ˇ
P. Safa´rˇ et al. / Tetrahedron: Asymmetry 19 (2008) 467–475
473
1
1660 (C@O), 1487, 1465, 1439, 1419; H NMR (600 MHz,
CDCl3): d 1.94 (dddd, 1H, H5; J = 5.1, 7.3, 9.9 and
14.5 Hz), 2.04–2.12 (m, 2H, H3 and H3a), 2.18 (ddd, 1H,
85 (5), 84 (24). Anal. Calcd for C10H15NO3 (197.23): C,
60.90; H, 7.67; N, 7.10. Found: C, 60.79; H, 7.54; N, 6.99.
0
0
H3 ; J = 3.8, 8.0 and 11.6 Hz), 2.28 (tdd, 1H, H5 ; J = 7.8,
9.0 and 14.5 Hz), 2.35–2.46 (m, 2H, 2 ꢁ H6), 2.96 (dd,
1H, H9ax; J = 2.3 and 14.6 Hz), 3.10 (t, 1H, H4; J =
9.5 Hz), 3.29 (ddd, 1H, H4a; J = 5.0, 8.2 and 9.4 Hz),
3.38 (br s, 1H, OH), 3.85–3.93 (m, 3H, 2 ꢁ H2 and H9a),
4.30 (d, 1H, H9eq; J = 14.7 Hz); 13C NMR (150 MHz,
CDCl3): d 21.7 (C5), 29.0 (C3), 30.1 (C6), 40.7 (C9), 45.4
(C3a), 60.8 (C4a), 66.1 (C2), 72.3 (C4), 76.6 (C9a), 174.9
(C7); MS (m/z, (%)): 199 ([M+2]+, 12), 198 ([M+1]+, base),
197 (M+, 6), 180 (14), 179 (32), 169 (23), 168 (13), 152 (8),
136 (19), 124 (5), 113 (8), 99 (25), 98 (32), 97 (11), 86 (6), 85
(14), 84 (52). Anal. Calcd for C10H15NO3 (197.23): C,
60.90; H, 7.67; N, 7.10. Found: C, 60.85; H, 7.52; N, 6.95.
4.2.5. (8aS,9S)-9-Hydroxyoctahydro[3,2-f]indolizin-6(2H)-
ones 10 and 11. These products were isolated by the
hydrogenation of 9-hydroxyfuroindolizinone 12 (0.39 g,
2.0 mmol) in dry methanol (30 mL) with 5% Rh on
Al2O3 (0.04 g) at 60 °C and 203 kPa for 16 h. The obtained
residue (after successive filtration of the solution through a
Celite pad, washing with methanol and concentration in
vacuo), was treated with acetone (10 mL) and the precipi-
tate was filtered off. The filtrate was subjected to the same
procedure for 3 times and finally concentrated in vacuo.
The resulting crystals were collected and recrystallized
from acetone to furnish optically pure indolizinone (minor
diastereomer) 11 (0.035 g, 9%) as colorless crystals. Ulti-
mately, the filtrates were collected and evaporated in vacuo
to give the major diastereomer 10 as a thick colorless oil in
63% yield (m = 0.25 g).
4.2.3.
