Chemistry of dioxine-annelated cycloheptatriene endoperoxides and their conversion into tropolone derivatives: an unusual non-benzenoid singlet oxygen source

Article abstract of DOI:10.1016/j.tet.2006.02.026

The chemistry of two bicyclic endoperoxides, obtained by photooxygenation of 2,3-dihydro-7H-cyclohepta[1,4]dioxine and 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one was investigated with the aim of synthesizing the respective tropolone derivatives. The reaction of these endoperoxides with base, thiourea and their thermolysis provided the desired tropolone derivatives in high yield. On the other hand, the thermolysis of the endoperoxide derived from 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one underwent an unprecedented route and formed parent molecule and singlet oxygen instead of the expected troponoids. The formation mechanisms of all products are discussed.

Full text of DOI:10.1016/j.tet.2006.02.026

Tetrahedron 62 (2006) 4003–4010
Chemistry of dioxine-annelated cycloheptatriene endoperoxides
and their conversion into tropolone derivatives: an unusual
non-benzenoid singlet oxygen source
b,
Arif Das¸tana, and Metin Balci
*
*
a
¨
Department of Chemistry, Ataturk University, 25240 Erzurum, Turkey
bDepartment of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 1 November 2005; revised 23 January 2006; accepted 10 February 2006
Available online 9 March 2006
Abstract—The chemistry of two bicyclic endoperoxides, obtained by photooxygenation of 2,3-dihydro-7H-cyclohepta[1,4]dioxine and 2,3-
dihydro-7H-cyclohepta[b][1,4]dioxin-7-one was investigated with the aim of synthesizing the respective tropolone derivatives. The reaction of
these endoperoxides with base, thiourea and their thermolysis provided the desired tropolone derivatives in high yield. On the other hand, the
thermolysis of the endoperoxide derived from 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one underwent an unprecedented route and formed
parent molecule and singlet oxygen instead of the expected troponoids. The formation mechanisms of all products are discussed.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
antibiotic,3 antitumor,3a,4 antibacterial activity,5 and lip-
oxygenase inhibitor activity.6
Tropone (1) and tropolone (2) have fascinated organic
chemists for well over 50 years. The most significant reason
fortheinterestinringsystemtroponesisthattheyrepresent the
key structural element in a wide range of natural products,
many of which 3–14 display interesting biological activity1
such as the inhibitor activity of inositol monophosphatase,2
The synthesis of substituted tropone as well as tropolones
continues to be a considerable synthetic challenge. Recently,
renewedinterestintheabilityofcolchicine14toinhibittubulin
polymerisation has been complemented by special new
approaches to tropolone structures.7 A number of syntheses
of tropolone derivatives have been developed.8 Although the
tropones can be oxidized to the tropolones, those approaches
suffer from regiochemical control problems when the
substituted tropones are used as starting materials. In
connection with the development of new synthetic strategies
to tropolones, we recently studied the applicability of bicyclic
endoperoxidesderivedbythecycloadditionofsingletoxygen9
totheappropriatecyclicdienesandsubsequentlysynthesizeda
new isomer of stipitatic acid 1310 and some benzotroponoid
systems.11
In this paper, we report on the synthesis of new and possible
bioactive tropolones via photooxygenation of oxygen-
functionalized cycloheptatriene derivatives.
2. Results and discussion
The starting materials 16 and 18 were synthesized as
reported in the literature. The thermolysis of tropone
Keywords: Tropone; Tropolone; Endoperoxide; Singlet oxygen; Rearrangement.
*
Corresponding authors. Tel.: C90 442 2314405; fax: C90 442 2360948 (A.D.); tel.: C90 312 2105140; fax: C90 312 2101280 (M.B.); e-mail
addresses: adastan@atauni.edu.tr; mbalci@metu.edu.tr
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.02.026

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A. Das¸tan, M. Balci / Tetrahedron 62 (2006) 4003–4010
ethylene ketal 1512 provided the cycloheptatriene derivative
16.13 The photooxygenation of 15, followed by the reaction
of the formed bicyclic endoperoxide with NEt3 gave the
tropolone derivative 17.14 The thermolysis of 17 in
dioxane resulted in the formation of the starting material
18 (Scheme 1).
Scheme 3.
Scheme 1.
m-CPBA at room temperature in an ultrasonic bath gave
four products; two tropolone derivatives 2613 and 27, where
m-CPBA was incorporated into the molecule, dilactone 20
and an unusual rearranged product 28 in yields of 3, 26, 16
and 5% yields, respectively (Scheme 4). Full characteri-
zation of all of the formed products was accomplished by
means of detailed NMR analysis.
The tetraphenylporphyrin-sensitized photooxygenation of
16 produced the tricyclic endoperoxide 19 in 73% yield
(Scheme 2). The sensitized photooxygenation of electron-
rich olefins constitutes an effective means of preparing 1,2-
dioxetanes through [2C2] cycloaddition.15 During the
photooxygenation reaction of 16 we expected a large
amount of dioxetane 21. Careful inspection of the reaction
mixture showed the formation of dilactone 20 in trace
amounts, which is a secondary product formed by the
cleavage of the initially formed dioxetane 21. The structural
1
assignments of the products were performed from H and
13C NMR spectra.
