Synthesis of Iodofurans by Electrophilic Cyclization
2-(2-Bromophenyl)-4,5,6,7-tetrahydro-3-iodobenzofuran (2b): Color-
less oil. 1H NMR (300 MHz, CDCl3): δ = 1.75–1.88 (m, 4 H), 2.29–
2.32 (t, J = 4.5 Hz, 2 H), 2.61–2.65 (t, J = 6.0 Hz, 2 H), 7.22–7.24
2.45–2.47 (t, J = 6.4 Hz, 2 H), 2.82–2.85 (t, J = 5.6 Hz, 1 H), 7.27–
7.29 (d, J = 7.2 Hz, 1 H), 7.36–7.40 (m, 2 H), 7.93–7.95 (t, J =
1.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.2, 27.3,
(d, J = 5.7 Hz, 1 H), 7.38–7.40 (t, J = 6.9 Hz, 1 H), 7.92–7.94 (d, 27.9, 28.9, 30.3, 70.3, 125.4, 125.9, 127.5, 128.2, 130.8, 148.2,
J = 5.7 Hz, 1 H), 8.10 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 22.8, 23.1, 23.2, 67.9, 122.5, 123.6, 124.0, 128.3, 129.8, 130.2,
152.7 ppm. IR (neat): ν = 2928, 2253, 1480, 908, 734, 650 cm–1.
C15H15IO (338.0): calcd. C 53.27, H 4.47; found C 53.31, H 4.54.
˜
132.7, 147.2, 151.8 ppm. IR (neat): ν = 2936, 1593, 909, 737 cm–1.
˜
4,5,6,7,8,9-Hexahydro-3-iodo-2-phenylcycloocta[b]furan (2k): Color-
less oil. 1H NMR (400 MHz, CDCl3): δ = 1.47–1.54 (m, 4 H), 1.65–
1.76 (m, 4 H), 2.52–2.55 (t, J = 6.4 Hz, 2 H), 2.83–2.86 (t, J =
6.4 Hz, 2 H), 7.25–7.29 (t, J = 7.2 Hz, 1 H), 7.37–7.41 (m, 2 H),
7.96–7.99 (t, J = 1.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 24.7, 25.4, 25.7, 26.4, 27.7, 27.9, 69.1, 123.3, 125.8, 127.4, 128.2,
C14H12BrIO (401.9): calcd. C 41.72, H 3.00; found C 41.79, H 2.94.
2-(3-Bromophenyl)-4,5,6,7-tetrahydro-3-iodobenzofuran (2c): Color-
less oil. 1H NMR (300 MHz, CDCl3): δ = 1.76–1.91 (m, 4 H), 2.32–
2.36 (m, 2 H), 2.62–2.66 (m, 2 H), 7.21–7.26 (m, 1 H), 7.23–7.37
(m, 1 H), 7.45–7.48 (q, J = 1.8, J = 7.8 Hz, 1 H), 7.64–7.67 (q, J
= 0.9, J = 7.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
22.8, 22.9, 23.2, 23.3, 70.9, 121.8, 123.8, 126.9, 130.3, 131.9, 132.7,
130.8, 148.6, 151.4 ppm. IR (neat): ν = 2926, 1602, 1447, 1072, 908,
˜
733 cm–1. C16H17IO (352.0): calcd. C 54.56, H 4.86; found C 54.58,
H 4.82.
133.2, 150.0, 151.8 ppm. IR (neat): ν = 3346, 2974, 1452, 1049,
˜
881 cm–1. C14H12BrIO (401.9): calcd. C 41.72, H 3.00; found C
41.77, H 3.03.
4,5,6,7,8,9,10,11,12,13-Decahydro-3-iodo-2-phenylcyclododeca[b]-
furan (2l): Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.26–
1.43 (m, 12 H), 1.72–1.79 (m, 4 H), 2.38–2.42 (t, J = 6.4 Hz, 2 H),
2.63–2.67 (t, J = 6.8 Hz, 2 H), 7.28–7.30 (q, J = 5.2, J = 2.4 Hz 1
H), 7.37–7.41 (m, 2 H), 7.96–7.98 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 22.2, 22.8, 23.0, 23.5, 24.0, 24.8, 24.9, 26.1,
26.9, 67.9, 123.8, 126.0, 127.5, 128.2, 130.8, 149.5, 151.9 ppm. IR
2-(4-Bromophenyl)-4,5,6,7-tetrahydro-3-iodobenzofuran (2d): Color-
1
less solid; m.p. 82–83 °C. H NMR (400 MHz, CDCl3): δ = 1.75–
1.89 (m, 4 H), 2.29–2.33 (t, J = 7.6 Hz, 2 H), 2.61–2.65 (t, J =
6.8 Hz, 2 H), 7.49–7.52 (d, J = 8.8 Hz, 2 H), 7.84–7.86 (d, J =
11.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.8, 23.1,
23.2, 29.7, 67.2, 121.2, 123.5, 127.1, 129.7, 131.4, 147.9, 151.6 ppm.
