2096
H. Tran et al. / Tetrahedron Letters 54 (2013) 2093–2096
(100 MHz, CDCl3): 55.2 (40-OCH3), 55.8 (300-OCH3, 500-OCH3), 56.3 (6-OCH3),
References and notes
57.9 (C-3), 93.7 (C-2), 95.7 (C-7), 99.5 (C-400), 106.7 (C-200 and C-600), 112.0 (C-30
and C-50), 119.3 (C-4), 120.8 (C-3a), 123.7 (2 ꢁ Ar-CH), 127.4 (C-20 and C-60),
131.4 (2 ꢁ Ar-CH), 131.3 (C-10), 134.5 (Ar-C), 144.0 (C-5), 145.3 (C-100), 150.6
(Ar-C), 151.6 (C-6), 153.2 (C-7a), 158.6 (C-40), 159.9 (C-300 and C-500), 164.1
1. (a) Langcake, P.; Pryce, R. J. Experientia 1977, 33, 151–152; (b) Suzuki, K.;
Shimizu, T.; Kawabata, J.; Mizutani, J. Agric. Biol. Chem. 1987, 51, 1003–1008; (c)
Kurihara, H.; Kawabata, J.; Ichikawa, S.; Mizutani, J. Agric. Biol. Chem. 1990, 54,
1097–1099.
2. (a) Privat, C.; Telo, J. P.; Bernardes-Genisson, V.; Vieira, A.; Souchard, J.-P.;
Nepveu, F. J. Agric. Food Chem. 2002, 50, 1213–1217; (b) Mikulski, D.; Molski, M.
Eur. J. Med. Chem. 2010, 45, 2366–2380; (c) Kim, H. J.; Chang, E. J.; Cho, S. H.;
Chung, S. K.; Park, H. D.; Choi, S. W. Biosci. Biotechnol. Biochem. 2002, 66, 1990–
1993.
3. Zghonda, N.; Yoshida, S.; Araki, M.; Kusunoki, M.; Mliki, A.; Ghorbel, A.;
Miyazaki, H. Biosci. Biotechnol. Biochem. 2011, 75, 1259–1267.
4. Zghonda, N.; Yoshida, S.; Ezaki, Sh.; Murakami, C.; Mliki, A.; Ghorbel, A.;
Miyazaki, H. Biosci. Biotechnol. Biochem. 2012, 76, 954–960.
5. Fu, J.; Jin, J.; Cichewicz, R. H.; Hageman, S. A.; Ellis, T. K.; Xiang, L.; Peng, Q.;
Jiang, M.; Arbez, N.; Hotaling, K.; Ross, C. A.; Duan, W. J. Biol. Chem. 2012, 287,
24460–24472.
6. (a) Kokubo, K.; Harada, K.; Mochizuki, E.; Oshima, T. Tetrahedron Lett. 2010, 51,
955–958; (b) Bertolini, F.; Crotti, P.; Di Bussolo, V.; Macchia, F.; Pineschi, M. J.
Org. Chem. 2007, 72, 7761–7764; (c) Cheung, W.-H.; Zheng, S.-L.; Yu, W.-Y.;
Zhou, G.-C.; Che, C.-M. Org. Lett. 2003, 5, 2535–2538; (d) Li, X.-C.; Ferreira, D.
Tetrahedron 2003, 59, 1501–1507; (e) Oshima, T.; Nakajima, Y.; Nagai, T.
Heterocycles 1996, 43, 619–624.
7. (a) Yao, C.-S.; Lin, M.; Wang, Y.-H. Chin. J. Chem. 2004, 22, 1350–1355; (b) Li, W.;
Luo, Y.; Li, H.; Zang, P.; Han, X. Synthesis 2010, 3822–3826; (c) Zhang, C.; Shen,
H.; Zou, L.; Xu, Y.; Guang, D.; Li, Y.; Wang, Y.; Wang, L. Yingyong Huaxue 2009,
26, 1180–1183; (d) Velu, S. S.; Buniyamin, I.; Ching, L. K.; Feroz, F.; Noorbatcha,
I.; Gee, L. C.; Awang, K.; Wahab, I. A.; Faizal Weber, J.-F. Chem. Eur. J. 2008, 14,
11376–11384; (e) Panzella, L.; De Lucia, M.; Amalfitano, C.; Pezzella, A.;
Evidente, A.; Napolitano, A.; D’Ischia, M. J. Org. Chem. 2006, 71, 4246–4254; (f)
Takaya, Y.; Terashima, K.; Ito, J.; He, Y.-H.; Tateoka, M.; Yamaguchi, N.; Niwa, M.
