Thermal intramolecular Diels-Alder reaction of furan; synthesis of nitrogen tetracycles, isobenzofuran and isobenzothiophene

Article abstract of DOI:10.3184/030823407X191967

Thermal intramolecular Diels-Alder (IMDA) reaction of furan cored compounds has been further investigated; a series of key precursors to the IMDA reaction of furan diene (9a-c) have been prepared via facile alkylation and protection. While the cycloadditi

Full text of DOI:10.3184/030823407X191967

JOURNAL OF CHEMICAL RESEARCH 2007
FEBRUARy, 117–120
RESEARCH PAPER 117
Thermal intramolecular Diels–Alder reaction of furan; synthesis of
nitrogen tetracycles, isobenzofuran and isobenzothiophene
Muhsin Karaarslan, Ersen Gokturk and Aydin Demircan*
Department of Chemistry, Faculty of Liberal Arts & Sciences, University of Nigde, Kampus, 51100, Nigde, Turkey
Thermal intramolecular Diels–Alder (IMDA) reaction of furan cored compounds has been further investigated;
a series of key precursors to the IMDA reaction of furan diene (9a–c) have been prepared via facile alkylation and
protection. While the cycloaddition process for (10a–c) was afforded in hot toluene, a commercial microwave
(2450 MHz) was used for the synthesis of (12a–b). Treatment of fused oxy- and thio-heterotricycles (12a–b) with
borontrifluoride-etherate in dichloromethane at –78°C cleaved epoxy bridge and concomitant aromatisation gave
the isobenzo-furan and thiophene (13a–b) in 72–76% yields respectively.
Keywords: intramolecular Diels–Alder, cycloaddition, aromatisation.
O
Introduction
R
R
Diels–Alder reactions involving furan as a diene form
oxanobornenes that have been used in the synthesis of numerous
complex targets and as an intermediate in the synthesis of
natural products such as carbohydrates and prostaglandins.1
However, the facile retro-Diels–Alder reaction and the
low reactivity of furan as a diene as a result of its aromatic
character make the Diels–Alder reaction of furan one of the
most difficult cycloaddition.2 We have been studying intra-
molecular free radical reaction of furan with carbon chain
tether,3 and recently reported that the under thermal condition
the bromofurfurylalkenes, (1) with heteroatom possessed tether
undergoes intramolecular cycloaddition and gives heterofused
tricycles (2) (32–44% overall) as shown in Fig. 1.4
PhMe, 110 °C
R= H, CH 3
X=N–Boc, O, S
32-44%
O
Br
X
X
Br
1
2
Fig. 1
available cyclopentenone, (3) by employing molecular
bromine and triethylamine was followed by selective Luche’s
reduction of 2-bromocyclopentenone. Reaction of resulting
alcohol with phosphorous tribromide and pyridine gave 2,3-
dibromocyclopentene, (4) (n = 1) in high yields.7 Known 2,3-
dibromocyclohexene (4) (n = 2) was derived from cyclopentene,
(6) by a step economy; addition of dibromocarbene to
cyclopentene, followed by thermal ring expansion gave the
corresponding 2,3-dibromocyclohexene, (4) (n = 2) in 78%
yield.8 Displacement of allylic bromide in 4 (n = 1, 2) generated
(8a–c) in 90–93% yields, which were then converted to their
carbamates, (9a–c) under standard condition.9
Having seen recent papers5 on IMDA reactions, we now
report our additional findings regarding synthesis of fused
tetracycles and substituted aromatic structures. One can utilise
these compounds as a powerful strategy at the intermediate
stages in a total synthesis, and develop the furan chemistry.
