Synthesis of 1,4,5,16-tetrahydroxytetraphenylene

Article abstract of DOI:10.1016/j.tet.2004.02.022

This paper concerns the synthesis of 1,4,5,16-tetrahydroxytetraphenylene, which may function as a building block for the construction of molecular scaffolds. The synthesis of 1,4,5,16-tetrahydroxytetraphenylene was realized by stepwise Diels-Alder reactions to form two benzene rings using 1,10-dimethoxydibenzo[a,e]cyclooctene as a precursor. This key intermediate, in turn, could be obtained by photo-rearrangement of its corresponding barrelene.

Full text of DOI:10.1016/j.tet.2004.02.022

Tetrahedron 60 (2004) 3523–3531
Synthesis of 1,4,5,16-tetrahydroxytetraphenylene
a,b
Chi Wai Hui, Thomas C. W. Mak and Henry N. C. Wong
a
a,b,*
a
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
†
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The Chinese University of Hong Kong,
b
Shatin, New Territories, Hong Kong SAR, China
Received 20 December 2003; revised 30 January 2004; accepted 2 February 2004
Dedicated to Professor Cheng-Ye Yuan on the occasion of his 80th birthday
Abstract—This paper concerns the synthesis of 1,4,5,16-tetrahydroxytetraphenylene, which may function as a building block for the
construction of molecular scaffolds. The synthesis of 1,4,5,16-tetrahydroxytetraphenylene was realized by stepwise Diels–Alder reactions to
form two benzene rings using 1,10-dimethoxydibenzo[a,e]cyclooctene as a precursor. This key intermediate, in turn, could be obtained by
photo-rearrangement of its corresponding barrelene.
q 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
enols are placing in different positions which could be
interconnected with guest molecules via non-covalent
4
Tetraphenylene (tetrabenzo[a,c,e,g]cyclooctatetraene) (1) is
a structurally highly interesting molecule; it contains four
benzene rings, which are disposed alternately above and
below the main plane of the molecule, this molecule belongs
interaction, or with central metal linkages via covalent
5
interaction in diversified combination to form ordered
linear, two- and three-dimensional scaffolds.
1
to a D2d symmetry point group (Scheme 1).
In this paper, we would like to report the synthesis of
1
1
,4,5,16-tetrahydroxytetraphenylene (4), by employing
,10-dimethoxydibenzo[a,e]cyclooctene (9) as the key
intermediate.
2. Results and discussion
After the first synthesis of tetraphenylene (1) was reported in
6
1
943, considerable efforts has been devoted to the
7
Scheme 1.
improved synthesis of 1 and its derivatives. Because of
the structural characteristics of our target molecule, we
would like to utilize an eight-membered ring compound 9 as
a precursor. Two benzene rings will then be introduced into
Triggered by the aforementioned reasons, we have begun
a research program with the aim to construct three-
dimensional molecular scaffolds using tetraphenylenols as
building blocks. In our program, we would like to synthesize
five tetraphenylenols 2, 3, 4, 5 and 6 (Scheme 2), as
different modules which would subsequently serve to build
various molecular scaffolds.
8
the skeleton of 9 via stepwise Dieds–Alder reactions. The
retro-synthetic pathway is shown in Scheme 3. It is
noteworthy that in our synthetic route, four hydroxyl groups
could be introduced in a regiospecific manner.
2
3
As can be seen in Scheme 4, the hydroxyl groups in 1,10-
dihydroxyanthraquinone (11) were converted to methoxy
As can be seen, the hydroxyl groups of these tetraphenyl-
9
groups. The protected anthraquinone 12 was then reduced
smoothly to its corresponding anthracene 13 in the presence
Keywords: Diels–Alder reaction; Tetraphenylene; Strained acetylene;
Photo-rearrangement.
10
of zinc under an alkaline environment. With 1,8-
dimethoxyanthracene (13) in hand, a Diels–Alder
*
Corresponding author. Tel.: þ852-2609-6329; fax: þ852-2603-5057;
1
1
e-mail address: hncwong@cuhk.edu.hk
An Area of Excellence of the University Grants Committee (Hong Kong).
reaction between the anthracene 13 and dimethyl
acetylenedicarboxylate (DMAD) provided dimethyl
†
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.02.022

3524
C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
Scheme 2.
Scheme 3.
Scheme 4.

