Reactions of 3,10-epoxycyclo[10.2.2.02,11.04,9]hexadeca-4,6,8,13-tetraene: a new intramolecular 1,5-oxygen migration

Article abstract of DOI:10.1016/j.tet.2006.10.012

Bromination of 3,10-epoxycyclo[10.2.2.0^2,11.0^4,9]hexadeca-4,6,8,13-tetraene gave 13-bromo-11-oxapentacyclo[8.7.0.0^2,4.0^12,17]heptadeca-4,6,8-triene-3-ol, 12-bromo-1,2,3,4-tetrahydro-1,4-ethano-antracen-11-ol, 13

Full text of DOI:10.1016/j.tet.2006.10.012

Tetrahedron 62 (2006) 12318–12325
Reactions of 3,10-epoxycyclo[10.2.2.02,11.04,9]hexadeca-4,6,8,13-
tetraene: a new intramolecular 1,5-oxygen migration
b
Abdullah Menzeka, and Aliye Altundaxs
*
aDepartment of Chemistry, Atatu€rk University, 25240 Erzurum, Turkey
bDepartment of Chemistry, Gazi University, 06500 Ankara, Turkey
Received 18 June 2006; revised 18 September 2006; accepted 5 October 2006
Available online 31 October 2006
Abstract—Bromination of 3,10-epoxycyclo[10.2.2.02,11.04,9]hexadeca-4,6,8,13-tetraene gave 13-bromo-11-oxapentacyclo[8.7.0.02,4.012,17]-
heptadeca-4,6,8-triene-3-ol, 12-bromo-1,2,3,4-tetrahydro-1,4-ethano-antracen-11-ol, 13-hydroxy-3,14-dibromotetracyclo[10.2.2.02,11.04,9]-
hexadeca-2,4,6,8,10-pentaene, and 13-hydroxy-3,10,14-tribromotetracyclo[10.2.2.02,11.04,9]hexadeca-2,4,6,8,10-pentaene by cleavage of
the carbon–oxygen bonds and intramolecular 1,5-migration of the oxygen atom of 1,4-epoxide. Reactions of epoxide 14,18-dioxahexa-
cyclo[10.3.2.13,10.02,11.04,9.013,15]octadeca-4,6,8-triene obtained from 3,10-epoxycyclo[10.2.2.02,11.04,9]hexadeca-4,6,8,13-tetraene gave
also similar products, in acidic media. Compound 3,10-epoxycyclo[10.2.2.02,11.04,9]hexadeca-4,6,8,13-tetraene was converted into tetra-
cyclo[10.2.2.02,11.04,9]hexadeca-2(11),3,9-triene in two ways. The reactions, especially intramolecular oxygen migration, are discussed.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The structure of 3,10-epoxycyclo[10.2.2.02,11.04,9]hexa-
deca-4,6,8,13-tetraene (6) is similar to that of 4 as it includes
1,4-epoxide, an isolated double bond, and a benzene ring as
functional groups. Its reactions with reagents such as bro-
mine and meta-chloroperbenzoic acid (m-CPBA) will be
important. Its importance is the following: (1) From which
face does bromine or m-CPBA attack the double bond in
6? (2) How does epoxide act in 6 when the reagents such
as Br2 or m-CPBA react with the double bond? Does a cis-
dibromide 7 similar to 5 happen? Or does this epoxide in 6
rearrange? (3) Does anthracene derivative 8 obtained from
6, by elimination of water? At the same time, 8 is an adduct
of cyclohexadiene and was obtained by two different ways
(from reactions of 1,3-cyclohexadiene with naphthyne and
1,4-naphthoquinone separately).4 (4) It will also be possible
that the aromatic ring shifts from terminal ring to the central
ring in the same compound if 9 is obtained from 6 by
reduction reactions from 6 (Scheme 2). Therefore, reactions
of the compound 6 with these reagents were investigated
separately.
Molecular rearrangementsoccur in some reactions of organic
compounds. According to the processes desired in the syn-
thesis, rearrangements may be of value or a disadvantage
for researchers. These rearrangements depend on the struc-
tures of the compounds and reaction conditions.1 Oxabenzo-
norbornadiene (1), barralene (2), and benzhomobarralene
derivative 3 give skeleton rearrangements.1a,2 The structures
of compounds 4 and 6 include both oxabenzonorbornane and
barrelene derivatives as annulated structures. Dibromide 53
was selectively formed in the bromination of compound 4
by neighboring group participation of the oxygen atom
in 4 (Scheme 1).
R
O
3
1
2
Br
R
Br
R
O
O
O
2. Results and discussion
5
6
4
Adduct 6 was obtained from the Diels–Alder cycloaddition
reaction of 1,4-dihydronaphthalene-1,4-epoxide with cyclo-
hexadiene.3 Adduct 6 was reacted with Br2 (1.1 equiv) in
a CCl4 solution at 0 ꢀC for 30 min (Scheme 3). It was seen
that adduct 6 was absent in the H NMR spectrum of the
reaction mixture. Careful PLC (preparative thick-layer chro-
matography) allowed us to isolated two products, 10 and 11.
Scheme 1.
Keywords: Aromatization; Bromination; Epoxide; Epoxidation; Naphthyne;
Oxygen migration; Rearrangement; Reduction.
* Corresponding author. Tel.: +90 4422314423; fax: +90 4422360948;
e-mail: amenzek@atauni.edu.tr
1
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.012

A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
12319
Br
Br
O
?
?
Br2
O
?
7
?
8
?
Br2
6
?
Rearrangement product (s)
9
Scheme 2.
13
12
13
13
HO
O
O
Br
Br
10
10
Br2 (1.1 equ.)
