Synthesis of Tribenzotropone by Ring Expansion of Phenanthrene-9,10-dione

Article abstract of DOI:10.1055/s-0034-1381045

Tribenzotropone was efficiently synthesized by a ring-expansion method from readily available phenanthrene-9,10-dione via a ring-opened diketone as a key intermediate; the diketone was prepared by nucleophilic addition of allyl and vinyl groups, followed by an oxidative ring-opening reaction with lead(IV) acetate. Ring closure by an intramolecular Diels-Alder reaction and subsequent dehydrogenation produced tribenzotropone in 38% overall yield. Ring closure by a Morita-Baylis-Hillman reaction, on the other hand, produced a dibenzo-fused nonanedione in 22% overall yield.

Full text of DOI:10.1055/s-0034-1381045

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, 2957–2960
2957
special topic
J. Choi et al.
Special Topic
Synthesis
Synthesis of Tribenzotropone by Ring Expansion of Phenan-
threne-9,10-dione
Jeongae Choia
Hyunuk Junga
Jeong-Eun Yeob
Sangho Koo*a,b
O
O
O
ring
closure
ring
opening
O
O
a Department of Energy and Biotechnology, Myong Ji University,
Myongji-Ro 116, Cheoin-Gu, Yongin, Gyeonggi-Do, 449-728,
Republic of Korea
b Department of Chemistry, Myong Ji University, Myongji-Ro 116,
Cheoin-Gu, Yongin, Gyeonggi-Do, 449-728, Republic of Korea
sangkoo@mju.ac.kr
Received: 15.04.2015
Accepted after revision: 05.06.2015
Published online: 07.08.2015
O
O
DOI: 10.1055/s-0034-1381045; Art ID: ss-2015-c0244-st
Abstract Tribenzotropone was efficiently synthesized by a ring-expan-
sion method from readily available phenanthrene-9,10-dione via a ring-
opened diketone as a key intermediate; the diketone was prepared by
nucleophilic addition of allyl and vinyl groups, followed by an oxidative
ring-opening reaction with lead(IV) acetate. Ring closure by an intra-
molecular Diels–Alder reaction and subsequent dehydrogenation pro-
duced tribenzotropone in 38% overall yield. Ring closure by a Morita–
Baylis–Hillman reaction, on the other hand, produced a dibenzo-fused
nonanedione in 22% overall yield.
H
H
H
H
1
less contribution
O
HO
OH
Key words annulations, cycloadditions, Diels–Alder reactions, fused-
ring systems, ring expansion
OH
3
2
Tropone is an unusual carbonyl compound with a rela-
tively high dipole moment of 4.17 D (c.f. acetone, 2.91 D), in
which a dipolar resonance structure contributes to the non-
benzenoid aromatic character of the molecule.1 Tropone
has been extensively studied as a material for liquid crystals
because of its polarity and planarity.2–4 Tribenzotropone (1;
9H-tribenzo[a,c,e][7]annulen-9-one) on the other hand, is
peculiar in that all the alkene moieties in the seven-mem-
bered ring are incorporated into fused benzene rings (Fig-
ure 1). Structurally, the molecule deviates from planarity to
reduce its angular strain as well as the unfavorable steric
interactions between the ortho-hydrogen atoms;5,6 conse-
quently, the carbonyl group participates in various reac-
tions, including reduction and nucleophilic addition.7,8
There have been reports on modifications of the carbonyl
group of tribenzotropone to give materials for use as ther-
mochromic dyes8 or as photo- or thermoresponsive molec-
ular switches.9,10
Figure 1 Disconnection approach to tribenzotropone (1) by means of
an intramolecular Diels–Alder reaction
lenging due to the presence of three fused benzene rings.
