Gold-catalyzed tandem Diels-Alder reactions of enynals/enynones with alkenes: Generation and trapping of cyclic o-QDMs

Article abstract of DOI:10.1039/c4ob00321g

An efficient gold-catalyzed method to generate the highly reactive cyclic o-QDM species from the enynal/enynone and alkene is reported. This method allows rapid access to a variety of structurally unique propeller-like products through tandem Diels-Alder reactions. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00321g

Volume 12 Number 24 28 June 2014 Pages 4033–4266
Organic &
Biomolecular
Chemistry
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ISSN 1477-0520
PAPER
Shifa Zhu et al.
Gold-catalyzed tandem Diels–Alder reactions of enynals/enynones with
alkenes: generation and trapping of cyclic o-QDMs

Organic &
Biomolecular Chemistry
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PAPER
Gold-catalyzed tandem Diels–Alder reactions of
enynals/enynones with alkenes: generation and
trapping of cyclic o-QDMs†
Cite this: Org. Biomol. Chem., 2014,
12, 4104
Shifa Zhu,* Lang Hu and Huanfeng Jiang
Received 12th February 2014,
Accepted 18th February 2014
An efficient gold-catalyzed method to generate the highly reactive cyclic o-QDM species from the
enynal/enynone and alkene is reported. This method allows rapid access to a variety of structurally unique
propeller-like products through tandem Diels–Alder reactions.
DOI: 10.1039/c4ob00321g
www.rsc.org/obc
derivatives as the substrates, which severely limited the
applications.
Introduction
Recently, we reported an efficient gold-catalyzed reaction of
Mechanically speaking, the cyclic-o-QDM intermediate is an
enynal/enynone with norbornenes to synthesize of a variety of electronic-rich diene. It would react with electron-deficient
structurally symmetrical propeller-like molecules (Scheme 1, dienophiles more easily than norbornene. Therefore, if an elec-
path a).1 This reaction was believed to proceed through the tron-deficient alkene or alkyne was added as the dienophile
gold-catalyzed tandem Diels–Alder reactions via trapping of for the cyclic-o-QDM intermediate, a three-component reaction
the key intermediate cyclic o-quinodimethane (cyclic-o- may be realized. Thus, the structurally nonsymmetrical propel-
QDM),1,2
a highly reactive species. However, this two- ler-like product would be formed (Scheme 1, path b). In this
component reaction occurred only with the norbornene paper, we would like to report the results of our investigations.
Results and discussion
Initial efforts were made to systematically investigate various
catalytic reaction conditions for the reaction of enynal 1a, nor-
bornene 2a and 1,4-benzoquinone 3a (electron-deficient dieno-
phile). By following the conditions reported in our previous
work, different metal salts were then tested (Table 1, entries
1–8). No desired product 4a was detected when AgOTf and
FeCl3 were used as catalysts (entries 1 and 2). Gratifyingly, the
desired product 4a could be obtained in low yields when InCl3,
ZnCl2 and CuCl2·2H2O were used as catalysts (entries 3–5). In
these cases, the product 4a was formed in an endo/exo mixture.
Further screening of the catalysts revealed that KAuCl4·2H2O
can catalyze this reaction leading to 4a as well, although in
only 12% yield (entry 6). N-heterocyclic carbene (NHC)-sup-
ported gold(I) complex (IMes-AuCl) was inefficient for this
transformation (entry 7). Interestingly, a significant positive
Scheme 1 Proposed reaction mechanism.
effect was observed when 15 mol% Selectfluor® was added as
additive.1,3 The yield of 4a was improved to 92% (entry 8).
Such a positive effect was consistent with our previous work,1
School of Chemistry and Chemical Engineering, South China, University of
Technology, Guangzhou City, Guangdong Province 510640, China.
and it was assumed that IMes-AuCl was oxidized into IMes-
E-mail: zhusf@scut.edu.cn; Fax: +86-20-87112906
†Electronic supplementary information (ESI) available: Experimental procedure
AuIII in situ. Based on the results above, three other NHC-AuCl/
Selectfluor® combinations were then investigated as well
and spectral data. CCDC 983251–983252. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c4ob00321g
(entries 9–11). Among four different NHC-AuCl complexes
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Table 1 Optimization of reaction conditionsa
Table 2 Substrate scopea
Entry
Catalyst
Additive
Yieldb (4a)
endo/exoc
1
2
AgOTf
FeCl3
—
—
ND
ND
ND
ND
3
4
5
6
7
8
9
10
11
12d
13e
14f
15
16
InCl3
ZnI2
—
—
—
—
22%
51%
35%
12%
ND
92%
97%
74%
43%
15%
73%
71%
35%
ND
2.7/1.0
4.6/1.0
5.9/1.0
ND
CuCl2·2H2O
KAuCl4·2H2O
IMes-AuCl
IMes-AuCl
SIMes-AuCl
IPr-AuCl
SIPr-AuCl
SIMes-AuCl
SIMes-AuCl
SIMes-AuCl
Ph3P-AuCl
—
—
ND
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
3.1/1.0
3.7/1.0
8.3/1.0
5.6/1.0
1.9/1.0
8.3/1.0
3.1/1.0
6.1/1.0
ND
a Unless otherwise noted, the reaction was performed at 80 °C for 24 h
using 5 mol% catalyst and 15% additive under N2, 1a : 2a : 3a = 1 : 5 : 2
[1a]
= 0.25 M, IMes: 1,3-dimesitylimidazol-2-ylidene; SIMes: 1,3-
dimesitylimidazolin-2-ylidene; IPr: 1,3-bis(2,6-diisopropylphenyl)-
imidazol-2-ylidene; SIPr: 1,3-bis(2,6-diisopropylphenyl)imidazolin-
2-ylidene. b NMR yield. c Determined by 1H NMR. d Room temp.
e 100 °C. f 1a : 2a : 3a = 1 : 5 : 1.
Scheme 2 Oxidation of 1,4-dione 4a to 1,4-benzoquinone 5a.
being tested, SIMes-AuCl functioned better than the other
three (entries 8–11). The yield of 4a was enhanced to 97% for
the combination of SIMes-AuCl/Selectfluor® (entry 9). Lower
temperature (entry 12: room temp.) or higher temperature
(entry 13: 100 °C) resulted in inferior results. The yield of 4a
dropped to 71% when the amount of 1,4-benzoquinone 3a was
decreased to 1.0 equivalent (entry 14). Furthermore, the yield
was only 35% when Ph3P-AuCl was used as catalyst instead
(entry 15). The reaction did not occur without the gold catalyst
(entry 16). It is worth noting that in all cases, the product 4a
was obtained in mixtures of endo/exo isomers. Interestingly,
the cyclohexene-1,4-dione 4a could be oxidized into 1,4-benzo-
quinone 5a quickly upon purification on silica gel (Scheme 2).
a The reaction was performed at 80 °C for 24 h using 5 mol% catalyst
and 15% additive under N2; 1 : 2 : 3 = 1 : 5 : 2; [1] = 0.25 M, isolated
yield. b Purified by crystallization. c endo/exo = 7.7/1. d endo/exo > 20/1.
e The stereochemistry was determined by noe.
Both 4a and 5a were confirmed by the X-ray diffraction summarized in Table 2, the catalytic process could be success-
analysis.
fully applied to a variety of enynals/enynones 1, alkenes 2 and
With the optimized reaction conditions (Table 1, entry 9) in 3. For example, in addition to enynal 1a, a variety of enynal or
hand, the substrate scope was then examined in detail. As enynone derivatives could be effectively reacted with norbor-
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nene 2a and 1,4-benzoquinone 3a as well (Table 2, 5a–5m).
