A novel synthesis of 2-alkoxy-3-hydroxytropones and 2,7-dihydroxytropones from dialkoxy-8-oxabicyclo[3.2.1]oct-6-en-3-ones

Article abstract of DOI:10.1002/ejoc.200300600

Trichloro-substituted 8-oxabicyclo[3.2.1]oct-6-en-3-ones 6 and 7 are solvolysed by methanolic sodium methoxide to form the bicyclo[3.2.1] α,α-dimethoxy ketones 13 and 14, with preservation of one chloro substituent. In the case of 6a, prolonged reaction time with an excess of methanolic sodium methoxide provides a trimethoxy-substituted oxanorbornene aldehyde 19 through ring contraction. Treatment of the mixture of 13 and 14 with zinc and aqueous acetic acid affords dechlorinated α-oxo acetals 15 and 16. Starting with the [4+3] cycloadducts derived from 2-methylfuran and tetrachloroacetones (6b and 7b), the same procedure, but with use of ethanol or trifluoroethanol, results in the corresponding ethoxy- and trifluoroethoxy acetals. These compounds can be converted into the oxabicyclic compounds 15, which undergo cleavage of the ether bridge on heating with KOH in methanol, thus providing 2-alkoxy-3-hydroxytropones 20, which can be dealkylated to give the 2,7-dihydroxytropones (7-hydroxytropolones) 29. The lithium enolate generated from the α-oxo acetal 15a can be exo-alkylated with methyl iodide. Michael addition with 2-nitro-1-butene followed by a Nef reaction furnishes the bicyclic dioxo acetal 5. Treatment of 5 with basic methanol results in an epoxyazulenone derivative 26, and a hydroxytropone 20f, which is in equilibrium with the cyclic hemiacetal form 28. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300600

FULL PAPER
A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
from Dialkoxy-8-oxabicyclo[3.2.1]oct-6-en-3-ones
Hartmut Zinser,[a][‡] Sonja Henkel,[a][‡‡] and Baldur Föhlisch*[a]
Keywords: Acetals / Cleavage reactions / Ketones / Solvolysis / Tautomerism
Trichloro-substituted 8-oxabicyclo[3.2.1]oct-6-en-3-ones
6
be converted into the oxabicyclic compounds 15, which un-
dergo cleavage of the ether bridge on heating with KOH in
methanol, thus providing 2-alkoxy-3-hydroxytropones 20,
which can be dealkylated to give the 2,7-dihydroxytropones
(7-hydroxytropolones) 29. The lithium enolate generated
from the α-oxo acetal 15a can be exo-alkylated with methyl
iodide. Michael addition with 2-nitro-1-butene followed by a
Nef reaction furnishes the bicyclic dioxo acetal 5. Treatment
of 5 with basic methanol results in an epoxyazulenone deriv-
and 7 are solvolysed by methanolic sodium methoxide to
form the bicyclo[3.2.1] α,α-dimethoxy ketones 13 and 14,
with preservation of one chloro substituent. In the case of 6a,
prolonged reaction time with an excess of methanolic sodium
methoxide provides a trimethoxy-substituted oxanorbornene
aldehyde 19 through ring contraction. Treatment of the mix-
ture of 13 and 14 with zinc and aqueous acetic acid affords
dechlorinated α-oxo acetals 15 and 16. Starting with the [4+3]
cycloadducts derived from 2-methylfuran and tetrachlo- ative 26, and a hydroxytropone 20f, which is in equilibrium
roacetones (6b and 7b), the same procedure, but with use of with the cyclic hemiacetal form 28.
ethanol or trifluoroethanol, results in the corresponding ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ethoxy- and trifluoroethoxy acetals. These compounds can
Germany, 2004)
Introduction
cal shift of the methyl group (δH ϭ 1.42 ppm; δC ϭ
15.8 ppm), and the small coupling constant between 4-H
and the bridgehead proton 5-H (J4,5 ϭ 0.7 Hz).
Recently, we reported our finding that 2,4-dichloro-8-
oxabicyclo[3.2.1]oct-6-en-3-one (1) undergoes solvolysis in
methanol/methoxide to form 2,2-dimethoxy-8-oxabicy-
clo[3.2.1]oct-6-en-3-one (2), resulting in the 1,3-transpo-
sition of substituents through an enolization/ionization
mechanism.[1,2] In the course of another study,[3] we were
interested in utilizing the enolate generated from the bicyc-
lic α-oxo acetal 2, with the ultimate goal of cleaving the
ether bridge of the oxabicyclic compound. This report de-
scribes our results, which include some unexpected obser-
vations.
Results and Discussion
As expected, the lithium enolate prepared from 2 with
LDA/THF was methylated using a conventional protocol
(MeI, HMPA), resulting in the 4-methyl-bicyclic compound
3 (Scheme 1). Since alkylations of oxabicyclic enolates pre-
fer to occur on the exo face,[4] the configuration at C-4
should be 4-exo.[4] This was proved by the low-field chemi-
Scheme 1. Formation and alkylation of 2: a) CH3ONa/CH3OH,
38%; b) LDA, THF; c) CH3I, HMPT, 82%; d) 2-nitrobut-1-ene; e)
3  H2SO4, H2O/CH3OH, 64%
A functionalized side chain could be attached by treating
the lithium enolate with 2-nitro-1-butene.[5] We did not at-
tempt to isolate the expected nitronate 4 or the correspond-
ing nitro compound (i.e. the Michael adduct), but instead
immediately subjected the reaction mixture to the con-
ditions of a Nef reaction.[6] The dioxo acetal 5 was isolated
in a 64% yield. The NMR spectra indicated that the con-
figuration of 5 was also exo.
[a]
Institut für Organische Chemie der Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: (internat.) ϩ 49-(0)711-6854269
E-mail: baldur.foehlisch@po.uni-stuttgart.de
[‡]
Taken from the Diploma thesis and doctoral dissertation of H.
Zinser, Univ. Stuttgart, 1994 and 1999, respectively.
[‡‡]
X-ray analysis.
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300600
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A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
FULL PAPER
Unfortunately, our preparation of the starting material 2
Four diastereomeric oxabicyclic compounds (6n, 6x, 7n,
from the dichloro-substituted bicyclic compound 1 gave an 7x) could be envisaged to arise from the [4ϩ3] cycload-
unsatisfying yield.[1] Instead of trying to optimize this reac- dition of a 2-substituted furan with a trichlorooxyallyl in-
tion, we investigated the alcoholysis of the oxabicyclic termediate.
α,α,αЈ-trichloro analogues, expecting better stabilization of
the intermediate(s), e.g. 11 (Scheme 2), by the additional
chloro substituent.
With 2-methylfuran, two major products were formed in
the ratio of ca. 70:30. A third product (Ͻ 5%) was detected
by GLC, but we were unable to isolate it. The main prod-
uct, obtained in pure form by recrystallization from meth-
anol, proved to be 6bn.[7] Repeated chromatography
(MPLC) of the mother liquor furnished a small amount of
Scheme 2. Methanolysis and dechlorination of trichloro-8-oxabicy-
clo[3.2.1]oct-6-en-3-ones 6, 7
the minor product. Its structure was unequivocally proved
by an X-ray crystal structure analysis, which showed that
the 2-endo regioisomer, namely 2,4,4-trichloro-1-methyl-
Synthesis of Trichlorooxabicyclic Compounds
8-oxabicyclo[3.2.1]oct-6-en-3-one (7bn, Figure 1), was
The endo-configured oxabicyclic compounds 6an and 6bn formed too.[9]
have previously been obtained in a 45Ϫ54% yield by the
It should be noted that the ‘‘unsymmetrical’’ isomer of
[4ϩ3] cycloaddition reactions of furan and 2-methylfuran 1,1,3,3-tetrachloroacetone (namely, 1,1,1,3-tetrachloroace-
(respectively) with the oxyallyl intermediate generated from tone), would be expected to form the same trichlorooxyallyl
1,1,3,3-tetrachloroacetone in methanol/triethylamine.[7] intermediate(s), and hence should furnish the same oxab-
Hoping for improved yields, we instead used trifluoroe- icyclic compounds with 2-methylfuran. Indeed, the re-
thanol/sodium trifluoroethoxide (TFE/NaTFE).[8] In cases gioisomers 6bn and 7bn were formed in a 67% yield with a
when the furan component was readily available, it was used ratio of 67:33, i.e. practically the same result.
in excess (Table 1). Indeed, furan itself gave the known 4-
2-Isopropylfuran and 2-(benzyloxymethyl)furan, on reac-
endo-bicyclic compound 6an in a 72% yield, purified by ad- tion with 1,1,3,3-tetrachloroacetone, also gave a mixture of
sorptive filtration and crystallization; we did not check the regioisomers 6 and 7. In all the cases studied, the bicyclic
mother liquor for other products such as the 4-exo epimer. compounds 6 are favoured, but the regioselectivity is low
Table 1. Synthesis of trichloro-8-oxabicyclo[3.2.1]oct-6-en-3-ones 6 and 7 from 1,1,3,3-tetrachloroacetone and furans with sodium tri-
fluoroethoxide/trifluoroethanol
6, 7
R
Equiv. of furan
Combined yield (6 ϩ 7) [%]
Ratio 6/7
a
b
c
H
CH3
i-C3H7
BnOCH2
5
5
0.83
1.8
72
65
62
78
Ϫ
2.3:1
3.4:1
1.2:1
d
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1345

H. Zinser, S. Henkel, B. Föhlisch
FULL PAPER
coupling in 1 and 6an, thus proving the formula as 13an.
For the minor isomer, a high-field shift was observed (δ ϭ
3.93 ppm), and the small coupling constant (0.9 Hz) clearly
indicates a 4-endo proton (13ax). The fact that only two
chloro substituents are displaced by methoxy groups is in
line with the enolization/ionization mechanism postulated
for the reaction 1 Ǟ 2.[1] As for the epimerization at C-4,
protonation of the chloroenol(ate) intermediate at equilib-
rium is possible from both faces of the molecule.
After allowing the bicyclic trichloro ketone 6an to react
with an excess of methanolic sodium methoxide at room
temperature for several days, we found that all the chloro
substituents were displaced by methoxy groups. However,
the product contained an aldehyde functionality and three
methoxy groups, as verified by the NMR spectrum (δH
ϭ
9.60, 3.39, 3.36 and 3.26 ppm). Presumably, the oxo acetal
13a is attacked by methoxide at the carbonyl group with
the formation of an epoxide. The latter would undergo a
dyotropic rearrangement with ring contraction to form the
oxanorbornene derivative 19 (Scheme 3).
Scheme 3. Proposed rearrangement mechanism of the chloro ace-
tal 13a
In analogy to the behaviour of the dichloride 1,[1] al-
coholysis of the regioisomers 6bϪd and 7bϪd was expected
to proceed via the same intermediate, i.e. the ion pair 11
(Scheme 2). Hence, and because separation of 6 and 7 pro-
ved to be cumbersome, the trichlorobicyclic compounds
were subjected to alcoholysis as a regioisomeric mixture,
except for 6a. To avoid separation of the endo and exo iso-
mers of the dialkoxychlorobicyclic compounds 13 and 14,
the methanolic product mixture was treated with aqueous
acetic acid and dehalogenated immediately with zinc pow-
Figure 1. X-ray structure of (2-endo)-2,4,4-trichloro-1-methyl-8-
oxabicyclo[3.2.1]oct-6-en-3-one (7bn); see also ref.[9]
(Table 1). It should be noted that a vicinal relationship be-
tween the substituents (R and geminal Cl2) would be ex-
pected to induce more torsional strain in 6 than in 7; that
is, the latter would be thermodynamically more stable. The
fact that 6 is nevertheless favoured points to a stepwise
cycloaddition in which the intermediate(s) 8 are more stable
than 9.[10]
Table 2. Dimethoxy-8-oxabicyclo[3.2.1]oct-6-en-3-ones 15 and 16
formed by methanolysis and dechlorination of trichlorobicyclic
compounds 6 and 7
Solvolysis of Trichlorooxabicyclic Compounds and
Dechlorination
The trichlorobicyclic compound 6an was treated with
methanolic sodium methoxide at 0 °C. After 2.5 h, a mix-
15, 16
R1
Combined yield (15 ϩ 16) [%] Ratio 15/16
ture of the endo- and exo-chlorodimethoxy ketones 13a was a (15a ϭ 2)
H
CH3
i-C3H7 93
BnOCH2 75
97
95
Ϫ
2:1
Ͼ 19:1
8.4:1
obtained in a 93% combined yield (Scheme 2). The 1H
NMR spectrum of the major isomer showed a doublet at
δ ϭ 4.79 ppm with J ϭ 4.5 Hz, consistent with the J4,5
b
c
d
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Eur. J. Org. Chem. 2004, 1344Ϫ1356

A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
FULL PAPER
der, thus affording the dialkoxy ketones 15 and 16 (Table 2).