(neat): ν = 2934, 2253, 1472, 908, 737, 651 cm–1. C H IO (408.1):
˜
20 25
IR (KBr): ν = 3334, 2973, 1380, 1090, 1049, 881 cm–1. C H BrIO
˜
calcd. C 58.83, H 6.17; found C 58.78, H 6.22.
14 12
(401.9): calcd. C 41.72, H 3.00; found C 41.66, H 3.05.
3-Iodo-4-methyl-2-phenylfuran (2m): Colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 1.83–1.84 (d, J = 1.0 Hz, 3 H), 7.14–7.16
(t, J = 1.2 Hz, 2 H), 7.24–7.28 (q, J = 6.8, J = 8.4 Hz, 2 H), 7.84–
7.86 (t, J = 1.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
11.8, 68.9, 125.7, 126.0, 127.9, 128.3, 130.4, 138.1, 151.5 ppm. IR
2-(4-Chlorophenyl)-4,5,6,7-tetrahydro-3-iodobenzofuran (2e): Color-
1
less viscous oil. H NMR (400 MHz, CDCl3): δ = 1.67–1.70 (m, 4
H), 1.77–1.79 (m, 2 H), 2.21–2.24 (m, 2 H), 2.53–2.56 (m, 2 H),
7.26–7.28 (q, J = 1.2, J = 6.4 Hz, 2 H), 7.81–7.83 (q, J = 2, J =
6.8 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.1, 23.4,
23.5, 29.9, 67.4, 123.7, 127.1, 128.7, 129.5, 133.3, 148.2, 151.8 ppm.
(neat): ν = 2920, 1765, 1481, 1024, 764, 690 cm–1. C H IO (284.0):
˜
11
9
calcd. C 46.51, H 3.19; found C 46.47, H 3.25.
IR (KBr): ν = 3334, 2973, 1453, 1090, 881, 667 cm–1. C H ClIO
˜
14 12
2-(2-Bromophenyl)-3-iodo-4-methylfuran (2n): Colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 1.98 (s, 3 H), 7.22–7.30 (m, 2 H),
7.40–7.44 (m, 1 H), 7.91–8.10 (m, 1 H), 8.11 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 11.7, 70.1, 122.5, 124.4, 126.0, 128.7,
(358.0): calcd. C 46.89, H 3.37; found C 46.84, H 3.44.
4,5,6,7-Tetrahydro-3-iodo-2-(p-tolyl)benzofuran (2f): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.76–1.88 (m, 4 H), 2.29–2.37
(m, 2 H), 2.41 (s, 1 H), 2.62–2.65 (m, 2 H), 7.19–7.22 (t, J = 8.0 Hz,
2 H), 7.83–7.85 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.3, 22.9, 23.3, 29.7, 65.8, 123.0, 125.8, 128.1, 128.9,
129.8, 130.8, 132.3, 138.6, 149.9 ppm. IR (neat): ν = 2924, 1769,
˜
1467, 908, 733 cm–1. C11H8BrIO (361.9): calcd. C 36.40, H 2.22;
found C 36.45, H 2.27.
137.4, 149.3, 150.9 ppm. IR (neat): ν = 3334, 2973, 1452, 1379,
˜
1090, 1049, 881 cm–1. C15H15IO (338.0): calcd. C 53.27, H 4.47;
found C 53.33, H 4.41.
2-(4-Bromophenyl)-3-iodo-4-methylfuran (2o): Colorless viscous oil.