The enynals substituted with electron-donating groups gave
higher yields (5a–5e: 63%–97%) than those with electron-with-
drawing groups (5f–5h: 32%–63%). For example, CF3-substi-
tuted enynal gave the corresponding product 5h only in 32%
yield. It is worth mentioning that hydroquinones were
obtained instead in the cases of 5b, and 5f. For the enynals
bearing alkyl alkyne or cyclopropyl alkyne, the reactions
proceed smoothly as well (5i, 5j). The reaction functioned par-
ticularly efficiently for the cyclopropyl-substituted enynal,
giving the corresponding product 5j in 85% yield. Further-
more, the 1,4-benzoquinone 5k with a free formyl group could
be obtained in 62% yield when the enynal with a terminal
alkyne was used as the substrate. In addition to the enynals,
enynones can serve as efficient substrates as well (4l, 5m). For
example, both the methyl ketone and phenyl ketone success-
fully furnished the corresponding products 4l and 5m in 80%
and 68% yields, respectively. In addition to the simple norbor-
nene 2a, norbornenes containing an extra exocyclic double
bond or benzonorbornene could be used as potential sub-
strates as well, furnishing the desired products 5n and 5o in
85% and 79% yields. When 2,3-dihydrofuran was used as an
electron-rich alkene, the cyclohexene-1,4-dione 4p was
obtained directly, and no 1,4-benzoquinone was detected.
More interestingly, only the endo adduct isomer was formed.
Styrene derivatives and aliphatic olefins failed to give the
desired products. As for the electron-deficient olefins, the reac-
tion has better substrate scopes. For example, 1,4-naphtho-
quinone can be used to replace 1,4-benzoquinone, and it gave
the corresponding product 5q in 87% yield. Furthermore, a
variety of mono-, di- and tetra-substituted electron-deficient
alkenes can also be used to trap the cyclic-o-QDM intermediate
(5r–5w).
As summarized in Table 2, the alkenes disubstituted or
tetra-substituted with electron-withdrawing groups served as
better dienophiles than the mono-substituted one in trapping
the o-QDM. For example, acrylonitrile gave the product 5r only
in 35% yield, while the free maleimide and its N-protected
derivatives smoothly furnished the desired adducts 5s–5v in
good to excellent yields. Even tetracyanoethylene can be suc-
cessfully applied to produce the product 5w in 80% yield. It is
noteworthy that products 5r–5w were obtained as single
isomers. Dimethyl acetylenedicarboxylate can also be used as
the dienophile, giving the product 5x in 51% yield.
With the nonsymmetrical propeller-like molecules 5 in
hand, especially for those 1,4-benzoquinone derivatives with
the bicyclo[2.2.1]heptane moiety, we then proceeded to study
their potential further chemical transformations (Scheme 3).
Simply refluxing the xylene solutions of 5a or 5q resulted in
the occurrence of the retro-Diels–Alder reaction, whcih furn-
Scheme 3 Further chemical transformation of 5.
diester 5x under the same reaction conditions led to the tri-
substituted naphthalene 6d in quantitative yield.
A plausible mechanism was proposed based on our pre-
vious work (Scheme 1, path b).1 The coordination of the triple
bond of enynal 1 to [Au] enhanced the electrophilicity of
alkyne, and the subsequent nucleophilic attack of the carbonyl
oxygen to the electron-deficient alkyne would form the inter-
mediate pyrylium A.6 A Diels–Alder reaction between pyrylium
A and norbornene 2 followed to furnish the intermediate B.
Then elimination of the catalyst [Au] led to the key intermedi-
ate, cyclic-o-QDM, which was then trapped by the electron-
deficient alkene or alkyne to furnish the product 4 via a
second Diels–Alder reaction.
Conclusions
ished the anthraquinones 6a and 6b in 92% and 80% yields, In summary, we have developed an efficient gold-catalyzed
respectively. Interestingly, when heating the mixture of 5a and method to synthesize a variety of structurally unique propeller-
anthracene, another propeller-like molecule 6c was formed in like molecules. The reaction proceeded through tandem Diels–
72% yield. The resulting anthraquinone is the core structure of Alder reactions via trapping of the cyclic-o-QDM. For those pro-
many naturally occurring and biologically active substances, peller-like products containing a 1,4-benzoquinone moiety, a
such as doxorubicin4 and aklavinone.5 Similarly, heating the retro-Diels–Alder reaction could occur smoothly in refluxing
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xylene, forming anthraquinone derivatives. Owing to the mild Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 203.7, 197.5, 196.9,
reaction conditions and high functional group tolerance, this 141.24, 141.1, 140.8, 137.2, 137.2, 130.1, 128.1, 127.8, 127.3,
system holds considerable potential in the synthesis of structu- 127.2, 127.0, 125.5, 57.0, 52.2, 50.9, 49.1, 48.6, 44.6, 41.2, 38.8,
rally interesting propeller-like molecules and bioactive anthra- 33.5, 31.1, 30.2; HRMS (MALDI-FTMS): calcd for C28H24O3Na+
quinone molecules.
[M + Na+] = 431.1618; found = 431.1622.
9-Benzoyl-octahydro-9,10-[2]bicycloanthracene-1,4-dione (5a).
Yellow solid; mp 221 °C; yield: 99.0%; IR (KBr): 3681, 2944,
2879, 1688, 1656, 1583, 1463, 1305, 1241, 833, 767, 734, 693,
473; 1H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 7.49 (s, 1H),
7.37 (t, J = 7.3 Hz, 1H), 7.26 (d, J = 7.3 Hz, 1H), 7.15 (t, J = 7.4
Hz, 2H), 6.95 (t, J = 7.5 Hz, 3H), 6.68 (d, J = 7.7 Hz, 1H), 6.60
(d, J = 10.1 Hz, 1H), 6.41 (d, J = 10.1 Hz, 1H), 4.66 (d, J = 2.3
Hz, 1H), 2.35 (s, 1H), 2.22 (d, J = 8.5 Hz, 1H), 1.88 (s, 1H), 1.66
(d, J = 6.8 Hz, 1H), 1.39–1.30 (m, 2H), 1.14 (d, J = 6.4 Hz, 1H),
0.95 (d, J = 7.4 Hz, 1H), 0.15 (d, J = 10.8 Hz, 1H), −1.23 (d, J =
10.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 197.2, 183.3, 183.2,
148.9, 148.9, 139.3, 137.8, 137.0, 136.4, 135.1, 132.3, 127.2,
126.4, 126.3, 124.8, 77.3, 77.0, 76.7, 59.1, 51.0, 49.6, 42.2, 39.5,
38.5, 32.3, 31.1, 30.7, 29.7. HRMS (MALDI-FTMS): calcd for
C28H22O3Na+ [M + Na+] = 429.1461; found = 429.1472.
Experimental
General information
Unless specified, all reactions were carried out under an inert
atmosphere of nitrogen in Schlenk tubes with dry solvents,
using anhydrous conditions unless otherwise stated. 1,2-
Dichloroethane (DCE) was distilled over calcium hydride
under nitrogen prior to use. Acetonitrile (CH3CN), dichloro-
methane (CH2Cl2), tetrahydrofuran (THF), toluene and triethyl-
amine (NEt3) were distilled under nitrogen prior to use by
standard methods. NHC-Au catalysts were prepared as
described in the literature.1 Unless otherwise stated, other
reagents were used as received from commercial sources.
Melting points were recorded on a BUCHI Melting Point
B-545 apparatus and were uncorrected. NMR spectra were
recorded on a Bruker Avance III 400 MHz spectrometer in
deuterated chloroform (CDCl3) solutions, with residual chloro-
1,4-Dihydroxy-7-methyl-octahydro-9,10-[2]bicycloanthracen-
9-yl)(phenyl)methanone (5b). Yellow solid; mp 164.8 °C;
yield: 83.5%; IR (KBr): 3873, 2949, 2875, 2359, 1744,
1
1662, 1492, 1252, 1081, 1031, 869, 807, 694, 575, 478; H NMR
form (δ 7.26 ppm for H NMR and δ 77.00 ppm for 13C NMR)
1
(400 MHz, CDCl3) δ 7.74 (s, 1H), 7.34 (t, J = 7.4 Hz, 1H), 7.17
(d, J = 10.7 Hz, 2H), 7.08 (d, J = 7.5 Hz, 1H), 6.84 (t, J = 6.8 Hz,
1H), 6.50 (d, J = 8.5 Hz, 1H), 6.34 (s, 1H), 6.24 (d, J = 8.5 Hz,
1H), 5.14 (s, 1H), 4.59 (dd, J = 11.7, 2.4 Hz, 1H), 2.29 (d, J =
8.5 Hz, 1H), 2.10 (s, 1H), 1.94 (s, 1H), 1.81 (s, 1H), 1.66–1.57
(m, 1H), 1.26 (dd, J = 11.7, 8.6 Hz, 1H), 1.10 (d, J = 10.7 Hz,
1H), 0.90 (t, J = 7.8 Hz, 1H), 0.11 (d, J = 10.6 Hz, 1H), −1.07 (d,
J = 10.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 200.31, 143.27,
142.47, 139.24, 138.35, 136.72, 133.72, 131.30, 130.82, 130.26,
taken as the internal standard, and were reported in parts per
million (ppm). The following abbreviations were used to
explain the multiplicities: s = singlet, d = doublet, t = triplet, q
= quartet, m = multiplet, br = broad. Infrared (IR) spectra were
recorded on a Nicolet 210 spectrophotometer.