Even though the oxidation of tribenzocycloheptatriene and
the rearrangement of the diazonium salt of 9-(2-aminophe-
nyl)-9H-fluoren-9-ol have been reported to produce 1, the
preparations of the necessary substrates required multistep
sequences with difficulties or poor yields.5,6 On the other
hand, the Diels–Alder reaction of furan with an alkyne de-
rived from dibenzosuberone is an excellent approach to the
synthesis of tribenzotropone (1), giving a 31% overall yield
in five steps.12 We surmised that the ring-expansion of a
benzo-fused cyclohexanone might constitute another effi-
cient synthetic path to benzotropone. In a continuation of
our ring-expansion study, we were able to demonstrate an
easy and practical synthesis of tribenzotropone (1) from
readily available phenanthrene-9,10-dione (4).13,14 We
herein disclose the details of our ring-expansion study.
Tropones have been synthesized either by oxidation of
cycloheptanones or by ring-expansion of benzene deriva-
tives.1,11 The synthesis of tribenzotropone (1) is more chal-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2957–2960

2958
J. Choi et al.
Special Topic
Synthesis
As delineated in the disconnection strategy shown in
Figure 1, we planned to use the intramolecular Diels–Alder
reaction of ketone 2 as the key step to install the benzo-
fused tropone skeleton;15 ketone 2, in turn, might be ob-
tained by the oxidative ring-opening reaction of diol 3.13,14
Readily available phenanthrene-9,10-dione (4) was used as
the starting material, in which the cyclohexanedione core
underwent ring-expansion after incorporation of two alke-
nyl tethers (Scheme 1). A mild and selective indium-medi-
ated addition of an allyl group to dione 4 produced hydroxy
ketone 5 in 89% yield.16 The addition of vinylmagnesium
bromide (3 equiv) provided dihydrophenanthrene-9,10-
diol 3, with vinyl and allyl substituents, in 83% yield. Only
one diastereomer was obtained, according to thin-layer
chromatography and 13C NMR spectrometric analysis. We
expected the anti-diol to be formed as a result of chelation
control of the neighboring hydroxy group in the Grignard
addition, but it was not necessary to assign the stereochem-
istry of the product. Oxidation of diol 3 by lead(IV) acetate
proceeded efficiently to give the ring-opened diketone 6 in
92% yield.
tion between the electron-rich diene and the electron-defi-
cient dienophile proceeded even at room temperature
within 1.5 hours to produce the cycloadduct 8, which upon
filtration through a short pad of silica gel gave an insepara-
ble mixture of the desired tribenzotropone (1) and its dihy-
dro analogue. The crude mixture was treated with 2,3-di-
chloro-5,6-dicyano-1,4-benzoquinone to complete the oxi-
dation to
a
benzene ring, thereby producing
tribenzotropone (1) in 56% yield. This four-step ring-expan-
sion strategy from phenanthrene-9,10-dione (4) offers an
easy and efficient method for the synthesis of tribenzotro-
pone (1) in 38% overall yield. The ring-opened diketone 6 is
highly functionalized, and it was envisioned that other type
of cyclization might lead to a medium-sized benzo-fused
ring compound. The Morita–Baylis–Hillman reaction of
diketone 6 on treatment with trimethylamine in methanol
was used as a mild protocol to induce cyclization to form
the nine-membered cyclic structure 9 (33% yield; Scheme
2).13 A single stereoisomer was obtained under these condi-
tions. An E-configuration was assigned to the alkene moiety
of 9 on the basis of the magnetic anisotropy effect of the
carbonyl group. The chemical shift of the vinylic proton was
observed at δ = 6.17 ppm, whereas the Z-isomer (obtained
as a mixture under reflux condition with triphenylphos-
phine in tert-butanol) showed a peak at δ = 5.19 ppm. The
reaction is presumably initiated by conjugate addition of
trimethylamine to form the transient intermediate 11,
which deprotonates the α-proton of the neighboring allyl
ketone moiety to give the intermediate 12. The α-alkylation
of the dienolate by the β-carbon of the neighboring ketone,
with trimethylamine as a leaving group, produced the nine-
membered cyclic diketone 9 after migration of the terminal
alkene to the conjugation site. Direct deprotonation of α-
hydrogen in allyl ketone of 6 by trimethylamine is unlikely,
if we consider the pKa of its conjugated acid (<11), and
therefore the possibility of intramolecular conjugate addi-
tion of the dienolate can be ruled out. The acyclic side-
product 10 (8% yield) is believed to have been formed by the
proton exchange of dienolate 12 with the α-hydrogen of the
neighboring ketone, with concomitant elimination of
trimethylamine.
