Furo[3,4-b]benzofurans: Synthesis and reactions

Article abstract of DOI:10.1039/b000619j

Starting with coumarin (1) furo[3,4-b]benzofuran 4 was synthesized using the Hamaguchi-Ibata methodology. Intermolecular Diels-Alder reactions provide compounds 5-8. In a [4 + 3] cycloaddition reaction with oxyallyl compound 9 was obtained. The C-annulated furans 16a (in situ) and 16b have been prepared by a similar methodology starting with 10a,b. In an intramolecular Diels-Alder reaction compounds 17a,b were obtained. Computational studies concerning the reactivity of furo[3,4-b]benzofurans in inter- and intramolecular Diels-Alder reactions using both semiempirical (AM1, PM3) and density functional theoretical methods (B3LYP/6-31G*) are reported.

Full text of DOI:10.1039/b000619j

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Furo[3,4-b]benzofurans: synthesis and reactions
Tim Traulsen and Willy Friedrichsen
Institute of Organic Chemistry, University of Kiel, Otto-Hahn-Platz 4, D-24098 Kiel, Germany
1
Received (in Cambridge, UK) 24th January 2000, Accepted 7th March 2000
Starting with coumarin (1) furo[3,4-b]benzofuran 4 was synthesized using the Hamaguchi–Ibata methodology.
Intermolecular Diels–Alder reactions provide compounds 5–8. In a [4 ϩ 3] cycloaddition reaction with oxyallyl
compound 9 was obtained. The C-annulated furans 16a (in situ) and 16b have been prepared by a similar
methodology starting with 10a,b. In an intramolecular Diels–Alder reaction compounds 17a,b were obtained.
Computational studies concerning the reactivity of furo[3,4-b]benzofurans in inter- and intramolecular Diels–Alder
reactions using both semiempirical (AM1, PM3) and density functional theoretical methods (B3LYP/6-31G*) are
reported.
in the formation of a 1:2 adduct (8)17 in 35% yield. A [4 ϩ 3]
Introduction
cycloaddition with oxyallyl18,19 (generated from 2,4-dibromo-
pentanone with NaI–Cu in acetonitrile) gave compound 9
(as cis-endo, cis-exo mixture).
Annulated derivatives of benzofuran A1 (Scheme 1) constitute
Intramolecular cycloadditions of C-annulated furans offer the
possibility for the preparation of a great variety of polycyclic
systems.20 Especially 2-benzofurans have been used repeatedly
for this purpose.21,22 This type of reaction has also been carried
out with suitably substituted furo[3,4-b]benzofurans (16a,b).
The starting materials are available as follows: saponification of
3a yields 10a which on treatment with acetyl chloride gives the
corresponding anhydride 11. Nucleophilic ring opening with
methanol occurs regioselectively23 to give monoester 12a. The
second regioisomer (14) has been prepared from 3a by (regio-
selective) transesterification with benzylic alcohol (to 13a with
13b as by-product) and subsequent catalytic hydrogenation.
Esterification of 14 with O-pentenyl-N,NЈ-dicyclohexyliso-
urea25 (to 15a) with subsequent diazotransfer gives 15b. Treat-
ment of 15b with Rh2(OAc)4 and subsequently with ZnI2 yields
17a (via 16a, not isolated) in 47% yield. A methoxy-substituted
dioxabenzo[a]fluorene (17b) was similarly accessible. Starting
with dicarboxylic acid 10b,26 anhydride 11b was prepared with
acetyl chloride and without further purification treated with
methanol to give 12b. Esterification with O-pentenyl-N,NЈ-
dicyclohexylisourea with subsequent diazo transfer gives 15d.
Treatment of this diazoester with Rh2(OAc)4 yields furo[3,4-b]-
benzofuran 16b, which in this case was isolated as a stable
crystalline compound. The annulated furan 17b was available
in a one-step reaction from 15d after heating with Rh2(OAc)4
and subsequent treatment with ZnI2 in 39% yield. Obviously
furo[3,4-b]benzofurans of type 4 and 16a,b offer a convenient
way to prepare condensed systems with a 1-benzofuran moiety.
Although it was also possible to prepare diazoester 18b (trans-
esterification of 3a with allylic alcohol and diazo group transfer
with 4-azidosulfonylbenzoic acid) and 18e (from 14 with
O-pentenyl-N,NЈ-dicyclohexylisourea and subsequent diazo
transfer) intramolecular cycloadditions to 20 (or related com-
pounds) failed.
Scheme 1
a major class of natural products. It can be expected that
furo[3,4-b]benzofurans of type B offer the opportunity to give
access to a variety of condensed benzofuran derivatives, as it is
well known that C-annulated furans of type C (A = benzo,2
furo,3 thiopheno,4,5 oxazolo,6 isoxazolo,7 thiazolo,6b,8 indolo4f,9
and others2) as more or less stable analogues of o-quino-
dimethanes10 may serve as starting materials for the synthesis
of a great variety of polycyclic systems (e.g., C→D). In this
paper we report on a new synthesis of furo[3,4-b]benzofurans11
and some cycloaddition reactions of this system.
Preparative results
The starting material for furo[3,4-b]benzofuran 4 (3a) (Scheme
2) has been reported in the literature.12 In our hands the prepar-
ation of this compound from coumarin 1 via diesters 2a and 2b
could be improved considerably (see Experimental section).
Diazo group transfer (Regitz reaction)13 with 4-azidosulfonyl-
benzoic acid14–DBU in acetonitrile gives 3b as citrine crystals
in 77% yield. Nitrogen extrusion under the catalytic influence
of Rh2(OAc)4 (Hamaguchi–Ibata reaction)15 results in the
generation of 4 as colorless crystals in 78% yield. Although
less reactive than other C-annulated furans (see Computational
results), compound 4 undergoes Diels–Alder reactions with
N-phenylmaleimide and naphtho-1,4-quinone (ZnI2 as Lewis
catalyst)16 to form cycloadducts 5 and 6. With benzo-1,4-
quinone compound 7 an endo–exo mixture is obtained. Adding
ZnI2 to the reaction mixture of 4 and benzo-1,4-quinone results
Computational results
(a) As has been pointed out in the preceding section the ring
opening reaction of anhydrides 11a,b with methanol occurs
regioselectively to give 12a,b.23,27 From a computational point
of view this result is not unexpected. If one assumes that in the
first—fast and reversible—reaction step orthoesters of type 21
and 22 are formed (Scheme 3), then the product ratio of the
DOI: 10.1039/b000619j
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398
This journal is © The Royal Society of Chemistry 2000
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Scheme 2
regioisomeric methyl esters depends on the thermodynamic
stability of 21 and 22. An ab initio calculation (density func-
tional theory, DFT)28,29,30 reveals, that—at least for the gas
phase—21 is more stable than 22 by 6.7 kcal molϪ1. This result
also holds for similar reactions.22
(b) Qualitative observations suggest that furo[3,4-b]benzo-
furans are less reactive in Diels–Alder reactions than corre-
sponding 2-benzofurans. This is in agreement with ab initio
studies on model systems. These computations reveal that the
transition state energies (∆E(ts)) of the intermolecular reactions
(3) and (4) (Scheme 4) are 5 kcal molϪ1 higher than those for
reactions (1) and (2)22 (Tables 1 and 2). The introduction of
substituents into the diene (as in 29a,b; reactions (5), (6) and (7),
(8)) seems to have only a minor effect on ∆E(ts) (in contrast to the
corresponding values of 2-benzofuran).22
reaction (5) reveals similar transition state energies (Table 2).
Additionally, the transition state energies for the endo-products
(see e.g., Fig. 1) are generally higher than those for the exo-
products (see e.g., Fig. 2). According to these results com-
pounds 17a,b are probably formed in an exo cycloaddition
reaction with subsequent loss of water. In Table 3 the transition
state geometries of reactions (1)–(16) are given. As can be
seen from these values AM1 and PM3 calculations24 give
more tightly bound transition states than the B3LYP/6-31G*
methodology.31 In line with these results AM1 and PM3 transi-
tion state energies are higher than the B3LYP/6-31G* values.
Additionally, there is only a poor relationship between
∆E(ts)(B3LYP/6-31G*) and ∆E(ts)(PM3) (Fig. 3, r2 = 0.76).
Generally speaking, geometries of AM1 and PM324 transition
states may differ considerably from ab initio results. If the asyn-
A comparison of an intramolecular Diels–Alder reaction
(e.g. (13), Scheme 5) with the corresponding intermolecular
1388
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Table 1 DFT28 energies (E)a,b for 26–40 and transition state energies
[E(ts)] of reactions (1)–(16)c (in arbitrary units)
chronicity of the transition states (defined as ∆r = (rac Ϫ rbd)/
(rac ϩ rbd) × 100, for a definition of a, b, c, d see Scheme 4)
for DFT and PM3 results is compared, again only a poor
relationship is observed (Fig. 4, r2 = 0.67). For these reasons
it seems inappropriate to carry out single point ab initio
calculations of transition state geometries, which have been
optimized on a semiempirical (e.g., PM3) level.32,33
Compound
E
Reaction
E(ts)
26
Ϫ535.07523
Ϫ613.68988
Ϫ612.43004
Ϫ877.47973
Ϫ877.48298
Ϫ956.08503
Ϫ956.08331
Ϫ954.82645
Ϫ954.82529
Ϫ805.61808
Ϫ805.63839
Ϫ805.63116
Ϫ805.61660
Ϫ1033.49992
Ϫ805.64314
Ϫ1033.51541
Ϫ805.62797
Ϫ1033.50005
Ϫ1185.92821
Ϫ1185.93879
Ϫ1185.92628
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
Ϫ613.62985
Ϫ612.36434
Ϫ956.03358
Ϫ954.76995
Ϫ956.03362
Ϫ954.76984
Ϫ805.57739
Ϫ805.57406
Ϫ805.58270
Ϫ805.56911
Ϫ1033.46464
Ϫ1033.45053
Ϫ1185.88490
Ϫ1185.88306
27
28
29a
29b
30a
30b
31a
31b
32
33
34
35a
35b
36a
36b
37a
37b
38
39
40
a B3LYP/6-31G*. b Ethylene: Ϫ78.5876 arbitrary units, acetylene:
Ϫ77.32565 arbitrary units. c For computational reasons the Hesse
matrix of the transition states has been calculated only for selected
examples. In all cases only one negative eigenvalue was found.
Fig. 1 Transition state geometry for reaction (14) (B3LYP/6-31G*).
Scheme 3 Results of ab initio calculations (DFT; B3LYP/6-31G*).28
Fig. 2 Transition state geometry for reaction (13) (B3LYP/6-31G*).
Scheme 4
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Materials
Experimental
All solvents were dried or purified using standard procedures.
All mps were determined on a Dr Tottoli melting point appar-
atus and are uncorrected. IR spectra were recorded on a Perkin-
Elmer FTIR 1600 spectrophotometer. NMR spectra: Bruker
3-(2-Methoxycarbonylmethoxyphenyl)acrylic acid methyl ester
1
DRX 500 (500 MHz: FT H NMR; 125 MHz: 13C NMR);
Coumarin 1 (14.6 g, 100 mmol) was added to a solution of 2.4 g
(104 mmol) sodium in 35 ml dry methanol. After refluxing for
10 min, 16.0 g (105 mmol) of bromoacetic acid methyl ester was
added dropwise and refluxing was continued for a further 3.5 h.