Results and discussion
Fused tetracyclic bromides, (10a–c) were prepared by a
procedure shown in Fig. 2. Bromination6 of the commercially
O
Br
NH2
O
iv
i
R
iii
ii
Br
Br
n=1
n=2
Br
n
4
R= H
R= H
R= CH3 7c
7a
7b
n= 1
n= 2
n= 2
3
5
6
R
O
O
H
n
HN
v
Br
vi
n
O
O
N
N
O
H
R
n
O
R
O
Br
Br
8a 90 %
8b 92 %
8c 93 %
R= H
R= H
R=CH3
9a 88 %
9b 80 %
9c 82 %
n=1
n=2
n=2
10a
10b
10c
45 %
15 %
17 %
Fig. 2 (i) Br2, Et3N, DCM, 0°C, 98%; NaBH4, CeCl3.7H2O, MeOH, 0°C, 97%; PBr3, pyridine, PhH, 0°CÆ reflux, 68%; (ii) KOtBu, CHBr3,
pentane, 0°C; (iii) heat 155°C, 1 h, 78%; (iv) 2,3-dibromocyclopentene or 2,3-dibromocyclohexene (4), K2CO3, THF, reflux, 3 d;
(v) (BOC)2O, DMAP, DCM, 0°C, 2 h; (vi) heat, PhMe, 4 days.
* Correspondent. E-mail: ademircan@nigde.edu.tr
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118 JOURNAL OF CHEMICAL RESEARCH 2007
Non-protected bromoalkenylfuran compounds (8a–c)
do not proceed cycloaddition even under forced condition.
Therefore, tert-butoxy, as a bulky protecting group, was
used as a steric buttress10 on nitrogen to encourage the
cycloaddition process. The N-alkylated derivatives (9a–c)
were heated as solution in toluene at temperatures between
95 and 110°C. Of these derivatives the carbamate (9a),
showed greatest degree of intra-molecular cycloaddition; at
110°C, 45% of the cycloadduct (10a) formed, the remainder
being uncyclised starting material. According to the our
previous X-ray crystallographic report11 on (9b) as an
example; the molecules are linked only by weak van der
Waals interactions and it is found that the bromo attached
cyclohexane ring adopts a half-chair conformation with
torsion angle as given. The Br–C bond distance [1.939(9)
Å] is not significantly different from the value reported for
a pure Br–C single bond (1.94 Å).12 Presumably, the position
of dien-dienophile to each other is the main reason of modest
yields.
However, this facile thermal closure gives an unusual
tetracycles, possessed a quaternary carbon with a bromine
atom. Additionally, the process could also be an initiation step
to the some problematic intermediate of synthetic projects,
like in which, even nitrogen tricycle opens and gives acyclic
product as soon as the adjacent carbonyl group has been
reduced.13
In order to utilise our chemistry, we also achieved the
cycloaddition process in a commercial microwave under
solvent free condition. It is found that, 12 min irradiation for
(11a–b)3b gives the best result, further irradiation decomposes
the furans. Although, the yields was slightly lower than the
thermal process, the considerable time saving make this
procedure as an alternative application (Fig. 3).14,15
decomplexation affords the enol (15a–b), which undergoes
hydrogen bromide elimination to fused aromatic derivatives
(13a–b).
Once again, thermal IMDAF reaction could be used as a
key step as an entrance to more complex fused ring systems in
combinatorial organic chemistry. Additionally, intramolecular
Diels–Alder cycloadditon process of furans is achievable in
a microwave under solvent free condition. Utility of thermal
IMDAF reaction was shown by transforming heteroaromatic
compounds to the bicycle-benzoaromatic compounds. Further
progress has been carrying out about to cleavage of oxa-
bridge by using different Lewis acids and will be reported in
due course.
Experimental
Solvents and reagents were freshly distilled as follows:
tetrahydrofuran (THF) and diethyl ether (E) were distilled from
sodium/benzophenone; dichloromethane (DCM) and toluene
were distilled from calcium hydride. Reactions were monitored
by thin layer chromatography (TLC) using pre-coated silica plates
(Macharey Nagel sil G UV254). Compounds were visualised using
UV fluorescence, alkaline potassium permanganate solution or acidic
cerium (IV) sulfate solution. Column chromatography was carried out
Macharey Nagel Kieselgel 60 (230–240 mesh). 1H NMR spectra were
recorded on a Bruker 300 MHz DPX 300 spectrometer. The chemical
shifts are quoted in ppm, as d values downfield of tetramethylsilane
(TMS) or relative to the residual solvent resonance. IR spectra were
recorded on a Perkin-Elmer 1720 spectrophotometer; solid samples
were recorded using potassium bromide discs, and liquid samples
were recorded as thin films. Elemental analysis (EA) were carried out
by the microanalytisches laborataorium des institüts für Organische
und Biomoleculare Chemie der Universitat Gottingen, electron
ionisation mass spectra (EI, 70eV) were obtained on a Fisions VG
Autospec mass spectrometer.