OH
O
O
O
In
Br
4
5
89%
OH
MgBr
HO
O
O
Pb(OAc)4
6
3
83%
92%
1. TIPSOTf Et3N
CH2Cl2
r.t., 1.5 h
OTIPS
O
O
OTIPS
2. SiO2
3. DDQ
1
56%
In conclusion, we have demonstrated a practical ring-
expansion strategy for constructing benzo-fused medium-
sized ring compounds from readily available phenan-
threne-9,10-dione (4) through the formation of diketone 6
by the introduction of vinyl and allyl tethers and oxidative
ring-opening of the resulting diol 3. The intramolecular
Diels–Alder reaction of 6 followed by dehydrogenation pro-
duced tribenzotropone (1) in 38% overall yield from 4. The
intramolecular Morita–Baylis–Hillman reaction of 6 with
trimethylamine, on the other hand, produced the dibenzo-
fused nine-membered diketone 9 in 22% overall yield from
4.
8
7
Scheme 1 Synthesis of tribenzotropone (1) from readily available
phenanthrene-9,10-dione (4) by introduction of C3 and C2 units, oxida-
tive ring opening, intramolecular Diels–Alder reaction, and oxidation
The required diene 7 for the intramolecular Diels–Alder
reaction was prepared in situ by the reaction of diketone 6
with triisopropylsilyl triflate in the presence of triethyl-
amine. The triisopropylsilyl group was selected to provide a
stable silyl enol ether that would permit an efficient cyc-
loaddition reaction to be performed at a high temperature.
It was surprising that the intramolecular Diels–Alder reac-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2957–2960

2959
J. Choi et al.
Special Topic
Synthesis
(K2CO3), filtered, and concentrated under reduced pressure. The crude
product was purified by silica gel flash column chromatography to
give a light-yellow oil; yield: 0.99 g (3.56 mmol, 83%); Rf = 0.46
(EtOAc–hexane, 1:4).
Me3N
H
O
6
O
O
O
+
MeOH
IR (KBr): 3489, 3069, 1732, 1642, 1486, 1453, 1345, 1199, 1161, 1000,
924, 863, 745 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.31 (d of A of ABq, JAB = 14.0, Jd = 6.0
Hz, 1 H), 2.32 (br s, 1 H), 2.67 (d of B of ABq, JAB = 14.0, Jd = 8.8 Hz, 1 H),
2.70 (br s, 1 H), 4.95 (d, J = 17.6 Hz, 1 H), 5.03 (d, J = 9.2 Hz, 1 H), 5.05
(d, J = 10.4 Hz, 1 H), 5.34 (d, J = 16.8 Hz, 1 H), 5.59 (dddd, Jd = 17.6, 9.2,
8.8, 6.0 Hz, 1 H) 5.99 (dd, J = 16.8, 10.4 Hz, 1 H), 7.29–7.40 (m, 4 H),
7.45–7.49 (m, 1 H), 7.62–7.67 (m, 1 H), 7.68–7.74 (m, 2 H).
33%
8%
10
9
Me3N
–O
Me3N
O
O
O–
13C NMR (100.6 MHz, CDCl3): δ = 39.1, 78.3, 79.6, 115.4, 119.0, 123.5,
123.7, 124.4, 125.3, 127.8, 127.9, 128.0, 128.5, 132.0, 132.1, 133.5,
138.7, 139.3, 139.7.
12
11
HRMS (CI): m/z calcd for C19H17O2: 277.1229; found: 277.1227.
Scheme 2 Synthesis of the benzo-fused nine-membered dione 9 by
the intramolecular Baylis–Hillman reaction of diketone 6.