The reaction mixture was cooled down to room temperature,
poured into 200 ml of ice–water and was left to stand over-
night. The organic layer was separated and the aqueous phase
was extracted four times with diethyl ether. The combined
organic phases were dried with sodium sulfate, evaporated and
the residue distilled under reduced pressure (bp 170 ЊC, 0.04
mbar). The product (19.4 g, 77%) was obtained as a yellowish
oil. It could also be purified by recrystallization from dry
Bruker AM 300 (300 MHz: FT 1H NMR; 75 MHz: 13C NMR);
Bruker AC 200 (200 MHz: FT 1H NMR; 50 MHz: 13C NMR);
internally referenced on Me4Si (CDCl3) or DMSO ([D6]-
DMSO). J values are given in Hz. UV spectra: Zeiss DMR 10
spectrophotometer; mass spectra: Finnigan MAT 8230 mass
spectrometer by using 70 eV ionization potential (EI) or the
chemical ionization (CI) (isobutane (2-methylpropane))
method. Radial chromatography was carried out with a
Harrison-Research Chromatotron on silica gel PF245 (Merck,
Darmstadt).
Table 2 Reaction energies (∆E) and transition state energies [∆E(ts)]
for reactions (1)–(16) (DFT28 results;a AM1 and PM3 results in paren-
theses); all values in kcal molϪ1
Table 3 Transition state geometries for reactions (1)–(16) (B3LYP/
6-31G*, AM1, PM3)
Reaction
∆Eb
∆E(ts)c
a,b
a,b
Reaction
r1
r2
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
Ϫ29.8 (Ϫ34.8, Ϫ32.5)
Ϫ34.4 (Ϫ28.9, Ϫ28.3)
Ϫ17.1 (Ϫ19.2, Ϫ17.1)
Ϫ18.3 (Ϫ12.3, Ϫ12.7)
Ϫ11.2 (Ϫ17.7, Ϫ15.0)
Ϫ13.2 (Ϫ10.5, Ϫ10.3)
Ϫ8.1 (Ϫ13.4, Ϫ14.0)
Ϫ10.5 (Ϫ6.4, Ϫ9.4)
Ϫ12.7 (Ϫ14.4, Ϫ11.3)
Ϫ8.2 (Ϫ6.7, Ϫ6.7)
Ϫ22.9 (Ϫ15.2, Ϫ14.8)
Ϫ7.1 (Ϫ6.2, Ϫ5.8)
Ϫ9.7 (Ϫ11.1, Ϫ14.3)
Ϫ0.1 (Ϫ2.4, Ϫ5.2)
15.4 (20.2, 25.2)
17.8 (28.2, 30.5)
20.6 (27.2, 30.9)
22.9 (35.7, 36.4)d
21.1 (25.8, 30.3)
22.2 (34.1, 36.3)
23.1 (28.6, 29.9)
24.3 (36.9, 36.0)
25.5 (30.3, 35.7)
27.6 (33.9, 35.8)
21.3 (29.2, 31.7)
29.8 (35.9, 38.7)
22.1 (30.3, 30.1)
31.0 (37.1, 37.2)
27.2 (31.9, 33.9)
28.3 (34.4, 35.7)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
2.260 (2.146, 2.188)
2.277 (2.101, 2.138)
2.163 (2.071, 2.123)
2.181 (2.012, 2.081)
2.189 (2.142, 2.170)
2.223 (2.155, 2.122)
2.120 (2.026, 2.125)
2.128 (1.919, 2.080)
2.263 (2.169, 2.195)
2.102 (2.059, 2.123)
2.157 (2.058, 2.130)
2.211 (2.086, 2.129)
2.185 (2.105, 2.157)
2.248 (2.145, 2.157)
2.244 (2.152, 2.194)
2.127 (2.059, 2.137)
2.260 (2.146, 2.188)
2.277 (2.101, 2.138)
2.229 (2.103, 2.138)
2.245 (2.088, 2.092)
2.169 (2.060, 2.145)
2.166 (1.966, 2.095)
2.209 (2.153, 2.167)
2.236 (2.197, 2.117)
2.169 (2.050, 2.122)
2.264 (2.096, 2.144)
2.308 (2.163, 2.196)
2.173 (2.091, 2.154)
2.181 (2.104, 2.167)
2.077 (2.032, 2.127)
2.145 (2.071, 2.139)
2.143 (2.107, 2.150)
Ϫ6.6 (Ϫ12.1, Ϫ13.0)
1.2 (Ϫ2.5, Ϫ4.5)
a B3LYP/6-31G*. b ∆E = E(product) Ϫ E(reactant). c Energy difference
between the initial state and the transition state. d ∆E(ts) = 16.8 kcal
molϪ1 (B3LYP/6-31G*//PM3).
a Values in Å. b Values in parentheses: results of AM1 and PM3
calculations.24
Scheme 5
1390
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mixture was heated for 15 min to 70 ЊC, cooled down to 0 ЊC
and poured into 100 ml of water. The mixture was acidified
with 2 M acetic acid and extracted three times with diethyl ether.
The ethereal layers were washed once with conc. sodium
bicarbonate solution, water and a saturated sodium chloride
solution, dried with magnesium sulfate and evaporated. The
viscous yellowish residue could be purified by distillation (bp
155 ЊC, 0.04 mbar) or by recrystallization from dry methanol to
provide 13.1 g (68%) colorless crystals with mp 53 ЊC.
νmax/cmϪ1 1735 (C᎐O, s), 1479 (C᎐C, s); λmax(EtOH)/nm (log
᎐
᎐
ε) 212 (3.772), 277 (3.503), 283 (3.454); δH(200 MHz; CDCl3)
2.77 (dd, 1H, C3-CH2, J1 5.45, J2 1.34), 2.80 (d, 1H, C3-CH2,
J 0.98), 3.73 (s, 3H, CH2-CO2-CH3), 3.81 (s, 3H, C2-CO2-CH3),
4.05 (dt, 1H, C3-H, J1 6.67, J2 6.50), 4.94 (d, 1H, C2-H, J 6.50),
6.84–6.98, 7.10–7.25 (2m, 4H, C4-H, C5-H, C6-H, C7-H);
δC(50 MHz; CDCl3) 42.77 (t, CH2), 46.30 (d, C3), 55.37 (q,
CH2-CO2-CH3), 56.08 (q, C2-CO2-CH3), 87.49 (d, C2), 113.52
(d, C7), 124.97 (d, C4), 127.71 (d, C5), 130.88 (s, C3a), 132.60
(d, C6), 162.11 (s, C7a), 174.29 (s, CH2-CO2-CH3), 174.91 (s,
C2-CO2-CH3); m/z 250 (21%, Mϩ), 191 (21), 190 (36), 177 (81),
131 (100); C13H14O5 requires: 250.08441. Found: 250.08510
(MS).
Fig. 3 ∆E(ts)(B3LYP/6-31G*) vs. ∆E(ts)(PM3); ∆E(ts)(B3LYP/6-
31G*) = 1.084 × ∆E(ts)(PM3) ϩ 1.579 (r2 = 0.76).
3-Bromo-3-methoxycarbonylmethyl-2,3-dihydrobenzofuran-2-
carboxylic acid methyl ester 2b
To a solution of 10.1 g (40 mmol) 2a in 250 ml of dry tetra-
chloromethane was added 7.6 g (43 mmol) of N-bromosuccin-
imide. The radical reaction was started by adding a trace of
dibenzoyl peroxide. The mixture was refluxed for 5 h under dry
conditions. After cooling down to 0 ЊC the mixture was filtered
and evaporated under reduced pressure. The viscous orange
residue was taken up in ethyl acetate, refluxed for 5 min with
active charcoal, filtered and evaporated. The colorless oily raw
product was crystallized from 100 ml of dry methanol at
Ϫ20 ЊC to yield 10.6 g (80%) of 2b as colorless crystals with mp
84 ЊC.
νmax/cmϪ1 1732 (C᎐O, s), 1711 (C᎐O, s), 750 (s); λmax(EtOH)/
᎐
᎐
nm (log ε) 203 (4.296), 220 (4.186), 275 (4.424), 285 (sh, 4.082);
δH(300 MHz; CDCl3) 2.20 (s, 1H, C2-H), 3.73 (s, 3H, CH2-CO2-
CH3), 3.99 (s, 3H, C2-CO2-CH3), 4.19 (s, 2H, C3-CH2), 7.33
(ddd, 1H, C5-H, J1 0.99, J2 7.05, J3 8.01), 7.48 (ddd, 1H, C6-H,
J1 1.31, J2 7.07, J3 8.39), 7.58 (ddd, 1H, C7-H, J1 0.91, J2 0.91,
J3 8.29), 7.64 (ddd, 1H, C4-H, J1 0.76, J2 1.31, J3 7.93); δC(50
MHz; CDCl3) 29.90 (t, CH2), 52.31 (q, CH2-CO2-CH3), 55.32
(q, C2-CO2-CH3), 112.35 (d, C7), 121.23 (d, C4), 122.13 (s, C3),
123.69 (d, C5), 127.91 (m, C3a), 128.11 (d, C6), 141.66 (s, C2),
154.40 (s, C7a), 160.35 (s, CH2-CO2-CH3), 170.27 (s, C2-CO2-
CH3); m/z 249 (100%, Mϩ), 250 (14), 251 (5).
Fig.
4
∆r(B3LYP/6-31G*) vs. ∆r(PM3); ∆r(B3LYP/6-31G*) =
2.044 × ∆r(PM3) Ϫ 0.169 (r2 = 0.67) (∆r = (rac Ϫ rbd)/(rac Ϫ rbd) × 100).
methanol. On cooling to Ϫ20 ЊC 20.2 g (80%) of colorless
crystals with mp 64 ЊC (70 ЊC)34 were obtained.
νmax/cmϪ1 1758 (C᎐O, s), 1631 (C᎐C, s), 1599 (m), 1576 (m),
᎐
᎐
764 (s); λmax(EtOH)/nm (log ε) 212 (4.218), 223 (4.172), 275
(4.226), 320 (3.491); δH(200 MHz; CDCl3) 3.81 (s, 3H,
CH2-CO2-CH3), 3.82 (s, 3H, CH-CO2-CH3), 4.72 (s, 2H, CH2),
3-Methoxycarbonylmethylbenzofuran-2-carboxylic acid methyl
ester 3a
A solution of 1.17 g (1.2 ml, 7.7 mmol) DBU in 0.8 ml dry
dichloromethane was added dropwise at room temperature
under nitrogen to a stirred solution of 2.48 g (7.6 mmol) 2b in
10 ml of dry dichloromethane. The reaction mixture was stirred
for about 1.5 h and afterwards subjected to column filtration on
silica gel. The filtrate was evaporated and the colorless oily
residue taken up with 15 ml of dry methanol. The product 3a
precipitated at room temperature as colorless crystals (1.83 g,
97%) with mp 82 ЊC.
6.66 (d, 1H, C1-CH᎐CH, J 16.36), 6.78 (dd, 1H, C5-H, J 0.85,
᎐
1
J2 8.42), 7.01 (ddd, 1H, C4-H, J1 0.79, J2 7.39, J3 7.39), 7.32
(ddd, 1H, C3-H, J1 1.59, J2 7.69, J3 8.18), 7.53 (dd, 1H, C6-H, J1
1.71, J2 7.81), 8.03 (d, 1H, C1-H, J 16.36); δC(50 MHz; CDCl3)
54.93 (q, CH2-CO2-CH3), 55.64 (q, CH-CO2-CH3), 68.78 (t,
CH2), 115.34 (d, C6), 122.47 (d, C5), 125.17 (d, C4), 127.28 (s,
C1), 132.76 (d, CH᎐CH-CO ), 134.60 (d, C6), 143.22 (d, CH᎐
᎐
᎐
2
CH-CO2), 159.79 (s, C2), 171.27 (s, CH2-CO2-CH3), 172.27 (s,
CH-CO2-CH3); m/z 250 (29%, Mϩ), 219 (14), 161 (100), 131
(44); C13H14O5 requires: 250.08412. Found: 250.08390 (MS).