The cleavage of the ether bridge in 2 can be rationalized
In contrast to the preferred 1,2-position of substituents by the mechanism shown in Scheme 4. In a protic solvent,
in the starting materials 6bϪd, in this case the favoured formation of the enolate derived from 15a (ϭ 2) is revers-
products had the substituents in a 1,4-relationship, that is ible, and a second equilibrium is established, which results
in the ‘‘opposite’’ orientation. Obviously, the oxyallyl inter- in the formation of the ‘‘oxidocycloheptadienone’’ 22.
mediate 11 preferentially associates with alcohol molecules Irreversible elimination of one molecule of methanol gives
at the less hindered (C-4) position. The regioselectivity the delocalized β-tropolonate anion 23.
seems to be influenced by steric interactions of the substitu-
ent R and the alcohol molecule, as indicated by the 15/16
ratio (Table 2).
In the case of 6b, we also replaced methanol by ethanol
and 2,2,2-trifluoroethanol, in the presence of the corre-
sponding sodium alkoxides. The ratio of the regioisomeric
α,α-dialkoxy ketones 15b/16b (with C2H5 or CF3CH2, in-
stead of CH3), produced in a 96% yield after dechlorination
with zinc, was 3.1:1 and 5.1:1, i.e. higher than with meth-
anol (see the Exp. Sect.).
Synthesis of β-Tropolones by Cleavage of Dialkoxybicyclic
Compounds
The pioneering work of Noyori et al. on the transform-
ation of 2- or 3-isopropyl-8-oxabicyclo[3.2.1]oct-6-en-3-one
into isopropyl-substituted tropones and α-tropolones[11] has
initiated the development of improved procedures for the
Scheme 4. Cleavage of oxabicyclic oxo acetals 15: a) KOH,
CH3OH, 65 °C
synthesis of troponoids by cleavage of the bicyclic ether
functionality.[4b,12Ϫ14]
Our attempts to cleave the oxygen bridge in 2 by
TMSOTf/TEA,[12] ZrCl4/piperidine[14] and TiCl4/TEA[15]
gave unsatisfactory results. Surprisingly, it appeared that a
very simple protocol was sufficient; refluxing 15a (ϭ 2) with
10% methanolic KOH solution, followed by acidification
with mineral acid, gave a solid product in 84% yield with
empirical formula C8H8O3 (as deduced from the mass spec-
trum and combustion analysis), thus indicating the elimin-
ation of 1 equiv. of CH3OH.
Similar treatment of the 1-substituted 4,4-dialkoxy ke-
tones 15bϪd furnished the 6-substituted 3-hydroxy-2-meth-
oxytropones 20bϪd in high yields (Table 3). In analogy to
20a, the solution NMR spectra showed a reduced number
of resonances (i.e. averaged signals), due to the rapid taut-
omerism between 20 and 20Ј. Likewise, the intensity of the
averaged signals of the quaternary carbon atoms C-1 and
C-3 was too low to be observed.
The IR spectrum of the solid (as a KBr mull) shows an
extended band between ca. 3500 and 1800 cmϪ1, with peaks
at 3010 and 2920 cmϪ1. The first sharp peaks (of medium
intensity) at 1625 cmϪ1 are inconsistent with the value ex-
pected for the carbonyl absorption of a carboxylic acid, but
in line with a hydroxytropone structure (20a). Further indi-
cations of this structure were provided by the strong ab-
Table 3. Synthesis of 2-alkoxy-3-hydroxytropones 20 by cleavage of
2,2-dialkoxybicyclic compounds
Compound Reaction time Product R1
R2
Yield [%]
sorptions at 1570, 1535 and 1500 cmϪ1 [16]
.
15a ؍ 2
16 h
16 h
24 h
16 h
12 h
8 h
20a
20b
20c
20d
20e
20f
H
CH3
i-C3H7
BnOCH2 H
H
H
H
H
H
85
84
78
58
88
15b
15c
15d
3
1
Unambiguous proof of the structure came from the H
NMR solution spectrum (CDCl3) which indicates an ‘‘enol-
ic’’ hydroxy group (δ ϭ 7.40 ppm) and the presence of one
methoxy group (δ ϭ 4.03 ppm). A symmetrical multiplet,
presumably of an AAЈBBЈ type, centered at δ ϭ 7.05 ppm
(cf. δ ϭ 7.04 ppm reported for 3-hydroxytropone[17]), is in
accordance with a rapid tautomeric equilibrium through in-
CH3
2-oxobutyl 72
5
The minor alcoholysis products 16bϪd did not react un-
termolecular proton transfer between the hydroxy and oxo der these conditions. Evidently, elimination of methanol is
groups (20a o 20aЈ). This degenerate isomerization leads not possible from the cleavage product 25, which is in equi-
to averaged signals in the NMR spectra (C2v pseudosym- librium with 24 and 16. Hence, when the mixtures from
metry). However, only three out of the four lines expected alcoholysis 15 ϩ 16 were treated with water, unchanged 16
from the sp2 carbon nuclei in the 13C NMR spectrum of could be separated easily from the anions 23 by extraction
20a were found. Obviously, the intensities of the averaged of the alkaline aqueous phase. Undoubtedly, this separation
signals of the quaternary carbon atoms C-1 and C-3 were protocol is preferable to chromatography of the mixtures of
too low to be observed.
15 and 16.
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1347

H. Zinser, S. Henkel, B. Föhlisch
FULL PAPER
The cleavage of the ethyl and trifluoroethyl oxo acetals
prepared from 6b ϩ 7b by heating with 10% methanolic
KOH led to the ethoxy and trifluoroethoxy analogues of
20b, in 82 and 90% yield, respectively (see the Exp. Sect.).
In other words, the alkoxy substituents were preserved, in
accordance with the mechanism shown in Scheme 4.
However, in contrast, the oxabicyclic compounds 3 and
5, bearing a substituent in α-position to the carbonyl group
(Scheme 1), were transformed to the corresponding
hydroxytropones 20e and 20f in good yield. In the case of
5, an oxabicyclic by-product 26 was found, which proved to
arise from an intramolecular aldol condensation of this 1,4-
diketone (Scheme 5). This epoxyazulenone 26 was formed
preferentially on reaction with methanolic KOH under
‘‘mild’’ conditions (room temperature, 3 d) in a 68% yield.
Refluxing a solution of 5 in methanolic sodium methoxide
for 6 h gave the tropone 20f as the main product (72%
yield), with 16% of 26.
Demethylation of the Methoxytropones
4-Methyl- and 4-isopropyl-7-methoxy-(α)-tropolone, iso-
mers of the β-tropolones 20b and 20c, respectively, have
previously been demethylated by HBr/acetic acid to give
2,7-dihydroxy-4-methyltropone (29b) and 2,7-dihydroxy-4-
isopropyltropone (29c).[18] The latter is the natural product
β-thujaplicinol, which was isolated from the heartwood of
the Western red cedar (Thuja plicata Donn.), and other
species of the family Cupressaceae.[19,20] We therefore
treated the methoxytropones 20aϪc and 20e with HBr/
acetic acid, and obtained the 7-hydroxytropolones 29aϪd
in very good yields (Ͼ 94%) (Table 4). Banwell’s syn-
thesis[18] used expensive organostannanes and palladium
catalysts, but our methodology avoids this. However, the
present approach hinges on the availability of the substi-
tuted furans needed for the [4ϩ3] cycloadducts. A drawback
is formation of the ‘‘wrong’’ oxabicyclic compounds 16,
that result in diminished yields of the alkoxytropones 20.
Table 4. Synthesis of hydroxytropolones 29 by demethylation of 2-
alkoxy-3-hydroxytropones 20
Compound
R1
R2
Yield [%]
29a
29b
29c
29d
H
H
H
H
CH3
94
Ͼ 99
96
CH3
i-C3H7
H
97
Scheme 5. Intramolecular aldol condensation versus cleavage of the
diketone 5
Regarding the structure of the compound assigned to for-
mula 20f, spectroscopy showed that it can exist in rapidly
interconverting forms. No absorption in the range expected
for the carbonyl band of the oxobutyl side chain was pre-
sent in the IR spectrum of solid 20f (cf. 5: 1715 and 1735
cmϪ1). This observation, together with the presence of a
strong absorption at 3120 cmϪ1, is consistent with the cyclic
hemiacetal form 28. Obviously the tautomeric form 27, or
rather its anion 20f؊, undergoes ring closure (Scheme 5).
The NMR spectra of a [D6]acetone solution of this mix-
ture were consistent with a rapid equilibrium between the
tautomers 20f and 27 and the hemiacetal 28, the latter com-
prising 45% of the mixture. In the 13C NMR spectrum, res-
onances at δ ϭ 110.9 and 180.2 ppm indicate the ‘‘acetalic’’
Scheme 6. Demethylation of 3-hydroxy-2-methoxytropones 20
Conclusions
The cleavage of the α-oxo acetal 2 and its analogues with
carbon atom and the ‘‘troponoid’’ carbonyl carbon atom, the formation of 3-hydroxytropones opens a novel route to
respectively. In [D6]DMSO solution, the exchange is so ra- 2-alkoxy-3-hydroxytropones, which can be dealkylated to
pid that no carbon resonances from the tropone nucleus give dihydroxytropones. The former are structural isomers
1
were found. The H NMR spectrum showed a few, very of the natural products MY3-469[21] and β-thujaplicinol
broad signals. Unfortunately, the solubility in CDCl3 was methyl ether.[22] Several hydroxytropones, among them 20a,
too low to obtain satisfying spectra.
are reported to exhibit interesting pharmacological
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A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
FULL PAPER
properties.[21,23Ϫ25] As for the preparation of α-oxo acetals,
it is not unreasonable that optimization of the reaction of
dichlorooxabicyclic ketones (e.g. 1) would simplify the
hydroxytropone synthesis.
less oil that solidified on standing. Recrystallization form MTBE/
hexane gave a colourless solid with m.p. 37Ϫ39 °C. C10H14O4
(198.2): calcd. C 60.59, H 7.12; found C 60.56, H 7.10. IR (KBr):
ν˜ ϭ 3060 (w, ϭCϪH), 2960, 2930, 2890, 2820 (m, CϪH), 1715 (s,
CϭO), 1590 cmϪ1 (w, CϭC). 1H NMR (250 MHz, CDCl3): δ ϭ
1.42 (d, J ϭ 7.4 Hz, 3 H, CH3), 2.40 (dq, J ϭ 7.4, 0.7 Hz, 1 H, H-
4), 3.29 (s, 3 H, endo-OCH3), 3.43 (s, 3 H, exo-OCH3), 4.67 (s, 1
H, H-5), 4.95 (d, J ϭ 1.8 Hz, 1 H, H-1); AB subspectrum centered
at δ ϭ 6.29, with δA ϭ 6.37 and δB ϭ 6.21 (JAB ϭ 6.0 Hz; the lines
of the A-part are split into a dd with J ϭ 1.8, 0.5 Hz; the lines of
the B-part are split into doublets with J ϭ 1.8 Hz, 6-H and 7-H)
ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 15.8 (4-CH3), 49.5 (C-4),
49.6 (endo-OCH3), 50.8 (exo-OCH3), 80.4 (C-5) 83.0 (C-1), 99.8 (C-
2), 129.8 (C-7), 136.2 (C-6), 204.3 (C-3) ppm.
Experimental Section
General Remarks: IR spectra were recorded with a PerkinϪElmer
457 instrument. NMR spectra were recorded with a Bruker AC 250
spectrometer (for 62.9 MHz 13C NMR and 250 MHz 1H NMR
spectra) and a Bruker ARX 500 spectrometer (for 500 MHz 1H
NMR spectra and 125.8 MHz 13C NMR spectra). Tetramethylsil-
ane was used as an internal standard; the solvents are specified in
the text. For higher-order 1H NMR spectra that could not be fully
analyzed, chemical shift ranges or, in the case of symmetrical sig-
nals, centers of the multiplets (mc) are given. EIMS were recorded
with a Varian MAT 711 spectrometer with data system SS 100.
Analytical TLC was performed on precoated sheets [Polygram Sil
G/UV254(silica)], distributed by MachereyϪNagel & Co. (Düren,
Germany). Detection was by UV extinction, or by spraying with
KMnO4 or vanillin/H2SO4 solution, followed by warming. Pre-
parative column chromatography employed Silica 60 (40Ϫ63 µm),
distributed by MachereyϪNagel & Co. (Düren, Germany). Melting
points were determined with a Büchi 510 apparatus from Büchi
Laboratoriumstechnik AG (Flawil, Switzerland), and are not cor-
rected. Elemental analyses were performed at the Institut für Or-
ganische Chemie, University of Stuttgart. Dry petroleum ether
(PE) was distilled (b.p. 40Ϫ65 °C). Ethyl acetate (EA) was dried
(4-exo)-2,2-Dimethoxy-4-(2-oxobutyl)-8-oxabicyclo[3.2.1]oct-6-en-3-
one (5): A solution of LDA (5.2 mmol) in THF (15 mL) was pre-
pared under nitrogen and cooled to Ϫ40 °C. With magnetic stir-
ring, a solution of 2 (800 mg, 4.35 mmol) in dry THF (10 mL) was
added. The mixture was stirred for 30 min, and a solution of 2-
nitro-1-butene[31] (600 mg, 5.94 mmol) in dry THF (1 mL) was ad-
ded. The mixture was warmed to 0 °C (2 h) and then stirred for
30 min at this temperature. A solution of concd. H2SO4 (10.0 mL)
in methanol/water (2:1, 50 mL) was prepared. With vigorous stir-
ring, the THF reaction mixture was added slowly to the acid, which
became turquoise-green in colour. When the colour had faded, stir-
ring was continued for 30 min. Ice-cold water (50 mL) and diethyl
ether (50 mL) were added, and the layers separated. The aqueous
layer was saturated with NaCl and extracted with diethyl ether (4
ϫ 50 mL). The combined diethyl ether extracts were washed with
saturated solutions of NaHCO3 (30 mL) and NaCl (30 mL), and
dried with Na2SO4. The solvent was evaporated, and the remaining
orange-coloured oil subjected to chromatography on silica (100 g),
eluting with EA/PE (1:7). The colourless oil (5, 710 mg, 64%) ob-
tained after evaporation solidified on standing. Recrystallization
from MTBE/hexane gave a colourless solid with m.p. 55Ϫ56 °C.