1-(2′-Acryloylbiphenyl-2-yl)but-3-en-1-one (6)
To a stirred solution of diol 3 (1.12 g, 4.02 mmol) in MeCN (25 mL) at
r.t. under argon was added Pb(OAc)4 (2.00 g, 4.43 mmol), and the
mixture was stirred at r.t. for 30 min. The reaction was quenched with
1 M aq HCl, the mixture was extracted with EtOAc. The extracts were
dried (Na2SO4), filtered, and concentrated under reduced pressure.
The crude product was purified by silica gel flash column chromatog-
raphy to give a yellow oil; yield: 1.02 g (3.70 mmol, 92%); Rf = 0.41
(EtOAc–hexane, 1:4).
IR spectra were recorded on a Varian 2000 FTIR spectrophotometer.
1H and 13C NMR spectra were recorded on a Varian VNMRS-400 spec-
trometer, in CDCl3 with TMS as an internal reference. High-resolution
mass spectrometry was performed by using a magnetic sector analyz-
er in a JEOL JMS-600W spectrometer. Solvents for extraction and
chromatography were of reagent grade and were used as received.
Column chromatography was performed with silica gel 60 (70–230
mesh) and a mixture of EtOAc and hexanes. Reactions were per-
formed in a well-dried flask under argon unless noted otherwise.
IR (KBr): 3081, 1685, 1604, 1477, 1447, 1411, 1300, 1218, 1126, 1000,
924, 817, 766, 659 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.38 (br s, 2 H), 4.97 (dd, J = 17.2, 1.6
Hz, 1 H), 5.09 (dd, J = 10.0, 1.6 Hz, 1 H), 5.75 (dd, J = 10.4, 1.2 Hz, 1 H),
5.86 (ddt, Jd = 17.2, 10.0, Jt = 6.8 Hz, 1 H), 6.17 (dd, J = 17.2, 1.2 Hz, 1
H), 6.52 (dd, J = 17.2, 10.4 Hz, 1 H), 7.14–7.22 (m, 2 H), 7.39–7.52 (m,
4 H), 7.61–7.68 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 46.1, 118.3, 127.3, 127.6, 128.2,
128.7, 130.3, 130.6, 130.6, 130.7, 130.8, 131.1, 135.5, 138.0, 138.8,
139.6, 140.3, 195.1, 202.2.
10-Allyl-10-hydroxyphenanthren-9(10H)-one (5)
To a stirred solution of phenanthrene-9,10-dione (4) (3.00 g, 14.41
mmol) in DMF (80 mL) at 0 °C under argon were added allyl bromide
(1.25 mL, 14.41 mmol), In (1.74 g, 15.1 mmol), and NaI (2.16 g, 14.41
mmol). The orange solution turned dark green at this point. The mix-
ture was stirred at 0 °C for 15 min and then the reaction was
quenched with 1 M aq HCl. The mixture was extracted with EtOAc
and the extracts were dried (Na2SO4), filtered, and concentrated un-
der reduced pressure. The crude product was purified by silica gel
flash column chromatography to give a light-yellow oil; yield: 3.20 g
(12.79 mmol, 89 %); Rf = 0.49 (EtOAc–hexane, 1:4).
HRMS (CI): m/z calcd for C19H17O2: 277.1229; found: 277.1225.
9H-Tribenzo[a,c,e][7]annulen-9-one (1)
To a stirred solution of diketone 6 (0.50 g, 1.81 mmol) in CH2Cl2 (30
mL) at r.t. under argon were added TIPSOTf (0.6 mL, 2.15 mmol) and
Et3N (0.25 mL, 2.00 mmol). The mixture was stirred at r.t. for 1.5 h,
then filtered through a short pad of silica gel. The filtrate was concen-
trated under reduced pressure. The crude product was dissolved in
CH2Cl2 (20 mL), and treated with DDQ (0.41 g, 1.81 mmol). The mix-
ture was stirred at r.t. for 1.5 h, and then the reaction was quenched
with H2O. The mixture was extracted with CH2Cl2, and the extracts
were dried (Na2SO4), filtered, and concentrated under reduced pres-
sure (single spot in TLC). The crude product (0.42 g) was purified by
trituration with hexane to give a white solid; yield: 0.26 g (1.03
mmol, 57%); mp 177–178 °C; Rf = 0.53 (EtOAc–hexane, 1:4).