νmax/cmϪ1 1732 (C᎐O, s), 1712 (C᎐O, s), 750 (s); λmax(EtOH)/
᎐
᎐
nm (log ε) 203 (4.281), 220 (4.127), 275 (4.354), 284 (sh, 4.300);
δH(200 MHz; CDCl3) 3.72 (s, 3H, CH2-CO2-CH3), 3.99 (s, 3H,
C2-CO2-CH3), 4.19 (s, 2H, C3-CH2), 7.26 (ddd, 1H, C5-H,
J1 0.98, J2 7.08, J3 7.81), 7.41 (ddd, 1H, C6-H, J1 1.34, J2 6.96,
J3 8.30), 7.52 (d, C7-H, J 8.06), 7.58 (d, C4-H, J 7.81); δC(75
MHz; CDCl3) 29.91 (t, CH2), 52.29 (q, CH2-CO2-CH3), 52.31
(q, C2-CO2-CH3), 112.35 (d, C7), 121.21 (d, C4), 122.22 (s, C3),
123.73 (d, C5), 127.88 (s, C3a), 128.08 (d, C6), 141.66 (s, C2),
3-Methoxycarbonylmethyl-2,3-dihydrobenzofuran-2-carboxylic
acid methyl ester 2a
A solution of 360 mg (16 mmol) sodium in 7 ml dry methanol
was added dropwise at room temperature to a stirred solution
of 19.4 g (77 mmol) 3-(2-methoxycarbonylmethoxyphenyl)-
acrylic acid methyl ester in 40 ml of dry methanol. The yellow
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154.40 (s, C7a), 160.33 (s, CH2-CO2-CH3), 170.25 (s, C2-CO2-
CH3); m/z 248 (48%, Mϩ), 216 (100), 189 (48), 188 (20), 159
(28); C13H12O5 requires: 248.06847. Found: 248.06830 (MS).
νmax/cmϪ1 1763 (C᎐O, s), 1717 (s), 1663 (s), 1247 (m), 750 (s);
λmax(EtOH)/nm (log ε) (sh, 4.583), 220 (4.531), 272 (4.392), 345
᎐
(3.936); δH(300 MHz; CDCl3) 4.13 (s, 3H, CO2-CH3), 4.56 (s,
3H, O-CH3), 7.38 (dd, 1H, C6-H, J1 7.03, J2 2.96), 7.41–7.51
(m, 5H, N-Ph), 7.61 (dd, 1H, C7-H, J1 7.82, J2 1.23), 7.68 (d,
1H, C8-H, J 8.37), 7.98 (d, 1H, C5-H, J 8.03); δC(125 MHz;
CDCl3) 53.28 (s, CO2-CH3), 62.54 (s, O-CH3), 112.43 (dd, C8),
117.22 (s, C10a), 118.64 (s, C3a), 121.84 (s, C4a), 123.13 (d, C5),
124.46 (d, C6), 125.31 (s, N-C1Ј), 126.82 (d, C2Ј), 128.81 (d,
C3Ј), 128.39 (s, C4b), 129.09 (d, C3Ј), 130.06 (d, C7), 131.89
(s, C4), 144.99 (s, C10), 149.77 (s, C9a), 157.70 (s, C8a), 164.54
(s, C1), 165.11 (s, C3), 165.93 (s, CO-CH3); m/z 401 (100%, Mϩ),
386 (10), 370 (19), 342 (20); C23H15NO6 requires: 401.08994.
Found: 401.08977 (MS).
3-[Diazo(methoxycarbonyl)methyl]benzofuran-2-carboxylic acid
methyl ester 3b
A solution of 426 mg (4.17 ml, 2.8 mmol) DBU in 10 ml dry
acetonitrile was added dropwise under nitrogen at room tem-
perature to a well-stirred suspension of 318 mg (1.4 mmol)
4-azidosulfonylbenzoic acid and 306 mg (1.2 mmol) 3a in 40 ml
dry acetonitrile. The yellow solution was stirred at room tem-
perature for 14 h, 40 ml of acetonitrile was evaporated under
reduced pressure and the oily orange residue purified by column
chromatography on silica gel with ether–pentane (1:1). The
solvent was evaporated and the residue recrystallized from dry
methanol to yield 260 mg (77%) yellow crystals with mp 121 ЊC
(decomp.).
12-Methoxy-6,11-dioxo-6,11-dihydro-13-oxaindeno[1,2-b]-
anthracene-5-carboxylic acid methyl ester 6
νmax/cmϪ1 2125 (C᎐N , s), 1714 (C᎐O, s), 753 (s); λmax(EtOH)/
᎐
᎐
2
A solution of 308 mg (1.3 mmol) of compound 4 in 20 ml dry
dioxane was added at 100 ЊC under nitrogen to a mixture of 198
mg (1.3 mmol) naphtho-1,4-quinone and 399 mg (1.3 mmol) of
zinc iodide in 20 ml dry dioxane. After further stirring for 30
min the reaction mixture was allowed to cool down to room
temperature. The precipitated crystals were collected, washed
with 1 M hydrochloric acid and water and dried under reduced
pressure over diphosphorus pentaoxide. The reaction yielded
391 mg (79%) of 6 as yellow crystals with mp 260 ЊC.
nm (log ε) 220 (4.232), 260 (4.297), 293 (4.183), 395 (1.785);
δH(300 MHz; CDCl3) 3.89 (s, 3H, CH2-CO2-CH3), 4.03 (s, 3H,
C2-CO2-CH3), 7.34 (ddd, 1H, C5-H, J1 1.09, J2 7.00, J3 8.06),
7.51 (ddd, 1H, C6-H, J1 1.34, J2 7.05, J3 8.41), 7.58 (ddd, 1H,
C7-H, J1 0.86, J2 1.01, J3 8.39), 7.70 (d, 1H, C4-H, J 7.98);
δC(75 MHz; CDCl3) 52.39 (q, CH2-CO2-CH3), 52.65 (q,
C2-CO2-CH3), 73.98 (s, CN), 112.31 (d, C7), 115.17 (s, C3),
123.35 (d, C4), 123.89 (d, C5), 126.70 (s, C3a), 128.54 (d, C6),
138.95 (s, C2), 154.64 (s, C7a), 159.36 (s, CH2-CO2-CH3),
165.09 (s, C2-CO2-CH3); m/z 274 (11%, Mϩ), 246 (41), 203
(100), 173 (38); C13H10N2O5 requires: 274.05900. Found:
274.05896 (MS).
νmax/cmϪ1 1723 (C᎐O, s), 1671 (s), 1371 (s), 1258 (s);
᎐
λmax(CH3CN)/nm (log ε) 215 (3.770), 245 (3.638), 290 (3.994),
375 (3.078); δH(500 MHz; CDCl3) 4.22 (s, 3H, CO2-CH3), 4.42
(s, O-CH3), 7.44 (dd, 1H, C3-H, J1 7.57, J2 0.73), 7.63 (ddd, 1H,
C2-H, J1 8.37, J2 7.19, J3 1.17), 7.70 (d, 1H, C1-H, J 8.36), 7.76
(dd, 1H, C8-H, J1 7.45, J2 1.51), 7.80 (dd, 1H, C9-H, J1 7.44,
J2 1.51), 7.89 (d, 1H, C4-H, J 7.45), 8.24 (dd, 1H, C10-H, J1
7.51, J2 1.34), 8.29 (dd, 1H, C7-H, J1 7.61, J2 1.09); δC(125
MHz; CDCl3) 53.31 (q, CO2CH3), 62.17 (q, O-CH3), 112.42 (d,
C1), 121.56 (s, C4b), 122.60 (d, C4), 123.51 (s, C5a), 123.81
(s, C11a), 124.45 (d, C3), 127.04 (d, C10), 127.24 (d, C7), 127.50
(s, C10a), 127.55 (s, C4a), 130.23 (d, C2), 132.46 (s, C6a), 133.68
(d, C8), 134.47 (d, C9), 134.93 (s, C5), 147.30 (s, C12), 150.95
(s, C12a), 157.50 (s, C13a), 168.94 (s, CO2Me), 182.11 (s, C6),
182.45 (s, C11); m/z 386 (100%, Mϩ), 355 (27), 327 (27), 299
(23); C23H14O6 requires: 386.07904. Found: 386.07890 (MS).
1-Methoxy-2,8-dioxacyclopenta[a]indene-3-carboxylic acid
methyl ester 4
A mixture of 305 mg (1.1 mmol) 3b and 10 mg (0.023 mmol)
dirhodium tetraacetate was refluxed in 25 ml dry toluene until
the yellow color of the diazo compound completely dis-
appeared. The progress of the cyclization reaction could also be
monitored by TLC chromatography with ether–pentane (1:1).
The solvent was evaporated, the residue taken up in ether–
pentane (1:1) and filtered through a short column of silica gel
to separate it from the catalyst. The filtrate was evaporated and
the residue recrystallized from dry methanol to give 214 mg
(78%) of compound 4 as colorless needles with mp 164 ЊC.
νmax/cmϪ1 1716 (C᎐O, s), 1669 (s), 1565 (s), 1299 (s), 1199 (s),
6,11-Epoxy-6-methoxy-7,10-dioxo-7,10-dihydrobenzo[b]-
naphtho[2,3-d]furan-11-carboxylic acid methyl ester 7
᎐
1145 (s), 1027 (s), 774 (m), 754 (m); λmax(CH3CN)/nm (log ε)
240 (3.771), 265 (sh, 3.582), 310 (3.582); δH(300 MHz; CDCl3)
3.98 (s, 3H, CO2-CH3), 4.23 (s, 3H, O-CH3), 7.31 (ddd, 1H, C5-
H, J1 1.06, J2 7.28, J3 7.73), 7.39 (ddd, 1H, C6-H, J1 0.63,
J2 1.09, J3 8.41), 7.49 (ddd, 1H, C7-H, J1 1.41, J2 7.23, J3 8.49),
8.05 (dd, 1H, C4-H, J1 0.81, J2 7.68); δC(75 MHz; CDCl3) 51.65
(q, OCH3), 59.41 (q, CO2CH3), 112.19 (dd, C7), 119.09 (ddd,
C3b), 120.05 (s, C8a), 123.39 (dd, C4), 124.89 (dd, C5), 127.53
(s, C3a), 129.85 (dd, C6), 130.05 (s, C1), 141.60 (s, C3), 158.58
(q, C7a), 164.19 (s, CO2Me); m/z 246 (63%, Mϩ), 203 (100), 173
(27), 88 (25); C13H10O5 requires: 246.05283. Found: 246.05280
(MS).
A solution of 35.3 mg (0.3 mmol) benzo-1,4-quinone in 10 ml
dry toluene was added at 50 ЊC dropwise to a solution of 78.8
mg (0.3 mmol) 4 in 10 ml dry toluene. The reaction mixture was
stirred at 50 ЊC for 2.5 h and for a further 16 h at room tem-
perature. The solvent was evaporated under reduced pressure at
50 ЊC, the residue taken up with dichloromethane and subjected
to column chromatography on alumina. The excess of benzo-
1,4-quinone and by-products of the reaction were eluted with
dichloromethane, whereas the product 7 was eluted with ethyl
acetate. After evaporation of the solvent an endo–exo-mixture
of 7 was obtained. Yellow crystals (11 mg, 10%) with mp 158–
160 ЊC.