Scheme 4.
Base-catalyzed decomposition of unsaturated bicyclic
peroxides generally results in the formation of hydroxy
ketones.9,17 Application of this reaction to the cyclohepta-
triene endoperoxides opens up an entry to the synthesis of
troponoid compounds.8g,10,11
Scheme 2.
On the other hand, the oxidation of 16 with 3,3-dimethyl-
dioxirane (DMD)16 in acetone at K78 8C followed by column
chromatography gave tropone derivative 26 as the major
product as well as dilactone 20 in only 8% yield (Scheme 3).
The formation of those products can be rationalized by the
following mechanism. The initially formed monoepoxide 22
can undergo two different reactions; (i) forming the diol 23 by
the opening of epoxide 22 with water to produce dilactone 20,
and (ii) opening of epoxide 22 to stable oxy-cation 24, which
can be rearranged through the intermediate 25 to the stable
tropone 2613b (Scheme 3).
Treatment of endoperoxide 19 with a catalytic amount of
triethylamine in dichloromethane at K30 8C provided a new
tri-oxygenated tropolone 29 as the sole product in 97% yield
(Scheme 5). The unsymmetrical tropolone derivative 29 can
be in equilibrium with its tautomer 32 (Scheme 6). In order
to determine, which is the most stable tautomer we
undertook some AM1 calculations. The results show that
the tautomer 29 has 0.48 kcal/mol lower heat of formation
than the tautomer 32. Therefore, the structure was
tentatively assigned as 29.
For the conversion of 19 to 29 we propose the mechanism
depicted in Scheme 6. The abstraction of the bridgehead
proton in 19 by the amine catalyst with the concomitant
For the further conversion of cycloheptatriene derivative 16
to tropolone derivatives, it was oxidized with m-chloro-
perbenzoic acid (m-CPBA). The reaction of 16 with

A. Das¸tan, M. Balci / Tetrahedron 62 (2006) 4003–4010
4005
Scheme 5.
Scheme 8.
attributed to the reduced electron density caused by the
carbonyl group.
It is well established that thiourea reduces the oxygen–
oxygen bond to give a diol.9 Recently, we showed that the
substituted cycloheptatriene endoperoxide can easily form
troponoid systems upon treatment with thiourea.10,11a
Therefore, the bicyclic endoperoxide 35 was reacted with
thiourea in methanol at 10 8C and the desired tetra-
oxygenated tropolone 37 was obtained in 94% yield
(Scheme 8). The structure of 37 was characterized by its
1H NMR spectrum. Vicinal olefinic protons (H5 and H6) of
37 resonate as an AB-system. The A-part of the AB-system
appears at d 7.08 ppm as a doublet (JZ11.3 Hz) and the
B-part at d 6.95 ppm again as doublet, whereas the olefinic
proton H3 resonates at d 7.04 ppm as a singlet. Its nine-line
13C NMR spectrum supports the suggested unsymmetrical
structure. For this compound, three different tautomers
(37A, 37B and 37C) can be written (Scheme 9).
Scheme 6.
cleavage of O–O bond followed by ring opening can
generate the unsaturated alkoxydiketone 33, which could
then afford substituted tropolone 29 by tautomerization
(Scheme 6). Furthermore, we noticed that the endoperoxide
19 was partly rearranged during column chromatography on
aluminum oxide to give troponoids 31 and 26 in 13 and 3%
yields, respectively (Scheme 5).
Thermal decomposition of endoperoxides generally results
in the formation of bisepoxides.9,18 When endoperoxide 19
was heated to 160 8C in toluene in a sealed tube for 6 h, the
epoxyketal 30 was isolated after chromatography on a
florisil column in 53% yield (Scheme 5). Full characteri-
zation of the product was accomplished by means of 1H and
13C NMR spectra. No trace of any bisepoxide was detected.
The formation of this product can be rationalized by the
following mechanism. An initial cleavage of the peroxide
linkage to diradical 34, followed by rearrangement forms
the product 30 (Scheme 7).
Scheme 7.
Scheme 9.
The tetraphenylporphyrin-sensitized photooxygenation of
the cycloheptatriene derivative 18 produced only tricyclic
endoperoxide 35 in 94% yield (Scheme 8). The expected
[2C2] cycloaddition product was unformed, which may be
In order to find the most stable tautomer we carried out AM1
calculations for the three possible tautomers and found that
the isomer 37A is thermodynamically about 2.76 and
5.96 kcal/mol more stable than the isomers and 37C and

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A. Das¸tan, M. Balci / Tetrahedron 62 (2006) 4003–4010
37B, respectively. Therefore, the structure 37A was
assigned tentatively.
endoperoxides with base, thiourea and their thermolysis
provided an entry to the synthesis of new tropolone
derivatives in high yield. Furthermore, we have studied
their oxidation and thermal reactions. The tricyclic
endoperoxide 35 obtained by the photooxygenation of 18
showed an unprecedented behavior and produced singlet
oxygen and the parent tropone upon thermolysis. To the best
of our knowledge it is the first report where a non-benzonoid
system generative singlet oxygen. The results described
here should lead to the synthesis of new tropon and
tropolone derivatives upon photooxygenation of highly
oxygenated cycloheptatriene derivatives.