CCl4
+
3
1
3
H
10
6
11
OH
H
KOBut
O
56%
31%
Br2 (Excess)
CCl4
13
13
HO
HO
Br
Br
10
Br
10
+
3
12
3
13
14
80%
Br
Br
13%
59%
Scheme 3.
On the basis of the NMR spectra of these compounds, it was
determined that they are asymmetrical structures, but it
was not easy to establish their exact configurations. NMR
spectroscopic data of 11 indicated that it is a naphthalene
derivative with Br and OH functional groups. To confirm
the configuration of Br and OH groups in 11, compound
11 was reacted with potassium tert-butoxide to give epoxide
12. Epoxide 124a has a symmetrical structure and its
structure is consistent with its NMR spectra (Scheme 3).
To determine the exact structures of 10 and 11, X-ray crys-
tallographic analyses were carried out.5 We assumed that 10
might be formed during PLC by the hydrolysis of intermedi-
ate bromide (probable 24, Scheme 5) whose structure is not
known.
groups (Br and OH) should be at the bridgehead as in 11. The
region of Br at aromatic carbon (C3) was regarded as com-
pound 13 because greater steric effect(s) can occur between
the Br and OH groups in it and its intermediate(s) if Br is at
C10 rather than the other position (if Br is at C3). Tribromide
14 does not have a symmetrical structure and is consistent
with its NMR spectra.
In the reactions of compound 6 with bromine, the epoxide
ring of 6 is opened and tetrahydrofuran rings occur in this
structure, as in 10, by intramolecular 1,5-migration of the
oxygen atom. Then halohydrins 11, 13, and 14 occur by
the aromatization of these structures.
Intramolecular 1,5-migration of the oxygen atom and forma-
tion of tetrahydrofuran derivative are important in the bromi-
nation of 6. There are intramolecular oxygen migrations.6
One of them is migration of the oxygen atom, which is ob-
served in the conversion of compound 15 to compound
18.6b According to the data, epoxide (oxa norcaradiene) 16
was formed by nucleophilic attack of oxygen, and then 18
was formed (via 17) by ring opening of epoxide and aroma-
tization of ring in this reaction (Scheme 4). The migration of
the oxygen atom in the formation of 18 is an intramolecular
1,2-migration and is similar to that of 6. However, the
In a similar manner, adduct 6 was reacted with excess Br2.
After evaporation of excess Br2 and solvent, dibromide 13
and tribromide 14 were isolated in this bromination reaction
by column chromatography (Scheme 3). The 1H NMR spec-
trum of dibromide 13 showed absorptions at d 8.29 (d), 7.81
(d), 7.64 (s), and 7.63–7.27 (m), with relative intensities of
1:1:1:2. However, dibromide 13 does not have a symmetrical
structure and exhibits ten lines in the aromatic and six lines
in the aliphatic regions of its 13C NMR spectrum. One of the
five quaternary carbons should be CBr and other substituent
HO
OH
H2O
N
NH
15
18
R
R
O
O
O
H
H
H
+
OH
NH
- H+
O
- HO-
NH
16
17
R
R
O
O
Scheme 4.

12320
A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
13
13
Br
13
+
Br+
:
:
O
:
O
14
O
8
10
10
H
12
Br Br
Br-
10
6
3
3
19
3
20
1
H
H
H
6
H
H
H
13
13
13
+
:
O
H
:
O
HO
Br
HO
+
Br
Br
Br
+
10
- H
+
21
11
22
H
H
23
H
-
Br2
Br
2 Br2
- HBr
- 2 HBr
13
Br
13
13
Br
13
:
:
O
O
H
HO
Br
HO
10
Br
Br
H2O
- HBr
Br2
3
3
- HBr
3
3
Br
OH
14
Br
H
Br
10
24
13
H
H
Scheme 5.
intramolecular 1,5-migration of the oxygen atom is a new
oxygen migration.
be added to its ring, which is electron-rich. Compound 11 is
converted into 13 by the addition of Br2 and then the elimi-
nation of HBr. Compound 14 can be formed by either the
addition of 2 equiv of Br2 to 11 and then the elimination
of 2 equiv of HBr or the addition of Br2 to 13 and then the
elimination of HBr.
To rationalize the formation of compounds 10, 11, 13, and
14, we propose the following reaction mechanism as favor-
able mechanism. As shown in the bromination of compound
5,3 bromine can attack the double bond in 6 from the exo face
(Scheme 5). A bridged bromonium ion 19 is produced and
the oxygen of the epoxide acts as a nucleophile to yield
20. Intermediate 21 is produced from 20 by the opening of
the epoxide ring. Brꢁ can attack intermediate 21 to give
24 (probable) as a nucleophile. Intermediate 24 whose struc-
ture is not known may hydrolyze to give 10. Intermediate 21
is converted into 11 through intermediates 22 and 23 by aro-
matization of the ring. As reported in the literature,7 bromine
is added to naphthalene and its derivatives, and then bromi-
nated naphthalenes are produced by the elimination of HBr.
Compound 11 is a naphthalene derivative, and bromine will
As mentioned above, bromine attacks the double bond in 4
and 6 from the exo face. m-CPBA can attack the double
bound in 6 by approach from exo and endo (toward 1,4-
epoxide) faces. To investigate the approach of m-CPBA to
the double bond in 6 and to confirm the intramolecular
1,5-migration of the oxygen atom, compound 6 was reacted
with m-CPBA (Scheme 6). In this epoxidation, epoxide 25
and ester 268 were obtained. According to its NMR data
such as HETCOR and COSY, 25 has a symmetrical structure
and is consistent with the proposed structure. In the forma-
tion of epoxide 25, m-CPBA also attacks the double bond
in 6. As shown in Scheme 7, ester 26 is a secondary product
formed from 25.
