E. M. Beccalli, M. L. Gelmi, A. Marchesini
FULL PAPER
4-H), 6.75 (dd, J ϭ 1.8/2.6 Hz, 1 H, pyrrole 5-H), 7.44 (d, J ϭ
4.22 (m, 4 H, OCH2), 4.44 (q, J ϭ 7.2 Hz, 2 H, OCH2), 6.49 (s, 1
1.7 Hz, 1 H, furan 5-H). Ϫ C15H15NO5 (289.28): calcd. C 62.28, H H, indole 3Ј-H), 6.75 (s, 1 H, indole 2-H), 7.15Ϫ7.45 (m, 7 H,
5.23, N 4.84; found C 62.12, H 5.10, N 4.75.
arom.), 7.62 (m, 2 H, arom.), 7.90 (m, 2 H, arom.), 8.06 (m, 2 H,
arom.). Ϫ H NMR (C6D6): δ ϭ 0.72 (t, J ϭ 7.1 Hz, 3 H, CH3),
1
5bc: Prepared from 3b and 4c; reflux for 2 h; eluent pentane/
CH2Cl2 (1:1); m.p. 131Ϫ132°C (pentane/Et2O); yield 95%. Ϫ IR:
1.10 (t, J ϭ 7.1 Hz, 3 H, CH3), 1.23 (t, J ϭ 7.1 Hz, 3 H, CH3),
3.70 (q, J ϭ 7.1 Hz, 2 H, NCOOCH2), 4.20 (q, J ϭ 7.1 Hz, 2 H,
OCH2), 4.49 (q, J ϭ 7.1 Hz, 2 H, OCH2), 6.35 (s, 1 H, 3Ј-H), 6.74
(m, 3 H, arom.), 6.96 (t, J ϭ 7.4 Hz, 1 H, indole 5-H), 7.07 (m, 2
H, indole), 7.11 (t, J ϭ 8.4 Hz, 1 H, indole 6-H), 7.24 (m, 2 H,
indole), 8.03 (m, 2 H, arom.), 8.20 (m, 1 H, 4Ј-H), 8.34 (d, J ϭ
8.4 Hz, 1 H, indole 7-H), 8.40 (br. s, 1 H, indole 7Ј-H). Ϫ
C33H30N2O8S (614.67): calcd. C 64.48, H 4.92, N 4.56; found C
64.35, H 4.82, N 4.45.
1
ν˜ ϭ 1720, 1702, 1560 cmϪ1. Ϫ H NMR: δ ϭ 3.45 (s, 3 H, NMe),
3.62 (s, 3 H, OMe), 3.91 (s, 3 H, OMe), 5.67 (dd, J ϭ 1.7/3.9 Hz,
1 H, pyrrole 3-H), 5.87 (dd, J ϭ 2.6/3.9 Hz, 1 H, pyrrole 4-H), 6.45
(s, 1 H, indole 3-H), 6.55 (dd, J ϭ 1.7/2.6 Hz, 1 H, pyrrole 5-H),
7.25 (m, 2 H, arom.), 7.40Ϫ7.55 (m, 4 H, arom.), 7.85 (m, 3 H,
arom.). Ϫ C25H22N2O6S (478.52): calcd. C 62.75, H 4.63, N 5.85;
found C 62.78, H 4.58, N 5.72.
5bd: Prepared from 3b and 4d; reflux for 2 h; eluent pentane/
CH2Cl2 (1:1) to CH2Cl2/Et2O (30:1); m.p. 152Ϫ153°C (pentane/
CH2Cl2); yield 85%. Ϫ IR: ν˜ ϭ 1719, 1695 cmϪ1. Ϫ 1H NMR: δ ϭ
3.08 (s, 3 H, NMe), 3.84 (s, 3 H, OMe), 3.85 (s, 3 H, OMe), 6.10
(m, 2 H, pyrrole), 6.52 (d, J ϭ 2.1 Hz, 1 H, pyrrole 5-H), 7.07 (s,
1 H, indole 2-H), 7.20 (m, 3 H, arom.), 7.50 (m, 3 H, arom.), 7.80
(m, 2 H, arom.), 7.95 (d, J ϭ 8.1 Hz, 1 H, indole 7-H). Ϫ
C25H22N2O6S (478.52): calcd. C 62.75, H 4.63, N 5.85; found C
62.63, H 4.55, N 5.80.