Tetrahedron 2005, 61, 10285–10290; (g) Sako, M.; Hosokawa, H.; Ito, T.; Iinuma,
M. J. Org. Chem. 2004, 69, 2598–2600; (h) Nicotra, S.; Cramarossa, M. R.; Mucci,
A.; Pagnoni, U. M.; Riva, S.; Forti, L. Tetrahedron 2004, 60, 595–600.
8. (a) Engler, T. A.; Gfesser, G. A.; Draney, B. W. J. Org. Chem. 1995, 60, 3700–3706;
(b) Engler, T. A.; Draney, B. W.; Gfesser, G. A. Tetrahedron Lett. 1994, 35, 1661–
1664.
(C@O); IR m
max/cmꢀ1 3014, 2915, 1740, 1529, 1351, 948, 872. HRMS (ESI+): found
(MH+) 558.1760, C31H28NO9 requires 558.1764. Data for 2,3-trans-3-[300,500-
bis(allyloxy)phenyl]-6-methoxy-2-(40-methoxyphenyl)-2,3-dihydrobenzofuran-
5-yl 4-nitrobenzoate (15b): Rf (3:1, hexanes–EtOAc) = 0.6; 1H NMR (400 MHz,
CDCl3): 3.82 (6H, s, 40-OCH3 and 6-OCH3), 4.44–4.48 (5H, m, 2 ꢁ OCH2CH@CH2,
3-H), 5.26–5.37 (4H, m, 2 ꢁ OCH2CH@CH2), 5.52 (1H, d, J = 8.4 Hz, 2-H), 5.96–
6.05 (2H, m, 2 ꢁ OCH2CH@CH2), 6.34 (2H, d, J = 2.4 Hz, 200-H and 600-H), 6.41
(1H, t, J = 2.4 Hz, 400-H), 6.66 (1H, s, 7-H), 6.81 (1H, s, 4-H), 6.90 (2H, d,
J = 8.8 Hz, 20-H and 60-H), 7.28 (2H, d, J = 8.8 Hz, 30-H and 50-H), 8.34 (4H, br s,
13
4-NO2-Ar-H); C NMR (100 MHz, CDCl3): 55.2 (40-OCH3), 56.2 (6-OCH3), 57.6
(C-3), 68.9 (2 ꢁ OCH2CH@CH2), 93.7 (C-2), 95.0 (C-7), 100.5 (C-400), 107.2 (C-200
and C-600), 112.1 (C-30 and C-50), 117.9 (2 ꢁ OCH2CH@CH2), 119.0 (C-4), 121.0
(C-3a), 123.7 (2 ꢁ Ar-CH), 127.4 (C-20 and C-60), 131.3 (2 ꢁ Ar-CH), 131.5 (C-10),
133.0 (2 ꢁ OCH2CH@CH2), 134.5 (Ar-C), 143.8 (C-5), 145.4 (C-100), 150.8 (Ar-C),
151.7 (C-6), 153.4 (C-7a), 158.6 (C-40), 160.0 (C-300 and C-500), 163.3 (C@O); IR
m
max/cmꢀ1 3021, 2909, 1741, 1525, 1497, 1259, 960, 780. HRMS (ESI+): found
(MH+) 610.2067, C35H32NO9 requires 610.2072. Data for 2,3-trans-3-[300,500-
bis(benzyoxy)phenyl]-6-methoxy-2-(40-methoxyphenyl)-2,3-dihydrobenzo-
furan-5-yl 4-nitrobenzoate (15c): Rf (2:1, hexanes–EtOAc) = 0.6; 1H NMR
