Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids
J . Org. Chem., Vol. 62, No. 23, 1997 7955
7.37 (d, J ) 8.0 Hz, 1 H), 7.28 (m, 6 H), 7.25 (t, J ) 7.5 Hz, 1
H), 7.16 (t, J ) 7.3 Hz, 1 H), 6.26 (qd, J ) 6.8, 13.6 Hz, 1 H),
6.05 (dd, J ) 11.3, 13.6 Hz, 1 H), 5.77 (s, 2 H), 3.79 (d, J )
13.9, 1 H), 3.74 (m, 1 H), 3.73 (s, 3 H), 3.52 (d, J ) 13.9 Hz, 1
H), 2.75 (m, 2 H), 2.60 (m, 2 H), 2.20 (ddd, J ) 5.0, 10.9, 10.9
Hz, 1 H), 2.12 (m, 1 H), 1.94 (m, 1 H), 1.78 (d, J ) 6.8 Hz, 3
H), 1.69 (m, 1 H), 0.99 (d, J ) 6.5 Hz, 3 H); 13C NMR (125
MHz, CDCl3) δ 205.26, 167.58, 144.44, 141.53, 140.09, 136.05,
129.04, 128.80, 128.61, 128.20, 128.13, 127.92, 126.90, 125.54,
122.18, 120.89, 119.26, 119.10, 114.08, 110.83, 57.93, 57.69,
55.33, 52.11, 50.76, 33.92, 29.42, 25.15, 19.61, 18.92; MS m/z
(relative intensity) 497 (1), 496 (M+, 2), 374 (1), 274 (2), 268
(2), 255 (7), 242 (94), 222 (2), 208 (3), 194 (11), 181 (2), 179
(8), 167 (5), 154 (2), 146 (3), 142 (2), 123 (12), 120 (58), 105
(6), 91 (100); HRMS calcd for C32H36N2O3 496.2726, found
496.2701.
6.00 (dd, J ) 4.8, 14.8 Hz, 1 H), 5.45 (qd, J ) 6.3, 14.8 Hz, 1
H), 4.19 (d, J ) 13.4 Hz, 1 H), 3.76 (s, 3 H), 3.67 (s, br, 1 H),
3.53 (d, J ) 13.4 Hz, 1 H), 3.32 (d, J ) 5.5 Hz, 1 H), 2.89 (dd,
J ) 6.4, 8.8 Hz, 1 H), 2.55 (ddd, J ) 4.8, 8.8, 11.9 Hz, 1 H),
2.26 (ddd, J ) 6.4, 11.9, 11.9 Hz, 1 H), 2.03 (d, J ) 13.8 Hz, 1
H), 1.73 (d, J ) 6.3 Hz, 3 H), 1.62 (dd, J ) 4.8, 11.9 Hz, 1 H),
1.42 (ddd, J ) 5.5, 5.5, 12.8 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 168.88, 166.23, 142.88, 139.88, 138.19, 136.34, 128.38,
128.14, 127.63, 126.73, 122.57, 121.55, 120.22, 109.14, 97.48,
66.22, 58.16, 55.56, 50.91, 50.77, 44.38, 36.80, 33.80, 17.73;
MS m/z (relative intensity) 401 (5), 400 (M+, 14), 332 (2), 309
(2), 267 (15), 254 (3), 222 (4), 208 (7), 199 (4), 194 (10), 180
(5), 175 (7), 167 (6), 154 (3), 146 (71), 134 (3), 117 (5), 91 (100).
Anal. Calcd for C26H28N2O2‚0.5CH2Cl2: C, 71.85; H, 6.60; N,
6.32. Found: C, 72.06; H, 6.54; N, 6.37.
(()-Met h yl (3a S*,5-(S* a n d R*),11b R*)-3-Ben zyl-
2,3,3a ,4,5,7-h exa h yd r o-5-(2-m eth oxyp h en yl)-1H-p yr r olo-
[2,3-d ]ca r ba zole-6-ca r boxyla te (1h a n d 1i). The Nb/aryl
cis product 1h was obtained in 58% yield, using the general
procedure with o-methoxycinamaldehyde and benzoic acid as
catalyst, together with 7.5% of its C-5 (R*)-epimer 1i.