5dd: Prepared from 3d and 4d; reflux for 3 h; eluent pentane/
CH2Cl2 (1:1) to CH2Cl2; m.p. 175Ϫ176°C (Et2O); yield 90%. Ϫ
IR: ν˜ ϭ 1730, 1719, 1697 cmϪ1. Ϫ 1H NMR ([D6]DMSO): δ ϭ
1.26 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.31 (t, J ϭ 7.2 Hz, 3 H, CH3),
1.37 (t, J ϭ 7.2 Hz, 3 H, CH3), 4.25 (m, 4 H, OCH2), 4.38 (q, J ϭ
7.2 Hz, 2 H, OCH2), 6.98 (t, J ϭ 7.1 Hz, 1 H, indole), 7.15 (m, 2
H, arom.), 7.28 (m, 3 H, arom.), 7.50 (m, 2 H, arom.), 7.62 (s, 1
H, indole 2-H), 7.70 (m, 3 H, arom.), 7.76 (s, 1 H, indole 2Ј-H),
7.80 (d, J ϭ 8.1 Hz, 1 H, indole 7Ј-H), 8.03 (d, J ϭ 8.2 Hz, 1 H,
indole 7-H). Ϫ C33H30N2O8S (614.67): calcd. C 64.48, H 4.92, N
4.56; found C 64.37, H 4.81, N 4.58.
5cb: Prepared from 3c and 4b; reflux for 1.5 h; eluent pentane/Et2O
(3:1); m.p. 48°C (pentane); yield 98%. Ϫ IR: ν˜ ϭ 1718, 1698, 1590
1
cmϪ1. Ϫ H NMR: δ ϭ 1.30 (m, 6 H, CH3), 4.35 (m, 4 H, OCH2),
Diethyl 2,3-Diphenylmaleate (5ae):[16] Compound 3a (900 mg,
2.28 mmol) was dissolved in DMF (6 mL) and nBu3SnPh (4e) (1.1
mL, 3.4 mmol), Ph3P (60 mg, 0.23 mmol) and tris(dibenzylidenea-
cetone)palladium (105 mg, 0.11 mmol) were added. The resulting
mixture was heated at 75Ϫ80°C for 3 h, then poured into a satu-
rated NaCl solution (150 mL), and extracted with Et2O (2 ϫ 30
mL). The organic phase was dried, filtered, and the solvent was
evaporated. Purification of the residue by chromatography on silica
gel with pentane/CH2Cl2 (3:1) as eluent afforded 5ae; m.p. 56°C,
yield 88%.
6.08 (d, J ϭ 3.7 Hz, 1 H, furan 3-H), 6.38 (dd, J ϭ 1.8/3.6 Hz, 1
H, furan 4-H), 7.04 (m, 2 H, thiophene), 7.43 (m, 2 H, arom.). Ϫ
C16H16O5S (320.36): calcd. C 59.99, H 5.03; found C 59.88, H 4.99.
5cc: Prepared from 3c and 4c; reflux for 1 h; eluent pentane/CH2Cl2
(1:1); m.p. 142°C (Et2O); yield 98%. Ϫ IR: ν˜ ϭ 1718, 1698, 1595
cmϪ1. Ϫ 1H NMR: δ ϭ 1.24 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.52 (t,
J ϭ 7.2 Hz, 3 H, CH3), 4.25 (m, 2 H, OCH2), 4.57 (q, J ϭ 7.2 Hz,
2 H, OCH2), 6.79 (s, 1 H, indole 3-H), 6.80 (dd, J ϭ 3.8/5.1 Hz, 1
H, thiophene 4-H), 6.92 (dd, J ϭ 1.1/5.1 Hz, 1 H, thiophene 5-H),
7.06 (dd, J ϭ 1.1/3.8 Hz, 1 H, thiophene 3-H), 7.14 (m, 2 H, arom.),
7.30 (m, 2 H, arom.), 7.48 (m, 1 H, indole), 7.62 (d, J ϭ 7.7 Hz, 1
H, indole 4-H), 7.90 (m, 2 H, arom.), 8.39 (d, J ϭ 7.7 Hz, 1 H,
indole 7-H). Ϫ C26H23NO6S2 (509.59): calcd. C 61.28, H 4.55, N
2.75; found C 61.16, H 4.46, N 2.68.
Diarylmaleic Anhydrides 6. ؊ General Method: To a solution of the
appropriate compound 5 (1.5 mmol) in EtOH (30 mL) was added
a solution of NaOH (540 mg, 13.5 mmol) in EtOH (10 mL) and
H2O (4 mL). The mixture was heated to reflux for 30 min. The
solvent was then evaporated, the residue was acidified with 5%
HCl, and extracted with CH2Cl2 (2 ϫ 20 mL). The organic phase
was dried, filtered, and the solvent was evaporated. The residue
was purified either by chromatography on silica gel or by crystalli-
zation.
