Atom-Economic Synthesis of Highly Functionalized Bridged Ring Systems Initiated by Ring Expansion of Indene-1,3-dione

Article abstract of DOI:10.1021/acs.joc.1c00487

An atom economic procedure for the regioselective synthesis of bridged seven-membered-ring compounds from simple reactants such as ynones and indene-1,3-dione has been developed. This process was realized through the one-pot reactions of ring-expansion of

Full text of DOI:10.1021/acs.joc.1c00487

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Article
Atom-Economic Synthesis of Highly Functionalized Bridged Ring
Systems Initiated by Ring Expansion of Indene-1,3-dione
Yuanyang Mu, Qiyi Yao, Liqiang Yin, Siyi Fu, Mengdan Wang, Yang Yuan, Lingkai Kong,*
and Yanzhong Li*
Cite This: J. Org. Chem. 2021, 86, 6755−6764
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ABSTRACT: An atom economic procedure for the regioselective synthesis of bridged seven-membered-ring compounds from
simple reactants such as ynones and indene-1,3-dione has been developed. This process was realized through the one-pot reactions
of ring-expansion of indene-1,3-dione with alkynyl ketones and successive formal [4+2] cycloaddition. The Michael addition
reaction is the key for the regioselectivity of the formal [4+2] cycloaddition.
seven-membered-ring compound (4π component, such as
tropone) with an unsaturated molecule (2π component).6
However, control of the regioselectivity is a great challenge.6a−c
Consequently, symmetrical substrates7 or intramolecular
cyclization reactions5b,c,8 were applied in the reported
protocols to avoid such problems. Generally speaking, there
are two types of [4+2] cycloaddition toward bridged seven-
membered-ring compounds starting from tropones: (1) Lewis
acid-catalyzed or -mediated reactions and (2) thermal
promoted reactions. For example, Yamamoto et al.6a described
an efficient Lewis acid-catalyzed Diels−Alder reaction of
tropones with inverse-electron-demand dienophiles, delivering
bridged ring compounds with high enantioselectivity (Scheme
1a). Uyehara group6b reported a Diels−Alder reaction of
tropones with methyl propiolate (Scheme 1b). Biju et al.6c also
developed the Diels−Alder reaction of tropones with arynes to
synthesize functionalized benzobicyclo[3.2.2]nonatrienones
(Scheme 1c). However, regioisomers were usually obtained
by these procedures. Besides, these protocols relied on
cycoheptatrienones as starting materials, and the narrow
INTRODUCTION
■
Bridged ring systems are ubiquitous in pharmaceuticals and
natural products with a variety of biological activities. There
have been many effective protocols for the syntheses of these
compounds.1a,d,e Among them, bridged seven-membered-ring
systems are of particular important because of the remarkable
biological properties;1b,c,f−h examples include goupiolone B
(I),1g phleghenrine A (II),1h ingenol (III), and neocycloci-
trinol A (IV) (Figure 1). As a result, several effective
Figure 1. Selected natural products containing bridged seven-
membered-ring system.
procedures toward the bridged seven-membered-ring com-
pounds have been developed, such as intramolecular
cyclization,2 ring-closing metathesis,3 and C−C bond
activation.4 Nevertheless, general procedures for the prepara-
tion of bridged seven-membered-ring systems are rare.5 One of
the most straightforward ways to the synthesis of the bridged
seven-membered-ring systems is the [4+2] cycloaddition of a
Received: February 27, 2021
Published: April 13, 2021
https://doi.org/10.1021/acs.joc.1c00487
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 6755−6764
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Scheme 1. Cycloaddition Reactions of Tropones or
Benzocycloheptadienones toward Bridged Seven-
Membered-Ring Systems
RESULTS AND DISCUSSION
■
The reactions of 1-phenyl-3-(p-tolyl)prop-2-yn-1-one (1a)
(2.2 equiv) bearing a tolyl substituent at the alkyne terminus
with indene-1,3-dione (2a) were first carried out in the
presence of 3.0 equiv of Cs2CO3 at 110 °C in N,N-dimethyl
formamide (DMF) (5.0 mL) under air. The results are shown
in Table 1. To our surprise, only the complex reaction mixture
a
Table 1. Screening of Reaction Conditions
entry 1a (equiv)
base (equiv)
solvent
N2/air yield (%)
b
1
2
3
4
5
6
7
8
2.2
2.2
1.0
2.2
2.4
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
Cs2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (2.0)
K2CO3 (1.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
NaOH (3.0)
DABCO (3.0)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMAc
toluene
DMF
DMF
air
air
air
N2
N2
N2
N2
N2
N2
N2
N2
N2
N2
C
76
47
85
84
76
47
c
52
9
84
80
d
10
11
12
13
NR
C
b
trace
a
Unless otherwise noted, the reactions were conducted on a 0.3 mmol
b
c
scale in 5.0 mL of solvent at 110 °C. Complex reaction mixture. The
reaction was carried out at 80 °C. No reaction.
d
substrate scope of commercially available tropones greatly
limited its application of such transformations. Methodologies
starting from simple and easily accessible reactants are highly
desirable. On the other hand, the [4+2] cycloaddition of
alkynones has been greatly developed.9 However, the use of
[4+2] cycloaddition of benzo-fused tropones with alkynones
for the construction of bridged seven-membered-ring com-
pounds has not been reported, to the best of our knowledge.
Therefore, the development of new reaction types other than
the aforementioned ones, especially the efficient, regioselective
procedures starting from readily accessible precursors for the
synthesis of bridged seven-membered-ring systems is greatly
appealing. It would enrich the tropone chemistry10 and further
broaden the boundary of bridged seven-membered ring
skeletons. As part of our ongoing studies on C−C bond
activation chemistry, we have developed base-promoted
protocols for the C−C σ-bonds activation of 1,3-diketones11
including the preparation of benzo[7]annulen-5-ones via
insertion of alkyne into indene-1,3-dione.12e During the
study, we found that the formal [4+2] cycloaddition reaction
could be promoted by a base. In this process, the formal [4+2]
cycloaddition was realized through the Michael addition and
subsequent ring-closure reaction to afford bridged compounds
containing seven-membered rings. It is quite different from the
reported procedures in which the bridged compounds were
usually obtained through the Diels−Alder reaction. Herein, we
report a base-promoted regioselective synthesis of bridged
seven-membered-ring compounds with 100% atom-economy
(Scheme 1d).
was observed (Table 1, entry 1). When K2CO3 was employed
instead of Cs2CO3, the expected bridged seven-membered ring
3a could be obtained in 76% yield within 3 h (Table 1, entry
2). The structure of 3a was further confirmed by X-ray analysis.
