A Novel One-Pot, Two-Step Reaction for the Synthesis of Indenopyrrolo[3,2- c ]pyridinone Derivatives with a Recyclable Catalyst

Article abstract of DOI:10.1055/s-0037-1609655

An efficient strategy was developed for the synthesis of indenopyrrolopyridinone derivatives from 4-hydroxy-6-methyl-2 H -pyran-2-one, an amine, and 2,2-dihydroxy-1 H -indene-1,3(2 H)-dione by a one-pot, two-step, four-component process. The one-pot react

Full text of DOI:10.1055/s-0037-1609655

SYNLETT
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0
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6
© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–E
letter
A
en
C. Li et al.
Letter
Synlett
A Novel One-Pot, Two-Step Reaction for the Synthesis of Indeno-
pyrrolo[3,2-c]pyridinone Derivatives with a Recyclable Catalyst
Chunmei Li
Furen Zhang*
Chenze Qi
O
O
O
O
O
HO
OH
OH
R
R
2 RNH2
N
N
O
OH
CSO3H, H2O
80 °C
O
N
NH
R
OH
School of Chemistry and Chemical Engineering, Zhejiang Key
Laboratory of Alternative Technologies for Fine Chemicals
Process, Shaoxing University, Shaoxing, Zhejiang Province
312000, P. R. of China
R
R = Ar, Bn, nBu, nPr
12 examples prepared
up to 87% yields
frzhang@usx.edu.cn
Received:13.09.2018
Accepted after revision: 16.10.2018
Published online: 14.11.2018
O
H
N
O
Me
O
N
NH
HN R1
N
DOI: 10.1055/s-0037-1609655; Art ID: st-2018-k0592-l
N
H
N
R4
H2N
F
X2
Abstract An efficient strategy was developed for the synthesis of inde-
nopyrrolopyridinone derivatives from 4-hydroxy-6-methyl-2H-pyran-2-
one, an amine, and 2,2-dihydroxy-1H-indene-1,3(2H)-dione by a one-
pot, two-step, four-component process. The one-pot reaction gives
various substituted indenopyrrolopyridinones in good yields and uses a
solid acid as a recyclable catalyst in water. This procedure has the ad-
vantages of inexpensive substrates, a reusable solid-supported catalyst,
and a convenient one-pot operation.
II
X1
OH
R2
R3
R5
I
O
N
H
N
O
N
R1
N
R2
Cl
R3
N
R4
R5
R6
Key words multicomponent reaction, one-pot reaction, hydroxy-
methylpyranonone, amines, dihydroxyindenedione, indenopyrrolopyr-
idinones
MeO
III
IV
Figure 1 Biologically active pyrrolopyridinone derivatives
The simple and efficient construction of heterocyclic
scaffolds that display biological and pharmaceutical activi-
ties is an active research theme in organic synthesis. Among
these scaffolds, the pyrrolopyridines have distinguished
themselves as heterocycles of profound chemical and bio-
logical significance.1 For example, compounds I and their
analogues (Figure 1) are inhibitors of BET proteins,2 com-
pound II is a potent and orally active antitumor agent,3
compounds III are TAF1 inhibitors,4 and compound IV and
its analogues can inhibit proliferation of various tumor cells
and can constrain analogues of CB-1 antagonists.5 Other
pyrrolopyridine derivatives also exhibit various biomedical
and pharmacological activities.6 Because of the unique
chemical and biological characteristics of pyrrolopyridines,
many methods for their synthesis have been developed.7
However, most of these strategies involve multistep reac-
tions and laborious operational procedures, apply to only a
limited range of substrates, or require a nonreusable cata-
lyst. Therefore, the development of more-efficient methods
for the synthesis of this family of heterocyclic compounds is
of great interest and is challenging.
Indenopyrrole and its analogues are also common struc-
tural motifs in many biologically active molecules and
pharmaceutical substances.8 Some of them have been re-
ported to act as powerful lipid peroxidation inhibitors,9
potassium-channel openers,10 DNS intercalators, or
topoisomerase II inhibitors.11 Consequently, many modern
methods have been developed for the formation of these
compounds.12 However, most of these methods involve
expensive substrates, laborious steps, or nonreusable cata-
lysts. Therefore, the exploration of a versatile strategy for
the formation of these scaffolds is still highly desirable.
In recent decades, solid acids as heterogeneous catalysts
for organic synthesis have gained much attention due to
their recyclability, mildness, and environmentally friendly
nature.13 More importantly, because they are insoluble in
almost all solvents, it is easy to separate the catalyst from
reaction mixtures. Thus, a series of organic reactions cata-
lyzed by various solid acids have been developed.14 Recent-
ly, our group has developed a series of multicomponent re-
actions for the synthesis of heterocycles of chemical and
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