5da: Prepared from 3d and 4a; reflux for 1.5 h; eluent pentane to
CH2Cl2; m.p. 88Ϫ89°C (pentane/Et2O); yield 98%. Ϫ IR: ν˜ ϭ
1718, 1698, 1690 cmϪ1. Ϫ 1H NMR: δ ϭ 1.20 (t, J ϭ 7.2 Hz, 3 H,
CH3), 1.44 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.48 (t, J ϭ 7.2 Hz, 3 H,
CH3), 4.21 (q, J ϭ 7.2 Hz, 2 H, OCH2), 4.50 (m, 4 H, OCH2), 6.86
(dd, J ϭ 3.7/5.1 Hz, 1 H, thiophene 4-H), 7.12 (dd, J ϭ 1.3/3.7 Hz,
1 H, thiophene 3-H), 7.15 (m, 2 H, arom.), 7.35 (m, 2 H, arom.),
7.68 (s, 1 H, indole 2-H), 8.23 (d, J ϭ 8.4 Hz, 1 H, indole 7-H). Ϫ
C23H23NO6S (441.50): calcd. C 62.57, H 5.25, N 3.17; found C
62.46, H 5.19, N 3.11.
6aa: Purified by chromatography on silica gel, eluent pentane/
CH2Cl2 (1:1); m.p. 149°C (sublimes) (pentane/CH2Cl2); yield 60%.
Ϫ IR: ν˜ ϭ 1800, 1732, 1600 cmϪ1. Ϫ 1H NMR: δ ϭ 7.11 (dd, J ϭ
3.9/5.1 Hz, 1 H, thiophene 4-H), 7.52Ϫ7.55 (m, 5 H), 7.59 (dd, J ϭ
1.1/5.1 Hz, 1 H, thiophene 5-H), 7.95 (dd, J ϭ 1.1/3.9 Hz, 1 H,
thiophene 3-H). Ϫ C14H8O3S (256.28): calcd. C 65.61, H 3.15;
found C 65.81, H 3.09.
5db: Prepared from 3d and 4b; reflux for 1 h; eluent pentane/Et2O
(3:1); m.p. 85°C (pentane/Et2O); yield 99%. Ϫ IR: ν˜ ϭ 1738, 1719,
1
1700 cmϪ1. Ϫ H NMR: δ ϭ 1.22 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.42
6ac: Purified by chromatography on silica gel, eluent pentane/
CH2Cl2 (1:1); m.p. 259°C (pentane/CH2Cl2); yield 98%. Ϫ IR: ν˜ ϭ
(t, J ϭ 7.2 Hz, 3 H, CH3), 1.48 (t, J ϭ 7.2 Hz, 3 H, CH3), 4.23 (q,
J ϭ 7.2 Hz, 2 H, OCH2), 4.48 (m, 4 H, OCH2), 6.10 (d, J ϭ 3.5 Hz,
1 H, furan 3-H), 6.23 (dd, J ϭ 1.8/3.5 Hz, 1 H, furan 4-H), 7.15
(m, 1 H, arom.), 7.30 (m, 3 H, arom.), 7.66 (s, 1 H, indole 2-H),
8.21 (d, J ϭ 8.4 Hz, 1 H, indole 7-H). Ϫ C23H23NO7 (425.44):
calcd. C 64.93, H 5.45, N 3.29; found C 64.81, H 5.40, N 3.21.
1
3360, 1800, 1738, 1604 cmϪ1. Ϫ H NMR: δ ϭ 7.12 (m, 1 H), 7.35
(m, 3 H, arom.), 7.60 (m, 4 H, arom.), 7.70 (m, 2 H, arom.), 9.55
(s, 1 H, H/D exchangeable). Ϫ C18H11NO3 (289.29): calcd. C 74.73,
H 3.83, N 4.84; found C 74.52, H 3.69, N 4.75.
6ad: Purified by chromatography on silica gel, eluent pentane/
CH2Cl2 (1:2); m.p. 218Ϫ219°C (hexane/CH2Cl2); yield 68%. Ϫ IR:
5dc: Prepared from 3d and 4c; reflux for 1.5 h; eluent pentane/Et2O
(2:1); m.p. 143Ϫ145°C (Et2O); yield 87%. Ϫ IR: ν˜ ϭ 1733, 1721,
1
ν˜ ϭ 3395, 1803, 1730 cmϪ1. Ϫ H NMR: δ ϭ 6.39 (d, J ϭ 8.1 Hz,
1710, 1595 cmϪ1. Ϫ 1H NMR: δ ϭ 1.16 (t, J ϭ 7.2 Hz, 3 H, CH3), 1 H, indole 7-H), 6.84 (dt, J ϭ 1.0/8.1 Hz, 1 H, indole 5-H), 7.20
1.25 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.38 (t, J ϭ 7.2 Hz, 3 H, CH3), (dt, J ϭ 1.0/8.1 Hz, 1 H, indole 6-H), 7.40 (m, 4 H, arom.), 7.66
1424
Eur. J. Org. Chem. 1999, 1421Ϫ1426