(3aS,4R,4aS,9aS)-4-Hydroxyoctahydrofuro[2,3-f]-
indolizin-7(2H)-one 5. The characteristics of this product
were extracted from a spectra of two diastereomers 4 and
5 and are as following; H NMR (600 MHz, CDCl3): d
1
4.2.6. (3aS,8aS,9S,9aS)-9-Hydroxyoctahydro[3,2-f]-indol-
izin-6(2H)-one 10. [a]D = ꢀ35.6 (c 1.0, EtOH); IR (m,
cmꢀ1, KBr): 3373 (OH), 2887, 1769, 1667 (C@O), 1460,
1.86–1.93 (m, 1H, H5), 2.04–2.12 (m, 2H, 2 ꢁ H3), 2.28
0
(tdd, 1H, H5 ; J = 7.8, 9.0 and 14.5 Hz), 2.35–2.46 (m,
1
2H, 2 ꢁ H6), 2.68 (dd, 1H, H9ax; J = 8.8 and 13.3 Hz),
2.77 (tdd, 1H, H3a; J = 6.2, 7.5 and 11.6 Hz), 2.92 (br s,
1H, OH), 3.50 (ddd, 1H, H4a; J = 5.3, 7.8 and 9.6 Hz),
3.70 (dd, 1H, H4; J = 5.9 and 9.8 Hz), 3.85–3.93 (m, 1H,
H2), 3.98 (dd, 1H, H9eq; J = 6.7 and 13.3 Hz), 4.10 (dt,
1447, 1423, 1371, 1281; H NMR (600 MHz, CDCl3): d
1.73 (tt, 1H, H3; J = 9.5 and 12.3 Hz), 1.97 (dddd, 1H,
0
H8; J = 4.5, 7.1, 9.8 and 12.8 Hz), 2.03 (dtd, 1H, H3 ;
0
J = 2.6, 7.7 and 12.5 Hz), 2.27 (tdd, 1H, H8 ; J = 7.6, 9.1
and 13.2 Hz), 2.42–2.48 (m, 2H, 2 ꢁ H7), 2.49 (tdd, 1H,
H3a; J = 5.1, 7.0 and 12.1 Hz), 2.73 (br s, 1H, OH), 3.07
(dd, 1H, H4ax; J = 5.0 and 14.0 Hz), 3.23 (dd, 1H, H9;
J = 7.9 and 10.0 Hz), 3.29 (ddd, 1H, H8a; J = 4.5, 7.9
and 10.1 Hz), 3.89 (t, 1H, H9a; J = 7.7 Hz), 3.92 (dd, 1H,
0
1H, H2 ; J = 2.5 and 8.9 Hz), 4.10 (td, 1H, H9a; J = 6.9
and 8.9 Hz); 13C NMR (150 MHz, CDCl3): d 21.9 (C5),
23.8 (C3), 30.2 (C6), 39.9 (C9), 44.6 (C3a), 56.3 (C4a), 67.4
(C2), 71.3 (C4), 73.9 (C9a), 174.3 (C7).
0
H2; J = 7.7 and 9.2 Hz), 3.99 (dt, 1H, H2 ; J = 2.6 and
4.2.4.
(3aS,8aS,9R,9aS)-9-Hydroxyoctahydrofuro[3,2-f]-
9.2 Hz), 4.15 (d, 1H, H4eq; J = 13.9 Hz); 13C NMR
(150 MHz, CDCl3): d 21.1 (C8), 28.4 (C3), 29.9 (C7), 38.1
(C3a), 38.3 (C4), 58.7 (C8a), 66.9 (C2), 73.0 (C9), 82.6
(C9a), 174.9 (C6); MS (m/z, (%)): 199 ([M+2]+, 8), 198
([M+1]+, 66), 197 (M+, 4), 196 (5), 180 (19), 179 (8), 178
(8), 168 (14), 166 (6), 155 (9), 154 (base), 152 (7), 151
(14), 150 (9), 148 (5), 136 (11), 134 (5), 124 (5), 122 (5),
114 (6), 112 (7), 110 (6), 99 (8), 98 (29), 97 (15), 96 (7),
86 (5), 84 (21). Anal. Calcd for C10H15NO3 (197.23): C,
60.90; H, 7.67; N, 7.10. Found: C, 60.73; H, 7.46; N, 6.85.