(400 MHz, CDCl3): 3.81 (3H, s, 40-OCH3) 3.82 (3H, s, 6-OCH3), 4.52 (1H, d,
J = 8.0 Hz, 3-H), 5.15–5.50 (5H, m, 2-H, 2 ꢁ OCH2Ph), 6.35 (2H, d, J = 2.2 Hz, 200-
H and 600-H), 6.49 (1H, t, J = 2.2 Hz, 400-H), 6.62 (1H, s, 7-H), 6.81 (1H, s, 4-H),
6.90 (2H, d, J = 8.7 Hz, 20-H and 60-H), 7.25–7.40 (12H, m, 30-H, 50-H,
2 ꢁ OCH2Ph), 8.31–8.33 (4H, m, 4-NO2-Ar-H); 13C NMR (100 MHz, CDCl3):
55.1 (40-OCH3), 56.3 (6-OCH3), 58.0 (C-3), 72.2 (2 ꢁ OCH2Ph), 93.9 (C-2), 95.2
(C-7), 98.2 (C-400), 106.5 (C-200 and C-600), 112.0 (C-30 and C-50), 119.5 (C-4),
121.0 (C-3a), 123.7 (2 ꢁ Ar-CH), 127.2 (2 ꢁ Ar-CH), 127.3, 127.5, 128.2 (C-20
and C-60, 8 ꢁ Ar-CH), 131.3 (2 ꢁ Ar-CH), 131.3 (C-10), 134.5 (Ar-C), 135.9
(2 ꢁ Ar-C), 143.9 (C-5), 145.5 (C-100), 150.6 (Ar-C), 151.6 (C-6), 153.4 (C-7a),
158.6 (C-40), 160.1 (C-300 and C-500), 165.0 (C@O); IR
1748, 1529, 1501, 1348,1156, 947, 877. HRMS (ESI+): found (MH+) 710.2388,
43H36NO9 requires 710.2390. Data for 2,3-trans-5,6-dimethoxy-2-(40-
m
max/cmꢀ1 3091, 2922,
C
methoxyphenyl)-3-[300,500-phenylene-bis(4-nitrobenzoate)]-2,3-dihydrobenzo-
furan (16a): Rf (3:1, hexanes–EtOAc) = 0.3; 1H NMR (400 MHz, CDCl3): 3.83
(9H, br s, 40-OCH3, 5-OCH3, 6-OCH3), 4.57 (1H, d, J = 8.0 Hz, 3-H), 5.56 (1H, d,
J = 8.0 Hz, 2-H), 6.68 (2H, d, J = 2.1 Hz, 200-H and 600-H), 6.73 (1H, s, 7-H), 6.76
(1H, t, J = 2.1 Hz, 400-H), 6.90 (1H, s, 4-H), 6.92 (2H, d, J = 8.2 Hz, 20-H and 60-H),
7.30 (2H, d, J = 8.2 Hz, 30-H and 50-H), 8.34 (8H, br s, 4-NO2-Ar-H); 13C NMR
(100 MHz, CDCl3): 55.3 (40-OCH3), 56.2, 56.4 (5-OCH3, 6-OCH3), 57.3 (C-3), 93.7
(C-2), 95.4 (C-7), 107.1 (C-400), 113.1 (C-200 and C-600), 114.1 (C-30 and C-50),
119.2 (C-4), 120.2 (C-3a), 123.7 (4 ꢁ Ar-CH), 127.5 (C-20 and C-60), 131.2
(4 ꢁ Ar-CH), 132.0 (C-10), 134.1 (C-5), 134.8 (2 ꢁ Ar-C), 144.6 (C-6), 145.8 (C-
100), 150.9 (C-300 and C-500), 151.7 (2 ꢁ Ar-C), 153.4 (C-7a), 158.7 (C-40), 163.5