Foote et al.19 and our group20 have reported that cobalt meso-
tetraphenylporphyrin (CoTPP) promotes the rearrangement of
the bicyclic endoperoxides to the corresponding bis-epoxide
with syn-configuration. In addition to this previously observed
reaction of CoTPP we further demonstrated that some bicyclic
endoperoxides derived from cycloheptatriene can be con-
verted into tropolone derivatives upon treatment with
CoTPP.10 For that reason, endoperoxide 35 was treated with
a catalytic amount of CoTPP at a low temperature. The
corresponding bisepoxide 38 was isolated in 87% yield
(Scheme 8). It was noticed that the bis-epoxide 38 was
unstable at room temperature and was rearranged smoothly to
epoxyketal 39 by way of standing at room temperature over a
period of 5 days.
4. Experimental
4.1. General
It is well known that benzenoid aromatic hydrocarbons such
as anthracene, rubrene, tetracene, and substituted naphtha-
lanes21 undergo photosensitized autoxidation to form bicyclic
endoperoxides. These peroxides undergo dissociation on
heating to regenerate singlet oxygen and the parent aromatic
compounds. The ease of oxygen release from these systems
depends on the polycyclic aromatic system and the nature of
the substituents. During the thermal reaction of endoperoxide
35 we observed that it loses oxygen and forms the parent
tropone 18 as the sole product (Scheme 10). In order to test
whether the formed oxygen is singlet or molecular oxygen,
the thermolysis reaction of endoperoxide 35 was carried out
in the presence of the known singlet oxygen acceptors, such
as 1,3-diphenylisobenzofuran (DBI)22 and tetramethylethy-
lene. The decomposition of 35 in the presence of
tetramethylethylene gave the ene-product 41, whereas the
DBI formed 40 as the trapping product.
Melting points are uncorrected. Infrared spectra were
obtained from solution in 0.1 mm cells or KBr pellets on a
regular instrument. The 1H and 13C NMR spectra were
recorded on 200 (50) MHz spectrometers. Apparent
splittings are given in all cases. Column chromatography
was performed on silica gel (60-mesh, Merck). TLC was
carried out on Merck 0.2 mm silica gel 60 F254 analytical
aluminum plates. All substances reported in this paper are in
their racemic form.
4.1.1. Synthesis of 2,3-dihydro-7H-cyclohepta[1,4]-
dioxine (16). The tropone ethylene ketal 1512 (3.0 g,
0.02 mol) was dissolved in cyclohexane (3 mL) and heated
to 123G2 8C for 16 days in a sealed tube. After evaporation
of the solvent the residue was distilled to give 1613 (2.04 g,
1
68%, pale yellow liquid). H NMR (200 MHz, CDCl3): d
5.99 (d, A-part of, AX system, J5,6ZJ8,9Z9.8 Hz, 2H, H5
and H9), 5.27 (dt, X-part of, AX system, J5,6ZJ8,9Z9.8 Hz,
J6,7ZJ8,7Z6.9 Hz, 2H, H6 and H8), 4.16 (s, 4H, OCH2),
2.33 (t, J6,7ZJ8,7Z6.9 Hz, 2H, H7). 13C NMR (50 MHz,
CDCl3): d 139.1, 123.4, 118.5, 64.4, 28.0.
4.1.2. Synthesis of 2,3-dihydro-cyclohepta[1,4]dioxin-7-
one (18). Tropolone 1714 (300 mg, 1.65 mmol) was
dissolved in dioxane (5 mL) and heated to 160 8C for 48 h
in a sealed tube. After evaporation of the solvent the residue
was filtered through silica gel column (30 g) eluting with
n-hexane–ethyl acetate (6/4) to give 1814a (197 mg, 73%,
pale yellow crystals), mp 150–151 8C from methylene
chloride/n-hexane 1:1 (lit. mp 151–152 8C).104a 10H NMR
(200 MHz, CDCl3): d 7.03 (AA0 part of AA BB system,
2H, H5 and H9), 6.82 (BB0 part of AA0BB0 system, 2H, H6
and H8), 4.24 (s, 4H, OCH2). 13C NMR (50 MHz, CDCl3): d
187.2, 146.4, 136.1, 135.4, 65.8.
