J ) 5.6, 5.6, 12.3 Hz, 1 H), 3.05 (d, J
) 15.4 Hz, 1 H), 3.01 (m, 1 H), 2.55 (ddd, J ) 6.8, 6.8, 12.5
Hz, 1 H), 2.38 (apparent d, J ) 13.4 Hz, 1 H), 1.87 (dd, J )
5.6, 12.5 Hz, 1 H), 1.34 (apparent dd, J ) 3.0, 13.4 Hz, 1 H);
13C NMR δ 168.5, 167.6, 143.3, 140.6, 136.3, 127.9, 125.7,
121.2, 120.7, 109.6, 100.6, 61.5, 58.3, 57.6, 56.1, 55.7, 51.3, 45.8,
30.7, 29.8; MS m/z 339 (7), 338 (M+, 20), 180 (9), 149 (31), 137
(100), 121 (10), 119 (10).
1
cm-1; H NMR δ 8.90 (s, 1 H), 7.82 (d, J ) 8.3 Hz, 2 H), 7.33
(d, J ) 8.3 Hz, 2 H), 7.22 (d, J ) 7.3 Hz, 1 H), 7.15 (ddd, J )
0.9, 7.7, 7.7 Hz, 1 H), 6.90 (t, J ) 7.4 Hz, 1 H), 6.81 (d, J ) 7.7
Hz, 1 H), 5.66 (s, 1 H), 4.01 (d, J ) 2.0 Hz, 1 H), 3.74 (s, 3 H),
3.49 (d, J ) 1.9 Hz, 1 H), 3.19 (ddd, J ) 4.8, 12.4, 12.4 Hz, 1
H), 3.00 (dd, J ) 6.4, 11.9 Hz, 1 H), 2.46 (s, 3 H), 2.22 (ddd, J
) 6.4, 12.5, 12.5 Hz, 1 H), 2.13 (ddd, J ) 3.0, 3.0, 12.7 Hz, 1
H), 1.75 (dd, J ) 4.8, 11.9 Hz, 1 H), 1.37 (ddd, J ) 2.9, 2.9,
12.7 Hz, 1 H); 13C NMR δ 167.5, 167.3, 145.0, 143.6, 138.3,
135.4, 133.3, 129.6, 128.5, 128.0, 121.0, 120.1, 109.7, 101.2,
58.8, 58.1, 53.24, 51.1, 46.0, 30.8, 29.5, 21.7; MS m/z 464 (M+,
2), 309 (35), 281 (12), 278 (23), 249 (34), 221 (13), 194 (13),
167 (24), 156 (19), 139 (67), 123 (20), 91 (100).
(-)-Meth yl (2S,3aS,5R,11bR)-3-Ben zyl-2,3,3a,4,5,7-h exa-
hydro-3,5-ethano-12-(Z)-[(hydroxymethyl)methylene]-1H-pyrrolo-
[2,3-d ]ca r ba zole-6-ca r boxyla te (22). For confirmation of the
structure of isolated ester 20, contaminated with Wittig
reagent, a DIBALH reduction of the (Z)-ester, using the
preceding procedure, gave the title compound in 65% yield:
Rf ) 0.18 (CHCl3/MeOH, 98:2, CAS blue); UV λmax (EtOH) 206,
(-)-Meth yl (2S,3aS,5R,11bR)-3-Ben zyl-2,3,3a,4,5,7-h exa-
h yd r o-3,5-eth a n o-12-(E a n d Z)-[(m eth oxyca r bon yl)m eth -
ylen e]-1H-pyr r olo[2,3-d]car bazole-6-car boxylates (19 an d
20). To a solution of potassium hexamethyldisilazane (414 mg,