13
13
13
O
O
O
3
O
OH
10
10
10
m-CPBA
CHCl3
Epoxide 25 was refluxed with TsOH (p-toluenesulfonic
acid) in MeOH for 1 week (Scheme 7). In this reaction,
only diol 27 was obtained and epoxide 25 was not present.
However, when the opening of the ring of epoxide 25 with
NaOMe in similar conditions was attempted, we isolated
only unreacted starting material.
+
3
25
3
H
H
Cl
6
O
26
H
H
O
9%
71%
Scheme 6.
13
13
OH
:
O
:
O
HO
14
10
AcO
OAc
HOTs
Ac2O
MeONa
MeOH
MeOH
3
25
Pyridine
H
27
28
H
H+
-H+
13
OH
H
13
O+
HO
+
:
:
:
O
O
OH
+
10
H
10
3
29
H
H
H
33
32
- H+
H
13
OH
13
+
:
:
O
O
O
OH
OH
Nu-
3
30
3
31
3
H
H
26
+
H
Nu
H
H
H
Nu- = m-ClC6H4COO-
Scheme 7.

A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
12321
For the formation of diol 27, we can propose the following
reaction mechanism as favorable mechanism. The fact that
no product with OMe was observed in either of them by the
opening of 1,2-epoxide, which shows that the oxygen of
1,4-epoxide only attacked the 1,2-epoxide as a nucleophile.
First, 1,2-epoxide is protonated with TsOH and it converts
into structure 31 via 29 and 30 because it is more strained
than the 1,4-epoxide.9 Intermediate 31 can convert into
both 32, by the departure of the proton and the formation of
a double bond, and 26 by the attack of a nucleophile. Ester
26,8 a substitution product, was obtained in the epoxidation
of compound 6 because m-chlorobenzoic acid (m-ClC6-
H4COOH) or m-chlorobenzoate (m-ClC6H4COOꢁ) trans-
ferred from m-CPBA is present. Intermediate 32, a
protonated tetrahydrofuran derivative, can convert into diol
27 via 33 by the opening of the tetrahydrofuran ring, the
departure of the proton, and aromatization of ring. The syn-
thesis and structure of diacetate 28 also confirm diol 27.
cyclohexadiene and 7-methoxycarbonylcycloheptatriene,
respectively.3 However, a diol derivative of 34 was
synthesized from reaction of 1,4-naphthoquinone with
7-methoxycarbonylcycloheptatriene as adduct.11 Therefore,
1,4-dihydronaphthalene-1,4-epoxide can act as a synthetic
equivalent of naphthyne.
In compound 6, aromatic and olefinic double bonds can be
reduced, and these reduced products will be interesting.
With this in mind, reduction reactions of 6 were investigated
in two ways. One synthetic path is via 6, 37, 38, 39, and 9,
while the other is via 6, 8, 40, and 9 (Scheme 9). Catalytic
hydrogenation of compound 6 quantitatively gave 37
(Scheme 9). Reaction of compound 37 with TsOH gave an-
thracene derivative 38 in 72% yield. The data of 384a and 39
are in complete agreement with the proposed structures. We
performed the reductions of aromatic compounds such as
naphthalene with alkali metals and tert-butyl alcohol in
high yield at room temperature.12 Reduction reactions of 8
and 38 with Na/tBuOH were carried out separately. Reduc-
tion of 8 produced a mixture of 8 and 40 while reduction
of 38 produced a mixture of 38 and 39. These mixtures could
not be separated by chromatographic methods. Unsubsti-
tuted aromatic rings of 8 and 38 were reduced in these reac-
tions because their electron densities are less than the
others.13 Catalytic hydrogenations of 39 and 40 in these mix-
tures gave compound 9 in high yields (Scheme 9). The aro-
matic protons of 9, 39, and 40 resonate at 6.91, 6.98, and
6.98 ppm, respectively, as singlets.
A compound such as epoxide 6 reacted with acids gives an
aromatic product by the elimination of water.10 Epoxide 6
was reacted with TsOH in a methanol solution at 65ꢂ5 ꢀC
(in a sealed tube) for 12 days and only an anthracene deriv-
ative 8 was isolated (Scheme 8). However, anthracene deriv-
ative 8 was also obtained when epoxide 6 was heated at
200ꢂ5 ꢀC (in a sealed tube) for 12 days. In a similar manner,
the reaction of compound 4 with TsOH in a methanol solu-
tion at 65ꢂ5 ꢀC (in a sealed tube) for 12 days gave only an
anthracene derivative 34 (Scheme 8). According their NMR
data, both 84a and 34 have symmetrical structures. Aromatic
protons of 34 resonate as an AA0BB0 system and a singlet.
Compounds 8 and 34 represented by a generic structure 36
are adducts of naphthyne with cyclohexadiene and 7-meth-
oxycarbonylcycloheptatriene, respectively, and they were
obtained from adducts 6 and 4, which were synthesized
from reactions of 1,4-dihydronaphthalene-1,4-epoxide with
There is an aromatic ring in compounds 6 and 9, but these
aromatic rings are in different units of these structures.
Therefore, the aromatic ring in 6 was transferred into another
ring in 9 by chemical reactions.
3. Conclusion
COOMe
O
The reaction of compound 6 with Br2 (1.1 equiv) gave tetra-
hydrofuran derivative 10 and anthracene derivative 11, while
with excess Br2 it gave anthracene derivatives 13 and 14. As
shown in Scheme 5, compounds 13 and 14 are not primary
products and they are formed from 11. Compound 10 is
formed by the cleavage of a carbon–oxygen bond and intra-
molecular 1,5-migration of the oxygen atom of 1,4-epoxide.