10-Methoxy-1,3-dioxo-2-phenyl-2,3-dihydro-1H-9-oxa-2-aza-
cyclopenta[b]fluorene-4-carboxylic acid methyl ester 5
νmax/cmϪ1 1734 (C᎐O, s), 1661 (s), 1342 (m), 1304 (s), 1256
᎐
(m), 743 (w); λmax(EtOH)/nm (log ε) 226 (4.020), 285 (4.073);
δH(300 MHz; CDCl3) (signals marked with * and ** could not
be clearly assigned and could be interchanged) 3.49 (q, JAB
7.73), 3.69, 3.97, 4.16, 4.39 (4s, OCH3), 6.09 (q, JAB 10.47), 6.92
(s, 1H, C8-H*, C9-H**), 6.93 (s, 1H, C8-H*, C9-H**), 7.28–
7.88 (m, 4H, C1-H, C2-H, C3-H, C4-H); δC(75 MHz; CDCl3)
52.96 [53.36] (CO2CH3), 53.96 [62.08] (C6-OCH3), 112.42
[112.65] (C4), 122.53 [122.53] (C1), 124.41 [124.51] (C2), 121.27
[121.43] (C6), 123.03 [125.98] (C11), 122.53 [122.89] (C10a),
124.41 [124.51] (C6a), 127.28 [127.74] (C11b), 136.73 [137.76]
(C9), 138.73 [140.94] (C8), 145.36 [146.84] (C5a), 150.33
To a solution of 415 mg (2.4 mmol) of N-phenylmaleimide in
20 ml dry toluene 10 mg (0.023 mmol) of dirhodium tetra-
acetate was added. The mixture was heated to 80 ЊC and a solu-
tion of 165 mg (0.6 mmol) 3b in 20 ml dry toluene was added
slowly under nitrogen. After the complete addition of the diazo
compound 3b the reaction mixture was cooled down to room
temperature and stirred for a further 36 h. The solvent was
evaporated and the residue taken up with ethyl acetate. The
insoluble solid was collected and recrystallized from toluene to
yield 169 mg (70%) of yellow crystals with mp 273 ЊC.
1392
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398

View Article Online
[154.43] (C11a), 157.41 [158.80] (C4a), 168.50 [169.20] (C11-
CO2CH3), 183.67 [184.13] (C10), 190.06 [192.11] (C7); m/z 354
(100%, Mϩ), 336 (63), 295 (85).
ml methanol. The mixture was refluxed until a clear yellowish
solution was obtained and left to stand at room temperature
for 15 h. The alcohol was evaporated completely and the aque-
ous layer acidified with 5 M hydrochloric acid. The separated
solid was filtered off, dried under reduced pressure over diphos-
phorus pentaoxide and recrystallized from glacial acetic acid.
Compound 10a was obtained as colorless crystals (581 mg,
56%) with mp 225 ЊC (decomp.).
8,16-Dimethoxy-7,15-dihydro-7,15-dioxo-anthra[2,3-b:6,7-bЈ]-
bis[1]benzofuran-6,14-dicarboxylic acid dimethyl ester 8
A solution of 313 mg (1.3 mmol) 4 in 20 ml of dry dioxane was
added dropwise at 100 ЊC to a mixture of 137 mg (1.3 mmol)
benzo-1,4-quinone and 406 mg (1.3 mmol) of zinc iodide in 20
ml of dry dioxane. After complete addition the reaction mix-
ture was kept at this temperature for 10 min, the solvent was
evaporated and the residue taken up with ethyl acetate. The
insoluble yellow solid was collected and recrystallized from dry
toluene to yield 25 mg (35%) yellow crystals which decomposed
at about 320 ЊC.
νmax/cmϪ1 2920 (s), 1720 (s), 1767 (s); λmax(CH3CN)/nm (log ε)
220 (3.756), 273 (3.976), 282 (sh, 3.905); δH(200 MHz; CDCl3)
4.12 (s, 2H, C3-CH2), 7.37 (dd, 1H, C5-H, J1 6.94, J2 6.94), 7.53
(dd, 1H, C6-H, J1 7.13, J2 7.13), 7.69 (d, 1H, C7-H, J 8.41), 7.82
(d, 1H, C4-H, J 7.68), 13.10 (s, 2H, CO2H, exchanges with
D2O); δC(50 MHz; CDCl3) 29.69 (t, CH2), 112.00 (d, C7),
121.96 (d, C4), 122.26 (s, C3), 123.51 (d, C5), 127.87 (d, C6),
128.27 (s, C3a), 142.41 (s, C2), 153.62 (s, C7a), 160.87 (s,
CH2-CO2-CH3), 171.22 (s, C2-CO2-CH3); m/z 220 (51%, Mϩ),
202 (14), 176 (100), 175 (30), 131 (38); C11H8O5 requires:
220.03710. Found: 220.03717 (MS).
νmax/cmϪ1 1720 (C᎐O, s), 1339 (s), 1239 (s), 1207 (s), 1006 (m),
᎐
749 (m); λmax(CH3CN)/nm (log ε) 218 (3.718), 306 (3.956), 385
(3.113); δH(500 MHz; CDCl3) 4.21 (s, 6H, C5-CO2-CH3, C13-
CO2-CH3), 4.39 (s, 6H, C7-O-CH3, C15-O-CH3), 7.44 (dd, 2H,
C3-H, C11-H, J1 7.50, J2 0.76), 7.63 (dd, 2H, C2-H, C10-H,
J1 7.79, J2 1.30), 7.70 (d, 2H, C1-H, C9-H, J 8.25), 7.95 (d,
2H, C4-H, C12-H, J 7.33); δC(125 MHz; CDCl3) 53.31 (C5-
CO2CH3, C13-CO2CH3), 62.37 (C7-O-CH3, C15-O-CH3),
112.38 (C1, C9), 121.64 (C4b, C12b), 122.78* (C4, C12),
122.78* (C14a, C6a), 122.93 (C5a, C13a), 124.37 (C3, C11),
127.89 (d, C4a, C12a), 130.24 (C2, C10), 135.46 (C5, C13),
146.80 (C7, C15), 150.13 (C6a, C15a), 157.59 (C16a, C8a),
168.69 (C5-CO2CH3, C13-CO2CH3), 181.57 (C6, C14); m/z 564
(94%, Mϩ), 534 (37), 532 (100), 504 (57), 502 (53).
3-Carboxymethyl-6-methoxybenzofuran-2-carboxylic acid 10b
This compound was prepared according to literature pro-
cedures. (7-Methoxy-2-oxo-2H-chromen-4-yl)acetic acid was
prepared from 3-oxopentanedioic acid dimethyl ester and
3-methoxyphenol (mp 169 ЊC, yield 84%).35 This compound
was brominated to give (3-bromo-7-methoxy-2-oxo-2H-
chromen-4-yl)acetic acid (mp 205–206 ЊC, yield 68%),26 which
was subsequently used in a ring contraction reaction to obtain
3-carboxymethyl-6-methoxybenzofuran-2-carboxylic acid 10b
(mp 212 ЊC (decomp.), yield 59%).26
5,9-Epoxy-9-methoxy-6,8-dimethyl-7-oxo-6,7,8,9-tetrahydro-10-
oxabenzo[a]azulene-5-carboxylic acid methyl ester 9
4H-2,9-Dioxafluorene-1,3-dione 11a and 7-methoxy-4H-2,9-
dioxafluorene-1,3-dione 11b
Copper powder (1.55 g, 24 mmol) and 4.87 g (33 mmol) of
sodium iodide were suspended in a solution of 2.00 g (8 mmol)
4 in 50 ml of dry acetonitrile. Within 15 min a solution of 4.95 g
(20 mmol) 2,4-dibromopentan-3-one in 20 ml acetonitrile
was added at room temperature under nitrogen. The mixture
was stirred for a further 16 h at room temperature, 100 ml of
dichloromethane were added, after 10 min of vigorous shaking
the organic layer was separated and the aqueous phase was
extracted twice with dichloromethane. The combined organic
layers were washed twice with 2 M ammonia solution and once
with conc. sodium hydrogen carbonate solution, and were dried
with sodium sulfate and evaporated. The residue was taken up
with ethyl acetate–cyclohexane (1:1) and filtered through a
short column of silica gel. The filtrate was evaporated, taken up
with ethyl acetate–cyclohexane (1:3) and subjected to column
chromatography on silica gel to give 2.17 g (81%) of a colorless
oil.
A mixture of 4.15 g (18 mmol) 10a (3.35 g (13 mmol) 10b) and
15 ml freshly distilled acetyl chloride in 40 ml dry benzene was
refluxed for 5 h. The reaction mixture was evaporated and
traces of the solvent and acetyl chloride removed under reduced
pressure. As several attempts to purify the anhydrides 11a and
11b by recrystallization or sublimation failed the solid product
11a (11b) was used for the following reactions without further
purification.
3-Methoxycarbonylmethylbenzofuran-2-carboxylic acid 12a and
6-methoxy-3-methoxycarbonylmethylbenzofuran-2-carboxylic
acid 12b
The anhydride 11a (prepared from 4.15 g (18 mmol) 10a) (11b,
prepared from 3.35 g (13 mmol) 10b) was refluxed in 30 ml dry
methanol for 4 h, the excess of methanol was evaporated and
the residue recrystallized from toluene. The reaction yielded the
half-ester 12a (3.53 g (80% calculated on consumed starting
material 10a)) as colorless crystals with mp 125 ЊC or 12b
(2.83 g (68% calculated on consumed starting material 10b)) as
colorless crystals with mp 193 ЊC (decomp.).
νmax/cmϪ1 1280 (s), 1241 (s), 1749 (s), 1715 (s), 1616 (w), 1442
(s), 750 (m); λmax(CH3CN)/nm (log ε) 210 (3.063), 252 (2.749);
δH(300 MHz; CDCl3) 1.06 [1.07] (d, 3H, C6-CH3, J 5.86 [5.86]),
1.14 [1.15] (d, 3H, C8-CH3, J 7.03 [7.03]), 3.065 [3.07] (q, 1H,
C6-H, J 6.92 [6.92]), 3.13 [3.14] (q, 1H, C8-H, J 6.97 [6.92]),
3.59 [3.61] (s, 3H, C5-CO2CH3), 3.997 [4.00] (s, 3H, C9-OCH3),
7.29–7.81 (m, 3H, C1-H-C4-H); δC(75 MHz; CDCl3) 8.24 [8.29]
(dq, C6-CH3), 9.61 [9.67] (dq, C8-CH3), 50.54 [50.63] (dq, C6),
52.99 [53.09], (q, C5-CO2CH3), 53.73 [53.74] (q, C9-OCH3),
54.53 [54.53] (dq, C8), 83.17 [83.23] (s, C5), 107.79 [107.80]
(s, C9), 112.80 [112.90] (d, C1), 117.35 [117.48] (m, C4b), 123.65
[123.74] (m, C4), 124.13 [124.24] (d, C3), 125.30 [125.20]
(s, C4a), 128.06 [128.32] (d, C2), 159.84 [159.86] (s, C10a),
161.17 [161.29] (C9a), 168.05 [168.33] (C5-CO2CH3), 205.22
[205.59] (s, C7); m/z 330 (7%, Mϩ), 322 (25), 271 (47), 242
(100).
Spectroscopic data of 12a: νmax/cmϪ1 3500 (OH, m), 1740
(C᎐O, s), 1680 (s), 1599 (s), 1442 (s), 1305 (s), 751 (s);
᎐
λmax(CH3CN)/nm (log ε) 220 (3.492), 273 (3.671); δH(500 MHz;
CDCl3) 3.63 (s, 3H, CO2-CH3), 4.20 (s, 2H, C3-CH2), 7.36 (ddd,
1H, C5-H, J1 0.92, J2 7.53, J3 7.53), 7.52 (ddd, 1H, C6-H, J1
1.20, J2 7.16, J3 8.42), 7.69 (ddd, 1H, C7-H, J1 0.74, J2 0.74, J3
8.42), 7.80 (ddd, 1H, C4-H, J1 0.74, J2 1.20, J3 7.96), 12.50–
15.00 (s, 1H, CO2H, exchanges with D2O); δC(125 MHz;
CDCl3) 29.31 (t, CH2), 51.95 (q, CO2CH3), 112.01 (d, C7),
121.48 (s, C3), 121.82 (d, C4), 123.56 (d, C5), 127.90 (d, C6),
128.04 (m, C3a), 142.51 (m, C2), 153.64 (dddd, C7a), 160.77
(s, C2-CO2-CH3), 170.23 (tq, C3-CH2-CO2-CH3); m/z 234
(78%), 202 (100), 175 (81); C12H10O5 requires: 234.05283.
Found: 234.05260 (MS).
