4
336 J . Org. Chem., Vol. 63, No. 13, 1998
Rodr ´ı guez et al.
1
23.9, 119.6, 62.4, 35.3, 32.2, 29.7, 25.6, 23.0, 21.0, 15.3. MS
(1R*,2S*)-2′-E t h ylsp ir o[2-m et h ylcycloh exa n -1,3′-3′H -
+
-1
1
(70 eV): m/z 213 (M , 100); 198 (95); 184 (40); 170 (43); 156
in d ole] (2b). IR (film): 1690, 1570, 785, 750 cm
(CDCl ): δ 7.52 (d, 1H, J ) 7.1 Hz), 7.3-7.1 (m, 3H), 2.74 (q,
1H, J ) 7.0 Hz), 2.70 (q, 1H, J ) 7.5 Hz), 2.1-1.4 (m, 9H),
1.38 (dd, 3H, J ) 7.5 Hz, J ) 7.0 Hz), 0.35 (d, 3H, J ) 6.8
Hz). C NMR (CDCl
. H NMR
(19); 144 (72); 130 (22); 115 (35). Anal. Calcd for C15
H
19N:
3
C, 84.46; H, 8.98; N, 6.57. Found: C, 84.12; H, 8.56; N, 6.25.
Rea ction of 2′-Meth ylsp ir o[cycloh exa n -1,3′-3′H-in d ole]
1
2
1
3
(
1a ) w ith m eth ylm a gn esiu m iod id e (2a , 3a , 4a ). (a ) 2′-
3
): δ 189.9, 153.5, 147.5, 127.1, 124.9,
Eth ylsp ir o[cycloh exa n -1,3′-3′H-in d ole], 2a . To a solution
of methylmagnesium iodide (25 mmol) in anhydrous diethyl
ether (7 mL) was added dropwise at 0 °C a solution of 1a (500
mg, 2.5 mmol) in THF (35 mL). The flask was covered from
the sunlight, and the mixture was stirred at 0 °C for 4 h and
then hydrolyzed with a saturated aqueous solution of am-
monium chloride (30 mL), extracted with dichloromethane (50
121.4, 120.5, 61.6, 37.7, 33.2, 30.3, 25.6, 22.1, 21.4, 16.1, 10.8.
MS (70 eV): m/z 227 (M , 45), 212 (34), 198 (100), 184 (43),
+
170 (45), 156 (44), 144 (25), 130 (58), 115 (29). Anal. Calcd
for C16H21N: C, 84.53; H, 9.31; N, 6.16. Found: C, 84.23; H,
9.44; N, 5.85.
(1R*,2R*)-2′-E t h ylsp ir o[2-m et h ylcycloh exa n -1,3′-3′H -
-
1
1
in d ole] (2b). IR (film): 1680, 1570, 780, 750 cm
(CDCl ): δ 7.61 (d, 1H, J ) 7.4 Hz), 7.60 (d, 1H, J ) 7.5 Hz),
7.33 (ddd, 1H, J ) 7.6 Hz, J ) 7.4 Hz, J ) 1.4 Hz), 7.17
(ddd, 1H, J ) 7.5 Hz, J ) 7.4 Hz, J ) 1.3 Hz), 2.54 (q, 1H,
. H NMR
mL), and dried with Na
2
SO
4
. The solvent was removed, and
3
the residual brown oil was purified by silica gel column
chromatography using 1:5 ethyl acetate/hexane as the eluent.
The title compound 2a was isolated as a yellow solid, mp
1
1
1
2
3
1
2
3
J ) 7.4 Hz), 2.51 (q, 1H, J ) 7.3 Hz), 2.1-1.4 (m, 5H), 1.37 (t,
05-7 °C, 420 mg, 79% yield. IR (film): 2920, 2860, 1670,
3H, J ) 7.3 Hz), 1.25 (m, 2H), 0.93 (m, 2H), 0.26 (d, 3H, J )
-
1
1
13
570, 1450, 1350, 750 cm
.
H NMR: δ 7.62 (d, 1H, J ) 6.5
6.6 Hz). C NMR (CDCl
3
): δ 192.8, 148.2, 142.7, 127.3, 124.6,
Hz), 7.35 (t, 1H, J ) 6.5 Hz), 7.32 (d, 1H, J ) 8.2 Hz), 7.18 (t,
121.0, 120.1, 63.6, 35.5, 32.4, 30.1, 25.9, 21.8, 21.3, 16.3, 10.6.
MS (70 eV): m/z 227 (M , 45), 212 (34), 198 (100), 184 (43),
+
1
1
1
2
H, J ) 8.1 Hz), 2.60 (q, 2H, J ) 7.3 Hz), 1.5-2.2 (m, 8H),
1
3
.35 (t, 3H, J ) 7.3 Hz), 1.25 (m, 2H). C NMR: δ 191.3,
170 (45), 156 (44), 144 (25), 130 (58), 115 (29). Anal. Calcd
for C16H21N: C, 84.53; H, 9.31; N, 6.16. Found: C, 84.21; H,
9.47; N, 5.87.