Typical procedure for gold-catalyzed tandem reaction of
enynals/enynones with norbornene (NB) and benzoquinone
To a solution of the catalyst combination of SIMes-AuCl 127.96, 127.32, 126.58, 125.86, 123.26, 115.18, 113.61,
(2.70 mg, 0.005 mmol) and Selectfluor® (5.30 mg, 113.53, 59.50, 58.29, 50.10, 48.81, 40.87, 38.77, 37.50, 31.59,
0.015 mmol) in DCE (1 mL, 0.1 M) was added the corres- 30.17, 20.34, 20.00, 13.16. HRMS (MALDI-FTMS): calcd for
ponding enynals/enynones (0.1 mmol) with norbornene (NB, C29H26O3Na+ [M + Na+] = 445.1774; found = 445.1786.
47.10 mg, 0.5 mmol) and benzoquinone (21.60 mg, 0.2 mmol).
9-Benzoyl-6-methoxy-octahydro-9,10-[2]bicycloanthracene-
The reaction mixture was stirred under nitrogen atmosphere at 1,4-dione (5c). Yellow solid; mp 200.8 °C; yield: 76.0%;
80 °C for 24 hours. The reaction afforded the crude unstable IR (KBr): 2880, 2359, 1734, 1689, 1655, 1585, 1488, 1303,
1,4-dione 4, which could be purified by recrystallization. The 1249, 1144, 1037, 832, 695; 1H NMR (400 MHz, CDCl3)
crude mixture of the initially formed unstable 1,4-dione 4 was δ 8.31 (s, 1H), 7.45 (s, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.00 (s, 2H),
filtered through a short silica plug, then the solvent was evap- 6.82 (d, J = 2.4 Hz, 1H), 6.60 (d, J = 10.1 Hz, 1H), 6.54 (d, J =
orated under reduced pressure and the residue was purified by 8.5 Hz, 1H), 6.47 (dd, J = 8.5, 2.4 Hz, 1H), 6.41 (d, J = 10.1 Hz,
flash chromatography on silica gel to afford the product 5.
1H), 4.65 (s, 1H), 4.59 (d, J = 2.4 Hz, 1H), 3.70 (s, 3H), 2.35 (s,
9-Benzoyl-decahydro-9,10-[2]bicycloanthracene-1,4-dione (4a). 1H), 2.19 (d, J = 8.5 Hz, 1H), 1.89 (s, 1H), 1.65 (d, J = 8.3 Hz,
Yellow solid; mp 162 °C; yield: 99.0%; IR (KBr): 3688, 3062, 1H), 1.35 (d, J = 3.2 Hz, 1H), 1.14 (d, J = 6.1 Hz, 1H), 0.93 (t, J =
2949, 2880, 2360, 1647, 1470, 1271, 1093, 767, 699, 645, 520, 8.5 Hz, 1H), 0.20 (d, J = 10.9 Hz, 1H), −1.05 (d, J = 10.9 Hz,
438; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.8 Hz, 1H), 1H); 13C NMR (101 MHz, CDCl3) δ 197.40, 183.41, 183.29,
7.74–7.60 (m, 1H), 7.47–7.33 (m, 2H), 7.17 (td, J = 7.7, 1.3 Hz, 159.00, 149.48, 148.68, 139.33, 136.96, 136.41, 135.07, 132.27,
1H), 7.10 (dt, J = 7.4, 6.0 Hz, 1H), 6.94 (d, J = 7.2 Hz, 1H), 6.32 131.40, 127.14, 111.38, 110.87, 58.59, 55.40, 51.06, 49.65,
(d, J = 10.3 Hz, 1H), 6.24 (d, J = 10.3 Hz, 1H), 4.07 (d, J = 42.42, 39.45, 38.49, 32.56, 30.99, 30.69, 29.70. HRMS (MALDI-
9.8 Hz, 1H), 3.60 (s, 1H), 3.24 (dd, J = 9.8, 1.4 Hz, 1H), 2.35 (d, FTMS): calcd for C29H24O4Na+ [M + Na+] = 459.1569; found =
J = 9.0 Hz, 1H), 2.19–2.05 (m, 1H), 1.96 (s, 1H), 1.38 (d, J = 12.7 459.1576.
Hz, 1H), 1.30 (d, J = 6.7 Hz, 1H), 1.15 (d, J = 10.7 Hz, 1H), 0.42
9-(4-Methylbenzoyl)-decahydro-9,10-[2]bicycloanthracene-
(d, J = 10.1 Hz, 1H), 0.39 (d, J = 10.7 Hz, 1H), −0.01 (d, J = 10.7 1,4-dione (4d). Brown solid; mp 189 °C; yield: 96.0%;
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IR (KBr): 3683, 3620, 2949, 2877, 2358, 1658, 1601, 1464, 127.56, 113.18, 112.96, 112.42, 112.20, 58.68, 50.96, 49.60,
1303, 1246, 1183, 1036, 836, 734, 480; 1H NMR (400 MHz, 42.19, 39.40, 38.51, 32.52, 30.98, 30.66; 19F NMR (376 MHz,
CDCl3) δ 7.95 (d, J = 7.7 Hz, 1H), 7.58 (d, J = 7.9 Hz, 2H), CDCl3) δ −114.82. HRMS (MALDI-FTMS): calcd for C28H21O3F+
7.16 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 7.7 Hz, 1H), 7.06 (t, J = [M + H+] = 425.1548; found = 425.1556.
7.3 Hz, 1H), 6.91 (d, J = 7.2 Hz, 1H), 6.28 (d, J = 10.3 Hz, 1H),
9-Benzoyl-6-(trifluoromethyl)-octahydro-9,10-[2]bicyclo-
6.20 (d, J = 10.3 Hz, 1H), 4.12 (d, J = 9.8 Hz, 1H), 3.58 (s, 1H), anthracene-1,4-dione (5h). Yellow solid; mp 130.3–131.4 °C;
3.23 (d, J = 9.8 Hz, 1H), 2.35 (s, 1H), 2.34 (s, 3H), 2.13 (d, J = yield: 32.3%; IR (KBr): 3328, 2934, 2879, 2358, 1666,
8.9 Hz, 1H), 2.07 (s, 1H), 1.94 (s, 1H), 1.33 (t, J = 10.7 Hz, 2H), 1588, 1500, 1445, 1325, 1245, 1127, 1077, 827, 743, 696;
1.11 (t, J = 8.8 Hz, 1H), 0.96 (t, J = 9.5 Hz, 1H), 0.38 (d, J = 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.52 (s, 2H), 7.40 (t,
10.6 Hz, 1H), −0.01 (d, J = 10.6 Hz, 1H); 13C NMR (101 MHz, J = 7.0 Hz, 1H), 7.23 (d, J = 7.9 Hz, 1H), 7.00 (s, 1H), 6.82 (t, J =
CDCl3) δ 203.25, 197.63, 196.89, 141.28, 140.73, 140.53, 138.23, 15.1 Hz, 2H), 6.64 (d, J = 10.0 Hz, 1H), 6.45 (d, J = 10.2 Hz, 1H),
137.42, 137.25, 128.73, 128.04, 127.23, 126.97, 125.47, 57.03, 4.75 (s, 1H), 2.38–2.25 (m, 2H), 1.94 (s, 1H), 1.72 (d, J = 8.4 Hz,
52.34, 50.98, 49.06, 48.82, 44.57, 41.20, 38.80, 33.55, 31.13, 1H), 1.37 (s, 2H), 1.16 (s, 1H), 0.95 (d, J = 10.8 Hz, 1H), 0.19 (d,
30.24, 21.42.