IR (KBr): 3487, 3082, 1700, 1612, 1483, 1454, 1384, 1291, 1257, 1207,
1085, 926, 764, 719, 640 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.45 (d of A of ABq, JAB = 13.6, Jd = 7.6
Hz, 1 H), 2.54 (d of B of ABq, JAB = 13.6, Jd = 7.6 Hz, 1 H), 4.05 (s, 1 H),
4.86 (dd, J = 17.2, 1.6 Hz, 1 H), 5.04 (dd, J = 10.0, 0.8 Hz, 1 H), 5.63 (ddt,
Jd = 17.2, 10.0, Jt = 7.9 Hz, 1 H) 7.38–7.46 (m, 3 H), 7.68–7.77 (m, 2 H),
7.83–7.89 (m, 1 H), 7.89–7.98 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 49.0, 79.6, 119.5, 123.2, 124.0, 126.1,
127.3, 128.2, 128.4, 128.5, 129.0, 129.2, 131.4, 135.1, 137.5, 140.2,
202.9.
HRMS (CI): m/z calcd for C17H15O2: 251.1072; found: 251.1070.
IR (KBr): 2934, 1734, 1662, 1602, 1489, 1439, 1367, 1313, 1272, 1167,
1063, 927, 895, 750 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.44–7.52 (m, 4 H), 7.57–7.63 (m, 2 H),
9-Allyl-10-vinyl-9,10-dihydrophenanthrene-9,10-diol (3)
7.64–7.69 (m, 4 H), 7.71–7.75 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 126.5, 128.0, 128.3, 129.1, 131.1,
131.4, 136.7, 137.1, 143.0, 198.7.
To a stirred solution of hydroxy ketone 5 (1.07 g, 4.28 mmol) in THF
(50 mL) at –78 °C under argon was added a 1 M solution of vinylmag-
nesium bromide in THF (12.8 mL, 12.8 mmol), and the mixture was
stirred at –78 °C for 2 h. The reaction was quenched with 1 M aq HCl,
the mixture was extracted with EtOAc, and the extracts were dried
HRMS (CI): m/z calcd for C19H13O: 257.0966; found: 257.0968.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2957–2960

2960
J. Choi et al.
Special Topic
Synthesis
(6E)-6-Ethylidene-7,8-dihydro-5H-dibenzo[a,c][9]annulene-
5,9(6H)-dione (9) and (2E)-1-(2′-acryloylbiphenyl-2-yl)but-2-en-1-
one (10)
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1381045.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
To a stirred solution of diketone 6 (0.43 g, 1.60 mmol) in MeOH (25
mL) at r.t. under argon atmosphere was added Me3N (0.12 g, 1.90
mmol), and the mixture was stirred at r.t. for 4 h. The reaction was
quenched with H2O and the mixture was extracted with CHCl3. The
extracts were dried (MgSO4), filtered, and concentrated under re-
duced pressure. The crude product was purified by silica gel flash col-
umn chromatography to give cyclic diketone 9 [yield: 0.15 g (0.53
mmol, 33%)] and acyclic diketone 10 [yield: 0.04 g (0.13 mmol, 8%)].
References
(1) Pauson, P. L. Chem. Rev. 1955, 55, 9.
(2) Mori, A.; Takeshita, H. J. Am. Chem. Soc. 1990, 112, 8635.
(3) Mori, A.; Taya, H.; Takeshita, H.; Ujiie, S. J. Mater. Chem. 1998, 8,
595.
(4) Hashimoto, M.; Ujiie, S.; Mori, A. Adv. Mater. (Weinheim, Ger.)
2003, 15, 797.
9
(5) Stiles, M.; Libbey, A. J. Jr. J. Org. Chem. 1957, 22, 1243.