Compound 11 can also be formed from products and inter-
mediate(s) such as 21 and 24 by cleavage of the tetrahydro-
furan rings in them. Reactions of epoxide 25 obtained from 6
also gave similar products, 26 and 27, in acidic media. In
these reactions, the observed intramolecular 1,5-migration
of the oxygen atom of 1,4-epoxide is important and new.
O
H
H
4
6
35
H
H
a) HOTs / MeOH
HOTs / MeOH
65 5 °C / 12 days
65 5 °C / 12 days
or
b) 200 5 °C / 12 days
COOMe
34
8
36
Scheme 8.
O
O
HOTs
H2
HOTs
MeOH
Pd / C
MeOH
H
H
8
6
37
38
H
H
ROH
Na
Na
ROH
H2
H2
Pd / C
Pd / C
40
9
39
Scheme 9.

12322
A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
Compounds 8 and 34 represented by a generic structure 36
were formed from the reactions of 6 and 4 with TsOH, are
adducts of naphthyne with cyclohexadiene and 7-methoxy-
carbonylcycloheptatriene, respectively. Therefore, 1,4-di-
hydronaphthalene-1,4-epoxide can be used as a synthetic
equivalent of naphthyne.
(50 MHz, CDCl3) d 139.5 (C), 135.1 (C), 129.6 (CH),
127.1 (CH), 124.3 (CH), 52.0 (CH), 39.1, 24.9; Anal. Calcd
for C16H14O: C 86.45, H 6.35; found: C 86.29, H 6.37.
4.4. Bromimation of the compound 6 with excess
bromine
Compound 6 was converted into 9 by reactions of TsOH and
reduction. Aromatic rings are found in different units in the
structures of 6 and 9. Therefore, the aromatic ring in 6 was
transferred into another ring in 9 by these reactions.
To a stirred solution of compound 6 (1 g, 4.46 mmol) in CCl4
(45 mL) was added Br2 (2–3 mL, excess) dropwise at 0 ꢀC
over 5 min. The temperature of the bath was allowed to rise
gradually to room temperature. After the addition of Br2
was completed, the reaction mixture was stirred for 19 h.
Solvent and excess Br2 were evaporated. Chromatography
of the residue on silica gel (60 g) with hexane/ether (10/1)
gave the first fraction tribromide 14 (1.2 g, 2.61 mmol, 59%)
and the second fraction dibromide 13 (186 mg, 0.57 mmol,
13%).
4. Experimental
4.1. General methods
All chemicals and solvents are commercially available and
were used after distillation or treatment with drying agents.
Melting points were determined on Thomas-Hoover capil-
lary melting apparatus and are uncorrected. IR spectra were
obtained from solutions in 0.1 mm cells with a Perkin–Elmer
spectrophotometer. The 1H and 13C NMR spectra were
recorded on a 200 (50) and 400 (100)-MHz Varian spectro-
meter; d in parts per million, Me4Si as the internal standard.
Mass spectra were determined on VG ZabSpec, double
focusing, magnetic sector (100.000 resolution) max. range
1000 for EI and 10,000 for HRMS. Elemental analyses
were performed on Carlo Erba 1106 apparatus. All column
chromatography was performed on silica gel (60-mesh,
Merck). PLC is preparative thick-layer chromatography:
1 mm of silica gel 60 PF (Merck) on glass plates.
4.4.1. 1(R)S,12(S)R,13(R)S,14(R)S-13-Hydroxy-3,14-di-
bromotetracyclo[10.2.2.02,11.04,9]hexadeca-2,4,6,8,10-
pentaene (13). Mp 178–180 ꢀC; white crystal from ethyl
acetate/hexane; 1H NMR (200 MHz, CDCl3) d 8.29 (d, aro-
matic, J¼8.3 Hz, 1H), 7.81 (d, aromatic, J¼6.7 Hz, 1H),
7.64 (s, aromatic, 1H), 7.63–7.27 (m, aromatic, 2H), 4.36
(m, CH-O, 1H), 3.39 (m, 1H), 4.01 (m, 1H), 3.14 (m, 1H),
2.39 (m, methylenic, 1H), 1.95 (m, methylenic, 1H), 1.84
(br d, J¼6.5 Hz, OH, 1H), 1.69–1.40 (m, methylenic, 2H);
13C NMR (50 MHz, CDCl3) d 140.6 (C), 138.5 (C), 136.0
(C), 133.7 (C), 129.8 (CH), 129.6 (CH), 128.9 (CH), 128.4
(CH), 126.8 (CH), 121.5 (C), 81.7 (CH-O), 60.0 (CH),
45.2 (CH), 44.8 (CH), 25.0 (CH2), 20.9 (CH2); m/z: 384.2/
382.3/380.2 (61/41/41), 259.2/257.2 (54/47), 194.2/192.2/
191.2 (22/16/15), 178.2/179.2 (100/52), 166.2/165.2/164.2
(13/29/6); IR (CHCl3) 3301, 3270, 3062, 2939, 2869,
1496, 1419, 1326, 1257, 1187, 1064, 1033, 933, 887, 794,
775, 686 cmꢁ1. HRMS: Anal. Calcd for C16H14O79Br2
381.9568, found 381.9557.