C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
3525
9
,10-dihydro-9,10-etheno-1,8-dimethoxyanthracene-11,12-
dimethoxydibenzo[a,e]cyclooctene (16). The two isomers
were used directly without separation and purification in the
next dehydrobromination step by using potassium tert-
1
2
dicarboxylate (14) in high yield. This adduct was allowed
to undergo a saponification step to provide the correspond-
ing diacid, whose reductive bisdecarboxylation yielded 1,8-
dimethoxybarrelene (10). In the proton NMR spectrum of
barrelene 10, two bridge-head protons show two sets of
doublet of doublets at d 5.17–5.19 and d 6.10–6.13,
respectively. Photoinduced isomerization of barrelene 10
1
6
butoxide as the base. The reactive strained alkynes, after
their generation, underwent Diels–Alder reaction with
furan to yield endoxide 8 and endoxide 17, respectively.
Moreover, another product was found to be 5-tert-butoxy-
1,10-dimethoxydibenzo[a,c]cyclooctene (18) which was
1
2
1
3
17
furnished dibenzo[a,e]cyclooctene 9 in an excellent yield.
A significant difference was found in the proton NMR
generated in only 10% yield. A notable singlet at d 1.20
was found in the proton NMR spectrum of compound 18
which was due to the absorption of the tert-butyl group. The
structure of the major endoxide 8 was confirmed by an X-
ray crystallographic study (Fig. 1). To obtain the triben-
zo[a,c,e]cyclooctene framework, 8 was deoxygenated by
spectra between barrelene 10 and dibenzo[a,e]cyclooctene
, which is a direct evidence for the success of photo
9
rearrangement. As mentioned above, for barrelene 10, two
bridge-head protons give two sets of doublet of doublets,
while the rearrangement product show two sets of singlets at
d 6.73 and 6.74 which could be attributed to the olefinic
protons in the central cyclooctene ring.
1
8
the low-valent-titanium reagent, yielding 1,12-dimethox-
ytribenzo[a,c,e]cyclooctene (19) (Scheme 5). The reson-
ances of the proton NMR spectrum are assigned as the
following. Thus, the singlet at d 3.80 corresponds to the
methoxy protons. The olefinic protons (H-13, H-14) absorb
as a singlet at d 6.73. Also, two sets of doublet of doublets
belonging to the benzenoid protons (H-2, H-4, H-9, H-11)
appear at d 6.74–6.81. The multiplet due to the absorption
of the two protons (H-6, H-7) overlaps with those of H-3 and
H-10 in the region of d 7.14–7.7.19. Finally, the doublet of
doublets at d 6.36–6.39 (J¼5.7 Hz, 3.6 Hz) can be
attributed to two protons (H-5, H-8) of the newly
constructed benzene ring. The HRMS (EI) of 19 shows a
molecular peak at m/z 314.1305 (Calcd for C H O :
After a sufficient amount of the key intermediate, namely
1
,10-dimethoxydibenzo[a,e]cyclooctene (9) was secured,
the next step was to construct the pivotal tribenzo[a,c,e]-
cyclooctene skeleton. The synthesis of tribenzo[a,c,e]cy-
clooctene framework was not expected to be trivial, as can
1
4
be revealed by a literature survey.
1
5
First, bromination of dibenzo[a,e]cyclooctene 9 with one
molar equivalent of bromine at 0 8C in CCl gave a mixture
of 5,6-dibromo-5,6-dihydro-1,10-dimethoxydibenzo[a,e]-
cyclooctene (15) and 11,12-dibromo-11,12-dihydro-1,10-
4
22 18 2
314.1307). Furthermore, the elemental analysis result is
Figure 1. Molecular structure and atom labeling of 8. H atoms have been omitted for clarity. Ellipsoids are drawn at the 30% probability level.

3526
C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
Scheme 5.
Scheme 6.

C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
3527
Figure 2. The proton NMR spectrum of 24 with characterization in aromatic region.
consistent with the structure of 19 (Anal. Calcd for
C H O : C, 84.05; H, 5.77. Found: C, 84.28; H, 5.82).
stable compound with a sharp melting point (mp 204 8C).
However, tetrahydroxytetraphenylene 4 is relatively
unstable when it was exposed to air and light without
protection.
2
2 18 2
With 19 in hand, the introduction of the remaining
dihydroxybenzene ring towards the realization of our target
was then preformed.
The splitting patterns shown in the proton NMR spectra of
these three tetraphenylene derivatives, namely 4, 23 and 24
are quite similar at the downfield region (d 6.7–7.4).
However, we can still easily identify them by the number of
methoxy signals at about d 3.7 in their spectra. In Figure 2,
the downfield region in the proton NMR spectrum of
tetramethoxytetraphenylene 24 with full characterization is
shown.
As can be seen in Scheme 6, bromine was used again to
brominate the double bond of 19. However, the solubility of
dibromide 20 is generally low in common solvents and it
was difficult to purify 20 by column chromatography. As a
result, the crude product was directly used in the
dehydrobromination step and the freshly generated strained
alkyne was trapped by furan concomitantly to give endoxide
1
6,17
7
acid catalyzed ring opening reaction was performed to lead
in 42% yield in two steps.