The formation of 3a suggested that the cascade reactions of
C−C bond insertion/[4+2] cycloaddition did occur in a one-
pot manner during the reaction process, and 1.0 equiv of 1a
resulted in a lower yield of 47% (entry 3). When the reaction
was performed under N2, a higher yield of 85% was observed
(entry 4). However, 2.4 equiv of 1a gave no better result
(Table 1, entry 5). Decreasing K2CO3 to 2.0 equiv resulted in a
lower yield of 76% (Table 1, entry 6). Lowering the reaction
temperature to 80 °C afforded 3a in a yield of 52% within 3 h
(entry 8). The reactions proceed well in other dipolar aprotic
solvents such as dimethyl sulfoxide (DMSO) and N,N-
dimethyl acetamide (DMAc) (entries 9 and 10). Toluene as
the solvent resulted in no reaction at all (entry 11). Other
bases, such as NaOH or the organic base of 1,4-
diazabicyclo[2.2.2]octane (DABCO), were ineffective for this
reaction (entries 12 and 13).
Having established the best reaction conditions (Table 1,
entry 4), we next explored the substrate scope of this one-pot
C−C bond insertion/[4+2] cycloaddition reactions (Figure 2).
First, the R1 substituent on the carbonyl carbon was explored
(Figure 2, 3b−3h). It was found that R1 with electron-
donating (4-Me, 4-MeO, 3,4-(MeO)2, 3,4,5-(MeO)3) aryl
groups delivered the corresponding bridged products 3b, 3c,
3d, and 3e in 71%, 63%, 72%, and 62% yields, respectively,
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and subjected them to the reaction with another alkynone. To
our delight, the desired bridged compounds were obtained in
very high yields (Figure 3). When 4m (R2 = R3 = H) was
Figure 3. Synthesis of 3 from two different alkynones. Unless
otherwise noted, the reactions were carried out using 3.0 equiv of
K2CO3 in 5.0 mL of DMF at 110 °C under N2 on a 0.3 mmol scale
with the ratio of 1/4 = 1.2:1.
employed, R1 substituent on the terminal aryl rings of alkynone
could be electron-rich (4-OMe, 4-Me) and electron-deficient
(4-Cl), all afforded the corresponding bridged ring compounds
in 71−88% yields (3p−3r). Compounds 4b (R2 = H, R3 =
Me) and 4c (R2 = OMe, R3 = H) reacted smoothly with 1-
phenyl-3-(p-tolyl)prop-2-yn-1-one to give 3s and 3t both in
83% yields. A 2-pyrrolyl-substituted 4j was well tolerated to
produce 3u in 76% yield. The reaction of 4a (R2 = Me, R3 =
H) with 1,3-diphenylprop-2-yn-1-one resulted in 85% of 3v. By
this method, we could assemble the functionalities of the
desired bridged seven-membered ring systems in a controllable
manner.
To show the applicability of this cascade reaction, the
transformation of the bridged seven-membered-ring com-
pounds 3a and 3q were conducted (Scheme 2). Wittig
olefination of 3a gave 5a in 78% yield. The etherification
reaction of 3q reacted with methyl iodide smoothly affording
methyl ether 5q in a good yield of 86%.
Figure 2. Synthesis of 3 from two identical alkynones. Unless
otherwise noted, the reactions were carried out using 3.0 equiv of
K2CO3 in 5.0 mL of DMF at 110 °C under N2 on a 0.3 mmol scale
with the ratio of 1/2a = 2.2:1.
whereas electron-withdrawing (4-F, 4-Cl, 4-Br) aryl groups
produced the desired bridged ring systems 3f, 3g, and 3h in
moderate yields. We could observe some unidentified
byproducts formed, and certain amount of ynones remained
during these reactions. It may account for the low yields in
these cases. Steric-demand substituents such as 1-naphthyl also
worked well to give the corresponding 3i in 68% yield.
Heteroaryl substituents, such as 2-pyrrolyl or 2-fural, afforded
the desired products 3j and 3k in 58% and 67% yields,
respectively. Subsequently, substituents (R2) on the terminal
alkyne were tested. Both electron-donating (4-OMe) and
electron-withdrawing (4-Cl) aryl groups were compatible to
the reaction, offering the corresponding bridged ring systems
in high yields (3l−3n). Notably, a substrate with 4-Cl aryl
groups was tolerable to the reaction conditions, resulting in 3n
in nearly a quantitatively yield. However, alkyl substituents
(R2) such as a methyl group could not give the desired bridged
product (3o).
Scheme 2. Further Transformations of the Bridged Seven-
Membered Rings 3a and 3q
It is believed that these cascade reactions took place in a
stepwise manner. That is, first the reaction of indene-1,3-dione
with alkynone to give a ring-expansion product. Then the
newly formed seven-membered ring react with alkynone again
via [4+2] cycloaddition reaction to afford the bridged ring
system. Thus, it is possible to incorporate another alkynyl
ketone which is different from the one for the first step into the
final bridged product. Consequently, the corresponding
bridged seven-membered compounds with a variety of
functionalities would be easily assembled. To test this
hypothesis, we prepared several seven-membered rings (4)12e
In order to clarify the reaction mechanism, several control
experiments were conducted (Scheme 3). First, the reaction of
4m with 1a was performed under the optimized reaction
conditions, and 3q was obtained in 79% yield. Reducing
K2CO3 to 0.5 equiv also gave 3q in 68% yield. However, no
desired product was observed in the absence of K2CO3. These
results indicated that the base played a crucial role in this
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Scheme 3. Control Experiments
EXPERIMENTAL SECTION
■
General Information. All reactions were performed in
flame-dried glassware under N2, unless otherwise noted. N,N-
Dimethylformamide (DMF) was dried and distilled from
calcium hydride. Column chromatographic purification of
products was carried out using silica gel (200−300 mesh). The
reagents were used without further purification. 1H NMR
spectra were recorded at 400, 500, or 600 MHz, and 13C NMR
spectra were recorded at 100, 125, or 150 MHz, in CDCl3
1
(containing 0.03% TMS) solutions. H NMR spectra were
recorded with tetramethylsilane (δ = 0.00 ppm) as an internal
reference; 13C NMR spectra were recorded with CDCl3 (δ =
77.00 ppm) as an internal reference. High-resolution mass
spectra were performed on a mass spectrometer with a TOF
(for EI or ESI) or FT-ICR (for MALDI) analyzer. Single-
crystal X-ray diffraction data was collected in Bruker
SMARTAPEX diffractiometers with molybdenum cathodes.