C13H18O5 (254.3): calcd. C 61.41, H 7.13; found C 61.37, H 7.11.
IR (KBr): ν˜ ϭ 3070, 3060 (m, ϭCϪH), 2980, 2950, 2920, 2890,
2860, 2820 (ms, CϪH), 1735, 1715 (s, CϭO), 1580 cmϪ1 (w, Cϭ
C). 1H NMR (250 MHz, CDCl3): δ ϭ 1.08 (t, J ϭ 7.3 Hz, 3 H,
CH2CH3), 2.46 (q, J ϭ 7.3 Hz, 2 H, CH2CH3), 2.81 (ddd, J ϭ 11.0,
3.0, 0.7 Hz, 1 H, H-4) ppm; AB subspectrum centered at δ ϭ 2.92,
with δA ϭ 3.20 and δB ϭ 2.63 (J ϭ 18.1 Hz; the lines of the A-
part are split into doublets with J ϭ 11.0 Hz; the lines of the B-
part are split into doublets with J ϭ 3.0 Hz, 4n-H and 4x-H), 3.31
(s, 3 H, endo-OCH3), 3.45 (s, 3 H, exo-OCH3), 4.78 (d, J ϭ 0.6 Hz,
1 H, H-5), 4.91 (d, J ϭ 1.8 Hz, 1 H, H-1) ppm; AB subspectrum
centered at δ ϭ 6.31, with δA ϭ 6.41 and δB ϭ 6.20 (J ϭ 6.1 Hz;
the lines of the A-part are split into a dd with J ϭ 1.6, 0.5 Hz; the
lines of the B-part are split into doublets with J ϭ 1.6 Hz, 6-H and
7-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 7.8 (CH2CH3), 36.1
(CH2CH3), 41.2 (CH2 at C-4), 49.8 (C-4), 50.2 (endo-OCH3), 50.5
(exo-OCH3), 80.1 (C-5), 80.6 (C-1), 99.6 (C-2), 129.9 (C-7), 136.2
(C-6), 203.6 (C-3), 208.3 (CϭO) ppm.
˚
with calcium chloride, distilled, and kept dry over 4-A molecular
sieves. Methanol was dried by refluxing with magnesium turnings,
followed by distillation. Ethanol was dried with sodium and diethyl
phthalate, followed by distillation. Tetrahydrofuran (THF) was
dried with sodium and distilled in presence of benzophenone indi-
cator. Sodium trifluoroethoxide/trifluoroethanol (NaTFE/TFE)
was prepared according to the literature method.[8c]. Hexameth-
ylphosphoric acid triamide (HMPA) and diisopropylamine were
dried with and distilled from powdered calcium hydride. For the
preparation of lithium diisopropylamide (LDA), a 1.6  solution
of n-butyllithium in hexane (Merck) was used. Furan and 2-meth-
ylfuran (Merck, Fluka) were stored over KOH pellets and distilled
from KOH prior to use. 2-Isopropylfuran and 2-(benzyloxymethyl)-
furan were prepared according to literature procedures.[26,27]
1,1,3,3-Tetrachloroacetone (1,1,3,3-TeCA) was prepared from
1,1,3-trichloroacetone (Merck, Fluka) and sulfuryl chloride;[28] for
an alternative preparation see ref.[29] 1,1,1,3-Tetrachloroacetone
(1,1,1,3-TeCA) was obtained by chlorination of 1,1,1-trichloroace-
tone.[30]
(4-exo)-2,2-Dimethoxy-4-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one
(3): A solution of LDA (4.9 mmol) in THF (10 mL) was prepared
under nitrogen and cooled to 0 °C. With magnetic stirring, a solu-
tion of 2 (753 mg, 4.09 mmol) in dry THF (8 mL) was added, and
stirred for 30 min. Using a syringe, HMPA (700 µL, 4.0 mmol) was
added rapidly, followed by methyl iodide (400 µL, 6.4 mmol), and
stirring continued at 0 °C for 2.5 h. The reaction mixture was
(4-endo)-2,2,4-Trichloro-8-oxabicyclo[3.2.1]oct-6-en-3-one
(6an):
1,1,3,3-TeCA (19.60 g, 100 mmol) was mixed with furan (34.0 g,
quenched with 0.5  HCl (20 mL) and the organic layer separated. 500 mmol) and TFE (5 mL) and cooled in an ice bath. A 2  solu-
The aqueous layer was extracted with diethyl ether (3 ϫ 30 mL). tion of NaTFE in TFE (50 mL, 100 mmol) was added dropwise
The combined organic extracts were washed with saturated solu- with vigorous magnetic stirring over 2 h. The mixture was stirred
tions of NaHCO3 (15 mL) and NaCl (15 mL) and dried with
Na2SO4. The solvent was removed in a rotary evaporator, and the
remaining yellow oil subjected to chromatography on silica (40 g).
Elution with EA/PE (1:7) furnished 665 mg (82%) of 3, as a colour-
for a further 30 min and then diluted with water (50 mL) and di-
chloromethane (50 mL). The layers were separated, and the aque-
ous layer extracted with dichloromethane (2 ϫ 50 mL). The com-
bined organic extracts were washed with brine (2 ϫ 40 mL), dried
Eur. J. Org. Chem. 2004, 1344Ϫ1356
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1349

H. Zinser, S. Henkel, B. Föhlisch
FULL PAPER
with Na2SO4 and concentrated in a rotary evaporator. Recrystalli-
For the X-ray crystal structure determination a Nicolet P3 four-
zation of the remaining brown solid gave 13.51 g (59%) of 6an. The circle diffractometer equipped with a graphite monochromator was
brown residue from the mother-liquor was filtered through silica
(40 g), eluting with EA/PE (1:5). The residue of the eluate was
recrystallized from methanol, giving a further 2.89 g of 6an. Total
yield 16.40 g (72%) 6an as a pale yellow solid that was pure enough
(Ͼ 99%) for further reactions. Colourless crystals with m.p. 87Ϫ88
used, at 293 K. The X-ray source was monochromatic Mo-Kα radi-
ation, wavelength 71.069 pm. The lattice constants were a ϭ
702.49(10), b ϭ 1040.24(14), c ϭ 1329.06(17) pm, determined from
the 2θ values of 30 automatically centered reflexes (30° Ͻ 2θ Ͻ
35°) by means of the least-squares method;[32] the crystal lattice
°C were obtained by sublimation at 70 °C/0.001 Torr (ref.[7] 88Ϫ89 was orthorhomic. The intensity data were taken in the Wyckoff-
°C). IR (KBr): ν˜ ϭ 3080 (mϪw, ϭCϪH), 2920 (m, CϪH), 1745 scan mode with a 1° angle range and scan rates between 1.0 and
cmϪ1 (s, CϭO). 1H NMR (250 MHz, CDCl3): AB subspectrum 29.3 °/min, depending on reflection intensity. Thus, up to a maxi-
centered at δ ϭ 5.14, with δA ϭ 5.15 (H-4) and δB ϭ 5.13 (H-5)
(JAB ϭ 4.6 Hz; the lines of the B-part are split into doublets with
J ϭ 1.4 Hz); δ ϭ 5.16 (d, J ϭ 1.7 Hz, 1 H, H-1), AB subspectrum
centered at δ ϭ 6.56, with δA ϭ 6.63 (H-7) and δB ϭ 6.51 (H-6)
(JAB ϭ 6.0 Hz; the lines of the A-part are split into doublets with
mum scattering angle 2θmax. ϭ 55°, 1637 independent reflections
were found; among these 1552 with Iobsd. Ͼ 3σ(Iobsd.) were classi-
fied as ‘‘observed’’. The raw data were scaled from three check
reflections Ϫ the largest deviation was 3% Ϫ and subjected to a
Lorentz and polarization correction. By means of direct methods
J ϭ 1.8 Hz; the lines of the B-part are split into doublets with J ϭ (SHELX 86)[33] a structure model was obtained that was refined
1.2 Hz) ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 61.7 (C-4), 82.65
by the full-matrix least-squares procedure. In addition to the ob-
(C-5), 85.1 (C-2), 87.4 (C-1), 132.9 and 134.9 (C-6 and C-7), 186.2 served data further reflexes with intensities Ͼ 4σ(Iobsd.) were used.
(C-3) ppm.
Thus 1577 reflexes contributed to refinement of 147 parameters
(scaling factor, position parameter, anisotropic temperature factors
for C, O, and Cl atoms, isotropic temperature factors for H atoms)
up to R ϭ 0.030 and Rw ϭ 0.034, respectively, with 1/w ϭ 0.1 ϩ
σ(F)2 ϩ 10Ϫ4F ϩ 10Ϫ6F2 ϩ (3 ϫ 10Ϫ5)F3. The estimated overall
standard deviation of an observation with weight one was σ ϭ 1.11.
Reaction of 1,1,3,3-TeCA with 2-Methylfuran: (4-endo)-2,2,4-Tri-
chloro-1-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (6bn) and (2-endo)-
2,4,4-Trichloro-1-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (7bn)
Method a): 1,1,3,3-TeCA (7.8 g, ca. 40 mmol) was mixed with 2-
methylfuran (18 mL, 200 mmol) and cooled in an ice bath to 0 °C.
A 2  solution of NaTFE in TFE (20 mL, 40 mmol) was added
dropwise with vigorous magnetic stirring over 45 min. The mixture
was stirred at 0 °C for further 2 h, and then diluted with water
(40 mL). The layers were separated, and the aqueous layer was ex-
tracted with dichloromethane (3 ϫ 20 mL). The combined organic
extracts were washed with brine (30 mL), dried with Na2SO4 and
concentrated in a rotary evaporator. The brown residue was filtered
through silica (40 g), eluting with PE/EA (3:1). The residue from
the eluate was recrystallized from PE/EA, giving 4.45 g (46%) of
pale yellow crystals, a mixture of isomers 6bn and 7bn (70:30), ac-
cording to the NMR spectra. Fractional crystallization from meth-
anol gave 750 mg (8%) of colourless rhombic crystals (6bn) with
m.p. 91Ϫ94 °C (ref.[7] 93Ϫ94 °C). 6bn: 1H NMR (250 MHz,
CDCl3): δ ϭ 1.77 (s, 1-CH3), AB subspectrum with δA ϭ 5.14 (H-
Method b): 1,1,3,3-TeCA (1.96 g, 10 mmol) was mixed with 2-meth-
ylfuran (4.1 g, ca. 50 mmol) and cooled in an ice bath to 0 °C. A
1  solution of NaTFE in TFE (10 mL, 10 mmol) was added drop-
wise with vigorous magnetic stirring over 1 h. The mixture was
stirred at 0 °C for further 30 min, and then diluted with water
(30 mL) and dichloromethane (30 mL). The layers were separated,
and the aqueous layer extracted with dichloromethane (2 ϫ
20 mL). The combined organic extracts were washed with brine,
dried with Na2SO4 and concentrated in a rotary evaporator. The
brown residue was filtered through silica (50 g), eluting with PE/
EA (10:1). The residue from the eluate was recrystallized from
methanol, giving 1.57 g (65%) of a mixture of isomers 6bn and 7bn
1
(2:1), according to the H NMR spectrum. This mixture was used
for preparation of the oxo acetals 15b and 16b (see below).