With endoxide 7 in hand,
In summary, the synthesis of 1,4,5,16-tetrahydroxytetra-
phenylene (4), through 1,4-endoxo-1,4-dihydro-8,11-
dimethoxytribenzo[a,c,e]cyclooctene (8) as the inter-
mediate, was accomplished in 15 steps and the total yield
was found to be 3%.
1
9
to phenol 21 smoothly. Since the structure of phenol 21 is
unsymmetrical, its proton NMR signals are quite compli-
cated. The chemical shifts of two methoxy groups are found
at d 3.68 and 3.74, respectively. The phenolic proton
resonates at d 4.88. The benzenoid protons absorb at d
6
.74–6.86 (multiplet, 6H), and 7.12–7.26 (multiplet, 7H).
The molecular peak found in its HRMS (FAB) spectrum is
80.1418 (Calcd for C H O : 380.1412).
3. Experimental
3.1. General
3
2
6 20 3
To oxidize phenol to quinone, the typical reagent, Fremy’s
2
All reagents and solvents were reagent grade. Further
23
0
salt was employed. Through a radical mechanism, phenol
1 was successfully oxidized to quinone 22 by Fremy’s salt.
purification and drying by standard method
were
2
employed when necessary. All evaporations of organic
solvents were carried out with a rotary evaporator in
conjunction with a water aspirator. The plates used for thin-
layer chromatography (TLC) were E. Merck silica gel
60F254 (0.25 mm thickness) precoated on aluminum plates,
and they were visualized under both long (365 nm) and
short (254 nm) UV light. Compounds on TLC plates were
visualized with a spray of 5% dodecamolybdophosphoric
acid in ethanol and with subsequent heating. Column
chromatography was performed using E. Merck silica gel
(230–400 mesh).
Due to the low solubility and the almost identical polarities
of phenol 21 and quinone 22, it was difficult to separate 21
and 22 by column chromatography. Since phenol 21 would
not affect the reduction reaction from quinone 22 to
hydroquinone 23, we directly reduced the crude products
with zinc powder to form hydroquinone 23 under an acidic
2
1
condition. The reacted yield was found to be 82% in two
steps. Finally, the remaining two methoxy groups were
deprotected by BBr to give our target molecule, 1,4,5,16-
3
2
2
tetrahydroxytetraphenylene (4) in high yield. Further-
more, the free hydroxyl groups on 23 could also be
protected by dimethyl sulfate to give tetramethoxytetra-
phenylene 24 (Scheme 6).
Melting points were measured on a Reichert Microscope
apparatus and were uncorrected. NMR spectra were
recorded on a Bruker DPX-300 spectrometer (300.13 MHz
1
13
As expected, tetramethoxytetraphenylene 24 is a highly
for H and 75.47 MHz for C). All NMR measurements

3528
C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
1
were carried out at room temperature in deuterated chloro-
form solution unless otherwise stated. Chemical shifts are
reported as parts per million (ppm) in d units on the scale
downfield from tetramethylsilane (TMS) or relative to the
265 8C; H NMR (CDCl ) d 3.77 (s, 3H), 3.80 (s, 3H), 3.85
3
(s, 6H), 5.49 (s, 1H), 6.36 (s, 1H), 6.61 (dd, J¼8.1, 0.6 Hz,
2H), 6.96 (dd, J¼7.8, 7.8 Hz, 2H), 7.03 (d, J¼6.9 Hz, 2H);
1
3
C NMR (CDCl ) d 39.6, 52.3, 52.3, 52.5, 55.9, 109.0,
3
1
resonance of chloroform solvent (7.26 ppm in the H,
3
116.6, 126.2, 131.4, 146.7, 147.0, 148.5, 154.7, 165.8,
166.3. Anal. Calcd for C H O : C, 69.46; H, 5.30. Found:
C, 69.18; H, 5.42.
1
7
respectively). Coupling constants (J) are reported in hertz
7.0 ppm for the central line of the triplet in the C modes,
2
2 20 6
(
(
Hz). Splitting pattern are described as ‘s’ (singlet); ‘d’
1
doublet); ‘t’ (triplet); ‘q’ (quartet); ‘m’ (multiplet). H
27
3.1.4. 1,8-Dimethoxybarrelene (10). To a stirred solution
of NaOH (15.0 g, 380 mmol) in 40% aqueous methanol
(300 mL) was added dimethyl 9,10-dihydro-9,10-etheno-
1,8-dimethoxyanthracene-11,12-dicarboxylate (14) (10.0 g,
26.3 mmol). The mixture was allowed to reflux for 4 h, and
was then cooled to room temperature. The reaction mixture
was acidified with 36% HCl to pH 2, filtered with suction
filtration and dried under vacuum without further purifi-
cation to give 9,10-dihydro-9,10-etheno-1,8-dimethoxy-
anthracene-11,12-dicarboxylic acid.