4.2. Bromimation of the compound 6 with bromine
(1.1 equiv)
To a stirred solution of compound 6 (200 mg, 0.89 mmol) in
CCl4 (20 mL) was added Br2 (158 mg, 0.99 mmol, in 1 mL
of CCl4) dropwise at 0 ꢀC over 5 min. The mixture was
stirred for 30 min, and then the solvent was evaporated. Ac-
cording to the NMR spectrum of the residue, compound 6
was absent. The residue was submitted to PLC with ether/
hexane (1:1). Compounds 115b (150 mg, 0.50 mmol, 56%)
and 105a (90 mg, 0.28 mmol, 31%) were isolated pure.
4.4.2. 1(R)S,12(S)R,13(R)S,14(R)S-13-Hydroxy-3,10,14-
tribromotetracyclo[10.2.2.02,11.04,9]hexadeca-2,4,6,8,10-
pentaene (14). Mp 171–173 ꢀC; white crystal from ethyl
1
acetate/pentane; H NMR (200 MHz, CDCl3) d 8.37–8.32
(m, aromatic, 2H), 7.68–7.60 (m, aromatic, 2H), 4.44 (m,
CH-O, 1H), 4.07 (m, 1H), 3.91 (m, 1H), 3.83 (m, 1H), 2.39
(m, methylenic, 1H), 1.97 (m, methylenic, 1H), 1.83 (br d,
J¼5.5 Hz, OH, 1H), 1.70–1.27 (m, methylenic, 2H); 13C
NMR (50 MHz, CDCl3) d 141.0 (C), 138.7 (C), 134.6 (C),
134.4 (C), 130.1 (CH), 129.9 (CH), 129.7 (CH), 129.0
(CH), 123.9 (C), 121.4 (C), 81.8 (CH-O), 59.0 (CH),
45.3 (2CH), 23.8 (CH2), 20.5 (CH2); m/z: 464.1/462.2/
460.2/452.2 (35/76/76/35), 384.2/382.2/380.2 (18/34/20),
339.1/337.1 (35/48), 259.2/258.2/256.2 (50/86/81), 192.2/
191.2/189.2 (31/35/37), 179.2/178.2 (40/100), 165.2/163.2
(48/23); IR (CHCl3) 3284, 3228, 3096, 2916, 2869, 1592,
1492, 1446, 1323, 1253, 1192, 1176, 1076, 1038, 930, 761,
700, 684 cmꢁ1. HRMS: Anal. Calcd for C16H13O79Br3
459.8673, found 459.8686.
4.3. Treatment of halohydrine 11 with tBuOK
To a stirred solution of compound 115b (520 mg, 1.72 mmol)
in dry tetrahydrofuran (40 mL) was added BuOK (1.5 g,
t
13.40 mmol) at room temperature. The mixture was stirred
for 5 days. After the evaporation of solvent, a cold solution
of NH4Cl (5%, 100 mL) was added. The mixture was ex-
tracted with CHCl3 (3ꢃ50 mL). The combined organic layer
was dried over CaCl2 and filtered by a small column (2–3 g
silica gel). After the evaporation of solvent, epoxide 124a
(305 mg, 1.37 mmol, 80%) was crystallized from CHCl3/
hexane as white crystals.
4.3.1. 14-Oxo-1S(R),12R(S),13S(R),15R(S)-pentacyclo-
[10.3.2.02,11.04,9.013,15]heptadeca-2(11),3,5,7,9-pentaene
(12). Mp 166–168 ꢀC (lit. 173–174 ꢀC4a); 1H NMR (200 MHz,
CDCl3) d 7.91–7.85 (AA0 of AA0BB0, aromatic, 2H), 7.61 (s,
aromatic, 2H), 7.53–7.47 (BB0 of AA0BB0, aromatic, 2H),
3.68–3.66 (m, 2H), 3.60–3.54 (m, 2H), 1.98–1.88 (m, meth-
ylenic, 2H), 1.57–1.48 (m, methylenic, 2H); 13C NMR
4.5. Reaction of the compound 6 with m-CPBA
A solution of m-CPBA (2.392 g, 10.40 mmol) whose water
is 25% in CHCl3 (50 mL) was dried over Na2SO4 and fil-
tered. To this solution was added compound 6 (1.164 g,

A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
12323
5.20 mmol). After stirring at room temperature for 1 day, the
reaction mixture was washed with a solution of NaOH
(0.5%, 500 mL) and water (500 mL), dried over Na2SO4,
and the solvent was evaporated. The reaction mixture was
crystallized from CHCl3/ether, and epoxide 25 (735 mg,
3.10 mmol, 59%) was obtained as colorless crystals. The
residue was submitted to preparative thick-layer chromato-
graphy (PLC) with ethyl acetate/hexane (1/1). Epoxide 25
(150 mg, 0.60 mmol, 12%) and compound 268 (468 mg,
1.20 mmol, 9%) were obtained.
4.7.1. 1(R)S,12(S)R,13(S)R,14(S)R-14-(Acetyloxy)tetra-
cyclo[10.2.2.02,11.04,9]hexadeca-2,4,6,8,10-pentaen-13-yl
1
acetate (28). Mp 87–89 ꢀC; H NMR (400 MHz, CDCl3)
d 7.87–7.81 (AA0 of AA0BB0, aromatic, 2H), 7.70 (s, aro-
matic, 1H), 7.61 (s, aromatic, 1H), 7.50–7.44 (BB0 of
AA0BB0, aromatic, 2H), 5.06 (t, J¼2.6 Hz, H14, 1H), 4.80–
4.76 (m, H13, 1H), 3.43–3.41 (m, bridgehead, H12, 1H),
3.33–3.30 (m, bridgehead, H13, 1H), 2.33–2.00 (m, methyl-
enic, 2H), 2.17 (s, methyl, 3H), 1.91 (s, methyl, 3H), 1.62
(tt, J¼12.5, 4.03 Hz, methylenic, 1H), 1.45–1.33 (m, methyl-
enic, 1H); 13C NMR (100 MHz, CDCl3) d 170.7 (CO), 170.5
(CO), 137.8 (C), 137.4 (C), 133.3 (C), 133.2 (C), 128.0 (CH),
127.8 (CH), 125.8 (CH), 125.7 (CH), 124.0 (CH), 123.5
(CH), 77.8 (C–O), 77.7 (C–O), 39.3 (CH), 39.0 (CH), 23.4
(CH), 21.5 (CH3), 21.3 (CH3), 18.6 (CH); IR (CHCl3)
3055, 3018, 2953, 2872, 1739, 1371, 1245, 1214, 1054,
1039, 879, 752 cmꢁ1; Anal. Calcd for C20H20O4: C 74.06,
H 6.21; found: C 73.81, H 6.23.