Synthesis of furanyl amines (8a–c)
To a stirred solution of furfurylamine (7a–c) (7a,b supplied from
Fluka, Cat. No: 48120, 7c supplied from Aldrich, Cat. No: 415626)
(11.66 mmol) in THF (40 ml) was added 2,3-dibromocyclopentene or
2,3-dibromocyclohexene (5.83 mmol) and the resulting solution was
heated to reflux for 12 h. A portion of potassium carbonate (3.70 g,
26.02 mmol) was then added, and the reaction mixture was heated at
reflux for a further 48 h. On cooling, a precipitate was formed which
was washed with diethyl ether (3 × 25 ml). The filtrate was extracted
with 10% NaOH (40 ml) and the combined organic phases were
dried over MgSO4, filtered and concentrated under reduced pressure.
The residue was subjected to flash column chromatography to afford
following compounds;
2-Bromo-N-(furan-2-ylmethyl)cyclopent-2-en-1-amine (8a): Col-
ourless oil, (1.27 g, 90%). TLC, (hexane: EtOAc (7:3)), Rf: 0.32;
υmax (thin film)/cm-1: 3323 (w, N–H), 2924 (s, C–H), 2851 (w, C–H),
1153 (s, C–O), 607 (w, C–Br); δH (300 MHz, CDCl3): 7.30(d, 1H,
J = 1.8 Hz), 6.25 (dd, 1H, J1 = 1.8 Hz, J2 = 3.1 Hz, AB), 6.20 (d, 1H,
J = 3.1 Hz, AB), 5.98 (dd, 1H, J1 = 2.3 Hz, J2 = 3.8 Hz), 3.83–3.70
(m, 3H), 3.45 (brs, NH), 2.39–1.78 (m, 4H); δC (75.5 MHz, CDCl3):
152.7 (q), 142.1, 134.2, 123.3 (q), 110.3, 107.6, 65.9, 42.3, 30.8, 28.8;
m/z: 244 [M+ + H (81Br), 38%], 242 [M+ + H (79Br), 38%], 162 [M+
(81Br)–(81Br), 1.4%], 147 [(C5H681Br)+, 15%], 81 [(C5H5O)+; 100%],
EA. (C10H12BrNO): Calculated (Found)%: 49.61 (49.57)% C, 5.00
(5.16)% H, 5.79 (5.85)% N.
2-Bromo-N-(furan-2-ylmethyl)cyclohex-2-en-1-amine (8b): Col-
ourless oil, (1.38 g, 92%). TLC, (hexane: EtOAc (8:2)), Rf: 0.52;
υmax (thin film)/cm-1: 3330 (w, N–H), 2933 (s, C–H), 2859 (w, C–H),
1170 (s, C–O), 600 (w, C–Br); δH (300 MHz, CDCl3): 7.37 (d, 1H,
J = 2.0 Hz), 6.31 (dd, 1H, J1 = 2.0 Hz, J2 = 3.1 Hz, AB), 6.22 (d, 1H,
J = 3.1 Hz, AB), 6.19–6.16 (m, 1H), 3.88 (d, 1H, J = 12.4 Hz, AB),
3.77 (d, 1H, J = 12.4 Hz, AB), 3.32–3.30 (m, 1H), 2.11–1.57 (m,
6H), 1.26 (brs, NH); δC (75.5 MHz, CDCl3): 155.7 (q), 143.8, 134.6,
127.8 (q), 112.1, 109.0, 59.7, 45.4, 31.2, 29.9, 20.1; m/z: 258 [M+ +
H (81Br), 36%], 256 [M+ + H (79Br), 36%], 190 [M+(81Br)–(C4H3O),
6%], 176 [M+(81Br)–(C5H5O), 20%], 174 [M+(79Br)–(C5H5O), 20%]
96 [(C5H6ON)+, 20%], 81 [(C5H5O)+; 100%]; EA.(C11H14BrNO):
Calculated (Found)%: 51.58 (51.60)% C, 5.51 (5.48)% H, 5.47
(5.47)% N.