9. Denmark, S. E.; Kobayashi, T.; Regens, C. S. Tetrahedron 2010, 66, 4745–4759.
10. Zhang, W.; Go, M. L. Eur. J. Med. Chem. 2007, 42, 841–850.
11. Procedure and data for 2,3-trans-5-hydroxy-6-methoxy-2-(40-methoxyphenyl)-3-
[300,500-phenylene-bis(4-nitrobenzoate)]-2,3-dihydrobenzofuran
(13):
solution of stilbene 12 (0.46 g, 0.85 mmol) and benzoquinone
To
(0.14 g,
a
5
1.0 mmol) in CH2Cl2 (35 mL) at ꢀ78 °C, under an atmosphere of nitrogen was
added a 0.5 M solution of 3:1 TiCl4:Ti(OiPr)4 in CH2Cl2 (4.9 mL, 2.2 mmol) and
the mixture stirred for 3 h. The reaction was quenched by the addition of
chilled (ꢀ78 °C) iPrOH (30 mL) followed by solid NaHCO3 (1.0 g) and then H2O
(30 mL). The resultant mixture was filtered through celite and the aqueous
filtrate extracted with CH2Cl2 (3 ꢁ 30 mL). The combined organic extracts were
washed with brine, dried (MgSO4) and the solvent removed in vacuo. The crude
product was purified by flash chromatography (3:1, hexanes–EtOAc) to give
benzofuran 13 (0.53 g, 90%) as an orange solid. Mp 126–128 °C; Rf (3:1,
(2 ꢁ C@O); IR
m
max/cmꢀ1 3083, 2912, 1745, 1520, 1499, 1157, 945. HRMS
(ESI+): found (MH+) 693.1719, C37H29N2O12 requires 693.1721. Data for 2,3-
trans-5-allyloxy-6-methoxy-2-(40-methoxyphenyl)-3-[300,500-phenylene-bis(4-
nitrobenzoate)]-2,3-dihydrobenzofuran (16b): Rf (3:1, hexanes–EtOAc) = 0.3;
1H NMR (400 MHz, CDCl3): 3.82 (6H, s, 40-OCH3 and 6-OCH3), 4.50–4.52 (2H, m,
OCH2CH@CH2), 4.56 (1H, d, J = 8.0 Hz, 3-H), 5.29–5.39 (2H, m, OCH2CH@CH2),
5.56 (1H, d, J = 8.0 Hz, 2-H), 6.00–6.05 (1H, m, OCH2CH@CH2), 6.67 (2H, d,
J = 2.0 Hz, 200-H and 600-H), 6.70 (1H, s, 7-H), 6.76 (1H, t, J = 2.0 Hz, 400-H), 6.86
(1H, s, 4-H), 6.92 (2H, d, J = 8.4 Hz, 20-H and 60-H), 7.29 (2H, d, J = 8.4 Hz, 30-H
1
hexanes–EtOAc) = 0.25; H NMR (400 MHz, CDCl3): 3.80 (3H, s, 40-OCH3), 3.89
(3H, s, 6-OCH3), 4.59 (1H, d, J = 8.0 Hz, 3-H), 5.32 (1H, br s, 5-OH), 5.46 (1H, d,
J = 8.0 Hz, 2-H), 6.56 (1H, s, 7-H), 6.66 (1H, s, 4-H), 6.90 (2H, d, J = 8.8 Hz, 20-H
and 60-H), 7.01 (2H, d, J = 2.0 Hz, 200-H and 600-H), 7.21 (1H, t, J = 2.0 Hz, 400-H),
7.29 (2H, d, J = 8.8 Hz, 30-H and 50-H), 8.35–8.40 (8H, m, 4-NO2-Ar-H); 13C NMR
(100 MHz, CDCl3): 55.3 (40-OCH3), 56.2 (6-OCH3), 57.6 (C-3), 92.8 (C-2), 97.2
(C-7), 110.7 (C-4), 114.2 (C-30 and C-50), 114.3 (C-400), 119.0 (C-200 and C-600),
119.4 (C-3a), 123.8 (4 ꢁ Ar-CH), 127.4 (C-20 and C-60), 131.4 (4 ꢁ Ar-CH), 131.5
(C-10), 134.5 (2 ꢁ Ar-C), 140.4 (C-5), 145.4 (C-100), 147.3 (C-6), 151.0 (2 ꢁ Ar-C),
13
and 50-H), 8.34 (8H, br s, 4-NO2-Ar-H); C NMR (100 MHz, CDCl3): 55.3 (40-
OCH3), 56.2 (6-OCH3), 57.4 (C-3), 69.2 (OCH2CH@CH2), 93.7 (C-2), 95.2 (C-7),
107.1 (C-400), 113.0 (C-200 and C-600), 114.2 (C-30 and C-50), 118.2
(OCH2CH@CH2), 118.9 (C-4), 120.4 (C-3a), 123.7 (4 ꢁ Ar-CH), 127.4 (C-20 and
C-60), 131.3 (4 ꢁ Ar-CH), 132.0 (C-10), 132.6 (OCH2CH@CH2), 133.6 (C-5), 134.8
(2 ꢁ Ar-C), 144.3 (C-6), 145.7 (C-100), 150.9 (C-300 and C-500), 151.8 (2 ꢁ Ar-C),
151.1 (C-300 and C-500), 153.4 (C-7a), 159.8 (C-40), 162.8 (2 ꢁ C@O); IR mmax
/
cmꢀ1 3460, 3113, 2982, 1739, 1524, 1347, 1175, 967, 830. HRMS (ESI+): found
153.6 (C-7a), 158.7 (C-40), 163.3 (2 ꢁ C@O); IR
m
max/cmꢀ1 3084, 2917, 1742,
(MH+) 679.1562, C36H27N2O12 requires 679.1559.