3-Carboxymethylbenzofuran-2-carboxylic acid 10a
A solution of 3.6 g (64 mmol) potassium carbonate in 25 ml
water was added to a suspension of 1.55 g (4.7 mmol) 2b in 25
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398
1393

View Article Online
Spectroscopic data of 12b: νmax/cmϪ1 3500 (OH, m), 1740
(C᎐O, s), 1676 (C᎐O, s), 1583 (s), 1439 (m), 1243 (s);
The mixture was refluxed for 3 h, and a further 150 mg (0.5
mmol) isourea was added and refluxing continued for 1.5 h. The
suspension was filtered, evaporated, the residue taken up with
cyclohexane–ethyl acetate (3:1) and filtered through a short
column of silica gel. The solvents were evaporated and the oily
raw product subjected to radial chromatography on silica gel
with cyclohexane–ethyl acetate (5:1) to yield 569 mg (89%) of
15a as a colorless oil.
᎐
᎐
λmax(EtOH)/nm (log ε) 205 (4.444), 240 (4.087), 281 (4.308),
311 (4.565); δH(200 MHz; CDCl3) 3.62 (s, 3H, CO2-CH3),
3.83 (s, 3H, O-CH3), 4.14 (s, 2H, C3-CH2), 6.97 (dd, 1H,
C5-H, J1 2.19, J2 8.77), 7.26 (d, 1H, C4-H, J 2.19), 7.65 (d,
1H, C7-H, J 8.77), 12.50–15.00 (s, 1H, CO2H, exchanges with
D2O); δC(75 MHz; [D6]DMSO) 29.38 (t, CH2), 51.93 (q,
CO2CH3), 55.79 (q, OCH3), 95.75 (d, C5), 113.55 (d, C4),
121.29 (s, C3), 121.93 (ddd, C3a), 122.20 (d, C7), 141.60 (s, C2),
155.18 (ddd, C7a), 160.41 (s, C2-CO2-CH3), 160.73 (s, C6),
170.26 (tq, C3-CH2-CO2-CH3); m/z 264 (100%, Mϩ), 232 (43),
205 (53); C13H12O6 requires: 264.06339. Found: 264.06330
(MS).
νmax/cmϪ1 1742 (s), 1711 (s), 1601 (m), 1298 (s), 1152 (s), 749
(s); λmax(EtOH)/nm (log ε) 220 (4.168), 275 (4.410), 285 (sh,
4.333); δH(200 MHz; CDCl3) 1.91 (tt, 2H, O-CH2-CH2, J1 7.06,
J 7.01), 2.23 (dt, 2H, O-CH -CH᎐CH , J 6.97, J 7.14), 3.72 (s,
᎐
2
2
2
1
2
3H, CO2CH3), 4.18 (s, 2H, C3-CH2), 4.41 (t, 2H, O-CH2,
J 6.65), 5.02 (ddt, 1H, CH᎐CH , Z, J 1.48, J 1.52, J 10.21),
᎐
2
1
2
3
5.08 (ddt, 1H, CH᎐CH , E, J 1.80, J 1.82, J 17.26) (3J(E) >
᎐
2
1
2
3
3J(Z)), 5.86 (ddt, 2H, CH᎐CH , J 6.61, J 10.30, J 17.02),
3-Benzyloxycarbonylmethylbenzofuran-2-carboxylic acid methyl
ester 13a
᎐
2
1
2
3
7.10–7.85 (m, 4H, C4-H, C5-H, C6-H, C7-H); δC(50 MHz;
CDCl ) 27.62 (t, C3-CH ), 29.80 (t, CH -CH᎐CH ), 29.99 (t,
᎐
3
2
2
2
To a solution of 180 mg (0.7 mmol) 3a in 20 ml dry benzylic
alcohol a trace of toluene-p-sulfonic acid was added and the
mixture refluxed for 14 h. The excess of benzylic alcohol was
evaporated under reduced pressure, the oily residue taken up
with ether–pentane (1:1) and filtered over a short column of
silica gel. The filtrate was evaporated and the residue subjected
to radial chromatography on silica gel with ether–pentane
(1:10). The first fraction gave 74 mg (25%) of 3-benzyloxy-
carbonylmethylbenzofuran-2-carboxylic acid benzyl ester 13b
as a colorless oil. The second fraction was evaporated and taken
up with methanol to give 70 mg (35%) of ester 13a as colorless
crystals with mp 103–105 ЊC.
O-CH2-CH2-CH2), 52.27 (q, CO2CH3), 64.85 (t, O-CH2-CH2),
112.37 (dd, C7), 115.60 (t, CH᎐CH ), 116.79 (s, C3), 121.19 (dd,
᎐
2
C4), 123.64 (dd, C5), 127.98 (dd, C6), 128.06 (s, C3a), 137.13 (d,
CH᎐CH ), 141.98 (s, C2), 157.47 (s, C7a), 160.29 (s, C2-CO),
᎐
2
170.25 (s, CO2CH3); m/z 302 (14%, Mϩ), 234 (87), 202 (96), 189
(30), 168 (33), 68 (100); C17H18O5 requires: 302.11542. Found:
302.11520 (MS).
3-[Diazo(methoxycarbonyl)methyl]benzofuran-2-carboxylic acid
pent-4-enyl ester 15b
In a solution of 252 mg (0.8 mmol) 15a in 10 ml dry acetonitrile
200 mg (0.8 mmol) 4-azidosulfonylbenzoic acid was suspended.
A solution of 307 mg (0.3 ml, 2.0 mmol) DBU in 0.7 ml
acetonitrile was added dropwise under nitrogen at room tem-
perature. Stirring was continued for 1 h, the mixture filtered and
8 ml of acetonitrile evaporated under reduced pressure. The oily
residue was taken up with ether–pentane (1:2) and filtered
through a short column of silica gel. The filtrate was evap-
orated and purified by radial chromatography on silica gel
with ether–pentane (1:10) to give 156 mg (58%) of 15b as a
yellow oil.
νmax/cmϪ1 1726 (C᎐O, s), 1621 (s), 1398 (m), 1124 (m), 1057
᎐
(m), 847 (m); λmax(EtOH)/nm (log ε) 220 (3.649), 227 (sh, 3.453),
277 (3.521), 287 (sh, 3.440); δH(300 MHz; CDCl3) 3.93 (s, 3H,
CO2CH3), 4.21 (s, 2H, C3-CH2), 5.17 (s, 2H, Bn-CH2), 7.27–
7.70 (3 overlapping m, 9H, aromatic rings); δC(75 MHz;
CDCl3) 30.24 (t, C3-CH2), 52.24 (q, C2-CO2CH3), 66.93 (t,
Bn-CH2), 112.35 (d, C7), 121.34 (d, C4), 121.98 (s, C3), 123.66
(d, C5), 128.54 (d, C6), 129.6–129.5 (3 overlapping m, benzyl),
135.53 (m, C1, Bn), 141.77 (s, C2), 154.43 (s, C7a), 160.33 (s,
C2-CO2CH3), 169.65 (s, C3-CH2-CO2-Bn); m/z 324 (29%, Mϩ),
265 (11), 189 (62), 91 (100); C19H16O5 requires: 324.09976.
Found: 324.09970 (MS).
νmax/cmϪ1 2111 (C᎐N , s), 1711 (C᎐O, s), 1287 (s), 1166 (m),
᎐
᎐
2
747 (m); λmax(EtOH)/nm (log ε) 215 (sh, 4.141), 260 (4.188), 285
(4.024), 295 (4.024); δH(300 MHz; CDCl3) 1.93 (tt, 2H, O-CH2-
CH2, J1 7.24, J2 7.24), 2.22 (dt, 2H, O-CH2-CH2-CH2, J1 7.07,
J2 7.17), 3.88 (s, 3H, CO2CH3), 4.43 (t, 2H, O-CH2, J 6.77), 5.02
3-Carboxymethylbenzofuran-2-carboxylic acid methyl ester 14
Palladium (5 mg) on charcoal (10%) was added to a solution
of 60 mg (0.2 mmol) 13a in 30 ml of absolute ethanol and
hydrogenated at room temperature. The formation of com-
pound 14 could be monitored by TLC chromatography with
cyclohexane–ethyl acetate–triethylamine (10:20:1). The cat-
alyst was filtered off and the solvent evaporated. The residue
was recrystallized from toluene at Ϫ20 ЊC to yield 14 (37 mg,
89%) as colorless crystals with mp 185–187 ЊC (decomp.).
νmax/cmϪ1 1702 (s), 1305 (m), 1147 (s), 750 (s); λmax(CH3CN)/
nm (log ε) 220 (4.370), 225 (sh, 4.307), 275 (4.600), 286
(sh, 4.536); δH(300 MHz; CDCl3) 3.89 (s, 3H, CO2-CH3),
4.11 (s, 2H, C3-CH2), 7.38 (ddd, 1H, C5-H, J1 0.99, J2 7.15,
J3 7.10), 7.54 (ddd, 1H, C6-H, J1 1.34, J2 7.15, J3 8.45), 7.70
(ddd, 1H, C7-H, J1 0.81, J2 0.84, J3 8.37), 7.83 (ddd, 1H, C4-H,
J1 0.73, J2 0.77, J3 7.90); δC(75 MHz; CDCl3) 29.61 (t, CH2),
52.18 (q, CO2CH3), 112.05 (d, C7), 122.07 (s, C3), 123.21
(d, C4), 123.72 (d, C5), 127.29 (d, C6), 128.27 (m, C3a),
141.18 (m, C2), 153.72 (dddd, C7a), 159.77 (s, C2-CO2-CH3),
170.99 (tq, C3-CH2-CO2-CH3); m/z 234 (28%, Mϩ), 216 (9), 190
(63), 183 (11), 175 (26); C12H10O5 requires: 234.05283. Found:
234.05280 (MS).
(ddt, 1H, CH᎐CH , Z, J 1.48, J 1.52, J 10.21), 5.08 (ddt, 1H,
᎐
2
1
2
3
CH᎐CH , E, J 1.80, J 1.82, J 17.26), 5.85 (ddt, 1H, CH᎐CH ,
᎐
᎐
2
1
2
3
2
J1 6.69, J2 10.27, J3 17.01), 7.34 (ddd, 1H, C5-H, J1 1.04, J2 7.05,
J3 8.05), 7.49 (ddd, 1H, C6-H, J1 1.34, J2 7.10, J3 8.46), 7.59
(ddd, 1H, C7-H, J1 0.91, J2 0.91, J3 8.29), 7.69 (ddd, 1H, C4-H,
J1 0.73, J2 1.29, J3 8.01); δC(75 MHz; CDCl3) 26.93 (s, CN2),
29.86 (t, O-CH2-CH2-CH2), 29.97 (t, O-CH2-CH2), 53.37 (q,
CO2CH3), 65.25 (t, O-CH2), 112.41 (dd, C7), 114.67 (s, C3),
115.61 (t, CH᎐CH ), 123.19 (dd, C4), 123.86 (dd, C5), 126.84
᎐
2
(s, C3a), 128.41 (dd, C6), 137.16 (d, CH᎐CH ), 139.52 (s,
᎐
2
C2), 154.71 (s, C7a), 159.11 (s, C2-CO2-pentenyl), 165.19 (s,
CO2CH3); m/z 328 (8%, Mϩ), 232 (100), 203 (68), 189 (60), 173
(29), 145 (23); C17H16N2O5 requires: 328.10593. Found:
328.10580 (MS).
3,4-Dihydro-2H-1,11-dioxabenzo[a]fluorene-6-carboxylic acid
methyl ester 17a
A mixture of 1 mg dirhodium tetraacetate and 102 mg (0.3
mmol) 15b in 10 ml dry toluene was heated to 90 ЊC until com-
plete decomposition of the diazo compound (monitored by
TLC chromatography) and 100 mg (0.3 mmol) zinc iodide was
added and the mixture heated for a further 2 h at 90 ЊC. The
solution was filtered, washed with 0.5 M hydrochloric acid
and water and subsequently dried with sodium sulfate. After
evaporation of the solvent the residue was taken up with
3-Methoxycarbonylmethylbenzofuran-2-carboxylic acid pent-4-
enyl ester 15a
To a solution of 500 mg (2.1 mmol) 12a in 15 ml dry THF 465
mg (1.6 mmol) dicyclohexyl-2-pent-4-enylisourea25 was added.