(()-Met h yl (3a S*,5R* a n d 5S*,11b R*)-3-Ben zyl-
2,3,3a ,4,5,7-h exa h yd r o-5-(et h oxyca r b on yl)-1H -p yr r olo-
[2,3-d ]ca r ba zole-6-ca r boxyla te (1c a n d 1d ). Using the
general procedure, 3-formyl ethyl acrylate, and benzoic acid
as catalyst, a 74% yield of the Nb-ethoxycarbonyl cis product
1c was obtained, together with 9% of its C-5 epimer 1d . For
1c: TLC Rf ) 0.28 (hexane/EtOAc/CH2Cl2, 6:1:3, CAS blue
fades to gray); UV (EtOH) λmax 322, 296, 226, 204 nm; IR (KBr)
νmax 3374, 3060, 3028, 2980, 2950, 2927, 2788, 1724, 1682,
1609, 1477, 1463, 1438, 1379, 1341, 1279, 1256, 1231, 1210,
For 1h : TLC Rf ) 0.28 (hexane/CH2Cl2/Et2O, 7:2:1, CAS
blue); mp 212-3 °C (HCl salt); UV (EtOH) λmax 326, 298, 230,
206 nm; IR (KBr) νmax 3364, 3058, 3026, 2950, 2916, 2837,
2789, 1672, 1608, 1487, 1476, 1464, 1435, 1276, 1293, 1215,
1
1188, 1125, 1028, 750, 733 cm-1; H NMR (500 MHz, CDCl3)
1185, 1151, 1123, 1041, 747, 735 cm-1
;
1H NMR (500 MHz,
δ 9.42 (s, 1 H), 7.30 (d, J ) 7.3 Hz, 1 H), 7.23 (m, 2 H), 7.15
(m, 4 H), 6.89 (m, 4 H), 6.82 (m, 2 H), 4.47 (dd, J ) 3.7, 6.2
Hz, 1 H), 3.97 (d, J ) 13.5 Hz, 1 H), 3.82 (s, 3 H), 3.62 (s, 3 H),
3.37 (d, J ) 13.5 Hz, 1 H), 3.30 (dd, J ) 3.7, 4.7 Hz, 1 H), 2.66
(ddd, J ) 3.7, 3.7, 14.3 Hz, 1 H), 2.49 (m, 1 H), 2.39 (m, 2 H),
1.76 (ddd. J ) 4.7, 6.2, 14.3 Hz, 1 H), 1.61 (m, 1 H); 13C NMR
(125 MHz, CDCl3) δ 169.09, 167.25, 157.63, 143.24, 139.90,
138.34, 134.27, 128.73, 128.01, 127.91, 127.64, 126.43, 126.32,
121.88, 120.48, 120.04, 110.42, 109.18, 96.46, 65.90, 57.20,
55.20, 55.12, 50.99, 50.19, 42.36, 34.99, 29.94; MS m/z (relative
intensity): 467 (2), 466 (M+, 6), 345 (2), 333 (15), 320 (3), 300
(8), 288 (5), 274 (8), 265 (6), 260 (6), 241 (3), 230 (3), 225 (6),
217 (3), 180 (3), 167 (3), 154 (3), 146 (44), 135 (9), 130 (2), 212
(3), 117 (4), 107 (4), 91 (100). Anal. Calcd for C30H30N2O3‚
HCl‚0.5H2O: C, 70.37; H, 6.30; N, 5.47; Cl, 6.93. Found: C,
70.29; H, 6.24; N, 5.41, Cl, 7.22.