1H NMR (400 MHz, CDCl3): δ = 1.99–1.20 (d, J = 1.2 Hz, 3 H),
7.31–7.32 (d, J = 1.2 Hz, 1 H), 7.51–7.54 (d, J = 8.8 Hz, 2 H),
7.84–7.86 (t, J = 2.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 11.7, 69.6, 121.9, 126.0, 127.5, 129.4, 131.5, 138.4, 150.7 ppm.
4,5,6,7-Tetrahydro-3-iodo-5-methyl-2-phenylbenzofuran (2h): Color-
less oil. 1H NMR (400 MHz, CDCl3): δ = 1.06–1.08 (d, J = 8.8 Hz,
3 H), 1.24–1.42 (m, 1 H), 1.81–1.93 (m, 2 H), 2.19–2.32 (m, 3 H),
2.67–2.74 (d, J = 20.8, J = 6.0 Hz, 1 H), 7.23–7.28 (t, J = 10.0 Hz,
1 H), 7.35–7.40 (t, J = 10.0 Hz, 2 H), 7.94–7.96 (d, J = 10.0 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.3, 22.5, 29.9, 31.1,
31.3, 66.3, 122.8, 125.7, 127.4, 128.2, 130.8, 149.1, 150.9 ppm. IR
IR (neat): ν = 3340, 2973, 2885, 1452, 1089, 1049, 881 cm–1
.
˜
C11H8BrIO (361.9): calcd. C 36.40, H 2.22; found C 36.37, H 2.18.
4,5,6,7,8,9,10,11,12,13-Decahydro-2,3-diphenylcyclododeca[b]furan
(3l): Pd(OAc)2 (0.92 mg, 2 mol-%) was added to a solution of 2l
(81.60 mg, 0.20 mmol) and K2CO3 (55 mg, 0.40 mmol) in DMF
(2.0 mL). The mixture was stirred for 5 min and phenylboronic acid
(29.3 g, 0.24 mmol) was added. The resulting mixture was then
stirred under argon at 80 °C for 6 h and then diluted with aqueous
saturated ammonium chloride and extracted with EtOAc. The
combined extracts were washed with water four times. The solvent
was removed under reduced pressure and the residue upon work-
up was purified by chromatography on basic Al2O3 with petroleum
ether/EtOAc (100:1, v/v) as eluent to give 3l as a colorless viscous
oil (39.1 mg, 59%). 1H NMR (400 MHz, CDCl3): δ = 1.16–1.92 (t,
J = 5.2 Hz, 4 H), 1.25–1.45 (m, 10 H), 1.86–1.88 (t, J = 4.8 Hz, 2
H), 2.34–2.37 (t, J = 6.8 Hz, 2 H), 2.69–2.72 (t, J = 6.4 Hz, 2 H),
7.10–7.19 (m, 3 H), 7.31–7.41 (m, 7 H) ppm. 13C NMR (100 MHz,
(neat): ν = 3374, 2974, 1452, 1088, 1048, 881 cm–1. C H IO
˜
15 15
(338.0): calcd. C 53.27, H 4.47; found C 53.32, H 4.39.
5,5-Ethylenedioxy-4,5,6,7-tetrahydro-3-iodo-2-phenylbenzofuran
1
(2i): Colorless solid; m.p. 79–80 °C. H NMR (400 MHz, CDCl3):
δ = 1.91–1.96 (t, J = 8.8 Hz, 2 H), 2.44–2.48 (t, J = 8.0 Hz, 2 H),
2.93 (s, 1 H), 7.23–7.31 (m, 1 H), 7.36–7.41 (t, J = 9.2 Hz, 2 H),
7.91–7.94 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.5,
29.9, 31.9, 34.6, 64.7, 65.7, 109.1, 122.3, 125.8, 127.7, 128.3, 130.6,
147.8, 150.5 ppm. IR (neat): ν = 3333, 2973, 1452, 1090, 881,
˜
662 cm–1. C16H15IO3 (382.0): calcd. C 50.28, H 3.96; found C
50.33, H 3.92.
5,6,7,8-Tetrahydro-3-iodo-2-phenyl-4H-cyclohepta[b]furan (2j): Col-
orless oil. 1H NMR (400 MHz, CDCl3): δ = 1.70–1.78 (m, 7 H), CDCl3): δ = 20.7, 22.4, 22.7, 23.3, 24.4, 24.7, 25.2, 26.4, 26.8, 122.1,
Eur. J. Org. Chem. 2008, 1013–1018
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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