1394
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398

View Article Online
cyclohexane–ethyl acetate (5:1), filtered through a short
column of silica gel and purified by radial chromatography on
silica gel with cyclohexane–ethyl acetate (8:1). The residue was
recrystallized with dry methanol to give 41 mg (47%, calculated
on consumed starting material 15b) of colorless crystals with
mp 169 ЊC.
O-CH , J 6.77), 5.02 (ddt, 1H, CH᎐CH , Z, J 1.70, J 1.52,
᎐
2 2 1 2
J 10.19), 5.08 (ddt, 1H, CH᎐CH , E, J 1.68, J 1.73, J 17.15),
᎐
3
2
1
2
3
5.85 (ddt, 1H, CH᎐CH , J 6.69, J 10.31, J 17.04), 6.96 (dd, 1H,
᎐
2
1
2
3
C4-H, J1 8.84, J2 2.27), 7.04 (d, 1H, C7-H, J 2.02), 7.55 (d, 1H,
C5-H, J 8.89); δC(75 MHz; CDCl3) 27.92 (t, O-CH2-CH2-CH2),
29.99 (t, O-CH2-CH2), 52.34 (q, CO2CH3), 55.75 (q, 3H,
OCH3), 56.62 (s, CN2), 64.99 (t, O-CH2), 95.40 (d, C4), 114.21
νmax/cmϪ1 1707 (s), 1573 (m), 1334 (s), 1222 (s), 773 (m);
λmax(EtOH)/nm (log ε) 220 (3.685), 248 (4.229), 260 (sh, 4.071),
270 (4.071), 300 (4.211); δH(300 MHz; CDCl3) 2.16 (tt, 2H, C3-
H, J1 6.24, J2 10.64), 2.95 (t, 2H, C4-H, J 6.31), 4.01 (s, 3H,
CO2CH3), 4.46 (t, 1H, C2-H, J 5.31), 7.37 (ddd, 1H, C8-H,
J1 1.11, J2 7.17, J3 8.13), 7.49 (ddd, 1H, C9-H, J1 1.34, J2 7.15,
J3 8.31), 7.61 (ddd, 1H, C10-H, J1 0.61, J2 1.16, J3 8.24), 7.79
(s, 1H, C5-H), 8.82 (ddd, 1H, C7-H, J1 0.61, J2 1.36, J3 8.03);
δC(75 MHz; CDCl3) 22.06 (t, C4), 24.47 (tt, C3), 51.91 (q,
CO2CH3), 67.58 (t, C2), 111.49 (dd, C10), 116.16 (d, C4a),
120.05 (d, C11a), 122.90 (dd, C7), 123.88 (s, C5), 123.44 (s,
C6a), 126.02 (s, C6b), 127.74 (dd, C8), 128.13 (dd, C9), 144.63
(d, C6), 144.93 (s, C11a), 156.82 (d, C10a), 166.94 (s, CO2CH3);
m/z 282 (100%, Mϩ), 251 (50), 223 (21); C17H14O4 requires:
282.08920. Found: 282.08910 (MS).
(d, C5), 115.15 (s, C3), 115.56 (t, CH᎐CH ), 120.07 (s, C3a),
᎐
2
123.67 (d, C7), 137.22 (d, CH᎐CH ), 138.50 (s, C2), 156.16 (s,
᎐
2
C6), 159.06 (s, C7a), 161.08 (s, C2-CO2), 165.18 (s, CO2CH3);
m/z 358 (15%, Mϩ), 271 (38), 262 (100), 233 (98), 219 (63),
203 (30), 175 (21); C18H18N2O6 requires: 358.11649. Found:
358.11650 (MS).
6-Methoxy-1-pent-4-enyloxy-2,8-dioxacyclopenta[a]indene-3-
carboxylic acid methyl ester 16b
A solution of 101 mg (0.3 mmol) of 15d in 5 ml of dry benzene
was refluxed with a catalytic amount of dirhodium tetraacetate
for 2 h until complete decomposition of the diazo compound
(monitored by TLC chromatography). The solvent was removed
under reduced pressure, the residue taken up with cyclohexane–
ethyl acetate (5:1), filtered through a short column of silica
gel and purified by radial chromatography on silica gel with
cyclohexane–ethyl acetate (8:1) to give 68 mg (74%) of
colorless crystals with mp 73 ЊC (decomp.).
6-Methoxy-3-methoxycarbonylmethylbenzofuran-2-carboxylic
acid pent-4-enyl ester 15c
To a solution of 2.61 g (10 mmol) 12b in 50 ml dry THF, 2.88 g
(10 mmol) 1,3-dicyclohexyl-2-pent-4-enylisourea was added.
After refluxing for 3 h the precipitated solid was filtered off, the
solvent evaporated and the residue taken up with a few milli-
litres of dry acetone. The solution was cooled to Ϫ20 ЊC for a
few hours, filtered and the oily raw product filtered through a
short column of silica gel with cyclohexane–ethyl acetate (3:1).
The filtrate was evaporated and purified by radial chrom-
atography using silica gel and cyclohexane–ethyl acetate (15:1)
to give 900 mg (27%) of a yellowish oil.
νmax/cmϪ1 1723 (C᎐O, s), 1706 (s), 1672 (s), 1614 (s), 1565 (s),
᎐
1256 (s), 1098 (s); λmax(CH3CN)/nm (log ε) 245 (3.267), 285
(3.528), 295 (sh, 3.454), 335 (3.411); δH(300 MHz; CDCl3)
1.95 (tt, 2H, O-CH2-CH2-CH2, J1 6.55, J2 7.24), 2.28 (dt, 2H,
O-CH2-CH2-CH2, J1 7.12, J2 7.14), 3.88 (s, 3H, CO2CH3), 3.96
(s, 3H, OCH3), 4.45 (t, 2H, O-CH2, J 6.37), 5.03 (ddt, 1H,
CH᎐CH , Z, J 10.16, J 1.87, J 1.21), 5.09 (ddt, 1H, CH᎐CH ,
᎐
᎐
2
1
2
3
2
E, J 17.16, J 1.70, J 1.74), 5.84 (ddt, 1H, CH᎐CH , J 17.04,
᎐
1
2
3
2
1
J2 10.27, J3 6.75), 6.88 (dd, 1H, C5-H, J1 8.34, J2 2.27),
6.90 (d, 1H, C4-H, J 1.52), 7.90 (d, 1H, C7-H, J 8.08); δC(75
MHz) CDCl3 27.46 (t, O-CH2-CH2-CH2), 29.58 (t, O-CH2-
CH2), 51.33 (q, CO2CH3), 55.76 (q, 3H, OCH3), 72.17 (t,
O-CH2), 97.30 (dd, C5), 111.17 (d, C4), 112.11 (s, C3b), 115.75
νmax/cmϪ1 1734 (C᎐O, s), 1597 (m), 1438 (s), 1148 (s), 1096 (s),
᎐
802 (s), 749 (s); λmax(EtOH)/nm (log ε) 220 (sh, 3.300), 264 (sh,
3.367), 275 (3.425), 286 (sh, 3.238); δH(300 MHz; CDCl3) 1.95
(tt, 2H, O-CH2-CH2, J1 7.53, J2 6.61), 2.22 (dt, 2H, O-CH2-
CH2-CH2, J1 7.13, J2 7.26), 3.72 (s, 3H, CO2CH3), 3.99 (s, 3H,
C6-OCH3), 4.19 (s, 2H, C3-CH2), 4.43 (t, 2H, O-CH2, J 6.74),
(ddt, CH᎐CH ), 119.31 (s, C8a), 125.16 (d, C7), 128.18 (d,
᎐
2
C3a), 130.08 (s, C1), 137.08 (d, CH᎐CH ), 140.86 (s, C3),
᎐
2
4.99–5.12 (overlapping m, 2H, CH᎐CH ), 5.86 (ddt, 1H, CH᎐
158.81 (s, C7a), 161.82 (s, C6), 165.90 (s, CO2CH3); m/z 330
(8%, Mϩ), 271 (57), 262 (100), 233 (91), 219 (88), 203 (28), 175
(21).
᎐
᎐
2
CH2, J1 6.74, J2 10.26, J3 22.65), 7.32 (dd, 1H, C4-H, J1 7.96, J2
2.27), 7.48 (d, 1H, C7-H, J 2.02), 7.64 (d, 1H, C5-H, J 8.89);
δC(75 MHz; CDCl3) 25.70 (t, C3-CH2), 25.45 (t, O-CH2-CH2-
CH2), 29.94 (t, O-CH2-CH2), 52.31 (q, CO2CH3), 55.76 (q, 3H,
OCH3), 64.63 (t, O-CH2), 95.65 (d, C4), 112.38 (d, C5), 115.52
9-Methoxy-3,4-dihydro-2H-1,11-dioxabenzo[a]fluorene-6-carb-
oxylic acid methyl ester 17b
(t, CH᎐CH ), 115.52 (s, C3), 121.24 (s, C3), 123.70 (s, C3a),
᎐
2
A solution of 95 mg (0.3 mmol) 15d in 40 ml dry dioxane was
refluxed with a catalytic amount of dirhodium tetraacetate
until complete decomposition of the diazo compound (moni-
tored by TLC chromatography), and 93 mg (0.3 mmol) of
zinc iodide was added and refluxing continued for a further 1 h.
After evaporation of the solvent the residue was taken up
with cyclohexane–ethyl acetate (1:1), filtered through a short
column of silica gel and purified by radial chromatography on
silica gel with cyclohexane–ethyl acetate (3:1) to give 35 mg
(39%, calculated on consumed starting material 15d) of color-
less crystals with mp 166–167 ЊC.
128.11 (d, C7), 137.28 (d, CH᎐CH ), 141.69 (s, C2), 154.44 (s,
᎐
2
C7a), 160.38 (s, C3-CH2-CO2CH3), 170.28 (s, C2-CO2-
pentenyl); m/z 332 (76%, Mϩ), 264 (100), 232 (82), 205 (38), 189
(23), 161 (19); C18H20O6 requires: 332.12598. Found: 332.12570
(MS).
3-[Diazo(methoxycarbonyl)methyl]-6-methoxybenzofuran-2-
carboxylic acid pent-4-enyl ester 15d
A solution of 920 mg (0.9 ml, 6.0 mmol) DBU in 1 ml dry
acetonitrile was added under nitrogen at room temperature to
a mixture of 0.88 g (2.7 mmol) 15c and 0.68 g (3 mmol) 4-
azidosulfonylbenzoic acid in 30 ml dry acetonitrile. The mixture
was stirred for 16 h, filtered, 25 ml of the solvent evaporated
under reduced pressure and the residue purified by column
chromatography on silica gel using cyclohexane–ethyl acetate
(1:1). The reaction yielded 807 mg (85%) of yellow crystals
with mp 55 ЊC (decomp.).