Preparation of Acetyenic Ketones 1. To a solution of
alkyne (12 mmol) in anhydrous THF (30 mL), n-BuLi (2.5M,
10 mmol, 4 mL) was added at −78 °C. The resulting mixture
was stirred at −78 °C for 40 min, then the aldehyde (10
mmol) was added, and the reaction temperature was raised to
room temperature until the aldehyde disappeared by TLC
analysis. The resulting mixture was quenched with a saturated
solution of NH4Cl and extracted with ethyl acetate (20 mL ×
3). The combined organic layers were washed with brine, dried
over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by column chromatography with
petroleum ether/ethyl acetate = 10:1−5:1 as the eluent
afforded the substituted alkynol.
reaction. The role of a base might be the deprotonation of the
−OH group in 4a to give an enolate, which facilitates the
Michael addition to 1a and the following ring closure step (see
Scheme 4, D → 3a). These suggested that a concerted
pericyclic reaction path toward the final bridged ring systems
was less favorable.
Scheme 4. Plausible Reaction Mechanism
To a solution of substituted alkynol (10 mmol) in DMSO
(20 mL) in round-bottom flask was added IBX (12 mmol, 3.36
g) at room temperature. The reaction was stirred in air until
the full conversion of substituted alkynol monitored by thin-
layer chromatography. The resulting mixture was quenched
with water (20 mL) and filtered. Then, the filtrate was
extracted with ethyl acetate (20 mL × 3). The organic layer
was combined, washed with brine, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Purification by column chromatography with petroleum ether/
ethyl acetate = 20:1−10:1 as the eluent afforded the acetyenic
ketones. The acetyenic ketones 1 are known compounds, and
the spectroscopic data is in agreement with that previously
reported.12
Synthesis of Benzoannulated Seven-Membered
Rings 4. In a Schlenk tube, alkynones 1 (5.0 mmol),
Cs2CO3 (15.0 mmol, 4.89 g), DMSO (30 mL), and indene-
1,3-dione (7.0 mmol, 1.02 g) were stirred at 110 °C (oil bath)
under N2. After the reaction was completed as monitored by
thin-layer chromatography, the reaction mixture was then
quenched by water, and the water layers were extracted with
ethyl acetate (50 mL × 3). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by chroma-
tography on silica gel (petroleum ether/ethyl acetate = 10:1)
afforded desired benzoannulated seven-membered rings 4. The
benzoannulated seven-membered rings 4 are known com-
pounds, and the spectroscopic data is in agreement with that
previously reported.12e
Based on the experimental results and our previous
reports,11a,12 a possible reaction mechanism was proposed
with model substrates 1a and 2a (Scheme 4). In the presence
of a base, nucleophilic attack of indene-1,3-dione (2a) to 1a
gives an intermediate A, which undergoes an intramolecular
nucleophilic addition/ring-opening to offer a ring-expansion
product C. Tautomerization of C followed by protonation
results in product 4a, which undergoes a stepwise cyclo-
addition reaction with alkynone 1a under basic conditions to
afford the final product 3a.
In summary, an atom-economic base-promoted protocol for
the regioselective synthesis of bridged seven-membered-ring
systems has been developed. Cascade reactions of ring-
expansion of indene-1,3-diones with ynones and subsequent
cycloaddition were involved in this process. This method
provides simple and efficient access to bridged seven-
membered-ring compounds with multifunctionalities, which
were assembled in a controllable manner. The Michael
addition reaction is the key for the regioselectivity of the
formal [4+2] cycloaddition.
Synthesis of 3a−3n. In a Schlenk tube, 1-phenyl-3-(p-
tolyl)prop-2-yn-1-one 1a (0.66 mmol, 145 mg), K2CO3 (0.9
mmol, 124 mg), DMF (5 mL), and 1H-indene-1,3(2H)-dione
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2a (0.3 mmol, 44 mg) was stirred at 110 °C (oil bath) under
N2. After the reaction was completed as monitored by thin-
layer chromatography, the reaction mixture was then quenched
by water, and the water layers were extracted with ethyl acetate
(10 mL × 3). The combined organic layers were washed with
brine, dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure. Purification by chromatography on
silica gel (petroleum ether/ethyl acetate = 5:1) afforded
desired compound 3a (yellow solid, 149 mg, 85%).
Crystal Preparation and Measurement Methods of
3a. In a 50 mL round-bottom flask, 50 mg of 3a and 2 mL of
dichloromethane were placed; then, 6 mL of petroleum ether
was added. The prepared solution was well shaken and kept at
room temperature until crystals precipitate out. The crystals
were carefully picked out for single-crystal X-ray diffraction.
Single-crystal X-ray diffraction data was collected in Bruker
SMARTAPEX diffractiometers with molybdenum cathodes.
Synthesis of 3p−3v. In a Schlenk tube, 3-(4-methox-
yphenyl)-1-phenylprop-2-yn-1-one 1l (0.36 mmol, 84 mg),
K2CO3 (0.9 mmol, 124 mg), DMF (5 mL), and 8-benzoyl-9-
hydroxy-7-phenyl-5H-benzo[7]annulen-5-one 4m (0.30 mmol,
106 mg) were stirred at 110 °C (oil bath) under N2. After the
reaction was completed as monitored by thin-layer chromatog-
raphy, the reaction mixture was then quenched by water, and
the water layers were extracted with ethyl acetate (10 mL × 3).
The combined organic layers were washed with brine, dried
over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by chromatography on silica gel
(petroleum ether/ethyl acetate = 5:1) afforded desired
compound 3p (yellow solid, 126 mg, 71%).
Synthesis of 5a. Methyltriphenylphosphonium bromide
(1.2 mmol, 6.0 equiv, 429 mg) was suspended in dry toluene
(2 mL) and cooled to 0 °C, and t-BuOK (1.2 mmol, 6.0 equiv,
135 mg) was added in one portion under nitrogen. Then the
reaction was stirred at 0 °C for 3 h. Compound 3a (0.2 mmol,
1.0 equiv, 117 mg) was added, and the reaction was warmed to
80 °C (oil bath) and stirred until completion was observed by
TLC (6 h). The resulting mixture was quenched with water
and extracted with ethyl acetate. The combined organic layers
were washed with brine, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. Purification
by column chromatography with petroleum ether/ethyl acetate
= 15:1 as the eluent afforded the alkene 5a (white solid, 90 mg,
78%).