1525, 1499, 1346, 1157, 945, 870. HRMS (ESI+): found (MH+) 719.1862,
12. General procedure and data for compounds 15a–c and 16a–c: To a stirred
solution of dihydrobenzofuran 13 (0.10 g, 0.15 mmol) in dry acetone (2 mL),
under an atmosphere of nitrogen, were added K2CO3 (0.041 g, 0.30 mmol) and
the corresponding alkyl halide (0.6 mmol). The mixture was heated at reflux
for 20 h before being cooled to room temperature and saturated aqueous
NaHCO3 (5 mL) added. The aqueous mixture was extracted with CH2Cl2
(3 ꢁ 10 mL) and the combined organic extracts were washed with brine, dried
(Na2SO4) and the solvent removed in vacuo. The crude product was purified by
flash chromatography (2:1, hexanes–EtOAc) to give 15a–c and 16a–c as yellow
C
39H31N2O12 requires 719.1872. Data for 2,3-trans-5-benzyloxy-6-methoxy-2-
(40-methoxyphenyl)-3-[300,500-phenylene-bis(4-nitrobenzoate)]-2,3-dihydro-
benzofuran (16c): Rf (3:1, hexanes–EtOAc) = 0.4; 1H NMR (400 MHz, CDCl3):
3.81 (6H, br s, 40-OCH3 and 6-OCH3), 4.55 (1H, d, J = 8.1 Hz, 3-H), 5.23 (2H, s,
OCH2Ph), 5.56 (1H, d, J = 8.1 Hz, 2-H), 6.68 (2H, d, J = 2.0 Hz, 200-H and 600-H),
6.70 (1H, s, 7-H), 6.76 (1H, t, J = 2.0 Hz, 400-H), 6.85 (1H, s, 4-H), 6.92 (2H, d,
J = 8.4 Hz, 20-H and 60-H), 7.25–7.40 (7H, m, 30-H, 50-H, OCH2Ph), 8.33 (8H, br s,
13
4-NO2-Ar-H); C NMR (100 MHz, CDCl3): 55.3 (40-OCH3), 56.4 (6-OCH3), 57.1
(C-3), 73.1 (OCH2Ph), 93.7 (C-2), 95.2 (C-7), 107.0 (C-400), 113.1 (C-200 and C-600),
114.3 (C-30 and C-50), 119.1 (C-4), 120.4 (C-3a), 123.6 (4 ꢁ Ar-CH), 127.2, 127.4,
128.1 (C-20 and C-60, 5 ꢁ Ar-CH), 131.5 (4 ꢁ Ar-CH), 131.8 (C-10), 133.9 (C-5),
134.7 (2 ꢁ Ar-C), 135.7 (Ar-C), 144.2 (C-6), 145.8 (C-100), 151.0 (C-300 and C-500),
oils.
Data
for
2,3-trans-3-(300,500-dimethoxyphenyl)-6-methoxy-2-(40-
methoxyphenyl)-2,3-dihydrobenzofuran-5-yl 4-nitrobenzoate (15a): Rf (3:1,
1
hexanes–EtOAc) = 0.5; H NMR (400 MHz, CDCl3): 3.81 (9H, s, 40-OCH3, 300-
OCH3, 500-OCH3) 3.82 (3H, s, 6-OCH3), 4.45 (1H, d, J = 8.3 Hz, 3-H), 5.52 (1H, d,
J = 8.3 Hz, 2-H), 6.31 (2H, d, J = 2.4 Hz, 200-H and 600-H), 6.44 (1H, t, J = 2.4 Hz, 400-
H), 6.65 (1H, s, 7-H), 6.80 (1H, s, 4-H), 6.90 (2H, d, J = 8.8 Hz, 20-H and 60-H),
7.27 (2H, d, J = 8.8 Hz, 30-H and 50-H), 8.33–8.35 (4H, m, 4-NO2-Ar-H); 13C NMR
151.7 (2 ꢁ Ar-C), 153.5 (C-7a), 158.7 (C-40), 163.4 (2 ꢁ C@O); IR
m
max/cmꢀ1
3083, 2920, 1745, 1531, 1482, 1395, 1163, 946, 875. HRMS (ESI+): found (MH+)
769.2030, C43H33N2O12 requires 769.2034.