4), δB ϭ 5.08 (H-5) (JAB ϭ 4.5 Hz, centre at δ ϭ 5.11 ppm). The Reaction of 1,1,1,3-Tetrachloroacetone with 2-Methylfuran: A mix-
lines of the B part are duplicated with J ϭ 1.7 Hz. AB subspectrum
with δA ϭ 6.51 (H-6), δB ϭ 6.32 (H-7) (JAB ϭ 5.9 Hz, centre at
ture of 1,1,1,3-tetrachloroacetone[30] (2.85 g, 14.5 mmol) and 2-
methylfuran (5.95 g, 72.5 mmol) was treated with a 2  NaTFE
δ ϭ 6.41 ppm). The lines of the A part are duplicated with J ϭ solution in TFE for 2 h, as described for 1,1,3,3-TeCA (see above,
1.6 Hz. 13C NMR (62.9 MHz, CDCl3): δ ϭ 16.5 (1-CH3), 61.2 (C- first experiment). The same workup afforded 1.78 g (51%) of an
4), 82.5 (C-2), 90.3 (C-1), 91.7 (C-5), 134.15 and 136.5 (C-6 and C-
7), 186.6 (C-3) ppm. IR (KBr): ν˜ ϭ 3080, 2990, 2970, 2930 (CH),
1755 with shoulder at 1740 cmϪ1 (CϭO). The fractions enriched
with the isomer 7bn (280 mg) were subjected to MPLC on silica
using a 20 cm column, diameter 2.5 cm, packed with LiChroprep
Si 60, 15Ϫ25 mµ (Merck). Elution was made with PE/EA (4:96)
under pressure (10 bar). The residue of the eluates that contained
pure 7bn (32 mg) was dissolved in CDCl3 to record the NMR spec-
tra. 7bn: 1H NMR (250 MHz, CDCl3): δ ϭ 1.69 (s, 1-CH3), 4.90 (s,
1 H, H-2), 5.14 (d, J5,6 ϭ 1 Hz, 1 H, H-5), 6.39 (mc, 2 H, H-6, H-
7) ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 20.55 (1-CH3), 67.5
(C-2), 84.6 (C-1), 87.1 (C-4), 89.7 (C-5), 132.05 and 138.0 (C-6, C-
7), 186.4 (C-3) ppm. IR (KBr): ν˜ ϭ 3090, 2960, 2910 (CH), 1750,
isomeric mixture of 6bnϩ7bn in the ratio of 67:33, according to the
1H NMR spectrum.
Reaction of 1,1,3,3-TeCA with 2-Isopropylfuran: (4-endo)-2,2,4-
Trichloro-1-isopropyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (6cn) and (2-
endo)-2,4,4-Trichloro-1-isopropyl-8-oxabicyclo[3.2.1]oct-6-en-3-one
(7cn): Prepared from 2-isopropylfuran[26] (880 mg, 8.0 mmol) in
TFE (8 mL), and 1,1,3,3-TeCA (1.88 g, 9.6 mmol) with 1  NaTFE
solution in TFE (9.6 mL, 9.6 mmol), as described for 6b. The solu-
tion of base was added over 45 min, followed by 30 min of stirring.
The brown, oily product was subjected to chromatography on silica
(100 g), eluting with EA/PE (1:10). The regioisomers 6cn (1.03 g)
and 7cn (307 mg) were obtained with yields of 48% and 14%,
respectively. After recrystallization from methanol the isomers
showed m.p. 72 °C (6cn) and 98 °C (7cn). 6cn: C10H11Cl3O2 (269.6):
calcd. C 44.56, H 4.11, Cl 39.46; found C 44.59, H 4.16, Cl 40.41.
1730 cmϪ1 (CϭO) cmϪ1
.
X-ray Crystallographic Study of 6bn:[9] The CDCl3 solution was
transferred to a small test tube (5 ϫ 0.5 cm) and concentrated IR (KBr): ν˜ ϭ 3080 (s, ϭCϪH), 2960, 2920, 2860 (m, CϪH), 1750
1
slowly. The compound crystallized with space group P212121 with
Z ϭ 4 molecules/unit cell and had m.p. 120Ϫ121 °C. A crystal (1.0
ϫ 0.9 ϫ 0.8 mm) was selected and fixed onto a thin glass capillary.
(s, CϭO), 1590 cmϪ1 (s, CϭC). H NMR (250 MHz, CDCl3): δ ϭ
1.12 (d, J ϭ 6.9 Hz, 3 H, CH3), 1.20 (d, J ϭ 7.0 Hz, 3 H, CH3),
2.71 [sept, J ϭ 6.9 Hz, 1 H, CH(CH3)2] ppm; AB subspectrum
1350
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 1344Ϫ1356

A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
FULL PAPER
centered at δ ϭ 5.11, with δA ϭ 5.13 (H-4) and δB ϭ 5.09 (H-5)
(JAB ϭ 4.6 Hz; the lines of the B-part are split into doublets with
J ϭ 1.5 Hz); AB subspectrum centered at δ ϭ 6.41, with δA ϭ 6.49
washed with brine, dried with Na2SO4 and concentrated in a rotary
evaporator. The remaining yellow oil became crystalline and was
recrystallized from diethyl ether/pentane, giving 1.46 g (67%) of
(H-6) and δB ϭ 6.34 (H-7) (JAB ϭ 6.0 Hz; the lines of the A-part 13an as a colourless solid with m.p. 56Ϫ57 °C. Chromatography of
are split into doublets with J ϭ 1.4 Hz) ppm. 13C NMR (62.9 MHz, the mother liquor on silica (50 g) with EA/PE (1:5) gave a further
CDCl3): δ ϭ 18.7 and 20.2 (diastereotopic CH3), 29.9 [CH(CH3)2], 370 mg (17%) of 13an and 196 mg (9%) of 13ax with m.p. 73Ϫ74
61.3 (C-4), 82.2 (C-5), 90.6 (C-1), 96.0 (C-2), 133.7 and 134.6 (C-6
and C-7), 186.9 (C-3) ppm. 7cn: IR (KBr): ν˜ ϭ 3090 (w, ϭCϪH), 49.66, H 5.13, Cl 16.27. 13an: IR (KBr): ν˜ ϭ 3080 (m, ϭCϪH),
2960, 2850 (m, CϪH), 1740 (s, CϭO), 1590 cmϪ1 (w, CϭC). 1H
2980, 2960, 2920, 2830, 2820 (ms, CϪH), 1745 (s, CϭO), 1585
NMR (250 MHz, CDCl3): δ ϭ 1.08 (d, J ϭ 6.9 Hz, 3 H, CH3), cmϪ1 (m, CϭC). H NMR (250 MHz, CDCl3): δ ϭ 3.38 (s, 3 H,
1.27 (d, J ϭ 7.0 Hz, 3 H, CH3), 2.74 [sept, J ϭ 6.9 Hz, CH(CH3)2], endo-OCH3), 3.52 (s, 3 H, exo-OCH3), 4.79 (d, J ϭ 4.5 Hz, 1 H,
4.15 (d, J ϭ 1.0 Hz, H-2), 5.06 (mc, H-5) ppm; AB subspectrum H-4), 4.96 (d, J ϭ 1.7 Hz, 1 H, H-1), 5.05 (dd, J ϭ 4.5, 1.6 Hz, 1
centered at δ ϭ 6.39, with δA ϭ 6.45 (H-7) and δB ϭ 6.32 (H-6) H, H-5) ppm; AB subspectrum centered at δ ϭ 6.39, with δA
(JAB ϭ 6.0 Hz; the lines of the B-part are split into a dd with J ϭ 6.46 (H-7) and δB ϭ 6.33 (H-6) (JAB ϭ 6.1 Hz; the lines of the A-
1.8 Hz and 0.6 Hz) ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 18.5 part are split into doublets with J ϭ 1.8 Hz, the B-part with 1.6 Hz)
(CH3), 20.05 (CH3) (diastereotopic CH3), 30.5 [CH(CH3)2], 56.3
ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 50.6 (endo-OCH3), 51.1
(C-2), 82.6 (C-5), 88.0 (C-1), 95.6 (C-4), 132.5 and 135.3 (C-6 and (exo-OCH3), 62.8 (C-4), 80.7 (C-5), 82.5 (C-1), 102.7 (C-2), 132.7
°C. C9H11ClO4 (218.6): calcd. C 49.44, H 5.07, Cl 16.22; found C
1
ϭ
C-7), 190.3 (C-3) ppm.
and 133.4 (C-6 and C-7), 194.45 (C-3) ppm. 13ax: IR (KBr): ν˜ ϭ
3070 (m, ϭCϪH), 2970, 2940, 2920, 2810 (m, CϪH), 1735 (s, Cϭ
1
O), 1585 cmϪ1 (m, CϭC). H NMR (250 MHz, CDCl3): δ ϭ 3.35
Reaction of 1,1,3,3-TeCA with 2-Benzyloxymethylfuran: (4-endo)-1-
Benzyloxymethyl-2,2,4-trichloro-8-oxabicyclo[3.2.1]oct-6-en-3-one
(6dn) and (2-endo)-1-Benzyloxymethyl-2,4,4-trichloro-8-oxabicy-
clo[3.2.1]oct-6-en-3-one (7dn): Prepared from 2-(benzyloxymethyl)-
furan[27] (1.69 g, 9.0 mmol) in TFE (10 mL) and 1,1,3,3-TeCA
(980 mg, 5.0 mmol) with 1  NaOTFE solution in TFE (5 mL,
5 mmol), as described for 6b. The time taken for the addition was
45 min, followed by 30 min of stirring. The brown, oily product
was subjected to chromatography on silica (50 g), eluting with EA/
PE (1:10). Separation was not successful; according to the 1H
NMR the oil obtained (1.48 g, ca. 78%) consisted of the regioiso-
(s, 3 H, endo-OCH3), 3.44 (s, 3 H, exo-OCH3), 3.93 (d, J ϭ 1.1 Hz,
1 H, H-4), 5.01 (s, 1 H, H-5), 5.05 (d, J ϭ 1.8 Hz, 1 H, H-1) ppm;
AB subspectrum centered at δ ϭ 6.37, with δA ϭ 6.39 (H-7) and
δB ϭ 6.34 (H-6) (JAB ϭ 6.1 Hz; the lines of the A-part are split
into doublets with J ϭ 1.8 Hz, the B-part with J ϭ 1.5 Hz) ppm.
13C NMR (62.9 MHz, CDCl3): δ ϭ 49.5 (endo-OCH3), 51.5 (exo-
OCH3), 56.6 (C-4), 80.7 (C-5), 82.6 (C-1), 100.4 (C-2), 132.55 and
133.55 (C-6 and C-7), 194.6 (C-3) ppm.
2,3,3-Trimethoxy-7-oxabicyclo[2.2.1]hept-5-ene-2-carbaldehyde (19):
mers 6dn and 7dn, in the ratio of 1.2:1, and impurities (ca.10%). A solution of 2  sodium methoxide in methanol (6.0 mL) was
This impure product mixture was used for the methanolysis pro-
added with stirring over 10 min to a cooled (0 °C) solution of 6an
(455 mg, 2.0 mmol) in dry methanol (6 mL). Stirring was continued
cedure described below. IR (CDCl3): ν˜ ϭ 3080, 3050, 3020 (mw, ϭ
CϪH), 2930, 2910, 2850 (m, CϪH), 1765 (s, CϭO), 1590 cmϪ1 (w, for a further 30 min. The ice bath was then removed, and the mix-
CϭC). 6dn: 1H NMR (500 MHz, CDCl3): AB subspectrum with
δA ϭ 4.08, δB ϭ 4.27 (JAB ϭ 11.4 Hz, diastereotopic CH2OBn);
AB subspectrum with δA ϭ 4.72, δB ϭ 4.60 (JAB ϭ 12.1 Hz, dia-
stereotopic PhCH2); AB subspectrum centered at δ ϭ 5.15, with
δA ϭ 5.16 (H-5) and δB ϭ 5.14 (H-4) (JAB ϭ 4.5 Hz; the lines of
ture stirred at room temperature for 5 d. Water (20 mL) was added,
and the mixture extracted with dichloromethane (5 ϫ 20 mL). The
combined extracts were washed with brine, dried with Na2SO4 and
concentrated in a rotary evaporator. The remaining pale yellow oil
was chromatographed on silica (20 g). Elution with PE/EA (2:1)
the A-part are split into doublets with J ϭ 1.7 Hz); AB subspec- gave 160 mg (37%) of 19 as a colourless solid with m.p. 100Ϫ110
trum centered at δ ϭ 6.49, with δA ϭ 6.55 (H-6) and δB ϭ 6.42
(H-7) (JAB ϭ 5.9 Hz; the lines of the A-part are split into doublets
°C. C10H14O5 (214.2): calcd. C 56.07, H 6.59; found C 55.99, H
6.56. IR (KBr): ν˜ ϭ 2940, 2910, 2820, 2710 (ms, CϪH), 1720 (s,
1
with J ϭ 0.9 Hz), 7.25Ϫ7.40 (m, 5 H, C6H5) ppm. 13C NMR CϭO), 1570 cmϪ1 (CϭC). H NMR (500 MHz, CDCl3): δ ϭ 3.26
(125.8 MHz, CDCl3): δ ϭ 61.3 (C-4), 67.2 (CH2OBn), 73.9 (s, 3 H, CH3O at C-2), 3.36 (s, 3 H, endo-OCH3 at C-3), 3.39 (s, 3
(PhCH2), 82.4 (C-5), 87.6 (C-2), 92.0 (C-1), 128.0, 128.48 and
128.50 (phenyl-C), 133.5 and 134.4 (C-6 and C-7), 186.0 (C-3) ppm. AB subspectrum centered at δ ϭ 6.59, with δA ϭ 6.62 and δB
7dn: 1H NMR (500 MHz, CDCl3): AB subspectrum with δA
6.56 (JAB ϭ 5.8 Hz; the lines of the A-part are split into doublets
3.76, δB ϭ 3.99 (JAB ϭ 11.2 Hz, diastereotopic CH2OBn); AB sub- with J ϭ 1.9 Hz, the B-part with 1.7 Hz, 5-H and 6-H); 9.60 (s, 1
H, exo-OCH3 at C-3), 4.93 (s, 1 H, H-1), 5.22 (s, 1 H, H-5) ppm;
ϭ
ϭ
spectrum with δA ϭ 4.70, δB ϭ 4.62, JAB ϭ 12.1 Hz (diastereotopic
PhCH2); 5.20 (d, J ϭ 1.7 Hz, 1 H, H-5), 5.31 (s, 1 H, H-2) ppm;
AB subspectrum centered at δ ϭ 6.39, with δA ϭ 6.45 (H-6) and
δB ϭ 6.32 (H-7) (JAB ϭ 6.0 Hz; the lines of the A-part are split
into doublets with J ϭ 1.8 Hz); 7.25Ϫ7.40 (m, 5 H, C6H5) ppm.