CDCl3) δ 9.11 (s, 1 H), 7.34 (m, 4 H), 7.26 (m, 1 H), 7.14 (t, J
) 7.7 Hz, 1 H), 7.04 (d, J ) 7.3 Hz, 1 H), 6.86 (t, J ) 7.5 Hz,
1 H), 6.83 (d, J ) 8.0 Hz, 1 H), 4.23 (m, 1 H), 4.14 (d, J ) 13.1
Hz, 1 H), 4.08 (m, 1 H), 3.84 (dd, J ) 2.4, 6.9, 1 H), 3.76 (s, 3
H), 3.51 (d, J ) 13.1 Hz, 1 H), 3.27 (d, J ) 4.2 Hz, 1 H), 2.77
(dd, J ) 5.6, 8.0 Hz, 1 H), 2.63 (d, J ) 13.9 Hz, 1 H), 2.46 (m,
2 H), 1.58 (dd, J ) 4.1, 10.1 Hz, 1 H), 1.51 (ddd, J ) 5.6, 5.6,
13.9 Hz, 1 H), 1.21 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 174.59, 168.28, 167.25, 142.83, 138.48, 137.68, 129.17,
128.10, 127.80, 127.02, 121.42, 120.63, 109.39, 93.17, 65.02,
60.49, 58.04, 55.92, 51.08, 50.60, 43.81, 38.86, 30.79, 14.13;
MS m/z (relative intensity) 433 (7), 432 (M+, 7), 373 (2), 359
(2), 341 (2), 327 (2), 300 (15), 267 (2), 226 (4), 207 (3), 194 (6),
180 (8), 167 (10), 146 (52), 91 (100). Anal. Calcd for
C26H28N2O4: C, 72.20; H, 6.52; N, 6.48. Found: C, 71.92; H,
6.28; N, 6.48.
For 1i: TLC Rf ) 0.17 (hexane/CH2Cl2/Et2O, 7:2:1; CAS
blue); mp 215-216 °C (HCl salt); UV (EtOH) λmax 326, 296,
226, 204 nm; IR (KBr) νmax 3374, 3057, 3024, 2939, 2839, 1676,
1607, 1493, 1476, 1464, 1437, 1288, 1278, 1232, 1200, 1119,
For the C-5 (S*)-epimer 1d : TLC Rf ) 0.17 (hexane/EtOAc/
CH2Cl2, 6:1:3, CAS blue fades to gray); UV (EtOH) λmax 324,
294, 224, 206 nm; IR (KBr) νmax 3375, 3058, 3030, 2979, 2949,
2924, 2850, 2793, 1734, 1683, 1609, 1468, 1437, 1279, 1251,
1
1027, 751, 700 cm-1; H NMR (500 MHz, CDCl3) δ 9.07 (s, 1
1
1235, 1195, 1154, 1120, 1042, 746 cm-1; H NMR (500 MHz,
H), 7.40 (d, J ) 7.4 Hz, 2 H), 7.31 (t, J ) 7.4 Hz, 2 H), 7.27 (d,
J ) 7.3 Hz, 1 H), 7.23 (m, 1 H), 7.16 (dt, J ) 1.1, 7.6 Hz, 1 H),
7.12 (dt, J ) 1.6, 7.6 Hz, 1 H), 6.96 (d, J ) 7.2 Hz, 1 H), 6.85
(m, 4 H), 4.46 (s, br, 1 H), 3.95 (d, J ) 13.4 Hz, 1 H), 3.85 (s,
3 H), 3.71 (d, J ) 13.4 Hz, 1 H), 3.37 (s, 3 H), 3.30 (dd, J )
4.4, 4.4 Hz, 1 H), 2.83 (dd, J ) 8.1, 8.1 Hz, 1 H), 2.72 (ddd, J
) 5.4, 8.1, 11.7 Hz, 1 H), 2.26 (ddd, J ) 8.1, 11.7, 11.7 Hz, 1
H), 2.02 (ddd, J ) 4.4, 4.4, 13.5 Hz, 1 H), 1.80 (dd, J ) 5.4,
11.7 Hz, 1 H), 1.71 (m, 1 H); 13C NMR (125 MHz, CDCl3) δ
169.00, 166.12, 156.73, 143.68, 139.76, 137.62, 135.07, 128.59,
128.17, 127.94, 127.68, 126.82, 126.42, 122.18, 120.40, 120.35,
110.51, 109.18, 98.02, 62.55, 56.95, 55.56, 55.47, 50.28, 49.41,
44.12, 35.11; MS m/z (relative intensity) 467 (3), 466 (M+, 9),
345 (2), 333 (13), 320 (2), 300 (12), 288 (5), 274 (7), 265 (5),
260 (6), 240 (3), 230 (3), 225 (5), 217 (3), 209 (2), 180 (3), 167
(2), 154 (3), 146 (38), 135 (10), 130 (2), 121 (3), 117 (4), 107
(7), 91 (100). Anal. Calcd for C30H30N2O3‚HCl‚0.5H2O: C,
70.37; H, 6.30; N, 5.47; Cl, 6.93. Found: C, 70.48; H, 6.03; N,
5.40; Cl, 7.19.