J = 11.0 Hz, 1H), −1.25 (d, J = 10.7 Hz, 1H); 13C NMR
9-(4-Methoxybenzoyl)-octahydro-9,10-[2]bicycloanthracene- (101 MHz, CDCl3) δ 195.30, 181.98, 181.94, 147.12, 147.06,
1,4-dione (5e). Yellow solid; mp 201.8 °C; yield: 63.7%; 142.18, 137.93, 135.55, 135.45, 134.14, 131.60, 125.61, 122.31,
IR (KBr): 3336, 3064, 2944, 2878, 2359, 1662, 1598, 1498, 122.28, 120.51, 120.48, 58.03, 49.90, 48.43, 41.12, 38.36, 37.48,
1457, 1304, 1252, 1174, 1032, 819, 737, 609; 1H NMR 31.48, 30.04, 29.57; 19F NMR (376 MHz, CDCl3) δ −62.08 (s),
(400 MHz, CDCl3) δ 8.31 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 7.3 Hz, −62.16. HRMS (ESI-MS): calcd for C29H21O3F3Na+ [M + Na+] =
1H), 7.15 (t, J = 7.3 Hz, 1H), 6.97 (t, J = 7.3 Hz, 2H), 6.88 (d, J = 497.1335; found = 497.1352.
7.2 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.60 (d, J = 10.0 Hz, 1H),
9-Hexanoyl-octahydro-9,10-[2]bicycloanthracene-1,4-dione
6.43 (t, J = 10.3 Hz, 2H), 4.65 (s, 1H), 3.74 (s, 3H), 2.34 (s, 1H), (5i). Brown solid; mp 134.1 °C; yield: 41.7%; IR (KBr):
2.21 (d, J = 8.5 Hz, 1H), 1.87 (s, 1H), 1.65 (d, J = 8.5 Hz, 1H), 3328, 2945, 2867, 2357, 1705, 1656, 1462, 1383, 1303,
1
1.33 (t, J = 9.1 Hz, 2H), 1.17 (d, J = 6.3 Hz, 1H), 1.13 (d, J = 1025, 830, 763, 664, 470; H NMR (400 MHz, CDCl3) δ 7.54 (s,
6.8 Hz, 1H), 0.93 (t, J = 8.9 Hz, 1H), 0.13 (d, J = 10.8 Hz, 1H), 1H), 7.26–7.07 (m, 4H), 6.58 (d, J = 10.1 Hz, 1H), 6.52 (d, J =
−1.24 (d, J = 10.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) 10.1 Hz, 1H), 4.52 (d, J = 2.3 Hz, 1H), 2.92–2.72 (m, 1H),
δ 195.97, 183.41, 183.31, 162.59, 148.91, 148.86, 139.45, 2.63–2.48 (m, 1H), 2.22 (s, 1H), 1.97 (s, 1H), 1.91 (s, 3H), 1.80
137.89, 136.50, 134.98, 131.91, 130.61, 130.24, 127.16, 126.48, (s, 1H), 1.54 (d, J = 6.4 Hz, 2H), 1.05 (t, J = 8.3 Hz, 1H), 0.98 (d,
126.37, 124.80, 59.03, 55.36, 50.97, 49.60, 42.18, 39.45, 38.57, J = 6.8 Hz, 1H), 0.85 (t, J = 6.7 Hz, 3H), 0.21 (d, J = 10.4 Hz,
32.35, 31.08, 30.68.
1H), −0.98 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 208.38,
(4-Chlorophenyl)(1,4-dihydroxy-octahydro-9,10-[2]bicyclo- 183.49, 183.28, 151.41, 139.18, 138.15, 136.57, 134.89, 126.90,
anthracen-9-yl)methanone (5f). Brown solid; mp 219.3–221 °C; 126.71, 125.10, 50.51, 50.43, 41.89, 39.50, 38.83, 32.63, 31.83,
yield: 58.3%; IR (KBr): 3856, 2932, 2878, 2360, 1690, 30.94, 30.65, 29.70, 29.13, 24.14, 22.62, 14.12. HRMS (MALDI-
1656, 1584, 1475, 1304, 1240, 1095, 1013, 827, 738, 482; FTMS): calcd for C28H30O3H+ [M + H+] = 415.2268; found =
1H NMR (400 MHz, CDCl3) δ 8.28 (s, 1H), 7.45 (s, 1H), 7.26 (d, 415.2286.
J = 7.4 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H), 6.98 (t, J = 7.6 Hz, 2H),
9-(Cyclopropanecarbonyl)-octahydro-9,10-[2]bicycloanthracene-
6.63 (dd, J = 13.3, 8.9 Hz, 2H), 6.43 (d, J = 10.1 Hz, 1H), 4.67 (s, 1,4-dione (5j). Yellow solid; mp 164.8–166 °C; yield: 85.8%;
1H), 2.33 (s, 1H), 2.21 (d, J = 8.4 Hz, 1H), 1.88 (s, 1H), 1.67 (s, IR (KBr): 3692, 2950, 2358, 1702, 1657, 1577, 1467, 1377,
2H), 1.35 (s, 2H), 0.95 (d, J = 6.2 Hz, 1H), 0.15 (d, J = 10.9 Hz, 1304, 1034, 987, 830, 740, 473; 1H NMR (400 MHz, CDCl3)
1H), −1.24 (d, J = 10.6 Hz, 1H; 13C NMR (101 MHz, CDCl3) δ 7.52 (dd, J = 5.2, 3.4 Hz, 1H), 7.30–7.14 (m, 4H), 6.59
δ 196.07, 183.18, 149.19, 148.47, 138.97, 138.55, 137.89, (q, J = 10.1 Hz, 2H), 4.57 (d, J = 2.5 Hz, 1H), 2.12 (s, 2H), 1.96
136.38, 135.50, 135.20, 127.37, 126.46, 126.26, 124.98, 59.09, (s, 1H), 1.87 (s, 1H), 1.71 (d, J = 8.1 Hz, 1H), 1.57 (s, 1H), 1.34
51.05, 49.59, 42.24, 39.45, 38.50, 32.31, 31.04, 30.65, 29.68. (d, J = 6.6 Hz, 2H), 1.29 (dd, J = 8.7, 3.0 Hz, 2H), 1.13–0.96 (m,
HRMS (MALDI-FTMS): calcd for C28H23O3ClNa+ [M + Na+] = 4H), 0.91 (t, J = 8.7 Hz, 1H), 0.14 (d, J = 10.8 Hz, 1H), −1.08 (d,
465.1228; found = 465.1245.
J = 9.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 207.84, 183.30,
9-Benzoyl-6-fluoro-octahydro-9,10-[2]bicycloanthracene- 183.05, 151.14, 139.43, 138.23, 136.56, 134.97, 127.11, 126.69,
1,4-dione (5g). Yellow solid; mp 220.8 °C; yield: 63.7%; 125.22, 125.07, 50.27, 50.11, 42.08, 39.49, 38.34, 32.34, 30.90,
IR (KBr): 3660, 2937, 2878, 2358, 1687, 1586, 1485, 1385, 30.60, 29.71, 14.01. HRMS (MALDI-FTMS): calcd for
1241, 1144, 1118, 868, 828, 741, 650; 1H NMR (400 MHz, C25H22O3H+ [M + H+] = 371.1642; found = 371.1653.