Synthesis of 5q. To a stirred solution of 3q (0.2 mmol, 1.0
equiv, 114 mg) in anhydrous THF (2 mL) was added sodium
hydride (60% in oil, 2.2 equiv, 0.44 mmol, 18 mg) portion-wise
at room temperature. The mixture was further stirred at room
temperature for 1 h before the slow addition of CH3I (0.88
mmol, 4.4 equiv, 125 mg). The reaction was warmed to 100 °C
(oil bath) and stirred until completion was observed by TLC
(6 h). Then the resulting mixture was quenched with water
and extracted with ethyl acetate. The combined organic layers
were washed with brine, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. Purification
by column chromatography with petroleum ether/ethyl acetate
= 8:1 as the eluent afforded the ether 5q (white solid, 100 mg,
86%).
as monitored by thin-layer chromatography, the reaction
mixture was then quenched by water, and the water layers were
extracted with ethyl acetate (50 mL × 3). The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Purification by chromatography on silica gel (petroleum ether/
ethyl acetate = 5:1) afforded desired compound 3m (yellow
solid, 575 mg, 68%).
1.5 mmol Scale Synthesis of 3r from 4m and 1n. In a
Schlenk tube, 3-(4-chlorophenyl)-1-phenylprop-2-yn-1-one 1n
(1.8 mmol, 433 mg), K2CO3 (4.5 mmol, 620 mg), DMF (25
mL), and 8-benzoyl-9-hydroxy-7-phenyl-5H-benzo[7]annulen-
5-one 4m (1.5 mmol, 529 mg) were stirred at 110 °C (oil
bath) under N2. After the reaction was completed as
monitored by thin-layer chromatography, the reaction mixture
was then quenched by water, and the water layers were
extracted with ethyl acetate (50 mL × 3). The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Purification by chromatography on silica gel (petroleum ether/
ethyl acetate = 10:1) afforded desired compound 3r (yellow
solid, 721 mg, 81%).
(5-Hydroxy-9-oxo-7,10-di-p-tolyl-8,9-dihydro-5H-5,8-
ethenobenzo[7]annulene-6,11-diyl)bis(phenylmethanone)
(3a): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate
= 10:1), 149 mg (85% yield), mp 167−169 °C; 1H NMR (500
MHz, CDCl3, TMS) δ 8.36−8.35 (m, 1H), 7.58−7.56 (m,
1H), 7.46−7.42 (m, 5H), 7.37−7.34 (m, 1H), 7.31−7.28 (m,
2H), 7.19−7.17 (m, AA′BB′ system, 4H), 7.12−7.09 (m, 4H),
6.93−6.91 (m, AA′BB′ system, 4H), 5.20 (s, 1H), 4.65 (s,
1H), 2.15 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 197.1,
187.3, 146.4, 144.3, 138.6, 137.9, 136.5, 133.9, 133.3, 133.2,
130.9, 129.3, 129.1, 128.4, 128.2, 127.7, 127.3, 123.4, 77.9,
69.4, 21.0; HRMS (ESI) m/z [M + H]+ calcd for C41H31O4
[M + H]+ 587.2217, found 587.2219.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis(p-tolylmethanone) (3b):
yellow solid, obtained in 3 h and purified by chromatography
on silica gel (petroleum ether/ethyl acetate = 5:1), 125 mg
1
(71% yield), mp 114−115 °C; H NMR (400 MHz, CDCl3,
TMS) δ 8.37 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 7.6 Hz, 1H),
7.48−7.45 (m, 1H), 7.40−7.30 (m, 9H), 7.16−7.09 (m, 6H),
6.94−6.92 (m, AA′BB′ system, 4H), 5.22 (s, 1H), 4.54 (s,
1H), 2.23 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.1,
187.9, 146.5, 145.7, 144.9, 137.3, 137.2, 134.3, 133.6, 131.2,
129.7, 129.3, 128.7, 128.7, 128.0, 127.5, 123.8, 77.8, 69.0, 21.3;
HRMS (ESI) m/z [M + H]+ calcd for C41H31O4 [M + H]+
587.2217, found 587.2224.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis((4-methoxyphenyl)-
metanone) (3c): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
1
5:1), 117 mg (63% yield), mp 109−111 °C; H NMR (400
MHz, CDCl3, TMS) δ 8.37 (d, J = 8.0 Hz, 1H), 7.61 (d, J =
8.0 Hz, 1H), 7.46−7.39 (m, 6H), 7.33−7.31 (m, AA′BB′
system, 4H), 7.17−7.08 (m, 6H), 6.61−6.59 (m, AA′BB′
system, 4H), 5.21 (s, 1H), 4.56 (s, 1H), 3.70 (s, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 195.9, 188.0, 164.2, 146.6, 145.8,
137.3, 136.9, 133.6, 132.1, 131.2, 129.8, 128.7, 127.9, 127.6,
123.8, 113.8, 77.8, 68.9, 55.2; HRMS (ESI) m/z [M + H]+
calcd for C41H31O6 [M + H]+ 619.2115, found 619.2119.
1.5 mmol Scale Synthesis of 3m from 1m and 2a. In a
Schlenk tube, 1,3-diphenylprop-2-yn-1-one 1m (3.3 mmol, 681
mg), K2CO3 (4.5 mmol, 620 mg), DMF (25 mL), and 1H-
indene-1,3(2H)-dione 2a (1.5 mmol, 220 mg) were stirred at
110 °C (oil bath) under N2. After the reaction was completed
6759
https://doi.org/10.1021/acs.joc.1c00487
J. Org. Chem. 2021, 86, 6755−6764

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis((3,4-dimethoxyphenyl)-
methanone) (3d): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
7.24 (m, 12H), 7.18−7.15 (m, 6H), 5.22 (s, 1H), 4. 58 (s,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.4, 187.4, 146.2,
144.9, 138.4, 136.8, 135.4, 133.8, 131.9, 131.4, 130.9, 129.2,
129.1, 128.9, 127.9, 127.3, 123.7, 77.7, 69.1; HRMS (ESI) m/z
[M + H]+ calcd for C39H25Br2O4 [M + H]+ 715.0114, found
715.0112.