13C NMR (125.8 MHz, CDCl3): δ ϭ 62.8 (C-2), 68.5 (CH2OBn),
73.9 (PhCH2), 87.5 (C-5), 89.4 (C-4), 93.9 (C-1), 127.7, 127.9 and
127.95 (phenyl-C), 133.9 and 137.3 (C-6 and C-7), 186.9 (C-3) ppm.
H, CHO) ppm. 13C NMR/DEPT (125.8 MHz, CDCl3): δ ϭ 50.4
(CH3O at C-2), 51.5 (endo-OCH3 at C-3), 53.8 (exo-OCH3 at C-3),
78.6 (C-1), 80.2 (C-5), 88.4 (Cq, C-2), 110.6 (Cq, C-3), 133.3 and
135.5 (C-5 and C-6), 199.25 (CHO) ppm.
Methanolysis and Dechlorination of 6an: 2,2-Dimethoxy-8-oxabicy-
clo[3.2.1]oct-6-en-3-one (2): A 2  solution of sodium methoxide in
methanol (6 mL, 12 mmol) was added with stirring over 10 min to
a cooled solution (0 °C) of 6an (1.138 g, 5 mmol) in dry methanol
(15 mL). After stirring for further 30 min, acetic acid (1 mL) and
water (3 mL) were added, and the ice bath removed. With continu-
ous stirring, zinc dust (3.0 g, 46 mmol) was added in portions. After
18 h of stirring at room temperature, the heterogeneous mixture
Reaction of 6a with Sodium Methoxide: (4-endo)- and (4-exo)-4-
Chloro-2,2-dimethoxy-8-oxabicyclo[3.2.1]oct-6-en-3-one (13a): A 1
 solution of sodium methoxide in methanol (22 mL) was added
dropwise with stirring over 2 h to a cooled solution (0 °C) of 6a
(2.275 g, 10.0 mmol) in dry methanol (50 mL). The mixture was was filtered through a sintered glass frit. The filtrate was diluted
stirred for further 30 min, diluted with water (50 mL) and extracted
with water (30 mL) and extracted with dichloromethane (5 ϫ
with dichloromethane (4 ϫ 25 mL). The combined extracts were
100 mL). The combined extracts were washed with saturated solu-
Eur. J. Org. Chem. 2004, 1344Ϫ1356
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1351

H. Zinser, S. Henkel, B. Föhlisch
FULL PAPER
tions of NaHCO3 and NaCl and dried with Na2SO4. The solvent
was evaporated in vacuo, and the remaining pale yellow oil filtered
Methanolysis and Dechlorination of 6dn؉7dn: 1-Benzyloxymethyl-
4,4-dimethoxy-8-oxabicyclo[3.2.1]oct-6-en-3-one (15d) and 1-Benzyl-
through silica (15 g). Elution with EA/PE (1:5) afforded 890 mg oxymethyl-2,2-dimethoxy-8-oxabicyclo[3.2.1]oct-6-en-3-one (16d):
(97%) of 2, as a colourless solid. The 13C NMR and 1H NMR
Prepared from the crude regioisomeric mixture 6dnϩ7dn (1.48 g,
ca. 3.9 mmol) in dry methanol (15 mL) and a 2  NaOMe solution
spectra were in agreement with that reported,[1] and showed practi-
cally no impurities. Recrystallization from MTBE/hexane gave a in MeOH (4.0 mL), followed by zinc powder (2.0 g, 31 mmol), as
solid with m.p. 49Ϫ50 °C.
described for 6an Ǟ 2. The colourless, oily product was chromato-
graphed on silica (50 g). Elution with EA/PE (1:7) gave 802 mg
(67%) of solid colourless 15d and 120 mg (8%) of colourless, oily
16d. The main isomer 15d was recrystallized from MTBE/hexane:
m.p. 46Ϫ48 °C. 15d: C17H20O5 (304.3): calcd. C 67.09, H 6.62;
found C 67.13, H 6.62. IR (KBr): ν˜ ϭ 2980, 2960, 2930, 2890, 2850
2820, 2780 (wm, CϪH), 1735 cmϪ1 (s, CϭO). 1H NMR (500 MHz,
CDCl3): δ ϭ 2.39 (d, J ϭ 15.4 Hz, 1 H, endo-H-2), 2.86 (d, J ϭ
15.4 Hz, 1 H, exo-H-2), 3.32 (s, 3 H, endo-OCH3), 3.46 (s, 3 H,
exo-OCH3) ppm; AB subspectrum centered at δ ϭ 3.66, with δA ϭ
3.68 and δB ϭ 3.64 (JAB ϭ 10.5 Hz, diastereotopic CH2OBn); 4.62
(s, 2 H, OCH2Ph), 5.01 (d, J ϭ 1.8 Hz, 1 H, H-5) ppm; AB subspec-
trum centered at δ ϭ 6.22, with δA ϭ 6.23 (H-7) and δB ϭ 6.21
(H-6) (JAB ϭ 6.0 Hz; the lines of the B-part are split into doublets
with J ϭ 1.8 Hz); 7.26Ϫ7.34 (m, 5 H, C6H5) ppm. 13C NMR
(125.8 MHz, CDCl3): δ ϭ 46.3 (C-2), 50.1 (endo-OCH3), 50.9 (exo-
CH3), 71.3 (CH2OBn), 73.6 (PhCH2), 80.7 (C-5), 87.4 (C-1), 99.4
(C-4), 127.7, 128.4 and 130.4 (phenyl-C), 127.8 (C-6), 136.5 (C-7),
200.8 (C-3) ppm. 16d: IR (CDCl3): 3010 (w, ϭCϪH), 2950, 2920,
Methanolysis and Dechlorination of 6b؉7b: 2,2-Dimethoxy-5-
methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (15b) and 2,2-Dimethoxy-
1-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (16b): Prepared from the
regioisomeric mixture 6bnϩ7bn (723 mg, 3.0 mmol) in dry meth-
anol (10 mL) and 2  sodium methoxide solution in methanol
(4.0 mL, 8.0 mmol), followed by zinc dust (2.0 g, 31 mmol), as de-
scribed for 6an Ǟ 2. The colourless, oily product was chromato-
graphed on silica (100 g). Elution with EA/PE (1:8) afforded
374 mg (63%) of colourless solid 15b and 190 mg (32%) of oily,
colourless 16b. The main isomer 15b was recrystallized from
MTBE/pentane; m.p. 52 °C. 15b: C10H14O4 (198.2): calcd. C 60.59,
H 7.12; found C 60.33, H 7.23. IR (KBr): ν˜ ϭ 3080 (w, ϭCϪH),
2980, 2960, 2950, 2920, 2810 (m, CϪH), 1730 (s, CϭO), 1590 cmϪ1
(w, CϭC). 1H NMR (250 MHz, CDCl3): δ ϭ 1.51 (s, 3 H, CH3)
ppm; AB subspectrum centered at δ ϭ 2.59, with δA ϭ 2.78 (4x-
H) and δB ϭ 2.39 (4n-H) (JAB ϭ 15.3 Hz); 3.32 (s, 3 H, endo-
OCH3), 3.46 (s, 3 H, exo-OCH3), 4.95 (d, J ϭ 1.1 Hz, 1 H, H-
1), 6.14 (mc, 2 H, H-6 and H-7) ppm. 13C NMR/off-resonance
(62.9 MHz, CDCl3): δ ϭ 22.5 (5-CH3), 50.0 (endo-OCH3), 50.45
(CH2, C-4), 50.9 (exo-OCH3), 80.6 (CH, C-1), 85.0 (Cq, C-5), 99.1
(Cq, C-2), 129.7 (CH, C-7), 139.1 (CH, C-6) (C-6 and C-7), 201.0
(Cq, C-3) ppm. 16b: IR (film): ν˜ ϭ 2960, 2920, 2820 (m, CϪH),
1
2900, 2830 (m, CϪH), 1725 cmϪ1 (s, CϭO). H NMR (500 MHz,
CDCl3): δ ϭ 2.42 (dd, J ϭ 16.1, 1.0 Hz, 1 H, endo-H-4), 2.90 (dd,
J ϭ 16.1, 4.9 Hz, 1 H, exo-H-4), 3.36 (s, 3 H, endo-OCH3), 3.44 (s,
3 H, exo-OCH3) ppm; AB subspectrum centered at δ ϭ 3.94, with
δ
A ϭ 4.02 and δB ϭ 3.86 (JAB ϭ 11.2 Hz, diastereotopic CH2OBn);
AB subspectrum centered at δ ϭ 4.63, with δA ϭ 4.69 and δB
4.57 (JAB ϭ 12.4 Hz, diastereotopic PhCH2); 5.07 (d, J ϭ 5.0 Hz,
1 H, H-5) ppm; AB subspectrum centered at δ ϭ 6.27, with δA
1
1725 cmϪ1 (s, CϭO). H NMR (250 MHz, CDCl3): δ ϭ 1.54 (s, 3
ϭ
H, CH3) ppm; AB subspectrum centered at δ ϭ 2.64, with δA
ϭ
2.88 (4x-H) and δB ϭ 2.40 (4n-H) (JAB ϭ 15.8 Hz; the lines of the
A-part are split into doublets with J ϭ 4.8 Hz, the B-part with
1.1 Hz); 3.37 (s, 3 H, exo-OCH3), 3.48 (s, 3 H, endo-OCH3), 4.97
(dd, J ϭ 4.8, 1.3 Hz, 1 H, H-5) ppm; AB subspectrum centered at
δ ϭ 6.16, with δA ϭ 6.28 (H-6) and δB ϭ 6.05 (H-7) (JAB ϭ 5.9 Hz;
the lines of the A-part are split into doublets with J ϭ 1.7 Hz)
ppm. 13C NMR/off-resonance (62.9 MHz, CDCl3): δ ϭ 17.2 (1-
CH3), 45.6 (CH2, C-4), 52.2 (endo-OCH3), 53.5 (exo-OCH3), 78.2
(CH, C-5), 88.7 (Cq, C-1), 101.9 (Cq, C-2), 135.0 (CH), 135.3 (CH)
[C-6 and C-7], 202.65 (Cq, C-3) ppm.
ϭ
6.34 (H-6) and δB ϭ 6.21 (H-7) (JAB ϭ 6.0 Hz; the lines of the A-
part are split into doublets with J ϭ 1.5 Hz); 7.26Ϫ7.36 (m, 5 H,
C6H5) ppm. 13C NMR (125.8 MHz, CDCl3): δ ϭ 45.8 (C-4), 54.0
(OCH3), 67.65 (CH2OBn), 73.8 (PhCH2), 78.0 (C-5), 92.3 (C-1),
102.05 (C-2), 127.6, 127.65 and 128.4 (phenyl-C), 132.5 (C-7), 135.6
(C-6), 202.5 (C-3) ppm.