NMR data are reported in this order: chemical shifts;
multiplicity; coupling constant(s), number(s) of proton.
Mass spectra (MS and HRMS) were obtained with a
Thermofinnigan MAT95XL spectrometer, and recorded at
an ionization energy of 70 eV unless otherwise stated. In all
case, signals are reported as m/z. Elemental analyses were
performed at Shanghai Institute of Organic Chemistry, The
Chinese Academy of Sciences and MEDAC LTD at Brunel
Science Centre, UK.
2
4
3
.1.1. 1,8-Dimethoxyanthraquinone (12). To a vigor-
ously stirred solution of 1,8-dihydroxyanthraquinone (11)
To a vigorously stirred solution of 9,10-dihydro-9,10-
etheno-1,8-dimethoxyanthracene-11,12-dicarboxylic acid
(vide supra) (10.0 g, 29.8 mmol) in quinoline (250 mL)
was added copper powder (9.4 g, 142.0 mmol). The reaction
(
(
20.0 g, 83 mmol) in acetone (500 mL) was added K CO3
2
15 g). Then the mixture was heated to reflux and dimethyl
sulfate (23 mL, 250 mmol) was added through a dropping
funnel in 1 h. The mixture was refluxed for a further 12 h.
After cooling to room temperature, the residue was filtered
off and washed with acetone (2£20 mL). The combined
organic solvent was evaporated under reduced pressure. The
residue was chromatographed on silica gel (500 g, hexanes/
EtOAc 3:1) to afford 1,8-dimethoxyanthraquinone (12)
mixture was refluxed for 3 h under N . After cooling to
2
room temperature, CH Cl (250 mL) was added to the
2
2
mixture and the residue was then filtered. The filtrate was
washed with 1 N HCl (4£200 mL) and dried over MgSO .
4
After evaporation of the solvent, the residue was chromato-
graphed on a silica gel column (600 g, hexanes/EtOAc 10:1)
to afford 1,8-dimethoxybarrelene (10) (4.1 g, 52%) as
2
5
27
1
(
2
21.1 g, 92%) as a yellow solid: mp 223–224 8C (lit. 223–
1
colorless crystals: mp 210–211 8C (lit. 211–212 8C); H
NMR (CDCl ) d 3.87 (s, 6H), 5.18 (dd, J¼5.4, 1.5 Hz, 1H),
13
35 8C); H NMR (CDCl ) d 4.00 (s, 6H), 7.30 (dd,
3
3
J¼8.4 Hz, 0.6 Hz, 2H), 7.63 (dd, J¼8.0, 8.0 Hz, 2H), 7.82
6.12 (dd, J¼5.4, 1.8 Hz, 1H), 6.60 (dd, J¼7.8, 0.9 Hz, 2H),
1
3
(
1
dd, J¼7.8, 1.2 Hz, 2H); C NMR (CDCl ) d 56.5, 118.0,
6.91–7.06 (m, 6H); C NMR (CDCl ) d 37.4, 51.6, 55.8,
3
3
18.9, 124.0, 133.9, 134.7, 159.4, 182.9, 184.0.
108.2, 116.1, 125.1, 133.8, 139.7, 140.3, 149.1, 154.0. Anal.
Calcd for C H O : C, 81.79; H, 6.10. Found: C, 81.84; H,
6.17.
1
8 16 2
2
6
3
.1.2. 1,8-Dimethoxyanthracene (13). To a 10% NaOH
solution (300 mL) of 1,8-dimethoxyanthraquinone (12)
20.0 g, 74.6 mmol) was added zinc powder (25.0 g,
82 mmol). The mixture was stirred and heated for 24 h,
(
3
3.1.5. 1,10-Dimethoxydibenzo[a,e]cyclooctene (9). A sol-
ution of 1,8-dimethoxybarrelene (10) (1.0 g, 3.79 mmol) in
degassed anhydrous THF (500 mL) was irradiated with a
mercury lamp (125 W medium pressure) at room tempera-
ture for 3 h under a nitrogen atmosphere. After evaporation
of the solvent, chromatography on silica gel (100 g,
hexanes/EtOAc 7:1) afforded 1,10-dimethoxydibenzo[a,e]-
and then the reaction mixture was filtered and the filtered
cake was washed with CH Cl (5£300 mL). The organic
2
2
extracts were combined and evaporated. The residue was
chromatographed on silica gel (1000 g, hexanes/EtOAc 9:1)
to give 1,8-dimethoxyanthracene (13) (14.2 g, 80%) as
2
6
1
yellow needles: mp 198–199 8C (lit. 199–200 8C); H
NMR (CDCl ) d 4.09 (s, 6H), 6.74 (d, J¼7.5 Hz, 2H), 7.40
cyclooctene (9) (0.95 g, 95%) as colorless crystals: mp
1
207–208 8C; H NMR (CDCl ) d 3.78 (s, 6H), 6.65–6.70
3
3
(
1
1
dd, J¼8.1, 8.1 Hz, 2H), 7.59 (d, J¼8.7 Hz, 2H), 8.34 (s,
(m, 4H), 6.73 (s, 2H), 6.74 (s, 2H) 7.14 (dd, J¼8.0, 8.0 Hz,
1
3
13
H), 9.28 (s, 1H); C NMR (CDCl ) d 55.4, 101.5, 115.7,
3
2H); C NMR (CDCl ) d 55.5, 108.5, 121.1, 126.5, 127.8,
3
20.2, 124.4, 125.1, 125.6, 132.9, 155.9.