4.1.3. Photooxygenation of 2,3-dihydro-7H-cyclo-
hepta[1,4]dioxine (16). The cycloheptatriene derivative
1613a (1.0 g, 6.67 mmol) and tetraphenylporphyrin (10 mg)
were dissolved in 200 mL of CCl4. The solution was then
irradiated with a projection lamp (500 W) while a slow
stream of dry oxygen was passed through the solution at
10 8C. After 1.5 h, the solvent was evaporated (20 8C). The
crystallization of the residue from CH2Cl2–ether (1/4)
provided endoperoxide 19 as colorless crystals (886 mg,
Scheme 10.
3. Conclusions
In conclusion, we synthesized two bicyclic endoperoxides
by the photooxygenation reaction of two different dioxine-
annelated cycloheptatrienes. The reaction of these

A. Das¸tan, M. Balci / Tetrahedron 62 (2006) 4003–4010
4007
1
3-chlorobenzenecarboperoxoate (27): H NMR (200 MHz,
73%, mp 97–98 8C). (4aR(S),8S(R))-2,3,7,8-Tetrahydro-
4a,8-epidioxycyclohepta[b][1,4]-dioxine (19): 1H NMR
(200 MHz, CDCl3): d 5.95 (ddd, A-part of AB system.
0
0 0
CDCl3): d 8.03 (m, 1H, H2 ), 7.92 (br d, J5 6 Z7.6 Hz, 1H,
0
0
0
0
0
0
H6 ), 7.55 (br d, J4 ,5 Z7.6 Hz, 1H, H4 ), 7.40 (t, J4 ,5
Z
0
0
0
0
J5,6Z12.2 Hz, J5,7Z3.0 Hz, J5,7 Z1.8 Hz, 1H, H5), 5.65
J5 ,6 Z7.6 Hz, 1H, H5 ), 6.48 (bdd, A-part of AB system,
J6,7Z12.1 Hz, J2,7Z4.0 Hz, 1H, H7), 6.29 (dd, A-part of AB
system, J3,4Z11.4 Hz, J2,3Z5.1 Hz, 1H, H3), 6.04 (br d,
B-part of AB system, J3,4Z11.4 Hz, 1H, H4), 5.87 (d, B-part
(bddd, B-part of AB system, J5,6Z12.2 Hz, J6,7Z4.7 Hz,
0
J6,7 Z3.8 Hz, 1H, H6), 5.39 (d, J8,9Z7.7 Hz, 1H, H9), 4.87
(m, 1H, H8), 4.34–3.79 (m, 4H, OCH2), 2.89 (br d, A-part of
0
AB system, J7,7 Z19.5 Hz, 1H, H7), 2.35 (br d, B-part of
of AB system, J6,7Z12.1 Hz, 1H, H6), 5.17 (br d, J2,3Z
AB system, J7,7 Z19.5 Hz, 1H, H7 ). 13C NMR (50 MHz,
CDCl3): d 155.3, 133.7, 130.6, 101.0, 99.6, 79.4, 68.3, 63.6,
38.0. MS (EI, 70 ) m/z 182 (MC, 10), 164 (8), 154 (6), 139
(12), 125 (66), 112 (96), 81 (100), 68 (74). Anal. Calcd for
C9H10O4: C, 59.34; H, 5.53. Found: C, 59.20; H, 5.46.
5.1 Hz, 1H, H2). 4.52 (A2-part of A2B2 system, 2H, OCH2),
4.37 (B2-part of A2B2 system, 2H, OCH2). 13C NMR (APT,
50 MHz, CDCl3): d 168.7, 164.7, 153.7, 141.3 (K)(C7),
136.7, 135.8 (K), 132.5, 132.1 (K), 131.9 (K), 130.3 (K),
129.7 (K)(C4), 128.0 (K)(C3), 125.5 (K)(C6), 99.3 (K)(C2),
69.7 (OCH2), 65.2 (OCH2). IR (KBr film, cmK1): 3029,
2978, 1753, 1707, 1429, 1417, 1325, 1255, 1198, 1094, 1059,
1024, 885. MS (EI, 70 eV) m/z 320 (MC, 5), 232 (5), 183
(62), 139 (100), 111 (40), 75 (25%). Anal. Calcd for
C16H13ClO5: C, 59.92; H, 4.09. Found: C, 59.80; H, 4.06.
0
0
The 1H NMR spectral studies of the residue obtained
after crystallization showed the presence of dilactone 20,
which was formed in about 1–2% (for spectral data
see Section 4.1.4).