Ethanolysis and Dechlorination of (6bn؉7bn): 2,2-Diethoxy-5-
methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (A) and 2,2-Diethoxy-1-
methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (B): The mixture of re-
gioisomers 6bnϩ7bn (483 mg, 2.0 mmol, see above) in dry ethanol
(10 mL) was treated with 1  ethanolic sodium ethoxide (5.0 mL,
5.0 mmol), followed by zinc powder (2.0 g, 31 mmol), as described
for 6an. The colourless oil obtained after usual workup was chrom-
atographed on silica (50 g). Elution with EA/PE (1:8) gave 326 mg
Methanolysis and Dechlorination of 6cn؉7cn: 1-Isopropyl-4,4-di-
methoxy-8-oxabicyclo[3.2.1]oct-6-en-3-one (15c): Prepared from the
regioisomeric mixture 6cnϩ7cn (1.16 g, 4.32 mmol) in dry meth-
anol (15 mL) and 2  NaOMe solution in MeOH (5.0 mL,
10.0 mmol), followed by zinc dust (2.0 g, 31 mmol), as described
for 6an Ǟ 2. The yellow oily product was filtered through silica
(20 g). Elution with EA/PE (1:7) gave 904 mg (93%) of 15c as a (72%) of solid A and 110 mg (24%) of oily B. The main regioisomer
colourless solid. Recrystallization from hexane gave crystals with
m.p. 46Ϫ47 °C. C12H18O4 (226.3): calcd. C 63.70, H 8.02; found C
63.66, H 7.99. IR (KBr): ν˜ ϭ 3080 (w, CϪH), 2950, 2920, 2880,
A was recrystallized from MTBE/hexane and showed m.p. 63Ϫ65
°C. A: C12H18O4 (226.3): calcd. C 63.70, H 8.02; found C 63.55, H
8.13. IR (KBr): ν˜ ϭ 3070 (m, ϭCϪH), 2990, 2950, 2910, 2880,
1
2820 (m, CϪH), 1725 (s, CϭO), 1590 cmϪ1 (s, CϭC). 1H NMR 2840 (m, CϪH), 1730 (s, CϭO), 1590 cmϪ1 (w, CϭC). H NMR
(250 MHz, CDCl3): δ ϭ 0.97 (d, 3 H, CH3, J ϭ 6.9 Hz), 1.00 (d, (250 MHz, CDCl3): δ ϭ 1.233 (t, J ϭ 7.0 Hz, 3 H, OCH2CH3),
J ϭ 6.9 Hz, 3 H, CH3), 2.01 [dt, J ϭ 6.9 Hz, 1 H, CH(CH3)2] ppm; 1.236 (t, J ϭ 7.1 Hz, 3 H, OCH2CH3), 1.50 (s, 3 H, 1-CH3) ppm;
AB subspectrum centered at δ ϭ 2.58, with δA ϭ 2.73 (2x-H) and
δB ϭ 2.43 (2n-H) (JAB ϭ 15.2 Hz); 3.31 (s, 3 H, endo-OCH3), 3.45
(s, 3 H, exo-OCH3), 4.97 (d, J ϭ 1.8 Hz, 1 H, H-5) ppm; AB sub-
spectrum centered at δ ϭ 6.17, with δA ϭ 6.20 (H-7) and δB ϭ 6.17
AB subspectrum centered at δ ϭ 2.59, with δA ϭ 2.79 (4x-H) and
δB ϭ 2.39 (4n-H) (JAB ϭ 15.2 Hz); AB part of an ABX3 subspec-
trum from endo-OCH2CH3, with δA ϭ 3.45, δB ϭ 3.18 (JAB ϭ 9.4,
JAX ϭ JBX ϭ 7 Hz); AB part of an ABX3 subspectrum from exo-
(H-6) (JAB ϭ 6.0 Hz; the lines of the B-part are split into doublets OCH2CH3, with δA ϭ 3.91, δB ϭ 3.65 (JAB ϭ 9.6, JAX ϭ JBX
ϭ
with J ϭ 1.8 Hz) ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 17.3
(CH3), 17.6 (CH3), 32.9 [CH(CH3)2], 46.9 (C-2), 49.9 (endo-OCH3),
7 Hz); 4.93 (d, J ϭ 1.3 Hz, 1 H, H-1), 6.13 (mc, 2 H, H-6 and H-
7) ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 15.1 (endo-OCH2CH3),
51.0 (exo-OCH3), 80.35 (C-5), 91.0 (C-1), 99.3 (C-4), 129.8 (C-6), 15.6 (exo-OCH2CH3), 22.6 (5-CH3), 50.6 (C-4), 57.9 (endo-
136.5 (C-7), 201.7 (C-3) ppm. OCH2CH3), 58.7 (exo-OCH2CH3), 81.2 (C-1), 84.9 (C-5), 99.2 (C-
1352
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1344Ϫ1356

A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
2), 130.2 (C-7), 138.85 (C-6), 201.4 (C-3) ppm. B: IR (film): ν˜ ϭ 3) ppm. D: C12H12F6O4 (334.2): calcd. C 43.13, H 3.62; found C
FULL PAPER
3070 (m, ϭCϪH), 2960, 2920, 2880 (s, CϪH), 1725 (s, CϭO), 1590
43.11, H 3.67. IR (film): ν˜ ϭ 3070 (w, ϭCϪH), 2970, 2950, 2930,
1
1
cmϪ1 (w, CϭC). H NMR (500 MHz, CDCl3): δ ϭ 1.22 (m, over- 2880 (m, CϪH), 1730 (s, CϭO), 1590 cmϪ1 (w, CϭC). H NMR
lapping t, 6 H, OCH2CH3), 1.53 (s, 3 H, 1-CH3), 2.38 (dd, J ϭ (500 MHz, CDCl3): δ ϭ 1.52 (s, 3 H, 1-CH3), 2.47 (d, J ϭ 16.5 Hz,
16.0, 1.1 Hz, 1 H, endo-H-4) 2.87 (dd, J ϭ 15.9, 4.8 Hz, 1 H, exo-
1 H, endo-H-4), 2.89 (dd, J ϭ 16.7, 5.1 Hz, 1 H, exo-H-4) ppm;
H-4), 3.44Ϫ3.51 (m, 1 H, OCH2CH3), 3.65Ϫ3.79 (m, 3 H, AB part of an ABX3 subspectrum from endo-OCH2CF3, with δA ϭ
OCH2CH3), 4.95 (d, J ϭ 5.0 Hz, 1 H, H-5) ppm; AB subspectrum
centered at δ ϭ 6.15, with δA ϭ 6.26 (H-6) and δB ϭ 6.05 (H-7)
4.18, δB ϭ 4.03 (JAB ϭ 11.1, JAX ϭ JBX ϭ 8.1Ϫ8.2 Hz); AB part
of an ABX3 subspectrum from exo-OCH2CF3, with δA ϭ 4.29,
(JAB ϭ 5.9 Hz; the lines of the A-part are split into doublets with δB ϭ 4.26 (JAB ϭ 12, JAX ϭ JBX ϭ 8.5Ϫ8.6 Hz); 5.02 (d, J ϭ
J ϭ 1.6 Hz) ppm. 13C NMR (125.8 MHz, CDCl3): δ ϭ 15.3 (endo-
OCH2CH3), 15.9 (exo-OCH2CH3), 16.9 (1-CH3), 45.8 (C-4), 59.7
5.2 Hz, 1 H, H-5), 6.06 (d, J ϭ 5.9 Hz, 1 H, H-7), 6.35 (dd, J ϭ
5.9, 1.6 Hz, 1 H, H-6) ppm. 13C NMR (125.8 MHz, CDCl3): δ ϭ
(endo-OCH2CH3), 61.3 (exo-OCH2CH3), 78.1 (C-5), 88.9 (C-1), 16.2 (1-CH3), 46.0 (C-4), 62.9 (q, J ϭ 35.5 Hz, endo-OCH2CF3),
101.9 (C-2), 135.0 and 135.3 (C-6 and/or C-7), 203.4 (C-3) ppm.
63.3 (q, J ϭ 35.9 Hz, exo-OCH2CF3), 78.2 (C-5), 88.6 (C-1), 100.4
(C-2), 121.6 (CF3), 134.5 and 136.15 (C-6 and/or C-7), 202.5 (C-
3) ppm.
Cleavage of 2: 3-Hydroxy-2-methoxycyclohepta-2,4,6-trienone (20a):
A solution of 2 (368 mg, 2.0 mmol) in 10% methanolic KOH
(15 mL) was refluxed for 16 h. The mixture was diluted with water
(20 mL) and extracted with dichloromethane (3 ϫ 10 mL). The
combined extracts were shaken with an aqueous 0.5  KOH solu-
tion (10 mL), and the dichloromethane solution discarded. The
basic aqueous solutions were combined, cooled in an ice-bath,
acidified with dilute hydrochloric acid (1:2 v/v, 10 mL) and ex-
tracted with dichloromethane (5 ϫ 20 mL). The combined extracts
were washed with brine and dried with Na2SO4. After filtration,
the solvent was evaporated and the remaining brown oil subjected
to sublimation at 60Ϫ100 °C/0.001 Torr. The resulting yellow-or-
ange solid was recrystallized from EA/hexane, affording pale-yel-
low 20a (260 mg, 85%) with m.p. 113Ϫ115 °C (dec.). C8H8O3
(152.15): calcd. C 63.16, H 5.30; found C 62.91, H 5.32. EIMS
(70 eV): m/z (%) ϭ 152 (100) [Mϩ·], 134 (8) [M Ϫ H2O], 121 (31)
[M Ϫ OCH3], 109 (32) [M Ϫ CH3 Ϫ CO], 104 (12), 81 (24), 76
(17). IR (KBr): ν˜ ϭ 3050 (br. s, OϪH), 1625 (m, CϭO), 1570, 1535,
Trifluoroethanolysis and Dechlorination of (6b؉7b): 1-Methyl-4,4-
bis(2,2,2-trifluoroethoxy)-8-oxabicyclo[3.2.1]oct-6-en-3-one (C) and
1-Methyl-2,2-bis(2,2,2-trifluoroethoxy)-8-oxabicyclo[3.2.1]oct-6-en-
3-one (D): The mixture of regioisomers 6bnϩ7bn (725 mg,
3.0 mmol, see above) in dry TFE (15 mL) was treated with a 1 
solution of sodium trifluoroethoxide in TFE (5.0 mL, 5.0 mmol)
for 6 h, as described for 6an. Then the filtered mixture was treated
with acetic acid (0.5 mL) and concentrated in vacuo. The liquid
(ca. 2 mL) was diluted with methanol (10 mL) and water (1 mL);
zinc powder (2.0 g, 31 mmol) was then added. After 24 h of stirring
at room temperature, the heterogeneous mixture was filtered
through a sintered glass frit. The filtrate was diluted with water
(30 mL) and extracted with dichloromethane (5 ϫ 100 mL). The
combined extracts were washed with saturated solutions of
NaHCO3 and NaCl and dried with Na2SO4. The solvent was eva-
porated in vacuo, and the remaining colourless oil filtered through
silica (40 g). Elution with EA/PE (1:10) afforded 805 mg (80%) of
C, and 157 mg (16%) of colourless oily D. The main regioisomer C
was recrystallized from MTBE; m.p. 59Ϫ60 °C. C: IR (KBr): ν˜ ϭ
3080 (w, ϭCϪH), 2960 (m, CϪH), 1740 cmϪ1 (s, CϭO). 1H NMR
(500 MHz, CDCl3): δ ϭ 1.53 (s, 3 H, 1-CH3), 2.40 (d, J ϭ 15.1 Hz,
1 H, endo-H-2), 2.85 (d, J ϭ 15.2 Hz, 1 H, exo-H-2) ppm; AB part
of an ABX3 subspectrum from endo-OCH2CF3, with δA ϭ 4.15,
δB ϭ 4.03 (JAB ϭ 10.8, JAX ϭ JBX ϭ 8.2Ϫ8.3 Hz); AB part of an
ABX3 subspectrum from exo-OCH2CF3, with δA ϭ 4.51, δB ϭ 4.25
(JAB ϭ 12.3, JAX ϭ JBX ϭ 8.6 Hz); 4.84 (d, J ϭ 2.0 Hz, 1 H, H-5)
ppm; AB subspectrum centered at δ ϭ 6.17, with δA ϭ 6.19 (H-6)
1
1500 cmϪ1 (s, CϭC). H NMR (250 MHz, CDCl3): δ ϭ 4.03 (s, 3
H, OCH3), 7.05 [mc, AAЈBBЈ subspectrum with centers at δA
ϭ
7.13 (H-4, H-5) and δB ϭ 6.98 (H-3, H-6)], 7.40 (br. s, 1 H, OϪH)
ppm. 13C NMR (62.9 MHz, CDCl3): δ ϭ 59.2 (OCH3), 131.9 (C-
5 and C-6), 135.0 (C-4 and C-7), 150.1 (C-2) ppm.
3-Hydroxy-2-methoxy-6-methylcyclohepta-2,4,6-trienone (20b): Pre-
pared from 15b (200 mg, 1.01 mmol) with 10% methanolic KOH
(15 mL). Sublimation of the brown residue at 60Ϫ80 °C/0.001 Torr
gave a yellow oil which solidified in the air, forming a pale yellow
hydrate of 20b (156 mg, 84%) with m.p. 88Ϫ94 °C. Drying over
P4O10 gave an oil again. C9H10O3·H2O (184.2): calcd. C 58.69, H
6.56; found C 59.13, H 6.64. IR (CDCl3): ν˜ ϭ 3450 (m, OϪH),
2980, 2920, 2820 (wm, CϪH), 1645 (m, CϭO), 1585, 1560, 1545,
1
1520 cmϪ1 (s, CϭC). H NMR (250 MHz, CDCl3): δ ϭ 2.1 (very
br., H2O), 2.32 (d, J ϭ 0.8 Hz, 3 H, CH3), 4.00 (s, 3 H, OCH3),
6.83Ϫ7.04 ppm; ABC subspectrum from H-4, H-5 and H-7: an AB
analysis gives δA ϭ 7.01 (H-4), δB ϭ 6.86 (H-5) (JAB ϭ 12.2 Hz;
the lines of the B-part are split into doublets with J ϭ 1.6 Hz),
δC ϭ 7.00 (s, 1 H, H-7); 7.15 (br. s, 1 H, OH) ppm. 13C NMR
(62.9 MHz, CDCl3): δ ϭ 26.25 (CH3), 59.2 (OCH3), 133 (br., C-5),
135.5 (C-4 and C-7), 143.0 (C-6), 148.9 (C-2) ppm.