(6) Bergman, E. D.; Klein, J. J. Org. Chem. 1958, 23, 512.
(7) Shukla, D.; Lukeman, M.; Shi, Y.; Wan, P. J. Photochem. Photo-
biol., A 2002, 154, 93.
(8) Taljaard, B.; Taljaard, J. H.; Imrie, C.; Caira, M. R. Eur. J. Org. Chem.
2005, 2607.
(9) Luo, J.; Song, K.; Gu, F. l.; Miao, Q. Chem. Sci. 2011, 2, 2029.
(10) Udayakumar, B. S.; Schuster, G. B. J. Org. Chem. 1993, 58, 4165.
(11) Dahnke, K. R.; Paquette, L. A. Org. Synth. Coll. Vol. IX; Wiley:
London, 1998, 181.
(12) Tochtermann, W.; Oppenländer, K.; Walter, U. Chem. Ber. 1964,
97, 1329.
Yellow oil; Rf = 0.36 (EtOAc–hexane, 1:4).
IR (KBr): 3073, 2928, 1674, 1611, 1438, 1375, 1289, 1236, 1120, 995,
885, 764, 649 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.53 (dd, J = 7.2, 1.2 Hz, 3 H), 2.12–2.20
(m, 1 H), 2.61 (ddd, J = 13.2, 6.4, 4.0 Hz, 1 H), 2.68 (ddd, J = 13.2, 10.8,
6.4 Hz, 1 H), 2.85 (ddd, J = 14.4, 10.8, 6.8 Hz, 1 H), 6.17 (q, J = 7.2 Hz, 1
H), 7.11–7.15 (m, 1 H), 7.24–7.28 (m, 1 H), 7.37–7.42 (m, 1 H), 7.43–
7.47 (m, 1 H), 7.47–7.55 (m, 3 H), 7.79–7.82 (m, 1 H).
13C NMR (100.6 MHz, CDCl3): δ = 13.8, 23.9, 40.4, 126.1, 127.2, 128.0,
128.2, 129.4, 130.3, 131.4, 131.6, 136.3, 138.1, 139.4, 139.4, 139.7,
141.0, 199.7, 203.2.
(13) Yeo, J. E.; Yang, X.; Kim, H. J.; Koo, S. Chem. Commun. 2004, 236.
(14) Do, Y.-S.; Sun, R.; Kim, H. J.; Yeo, J. E.; Bae, S.-H.; Koo, S. J. Org.
Chem. 2009, 74, 917.
(15) For intramolecular Diels–Alder reactions with ring expansion,
see: (a) Fallis, A. G. Can. J. Chem. 1984, 62, 183. (b) Takao, K.-i.;
Munakata, R.; Tadano, K.-i. Chem. Rev. 2005, 105, 4779.
(c) Phillips, A. J.; Morris, J. C.; Abell, A. D. Tetrahedron Lett. 2000,
41, 2723.
HRMS (CI): m/z calcd for C19H17O2: 277.1229; found: 277.1222.
10
Yellow oil; Rf = 0.48 (EtOAc–hexane, 1:4).
1H NMR (400 MHz, CDCl3): δ = 1.78 (d, Jd = 6.8 Hz, 3 H), 5.70 (d,
J = 10.4 Hz, 1 H), 6.16 (d, J = 17.2 Hz, 1 H), 6.27 (d, J = 15.6 Hz, 1 H),
6.51 (dd, J = 17.2, 10.4 Hz, 1 H), 6.77 (dq, Jd = 15.6, Jq = 6.8 Hz, 1 H)
7.14–7.22 (m, 2 H), 7.36–7.48 (m, 4 H), 7.52–7.62 (m, 2 H).
(16) Min, J.-H.; Jung, S.-Y.; Wu, B.; Oh, J. T.; Lah, M. S.; Koo, S. Org.
Lett. 2006, 8, 1459.
Acknowledgment
This work was supported by the 2014 Research Fund of Myong Ji Uni-
versity.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2957–2960