4.1.4. Oxidation of 1613a with 3,3-dimethyl-dioxirane
(DMD) To a dioxirane–acetone solution (8.5 mL, 0.08 M)
synthesized as described in the literature16 was added a
solution of 16 (100 mg, 0.67 mmol) in acetone (10 mL) over
a period of 10 min at K78 8C. The reaction mixture was
allowed to come to room temperature during 1 h. After
additional stirring for 1 h at room temperature the solvent
was evaporated and the residue was chromatographed on a
silica gel (30 g) column eluting with n-hexane–ethyl acetate
(9/1). The first fraction was identified as dilactone 20 (9 mg,
The second fraction was identified as dilactone 20 (70 mg,
16%). The elution of the column was continued with ethyl
acetate–methanol (98/2) and as the third fraction; the
aldehyde 28 was isolated (20 mg, 5%, imp. 128–129 8C
from methylene chloride/n-hexane 1:1). (2E,4E)-4-(3-Oxo-
1
1,4-dioxan-2-ylidene)but-2-enal (28): H NMR (200 MHz,
Z
CDCl3): d 9.63 (d, J1,2Z7.8 Hz, 1H, H1), 7.44 (dd, J2,3
15.6 Hz, J3,4Z11.7 Hz, 1H, H3), 6.73 (d, J3,4Z11.7 Hz,
1H, H4), 6.33 (dd, J2,3Z15.6 Hz, J1,2Z7.8 Hz, 1H), 4.58
(AA0-part of AA0BB0 system, 2H, OCH2), 4.33 (BB0-part of
AA0BB0, 2H, OCH2). 13C NMR (APT) (50 MHz, CDCl3): d
195.1, 160.8, 147.1, 143.8, 136.3, 116.8, 68.6, 66.0. IR (KBr
film, cmK1): 3080, 2978, 2953, 2825, 1778, 1753, 1728,
1676, 1472, 1421, 1344, 1319, 1293, 1268, 1242, 1217,
1114, 1089. MS (EI, 70 eV) m/z 168 (MC, 19), 139 (41),
110 (13), 96 (95), 83 (19), 68 (100%). The last fraction was
identified as tropolone 26 (12 mg, 3%).
1
8%). 1,4-Dioxacycloundeca-6,9-diene-5,11-dione (20): H
NMR (200 MHz, CDCl3): d 6.15 (dt, A-part of AB system,
J6,7ZJ9,10Z11.7 Hz, J7,8ZJ8,9Z8.4 Hz, 2H, H7 and H9),
5.89 (dt, B-part of AB system, J6,7ZJ9,10Z11.7 Hz, J6,8
Z
J10,8Z1.1 Hz, 2H, H6 and H10), 4.48 (s, 4H, OCH2), 3.45 (tt,
J7,8ZJ8,9Z8.4 Hz, J6,8ZJ10,8Z1.1 Hz, 2H, Hg). 13C NMR
(50 MHz, CDCl3): d 169.0, 140.6, 125.0, 63.5, 31.4. IR
(KBr, cmK1): 3055, 3030, 2979, 2953, 2928, 1728, 1446,
1396, 1294, 1268, 1243, 1217, 1166, 1064, 911, 834. Anal.
MS (EI, 70 eV) m/z 138 (MCKCO2, 6), 122 (8), 94 (MCK
2!CO2, 100), 82 (9). Anal. Calcd for C9H10O4: C, 59.34;
H, 5.53. Found: C, 59.31; H, 5.72.
4.1.6. Reaction of the endoperoxide 19 with NEt3. To a
solution of endoperoxide 19 (200 mg, 1.10 mmol) in 10 mL
of CH2Cl2 at K30 8C, one drop of freshly distilled
triethylamine was added. The mixture was then stirred at
K30 8C for 3.5 h and to the residue ether (10 mL) was
added to precipitate the product. The formed product was
separated by filtration and crystallized from hot water to
give pure 29 (194 mg, 97%, mp 223–224 8C). 4-Hydroxy-3-
(2-hydroxyethoxy)cyclohepta-2,4,6-trien-1-one (29): 1H
NMR (200 MHz, CD3OD) 7.32 (dd, A-part of AB system
and A-part of AX system, J5,6Z11.7 Hz, J6,7Z10.4 Hz, 1H,
H6), 6.88 (d, J2,7Z2.3 Hz, 1H, H2), 6.86 (d, B-part of AB
system, J5,6Z11.7 Hz, 1H, H5), 6.62 (dd, X-part of AX
system, J6,7Z10.4 Hz, J2,7Z2.3 Hz, 1H, H7), 4.09 (A2-part
of A2B2 system, 2H, OCH2), 3.96 (B2-part of A2B2 system,
2H, OCH2). 13C NMR (CD3OD): 177.4, 173.4, 166.7,
141.8, 126.5, 119.5, 115.8, 74.2, 62.8. IR (KBr film, cmK1):
3464, 3004, 2979, 2953, 2927, 2570, 1600, 1548, 1523,
1446, 1421, 1191, 1165, 936. MS (EI, 70 eV) m/z 182 (MC,
12), 154 (18), 138 (3), 125 (66), 110 (100), 83 (17).
Anal. Calcd for C9H10O4: C, 59.34; H, 5.53. Found: C,
59.39; H, 5.63.