129.2, 133.0, 138.5, 157.3. Anal. Calcd for C H O : C,
1
8 16 2
81.79; H, 6.10. Found: C, 81.93; H, 6.16.
3.1.3. Dimethyl 9,10-dihydro-9,10-etheno-1,8-dimethoxy-
anthracene-11,12-dicarboxylate (14).
1
dimethyl acetylenedicarboxylate (8.9 g, 63.0 mmol) in
toluene (25 mL) was refluxed with stirring for 12 h. The
reaction mixture was cooled with an ice water bath and
filtered by suction. The filtered cake was washed with ice
cooled absolute ethanol (3£5 mL), and dried at room
temperature to give the crude product (13.9 g, 87%).
Recrystallization from absolute ethanol afforded dimethyl
A
mixture of
,8-dimethoxyanthracene (13) (10.0 g, 42.0 mmol) and
3.1.6. 5,6-Dibromo-5,6-dihydro-1,10-dimethoxydi-
benzo[a,e]cyclooctene (15); 11,12-dibromo-11,12-di-
hydro-1,10-dimethoxydibenzo[a,e]cyclooctene (16). To a
suspension of 1,10-dimethoxydibenzo[a,e]cyclooctene (9)
(0.60 g, 2.3 mmol) in anhydrous CCl (50 mL) was added
4
slowly a solution of bromine (0.36 g, 2.3 mmol) in
anhydrous CCl (10 mL) through a dropping funnel within
4
2 h at 0 8C under N . After addition, the temperature was
2
slowly allow to rise to room temperature and the mixture
was stirred for an additional 30 min. The reaction was
quenched by addition of 10% Na S O (3 mL). The mixture
9,10-dihydro-9,10-etheno-1,8-dimethoxyanthracene-11,12-
dicarboxylate (14) (12.8 g, 80%) as a white solid: mp 263–
2
2 5

C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
3529
was extracted with CH Cl (2£10 mL), and the combined
dropwise to the low-valent-titanium solution. The reaction
mixture was then stirred at refluxing temperature for 20 h.
Sat. K CO (5 mL) was added, and was followed by
2
2
organic extract was dried over MgSO and evaporated under
4
reduced pressure to give a mixture of 5,6-dibromo-5,6-
dihydro-1,10-dimethoxydibenzo[a,e]cyclooctene (15) and
11,12-dibromo-11,12-dihydro-1,10-dimethoxydibenzo[a,e]-
cyclooctene (16) as a white solid. These compounds were not
purified further and were used immediately in the next step.
2
3
extraction with CH Cl (3£20 mL). The combined organic
2
2
layer was dried over anhydrous MgSO and evaporated.
4
Chromatography on a column of silica gel (25 g, hexanes/
EtOAc 10:1) gave 1,12-dimethoxytribenzo[a,c,e]cyclo-
octene (19) (0.43 g 90%) as colorless crystals: mp 212–
1
3
.1.7. 1,4-Endoxo-1,4-dihydro-8,11-dimethoxytri-
benzo[a,c,e]cyclooctene (8); 1,4-endoxo-1,4-dihydro-
,14-dimethoxytribenzo[a,c,e]cyclooctene (17); 5-tert-
213 8C; H NMR (CDCl ) d 3.80 (s, 6H), 6.73 (s, 2H), 6.76
3
(dd, J¼8.4, 0.9 Hz, 2H), 6.79 (dd, J¼7.5, 0.9 Hz, 2H),
1
3
5
7.14–7.19 (m, 4H), 7.38 (dd, J¼5.7, 3.6 Hz, 2H); C NMR
butoxy-1,10-dimethoxydibenzo[a,c]cyclooctene (18). To
a solution of freshly sublimed KO-t-Bu (0.76 g 6.8 mmol) in
anhydrous THF (40 mL) and furan (20 mL) under N was
(CDCl ) d 55.7, 109.0, 122.1, 126.6, 127.1, 127.9, 128.9,
3
þ
Calcd for C H O : 314.1307. Found: 314.1305. Anal.