Treatment of (12a–b) with borontrifluorate-etherate in
dichloromethane at –78°C afforded the isobenzo-furanol
and thiophenol moieties, (13a–b) in 76% and 72% yields.
A mechanistic rationale for the formation of (13a–b) is also
outlined in Fig. 4. The mechanism presumably involves the
Lewis Acid (BF3.Et2O) catalysed ring opening of (12a–b) to
form allylic cation (14a–b) which upon proton exchange and
Br
MW
(2450 MHz)
HO
BF3.Et2O
X
X
Br
O
X
O
CH2Cl2
– 78°C
12 min
13a
13b
76%
72%
11a
11b
X= O
X= S
12a
12b
32 %
30%
Fig. 3
BF3.Et2O
CH2Cl2
X
X
.O.
LA
-78°C – 0°C, 3h
HO
Br
12a–b
RT, 4h
X= O, S
13a–b
–HBr
+
+
X
X
X
HO
LAO
LAO
Br
H
Br
Br
14a–b
15a–b
2-bromo-N-((5-methylfuran-2-yl)methyl)cyclohex-2-en-1-amine
(8c): Colourless oil, (1.46 g, 93%). TLC, (hexane: EtOAc (8:2)),
Fig. 4
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JOURNAL OF CHEMICAL RESEARCH 2007 119
Rf: 0.50; υmax (thin film)/cm-1: 3316 (w, N–H), 2927 (s, C–H), 2860
(w, C–H), 1180 (s, C–O), 600 (w, C–Br); δH (300 MHz, CDCl3): 6.12
(s, 1H), 6.02 (s, 1H), 5.80 (s, 1H), 3.75 (d, 1H, J = 12.2 Hz, AB),
3.65 (d, 1H, J = 12.2 Hz, AB), 3.27 (s, 1H), 2.20 (s, 3H), 2.05–1.67
(m, 6H), 1.53 (brs, NH); δC (75.5 MHz, CDCl3): 151.7 (q), 151.5 (q),
132.6, 125.9 (q), 107.9, 105.9, 57.6, 43.5, 29.2, 27.9, 18.2, 13.6; m/z:
271 [M+(81Br), 11%], 269 [M+(79Br), 11%], 190 [M+(81Br)–(81Br),
4%], 110 [ (C6H8ON) 19%], 95 [ (C6H7O) 100%]; EA.(C12H16BrNO),
Calculated (Found)%: 53.35 (53.51)% C, 5.97 (6.02)% H, 5.18
(5.10)% N.
Calculated (Found)%: 52.64 (52.65)% C, 5.89 (5.66)% H, 4.09
(4.15)% N.
tert-Butyl
8b-bromo-5a,6,7,8,8a,8b-hexahydro-5H-2a,5-epoxy-
cyclobenzo[cd]isoindole-1-carboxylate (10b): yellow solid, (0.26 g,
15%); m.p. 82–84°C; TLC, (hexane: EtOAc (4:1)): Rf: 0.18; υmax
(thin film)/cm-1: 2953 (s, C–H), 2924 (s, C–H), 1702 (s, C=O),
1169 (s, C–O), 709 (m, C–Br); δH (300 MHz, CDCl3): 6.44 (dd, 1H,
J = 1.8 Hz, J = 5.7, AB), 6.37 (d, 1H, J = 5.7 Hz, AB), 4.80 (d, 1H,
J = 1.8 Hz, AB), 4.64 (s, 1H), 4.28 (d, 1H, J = 12.5 Hz, AB), 3.52
(d, 1H, J = 12.5 Hz, AB), 2.31–1.40 (m, 7H), 1.19 (s, 9H); δC (75.5
MHz, CDCl3): 158.2 (q), 135.4, 134.7, 92.2 (q), 80.3 (q), 75.6,
70.1 (q), 54.2, 49.2,43.6, 28.4 (3 × C), 25.7, 21.5, 21.0; m/z: 357
[M+(81Br), 3%], 355 [M+(79Br), 3%], 256 [M+(81Br)–(Boc), 11%],
254 [M+(79Br)–(Boc), 3%], 241 [M+(81Br)–(Boc + CH3), 6%], 161
[(C6H881Br), 25%], 159 [(C6H879Br), 6%]; EA. (C16H22BrNO3),
Calculated (Found)%: 53.94 (53.90)% C, 6.22 (6.27)% H, 3.93
(3.92)% N.