The second fraction was identified as 26 (81 mg, 73%), mp
80–81 8C, (lit. mp13 83–84 8C). 2-(2-Hydroxyethoxy)-
cyclohepta-2,4,6-trien-1-one (26): 13 1H NMR (200 MHz,
CDCl3): d 7.34–7.05 (m, 5H, H3, H4, H5, H6 and H7), 4.90
(m, 1H, OH), 4.15 (A2-part of A2B2 system, 2H, OCH2),
4.05 (B2-part of A2B2 system, 2H, OCH2). 13C NMR
(CDCl3): d 182.8, 166.9, 139.1, 139.0, 135.0, 130.6, 116.7,
73.2, 62.4. IR (KBr, cmK1): 3361, 2953, 2876, 1626, 1603,
1568, 1475, 1290, 1279, 1209, 1094, 1024, 781, 723.
4.1.5. Oxidation of 16 with m-chloroperbenzoic acid
(m-CPBA). To a solution of 16 (360 mg, 2.40 mmol) in
methylene chloride (20 mL) was added Na2CO3 (1.27 g,
12 mmol) and m-CPBA (426 mg, 2.47 mmol). The
resulting mixture was stirred for 4 h at room temperature
in an ultrasound bath. The precipitate was filtered and the
solvent evaporated to dryness. The residue was chromato-
graphed on silica gel (100 g) eluting with n-hexane–ethyl
acetate (8/2). The first fraction was identified as 27
(200 mg, 26%, mp 105–106 8C from methylene chloride–
n-hexane 1/2). 2-[(5-Oxocyclohepta-1,3,6-trien-1-yl)oxy]ethyl
4.1.7. Reaction of endoperoxide 19 with Al2O3. A
solution of endoperoxide 19 (200 mg, 1.10 mmol) in 5 mL
of CHCl3 was loaded to an aluminum oxide column

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A. Das¸tan, M. Balci / Tetrahedron 62 (2006) 4003–4010
(30 g, neutral, activity 3) prepared with hexane, and the top
of the column was closed for 30 min. After a total waiting
time of 30 min, the top of the column was opened and
elution was continued with n-hexane–ethyl acetate (4/6) to
give 31 as pale yellow crystals (23 mg, 13%, mp 98 8C from
methylenechloride–n-hexane (1/2). Later, the elution was
continued with ethyl acetate and methanol (4:1) to give 2613
as pale yellow crystals (6 mg, 3%). 2,3-Dihydro-5H-
4.1.10. Reaction of endoperoxide 35 with thiourea.
The endoperoxide 35 (100 mg, 0.51 mmol) was dissolved in
CH3OH (10 mL) at 10 8C. A solution of thiourea (53 mg,
0.69 mmol) in CH3OH (3 mL) was added dropwise over
1 min, then the solution was stirred 3 h at room temperature.
The residue was filtered and the solvent was reduced to half
of its volume. After standing in freezer for one night, the
formed crystals were characterized as tropolone 37A
(93 mg, 92%, pale yellow crystals, mp 185–186 8C from
methanol). 2,5-Dihydroxy-4-(2-hydroxyethoxy)cyclohepta-
2,4,6-trien-1-one (37): 1H NMR (200 MHz, CD3OD): d
7.08 (d, A-part of AB system. J6,7Z11.3 Hz, 1H, H6), 7.04
(s, 1H, H3), 6.95 (d, B-part of AB system, J6,7Z1.3 Hz,
1H, H6), 4.20 (A2-part of A2B2 system, 2H, OCH2), 3.98
(B2-part of A2B2 system, 2H, 2H, OCH2). 13C NMR
(50 MHz, CD3OD): 176.7, 162.2, 161.21, 154.3, 119.9,
117.6, 115.7, 74.4, 62.7. IR (KBr, cmK1): 3423, 3269, 2436,
1603, 1549, 1472, 1425, 1263, 1197, 1078, 916, 870. MS
(EI, 70 eV) m/z 199 (MC, 5), 154 (10), 127 (52), 96 (16), 70
(24), 64 (100), 53 (39%). Anal. Calcd for C9H10O5: C,
54.55; H, 5.09. Found: C 54.01 H: 5.60.
1
cyclohepta[b][1,4]dioxin-5-one (31): H NMR (200 MHz,
CDCl3): d 6.95–6.84 (m, 3H, H7, H8 and H9 (or H6)), 6.61
(dd, JZ8.8, 1.7 Hz, 1H, H9 (or H6)), 4.30 (br s, 4H, OCH2).
13C NMR (CDCl3): d 186.4, 155.9, 154.7, 139.4, 134.4,
128.3, 118.5, 65.9, 65.7. IR (KBr, cmK1): 3055, 2978, 2927,
1651, 1548, 1472, 1425, 1293, 1217, 1191, 1089, 885, 808.
MS (EI, 70 eV) m/z) 164 (MC, 9), 136 (65), 80 (100), 52
(65%). Anal. Calcd for C9H8O3: C, 65.85; H, 4.91. Found:
C, 66.02; H, 4.95.