129.7, 141.9, 143.0, 156.3; MS m/z 314 (M ). HRMS (EI)
2
22 18 2
added slowly a solution of previously prepared dibromides
1
(
was stirred for 1 min, brine (15 mL) was added. The organic
Calcd for C H O : C, 84.05; H, 5.77. Found: C, 84.28; H,
22 18 2
5.82.
5 and 16 (1.0 g, 2.3 mmol) (vide supra) in anhydrous THF
40 mL) and furan (20 mL) within 3 min. After the solution
3.1.9. 13,14-Dibromo-13,14-dihydro-1,12-dimethoxy-
tribenzo[a,c,e]cyclooctene (20). To a suspension of 1,12-
layer was separated and dried over MgSO , and the filtrate
4
was then stirred for further 48 h under N . The solvent was
2
evaporated under reduced pressure and the residue was
separated by flash column chromatography on silica gel
dimethoxytribenzo[a,c,e]cyclooctene
(19)
(0.25 g,
0.81 mmol) in anhydrous CCl (47 mL) was added bromine
4
(0.26 g 3.2 mmol). The mixture was stirred and refluxed for
6 h, and then cooled to room temperature. The reaction was
quenched by addition of 10% Na S O (3 mL), and
(
8
3
30 g, hexanes/EtOAc 3:1) to give 1,4-endoxo-1,4-dihydro-
,11-dimethoxytribenzo[a,c,e]cyclooctene (8) (260 mg,
5%), 1,4-endoxo-1,4-dihydro-5,14-dimethoxytribenzo[a,-
2
2 5
extracted with CH Cl (2£10 mL). The combined organic
2
2
c,e]cyclooctene (17) (70 mg, 9%) and 5-tert-butoxy-1,10-
dimethoxydibenzoc[a,c]cyclooctene (18) (80 mg, 10%).
extract was dried over MgSO and evaporated under
4
reduced pressure to give 13,14-dibromo-13,14-dihydro-
1,12-dimethoxytribenzo[a,c,e]cyclooctene (20) as a white
solid. This compound was not purified further and was used
immediately in the next step.
1
Data of 8: mp 150–151 8C; H NMR (CDCl ) d 3.80 (s,
3
6
H), 5.44–5.45 (m, 2H), 6.36 (dd, J¼7.8, 0.9 Hz, 2H), 6.62
(
s, 2H), 6.71 (dd, J¼7.8, 8.1 Hz, 2H), 7.17 (dd, J¼8.0,
1
3
8
1
1
3
.0 Hz, 2H), 7.40 (s, 2H); C NMR (CDCl ) d 55.6, 87.9,
3
3.1.10. 1,4-Endoxo-1,4-dihydro-5,16-dimethoxytetra-
benzo[a,c,e,g]cyclooctene (7). To a solution of freshly
sublimed KO-t-Bu (0.48 g 4.3 mmol) in anhydrous THF
09.2, 114.8, 126.4, 128.3, 129.9, 136.4, 142.5, 151.5,
57.8. MS m/z 330 (M ). HRMS (EI) Calcd for C H O :
þ
30.1256. Found: 330.1250. Crystallization from 20%
2
2 18 3
(15 mL) and furan (15 mL) under N was added dropwise a
2
EtOAc in CH Cl at room temperature gave colorless
2
crystals, which were sufficiently good for an X-ray crystal-
lographic analysis.
solution of the previously prepared dibromides 20 (vide
supra) in anhydrous THF (25 mL) and furan (12 mL) within
60 min. After the solution was stirred for 3 h, 0.5 N HCl
2
(
10 mL) was added. The mixture was extracted with CH Cl
2 2
1
Data of 17: mp 145–146 8C; H NMR (CDCl ) d 3.75 (s,
3
(3£20 mL). The combined organic extract was washed with
6
0
7
1
1
3
H), 5.40–5.41 (m, 2H), 6.41 (s, 2H), 6.65 (dd, J¼8.1,
brine (10 mL), dried over MgSO , and evaporated under
4
.6 Hz, 2H), 6.70 (dd, J¼7.8, 0.9 Hz, 2H), 7.14 (dd, J¼7.4,
reduced pressure. The residue was chromatographed on a
column of silica gel (30 g, hexanes/EtOAc 3:1) to give 1,4-
endoxo-1,4-dihydro-5,16-dimethoxytetrabenzo[a,c,e,g]cyclo-
octene (7) (0.13 g, 42%) as colorless crystals: mp 251–253 8C;