1
3:1), 147 mg (72% yield), mp 133−135 °C; H NMR (500
MHz, CDCl3, TMS) δ 8.40 (d, J = 7.5 Hz, 1H), 7.64 (d, J =
8.0 Hz, 1H), 7.48−7.45 (m, 1H), 7.41−7.38 (m, 1H), 7.34−
7.32 (m, AA′BB′ system, 4H), 7.17−7.11 (m, 6H), 7.09−7.06
(m, 4H), 6.57−6.55 (m, AA′BB′ system, 4H), 3.78 (s, 6H),
3.60 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 195.9,
188.1, 154.0, 148.9, 146.5, 145.8, 137.3, 136.6, 133.7, 131.1,
129.7, 128.7, 128.7, 127.8, 127.7, 124.8, 124.1, 111.2, 110.2,
77.7, 68.7, 55.8, 55.4; HRMS (ESI) m/z [M + H]+ calcd for
C43H35O8 [M + H]+ 679.2326, found 679.2321.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis(naphthalen-1-ylmetha-
none) (3i): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
1
15:1), 134 mg (68% yield), mp 114−117 °C; H NMR (500
MHz, CDCl3, TMS) δ 8.86 (d, J = 9.0 Hz, 2H), 8.37 (d, J =
7.5 Hz, 1H), 7.73−7.71 (m, AA′BB′ system, 4H), 7.62−7.55
(m, 3H), 7.49−7.46 (m, 3H), 7.41−7.40 (m, 1H), 7.28−7.25
(m, 4H), 7.19−7.18 (m, AA′ part of AA′BB′ system, 2H),
7.00−6.94 (m, 8H), 5.37 (s, 1H), 5.15 (s, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 199.0, 187.0, 147.7, 147.2, 139.9, 137.2,
134.5, 134.0, 133.8, 133.6, 131.5, 131.2, 131.0, 128.8, 128.6,
128.5, 128.5, 128.0, 126.6, 126.0, 124.0, 123.9, 78.7, 70.1;
HRMS (ESI) m/z [M + H]+ calcd for C47H31O4 [M + H]+
659.2217, found 659.2209.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
n o - b e n z o [ 7 ] a n n u l e n e - 6 , 1 1 - d i y l ) b i s ( ( 3 , 4 , 5 -
trimethoxyphenyl)methanone) (3e): yellow solid, obtained in
3 h and purified by chromatography on silica gel (petroleum
ether/ethyl acetate = 3:1), 138 mg (62% yield), mp 171−173
°C; 1H NMR (400 MHz, CDCl3, TMS) δ 8.38 (d, J = 7.2 Hz,
1H), 7.67 (d, J = 7.2 Hz, 1H), 7.47−7.44 (m, 2H), 7.32−7.31
(m, AA′BB′ system, 4H), 7.20−7.15 (m, 6H), 6.74 (s, 4H),
5.25 (s, 1H), 4.39 (s, 1H), 3.78 (s, 6H), 3. 53 (s, 12H);
13C{1H} NMR (100 MHz, CDCl3) δ 196.2, 188.1, 153.1,
146.4, 145.6, 143.1, 137.3, 136.9, 134.0, 131.4, 131.0, 128.9,
128.9, 128.8, 127.7, 127.6, 124.5, 106.7, 77.7, 68.6, 60.7, 55.6;
HRMS (ESI) m/z [M + H]+ calcd for C45H39O10 [M + H]+
39.2538, found 739.2553.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis((4-fluorophenyl)-
methanone) (3f): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
10:1), 83 mg (46% yield), mp 84−87 °C; 1H NMR (500 MHz,
CDCl3, TMS) δ 8.41 (d, J = 7.5 Hz, 1H), 7.62 (d, J = 8.0 Hz,
1H), 7.48−7.45 (m, 5H), 7.40−7.37 (m, 1H), 7.32−7.30 (m,
AA′BB′ system, 4H), 7.14−7.07 (m, 6H), 6.77−6.73 (m, 4H),
5.26 (s, 1H), 4. 75 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3)
δ 195.1, 186.8, 165.6 (J = 255.0 Hz), 145.9, 144.8, 137.7,
136.5, 133.3, 132.7 (J = 2.5 Hz), 131.9 (J = 8.8 Hz), 131.1,
128.7, 128.6, 128.4, 127.6, 127.0, 123.3, 115.4 (J = 21.3 Hz),
77.7, 69.1; HRMS (ESI) m/z [M + H]+ calcd for C39H25F2O4
[M + H]+ 595.1715, found 595.1728.
5-Hydroxy-7,10-di-p-tolyl-6,11-bis(1-tosyl-1H-pyrrole-2-
carbonyl)-5,8-dihydro-9H-5,8-ethenobenzo[7]annulen-9-
one (3j): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
1
5:1), 151 mg (58% yield), mp 132−134 °C; H NMR (500
MHz, CDCl3, TMS) δ 8.27 (d, J = 8.0 Hz, 1H), 7.93−7.91 (m,
AA′BB′ system, 4H), 7.56−7.53 (m, 3H), 7.42−7.34 (m, 6H),
7.04−7.02 (m, AA′BB′ system, 4H), 6.87−6.85 (m, AA′BB′
system, 4H), 5.82−5.78 (m, 4H), 5.06 (s, 1H), 4.41 (s, 1H),
2.48 (s, 6H), 2.20 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 188.1, 182.9, 146.6, 145.2, 144.5, 138.6, 138.4, 135.9, 134.1,
133.5, 133.4, 131.0, 131.0, 129.6, 129.3, 128.9, 128.6, 127.8,
127.3, 127.3, 124.2, 110.5, 77.5, 68.9, 21.5, 20.9; HRMS (ESI)
m/z [M + Na]+ calcd for C51H40N2NaO8S2 [M + Na]+
895.2118, found 895.2117.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis(furan-2-ylmethanone)
(3k): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate
1
= 5:1), 109 mg (67% yield), mp 151−153 °C; H NMR (500
MHz, CDCl3, TMS) δ 8.33 (d, J = 7.5 Hz, 1H), 7.67(d, J = 8.0
Hz, 1H), 7.47−7.44 (m, 2H), 7.34−7.33 (m, 6H), 7.22−7.16
(m, 6H), 6.24 (s, 2H), 6.12 (s, 2H), 5.20 (s, 1H), 4.65 (s, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 187.2, 182.8, 152.1,
147.8, 146.1, 144.3, 138.6, 136.8, 133.2, 130.8, 128.7, 128.6,
128.6, 127.6, 126.9, 123.4, 121.2, 112.3, 77.4, 69.0; HRMS
(ESI) m/z [M + H]+ calcd for C35H23O6 [M + H]+ 539.1489,
found 539.1489.