4.5.1. 1R(S),2R(S),3R(S),10S(R),11S(R),12S(R),13S(R),
15R(S)-14,18-Dioxahexacyclo[10.3.2.13,10.02,11.04,9.013,15]-
octadeca-4,6,8-triene (25). Mp 202–204 ꢀC; colorless
1
crystals; H NMR (400 MHz, CDCl3) d 7.24–7.22 (AA0 of
AA0BB0, aromatic, 2H), 7.15–7.13 (BB0 of AA0BB0, aro-
matic, 2H), 5.22 (s, epoxide, H3–H10, 2H), 3.29 (br s, epox-
ide, H13–H15, 2H), 2.46 (br s, bridgehead, H1–H12, 2H),
1.86 (br s, H2–H11, 2H), 1.75 (br d, A of AABB, J¼8.1 Hz,
methylenic, 2H), 1.06 (br d, B of AABB, J¼8.1 Hz, methyl-
enic, 2H); 13C NMR (100 MHz, CDCl3) d 146.4 (C), 126.8
(CH), 119.1 (CH), 82.7 (CH, C3–C10), 52.3 (CH, C14–C15),
43.8 (CH, C1–C12), 31.3 (CH, C2–C11), 24.0 (CH2); IR
(CHCl3) 3077, 3023, 2939, 2861, 1457, 1419, 1272, 1133,
1079 cmꢁ1. Anal. Calcd for C16H16O2: C 79.97, H 6.71;
found: C 79.76, H 6.68.
4.8. Synthesis of anthracene derivative 84a from 6
This product 8 was synthesized in two different ways.
(a) A mixture of compound 6 (591 mg, 2.46 mmol),
TsOH (156 mg, 0.91 mmol), and MeOH (20 mL) in
a sealed tube was heated at 95ꢂ5 ꢀC for 12 days. The
other parts of the reaction were studied in the same man-
ner as for epoxide 25. CHCl3 (3ꢃ50 mL) was used in the
extraction and anthracene derivative 8 was obtained as
350 mg (1.70 mmol, 69%).
(b) Compound 6 (112 mg, 0.50 mmol) was heated at
200ꢂ5 ꢀC for 12 days alone. After the reaction mixture
with silica gel (2–3 g) was filtered by CHCl3 and the sol-
vent was evaporated, 8 (55 mg, 0.20 mmol, 40%) was
obtained.
4.6. Reaction of epoxide 25 with TsOH
A mixture of epoxide 25 (335 mg, 1.40 mmol), TsOH
(200 mg, 1.16 mmol), and MeOH (50 mL) was refluxed
for 1 week. After the solvent of the mixture was evaporated,
water (50 mL) was added and it was extracted with ethyl
acetate (3ꢃ50 mL). The combined organic layers were
washed with NaHCO3 (5%, 100 mL) and water (100 mL),
dried over CaCl2, and the solvent was evaporated. Diol 27
(175 mg, 73%) was crystallized from ethyl acetate.
4.8.1. 1(R)S,12(S)R-Tetracyclo[10.2.2.02,11.04,9]hexa-
deca-2,4,6,8,10,13-hexaene (8). Mp 102–104 ꢀC (lit. 112–
114 ꢀC4a); white crystals were obtained from CHCl3/hexane;
1H NMR (200 MHz, CDCl3) d 7.86–7.80 (AA0 of AA0BB0,
aromatic, 2H), 7.63 (s, aromatic, 2H), 7.48–7.42 (BB0 of
AA0BB0, aromatic, 2H), 6.63 (m, olefinic, 2H), 4.09 (m,
bridgehead, 2H), 1.73–1.60 (m, methylenic, 4H); 13C NMR
(50 MHz, CDCl3) d 144.8 (C), 137.1 (CH), 134.2 (C), 129.4
(CH), 126.9 (CH), 122.3 (CH), 42.2, 28.1; Anal. Calcd for
C16H14: C 93.16, H 6.84; found: C 92.99, H 6.86.
4.6.1. 1(R)S,12(S)R,13(S)R,14(S)R-Tetracyclo-
[10.2.2.02,11.04,9]hexadeca-2,4,6,8,10-pentaene-13,14-diol
(27). Mp 182–184 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.82–
7.80 (AA0 of AA0BB, aromatic, 2H), 7.66 (s, aromatic, 1H),
7.64 (s, aromatic, 1H), 7.47–7.42 (BB0 of AA0BB, aromatic,
2H), 3.84 (br s, OCH, 1H), 3.62 (br s, OCH, 1H), 3.20 (m,
bridgehead, 1H), 3.15 (m, bridgehead, 1H), 2.19 (m, methyl-
enic, 1H), 1.92 (m, methylenic, 1H), 1.72 (m, OH, 1H), 1.59
(tt, J¼12.7, 4.03 Hz, 1H), 1.31 (m, methylenic, 1H); 13C
NMR (100 MHz, CDCl3) d 139.4 (C), 137.4 (C), 133.2
(C), 133.0 (C), 127.8 (CH), 127.7 (CH), 125.7 (2CH),
124.7 (CH), 123.1 (CH), 79.7 (C–O), 78.8 (C–O), 42.8,
42.1, 23.7, 17.7.