3-Hydroxy-6-isopropyl-2-methoxycyclohepta-2,4,6-trienone
Prepared from 15c (679 mg, 3.0 mmol) with 10% methanolic KOH
and δB ϭ 6.15 (H-7) (JAB ϭ 6.0 Hz; the lines of the B-part are (20 mL) over 24 h, as described for 2. The resulting brown oil was
split into doublets with J ϭ 1.8 Hz) ppm. 13C NMR (125.8 MHz,
sublimed at 60Ϫ120 °C/0.001 Torr to afford a yellow solid. Recrys-
(20c):
CDCl3): δ ϭ 22.3 (1-CH3), 50.1 (C-2), 60.2 (q, J ϭ 35.8 Hz, endo- tallization from MTBE/pentane gave 20c (458 mg, 78%) as a yellow
OCH2CF3), 62.1 (q, J ϭ 35.3 Hz, exo-OCH2CF3), 79.7 (C-5), 85.8 solid with m.p. 89Ϫ90 °C. C11H14O3 (194.2): calcd. C 68.02, H
(C-1), 99.1 (C-4), 123.4 (q, J ϭ 277 Hz, endo-OCH2CF3), 123.5 (q, 7.26; found C 67.91, H 7.23. IR (KBr): ν˜ ϭ 3000 (br. s, OϪH),
J ϭ 277 Hz, exo-OCH2CF3), 129.2 (C-7), 139.95 (C-6), 199.5 (C-
2950, 2910 (m, CϪH), 1630 (m, CϭO), 1575, 1540, 1520 cmϪ1 (s,
Eur. J. Org. Chem. 2004, 1344Ϫ1356
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1353

H. Zinser, S. Henkel, B. Föhlisch
FULL PAPER
CϭC). 1H NMR (500 MHz, CDCl3): δ ϭ 1.22 (d, J ϭ 6.9 Hz, 6 3-Hydroxy-6-methyl-2-(2,2,2-trifluoroethoxy)cyclohepta-2,4,6-tri-
H, CH3), 2.76 [sept, J ϭ 6.9 Hz, CH(CH3)2], 4.01 (s, 3 H, OCH3), enone (F): Prepared from C (752 mg, 2.25 mmol) with 10% meth-
6.90Ϫ7.10 ppm; ABC subspectrum from H-4, H-5 and H-7: an AB anolic KOH (25 mL) over 4 h, as described for 2, with the same
analysis gives δA ϭ 7.08 (H-4), δB ϭ 6.90 (H-5) (JAB ϭ 12.5 Hz; workup. A grey solid remained after evaporation of the extracts.
the lines of the B-part are split into doublets with J ϭ 1.3 Hz), Recrystallization from acetone gave 473 mg (90%) of F as a pale
δC ϭ 7.06 (s, 1 H, H-7); 7.33 (br. s, 1 H, OH) ppm. 13C NMR yellow solid with m.p. 155Ϫ157 °C. C10H9F3O3 (198.2): calcd. C
(125.8 MHz, CDCl3): δ ϭ 22.8 (CH3), 37.8 [CH(CH3)2], 59.1
(OCH3), 133.7 (C-7 and C-4), 148.9 (C-5 and C-6), 152.8 (C-2)
ppm.
51.29, H 3.87; found C 51.29, H 3.88. IR (KBr): ν˜ ϭ 3450 (br.,
1
m, OϪH), 1645 (m, CϭO), 1520, 1505 cmϪ1 (s, CϭC). H NMR
(500 MHz, CDCl3): δ ϭ 2.34 (s, 3 H, CH3), 4.69 (q, J ϭ 8.6 Hz, 2
H, CH2CF3), 6.85 (br. s, 1 H, HO), 6.85Ϫ7.03 ppm; ABC subspec-
trum from H-4, H-5 and H-7: an AB analysis gives δA ϭ 7.01 (H-
4), δB ϭ 6.90 (H-5) (JAB ϭ 12.9 Hz), δC ϭ 7.00 (s, 1 H, H-7) ppm.
13C NMR (125.8 MHz, CDCl3): δ ϭ 26.35 (CH3), 67.5 (q, J ϭ
34.6 Hz, CH2CF3), 122.5 (C-5), 124.75 (C-4), 136.25 (C-7), 143 (C-
6), 146.7 (C-2) ppm.
6-Benzyloxymethyl-3-hydroxy-2-methoxycyclohepta-2,4,6-trienone
(20d): Prepared from 15d (400 mg, 1.31 mmol) with 10% meth-
anolic KOH (15 mL) over 12 h, as described for 2. After filtration
and evaporation of the solvent in vacuo, the resulting yellow oil
was purified by chromatography on silica (20 g). Elution with PE/
EA (1:1) followed by pure EA gave 220 mg (58%) of a brownish,
smeary solid that formed a crystalline hydrate of 20d in the air,
with m.p. 85Ϫ95 °C. C16H16O4·H2O (290.3): calcd. C 65.91, H 6.46;
found C 66.19, H 6.25. IR (KBr): ν˜ ϭ 3400 (br. s, OϪH), 2920 (m,
CϪH), 1650, 1640 (m, CϭO), 1570, 1510 cmϪ1 (s, CϭC). 1H NMR
(250 MHz, [D6]acetone): δ ϭ 2.93 (br. s, H2O), 3.87 (s, 3 H,
ϪOCH3), 4.45 (d, J ϭ 1.1 Hz, 2 H, CH2OBn), 4.61 (s, 2 H,
PhCH2O), 6.96Ϫ7.43 ppm; ABC subspectrum from H-4, H-5 and
H-7 and multiplet from C6H5: discrete signals δ ϭ 7.00 (s, 2 H)
and 7.10 (m, 1 H) can be assigned to H-4 ϩ H-5, and H-7, resp.);
8.84 (br. s, HO) ppm. 13C NMR (62.9 MHz, [D6]acetone): δ ϭ 59.0
(OCH3), 73.0 (CH2OBn), 74.1 (OCH2Ph), 128.5, 128.6 and 129.2
(phenyl-C), 133 (br., C-5 and C-6), 139.1 (C-7 and C-4), 150.4 (C-
2) ppm.
Reaction of 5 with Methanolic KOH Solution: (5α,8α,8aβ)-4,4-Di-
methoxy-3-methyl-5,8-epoxy-1,2,4,5,8,8a-hexahydroazulen-2-one
(26): A solution of 5 (254 mg, 1.0 mmol) in 1  KOH solution
(50 mL) was stirred under nitrogen at room temperature for 3 d.
The mixture was cooled to 0 °C and neutralized by slowly adding
2  HCl (25 mL). The mixture was concentrated to half its original
volume in a rotary evaporator and extracted with dichloromethane
(5 ϫ 20 mL). The combined extracts were washed with brine and
dried with Na2SO4. After filtration and evaporation in vacuo, the
remaining brown oil was chromatographed on silica (20 g). Elution
with EA/PE (1:2) gave 162 mg (68%) of 26 as a colourless solid.
For combustion analysis it was recrystallized from MTBE/hexane;
m.p. 93Ϫ95 °C. C13H16O4 (236.3): calcd. C 66.09, H 6.83; found C
66.06, H 6.94. IR (KBr): ν˜ ϭ 2970, 2950 (m, CϪH), 1710 (CϭO),
3-Hydroxy-2-methoxy-7-methylcyclohepta-2,4,6-trienone (20e): Pre-
pared from 3 (520 mg, 2.62 mmol) with 10% methanolic KOH
(25 mL) as described for 2. Sublimation of the resulting yellow oil
at 60Ϫ80 °C/0.001 Torr gave oily 20e, which solidified in the air,
forming a hydrate. Recrystallization from acetone/water afforded
425 mg (88%) as a pale yellow solid with m.p. 88Ϫ92 °C.
C9H10O3·H2O (184.2): calcd. C 58.69, H 6.57; found C 58.94, H
6.59. IR (KBr): ν˜ ϭ 3480, 3220 (s, OϪH), 1620 (m, CϭO), 1570,
1520, 1495 cmϪ1 (s, CϭC). 1H NMR (500 MHz, [D6]acetone): δ ϭ
2.25 (s, 3 H, CH3), 3.0 (very br., H2O), 3.87 (s, 3 H, OCH3),
6.90Ϫ6.98 ppm; ABC subspectrum from H-4, H-5 and H-7: an AB
analysis gives δA ϭ 6.96 (H-4) and δB ϭ 6.92 (H-5) (JAB ϭ 11.8 Hz;
the lines of the B-part are split into doublets with J ϭ 8.4 Hz),
δC ϭ 7.23 (d, J ϭ 8.4 Hz, 1 H, H-6) ppm. 13C NMR (125.8 MHz,
[D6]acetone): δ ϭ 23.4 (CH3), 59.3 (OCH3), 122.9 (C-4 and C-7),
130 (br., C-1, C-3), 131.0 (C-5), 132.5 (C-6), 150.3 (C-2) ppm.
1
1635 cmϪ1 (w, CϭC). H NMR (250 MHz, CDCl3): δ ϭ 1.87 (d,
J ϭ 2.1 Hz, 3 H, 3-CH3) ppm; AB part of an ABX subspectrum
with δA ϭ 2.51, δB ϭ 1.79 (JAB ϭ 18.4 Hz, 1-H2C); the X part,
with δX ϭ 3.18 (H-8a), shows 9 lines due to coupling with H-8 and
3-CH3; 3.26 (s, 3 H, endo-OCH3), 3.41 (s, 3 H, exo-OCH3), 4.87
(dd, J ϭ 4.1, 1.5 Hz, 1 H, H-8), 4.94 (d, J ϭ 1.8 Hz, 1 H, H-5)
ppm; AB subspectrum centered at δ ϭ 6.25, with δA ϭ 6.31 (H-6),
δB ϭ 6.19 (H-7) (JAB ϭ 6.1 Hz; the lines of the A-part are split
into doublets with J ϭ 1.8 Hz, the B-part with 1.5 Hz) ppm. 13C
NMR (62.9 MHz, CDCl3): δ ϭ 9.6 (3-CH3), 35.9 (C-1), 40.8 (C-
8a), 48.3 (endo-OCH3), 51.2 (exo-OCH3), 80.9 and 81.1 (C-5 and
C-8), 100.2 (C-4), 131.3 and 132.8 (C-6 and C-7), 142.9 (C-3), 163.4
(C-3a), 207.8 (C-2) ppm.
Cleavage of 5: 3-Hydroxy-2-methoxy-7-(2-oxobutyl)cyclohepta-
2,4,6-trienone (20f, 27, 28) and 2-Ethyl-2,3-dihydro-2-hydroxy-8-
methoxy-7H-cyclohepta[b]furan-7-one (26): A solution of 5 (254 mg,
1.0 mmol) in 1  methanolic NaOMe (50 mL) was refluxed under
nitrogen for 6 h. The mixture was cooled to 0 °C and acidified by
slowly adding 2  HCl (26 mL). The mixture was concentrated to
half its original volume in a rotary evaporator and extracted with
dichloromethane (5 ϫ 20 mL). The combined extracts were washed
2-Ethoxy-3-hydroxy-6-methylcyclohepta-2,4,6-trienone (E): Pre-
pared from A (250 mg, 1.11 mmol) with 10% methanolic KOH
(15 mL), as described for 2. The brown residue was sublimed at
60Ϫ80 °C/0.001 Torr to afford a yellow oil, which solidified in the
air, forming a hydrate. Recrystallization from acetone/water gave
180 mg of E (82%), a pale yellow solid with m.p. 87Ϫ94 °C.