4.1.8. Thermolysis of endoperoxide 19. The endoper-
oxide 19 (160 mg, 0.88 mmol) was dissolved in toluene
(5 mL) and heated to 160 8C for 6 h in a sealed tube. After
evaporation of the solvent the residue was filtered through
florisil column (30 g) eluting with n-hexane–ethyl acetate
(4/1) to give 30 (85 mg, 53%, pale yellow crystals, mp 94–
95 8C from ether/n-hexane 1:1). (7R(S),8R(S))-7,8-Epoxy-
1,4-dioxaspiro[4.6]undec-10-en-6-one (30): 1H NMR
(200 MHz, CDCl3): d 5.67 (m, 2H, H10 and H11), 4.17–
4.1.11. CoTPP-catalyzed reaction of endoperoxide
(35). To a magnetically stirred solution of endoperoxide 35
(100 mg, 0.51 mmol) in CH2Cl2 (10 mL) at K10 8C was
added cobalt-meso-tetraphenylporphyrin (C0TPP) (20 mg) in
portions. The mixture was stirred for 2 min. The
solvent was then evaporated. The 1H NMR spectral analysis
of the residue indicated the formation of bisepoxide 38
(87 mg, 87%, colorless crystals from methylenechloride/ether
1:1, mp 105–106 8C). 2,3,(7aR(S)),(8aS(R))-Tetra-hydro-
7H-(4aR(S)),8b(S(R))-epoxyoxireno[3,4]cyclohepta[1,2-
b][1,4]dioxin-7-one (38):1H NMR (200 MHz, CDCl3):d 6.38
(d, A-part of AB system, J5,6Z11.5 Hz, 1H, H5), 5.89 (dd,
B-part of AB system, J5,6Z11.5 Hz, J7a,6Z1.8 Hz, 1H, H6),
3.95 (m, 4H, OCH2), 3.74 (d, A-part of AB system, J7,8
4.8 Hz, 1H, H7), 3.54 (dd, B-part of AB system, J7,8
Z
Z
4.8 Hz, J8,9Z4.5 Hz, 1H, H8), 3.02 (ddt, A-part of AB
0
system, J9,9 Z19.2 Hz, J8,9ZJ9,10Z4.5 Hz, J9,11Z1.9 Hz,
0
1H, H9), 2.76 (br d, B-part of AB system, J9,9 Z19.2 Hz,
1H, H9 ). 13C NMR (CDCl3): d 200.6, 129.6, 128.4, 107.5,
0
68.3, 67.4, 59.2, 54.8, 28.7. IR (KBr film): 3029, 2998,
2985, 2896, 2883, 2870, 1727, 1446, 1395, 1217, 1191,
1089, 1012, 961. MS (EI, 70 eV) m/z 183 (MC, 1), 125 (19),
113 (43), 82 (69), 68 (56), 53 (100%). Anal. Calcd for
C9H10O4: C, 59.34; H, 5.53. Found: C, 59.14; H, 5.48.
3.98 (m, 2H, OCH2), 3.78 (d, A-part of AB system, J7a,8a
Z
4.3 Hz, 1H, H8a), 3.74 (m, 2H, OCH2), 3.68 (dd, B-part of AB
system, J7a,8aZ4.3 Hz, J7a,6Z1.8 Hz, 1H, H7a). 13C NMR
(50 MHz, CDCl3): d 199.3, 132.1, 129.8, 86.1, 84.6, 64.3,
63.4, 61.6, 56.4. IR (KBr, cmK1): 2961, 2899, 1641, 1449,
1410, 1317, 1171, 1101, 1032, 909. Anal. Calcd for C9H8O5:
C, 55.11; H, 4.11. Found: C, 55.20; H, 4.01.
4.1.9. Photooxygenation of 2,3-dihydro-7H-cyclo-
hepta[b][1,4]dioxin-7-one (18). The reaction was carried
out according to the above mentioned procedure (Section
4.1.2) by using 200 mg (1.22 mmol) of 1814 and TPP
(10 mg) in 200 mL of chloroform. After 45 min irradiation,
4.1.12. The formation of 39 from 38. Bisepoxide 38
(40 mg, 0.20 mmol) was dissolved in 0.5 mL of CDCl3
and its rearrangement was followed by the 1H NMR
spectroscopy. After 5 days, the bisepoxide was completely
rearranged to epoxy ketal 39 at room temperature. The
residue was recrystallized from methylene chloride–ether
(2/1) to give pure 39 (29 mg, 72%, colorless crystals mp 97–
98 8C). (7S(R),8R(S))-7,8-Epoxy-1,4-dioxaspiro[4.6]undec-
10-ene-6,9-dione (39): 1H NMR (200 MHz, CDCl3): d 6.25
(d, A-part of AB system, J10,11Z12.9 Hz, 1H, H11), 6.00
(dd, B-part of AB system, J1,11Z12.9 Hz, J8,10Z1.8 Hz,
1H, H10), 4.28–3.98 (m, 4H, OCH2), 4.01 (d, A-part of AB
system, J7,8Z5.0 Hz, 1H, H7), 3.88 (dd, B-part of AB
system, J7,8Z5.0 Hz, J8,10Z1.8 Hz, 1H, H8). 13C NMR
(50 MHz, CDCl3): d 197.7, 196.8, 140.1, 129.7, 106.3, 69.0,
67.9, 58.8, 58.1. IR (KBr, cmK1): 2976, 2902, 1730, 1702,
1611, 1384, 1173, 1030, 950, 782. MS (EI, 70 eV) m/z 196
(MC, 1), 167 (3), 140 (16), 126 (22), 114 (19), 99 (77), 86
(47), 69 (50), 54 (100%). Anal. Calcd for C9H8O5: C, 55.11;
H, 4.11. Found: C, 54.95; H, 4.05.