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis((4-chlorophenyl)-
methanone) (3g): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
1
10:1), 49 mg (26% yield), mp 123−125 °C; H NMR (400
MHz, CDCl3, TMS) δ 8.38 (d, J = 7.6 Hz, 1H), 7.58 (d, J =
8.0 Hz, 1H), 7.51−7.47 (m, 1H), 7.44−7.40 (m, 1H), 7.35−
7.33 (m, AA′BB′ system, 4H), 7.29−7.26 (m, 4H), 7.17−7.15
(m, 6H), 7.10−7.08 (m, AA′BB′ system, 4H), 5.21 (s, 1H),
4.59 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.2,
187.4, 146.3, 145.0, 140.3, 138.4, 136.8, 135.0, 133.8, 131.4,
130.8, 129.2, 129.1, 128.9, 128.9, 127.9, 127.3, 123.7, 77.8,
69.1; HRMS (ESI) m/z [M + H]+ calcd for C39H25Cl2O4 [M +
H]+ 627.1124, found 627.1130.
(5-Hydroxy-7,10-bis(4-methoxyphenyl)-9-oxo-8,9-dihy-
dro-5H-5,8-ethenobenzo[7]annulene-6,11-diyl)bis-
(phenylmethanone) (3l): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 5:1), 152 mg (82% yield), mp 107−109 °C; 1H
NMR (400 MHz, CDCl3, TMS) δ 8.34 (d, J = 7.6 Hz, 1H),
7.58 (d, J = 8.0 Hz, 1H), 7.46−7.42 (m, 5H), 7.39−7.29 (m,
3H), 7.24−7.22 (m, AA′BB′ system, 4H), 7.14−7.10 (m, 4H),
6.66−6.64 (m, AA′BB′ system, 4H), 5.18 (s, 1H), 4.70 (s,
1H), 3.65 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.9,
187.9, 160.1, 147.0, 143.9, 138.0, 136.8, 133.6, 133.5, 131.1,
129.5, 129.5, 129.4, 128.6, 128.5, 127.5, 123.6, 114.0, 77.9,
69.6, 55.0; HRMS (ESI) m/z [M + H]+ calcd for C41H31O6
[M + H]+ 619.2115, found 619.2128.
(5-Hydroxy-9-oxo-7,10-di-p-tolyl-8,9-dihydro-5H-5,8-
etheno-benzo[7]annulene-6,11-diyl)bis((4-bromophenyl)-
methanone) (3h): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate =
1
13:1), 48 mg (21% yield), mp 114−116 °C; H NMR (400
MHz, CDCl3, TMS) δ 8.38 (d, J = 8.0 Hz, 1H), 7.58 (d, J =
7.6 Hz, 1H), 7.51−7.48 (m, 1H), 7.44−7.40 (m, 1H), 7.28−
6760
https://doi.org/10.1021/acs.joc.1c00487
J. Org. Chem. 2021, 86, 6755−6764

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(5-Hydroxy-9-oxo-7,10-diphenyl-8,9-dihydro-5H-5,8-ethe-
no-benzo[7]annulene-6,11-diyl)bis(phenylmethanone)
(3m): yellow solid, obtained in 3 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate
= 5:1), 108 mg (64% yield), mp 167−169 °C; 1H NMR (400
MHz, CDCl3, TMS) δ 8.38 (d, J = 8.0 Hz, 1H), 7.60 (d, J =
7.6 Hz, 1H), 7.49−7.37 (m, 6H), 7.33−7.26 (m, 6H), 7.15−
7.10 (m, 10H), 5.23 (s, 1H), 4.68 (s, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 197.5, 187.7, 146.5, 145.4, 138.1, 137.1,
136.7, 133.7, 133.6, 131.3, 129.5, 128.9, 128.8, 128.7, 128.5,
128.0, 127.4, 123.7, 77.9, 69.2; HRMS (ESI) m/z [M + H]+
calcd for C39H27O4 [M + H]+ 559.1904, found 559.1913.
(7,10-Bis(4-chlorophenyl)-5-hydroxy-9-oxo-8,9-dihydro-
5H-5,8-ethenobenzo[7]annulene-6,11-diyl)bis-
(phenylmethanone) (3n): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 20:1), 185 mg (98% yield), mp 209−211 °C;
1H NMR (400 MHz, CDCl3, TMS) δ 8.38 (d, J = 8.0 Hz, 1H),
7.57 (d, J = 8.0 Hz, 1H), 7.51−7.47 (m, 1H), 7.42−7.35 (m,
7H), 7.26−7.22 (m, 4H), 7.17−7.11 (m, 8H), 5.08 (s, 1H),
4.57 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.2,
187.4, 146.1, 136.5, 136.4, 135.4, 135.1, 134.1, 133.8, 131.4,
129.5, 129.3, 129.0, 128.7, 127.3, 123.9, 77.9, 68.9; HRMS
(ESI) m/z [M + Na]+ calcd for C39H24Cl2NaO4 [M + Na]+
649.0944, found 649.0945.
5-Hydroxy-7-(4-methoxyphenyl)-9-oxo-10-phenyl-8,9-
diydro-5H-5,8-ethe-nobenzo[7]annulene-6,11-diyl)bis-
(phenylmethane) (3p): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 5:1), 126 mg (71% yield), mp 112−114 °C; 1H
NMR (400 MHz, CDCl3, TMS) δ 8.36 (d, J = 7.6 Hz, 1H),
7.60 (d, J = 8.0 Hz, 1H), 7.46−7.44 (m, 5H), 7.40−7.37 (m,
1H), 7.31−7.23 (m, 6H), 7.14−7.11 (m, 7H), 6.66 (d, J = 8.4
Hz, 2H), 5.20 (s, 1H), 4.69 (s, 1H), 3.66 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 197.9, 197.5, 187.8, 160.2, 146.8,
145.6, 143.8, 138.1, 138.0, 137.1, 136.8, 133.7, 133.6, 131.2,
129.6, 129.5, 129.4, 128.8, 128.7, 128.7, 128.5, 128.5, 128.0,
127.5, 123.7, 114.0, 77.9, 69.4, 55.0; HRMS (ESI) m/z [M +
Na]+ calcd for C40H28NaO5[M + Na]+ 611.1829, found
611.1838.
