4660
A. Seki, M. Asami / Tetrahedron 58 ꢀ2002) 4655±4663
detector, UV-8020). GC analyses were carried out with
Shimadzu GC 14 A. TLC analyses were done on silica-gel
in methanol*20 mL) was stirred vigorous ly overnight at rt.
After removal of catalyst by ®ltration, the ®ltrate was
concentrated in vacuo. The crude product was recrystallized
from ethylacetate to give 1-[*2 S,3aS,7aS)-octahydroindole-
2-carbonyl]pyrrolidine *3.4 g, 94%) as colorless crystals
6
0 F254-coated plates *E. Merck). Column chromatography
was carried out with WakogelC-200 gelwith indicated
eluent unless otherwise described. Preparative TLC was
performed on silica-gel-coated plates *Wakogel B-5F,
2
0
*mp 68±718C). [a]D 278.0 *c 1.61, CH OH); IR *KBr)
3
2
0 cm£20 cm).
n: 3300, 2950, 2850, 1630, 1450, 1410, 1340, 1220, 1190,
1
2
120, 1100, 1040, 1000, 960, 900, 800, 740, 700, 660 cm ;
1
1
4.1.1. (2S,3aS,7aS)-N-Benzyloxycarbonyloctahydro-
indole-2-carboxylic acid. To *2S,3aS,7aS)-octahydro-
H NMR *CDCl ) d: 1.14±2.25 *m, 16H), 3.07 *dd, J9.6,
3
5.0 Hz, 1H), 3.31±3.60 *m, 4H), 3.82 *dd, J9.9, 5.6 Hz, 1H).
Found: m/z 222.1733. Calcd for C H N O: M, 222.1732.
4
4,45
indole-2-carboxylic acid
45 mL) was added sodium hydrogencarbonate *6.0 g,
0 mmol) and the mixture was stirred vigorously at 08C.
After addition of benzyloxycarbonyl chloride *2.8 g,
6 mmol) in toluene *7.5 mL) at 08C, stirring was continued
at rt for 2 h. Then benzyloxycarbonyl chloride *2.8 g,
6 mmol) in toluene *7.5 mL) was again added to the
*5.0 g, 30 mmol) in water
13
22
2
*
6
4.1.4. (2S,3aS,7aS)-2-(Pyrrolidin-1-ylmethyl)octahydro-
indole (1b). To a THF suspension of lithium aluminum
hydride *1.7 g, 46 mmol) was added a THF solution
*40 mL) of 1-[*2S,3aS,7aS)-octahydroindole-2-carbonyl]-
pyrrolidine *3.4 g, 15 mmol) at 08C under argon
atmosphere, and the reaction mixture was re¯uxed for
18 h. Then saturated sodium sulfate solution was added to
the reaction mixture. After removalof the inorganic
materialthe organic la yer was concentrated in vacuo. Frac-
tional distillation of the resulting oil afforded *2S,3aS,7aS)-
2-*pyrrolidin-1-ylmethyl)octahydroindole *1b) *2.6 g, 83%,
bp 190±1958C/2.0 mmHg by bulb-to-bulb distillation).
1
1
mixture at 08C and the mixture was stirred overnight at rt.
The aqueous layer was washed several times with ether,
acidi®ed with 6 M HCl, and extracted with ethyl acetate.
The organic layer was washed with water and brine, and
dried over anhyd Na SO . The solvent was removed under
2
4
reduced pressure and the residue was puri®ed by column
chromatography *silica-gel, ether) to give *2S,3aS,7aS)-N-
4
6
20
benzyloxycarbonyloctahydroindole-2-carboxylic
acid
8.46 g, 95%) as colorless solid *mp 41±448C).
[a]D 12.09 *c 2.39, C H OH); IR *neat) n: 2900, 2775,
2
5
2
1
1
1650, 1440, 1140, 870, 790 cm ; H NMR *CDCl ) d:
*
[
3
2
0
a]D 243.8 *c 0.98, CHCl ); IR *neat) n: 2950, 1710,
1.19±2.08 *m, 17H), 2.40±2.65 *m, 5H), 3.05 *dt, J5.3,
3
1
5.3 Hz, 1H), 3.31 *m, 1H); C NMR *CDCl ) d: 64.5, 57.5,
3
1
7
1
5
430, 1370, 1300, 1250, 1180, 1120, 1100, 1050, 1010,
90, 750, 700 cm ; H NMR *CDCl ) d: 1.14±2.32 *m,
3
2
1
1
56.6, 54.6, 38.0, 36.2, 29.6, 28.6, 23.6, 23.4, 22.2; Anal.
Calcd for C H N O *dipicrate of 1b; mp 170.6±
3
1H), 3.88 *s, 1H), 5.11±5.15 *m, 2H), 7.29±7.36 *m,
H), 10.9 *s, 1H). Found: m/z 303.1463. Calcd for
2
5
30
8
14
171.88C): C, 45.05; H, 4.54; N, 16.81. Found: C, 44.83;
H, 4.54; N, 16.59.