1
1
3
.4 Hz, 2H), 7.16 (s, 2H); C NMR (CDCl ) d 55.2, 87.4,
3
08.9, 122.0, 124.2, 128.2, 133.4, 138.6, 142.5, 152.4,
58.0. MS m/z 330 (M ). HRMS (EI) Calcd for C H O :
þ
30.1256. Found: 330.1247.
2
2 18 3
H NMR (CDCl ) d 3.87 (s, 6H), 5.65 (d, J¼0.9 Hz, 2H), 6.59
3
(
d, J¼0.9 Hz, 2H), 6.79–6.84 (m, 4H), 6.97 (dd, J¼5.7,
1
13
Data of 18: mp 198–199 8C; H NMR (CDCl ) d 1.20 (s,
3
3.3 Hz, 2H), 7.20–2.26 (m, 4H); C NMR (CDCl ) d 55.7,
3
9
H), 3.77 (s, 6H), 6.37 (s, 1H), 6.61–6.86 (m, 5H), 6.99 (d,
1
85.5, 109.3, 122.1, 123.1, 126.6, 128.8, 130.7, 140.8, 143.3,
144.0, 151.6, 157.2; MS m/z 381 (M þ1), 380 (M ).
3
þ
þ
HRMS (FAB) Calcd for C H O : 381.1491. Found:
J¼7.8 Hz, 1H), 7.07–7.16 (m, 2H); C NMR (CDCl ) d
3
2
1
1
9.2, 55.5, 78.4, 108.1, 109.3, 120.2, 121.8, 126.1, 126.6,
27.6, 127.8, 128.9, 130.3, 137.6, 140.0, 151.8, 156.7,
57.3. MS m/z 279 (M 2C H ). HRMS (EI) Calcd for
4
26 21 3
381.1483.
þ
9
C H O : 279.1021. Found: 279.1019.
2 24 3
3.1.11. 1-Hydroxy-5,16-dimethoxytetrabenzo[a,c,e,g]-
cyclooctene (21). A mixture of 1,4-endoxo-1,4-dihydro-
5,16-dimethoxytetrabenzo[a,c,e,g]cyclooctene (7) (0.10 g,
0.26 mmol) and 36% HCl (0.5 mL) in MeOH (30 mL) was
refluxed with stirring for 4 h. After cooling to room
temperature, the reaction was quenched by addition of
brine (15 mL), and extracted with CH Cl (3£20 mL). The
2
3
.1.8. 1,12-Dimethoxytribenzo[a,c,e]cyclooctene (19).
Anhydrous THF (6 mL) was added to titanium(IV) chloride
1.0 mL, 9.1 mmol) dropwise under N with stirring at 0 8C.
(
2
Zinc powder (0.80 g, 12 mmol) was added, and was
followed by triethylamine (0.30 mL, 2.2 mmol). After
refluxing for 30 min, a suspension of 1,4-endoxo-1,4-
2
2
combined organic extract was dried over MgSO and
4
dihydro-8,11-dimethoxytribenzo[a,c,e]cyclooctene (8)
(0.50 g, 1.5 mmol) in anhydrous THF (30 mL) was added
evaporated under reduced pressure. The residue was
separated by flash column chromatography on silica gel

3530
C. W. Hui et al. / Tetrahedron 60 (2004) 3523–3531
1
3
6
(10 g, hexanes/EtOAc 3:1) to give 1-hydroxy-5,16-
dimethoxytetrabenzo[a,c,e,g]cyclooctene (21) (90 mg
7.22–7.25 (m, 2H); C NMR (d -Acetone) d 144.5, 121.6,
126.7, 127.2, 128.5, 128.6, 128.6, 130.5, 136.8, 141.0,
1
þ
C H O : 368.1049. Found 368.1038.
9
0%) as a white solid: mp 284–285 8C; H NMR (CDCl )
3
143.1, 151.6; MS m/z 368 (M ). HRMS (FAB) Calcd for
d 3.68 (s, 3H), 3.74 (s, 3H), 4.88 (s, 1H), 6.74 (dd, J¼2.7,
2
4 16 4
1
1
.2 Hz, 1H), 6.77 (dd, J¼2.7, 0.9 Hz, 1H), 6.80 (dd, J¼8.1,
.2 Hz, 1H), 6.84 (s, 1H), 6.86 (d, J¼0.9 Hz, 1H), 6.90 (dd,
3.1.15. 1,4,5,16-Tetramethoxytetraphenylene (24). To a
vigorously stirred solution of 1,4-dihydroxy-5,16-
dimethoxytetrabenzo[a,c,e,g]cyclooctene (23) (10 mg
0.025 mmol) in acetone (4 mL) was added K CO
(14 mg). Then the mixture was heated to reflux and
dimethyl sulfate (0.01 mL, 0.1 mmol) was added. The
mixture was refluxed for a further 4 h and NaOH (0.05 g)
was added. After cooling to room temperature, the residue
was filtered off and washed with acetone (2 mL). The
combined organic solvent was washed with brine (3 mL),
J¼8.4, 0.9 Hz, 1H), 7.10–7.17 (m, 3H), 7.19–7.29 (m, 4H);
1
3
C NMR (CDCl ) d 56.2, 56.5, 110.9, 114.2, 121.5, 122.6,
3
1
1
1
22.8, 123.8, 124.0, 127.1, 127.3, 127.8, 127.9, 128.0,
28.0, 128.3, 129.1, 130.2, 138.5, 140.8, 141.2, 143.1,
2
3
þ
þ
45.0, 152.5, 155.9, 156.1. MS m/e 381 (M þ1), 380 (M ).