CDCl3) δ 8.32 (s, 1H), 7.50 (s, 1H), 7.39 (d, J = 7.0 Hz, 1H), 7.00
9-Carbaldehyde-decahydro-9,10-[2]bicycloanthracene-
(d, J = 7.9 Hz, 2H), 6.92 (s, 1H), 6.70–6.58 (m, 3H), 6.44 (d, J = 1,4-dione (5k). Yellow solid; mp 167.1 °C; yield: 62.0%;
9.5 Hz, 1H), 4.64 (s, 1H), 2.35 (s, 1H), 2.21 (d, J = 8.2 Hz, 1H), IR (KBr): 3432, 2928, 2877, 2358, 1714, 1653, 1587, 1465,
1.91 (s, 1H), 1.68 (d, J = 8.4 Hz, 1H), 1.36 (s, 2H), 0.93 (d, J = 1385, 1308, 833, 760, 556, 511, 471; 1H NMR (400 MHz,
11.4 Hz, 1H), 0.22 (d, J = 10.6 Hz, 1H), −1.13 (d, J = 10.5 Hz, CDCl3) δ 10.58 (s, 1H), 7.59–7.35 (m, 2H), 7.29–7.07 (m, 5H),
1H); 13C NMR (101 MHz, CDCl3) δ 196.81, 183.16, 183.14, 6.72 (s, 1H), 6.59 (q, J = 10.1 Hz, 2H), 4.57 (d, J = 2.5 Hz, 1H),
148.96, 148.22, 136.77, 136.44, 135.12, 135.01, 132.44, 127.64, 2.16 (d, J = 8.7 Hz, 1H), 2.04 (s, 1H), 1.93 (s, 1H), 1.83–1.76 (m,
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2H), 1.33 (d, J = 7.0 Hz, 2H), 1.18 (s, 2H), 1.05 (t, J = 8.3 Hz,
5-Benzoyl-tetrahydro-5,12-[1,2]benzeno-6,11-methanotetracene-
1H), 1.00–0.92 (m, 1H), 0.23 (d, J = 10.8 Hz, 1H), −0.83 (d, J = 15,18-dione (5o). Yellow solid; mp 175.8–176 °C; yield:
10.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 198.44, 183.57, 79%; IR (KBr): 3308, 30668, 2933, 2357, 1608, 1589, 1386,
183.23, 151.40, 149.14, 139.51, 137.75, 136.56, 135.79, 135.43, 1241, 1081, 977, 843, 761, 694, 480; 1H NMR (400 MHz, CDCl3)
127.24, 126.89, 125.52, 123.53, 58.78, 48.71, 48.68, 41.93, δ 7.47 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.36
39.51, 37.88, 32.52, 30.79, 30.62. HRMS (ESI-MS): calcd for (d, J = 7.7 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.23 (d, J =
C22H18O3Na+ [M + Na+] = 353.1148; found = 353.1160.
7.1 Hz, 2H), 7.12 (s, 1H), 7.05–7.00 (m, 2H), 6.98 (d, J = 7.0 Hz,
9-Benzoyl-10-methyl-decahydro-9,10-[2]bicycloanthracene-1,4- 2H), 6.94 (d, J = 7.3 Hz, 1H), 6.91 (d, J = 4.2 Hz, 1H), 6.79 (d, J =
dione (4l). Yellow solid; mp 140–141 °C; yield: 80.0%; 7.6 Hz, 1H), 6.56 (d, J = 10.0 Hz, 1H), 6.37 (d, J = 10.1 Hz, 1H),
IR (KBr): 3659, 2959, 2878, 2358, 1673, 1458, 1382, 1259, 4.72 (s, 1H), 3.43 (s, 1H), 2.86 (s, 1H), 2.50 (d, J = 8.3 Hz, 1H),
1097, 863, 766, 700, 657; 1H NMR (400 MHz, CDCl3) δ 8.16 2.01 (d, J = 8.5 Hz, 1H), 0.91 (d, J = 10.3 Hz, 1H), −0.67 (d, J =
(d, J = 7.8 Hz, 1H), 7.78–7.65 (m, 2H), 7.43 (d, J = 7.2 Hz, 10.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 196.95, 183.34,
3H), 7.22 (dd, J = 6.6, 3.9 Hz, 3H), 7.04 (d, J = 7.2 Hz, 1H), 6.24 183.07, 150.77, 150.34, 150.21, 139.67, 138.09, 136.84, 136.37,
(d, J = 10.3 Hz, 1H), 6.03 (d, J = 10.3 Hz, 1H), 4.10 (d, J = 135.03, 132.45, 128.99, 128.41, 128.12, 127.63, 127.30, 127.12,
8.8 Hz, 1H), 3.08 (d, J = 8.8 Hz, 1H), 2.43 (d, J = 8.9 Hz, 1H), 127.02, 126.80, 125.79, 125.49, 125.36, 125.22, 124.17, 121.18,
2.14 (s, 1H), 2.07 (s, 1H), 1.88 (d, J = 8.9 Hz, 1H), 1.47 (s, 3H), 120.54, 120.28, 58.83, 51.93, 50.21, 46.30, 45.38, 41.69,
1.41 (dd, J = 10.6, 7.2 Hz, 2H), 1.10 (d, J = 10.8 Hz, 1H), 1.04 (d, 41.26; HRMS (MALDI-FTMS): calcd for C32H23O3 [M + H+] =
+
J = 10.4 Hz, 1H), 0.40 (d, J = 10.7 Hz, 1H), −0.01 (d, J = 10.6 Hz, 455.1642; found = 455.1640.
1H); 13C NMR (101 MHz, CDCl3) δ 204.42, 197.61, 197.61,
9-Benzoyl-hexahydro-9,10-[2,3]furanoanthracene-1,4-dione
141.54, 141.27, 140.61, 139.33, 136.97, 129.92, 128.17, 127.73, (4p). Green solid; mp 235–236 °C; yield: 45.6%; IR (KBr):
127.12, 127.06, 127.01, 123.24, 57.38, 57.11, 56.89, 52.41, 3308, 30668, 2933, 2357, 1608, 1589, 1386, 1241, 1081, 977,
47.99, 41.63, 39.42, 38.32, 33.80, 31.41, 19.45. HRMS (MALDI- 843, 761, 694, 480; 1H NMR (400 MHz, CDCl3) δ 8.38
FTMS): calcd for C29H26O3H+ [M + H+] = 423.1955; found = (s, 1H), 7.50 (s, 1H), 7.40 (t, J = 7.2 Hz, 1H), 7.32 (d, J =
423.1957.
7.3 Hz, 1H), 7.19 (d, J = 14.8 Hz, 2H), 7.00 (t, J = 7.2 Hz, 2H),
9-Benzoyl-10-phenyl-octahydro-9,10-[2]bicycloanthracene-1,4- 6.80 (d, J = 7.7 Hz, 1H), 6.66 (d, J = 10.1 Hz, 1H), 6.48 (d, J =
dione (5m). Colorless solid; mp 204.7 °C; yield: 68.1%; 10.1 Hz, 1H), 5.04 (d, J = 7.7 Hz, 1H), 4.62 (d, J = 2.6 Hz, 1H),
IR (KBr): 3683, 3291, 3065, 2931, 2338, 1692, 1658, 1554, 3.44 (td, J = 8.4, 4.4 Hz, 1H), 2.67–2.57 (m, 1H), 2.05–1.99 (m,
1296, 1050, 838, 767, 695, 474; 1H NMR (400 MHz, CDCl3) 1H), 1.92–1.84 (m, 1H), 1.54 (d, J = 6.8 Hz, 1H), 1.31–1.22 (m,
δ 8.37 (s, 1H), 7.52 (s, 3H), 7.40 (d, J = 6.5 Hz, 4H), 7.21 2H); 13C NMR (101 MHz, CDCl3) δ 195.50, 183.14, 183.01,
(d, J = 7.8 Hz, 3H), 7.11 (t, J = 7.6 Hz, 2H), 6.98 (t, J = 7.5 Hz, 150.39, 146.67, 138.11, 136.80, 136.66, 136.35, 135.17, 132.48,
1H), 6.77 (d, J = 7.6 Hz, 1H), 6.33 (d, J = 10.0 Hz, 1H), 6.29 (d, 128.33, 127.16, 126.74, 125.25, 83.61, 70.40, 61.82, 45.15,
J = 10.0 Hz, 1H), 2.60 (s, 1H), 2.37 (s, 2H), 2.17 (s, 1H), 42.46, 29.70, 29.42. HRMS (ESI-MS): calcd for C25H20O4Na+
1.44–1.34 (m, 2H), 1.19 (s, 1H), 0.05 (d, J = 10.9 Hz, 1H), −1.58 [M + Na+] = 407.1254; found = 407.1241.
(d, J = 11.1 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 197.27,
5-Benzoyl-hexahydro-5,12-[2]bicyclotetracene-6,11-dione
183.67, 183.19, 151.06, 147.85, 139.68, 139.09, 138.10, 137.34, (5q). Yellow solid; mp 272.6 °C; yield: 86.6%; IR (KBr):
137.06, 134.05, 132.11, 127.04, 126.79, 126.63, 126.39, 125.83, 3068, 2934, 2358, 1732, 1667, 1590, 1462, 1291, 1241, 960,
58.22, 56.27, 54.21, 51.98, 38.63, 38.16, 32.02, 31.02, 30.87. 691, 702, 623, 568; 1H NMR (400 MHz, CDCl3) δ 8.38 (s,
HRMS (MALDI-FTMS): calcd for C34H27O3Na+ [M + H+ + Na+] = 1H), 8.03 (d, J = 7.5 Hz, 1H), 7.67 (d, J = 7.7 Hz, 1H), 7.61 (t, J =
506.1852; found = 506.1866.
