LETTER
Reaction of 3-Nitrochromene Derivatives and Azomethine Ylides
2765
4
(
14) (a) Tsuge, O.; Kanemasa, S.; Yoshioka, M. J. J. Org. Chem.
988, 53, 1384. (b) Nyerges, M.; Rudas, M.; Tóth, G.;
Herényi, B.; Bitter, I.; Tőke, L. Tetrahedron 1995, 51,
3321. (c) Kanemasa, S. Synlett 2002, 1371. (d) Longmire,
J. M.; Wang, B.; Zhang, X. J. Am. Chem. Soc. 2002, 124,
3400.
(2 × CH, Ar -2¢ and 6¢C), 129.3 (CH, C-7), 129.2 (2 × CH,
3
1
Ar -3¢ and 5¢C), 128.5 (2 × CH, Bn-3¢ and 5¢C), 128.3 (2 ×
4
3
CH, Ar -3¢ and 5¢C), 128.1 (2 × CH, Ar -2¢ and 6¢C), 127.0
(CH, Bn-4¢C), 123.1 (CH, C-8), 122.2 (q, C-9a), 118.7 (CH,
C-6), 98.5 (q, C-3a), 77.0 (CH, C-4), 72.2 (q, C-1), 67.4
(CH, C-3), 52.7 (OCH ), 49.8 (CH, C-9b), 42.2 (CH ). IR
1
1
3
2
(
15) General Procedure: The corresponding 3-nitrochromene
derivatives (3a–e, 10 mmol) were dissolved in dry toluene
(KBr): 3341, 3031, 1751, 1601, 1542, 1491, 1456, 1436,
–
1
1239, 1208, 1130, 1111, 1096, 1079, 1042, 1014, 1006 cm .
(16) (a) Bende, Z.; Simon, K.; Tóth, G.; Tőke, L.; Weber, L.
Liebigs Ann. Chem. 1982, 924. (b) Bende, Z.; Bitter, I.;
Tőke, L.; Weber, L.; Tóth, G.; Janke, F. Liebigs Ann. Chem.
1982, 2146. (c) Bende, Z.; Tőke, L.; Weber, L.; Tóth, G.;
Janke, F.; Csonka, G. Tetrahedron 1983, 40, 369. (d) Tóth,
G.; Tischer, T.; Bende, Z.; Szejtli, G.; Tőke, L. Monatsh.
Chem. 1990, 121, 529. (e) Janke, F.; Himmelreich, U.; Tóth,
G.; Tischer, T.; Bende, Z.; Tőke, L. J. Heterocycl. Chem.
1991, 28, 867. (f) Fejes, I.; Nyerges, M.; Tőke, L.; Pak, C. S.
Tetrahedron 2000, 56, 639.
(50 mL) and ethyl (4-chlorobenzylideneamino)acetate (2.47
g, 11 mmol) or methyl 2-(4-chlorobenzylideneamino)-3-
phenyl-propionate (3.32 g, 11 mmol), silver acetate (2.50 g,
1
5 mmol), and Et N (1.11 g, 1.6 mL, 11 mmol) was added.
3
The reaction mixture was stirred at r.t. for 12 h. After the
completion of the reaction (judged by TLC) aq NH Cl
4
solution (25 mL) was added to the reaction mixture and this
was washed with H O (2 × 20 mL) and brine (20 mL). The
2
organic layer was dried over MgSO , evaporated and the
4
residue was trituated with Et O. The crystallized product
2
was collected to yield a white powder, which could be
recrystallized from EtOH to give 6a–j. The reaction times
and yields (based on the dipolarophiles) are summarized in
Table 2. Selected data for representative examples:
Ethyl 3-(4-chlorophenyl)-3a-nitro-4-phenyl-
(17) General Procedure for the Preparation of Compounds 8:
The corresponding 3-nitrochromene (3, 0.80 mmol) and 6,7-
dimethoxy-(2-methoxycarbonylmethyl)-3,4-dihydro-
isoquinolinium bromide (0.29 g, 0.85 mmol) was dissolved
in dry MeOH (10 mL) and Et N (0.14 mL, 0.10 g, 1.00
3
1
benzopirano[3,4-c]-pyrrolidine-1-carboxylate (6a): H
mmol) was added under argon atmosphere. The reaction
mixture was stirred at r.t. for 24 h. The solvent was removed
NMR (250 MHz, CDCl ): d = 7.51 (d, 1 H, J = 7.6 Hz, H-9),
3
3
7
8
.35 (2 H, d, J = 8.7 Hz, Ar -3¢ and 5¢H), 7.27 (2 H, d, J =
in vacuo, the residue was suspended in Et O (20 mL). The
2
3
.7 Hz, Ar -2¢ and 6¢H), 7.12 (7 H, m, Ar-H), 6.77 (d, 1 H,
ethereal solution was washed with H O (10 mL) and brine (5
2
J = 7.5 Hz, H-6), 5.48 (1 H, s, H-4), 4.88 (1 H, br m, H-3),
mL), dried over MgSO and evaporated in vacuo to yield a
4
4