1
the solvent was evaporated and the H NMR analysis of
residue indicated the formation of the endoperoxide 35 as
the sole product. The recrystallization of the residue from
CH2Cl2–ether (1/3) gave the endoperoxide 35 as colorless
crystals (225 mg, 94%, mp 106–107 8C). (4aR(S),8R(S))-
2,3-Dihydro-4a,8-epidioxycyclohepta[b][1,4]-dioxin-
1
7(8H)-one (35): H NMR (200 MHz, CDCl3): d 6.80 (d,
A-part of AX system, J5,6Z11.4 Hz, 1H, H5), 5.93, (dd,
B-part of AX system, J5,6Z11.4 Hz, J6,8Z1.9 Hz, 1H, H6),
5.52 (d, A-part of AX system, J8,9Z8.1 Hz, 1H, H9), 5.00
(dd, X-part of AX system, J8,9Z8.1 Hz, J6,8Z1.9 Hz, 1H,
H8), 4.41–3.94 (m, 4H, OCH2). 13C NMR (CDCl3): d 195.4,
159.0, 147.5, 130.3, 102.6, 97.0, 89.12, 68.3, 64.5. IR (KBr,
film): 3080, 3055, 2978, 2953, 2927, 1728, 1702, 1676,
1472, 1395, 1370, 1344, 1293, 1268, 1165, 1013, 859. MS
(EI, 70 eV) m/z 196 (MC, 2), 164 (MCKO2, 14), 137 (28),
83 (38), 69 (48), 54 (100%). Anal. Calcd for C9H8O5: C,
55.11; H, 4.11. Found: C, 55.13; H, 4.18.

A. Das¸tan, M. Balci / Tetrahedron 62 (2006) 4003–4010
4009
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4.1.13. Thermolysis of endoperoxide 35. Endoperoxide
35 (104 mg, 0.53 mmol) was dissolved in toluene (10 mL)
and heated to 80G2 8C for 2 days in a sealed tube. After
evaporation of the solvent, the H NMR spectrum of the
residue showed the formation of 18 as the sole product in
quantitative yield. (104 mg, 100%).
7. (a) Soung, M.-G.; Matsui, M.; Kitahara, T. Tetrahedron 2000,
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1
4.2. Thermolysis of endoperoxide 35 in the presence of
DBI. Endoperoxide 35 (200 mg, 1.02 mmol) and 1,3-
diphenyl-isobenzofuran (DBI) (551 mg, 2.04 mmol) were
dissolved in anhydrous benzene (10 mL) and heated to 80G
2 8C for 2 days in a sealed tube. After evaporation of the
solvent the residue was chromatographed on silica gel
(20 g) eluting with n-hexane–ethyl acetate (9/1). The first
fraction was identified as diketone 40 (240 mg, 82%).21a
Further elution with hexane–ethyl acetate (1/1) gave the
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8. (a) Scott, A. I.; Lee, E. J. Chem. Soc., Chem. Commun. 1972,
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Y. K.; Kazaz, C.; Balci, M. Turk. J. Chem. 2002, 26, 143–151.
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4.3. Thermolysis of endoperoxide in the presence of 2,3-
dimethyl-but-2-ene. The endoperoxide 35 (200 mg,
1.02 mmol) and 2,3-dimethyl-but-2-ene (172 mg,
2.04 mmol) in 10 mL of anhydrous benzene was reacted
1
in a sealed tube as described above. The H NMR analysis
of the residue showed the formation of the hydroperoxide
4121a in 24% yield and tropone 18 in 90% yield.
Acknowledgements
¨ ˙
The authors are indebted to TUBITAK (104T401) Atatu¨rk
9. Balci, M. Chem. Rev. 1981, 81, 91–108.
10. Das¸tan, A.; Saracoglu, N.; Balci, M. Eur. J. Org. Chem. 2001,
3519–3522.
University and Middle East Technical University for
financial supports. This work also has been supported by
the Turkish Academy of Sciences, in the framework of the
Young Scientist Award Program (AD/TUBA-GEBIP/2001-
1-3). Authors are also indebted to Professor Akira Mori
(Kyushu University) for some of the documents.
¨
˙
11. (a) Gu¨ney, M.; Das¸tan, A.; Balci, M. Helv. Chim. Acta 2005,
88, 830–838. (b) Gu¨ney, M.; C¸ elik, Z. C.; Das¸tan, A.; Balci,
M. Can. J. Chem. 2005, 83, 227–235.
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