7.2 Hz, 1H), 7.54 (d, J = 7.3 Hz, 1H), 7.50 (d, J = 11.8 Hz, 1H),
9-Benzoyl-16-ethylidene-octahydro-9,10-[2]bicycloanthracene- 7.35 (t, J = 7.3 Hz, 1H), 7.29 (d, J = 7.3 Hz, 1H), 7.16 (dd, J =
1,4-dione (5n). Yellow solid; mp 115–116 °C; yield: 85.3%; 15.7, 8.4 Hz, 2H), 6.94 (t, J = 7.4 Hz, 2H), 6.67 (d, J = 7.7 Hz,
IR (KBr): 3131, 2925, 2359, 1732, 1689, 1655, 1560, 1305, 1H), 4.87 (d, J = 2.1 Hz, 1H), 2.40 (s, 1H), 2.33 (d, J = 8.4 Hz,
1240, 1025, 834, 688, 474, 452; 1H NMR (400 MHz, CDCl3) 1H), 1.92 (s, 1H), 1.75 (s, 1H), 1.35 (s, 2H), 1.13 (d, J = 14.3 Hz,
δ 8.34 (s, 1H), 7.47 (s, 1H), 7.36 (s, 1H), 7.26 (d, J = 7.3 Hz, 1H), 0.94 (t, J = 9.2 Hz, 1H), 0.17 (d, J = 10.8 Hz, 1H), −1.18 (d,
1H), 7.16 (dd, J = 13.9, 6.3 Hz, 2H), 6.95 (t, J = 7.4 Hz, J = 10.9 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 197.43, 181.40,
2H), 6.74–6.63 (m, 1H), 6.59 (d, J = 10.0 Hz, 1H), 6.39 (d, J = 181.32, 151.37, 151.02, 139.33, 138.01, 137.24, 133.85, 133.56,
10.0 Hz, 1H), 5.46 (d, J = 6.4 Hz, 1H), 4.69 (s, 1H), 2.84 (s, 1H), 132.52, 132.13, 131.78, 127.16, 126.72, 126.50, 126.30, 126.27,
2.32 (dd, J = 15.2, 6.6 Hz, 1H), 2.02 (s, 1H), 1.92–1.82 (m, 1H), 124.86, 59.44, 51.05, 49.58, 42.58, 39.55, 38.64, 32.40, 31.12,
1.77 (d, J = 7.4 Hz, 1H), 1.58 (d, J = 15.6 Hz, 1H), 1.37 (t, J = 30.71, 29.70. HRMS (MALDI-FTMS): calcd for C32H24O3H+
6.5 Hz, 3H), 0.29 (d, J = 10.7 Hz, 1H), −1.15 (d, J = 9.6 Hz, 1H); [M + H+] = 457.1798; found = 457.1811.
13C NMR (101 MHz, CDCl3) δ 197.02, 183.33, 183.13, 149.05,
10-Benzoyl-octahydro-9,10-ethano-1,4-methanoanthracene-
148.86, 145.06, 139.34, 137.76, 136.94, 136.40, 135.07, 11-carbonitrile (5r). Yellow solid; mp 77–79 °C; yield:
132.31, 127.32, 126.51, 126.45, 124.89, 113.09, 59.08, 50.50, 35.8%; IR (KBr): 2964, 2880, 2358, 1729, 1678, 1587,
49.06, 46.82, 42.15, 39.69, 36.88, 32.76, 13.81; HRMS (MALDI- 1475, 1251, 939, 910, 762, 702, 604, 424; 1H NMR (400 MHz,
FTMS): calcd for C30H25O3 [M + H+] = 433.1789; found = CDCl3) δ 7.82 (d, J = 7.7 Hz, 2H), 7.47 (t, J = 7.3 Hz, 1H), 7.34
+
433.1810.
(t, J = 7.6 Hz, 2H), 7.26 (t, J = 7.3 Hz, 1H), 7.14 (t, J = 6.6 Hz, 2H),
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7.06 (d, J = 7.4 Hz, 1H), 3.28 (dd, J = 11.2, 4.9 Hz, 1H), 3.07 (s, 49.35, 47.98, 46.56, 45.66, 42.04, 41.50, 41.13, 38.53, 33.64,
1H), 2.64 (d, J = 8.6 Hz, 1H), 2.29 (s, 1H), 2.06 (d, J = 2.6 Hz, 30.93, 30.29. HRMS (MALDI-FTMS): calcd for C33H29NO3H+
1H), 2.02 (s, 1H), 1.99 (d, J = 9.3 Hz, 1H), 1.79 (s, 1H), 1.31 (s, [M + H+] = 488.2220; found = 488.2229.
2H), 1.12 (s, 1H), 0.16 (d, J = 10.7 Hz, 1H), −0.95 (d, J =
9-Benzoyl-13-phenyl-octahydro-9,10-[3,4]epipyrrolo-1,4-metha-
10.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 200.83, 141.62, noanthracene-12,14-dione (5v). White solid; mp 167.1 °C;
136.90, 132.68, 129.88, 129.57, 128.46, 128.22, 126.73, 126.29, yield: 60.3%; IR (KBr): 3064, 2950, 2357, 1776, 1708, 1495,
125.38, 120.95, 56.22, 47.99, 47.25, 40.78, 39.31, 38.60, 33.46, 1386, 1231, 1185, 1025, 913, 863, 747, 649, 471; 1H NMR
32.46, 32.40, 31.34, 30.53. HRMS (ESI-MS): calcd for (400 MHz, CDCl3) δ 7.95 (d, J = 7.5 Hz, 1H), 7.61–7.54
C29H24O3Na+ [M + Na+] = 443.1774; found = 443.1784.
(m, 2H), 7.27 (d, J = 8.6 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.09
9-Benzoyl-octahydro-9,10-[3,4]epipyrrolo-1,4-methanoanthra- (d, J = 7.3 Hz, 1H), 7.06 (d, J = 4.7 Hz, 1H), 7.05–6.99 (m, 3H),
cene-12,14-dione (5s). Colorless solid; mp 126–128 °C; 6.93 (d, J = 7.2 Hz, 1H), 6.27–6.13 (m, 2H), 3.79 (d, J = 8.5 Hz,
yield: 89.3%; IR (KBr): 3181, 2949, 2426, 1774, 1712, 1H), 3.45 (s, 1H), 3.04 (dd, J = 8.5, 2.6 Hz, 1H), 2.19 (d, J =
1470, 1347, 1235, 1177, 975, 765, 706, 642, 480; 1H NMR 8.9 Hz, 1H), 2.00 (d, J = 3.1 Hz, 1H), 1.97–1.86 (m, 2H),
(400 MHz, CDCl3) δ 8.11 (d, J = 7.5 Hz, 1H), 7.69 (d, J = 6.8 Hz, 1.34–1.22 (m, 2H), 1.01 (d, J = 11.6 Hz, 1H), 0.94 (d, J =
2H), 7.64 (s, 1H), 7.49–7.37 (m, 3H), 7.26 (d, J = 7.5 Hz, 1H), 10.3 Hz, 1H), 0.33 (d, J = 10.7 Hz, 1H), −0.01 (d, J = 10.6 Hz,
7.19 (t, J = 7.2 Hz, 1H), 7.05 (d, J = 7.0 Hz, 1H), 3.81 (d, J = 1H); 13C NMR (101 MHz, CDCl3) δ 204.47, 176.48, 176.29,
8.6 Hz, 1H), 3.49 (s, 1H), 3.04 (dd, J = 8.6, 2.5 Hz, 1H), 2.22 (d, 140.88, 136.52, 135.08, 131.21, 130.10, 129.02, 128.72, 128.20,
J = 8.8 Hz, 1H), 2.11 (s, 1H), 1.99 (d, J = 7.7 Hz, 2H), 1.50–1.33 127.77, 127.72, 127.64, 127.11, 126.39, 125.96, 55.94, 49.24,
(m, 2H), 1.14 (t, J = 9.8 Hz, 1H), 1.10–0.99 (m, 1H), 0.45 (d, J = 47.68, 46.86, 45.95, 42.08, 41.29, 38.66, 33.87, 30.98, 30.34.