.74 (1 H, d, J = 3.6 Hz, H-9b), 4.43 (2 H, q, J = 7.1 Hz,
white solid, which was recrystallized from EtOH to give
8a,b,d. The reaction times and yields are summarized in
Table 4. Selected data for representative example:
Methyl 8,9-dimethoxy-6a-nitro-6-(4-methoxyphenyl)-
6a,6b,11,12,14,14a-hexahydro-6H-
OCH ), 4.05 (1 H, br s, H-1), 2.99 (1 H, br s, H-2), 1.41
2
1
3
(
3 H, t, J = 7.1 Hz, CH CH ). C NMR (62.5 MHz, CDCl ):
2 3 3
3
d = 171.8 (q, C=O), 149.7 (q, C-5a), 135.4 (q, Ar -4¢C),
3
3
1
34.7 (q, Ar -1¢C), 129.1 (2 × CH, Ar -2¢ and 6¢C), 129.0
4
(
(
CH, C-7), 128.9 (CH, C-9), 128.8 (CH, Ar -1¢C), 128.5
chromeno[3¢,4¢:3,4]pyrrolidino[2,1-a]isoquinoline-14-
3
1
2 × CH, Ar -3¢ and 5¢C), 128.4 (q, C-9a), 128.3 (2 × CH,
carboxylate (8b): H NMR (500 MHz, CDCl ): d = 7.18 (1
3
4
4
Ar -2¢ and 6¢C), 128.2 (2 × CH, Ar -3¢ and 5¢C), 124.8 (CH,
Ar -4¢C), 123.2 (CH, C-8), 118.2 (CH, C-6), 96.4 (q, C-3a),
7
4
1
1
H, t, J = 7.5 Hz, H-3), 7.06 (1 H, d, J = 7.5 Hz, H-1), 6.93 (1
H, d, J = 7.5 Hz, H-4), 6.90 (1 H, t, J = 7.5 Hz, H-2), 6.85 (2
4
6
5.5 (CH, C-4), 69.4 (CH, C-3), 68.3 (CH, C-1), 62.2 (CH ),
H, d, J = 8.2 Hz, Ar -2¢ and 6¢H), 6.51 (1 H, s, H-10), 6.46 (2
2
6
5.6 (CH, H-9b), 14.3 (CH ). IR (KBr): 3334, 2979, 1733,
H, d, J = 8.2 Hz, Ar -3¢ and 5¢H), 6.10 (1 H, s, H-7), 5.77 (1
3
586, 1540, 1487, 1453, 1368, 1298, 1228, 1212, 1114,
H, s, H-6), 4.86 (1 H, s, H-6b), 4.12 (1 H, d, J = 11.3 Hz, H-
14a), 4.11 (1 H, d, J = 11.3 Hz, H-14), 3.83 (3 H, s, OMe),
3.70 (3 H, s, OMe), 3.36 (3 H, s, OMe), 3.32 (3 H, s, OMe),
3.18 (1 H, m, H-11), 3.01 (1 H, m, H-12), 2.70 (1 H, m, H-
–
1
094, 1015 cm .
Methyl 1-benzyl-3,4-bis-(4-chlorophenyl)-3a-nitro-
benzopirano[3,4-c]-pyrrolidine-1-carboxylate (6f): H
1
1
3
NMR (250 MHz, CDCl ): d = 7.76 (1 H, dd, J = 1.7 and 7.8
12), 2.62 (1 H, m, H-11). C NMR (125 MHz, CDCl ): d =
3
3
3
6
Hz, H-9), 7.35 (2 H, d, J = 8.6 Hz, Ar -3¢ and 5¢H), 7.27 (2
170.4 (q, C=O), 159.6 (q, Ar -4¢C), 153.6 (q, C-4a), 147.8
3
6
H, d, J = 8.6 Hz, Ar -2¢ and 6¢H), 7.15 (4 H, m, Bn-H and
(q, C-9), 146.7 (q, C-8), 129.9 (2 × CH, Ar -2¢ and 6¢C),
4
6
H-7), 7.14 (2 H, d, J = 8.5 Hz, Ar -3¢ and 5¢H), 7.10 (1 H, dt,
129.4 (CH, C-1), 128.8 (CH, C-3), 128.0 (q, Ar -1¢C), 127.5
4
J = 1.7 and 7.8 Hz, H-8), 7.05 (2 H, d, J = 8.5 Hz, Ar -2¢ and
(q, C-10a), 127.4 (C-14b), 123.4 (C-6c), 120.5 (CH, C-2),
6
6
¢H), 6.96 (2 H, m, Bn-H), 6.76 (1 H, dd, J = 1.7 and 7.8 Hz,
116.2 (CH, C-4), 113.2 (C-10), 112.9 (2 × CH, Ar -3¢ and
H-6), 5.55 (1 H, s, H-4), 5.10 (1 H, s, H-9b), 5.09 (1 H, d,
J = 7.8 Hz, H-3), 3.78 (3 H, s, OMe), 2.94 (1 H, br d, J = 7.8
5¢C), 109.8 (CH, C-7), 90.4 (q, C-6a), 75.8 (CH, C-6), 67.7
(CH, C-14), 65.7 (C-6b), 55.8 (OMe), 55.2 (OMe), 54.6
(OMe), 51.7 (OMe), 47.2 (CH, C-14a), 46.8 (C-12), 29.7 (C-
11). IR (KBr): 2990, 2945, 2913, 2835, 1749, 1612, 1585,
1552, 1519, 1490, 1459, 1437, 1353, 1249, 1212, 1193,
Hz, H-2), 2.81 (1 H, d, J = 13.7 Hz, a-CH ), 2.37 (1 H, d,
J = 13.7 Hz, b-CH ). C NMR (125 MHz, CDCl ): d = 174.4
2
1
3
2
3
3
(
4
1
q, C=O), 152.1 (q, C-5a), 136.0 (q, Bn-1¢C), 135.4 (q, Ar -
¢C), 134.9 (q, Ar -4¢C), 133.3 (q, Ar -1¢C), 132.9 (q, Ar -
¢C), 130.6 (CH, C-9), 129.9 (2 × CH, Bn-2¢ and 6¢C), 129.6
4
3
4
–1
1150, 1117, 1076, 1042, 1021 cm .
Synlett 2004, No. 15, 2761–2765 © Thieme Stuttgart · New York