Synthesis of furfuryl carbamides (9a–c)
To a stirred solution of amine (8a–c) (5.35 mmol) and di-tert-
butoxy dicarbonate (BOC)2O (1.17 g, 5.35 mmol) in DCM (10 ml)
was added N,N-dimethylaminopyridine (0.07 g, 0.54 mmol) at 0°C.
The reaction mixture was stirred for 2 hours at ambient temperature
and then concentrated under vacuum. The residue was subjected to
flash column chromatography to afford the precursors;
tert-Butyl 2-bromocyclopent-2-en-1-yl-(2-furylmethyl)carbamate
(9a): Colourless oil, (1.61 g, 88%). TLC, (hexane: EtOAc (7: 3)): Rf:
0.73; υmax (thin film)/cm-1: 2977 (s, C–H), 2929 (s, C–H), 1702 (s,
C=O), 1169 (s, C–O), 603 (m, C–Br). δH (300 MHz, CDCl3): 7.28
(d, 1H, J = 1.8 Hz), 6.28 (dd, 1H, J1 = 1.8 Hz, J2 = 3.0 Hz), 6.13–5.97
(m, 2H), 4.57–4.41 (m, 1H), 4.30 (d, 1H, J = 12.0 Hz), 3.95 (d, 1H,
J = 12.0 Hz), 2.30–1.92 (m, 4H), 1.40 (s, 9H); δC(75.5 MHz, CDCl3):
155.5 (q), 152.3 (q), 141.4, 135.0, 122.0 (q), 110.3, 106.9, 80.2 (q),
65.0, 40.1, 30.7, 28.3 (3 × C), 27.0; m/z (GC–MS): 343 [M+(81Br),
5%], 341 [M+(79Br), 5%], 286 [M+(81Br)–(tBu), 20%], 284 [M+(79Br)–
(tBu), 21%], 205 [M+(81Br)–(tBu + 81Br), 35%], 139 [M+(81Br)–(tBu +
C5H681Br), 75%], 81, 57; EA. (C15H20BrNO3), Calculated (Found)%:
52.64 (53.44)% C; 5.89 (5.96)% H, 4.09 (3.62)% N.
tert-Butyl 2-bromocyclohex-2-en-1-yl-(2-furylmethyl)carbamate
(9b): Colourless crystals, (1.52 g, 80%); m.p. 69–71°C;TLC, (Hexane:
EtOAc (4:1)): Rf: 0.75; υmax (thin film)/cm-1: 2975 (s, C–H), 2933
(s, C–H), 1702 (s, C=O), 1164 (s, C–O), 607 (m, C–Br). δH (300 MHz,
CDCl3): 7.32 (d, 1H, J = 1.9 Hz), 6.34–6.30 (m, 1H), 6.24 (dd, 1H,
J1 = 1.9 Hz, J2 = 3.1 Hz, AB), 6.14 (d, 1H, J = 3.1 Hz, AB), 4.92–4.90
(m, 1H), 4.51 (d, 1H, J = 12.4 Hz, AB), 3.92 (d, 1H, J = 12.4 Hz,
AB), 2.13–1.58 (m, 6H), 1.43 (s, 9H); δC (75.5 MHz, CDCl3): 155.3
(q), 153.7 (q), 143.4, 133.5, 127.3 (q), 113.4, 109.1, 82.2 (q), 58.0,
45.1, 29.7, 29.0 (3 × C), 28.4, 21.5; m/z: 357 [M+(81Br), 10%], 355
[M+(79Br), 10%], 300 [M+(81Br)–(tBu), 15%], 298 [M+(79Br)–(tBu),
15%], 256 [M+(81Br)–(Boc), 100%], 254 [M+(79Br)–(Boc), 100%],
161, 81, 57; EA.(C16H22BrNO3), Calculated (Found)%: 53.94
(53.61)% C, 6.22 (6.51)% H, 3.93 (3.70)% N.