10.7 Hz, 1H), −0.01 (d, J = 10.6 Hz, 1H); 13C NMR (101 MHz, HRMS (MALDI-FTMS): calcd for C32H27NO3H+ [M + H+] =
CDCl3) δ 204.55, 177.21, 176.92, 140.74, 136.17, 134.71, 130.06, 474.2064; found = 474.2066.
128.19, 127.75, 127.69, 127.53, 126.96, 125.94, 55.28, 49.18,
9-Benzoyl-octahydro-9,10-ethano-1,4-methanoanthracene-
47.80, 47.73, 46.98, 41.41, 41.13, 38.53, 33.64, 30.92, 30.27. 11,11,12,12-tetracarbonitrile (5w). Red solid; mp 194.2 °C;
HRMS (MALDI-FTMS): calcd for C26H23NO3H+ [M + H+] = yield: 80.4%; IR (KBr): 3720, 3665, 3070, 2956, 2924, 2359,
398.1751; found = 398.1754.
1716, 1664, 1551, 1456, 1247, 968, 672, 474; 1H NMR
9-Benzoyl-13-methyl-octahydro-9,10-[3,4]epipyrrolo-1,4-methano- (400 MHz, CDCl3) δ 7.96 (d, J = 7.9 Hz, 2H), 7.60 (t, J =
anthracene-12,14-dione (5t). Colorless solid; mp 262.4 °C; 7.4 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.48–7.32 (m, 5H), 3.91 (s,
yield: 80.1%; IR (KBr): 3068, 2749, 2358, 1772, 1698, 1540, 1H), 2.58 (dd, J = 21.6, 9.0 Hz, 2H), 2.26 (d, J = 18.3 Hz, 2H),
1
1439, 1381, 1269, 1234, 973, 762, 653, 462; H NMR (400 MHz, 1.37 (dd, J = 19.5, 8.9 Hz, 3H), 1.06 (d, J = 10.7 Hz, 1H), 0.75 (d,
CDCl3) δ 8.00 (d, J = 7.6 Hz, 1H), 7.68 (dd, J = 7.8, 1.6 Hz, J = 10.8 Hz, 1H), 0.59 (d, J = 10.8 Hz, 1H); 13C NMR (101 MHz,
2H), 7.38 (t, J = 7.2 Hz, 3H), 7.17 (td, J = 7.6, 1.5 Hz, 1H), 7.11 CDCl3) δ 194.86, 135.89, 134.68, 133.45, 131.78, 131.24, 131.12,
(td, J = 7.4, 1.2 Hz, 1H), 6.96 (dd, J = 7.3, 1.1 Hz, 1H), 3.73 129.88, 129.74, 128.27, 128.01, 111.75, 111.59, 110.92,
(d, J = 8.4 Hz, 1H), 3.46 (t, J = 2.5 Hz, 1H), 2.99 (dd, J = 8.4, 110.70, 65.87, 48.71, 48.53, 47.40, 46.41, 41.78, 41.18, 40.83,
2.7 Hz, 1H), 2.33 (s, 3H), 2.21 (d, J = 8.9 Hz, 1H), 2.06 (d, J = 33.73, 30.74, 29.99; HRMS (ESI-MS): calcd for C28H20N4ONa+
3.5 Hz, 1H), 1.98 (dd, J = 11.4, 2.5 Hz, 2H), 1.37 (dtdd, J = 27.2, [M + Na+] = 451.1529; found = 451.1528.
11.6, 7.8, 3.9 Hz, 2H), 1.10 (t, J = 9.9 Hz, 1H), 1.04–0.96
Dimethyl-9-benzoyl-octahydro-9,10-etheno-1,4-methanoanthr-
(m, 1H), 0.40 (d, J = 10.7 Hz, 1H), −0.01 (d, J = 10.7 Hz, 1H); acene-11,12-dicarboxylate (5x). Yellow solid; mp 175.7–177.3 °C;
13C NMR (101 MHz, CDCl3) δ 204.62, 177.26, 177.01, 140.90, yield: 51.2%; IR (KBr): 3825, 3807, 3069, 2956, 2358,
136.17, 134.68, 130.05, 128.17, 127.63, 127.57, 126.79, 2234, 1717, 1667, 1527, 1389, 1203, 950, 673, 612, 461;
125.71, 55.57, 49.29, 47.77, 46.68, 45.83, 41.69, 41.19, 38.56, 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.6 Hz, 2H), 7.41 (t, J =
33.71, 30.93, 30.30, 24.13. HRMS (MALDI-FTMS): calcd for 7.4 Hz, 1H), 7.24 (dd, J = 11.0, 8.6 Hz, 3H), 7.16 (dd, J = 13.3,
C27H25NO3H+ [M + H+] = 412.1907; found = 412.1910.
5.9 Hz, 1H), 7.01–6.96 (m, 1H), 6.75 (d, J = 7.6 Hz, 1H), 4.32
9-Benzoyl-13-benzyl-octahydro-9,10-[3,4]epipyrrolo-1,4-methano- (d, J = 2.5 Hz, 1H), 3.73 (s, 3H), 3.08 (s, 3H), 2.42 (s, 1H), 2.35
anthracene-12,14-dione (5u). Red solid; mp 140.1–143.4 °C; (d, J = 8.5 Hz, 1H), 2.23 (d, J = 3.5 Hz, 1H), 2.19 (s, 1H),
yield: 80%; IR (KBr): 3063, 2948, 2357, 1772, 1700, 1577, 1.86–1.78 (m, 2H), 1.33 (s, 1H), 0.98 (t, J = 9.2 Hz, 1H), 0.13 (d,
1399, 1346, 1234, 1171, 1068, 930, 743, 702, 469. 1H NMR J = 10.8 Hz, 1H), −1.22 (d, J = 10.8 Hz, 1H); 13C NMR
(400 MHz, CDCl3) δ 8.03 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 6.4 Hz, (101 MHz, CDCl3) δ 197.74, 166.18, 165.48, 143.32, 142.30,
2H), 7.38 (t, J = 7.2 Hz, 3H), 7.12–6.95 (m, 5H), 6.88 139.40, 138.60, 135.58, 132.96, 129.95, 128.02, 127.19, 126.29,
(d, J = 7.2 Hz, 1H), 6.55 (d, J = 7.2 Hz, 2H), 4.11 (d, J = 5.0 Hz, 125.46, 124.41, 62.12, 52.50, 51.56, 50.86, 49.57, 47.02, 39.21,
2H), 3.74 (d, J = 8.6 Hz, 1H), 3.46 (s, 1H), 2.99 (dd, J = 8.6, 38.72, 32.20, 31.04, 30.64. HRMS (MALDI-FTMS): calcd for
2.4 Hz, 1H), 2.21 (d, J = 8.9 Hz, 1H), 2.04 (d, J = 3.0 Hz, 1H), C28H26O5Na+ [M + Na+] = 465.1673; found = 465.1684.
1.95 (d, J = 11.6 Hz, 2H), 1.42–1.30 (m, 2H), 1.09 (t, J = 9.9 Hz,
Typical procedure for transformation from 5 to 6
1H), 1.05–0.95 (m, 1H), 0.37 (d, J = 10.6 Hz, 1H), −0.14 (d, J =
10.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 204.71, 176.91, To a solution of xylene (0.5 mL, 0.088 M) was added 5
176.63, 140.91, 136.02, 134.77, 134.57, 129.99, 128.34, 128.18, (18.0 mg, 0.044 mmol). The reaction was stirred under nitro-
127.80, 127.74, 127.70, 127.55, 127.29, 126.79, 125.75, 55.31, gen atmosphere at 170 °C for 6 hours. The solvent was
4110 | Org. Biomol. Chem., 2014, 12, 4104–4111
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removed under vacuum and the residue was purified by (973) (2011CB808600), the Changjiang Scholars and
flash chromatography on silica gel to afford the desired Innovation Team Project of Ministry of Education, SRF for
product 6 (12.7 mg, 92%).
ROCS, State Education Ministry,
Guangdong NSF
9-Benzoylanthracene-1,4-dione (6a). Yellow solid; mp (10351064101000000), and the Fundamental Research Funds
268.9–269.2 °C; isolated yield: 92.0%; IR (KBr): 2921, 2852, for the Central Universities.