indolizin-6(2H)-one 8. This product was obtained by the
hydrogenation of furoindolizindione 7 (0.38 g, 80%) in
dry methanol (30 mL) with 5% Rh on Al2O3 (0.045 g) at
60 °C and 203 kPa for 46 h. The catalyst was filtered
through a short column of Celite pad, washed twice with
methanol (5 mL) and the filtrate concentrated under
reduced pressure to afford a solid, which recrystallized
from acetone to give enantiomerically pure indolizinone 4
(0.30 g, 76%) as colorless crystals; mp 183–185 °C;
[a]D = ꢀ31.8 (c 1.0, EtOH); IR (m, cmꢀ1, KBr): 3223
(OH), 2980, 2938, 2894, 1659, 1639 (C@O), 1485, 1473,
4.2.7. (3aR,8aS,9S,9aR)-9-Hydroxyoctahydro[3,2-f]-indoli-
zin-6(2H)-one 11. This product melted at 190–193 °C;
[a]D = ꢀ17.8 (c 1.0, EtOH); IR (m, cmꢀ1, KBr): 3449
(OH), 2951, 2923, 2867, 1681 (C@O), 1639, 1452, 1473,
1
1444, 1422, 1367, 1358; H NMR (600 MHz, CDCl3): d
1.90–1.99 (m, 1H, H3), 1.97–2.02 (m, 1H, H3), 2.07–2.15
(m, 1H, H8), 2.17 (ddd, 1H, H8 ; J = 4.7, 8.6 and
13.9 Hz), 2.32–2.44 (m, 2H, H7 and H3a), 2.57 (ddd, 1H,
0
1
1439, 1427, 1370, 1262; H NMR (600 MHz, CDCl3): d
0
H7 ; J = 7.1, 10.1 and 17.0 Hz), 2.87 (br s, 1H, OH), 3.19
1.75 (ddd, 1H, H3; J = 3.4, 7.7 and 12.8 Hz), 1.92–1.99
0
0
(dd, 1H, H4ax; J = 5.9 and 13.7 Hz), 3.56 (ddd, 1H, H8a;
J = 1.3, 3.9 and 8.5 Hz), 3.83 (td, 1H, H2; J = 8.0 and
8.3 Hz), 3.86 (dd, 1H, H9; J = 1.0 and 3.1 Hz), 4.00 (dd,
1H, H4eq; J = 3.3 and 13.6 Hz), 4.06 (dd, 1H, H9a;
(m, 1H, H8), 2.05–2.13 (m, 1H, H3 ), 2.29 (qd, 1H, H8 ;
J = 8.2 and 13.3 Hz), 2.35–2.47 (m, 4H, 2 ꢁ H7, H4ax and
H3a), 3.42 (dd, 1H, H9; J = 3.0 and 9.7 Hz), 3.51 (ddd,
1H, H8a; J = 4.7, 8.1 and 9.7 Hz), 3.93 (dt, 1H, H2; J =
3.4 and 9.2 Hz), 3.96–4.02 (m, 2H, H9a and H4eq), 4.04
0
J = 4.7 and 7.7 Hz), 4.10 (dt, 1H, H2 ; J = 2.3 and
8.2 Hz); 13C NMR (150 MHz, CDCl3): d 20.2 (C8), 30.5
(C3), 30.7 (C7), 36.0 (C3a), 38.6 (C4), 57.4 (C8a), 69.2 (C2),
69.4 (C9), 77.2 (C9a), 175.4 (C6); MS (m/z, (%)): 199
([M+2]+, 9), 198 ([M+1]+, 80), 197 (M+, 6), 180 (18), 179
(5), 178 (9), 168 (13), 155 (9), 154 (base), 152 (8), 151
(15), 150 (10), 136 (10), 134 (6), 124 (5), 122 (7), 114 (6),
112 (6), 110 (7), 99 (10), 98 (33), 97 (19), 96 (7), 86 (6),
(q, 1H, H2 ; J = 8.3 Hz); 13C NMR (150 MHz, CDCl3): d
0
21.4 (C8), 29.7 (C3), 30.0 (C7), 37.2 (C3a), 38.9 (C4), 56.5
(C8a), 66.1 (C2), 72.6 (C9), 79.6 (C9a), 173.7 (C6); MS (m/
z, (%)): 199 ([M+2]+, 10), 198 ([M+1]+, 82), 197 (M+, 3),
196 (6), 181 (5), 180 (48), 179 (58), 178 (34), 169 (7), 168
(23), 166 (12), 155 (10), 154 (base), 152 (17), 151 (70),
150 (30), 148 (15), 141 (5), 138 (9), 137 (5), 136 (26), 135