tert-Butyl 2-bromocyclohex-2-en-1-yl[(5-methylfuran-2-yl)methyl]
carbamate (9c): Colourless crystals, (1.63 g, 82%); m.p. 65–67°C;
TLC, (hexane: EtOAc (4:1)): Rf: 0.72; υmax (thin film)/cm-1:
2986 (s, C–H), 2945 (s, C–H), 1716 (s, C=O), 1164 (s, C–O), 610
(m, C–Br). δH (300 MHz, CDCl3): 6.35–6.32 (m, 1H), 6.00 (d, 1H,
J = 3.0 Hz, AB), 5,88 (d, 1H, J = 3.0 Hz, AB), 4.70–4.90 (m, 1H),
4.45 (d, 1H, J = 12.1 Hz, AB), 3.80 (d, 1H, J = 12.1 Hz, AB), 2.26 (s,
3H), 2.11–1.55 (m, 6H), 1.45 (s, 9H); δC (75.5 MHz, CDCl3): 155.6
(q), 151.3 (q), 150.6 (q), 134.4, 124.3, 107.5, 106.2, 80.1 (q), 57.4,
41.3, 29.6, 28.3 (3 × C), 27.4, 21.1, 13.5.; m/z: 371 [M+(81Br), 1%],
369 [M+(79Br), 1%], 270 [M+(81Br)–(Boc), 6%], 268 [M+(79Br)–
(Boc), 3%], 161 [(C6H881Br), 22%], 159 [(C6H879Br), 21%], 81, 79;
EA. (C17H24BrNO3), Calculated (Found)%: 55.14 (55.29)% C, 6.53
(6.24)% H, 3.78 (3.80)% N.
tert-Butyl 8b-bromo-5-methyl-5a,6,7,8,8a,8b-hexahydro-5H-2a,5-
epoxycyclobenzo[cd]isoindole-1-carboxylate (10c): As yellow solid,
(0.31 g, 17%); m.p. 85–87°C; TLC, (hexane: EtOAc (4:1)): Rf: 0.16;
υmax (thin film)/cm-1: 2982 (s, C–H), 2942 (s, C–H), 1716 (s, C=O),
1168 (s, C–O), 614 (m, C–Br); δH (300 MHz, CDCl3): 6.32 (d, 1H,
J = 5.2 Hz, AB), 6.31 (d, 1H, J = 5.2 Hz, AB), 4.64 (s, 1H), 4.25 (d,
1H, J = 12.4 Hz, AB), 3.66 (d, 1H, J = 12.4 Hz, AB), 2.31 (s, 3H),
2.26–1.45 (m, 7H), 1.32 (s, 9H); δC (75.5 MHz, CDCl3): 151.5 (q),
132.2,131.8, 89.8 (q), 85.0 (q), 80.3 (q), 69.4 (q), 55.8, 52.9, 49.5,
28.4 (3 × C), 24.2, 21.0, 20.6, 17.5; m/z: 371 [M+(81Br), 5%], 369
[M+(79Br), 5%], 314 [M+(81Br)–(tBu), 6%], 270 [M+(81Br)–(Boc),
95%], 268 [M+(79Br)–(Boc), 96%],161 [(C6H881Br), 11%], 159
[(C6H879Br), 11%]; EA. (C17H24BrNO3), Calculated (Found)%: 55.14
(55.19)% C, 6.53 (6.43)% H, 3.78 (3.92)% N.
Synthesis of (13a–b)
To a solution of and bromo-oxa and thio heterotricycles (12a–b)
[synthesised as in ref. 2d] (0.80 mmol) in dry DCM (5 ml) cooled to
–78°C under N2 was added BF3·Et2O (0.11 ml, tech 50%, 0.88 mmol)
in DCM (5 ml) over 3 min. After being stirred at same temperature
for 15 min, the reaction mixture was warmed to 0°C over period of
3 h. The cooling bath was removed and the reaction mixture was
stirred at room temperature for another 4 h. The reaction mixture
was then diluted with water (5 ml) and the layers were separated.
The aqueous layer was further extracted with DCM (10 ml) and
the combined organic layers were washed with water (2 × 4 ml),
dried (anhydrous MgSO4) and concentrated in vacuo. The residue
was subjected to flash column chromatography to afford following
compounds.