5-Hydroxy-9-oxo-7-phenyl-10-(p-tolyl)-8,9-dihydro-5H-
5 , 8 - e t h e n o b e n z o [ 7 ] a n n u l e n e - 6 , 1 1 - d i y l ) b i s -
(phenylmethanone) (3q): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 10:1), 135 mg (79% yield), mp 111−113 °C;
1H NMR (400 MHz, CDCl3, TMS) δ 8.37 (d, J = 7.6 Hz, 1H),
7.60−7.58 (m, AA′ part of AA′BB′ system, 2H), 7.47−7.44
(m, 5H), 7.40−7.36 (m, 1H), 7.32−7.26 (m, 4H), 7.20−7.18
(m, AA′ part of AA′BB′ system, 2H), 7.15−7.10 (m, 7H),
6.95−6.93 (m, AA′ part of AA′BB′ system, 2H), 5.21 (s, 1H),
4.66 (s, 1H), 2.17 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 197.7, 197.6, 187.8, 146.7, 145.4, 144.6, 139.0, 138.2, 138.1,
137.1, 136.8, 136.8, 134.1, 133.7, 133.6, 133.6, 131.2, 129.6,
129.5, 129.4, 128.8, 128.7, 128.7, 128.5, 128.0, 128.0, 127.5,
123.7, 77.9, 69.3, 20.8; HRMS (ESI) m/z [M + Na]+ calcd for
C40H28NaO4 [M + Na]+ 595.1880, found 595.1891.
7.59 (d, J = 7.6 Hz, 1H), 7.50−7.47 (m, 1H), 7.43−7.36 (m,
5H), 7.31−7.26 (m, 5H), 7.17−7.09 (m, 10H), 5.22 (s, 1H),
4.64 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.6,
196.1, 187.5, 146.4, 145.4, 145.0, 140.3, 138.5, 138.1, 137.0,
136.9, 136.6, 135.1, 133.8, 133.7, 131.3, 130.8, 129.5, 129.1,
128.9, 128.8, 128.7, 128.5, 128.0, 127.9, 127.4, 123.7, 77.8,
69.2; HRMS (ESI) m/z [M + Na]+ calcd for C39H25ClNaO4
[M + Na]+ 615.1334, found 615.1345.
6-Benzoyl-5-hydroxy-11-(4-methylbenzoyl)-10-phenyl-7-
(p-tolyl)-5H-5,8-ethenobenzo[7]annulene-9(8H)-one (3s):
yellow solid, obtained in 3 h and purified by chromatography
on silica gel (petroleum ether/ethyl acetate = 10:1), 146 mg
1
(83% yield), mp 134−136 °C; H NMR (400 MHz, CDCl3,
TMS) δ 8.37 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H),
7.47−7.43 (m, 3H), 7.39−7.26 (m, 6H), 7.20−7.11 (m, 7H),
6.94−6.91 (m, 4H), 5.21 (s, 1H), 4.59 (s, 1H), 2.21 (s, 3H),
2.17 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.7,
197.1, 187.9, 146.6, 145.6, 144.8, 144.7, 138.9, 138.1, 137.4,
137.2, 136.8, 134.3, 134.2, 133.6, 133.5, 131.2, 129.7, 129.6,
129.4, 129.3, 128.7, 128.7, 128.5, 128.0, 128.0, 127.5, 123.7,
77.9, 69.2, 21.3, 20.8; HRMS (ESI) m/z [M + Na]+ calcd for
C41H30NaO4 [M + Na]+ 609.2036, found 609.2048.
5-Hydroxy-7-(4-methoxyphenyl)-9-oxo-10-(p-tolyl)-8,9-di-
hydro-5H-5,8-ethenobenzo[7]annulene-6,11-diyl)bis-
(phenylethaneone) (3t): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 5:1), 149 mg (83% yield), mp 125−127 °C; 1H
NMR (400 MHz, CDCl3, TMS) δ 8.35 (d, J = 8.0 Hz, 1H),
7.58 (d, J = 7.6 Hz, 1H), 7.47−7.45 (m, 5H), 7.39−7.30 (m,
3H), 7.26−7.10 (m, 8H), 6.95−6.93 (m, AA′ part of AA′BB′
system, 2H), 6.66−6.64 (m, BB′ part of AA′BB′ system, 2H),
5.19 (s, 1H), 4.67 (s, 1H), 3.65 (s, 3H), 2.17 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 197.9, 197.7, 187.9, 160.1, 146.9,
144.7, 143.8, 138.9, 138.2, 138.0, 136.8, 134.2, 133.6, 133.6,
133.5, 131.1, 129.6, 129.5, 129.4, 128.6, 128.5, 128.5, 128.0,
127.5, 123.6, 114.0, 77.9, 69.5, 55.0, 20.8; HRMS (ESI) m/z
[M + Na]+ calcd for C41H30NaO5 [M + Na]+ 625.1985, found
625.1992.
6-Benzoyl-5-hydroxy-7,10-di-p-tolyl-11-(1-tosyl-1H-pyr-
role-2-carbonyl)-5,8-dihdro-9H-5,8-ethenobenzo[7]-
annulen-9-one (3u): yellow solid, obtained in 3 h and purified
by chromatography on silica gel (petroleum ether/ethyl acetate
1
= 3:1), 165 mg (76% yield), mp 171−173 °C; H NMR (400
MHz, CDCl3, TMS) δ 8.15 (d, J = 7.6 Hz, 1H), 7.79−7.77 (m,
AA′ part of AA′BB′ system, 2H), 7.38−7.33 (m, 2H), 7.28−
7.25 (m, 3H), 7.20−7.10 (m, 4H), 7.05−7.03 (m, AA′ part of
AA′BB′ system, 2H), 6.99−6.95 (m, 4H), 6.83−6.81 (m, AA′
part of AA′BB′ system, 2H), 6.77−6.75 (m, BB′ part of
AA′BB′ system, 2H), 5.66 (s, 2H), 5.00 (s, 1H), 4.40 (s, 1H),
2.29 (s, 3H), 2.08 (s, 3H), 2.00 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 197.0, 187.9, 183.7, 146.8, 145.6, 145.3, 143.4,
140.4, 139.0, 138.7, 136.8, 136.6, 135.9, 134.2, 134.0, 133.7,
133.5, 133.4, 131.1, 131.0, 129.6, 129.5, 129.4, 128.9, 128.6,
128.5, 128.2, 127.8, 127.4, 127.0, 123.8, 110.6, 77.7, 69.2, 21.4,
20.9, 20.8; HRMS (ESI) m/z [M + Na]+ calcd for
C46H35NNaO6S [M + Na]+ 752.2071, found 752.2082.