C10H12O3·H2O (198.2): calcd. C 60.59, H 7.12; found C 60.35, H with brine, dried with Na2SO4, and the solvent was evaporated in
7.13. IR (KBr): ν˜ ϭ 3400 (br. s, OϪH), 2980, 2960 (m, CϪH), vacuo. The remaining brown oil was chromatographed on silica
1630 (m, CϭO), 1570, 1510 cmϪ1(s, CϭC). 1H NMR (250 MHz,
CDCl3): δ ϭ 1.37 (t, J ϭ 7.2 Hz, 3 H, CH2CH3), 2.1 (br., H2O),
(20 g). Elution with EA/PE (1:2) gave 38 mg (16%) of 26 (see the
preceding experiment). Elution with acetone/EA (1:9) then gave
2.32 (d, J ϭ 1.0 Hz, 3 H, 6-CH3), 4.34 (q, J ϭ 7.1 Hz, 2 H, 160 mg of a brown solid (20f, 27, 28; 72%), which was recrystallized
CH2CH3), 6.82Ϫ7.04 ppm; ABC subspectrum from H-4, H-5 and
H-7: an AB analysis gives δA ϭ 7.01 (H-4), δB ϭ 6.86 (H-5) (JAB ϭ
12 Hz; the lines of the B-part are split into doublets with J ϭ
from acetone; m.p. 112 °C (dec.). C12H14O4 (222.2): calcd. C 64.85,
H 6.35; found C 64.69, H 6.46. IR (KBr): ν˜ ϭ 3120 (s, OϪH),
2960, 2920 (s, CϪH), 1625 (CϭO), 1580, 1520 cmϪ1 (s, CϭC). The
1
1.6 Hz), δC ϭ 7.00 (s, 1 H, H-7); 7.21 (br. s, 1 H, HO) ppm. 13C peak integrals of a 500 MHz H NMR spectrum of this substance
NMR (62.9 MHz, CDCl3): δ ϭ 15.7 (CH2CH3), 26.2 (6-CH3), 67.3
(CH2CH3), 133.6 (b, C-5), 135.4 (C-4 and C-7), 142.8 (C-6), 147.8 present in the open-chain form (20f, 27), and 45% as the cyclic
(C-2) ppm.
hemiacetal 28. 20f, 27: 1H NMR: δ ϭ 1.00 (t, J ϭ 7.3 Hz, 3 H,
in [D6]acetone solution showed that 55% of the compound was
1354
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 1344Ϫ1356

A Novel Synthesis of 2-Alkoxy-3-hydroxytropones and 2,7-Dihydroxytropones
CH2CH3), 2.60 (q, J ϭ 7.3 Hz, 2 H, CH2CH3), 3.69 (s, 2 H, 7- [4-CH(CH3)2], 121.2 (C-6), and 121.8 (C-3), 128.4 (C-5), 152.5 (C-
FULL PAPER
CH2), 3.79 (s, 3 H, OCH3); 6.87Ϫ7.05 (m, H-4, H-5 and H-6) ppm. 4), 158.3 (C-2) and 159.8 (C-7), 166.9 (C-1) ppm.
28: 1H NMR: δ ϭ 1.06 (t, J ϭ 7.4 Hz, 3 H, CH2CH3), 2.02 (m,
2,7-Dihydroxy-3-methylcyclohepta-2,4,6-trienone (29d): Prepared
CH2CH3, partly superimposed with the [D6]acetone peak), 2.85 (br.
s, OH) ppm; AB subspectrum centered at δ ϭ 3.28, with δA
from 20e (112 mg, 0.67 mmol) with a 33% solution of HBr in gla-
cial acetic acid (5 mL), as described for 29b. The brown solid prod-
uct was sublimed at 60Ϫ80 °C/0.001 Torr, giving 99 mg (97%) of a
colourless, hygroscopic solid. After recrystallization from acetone/
water, the m.p. was 111Ϫ113 °C. The spectra were in agreement
with structure 29d; however, a satisfying combustion analysis of
29d could not be obtained. IR (KBr): ν˜ ϭ 3200 (s, OϪH), 1605,
ϭ
3.40 and δB ϭ 3.16 (JAB ϭ 17.6 Hz, 3-H2C); 3.83 (s, 3 H, OCH3),
6.92Ϫ7.05 (m, 3 H, H-4, H-5 and H-6) ppm. From the 13C NMR
spectrum (125.8 MHz, [D6]acetone) the following signals were ten-
tatively assigned: δ ϭ 8.1 (CH2CH3, 20f, 27), 8.8 (CH2CH3, 28),
33.2 (CH2CH3, 20f, 27), 36.2 (CH2CH3, 28), 43.4 (7-CH2, 20f), 49.9
(C-3, 28), 58.8, 58.9 (OCH3 from 20f, 27 and/or 28), 110.9 (C-1,
20f, 27), 125.4, 133.0, 139.25, (C-4, C-5 and C-6, 28), 142.2 (C-8,
28), 149.4 (C-3a, 28), 159.0 (C-8a, 28), 180.2 (C-7, 28), 207.35 (Cϭ
O, 20f, 27) ppm.
1
1580 (m, CϭO), 1520, 1500 cmϪ1 (s, CϭC). H NMR (500 MHz,
CDCl3): δ ϭ 2.33 (s, 3 H, 3-CH3) ppm; ABC subspectrum of H-4,
H-5 and H-6,
a first-order analysis gave 7.06 (‘‘t’’, J ϭ
10.1Ϫ10.5 Hz, 1 H, H-5), 7.41 (‘‘d, J ϭ 10.1 Hz’’, 1 H, H-4), 7.19
(‘‘d, J ϭ 10.7’’ 1 H, H-6); 7.9 (very br., 2 H, OH) ppm. 13C NMR
(125.8 MHz, CDCl3): δ ϭ 21.1 (CH3), 119.5 (C-6), 127.8 (C-4),
133.0 (C-3), 133.6 (C-5), 158.1 (C-7?), 159.1 (C-2?), 167.4 (C-1)
2,7-Dihydroxycyclohepta-2,4,6-trienone (29a): A 33% solution of
HBr in glacial acetic acid (5 mL) was added slowly to a solution
of 20a (152 mg, 1.0 mmol) in glacial acetic acid (2 mL). The mix-
ture was heated to 60 °C for 1 h. The volatile components were
then evaporated in vacuo. The dark, tarry residue was sublimed at
60Ϫ100 °C/0.01 Torr, resulting in a yellow solid that was resub-
limed at 60Ϫ70 °C/0.01 Torr. The isolated product (130 mg, 94%)
had an intense wood odour, and showed decomposition at the melt-
ing point (Ͼ 133 °C) (ref.[34] 136 °C). Despite the deficiency in
melting point, the 13C NMR spectrum was consistent with the data
reported for 29a, apart from negligible differences due to the differ-
ent solvent (CD3OD)[35]. IR (KBr): ν˜ ϭ 3230 (s, OH), 1605 (m, Cϭ
O), 1520 cmϪ1 (br. s, CϭC). 1H NMR (250 MHz, CDCl3): δ ϭ
7.35 [m, AAЈBBЈ subspectrum with centers at δA ϭ 7.52 (H-4, H-
5) and δB ϭ 7.20 (H-3, H-6)], 8.34 (br., 2 H, OH) ppm. For an
analyis of the 1H NMR spectrum in [D6]acetone see ref.[36] 13C
NMR/DEPT (62.9 MHz, CDCl3): δ ϭ 121.2 (CH, C-3, C-6), 130.0
(CH, C-4, C-5), 160.05 (Cq, C-2, C-7), 169.2 (Cq, C-1) ppm.
1
ppm. H NMR (250 MHz, [D6]DMSO): δ ϭ 2.39 (s, 3 H, 3-CH3),
6.96 (br. s, 2 H, OH) ppm; ABC subspectrum of H-4, H-5 and H-
6, a first-order analysis gave 7.03 (‘‘t, J ϭ 10.2 Hz’’, 1 H, H-5),
7.20 (‘‘d, J ϭ 10.4 Hz’’, 1 H, H-4), 7.31 (‘‘dd, J ϭ 10.2, 1.5 Hz’’,
1 H, H-6) ppm. 13C NMR (62.9 MHz, [D6]DMSO): δ ϭ 20.9
(CH3), 119.6 (C-6), 126.8 (C-4), 131.4 (C-3), 132.4 (C-5), 158.7 and
158.9 (C-2 and C-7), 166.75 (C-1) ppm. C8H8O3·H2O (170.2):
calcd. C 56.47, H 5.92; found C 58.72, H 5.39. EIMS (70 eV): m/z
(%) ϭ 152 (100) [Mϩ·], 124 (24) [M Ϫ CO], 106 (6), [M Ϫ CO Ϫ
H2O], 78 (19). HRMS: calcd. for C8H8O3 152.0473; found
152.0469.
Acknowledgments
We thank the analytical and spectroscopic service of the Institute
of Organic Chemistry for spectra and elemental analyses, especially
Jochen Rebell (NMR), and Dr. Wolfgang Frey for help with the
X-ray data. Thomas Haisch made an experimental contribution.
2,7-Dihydroxy-4-methylcyclohepta-2,4,6-trienone (29b):
A
33%
solution of HBr in glacial acetic acid (5 mL) was added slowly to
a solution of 20b (120 mg, 0.72 mmol) in acetic acid (2 mL). The
mixture was heated to 90 °C for 30 min. The volatile components
were then evaporated in vacuo. The remaining brown solid was
sublimed at 60Ϫ80 °C/0.001 Torr affording 110 mg (Ͼ 99%) of 29b
as a solid with m.p. 131Ϫ132 °C (ref.[18] 132.5Ϫ133.5 °C). The 13C
NMR spectrum was consistent with the data reported for 29b,
apart from negligible differences due to the different solvent
(CDCl3).[18] IR (KBr): ν˜ ϭ 3220 (s, OϪH), 1605 (m, CϭO), 1515
[1]
B. Föhlisch, A. Radl, R. Schwetzler-Raschke, S. Henkel, Eur.
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For a related reaction with a bicyclo[3.2.2] skeleton, see: A. A.
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O. Sarhan, H. M. R. Hoffmann, J. Prakt. Chem. 1997, 339,
390Ϫ393.
[3]
H. Zinser, Doctoral dissertation, Univ. Stuttgart, 1999.
[4] [4a]
1
cmϪ1 (s, CϭC). H NMR (250 MHz, [D6]DMSO): δ ϭ 2.39 [s, 3
M. F. Ansell, M. P. L. Caton, J. S. Mason, Tetrahedron
Lett. 1981, 22, 1141Ϫ1142; J. Chem. Soc., Perkin Trans. 1 1984,
H, CH3, AB subspectrum centered at δ ϭ 7.13, with δA ϭ 7.27 (H-
6) and δB ϭ 7.00 (H-5), JAB ϭ 10.8 Hz; the lines of the B-part are
split into doublets with J ϭ 0.7 Hz], 7.31 (d, J ϭ 1.5 Hz, 1 H, H-
3) ppm. 13C NMR (62.9 MHz, [D6]DMSO): δ ϭ 25.6 (4-CH3),
120.5 (C-6), 122.35 (C-3?), 128.5 (C-5?), 139.3 (C-4), 158.15 (C-2),
159.5 (C-7), 167.4 (C-1) ppm.
[4b]
1061Ϫ1068.
W. J. Cummins, M.G. B. Drew, J. Mann, J.
[4c]
Markson, Tetrahedron 1988, 44, 5151Ϫ5160.
B. Föhlisch,
G. Kreiselmeier, Tetrahedron 2001, 57, 10077Ϫ10088.
[5] [5a]
M. Miyashita, T. Yanami, T. Kumazawa, A. Yoshikoshi, J.
[5b]
Am. Chem. Soc. 1984, 106, 2149Ϫ2156.
Yamaguchi, A. Yoshikoshi, J. Org. Chem. 1984, 49,
M. Miyashita, R.
2857Ϫ2863.
2,7-Dihydroxy-4-isopropylcyclohepta-2,4,6-trienone (β-Thujaplici-
nol, 29c): Prepared from 20c (194 mg, 1.0 mmol) in acetic acid
(3 mL) and 33% HBr in glacial acetic acid (5 mL), as described for
29b. The dark, tarry residue was sublimed at 60Ϫ100 °C/0.001 Torr
to give 173 mg (96%) of a smeary yellow solid that was recrys-
tallized from MTBE/hexane. Yield: 145 mg (81%) of 29c with m.p.
54Ϫ55 °C (ref.[19] 57.5Ϫ58 °C). The IR spectrum (KBr) essentially
corresponded with the figure shown in ref.[19] The 1H NMR
(250 MHz, CDCl3) spectrum was fully consistent with the data
reported for the ‘‘viscous, red-brown’’ oily 29b;[18] moreover, the
resonance for the two HO protons appeared as a broad signal at
δ ϭ 8.3. Minor deviations were found for the 62.9 MHz 13C NMR
spectrum.[18] 13C NMR (62.9 MHz, CDCl3): δ ϭ 23.9 (CH3), 38.6
[6]
[7]
H. W. Pinnick, Org. React. 1990, 38, 655Ϫ792.
B. Föhlisch, W. Gottstein, R. Herter, I. Wanner, J. Chem. Res.
(S) 1981, 246Ϫ247.
[8] [8a]
B. Föhlisch, E. Gehrlach, R. Herter, Angew. Chem. 1984,
[8b]
94, 144.
B. Föhlisch, E. Gehrlach, B. Geywitz, Chem. Ber.
[8c]
1987, 120, 1815Ϫ1824.
S. Sendelbach, R. Schwetzler-
Raschke, A. Radl, R. Kaiser, G. H. Henle, H. Korfant, S. Re-
iner, B. Föhlisch, J. Org. Chem. 1999, 64, 3398Ϫ3408.
CCDC-198523 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
[9]
Eur. J. Org. Chem. 2004, 1344Ϫ1356
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1355

H. Zinser, S. Henkel, B. Föhlisch
FULL PAPER
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As outlined for the case of pentachloroacetone,[10a] an oxyallyl
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chloroacetone by ionization of the enolate anion, followed by
dissociation to the ‘‘free’’ oxyallyl intermediate. In TFE, a
strong hydrogen bond between the solvent and the negative
charge on the oxygen atom is expected, leading in the extreme
case to the trichloro2-hydroxyallylium chloride ion pair and the
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ˆ
Received September 25, 2003
1356
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