νmax/cmϪ1 1708 (C᎐O, s), 1570 (m), 1333 (s), 1186 (s), 1099 (s),
᎐
785 (m); λmax(EtOH)/nm (log ε) 225 (4.231), 252 (4.494), 272
(4.231), 311 (4.152); δH(300 MHz; CDCl3) 2.15 (tt, 2H, C3-H,
J1 6.38, J2 6.46), 2.94 (t, 2H, C4-H, J 6.24), 3.90 (s, 3H, OCH3),
4.00 (s, 3H, CO2CH3), 4.45 (t, 1H, J 5.25), 6.95 (dd, 1H, C8-H,
J1 2.42, J2 10.13), 7.10 (d, 1H, C7-H, J 2.39), 7.76 (s, 1H, C5-H),
8.93 (d, 1H, J 8.93); δC(75 MHz; CDCl3) 22.14 (t, C4), 24.40 (tt,
C3), 51.82 (q, CO2CH3), 55.60 (q, 3H, OCH3), 67.56 (t, C2),
97.87 (d, C8), 111.14 (d, C7), 115.20 (s, C4a), 116.70 (s, C6a),
119.02 (s, C11b), 124.36 (s, C6b), 126.54 (d, C10), 127.92 (d,
C5), 144.34 (s, C6), 144.83 (s, C11a), 158.12 (s, C10a), 160.23 (s,
C9), 167.03 (s, CO2CH3); m/z 312 (100%, Mϩ), 281 (26), 253
νmax/cmϪ1 2104 (C᎐N , s), 1700 (C᎐O, s), 1290 (s), 1108 (m),
᎐
᎐
2
1010 (m); λmax(EtOH)/nm (log ε) 250 (sh, 3.367), 260 (3.446),
312 (3.513); δH(300 MHz; CDCl3) 1.92 (tt, 2H, O-CH2-
CH2, J1 7.51, J2 6.65), 2.22 (dt, 2H, O-CH2-CH2-CH2, J1 7.12,
J2 7.10), 3.87 (s, 3H, CO2CH3), 3.88 (s, 3H, OCH3), 4.41 (t, 2H,
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398
1395

View Article Online
(13), 202 (7); C18H16O5 requires: 312.09976. Found: 312.09970
(MS).
3-[Diazo(pentyloxycarbonyl)methyl]benzofuran-2-carboxyclic
acid methyl ester 18e
A solution of 500 mg (0.51 ml, 3.3 mmol) DBU in 2 ml dry
acetonitrile was added dropwise under nitrogen at room tem-
perature to a mixture of 385 mg (1.3 mmol) 18c and 361 mg (1.6
mmol) 4-azidosulfonylbenzoic acid in 30 ml dry acetonitrile.
The mixture was stirred for 16 h, filtered, 25 ml of the solvent
evaporated under reduced pressure and the residue purified by
column chromatography on silica gel using cyclohexane–ethyl
acetate (12:1) to give 415 mg (99%) of a yellow oil.
3-Pent-4-enyloxycarbonylmethylbenzofuran-2-carboxylic acid
18c
A mixture of 7.12 g (32 mmol) 11a and 3.38 g (4.5 ml, 39.3
mmol) of pent-4-en-1-ol was heated to 50 ЊC for 3 h. The
reaction mixture was cooled in an ice bath and taken up with
ice-cold conc. sodium hydrogen carbonate solution. The
aqueous solution was extracted three times with methyl tert-
butyl ether (MTBE), acidified at 0 ЊC with 2 M hydrochloric
acid and extracted four times with 100 ml portions of MTBE.
The organic layer was washed with conc. sodium chloride
solution, dried with sodium sulfate, the solvent evaporated and
the residue subjected to column chromatography on silica gel
with cyclohexane–ethyl acetate–glacial acetic acid (16:4:1).
After recrystallization from benzene–n-hexane 5.22 g the acid
(56% calculated on starting material 11a) was isolated as color-
less crystals (mp 87–88 ЊC).
νmax/cmϪ1 2110 (s), 1711 (s), 1575 (m), 1442 (m), 1263 (s), 748
(s); λmax(CH3CN)/nm (log ε) 220 (4.245), 260 (4.268), 295
(4.136); δH(300 MHz; CDCl3) 1.80 (tt, 2H, O-CH2-CH2, J1 7.12,
J2 7.11), 2.14 (dt, 2H, O-CH2-CH2-CH2, J1 7.15, J2 7.28), 4.02
(s, 3H, CO2CH3), 4.31 (t, 2H, O-CH2, J 6.62), 4.31–5.08 (2m,
2H, CH᎐CH ), 5.81 (ddt, 1H, CH᎐CH , J 6.67, J2 10.32,
᎐
᎐
2
2
1
J3 17.06), 7.34 (ddd, 1H, C5-H, J1 1.09, J2 7.00, J3 8.06), 7.50
(ddd, 1H, C6-H, J1 1.34, J2 7.05, J3 8.41), 7.58 (ddd, 1H, C7-H,
J1 0.81, J2 1.01, J3 8.34), 7.71 (ddd, 1H, C4-H, J1 0.76, J2 1.21,
J3 8.03); δC(50 MHz; CDCl3) 27.93 (t, O-CH2-CH2-CH2), 27.97
(t, O-CH2-CH2), 52.62 (q, CO2CH3), 55.50 (s, CN2), 64.89 (t,
νmax/cmϪ1 1725 (C᎐O, s), 1684 (s), 1595 (s), 1440 (m), 1298 (s),
᎐
1177 (s), 748 (m); λmax(EtOH)/nm (log ε) 220 (4.029), 285
(4.209); δH(300 MHz; CDCl3) 1.72 (tt, 2H, O-CH2-CH2, J1 7.11,
J2 6.64), 2.06 (dt, 2H, O-CH2-CH2-CH2, J1 7.04, J2 7.16), 4.15
(t, 2H, O-CH2, J 6.59), 4.21 (s, 2H, C3-CH2), 4.95 (ddt, 1H,
O-CH ), 112.34 (dd, C7), 115.45 (t, CH᎐CH ), 115.28 (s, C3),
᎐
2
2
123.43 (dd, C4), 123.81 (dd, C5), 126.72 (s, C3a), 128.53 (dd,
C6), 137.29 (d, CH᎐CH ), 141.02 (s, C2), 154.66 (s, C7a),
᎐
2
CH᎐CH , Z, J 1.32, J 2.23, J 8.11), 4.99 (ddt, 1H, CH᎐CH ,
159.41 (s, C2-CO2-pentenyl), 164.98 (s, CO2CH3); m/z 328
(27%, Mϩ), 279 (6), 271 (40), 229 (74), 203 (52), 189 (100);
C17H16N2O5 requires: 328.10593. Found: 328.10580 (MS).
᎐
᎐
2
1
2
3
2
E, J1 1.39, J2 3.33, J3 9.67), 5.20–6.40 (br s, 1H, COOH,
exchanges with D O), 5.75 (ddt, 1H, CH᎐CH , J 6.68, J 10.30,
᎐
2
2
1
2
J3 16.98), 7.35 (ddd, 1H, C5-H, J1 1.00, J2 7.02, J3 7.99), 7.51
(ddd, 1H, C6-H, J1 1.33, J2 7.08, J3 8.44), 7.61 (ddd, 1H, C7-H,
J1 0.91, J2 0.91, J3 8.28), 7.67 (ddd, 1H, C4-H, J1 1.00, J2 1.00,
J3 7.92); δC(75 MHz; CDCl3) 27.66 (t, CH2), 29.92 (t, O-CH2-
CH2-CH2), 30.31 (t, O-CH2-CH2), 64.82 (t, O-CH2), 112.53 (dd,
3-Allyloxycarbonylmethylbenzofuran-2-carboxylic acid methyl
ester 18a and 3-allyloxycarbonylmethylbenzofuran-2-carboxylic
acid allyl ester
To a suspension of 221 mg (0.5 mmol) 3a in 20 ml of dry,
freshly distilled allylic alcohol 8 mg of toluene-p-sulfonic acid
was added and the mixture refluxed for 14 h. The excess of
allylic alcohol was evaporated under reduced pressure, the oily
residue taken up with ether–pentane (1:1) and filtered through
a short column of silica gel. The filtrate was evaporated and the
residue subjected to radial chromatography on silica gel with
ether–pentane (1:7). The first fraction gave 9 mg (6%) of
allyloxycarbonylmethylbenzofuran-2-carboxylic acid allyl ester
as colorless oil. The second fraction contained 46 mg (34%)
3-allyloxycarbonylmethylbenzofuran-2-carboxylic acid methyl
ester 18a as colorless oil and finally the third fraction gave 10
mg (8%) 3a.
C7), 121.51 (dd, C4), 124.29 (s, C3), 115.37 (t, CH᎐CH ),
᎐
2
123.85 (dd, C5), 128.70 (s, C3a), 128.70 (dd, C6), 137.26 (d,
CH᎐CH ), 141.02 (s, C2), 154.90 (s, C7a), 164.88 (s, C2-CO -
᎐
2
2
pentenyl), 169.74 (s, CO2CH3); m/z 288 (13%, Mϩ), 220 (40),
202 (14), 176 (100); C16H16O5 requires: 288.09976. Found:
288.09960 (MS).
3-Pent-4-enyloxycarbonylmethylbenzofuran-2-carboxylic acid
methyl ester 18d
To a solution of 450 mg (1.6 mmol) 3-pent-4-enyloxycarb-
onylmethylbenzofuran-2-carboxylic acid in 15 ml dry THF
375 g (1.6 mmol) 1,3-dicyclohexyl-2-methylisourea was added.
The mixture was refluxed for 2 h and stirred for a further 16 h at
room temperature. The precipitated solid was filtered off, the
solvent evaporated and the oily raw product filtered through a
short column of silica gel with cyclohexane–ethyl acetate (1:1).
The filtrate was evaporated and purified by radial chromato-
graphy using silica gel and cyclohexane–ethyl acetate (6:1) to
give 385 mg (82%) of colorless oil.
Spectroscopic data of 18a: νmax/cmϪ1 1737 (C᎐O, s), 1601 (m),
᎐
1438 (s), 1301 (s), 1272 (s), 1151 (s), 749 (s); λmax(EtOH)/nm (log
ε) 221 (4.005), 265 (sh, 4.201), 276 (4.256), 285 (4.239); δH(500
MHz; CDCl3) 3.99 (s, 3H, CO2CH3), 4.21 (s, 2H, C3-CH2), 4.63
(td, 2H, O-CH , J 1.42, J 5.69), 5.22 (ddt, 1H, CH᎐CH , Z,
᎐
2
1
2
2
J 1.30, J 1.30, J 10.43), 5.28 (ddt, 1H, CH᎐CH , E, J 1.51,
᎐
1
2
3
2
1
J 1.53, J 17.15), 5.89 (ddt, 1H, CH᎐CH , J 5.71, J 10.48,
᎐
2
3
2
1
2
νmax/cmϪ1 1738 (s), 1601 (w), 1300 (s), 1151 (s), 749 (m);
λmax(EtOH)/nm (log ε) 220 (4.003), 275 (4.117); δH(300 MHz;
CDCl3) 1.71 (tt, 2H, O-CH2-CH2, J1 6.55, J2 7.39), 2.05 (dt, 2H,
O-CH2-CH2-CH2, J1 6.84, J2 7.38), 3.99 (s, 3H, CO2CH3), 4.13
(t, 2H, O-CH2, J 6.57), 4.17 (s, 2H, C3-CH2), 4.95 (m, 1H,
J3 17.18), 7.33 (ddd, 1H, C5-H, J1 0.92, J2 7.11, J3 7.95), 7.48
(ddd, 1H, C6-H, J1 1.30, J2 7.15, J3 8.41), 7.58 (ddd, 1H, C7-H,
J1 0.79, J2 0.79, J3 8.41), 7.64 (ddd, 1H, C4-H, J1 0.84, J2 1.17,
J3 7.78); δC(125 MHz; CDCl3) 30.06 (t, C3-CH2), 52.31 (q,
CO2CH3), 65.81 (t, O-CH2), 112.36 (ddd, C7), 118.47 (t,
CH᎐CH , Z), 4.98 (ddt, 1H, CH᎐CH , E, J 1.80, J 1.81, J
᎐
᎐
2
2
1
2
3
CH᎐CH ), 121.25 (dd, C4), 122.03 (s, C3), 123.68 (dd, C5),
᎐
2
8.37), 5.75 (ddt, 1H, CH᎐CH , J 6.59, J 10.37, J 16.91), 7.32
᎐
2
1
2
3
127.93 (s, C3a), 128.10 (dd, C6), 131.79 (ddd, CH᎐CH ), 141.74
᎐
2
(ddd, 1H, C5-H, J1 0.96, J2 7.07, J3 7.98), 7.47 (ddd, 1H, C6-H,
J1 1.31, J2 7.07, J3 8.39), 7.57 (ddd, 1H, C7-H, J1 0.91, J2 0.91, J3
8.34), 7.64 (ddd, 1H, C4-H, J1 0.81, J2 1.31, J3 7.88); δC(75
MHz; CDCl3) 27.69 (t, CH2), 30.01 (t, O-CH2-CH2-CH2), 30.16
(t, O-CH2-CH2), 52.25 (q, CO2CH3), 64.61 (t, O-CH2), 112.34
(s, C2), 154.44 (s, C7a), 160.37 (s, C3-CH2-COCH3), 169.46 (s,
C2-CO2CH3); m/z 274 (43%, Mϩ), 216 (24), 189 (100), 159 (26);
C15H12O5 requires: 274.08414. Found: 274.08390 (MS).