54.2, 144.4, 127.2, 124.0, 123.9, 120.0, 57.8, 30.9, 25.1, 21.4,
2.0, 10.8. Anal. Calcd for C15
H
14N: C, 86.50; H, 6.78; N, 6.72.
Found: C, 86.24; H, 6.48; N, 6.35.
b) 2′-Isop r op ylsp ir o[cycloh exa n -1,3′-3′H-in d ole] (3a )
Meso-r,â-d i{(1R,2S),(1S,2R)}-2′-(sp ir o[2-m et h ylcyclo-
(
h exa n -1,3′-3′H-in d olyl]eth en e) (10). IR (KBr): 1690, 1600,
-
1
1
a n d 2′-ter t-bu tylsp ir o[cycloh exa n -1,3′-3′H-in d ole] (4a ). To
a solution of methylmagnesium iodide (37.7 mmol) in anhy-
drous diethyl ether (40 mL) was added dropwise at 0 °C a
solution of 1a (500 mg, 2.5 mmol) in anhydrous toluene (20
mL). The flask was covered from the sunlight, and the mixture
was stirred at room temperature for 60 h and then hydrolyzed
with a saturated aqueous ammonium chloride solution (30
mL), extracted with dichloromethane (50 mL), and dried with
770, 745 cm
.
3
H NMR (CDCl ): δ 7.85 (s, 2H), 7.65 (d, 2H,
J ) 7.0 Hz), 7.4-7.2 (m, 6H), 2.1-1.5 (m, 18H), 0.42 (d, 6H, J
1
3
) 6.6 Hz). C NMR (CDCl ): δ 181.6, 154.3, 146.8, 129.8, 127.6,
3
126.1, 120.9, 120.8, 61.5, 38.3, 34.0, 31.1, 26.0, 22.9, 16.3. MS
+
(70 eV): m/z 422 (M , 100), 407 (33), 393 (6), 379 (38), 365
(28), 351 (11), 339 (45), 211 (17), 180 (13), 168 (15), 154 (13),
141 (31). Anal. Calcd for C30
34 2
H N : C, 85.26; H, 8.11; N, 6.63.
Found: C, 84.92; H, 8.34; N, 6.55.
Na
2
SO
4
. The solvent was removed, and the residual brown
2′-Isop r op ylsp ir o[2-m e t h ylcycloh e xa n -1,3′-3′H -in -
d ole] (3b). In a round-bottom flask previously flamed and in
argon atmosphere was prepared a solution of methylmagne-
sium iodide (14.8 mmol) in diethyl ether (30 mL). On this
solution was slowly added a solution of 1b (211 mg, 0.99 mmol)
in dry toluene (30 mL). The mixture was vigorously stirred
at room temperature for 5 days and then was hydrolyzed with
a saturated aqueous solution of ammonium chloride (15 mL),
extracted with dichloromethane (20 mL), and dried on anhy-
drous magnesium sulfate.
oil was purified by column chromatography using 1:3 ethyl
acetate/hexane as the eluent. The title compound 3a was
obtained as an orange solid, mp 75-77 °C, 270 mg, 47% of
yield. The 2′-tert-butyl derivative 4a was also isolated as a
yellow oil, 30.8 mg (5%).
1
Com p ou n d 3a . H NMR: δ 7.71 (d, 1H, J ) 7.5 Hz), 7.60
(
(
d, 1H, J ) 7.5 Hz), 7.33 (td, 1H, J
1
) 7.4, J ) 1.1 Hz), 7.15
2
td, 1H, J
1
) 7.4, J ) 1.1 Hz), 2.97 (sept, 1H, J ) 6.8 Hz),
2
13
2
1
2
.1-1.8 (m, 10H), 1.30 (d, 6H, J ) 6.8 Hz). C NMR: δ 195.6,
54.5, 143.8, 127.3, 124.1, 124.0, 120.1, 58.4, 29.9, 27.5, 25.2,
After filtration the solvent was removed at reduced pressure,
giving a residual oil, which was purified by silica gel column
chromatography using 1:4 ethyl acetate/hexane as the eluent.
The title compound 3b was obtained as a red oil, 34.5 mg
(15%), as a diastereomeric mixture (1R*,2S* and 1R*,2R*, in
2:1 ratio) which was isolated by silica gel column chromatog-
raphy using 1:5 hexane/diethyl ether as the eluent. The 2′-
methylspiro derivative 2b was also isolated, 10.83 mg (5%).
(1R*,2S*)-2′-Isop r op ylsp ir o[2-m et h ylcycloh exa n -1,3′-
2.1, 22.0. IR (film): 2920, 1630, 1590, 740 cm-1. Anal. Calcd
for C16
.96; N, 6.35.