CDCl3) δ 8.99 (s, 1 H), 7.39 (d, J ) 7.2 Hz, 2 H), 7.34 (t, J )
7.3 Hz, 2 H), 7.27 (t, J ) 7.2 Hz, 1 H), 7.16 (t, J ) 7.5 Hz, 1
H), 7.05 (d, J ) 7.3 Hz, 1 H), 6.87 (t, J ) 7.5 Hz, 1 H), 6.83 (d,
J ) 7.7 Hz, 1 H), 4.19 (m, 1 H), 4.15 (m, 1 H), 4.08 (d, J ) 13.4
Hz, 1 H), 3.73 (d, J ) 13.4 Hz, 1 H), 3.72 (s, 3 H), 3.59 (dd, J
) 3.1, 10.7, 1 H), 3.33 (d, J ) 3.1, 1 H), 2.86 (dd, J ) 6.8, 7.8
Hz, 1 H), 2.64 (ddd, J ) 4.9, 7.8, 11.8 Hz, 1 H), 2.04 (ddd, J )
2.2, 2.2, 13.4, 1 H), 1.99 (ddd, J ) 6.8, 11.8, 11.8 Hz, 1 H),
1.72 (dd, J ) 4.9, 11.8 Hz, 1 H), 1.57 (ddd, J ) 4.1, 10.8, 13.4
Hz, 1 H), 1.27 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz, CDCl3)
δ 174.98, 167.55, 166.48, 142.90, 138.72, 136.92, 128.75,
128.24, 127.88, 127.02, 121.80, 120.71, 109.35, 94.02, 67.71,
60.40, 57.59, 55.86, 50.78, 49.84, 44.17, 37.92, 33.93, 14.17;
MS m/z (relative intensity) 433 (4), 432 (M+, 9), 299 (13), 226
(9), 194 (10), 180 (11), 166 (13), 154 (6), 146 (57), 134 (10), 117
(4), 107 (4), 91 (100).
(()-Met h yl (3a S*,5R*,11b R*)-3-Ben zyl-2,3,3a ,4,5,7-
h exa h yd r o-5-a llyl-1H-p yr r olo[2,3-d ]ca r ba zole-6-ca r boxy-
la te (1f). Using the general condensation procedure with 2,4-
hexadienal and with benzoic acid as catalyst, a 54% yield of
the tetracyclic product 1f was obtained: TLC Rf ) 0.38
(hexane/EtOAc, 9:1; CAS blue fade to violet); mp 140 °C (dec,
HCl salt); UV (EtOH) λmax 324, 298, 226, 208 nm; IR (KBr)
Equ ilibr a tion of C-5 Ar yl P r od u cts 1h a n d 1i w ith
Ben zoic Acid or HCl. a . A solution of 20 mg of the minor
epimer 1i and 2 mg of PhCOOH in 2 mL of dry benzene was
heated at reflux for 6 h. The solution was diluted with ethyl
acetate and washed with 5% Na2CO3 solution. The residue,
1
obtained upon drying and concentration, was subjected to H
ν
max 370, 3062, 3025, 2945, 2918, 2855, 2787, 1675, 1609, 1479,
NMR analysis, showing a 7:1 ratio of 1h /1i. Purification on a
silica gel column gave 15 mg of the epimer 1h (75% yield).
b. A solution of 20 mg of the 5S* epimer 1h and three drops
of 2 N HCl in 2 mL of THF-H2O (4:1) was kept at rt for 5 h.
1466, 1436, 1474, 1277, 1234, 1213, 1188, 1147, 1118, 1053,
744 cm-1; H NMR (500 MHz, CDCl3) δ 9.16 (s, 1 H), 7.42 (d,
1
J ) 7.5 Hz, 2 H), 7.33 (t, J ) 7.4 Hz, 2 H), 7.25 (m, 1 H), 7.16
(m, 2 H), 6.87 (t, J ) 7.5 Hz, 1 H), 6.82 (d, J ) 8.1 Hz, 1 H),