4.9. Synthesis of anthracene derivative 34
A mixture of compound 43 (125 mg, 0.43 mmol), TsOH
(160 mg, 0.93 mmol), and MeOH (25 mL) in a sealed tube
was heated at 95ꢂ5 ꢀC for 12 days. The other parts of the re-
action were studied in the same manner as for epoxide 25.
CHCl3 (3ꢃ50 mL) was used in the extraction and chromato-
graphy of the residue on PLC with hexane/ether (7/3) given
as an anthracene derivative 34 (80 mg, 0.29 mmol, 67%).
4.7. Synthesis of diacetate 28
Diol 27 (600 mg, 2.50 mmol) was allowed to react at
room temperature for 3 days with pyridine (2 mL) and
acetic anhydride (Ac2O) (3 mL). The reaction mixture was
poured into dilute aqueous HCl (100 g) with ice and checked
with pH paper. It was extracted with CHCl3 (2ꢃ40 mL),
the extract was washed with NaHCO3 (5%, 100 mL) and
water (100 mL), and dried over CaCl2. The solvent was evap-
orated and diacetate 28 (486 mg, 1.50 mmol, 60%) was ob-
tained in a refrigerator from CHCl3/hexane as white crystals.
4.9.1. 1(R)S,12(S)R,13(S)R,14(R)S-Methylpentacyclo-
[10.3.2.02,11.04,9.013,15]heptadeca-2,4,6,8,10,16-hexaene-
1
14-carboxylate (34). Mp (amorf) 146–148 ꢀC; H NMR
(200 MHz, CDCl3) d 7.80–7.72 (AA0 of AA0BB0, aromatic,
2H), 7.61 (s, aromatic, 2H), 7.47–7.27 (BB0 of AA0BB0,
aromatic, 2H), 6.26 (m, olefinic, 2H), 4.20 (m, bridgehead,

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A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
2H), 3.67 (s, OMe, 3H), 1.98–1.92 (m, cyclopropane, 3H);
13C NMR (50 MHz, CDCl3) d 174.4 (CO), 144.9 (C), 134.0
(C), 133.5 (CH), 129.5 (CH), 127.4 (CH), 123.3 (CH), 53.5
(OMe), 42.7, 28.5, 27.5; IR (CHCl3) 3080, 3029, 3004,
2953, 1710, 1676, 1625, 1497, 1472, 1319, 1242, 1191,
1165, 1114, 1063, 936, 885, 757 cmꢁ1; Anal. Calcd for
C19H16O2: C 82.55, H 5.84; found: C 82.24, H 5.81.
(278 mg) was obtained (8:40¼1:9). They were not isolated
by chromatographic methods.
4.12.1. 1(R)S,12(S)R-Tetracyclo[10.2.2.02,11.04,9]hexa-
deca-2(10),3,5,8,13-pentaene (40). 1H NMR (200 MHz,
CDCl3) d 6.98 (s, aromatic, 2H), 6.57–6.53 (m, olefinic,
2H), 5.95 (s, olefinic, 2H), 3.94 (m, bridgehead, 2H), 3.41
(s, methylenic, 4H), 1.68–1.54 (m, methylenic, 4H); 13C
NMR (50 MHz, CDCl3) d 144.3 (C), 137.3 (CH), 132.4
(C), 127.0 (CH), 124.6 (CH), 41.0, 31.0, 28.1.
4.10. Catalytic hydrogenation of the compound 6
Into a 250 mL, two necked, round-bottomed flask fitted with
a spinbar were placed 60 mg of Pd/C (5%) catalyst and 6
(1.04 g, 5.00 mmol) in ethyl acetate (100 mL). One of the
necks was attached to a hydrogen manifold with a three-
way stopcock and the other neck was capped with a rubber
septum, degassed and flushed with hydrogen gas, while stir-
ring magnetically. After stirring for 9 h the solution was dec-
anted to separate it from the catalyst, and the solvent was
evaporated. Compound 37 was quantitatively obtained and
crystallized from hexane as white crystals.
4.13. Reduction of anthracene derivative 38
This reaction was also studied in the same manner as for
compound 8. A mixture of anthracene derivative 38
(600 mg, 2.88 mmol), BuOH (2 mL), dry ether (40 mL),
t
and excess metallic Na (6 equiv) was stirred for 1 week. A
mixture of 38 and 39 (430 mg) was obtained (38:39¼1:6).
They were also not isolated by chromatographic methods.
4.13.1. Tetracyclo[10.2.2.02,11.04,9]hexadeca-2(10),3,5,8-
tetraene (39). H NMR (200 MHz, CDCl3) d 6.98 (s, aro-
1
4.10.1. 2R(S),3R(S),10S(R),11S(R)-3,10-Epoxytetracyclo-
[10.2.2.02,11.04,9]hexadeca-4,6,8-triene (37). Mp 127–
matic, 2H), 5.98 (s, olefinic, 2H), 3.46 (br s, methylenic,
4H), 3.00 (m, bridgehead, 2H), 1.83 (bd, A of AB, J¼
8.2 Hz, methylenic, 4H), 1.47 (bd, B of AB, J¼8.2 Hz,
methylenic, 4H); 13C NMR (50 MHz, CDCl3) d 144.2 (C),
133.3 (C), 129.0 (CH), 125.5 (CH), 35.7, 28.6, 20.4.