5-Hydroxy-9-oxo-7-phenyl-10-(p-tolyl)-8,9-dihydro-5H-
5 , 8 - e t h e n o b e n z o [ 7 ] a n n u l e n e - 6 , 1 1 - d i y l ) b i s -
(phenylmethanone) (3v): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 10:1), 147 mg (85% yield), mp 122−124 °C;
1H NMR (400 MHz, CDCl3, TMS) δ 8.37 (d, J = 8.0 Hz, 1H),
7.59 (d, J = 7.6 Hz, 1H), 7.47−7.44 (m, 5H), 7.40−7.36 (m,
7-(4-Chlorophenyl)-5-hydroxy-9-oxo-10-phenyl-8,9-dihy-
dro-5H-5,8-etheno-benzo[7]annulene-6,11-diyl)bis-
(phenylmethanone) (3r): yellow solid, obtained in 3 h and
purified by chromatography on silica gel (petroleum ether/
ethyl acetate = 10:1), 156 mg (88% yield), mp 131−133 °C;
1H NMR (400 MHz, CDCl3, TMS) δ 8.38 (d, J = 7.6 Hz, 1H),
6761
https://doi.org/10.1021/acs.joc.1c00487
J. Org. Chem. 2021, 86, 6755−6764

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Authors
Yuanyang Mu − School of Chemistry and Molecular
1H), 7.32−7.28 (m, 4H), 7.20−7.18 (m, AA′ part of AA′BB′
system, 2H), 7.14−7.09 (m, 7H), 6.95−6.93 (m, AA′ part of
AA′BB′ system, 2H), 5.21 (s, 1H), 4.67 (s, 1H), 2.16 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 197.7, 197.6, 187.8,
146.6, 145.4, 144.6, 138.9, 138.2, 138.1, 137.1, 136.8, 136.8,
134.1, 133.7, 133.6, 133.6, 131.2, 129.5, 129.5, 129.4, 128.8,
128.7, 128.7, 128.5, 128.0, 128.0, 127.5, 123.7, 77.9, 69.3, 20.8;
HRMS (ESI) m/z [M + Na]+ calcd for C40H28NaO4 [M +
Na]+ 595.1880, found 595.1887.
Engineering, East China Normal University, Shanghai
200241, China; orcid.org/0000-0002-0333-3025
Qiyi Yao − School of Chemistry and Molecular Engineering,
East China Normal University, Shanghai 200241, China
Liqiang Yin − School of Chemistry and Molecular Engineering,
East China Normal University, Shanghai 200241, China
Siyi Fu − School of Chemistry and Molecular Engineering, East
China Normal University, Shanghai 200241, China
Mengdan Wang − School of Chemistry and Molecular
Engineering, East China Normal University, Shanghai
200241, China; orcid.org/0000-0002-9840-5924
Yang Yuan − School of Chemistry and Molecular Engineering,
East China Normal University, Shanghai 200241, China;
orcid.org/0000-0002-7028-3646
5-Methylene-8,10-bis(1-phenylvinyl)-7,11-di-p-tolyl-6,9-
dihydro-5H-6,9-ethenob-enzo[7]annulen-9-ol (5a): white
1
solid (90 mg, 78% yield), mp 87−89 °C; H NMR (600
MHz, CDCl3, TMS) δ 7.85 (d, J = 7.8 Hz, 1H), 7.28−7.25 (m,
9H), 7.18 (s, 7H), 7.05 (d, J = 7.8 Hz, 5H), 5.73 (s, 1H), 5.56
(s, 2H), 5.04 (s, 1H), 4.82 (s, 2H), 4.63 (s, 1H), 2.45 (s, 1H),
2.32 (s, 6H); 13C{1H} NMR (150 MHz, CDCl3) δ 146.1,
144.4, 140.8, 139.9, 138.7, 136.7, 136.4, 130.7, 128.6, 128.0,
127.5, 127.1, 126.9, 126.7, 126.5, 123.5, 116.3, 110.4, 77.3,
61.2, 21.1; HRMS (ESI) m/z [M + Na]+ calcd for C44H36NaO
[M + Na]+ 603.2658, found 603.2658.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00487
Notes
The authors declare no competing financial interest.
(5-Methoxy-9-oxo-7,10-di-p-tolyl-8,9-dihydro-5H-5,8-
ethenobenzo[7]annulene-6,11-diyl)bis(phenylmethanone)
1
ACKNOWLEDGMENTS
(5q): white solid (100 mg, 86% yield), mp 138−140 °C; H
■
NMR (600 MHz, CDCl3, TMS) δ 8.21 (d, J = 7.8 Hz, 1H),
7.62 (d, J = 7.2 Hz, 1H), 7.52−7.50 (m, 4H), 7.43−7.37 (m,
2H), 7.31−7.28 (m, 4H), 7.23−7.21 (m, AA′ part of AA′BB′
system, 2H), 7.18−7.10 (m, 7H), 7.00−6.99 (m, AA′ part of
AA′BB′ system, 2H), 5.12 (s, 1H), 3.40 (s, 3H), 2.21 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3) δ 195.1, 194.7, 185.5,
147.4, 145.0, 144.5, 140.4, 140.1, 138.6, 136.5, 136.4, 136.3,
133.5, 132.9, 132.8, 132.7, 130.4, 129.2, 129.1, 128.6, 128.4,
128.1, 128.0, 127.9, 126.3, 124.1, 83.6, 70.1, 55.3, 21.0; HRMS
(ESI) m/z [M + Na]+ calcd for C41H30NaO4 [M + Na]+
609.2036, found 609.2051.
We thank the National Natural Science Foundation of China
(21871087) and the Natural Science Foundation of Shandong
Province (ZR2020QB013) for financial support.
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ASSOCIATED CONTENT
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sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00487.
Experimental details and spectroscopic characterization
of all new compounds (PDF)
Accession Codes
CCDC 1955910 (3a) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
CambridgeCB2 1EZ, UK; fax: + 44 1223 336033.
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AUTHOR INFORMATION
■
Corresponding Authors
Lingkai Kong − School of Chemistry and Chemical
Engineering, Linyi University, Linyi, Shandong 276000,
China; orcid.org/0000-0003-4162-2837;
Email: konglingkai@lyu.edu.cn
Yanzhong Li − School of Chemistry and Molecular
Engineering, East China Normal University, Shanghai
200241, China; orcid.org/0000-0002-2898-3075;
Email: yzli@chem.ecnu.edu.cn
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