1,3-dihydro-2-benzofuran-5-ol (13a): White solid, (0.08 g, 76%);
m.p. 67–69°C, TLC, (hexane: EtOAc (6:2)): Rf: 0.38; υmax (thin film)/
cm-1: 3226 (s, O–H), 2929 (s, C–H), 2867 (s, C–H), 1030 (s, C–O);
δH (300 MHz, CDCl3): 7.08 (d, 1H, J = 8.1 Hz, AB), 6.74 (d, 1H,
J = 8.1 Hz, AB), 6.71 (s, 1H), 5.06 (s, 4H), 3.61 (s, OH); δC (125
MHz, CDCl3): 155.4 (q), 140.9 (q), 130.9 (q), 121.8, 114.6, 106.4,
73.4, 73.2; m/z (GC–MS): 135 [M+–(H), 34%], 119 [M+–(OH),
13%], 75[C6H3, 22%]; EA. (C8H8O2), Calculated (Found)%: 70.57
(70.69)% C, 5.92 (6.14)% H.
Cycloaddition reactions for (10a–c)
1,3-dihydro-2-benzothiophene-5-ol (13b): yellow solid, (0,09 g,
72%); m.p. 62–64°C TLC, (hexane: EtOAc (6:2)): Rf: 0.43; υmax (thin
film)/cm-1: 3365 (s, O–H), 2920 (s, C–H), 2851 (s, C–H), 1100 (s,
C–O), 1026 (s, C–S); δH (300 MHz, CDCl3): 6.90 (d, 1H, J = 8.4 Hz,
AB), 6.72 (d, 1H, J = 8.4 Hz, AB), 6.51 (s, 1H), 4,97 (s, 4H), 4,25
(s, OH); δC (125 MHz, CDCl3): 154.2 (q), 138.2 (q), 131,0 (q),
122.6, 115.0, 104.3, 73.4, 73.3; m/z (GC–MS): 151 [M+–(H), 46%],
135 [M+–(OH), 8%], 75[C6H3, 20%]; EA. (C8H8OS), Calculated
(Found)%: 63.13 (63.31)% C, 5.30 (5.22)% H.
The furans (9a–c) (5 mmol) was heated up to 110°C in 10 ml of
toluene for 4 days at which time the reaction mixture was cooled and
concentrated. Purification by column chromatography afforded the
cycloadducts, and in all cases, the polarity of the cycloadduct was
greater that its precursor.
tert-Butyl 7b-bromo-5,5a,6,7,7a,7b-hexahydro-2a,5-epoxycyclo-
penta[cd]isoindole-1-carboxylate (10a): White solid, (0.77 g, 45%);
m.p. 77–79°C; TLC, (hexane: EtOAc (7:3)): Rf: 0.40; υmax (thin
film)/cm-1: 2980 (s, C–H), 2930 (s, C–H), 1716 (s, C=O), 1148 (s,
C–O), 612 (m, C–Br). δH (300 MHz, CDCl3): 6.59–6.50 (m, 2H),
4.84 (d, 1H, J = 1.5 Hz), 4.40 (t, 1H, J = 8.0 Hz), 4.06–3.88 (m, 2H),
2.30–2.16 (m, 1H), 1.93–1.85 (m, 2H), 1.66–1.58 (m, 1H), 1.45 (s,
9H); δC (75.5 MHz, CDCl3): 155.2 (q), 143.2,142.0, 95.4 (q), 80.3
(q), 79.7, 70.3 (q), 62.4,51.0, 49.2, 28.7 (3 × C), 25.4, 20.1; m/z: 343
[M+(81Br), 1%], 341 [M+(79Br), 1%], 286 [M+(81Br)–(tBu), 30%],
284 [M+(79Br)–(tBu), 29%], 205 [M+(81Br)–(tBu + 81Br), 85%],
139 [M+(81Br)–(tBu + C5H681Br), 100%], 81, 57. EA. (C15H20BrNO3),
We thank The Scientific & Research Council of Turkey
(TUBITAK, PN: 2377(103T121)) for generous financial
support of this work.
Received 16 January 2007; accepted 28 February 2007
Paper 07/4413
doi:10.3184/030823407X191967
PAPER: 06/4413

120 JOURNAL OF CHEMICAL RESEARCH 2007
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