1
129 ꢀC; H NMR (200 MHz, CDCl3) d 7.27–7.21 (AA0 of
AA0BB0, aromatic, 2H), 7.19–7.12 (BB0 of AA0BB0, aro-
matic, 2H), 5.17 (s, epoxide, 2H), 1.94–1.87 (m, 4H), 1.70
(m, 2H), 1.62–1.30 (m, 6H); 13C NMR (50 MHz, CDCl3)
d 149.0 (C), 128.1 (CH), 120.7 (CH), 84.3 (OCH), 44.7,
29.7, 28.7, 24.2; IR (CHCl3) 2914, 1458, 1351, 1247,
1208, 1023, 965, 919, 850, 758, 657 cmꢁ1; Anal. Calcd for
C16H18O: C 84.91, H 8.02; found: C 84.68, H 8.05.
4.14. Synthesis of compound 9
This compound was synthesized by two ways.
4.11. Synthesis of anthracene derivative 384a
(a) Catalytic hydrogenation of the compound 39: This re-
action was also studied in the same manner as for com-
pound 6. A mixture of compounds 38 and 39 (300 mg,
38:39¼1:6), Pd/C (25 mg, 5%) catalyst, and ethyl acetate
(30 mL) were used for this reaction. The residue was sub-
mitted to PLC with hexane and compound 9 (75 mg) was
obtained and crystallized from ethanol.
This reaction was also studied in the same manner as for
compound 6. Compound 37 (904 mg, 4.00 mmol), TsOH
(172 mg, 1.00 mmol), and MeOH (25 mL) were used for
this reaction. Compound 38 (600 mg, 72%) was obtained
and crystallized from ethanol.
(b) Catalytic hydrogenation of the compound 40: This re-
action was also studied in the same manner as for com-
pound 37. A mixture of compounds 8 and 40 (300 mg,
8:40¼1:9), Pd/C (25 mg, 5%) catalyst, and ethyl acetate
(40 mL) were used for this reaction. The residue was sub-
mitted to PLC with hexane and compound 9 (155 mg)
was obtained and crystallized from ethanol.
4.11.1. Tetracyclo[10.2.2.02,11.04,9]hexadeca-2,4,6,8,10-
pentaene (38). Mp 111–113 ꢀC (lit. 112–113 ꢀC4a); 1H
NMR (200 MHz, CDCl3) d 7.91–7.84 (AA0 of AA0BB0,
aromatic, 2H), 7.65 (s, aromatic, 2H), 7.52–7.45 (BB0 of
AA0BB0, aromatic, 2H), 3.17 (m, bridgehead, 2H), 1.97–
1.91 (m, methylenic, 4H), 1.59–1.54 (m, methylenic, 4H);
13C NMR (50 MHz, CDCl3) d 145.4 (C), 134.8 (C), 129.5
(CH), 127.7 (CH), 123.2 (CH), 36.2 (CH), 28.5 (CH2); Anal.
Calcd for C16H18: C 91.37, H 8.63; found: C 91.28, H 8.65.
4.14.1. Tetracyclo[10.2.2.02,11.04,9]hexadeca-2(11),3,9-
triene (9). Mp 88–90 ꢀC; 1H NMR (200 MHz, CDCl3)
d 6.91 (s, aromatic, 2H), 2.95 (m, bridgehead, 2H), 2.86–
2.80 (m, methylenic, 4H), 1.89–1.78 (m, methylenic, 8H),
1.46 (br d, B of AB, J¼8.0 Hz, methylenic, 4H); 13C NMR
(50 MHz, CDCl3) d 143.6 (C), 136.2 (C), 126.2 (CH), 35.7,
31.4, 28.6, 25.5; IR (CHCl3) 2929, 2864, 1466, 1143, 893,
630 cmꢁ1; m/z: 213.1/212.0 (8/49), 185.0/184.0/182.9 (8/
60/100), 169.0 (12), 156.0 (16), 142.0/140.9 (24/86), 128.0
(22), 114.9 (20), 18.41 (100); Anal. Calcd for C16H22:
C 89.65, H 10.35; found: C 89.60, H 10.37.
4.12. Reduction of anthracene derivative 8
t
Anthracene derivative 8 (340 mg, 1.65 mmol) and BuOH
(2 mL) were dissolved in dry ether (30 mL). Excess metallic
Na (1 g, 43.48 mmol), in small pieces, was added over
10 min. After stirring at room temperature for 4 days, un-
t
reacted Na and solid BuOK were removed by filtration
and washed with ether (40 mL). The solution was poured
into water (100 mL) and the mixture formed was shaken.
The organic layer was separated, and the water layer was ex-
tracted twice with ether (2ꢃ30 mL). The combined organic
layer was washed with water (20 mL), dried over CaCl2, and
then the solvent was evaporated. A mixture of 8 and 40
Acknowledgements
The authors are indebted to the Department of Chemis-
€
try (Ataturk University) for financial support, associate

A. Menzek, A. Altundaxs / Tetrahedron 62 (2006) 12318–12325
12325
o1234–o1236; (b) C¸ oruh, U.; Altundaxs, A.; Menzek, A.;
Garcia-Granda, S. Acta Crystallogr., E 2005, 61, o1869–o1871.
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J. Chem. Soc., Perkin Trans. 1 1993, 17, 1995–2000; (b)
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Professor Dr. Cavit Kazaz for technical assistant and associ-
ate Professor Dr. Thomas J. Cronin (SUNY Cobleskill,
NY) for proofread.
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