HRMS (FAB) Calcd for C H O : 380.1412. Found:
2
6 20 3
3
80.1418.
3
.1.12. 1,4-Dioxo-1,4-dihydro-5,16-dimethoxytetra-
benzo[a,c,e,g]cyclooctene (22). To a vigorously stirred
solution of 1-hydroxy-5,16-dimethoxytetrabenzo[a,c,e,g]-
cyclooctene (21) (50 mg 0.13 mmol) in acetone (6 mL) was
added a buffer solution (Na HPO , NaH PO , pH¼5.8,
dried over MgSO and evaporated under reduced pressure.
4
The residue was purified by flash column chromatography
on silica gel (6 g, hexanes/EtOAc, 3:1) to give 1,4,5,16-
tetramethoxytetraphenylene (24) (9.6 mg, 90%) as a white
2
4
2
4
1
6
mL) of Fremy’s salt (174 mg, 0.65 mmol). The resulting
solid: mp 204 8C; H NMR (CD Cl ) d 3.63 (s, 6H), 3.72 (s,
2
2
mixture was vigorously stirred for 6 h. The mixture was
extracted with CH Cl (3£10 mL). The combined organic
6H), 6.73 (dd, J¼7.5, 0.9 Hz, 2H), 6.77 (s, 2H), 6.86 (dd,
J¼8.1, 0.9 Hz, 2H), 7.16 (dd, J¼5.7, 3.3 Hz, 2H), 7.20–
2
2
1
3
extract was dried over MgSO and evaporated under
4
7.28 (m, 4H); C NMR (CD Cl ) d 56.7, 56.8, 110.7, 111.0,
2 2
reduced pressure to give 1,4-dioxo-5,16-dimethoxytetra-
benzo[a,c,e,g]cyclooctene (22), which was used in the next
step without further purification and characterization.
122.0, 126.9, 127.7, 128.6, 128.7, 128.9, 141.9, 143.6,
151.6, 157.4; MS m/e 424 (M ). HRMS (EI) Calcd for
þ
C H O : 424.1675. Found: 424.1661.
2
8 24 4
3
.1.13.1,4-Dihydroxy-5,16-dimethoxytetrabenzo[a,c,e,g]-
cyclooctene (23). A mixture of 1,4-dioxo-1,4-dihydro-5,16-
dimethoxytetrabenzo[a,c,e,g]cyclooctene (22) (vide supra)
and zinc powder (60 mg, 0.92 mmol) in acetic acid: water
Acknowledgements
The work described in this project is supported by a grant
from the Research Grants Council of the Hong Kong Special
Administrative Region, China (Project CUHK 4264/00P),
as well as partially by the Area of Excellence Scheme
established under the University Grants Committee of the
Hong Kong Special Administrative Region, China (Project
No. AoE/P-10/010).
(
2:1) solution (8 mL) was refluxed with stirring for 1 h. The
mixture was extracted with CH Cl (3£15 mL). The
2
2
combined organic extract was dried over MgSO and
4
evaporated under reduced pressure. The residue was
purified by flash column chromatography on silica gel
(
dimethoxytetrabenzo[a,c,e,g]cyclooctene (23) [17 mg,
8 g, hexanes/EtOAc 1:1) to give 1,4-dihydroxy-5,16-
1
8
NMR (CD Cl ) d 3.77 (s, 6H), 4.56 (s, 2H), 6.70 (s, 2H),
2% (reacted yield)] as a white solid: mp 241–242 8C; H
2
2
6
7
.83 (dd, J¼7.5, 0.9 Hz, 2H) 6.79 (dd, J¼7.5, 0.9 Hz, 2H),
References and notes
1
3
.17 (dd, J¼5.7, 2.4 Hz, 2H) 7.28–7.33 (m, 4H); C NMR
(
1
CD Cl ) d 56.9, 111.3, 116.2, 123.1, 125.5, 128.0, 128.6,
2
29.4, 129.8, 141.3, 145.0, 147.1, 156.5. MS m/e 396 (M ).
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6
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