3-[Diazo(allyloxycarbonyl)methyl]benzofuran-2-carboxylic acid
methyl ester 18b
(dd, C7), 115.35 (t, CH᎐CH ), 116.85 (s, C3), 121.23 (dd, C4),
᎐
2
123.63 (dd, C5), 127.99 (s, C3a), 128.05 (dd, C6), 137.30 (d,
CH᎐CH ), 141.68 (s, C2), 154.42 (s, C7a), 160.37 (s, C2-CO -
A solution of 470 mg (0.48 ml, 3.1 mmol) DBU in 5 ml of dry
acetonitrile was added dropwise under nitrogen at room tem-
perature to a mixture of 336 mg (1.2 mmol) 18a and 333 mg (1.5
mmol) of 4-azidosulfonylbenzoic acid in 15 ml dry acetonitrile.
᎐
2
2
pentenyl), 169.76 (s, CO2CH3); m/z 302 (14%, Mϩ), 234 (14),
216 (23), 190 (100), 189 (59), 159 (29); C17H18O5 requires:
302.11542. Found: 302.11520 (MS).
1396
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398

View Article Online
T. Durst, Tetrahedron, 1997, 53, 15969; (g) A. Roy, K. R. Reddy,
H. Ila and H. Junjappa, J. Chem. Soc., Perkin Trans. 1, 1999,
3001.
The mixture was stirred for 5 h, filtered and 15 ml of the solvent
evaporated under reduced pressure and the residue purified by
column chromatography on silica gel with ether. The product
18b was recrystallized from ether–pentane to give 340 mg (93%)
of yellow crystals with mp 114 ЊC.
11 Furo[3,4-b]benzofurans have been reported only occasionally: (a)
A. Shafiee and E. Behnam, J. Heterocycl. Chem., 1978, 15, 1459;
(b) W. Eberbach, N. Laber, J. Bussenius and G. Rihs, Chem. Ber.,
1993, 126, 975.
12 C. F. Koelsch, J. Am. Chem. Soc., 1945, 67, 569.
13 M. Regitz and G. Maas, Diazo Compounds, Academic Press,
Orlando, 1986.
14 J. B. Hendrickson and W. A. Wolf, J. Org. Chem., 1968, 33, 3610.
This reagent is especially suitable for diazo group transfer reactions,
as the 4-sulfamoylbenzoic acid can be separated quite easily from
the reaction mixture.
15 (a) M. Hamaguchi and T. Ibata, Chem. Lett., 1976, 287; (b) O. Peters
and W. Friedrichsen, in Trends in Heterocyclic Chemistry, Trivan-
drum, 1995, vol. 4, p. 217; (c) T. K. Sarkar, S. K. Ghosh, S. K.
Nandy and T. J. Chow, Tetrahedron Lett., 1999, 40, 397.
16 U. Pindur, G. Lutz and C. Otto, Chem. Rev., 1993, 93, 741.
17 Although 2 regioisomers (8 [C2h] and the corresponding Ci-isomer)
are conceivable according to the 13C NMR structure 8 is preferred
(see Experimental section).
νmax/cmϪ1 2112 (s), 1713 (s), 1574 (m), 1443 (m), 1281 (s),
1162 (m), 748 (m); λmax(CH3CN)/nm (log ε) 295 (1.011), 224
(sh, 3.273), 260 (3.330), 295 (3.154), 400 (1.398); δH(300 MHz;
CDCl3) 4.02 (s, 3H, CO2CH3), 4.79 (td, 2H, O-CH2, J1 1.33,
J 5.75), 5.25–5.50 (2m, 2H, CH᎐CH ), 5.97 (ddt, 1H, CH᎐
᎐
᎐
2
2
CH2, J1 5.77, J2 11.28, J3 16.36), 7.34 (ddd, 1H, C5-H, J1 1.05,
J2 7.02, J3 8.02), 7.50 (ddd, 1H, C6-H, J1 1.30, J2 7.05, J3 8.38),
7.58 (d, 1H, C7-H, J 8.85), 7.71 (d, 1H, C4-H, J 7.74); δC(75
MHz; CDCl3) 52.64 (q, CO2CH3), 65.99 (t, O-CH2), 66.16 (s,
CN ), 112.36 (s, C3), 113.83 (ddd, C7), 118.74 (t, CH᎐CH ),
᎐
2
2
123.41 (dd, C4), 123.86 (dd, C5), 126.68 (s, C3a), 128.54 (dd,
C6), 131.87 (ddd, CH᎐CH ), 139.02 (s, C2), 154.67 (s, C7a),
᎐
2
159.41 (s, C3-CH2-CO2CH2), 164.38 (s, C2-CO2CH3).
18 (a) A. Hosomi and Y. Tominaga, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford,
1995, vol. 5, ch. 5.1; (b) M. Harmata, in Advances in Cycloadditions,
ed. M. Lautens, JAI Press, Greenwich, Com., 1996, vol. 4; (c) M.
Harmata, Tetrahedron, 1997, 53, 6235.
Acknowledgements
The continuous support of our work by the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen
Industrie is gratefully acknowledged.
19 Recent work: (a) R. Dunkel, M. Mentzel and H. M. R. Hoffmann,
Tetrahedron, 1997, 53, 14929; (b) A. M. Montaña, S. Ribes, P. M.
Grima and F. García, Chem. Lett., 1997, 847; (c) M. Harmata and
D. E. Jones, J. Org. Chem., 1997, 62, 1578; (d) M. Harmata and M.
Kahraman, Tetrahedron Lett., 1998, 39, 3421; (e) M. Harmata
and L. Shao, Synthesis, 1999, 1534; ( f ) A. M. Montaña and D.
Fernández, Tetrahedron Lett., 1999, 40, 6499; (g) S. Y. Cho, J. C. Lee
and J. K. Cha, J. Org. Chem., 1999, 64, 3394; (h) S. Sendelbach, R.
Schwetzler-Raschke, A. Radl, R. Kaiser, G. H. Henle, H. Korfant,
S. Reiner and B. Fölisch, J. Org. Chem., 1999, 64, 3398; (i) S. Reck,
C. Näther and W. Friedrichsen, Heterocycles, 1999, in press.
20 The literature of intramolecular Diels–Alder reactions is extensive.
For reviews and examples see ref. 21.
21 (a) W. Oppolzer, Angew. Chem., 1977, 89, 10; Angew. Chem., Int. Ed.
Engl., 1977, 16, 10; (b) G. Brieger and J. N. Bennett, Chem. Rev.,
1980, 80, 63; (c) G. Desimoni, G. Tacconi, A. Barco and G. P.
Pollini, Natural Products Synthesis Through Pericyclic Reactions,
American Chemical Society, ACS Monograph 180, Washington,
1983; (d) E. Ciganek, Org. React., 1984, 32, 1; (e) A. G. Fallis, Can.
J. Chem., 1984, 62, 183; ( f ) D. F. Taber, Intramolecular Diels–Alder
and Alder Ene Reactions, Reactivity and Structure, Concepts in
Organic Chemistry, Springer-Verlag, Berlin, 1984, vol. 18; (g) J. D.
Winkler, Chem. Rev., 1996, 96, 167; (h) D. Craig, in Methods
of Organic Synthesis (Houben-Weyl ), ed. G. Helmchen, R. W.
Hoffmann, J. Mulzer and E. Schaumann, Thieme Verlag, Stuttgart,
1995, vol. E21c, p. 2872; (i) W. R. Roush, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford,
1991, vol. 5, p. 513. For the phrase “tandem” see also L. F. Tietze,
Chem. Rev., 1996, 36, 115, footnote 3; (j) A. Padwa, M. A. Brodney
and M. Dimitroff, J. Org. Chem., 1998, 63, 5304; (k) G. Himbert
and H. Schlindwein, Liebigs Ann./Recl., 1997, 435; (l) C. O. Kappe,
S. S. Murphree and A. Padwa, Tetrahedron, 1997, 53, 14179; (m)
N. Choony, A. Dadabhoy and P. G. Sammes, Chem. Commun.,
1997, 513; (n) A. Padwa, M. A. Brodney, K. Satake and C. S. Straub,
J. Org. Chem., 1999, 64, 4167; E. J. Bush, D. W. Jones and
F. M. Nongrum, J. Chem. Soc., Chem. Commun., 1994, 2145;
(o) D. W. Jones and F. M. Nongrum, J. Chem. Soc., Perkin Trans. 1,
1996, 705.
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23 Similar regioselectivities have been observed in related compounds
(see ref. 22 and literature cited therein). These observations cannot
be accounted for with simple charge density arguments. (AM1
and PM3 calculations24 for 11a reveal that the total charge
density at Cb is lower than at Ca), but can be explained when the
corresponding intermediates are taken into consideration (see
Computational results).
8 S. Reck, C. Näther and W. Friedrichsen, Heterocycles, 1998, 48, 853.
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24 These calculations have been carried out with the program system
HyperChem, version 5.11.
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26 P. Waykole and R. N. Usgaonkar, Indian J. Chem., Sect. B, 1984, 23,
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27 For an unregioselective ring opening reaction of homophthalic
anhydride see: W. V. Murray and S. K. Hadden, J. Chem. Res., 1991,
279.
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398
1397

View Article Online
28 These calculations have been carried out with the program system
Gaussian 9429 and Gaussian 98.30
M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, C. Gonzalez, M.
Challacombe, P. M. W. Gill, B. G. Johnson, W. Chen, M. W. Wong,
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29 Gaussian 94, Revision D.4, M. J. Frisch, G. W. Trucks, H. B.
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31 See also: (a) W. J. Hehre, L. D. Burke, A. J. Shusterman and
W. J. Pietro, Experiments in Computational Organic Chemistry,
Wavefunction, Inc., Irvine, CA, 1993; (b) W. J. Hehre, Practical
Strategies for Electronic Structure Calculations, Wavefunction, Inc.,
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Huang, A Laboratory Book of Computational Organic Chemistry,
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A
Guide to Density Functional Calculations in SPARTAN,
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G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski,
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32 G. Silvero, M. J. Lucero, E. Winterfeldt and K. N. Houk,
Tetrahedron, 1998, 54, 7293.
33 For reaction (4)
a
B3LYP/6-31G*//PM3 calculation gives
∆E(ts) = 26.8 kcal molϪ1 (compared with ∆E(ts) = 22.9 kcal molϪ1 as
a result of a B3LYP/6-31G*//B3LYP/6-31G* treatment (Table 2)).
34 J. N. Chatterjea and R. P. Sahai, J. Indian Chem. Soc., 1980, 57, 633.
35 A. N. Brubaker, J. DeRuiter and W. L. Whitmer, J. Med. Chem.,
1986, 29, 1094.
1398
J. Chem. Soc., Perkin Trans. 1, 2000, 1387–1398