Com p ou n d 4a . H NMR: δ 7.72 (d, 1H, J ) 7.5 Hz), 7.58
d, 1H, J ) 7.6 Hz), 7.32 (td, 1H, J ) 7.6, J ) 0.8 Hz), 7.14
td, 1H, J ) 7.5, J ) 0.8 Hz), 2.41 (td, 2H, J ) 12.98, J
.7 Hz), 1.48 (s, 9H), 2.1-1.2 (m, 8H). MS (70 eV): m/z 241
H21N: C, 84.52; H, 9.31; N, 6.16. Found: C, 84.25; H,
8
1
(
(
4
1
2
1
2
1
2
)
+
(
(
M , 11), 226 (12), 184 (100), 156 (46), 143 (13), 130 (16), 57
6). Anal. Calcd for C17 23N: C, 84.59; H, 9.60; N, 5.80.
-
1
1
H
3′H-in d ole], 3b. IR (film): 1680, 1600, 775, 750 cm
NMR (CDCl ): δ 7.58 (m, 1H), 7.4-7.1 (m, 3H), 3.25 (sept, 1H,
J ) 7.0 Hz), 2.1-1.4 (m, 9H), 1.39 (d, 3H, J ) 6.5 Hz), 1.29 (d,
.
H
Found: C, 84.37; H, 9.26; N, 5.55.
′-Eth ylsp ir o[2-m eth ylcycloh exa n -1,3′-3′H-in d ole] (2b).
3
2
1
3
In a round-bottom flask previously flamed, in argon atmo-
sphere, and covered from the sunlight was prepared a solution
of methylmagnesium iodide (6.04 mmol) in dry THF (60 mL).
To this solution was slowly added 1b (as the diastereomeric
pair 1R*,2S* and 1R*,2R*) (0.13 g, 0.6 mmol) in diethyl ether
3
3H, J ) 6.5 Hz), 0.39 (d, 3H, J ) 7.0 Hz). C NMR (CDCl ):
δ 194.9, 153.9, 145.4, 127.0, 125.0, 124.0, 119.4, 62.1, 38.7, 33.4,
+
30.3, 29.6, 25.9, 22.8, 21.4, 16.9. MS (70 eV): m/z 241 (M ,
41), 226 (28), 212 (7), 198 (100), 184 (27), 170 (38), 156 (20),
144 (13), 130 (25), 115 (17). Anal. Calcd for C17H23N: C, 84.59;
(12 mL). The mixture was stirred at room temperature
H, 9.60; N, 5.80. Found: C, 84.27; H, 9.38; N, 5.66.
overnight and then was hydrolyzed with a saturated aqueous
ammonium chloride solution (100 mL), extracted with dichlo-
romethane (50 mL), and dried on anhydrous magnesium
sulfate. After filtration the solvent was removed at reduced
pressure, giving a residual oil which was purified by silica gel
column chromatography using 1:4 ethyl acetate/hexane as the
eluent. Compound 2b was obtained as a red oil, 0.053 g, 40%
yield, as a 2:1 diastereomeric mixture. Moreover, luminescent
product 10 was isolated as a yellow solid, mp 99-102 °C, 13
mg (5%), which was identified unambiguously as the meso-
R,â-di{(1R,2S),(1S,2R)-2′-(spiro[2-methylcyclohexan-1,3′-3′H-
indolyl]}ethene. Starting product 1b was also recovered, 0.065
g (50%, 1R*,2S* and 1R*,2R*, in 2/1 ratio).
(1R*,2R*)-2′-Isop r op ylsp ir o[2-m et h ylcycloh exa n -1,3′-
-
1
1
3′H-in d ole], 3b. IR (film): 1680, 1600, 775, 750 cm
NMR (CDCl ): δ 7.58 (m, 1H), 7.4-7.1 (m, 3H), 2.93 (sept,
1H, J ) 6.5 Hz), 2.1-1.4 (m, 9H), 1.38 (d, 3H, J ) 6.5 Hz),
.
H
3
1
3
1.24 (d, 3H, J ) 6.5 Hz), 0.28 (d, 3H, J ) 6.5 Hz). C NMR
(CDCl
3
): δ 192.3 (C-2′), 155.5, 141.0, 127.3, 124.4, 122.1, 120.5,
64.6, 34.2, 32.5, 30.2, 29.0, 25.8, 22.4, 20.8, 16.5. MS (70 eV):
+
m/z 241 (M , 41), 226 (28), 212 (7), 198 (100), 184 (27), 170
(38), 156 (20), 144 (13), 130 (25), 115 (17). Anal. Calcd for
C
17
H
23N: C, 84.59; H, 9.60; N, 5.80. Found: C, 84.25; H, 9.35;
N, 5.45.
2′-Allyl-2′-m eth ylsp ir o[cycloh exa n -1,3′-3′H-in d ole], 5a .
To a solution of allylmagnesium chloride (6.04 mmol) in