2393, 2287, 1667, 1602, 1419, 1230, 1076, 911, 786, 701, 479;
1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 8.08 (d, J = 8.1 Hz,
1H), 7.72 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 5.2 Hz, 1H), 7.65 (d, J =
7.5 Hz, 1H), 7.58–7.52 (m, 1H), 7.49 (t, J = 7.3 Hz, 1H), 7.35 (t,
Notes and references
J = 7.6 Hz, 2H), 7.01 (d, J = 10.3 Hz, 1H), 6.88 (d, J = 10.3 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 197.53, 184.15, 184.08, 1 S. F. Zhu, Z. Zhang, X. Huang, H. Jiang and Z. Guo, Chem. -
141.23, 140.04, 139.73, 137.13, 134.71, 133.58, 132.61, 130.68,
Eur. J., 2013, 19, 4695.
130.51, 130.17, 130.01, 128.82, 128.71, 128.12, 127.62, 125.74; 2 For general reviews on o-QDMs: (a) J. L. Segura and
HRMS (MALDI-FTMS): calcd for C21H14O3 [M+] = 314.0938;
found = 314.0942.
N. Martin, Chem. Rev., 1999, 99, 3199; (b) N. Martin,
C. Seoane and M. Hanack, Org. Prep. Proced. Int., 1991,
23, 237 For the results reported by our group:
(c) S. F. Zhu, R. X. Liang, H. F. Jiang and W. Q. Wu,
Angew. Chem., Int. Ed., 2012, 51, 10861; (d) S. F. Zhu,
Y. Xiao, Z. Guo and H. Jiang, Org. Lett., 2013, 15, 898;
(e) S. F. Zhu, Z. Guo, Z. Huang and H. Jiang, Chem. - Eur.
J., 2014, 20, 2425.
+
6-Benzoyltetracene-5,12-dione (6b). Yellow solid; mp
256.0–256.1 °C; isolated yield: 80.0%; IR (KBr): 3056, 2972,
2392, 2286, 1661, 1312, 1459, 1296, 70, 722; 1H NMR
(400 MHz, CDCl3) δ 8.95 (s, 1H), 8.32 (d, J = 7.6 Hz, 1H),
8.15–8.07 (m, 2H), 7.79 (d, J = 7.3 Hz, 2H), 7.74 (dd, J = 8.0,
1.7 Hz, 1H), 7.71–7.66 (m, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.56 (d,
J = 7.2 Hz, 1H), 7.49 (d, J = 7.4 Hz, 1H), 7.36 (t, J = 7.7 Hz, 2H); 3 (a) A. D. Melhado, W. E. Brenzovich, A. D. Lackner Jr. and
13C NMR (101 MHz, CDCl3) δ 197.82, 182.59, 182.55, 141.85,
137.36, 135.03, 134.50, 134.39, 133.96, 133.42, 132.91, 130.88,
130.59, 130.38, 129.86, 129.58, 128.85, 128.71, 127.93,
F. D. Toste, J. Am. Chem. Soc., 2010, 132, 8885;
(b) W. E. Brenzovich, D. Benitez Jr., A. D. Lackner,
H. P. Shunatona, E. Tkatchouk, W. A. Goddard and
F. D. Toste, Angew. Chem., Int. Ed., 2010, 49, 5519;
(c) G. Zhang, L. Cui, Y. Wang and L. Zhang, J. Am. Chem.
Soc., 2010, 132, 1474.
+
127.53, 127.50; HRMS (MALDI-FTMS): calcd for C25H16O3
[M+] = 364.1094; found = 364.1099.
7-Benzoyl-5,14-[1,2]benzenopentacene-6,13-dione (6c).
Yellow solid; mp 302.7 °C; isolated yield: 72%; IR: 3304, 2920, 4 K. M. Laginha, S. Verwoert, G. J. R. Charrois and T. M. Allen,
2851, 2393, 2286, 1731, 1672, 1579, 1424, 1284, 1162, 985, 791, Clin. Cancer Res., 2005, 11, 6944.
718; 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 8.02 (d, J = 5 (a) P. Wang, G. Bashiri, X. Gao, M. R. Sawaya and Y. Tang,
8.2 Hz, 1H), 7.72 (d, J = 7.4 Hz, 2H), 7.60 (d, J = 8.1 Hz, 2H),
7.48 (d, J = 7.0 Hz, 2H), 7.43 (d, J = 6.9 Hz, 1H), 7.40 (d, J =
7.1 Hz, 1H), 7.35 (d, J = 7.5 Hz, 2H), 7.33–7.26 (m, 3H),
7.02–6.89 (m, 4H), 6.00 (s, 1H), 5.83 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 197.73, 180.40, 180.31, 155.55, 155.38,
143.62, 143.55, 143.38, 143.30, 141.26, 137.11, 134.59, 133.57,
132.53, 130.60, 130.24, 129.96, 129.78, 128.91, 128.79, 128.59,
J. Am. Chem. Soc., 2013, 135, 7138; (b) B. A. Pearlman,
J. M. McNamara, I. Hasan, S. Hatakeyama, H. Sekizaki and
Y. Kishi, J. Am. Chem. Soc., 1981, 103, 4248; (c) A. S. Kende
and J. P. Rim, J. Am. Chem. Soc., 1981, 103, 4247;
(d) P. N. Confalone and G. Pizzolato, J. Am. Chem. Soc., 1981,
103, 4251; (e) T.-T. Li and Y. L. Wu, J. Am. Chem. Soc., 1981,
103, 7007.
127.60, 125.73, 125.70, 125.64, 125.60, 124.66, 124.60, 124.48, 6 Representative examples of the benzopyrilium ion:
47.96, 47.89; HRMS (MALDI-FTMS): calcd for C35H22O3+ [M+] =
490.1564; found = 490.1568.
(a) N. Asao, K. Takahashi, S. Lee, T. Kasahara and
Y. Yamamoto, J. Am. Chem. Soc., 2002, 124, 12650;
(b) N. Asao, T. Nogami, S. Lee and Y. Yamamoto, J. Am.
Chem. Soc., 2003, 125, 10921; (c) N. Asao, T. Nogami,
K. Takahashi and Y. Yamamoto, J. Am. Chem. Soc., 2002,
124, 764; (d) N. Asao, H. Aikawa and Y. Yamamoto, J. Am.
Chem. Soc., 2004, 126, 7458; (e) N. Asao, T. Kasahara and
Y. Yamamoto, Angew. Chem., Int. Ed., 2003, 42, 3504;
(f) Q. Ding and J. Wu, Org. Lett., 2007, 9, 4959;
(g) G. Dyker, D. Hildebrandt, J. Liu and K. Merz, Angew.
Chem., Int. Ed., 2003, 42, 4399; (h) S. Bhunia, K.-C. Wang
and R.-S. Liu, Angew. Chem., Int. Ed., 2008, 47, 5063;
(i) R.-Y. Tang and J.-H. Li, Chem. - Eur. J., 2010, 16, 4733;
( j) D. Yue, N. D. Ca and R. C. Larock, J. Org. Chem.,
2006, 71, 3381; (k) S.-Y. Yu, H. Zhang, Y. Gao, L. Mo,
S. Wang and Z.-J. Yao, J. Am. Chem. Soc., 2013, 135,
11402.
Dimethyl-1-benzoylnaphthalene-2,3-dicarboxylate (6d).
White solid; mp 124.8 °C; isolated yield: 98%; IR: 3053, 2980,
1727, 1668, 1581, 1445, 1297, 1164, 1070, 944, 782, 640;
1H NMR (400 MHz, CDCl3) δ8.43 (s, 1H), 7.93 (d, J = 8.1 Hz,
1H), 7.72 (d, J = 7.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 1H), 7.55 (dd,
J = 12.9, 5.7 Hz, 1H), 7.52–7.44 (m, 2H), 7.36 (t, J = 7.7 Hz, 2H),
3.88 (s, 3H), 3.54 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 196.67,
167.41, 166.90, 138.59, 137.27, 133.91, 132.89, 132.20, 131.31,
129.72, 129.57, 129.38, 128.71, 128.57, 128.16, 126.98, 126.30,
52.80, 52.55.
Acknowledgements
The authors thank the NNSFC (21172077, 21372086),
NCET-10-0403, The National Basic Research Program of China
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 4104–4111 | 4111