C H NO : M, 303.1471.
21
1
7
4
4
.1.2. 1-[(2S,3aS,7aS)-N-Benzyloxycarbonyloctahydro-
4.1.5. Poly(styrene-co-N-isopropyl-p-vinylbenzylamine),
2% divinylbenzene cross-linked 3d. A solution of gelatin
*0.26 g), poly*diallyldimethylammonium chloride-co-sulfur
dioxide) *2.6 g, from Nittobo, Japan), boric acid *0.96 g,
15.5 mmol), and sodium nitrate *54 mg, 0.078 mmol) in
water *85 mL) was adjusted to pH 9.5 with 25 wt% aqueous
sodium hydroxide and was placed in a 200 mL round-
bottom ¯ask ®tted with a re¯ux condenser and a mechanical
stirrer. To the solution was added a mixture of N-isopropyl-
p-vinylbenzylamine *5.0 g, 28 mmol), styrene *11.4 g,
indole-2-carbonyl]pyrrolidine. To a dichloromethane
solution *35 mL) of *2S,3aS,7aS)-N-benzyloxycarbonyl-
octahydroindole-2-carboxylic acid *8.5 g, 28 mmol) was
0
added a dichloromethane solution *35 mL) of N,N -dicyclo-
hexylcarbodiimide *5.8 g, 28 mmol) at 08C under argon
atmosphere. After being stirred for 30 min dichloromethane
solution *35 mL) of pyrrolidine *2.0 g, 28 mmol) was
slowly added to the reaction mixture at 08C. The tempera-
ture was then gradually warmed to rt and stirring was
continued overnight at the temperature. After removalof
precipitates, the ®ltrate was washed successively with 2%
HCl, 4% sodium hydrogencarbonate, water, and brine. The
organic layer was dried over anhyd Na SO and the solvent
0
109 mmol), divinylbenzene *0.36 g, 2.8 mmol), and 2,2 -
azobisisobutyronitrile *0.14 g, 0.85 mmol). The ¯ask was
purged with nitrogen for 40 min, and a nitrogen atmosphere
was maintained throughout polymerization. The mixture
was stirred at 708C for 1 d keeping the stirring speed in
this preparation of 310 rpm. The insoluble polymer was
obtained by ®ltration with a glass funnel *G1), and it was
washed thoroughly with hot water, acetone, THF, and
CH Cl . Cross-linked polymer-bound N-isoprpopyl-p-
2
4
was removed under reduced pressure. The crude product
was puri®ed by column chromatography *silica-gel, hexane/
ethylacetate 1/2) to give 1-[*2S,3aS,7aS)-N-benzyloxy-
carbonyloctahydroindole-2-carbonyl]pyrrolidine
*5.5 g,
2
0
5
6%) as colorless crystals *mp 95±988C). [a]D 15.42
2
2
*
c 1.62, CH OH); IR *neat) n: 3050, 2950, 1690, 1650,
3
vinylbenzylamine 3d *13.7 g, 80%) was obtained as beads
after removalof the s ov le nt under reduced pressure
*,1 mmHg) at 908C for 16 h. IR *KBr): n 3319, 3026,
2
440, 1410, 1350, 1180, 1110, 980, 920, 750, 700 cm ;
1
1
1
H NMR *CDCl ) d: 1.04±2.33 *m, 15H), 3.21±3.97 *m,
3
2
1
5
5
7
H), 4.43±4.52 *m, 1H), 4.93±5.19 *m, 2H), 7.27±7.39 *m,
H). Anal. Calcd for C H N O : C, 70.76; H, 7.92; N,
.86. Found: C, 70.67; H, 7.96; N, 7.87.
2923, 2849, 1602, 1494, 1453, 758, 698 cm . Anal.
Calcd for *C H ) ´*C H N) ´*C H ) : C, 89.30; H,
8.34; N, 2.36. Found: C, 88.90; H, 8.58; N, 2.52.
2
1
28
2
3
8
8 0.78
12 17
0.2
10 10 0.02
4
.1.3. 1-[(2S,3aS,7aS)-Octahydroindole-2-carbonyl]pyr-
4.1.6. Poly(styrene-co-N-cyclohexyl-p-vinylbenzylamine),
2% divinylbenzene cross-linked 3e. According to the
similar procedure for the preparation of 3d as described
above, cross-linked polymer-bound N-cyclohexyl-p-vinyl-
rolidine. Under hydrogen atmosphere a mixture of 1-
*2S,3aS,7aS)-N-benzyloxycarbonyloctahydroindole-2-car-
bonyl]pyrrolidine *5.5 g, 16 mmol) and 5% Pd±C *0.17 g)
[