B
C. Li et al.
Letter
Synlett
pharmaceutical interest.15 As a result of our continuing
efforts on these one-pot processes, we wish to report a solid-
acid-promoted multicomponent reaction of 4-hydroxy-6-
methyl-2H-pyran-2-one, various amines, and 2,2-di-
hydroxy-1H-indene-1,3(2H)-dione in water to give poly-
substituted indenopyrrolo[3,2-c]pyridinone derivatives;
the reaction involves a one-pot, two-step strategy (Scheme
1). To the best of our knowledge, the use of a multicompo-
nent reaction to construct an indenopyrrolo[3,2-c]pyridi-
none scaffold has not been previously reported.
Table 1 Optimization of the Synthesis of Compound 5aa
O
O
O
O
O
HO
OH
OH
Ph
Ph
N
2 PhNH2
N
O
2a
OH
N
NH
Ph
4
O
OH
Conditions
3a
Ph
5a
1
Entry
Catalyst (mg)
Solvent
Temp (°C)
Yieldb (%)
1c
2
–
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
MeOH
EtOH
CHCl3
THF
80
80
–
HOAc (10)d
TsOH (10)d
H2SO4 (10)d
Y(OTf)3 (10)d
Sc(OTf)3 (10)d
55
42
30
46
49
18
32
81
36
83
57
71
19
16
42
46
–
O
3
80
O
O
O
OH
OH
O
4
80
R
HO
N
R
O
RNH2
2
N
5
80
O
NH
R
OH
OH
N
6
80
R
7
Amberlyst-15 (10)
zeolite HY (10)
CSO3H (10)
CSO3H (5)
80
Scheme 1 The synthesis of indenopyrrolopyridinone derivatives
8
80
9
80
To screen the reaction conditions, we chose 4-hydroxy-
6-methyl-2H-pyran-2-one, aniline, and 2,2-dihydroxy-1H-
indene-1,3(2H)-dione as model substrates in our one-pot,
two-step strategy. Representative results are summarized
in Table 1. The product 5a was not obtained when the mod-
el reaction was carried out in the absence of a catalyst
(Table 1, entry 1). Initially, 5a was obtained in yields of only
30–55% when various Brønsted acids (HOAc, TsOH, and
H2SO4) or Lewis acids [Y(OTf)3 or Sc(OTf)3] were used to
homogeneous catalysts for the model reaction (entries 2–
6). Heterogeneous catalysts, such as Amberlyst-15 or zeo-
lite HY exhibited even worse activities, giving 5a in yields of
only 18 and 32%, respectively (entries 7 and 8). However,
sulfonated amorphous carbon (CSO3H) as a solid-acid cata-
lyst exhibited a high reactivity and gave product 5a in 81%
yield (entry 9). Subsequent screening of the catalyst loading
indicated that CSO3H (10 mg) was enough to drive the reac-
tion forward successfully.
10
11
12
13
14
15
16
17
18c
19
20
21
80
CSO3H (15)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
CSO3H (10)
80
reflux
80
reflux
reflux
80
DMF
MeCN
H2O
H2O
H2O
H2O
80
r.t.
40
17
32
81
60
100
a Reaction conditions: 1 (0.5 mmol), 2a (1.0 mmol), catalyst, solvent
(3.0 mL), sealed tube, 2 h; then, 4 (0.5 mmol), 4 h.
b Isolated yield.
c Reaction time 24 h.
d 10 mol%.
Subsequently, the reaction was performed by using
CSO3H (10 mg) as the catalyst in various solvents (MeOH,
EtOH, CHCl3, THF, DMF, and MeCN); however, water proved
to be the best solvent (Table 1, entries 9 and 12–17). The re-
action in water was then repeated several times at various
temperature in a sealed tube, and the best yield of product
5a (81%) was obtained when the temperature was 80 °C
(entries 9 and 18–20). A further increase in the reaction
temperature did not enhance the yield of 5a (entry 21).
With the above optimized conditions in hand, we then
proceeded to probe the substrate diversity of this one-pot,
two-step reaction by using easily available starting materi-
als. The reactions of various amines 2 with 4-hydroxy-6-
methyl-2H-pyran-2-one (1) in water were performed for
two hours at 80 °C; this was followed by the addition of 2,2-
dihydroxy-1H-indene-1,3(2H)-dione (4) to the mixture un-
der the conditions described above. The results are summa-
rized in Scheme 2. Amines with either electron-deficient or
electron-rich substituents were suitable reactants. We also
noted that aromatic amines 2d–g with an electron-with-
drawing substituent (fluoro, chloro, bromo, or trifluoro-
methyl) in the para-position of the benzene ring exhibited
better reactivities and gave higher yields of the desired
products than did 2b or 2c, bearing electron-donating
methyl and methoxy substituents, respectively. In addition,
amines with ortho- or meta-substituents 2h and 2i exhibit-
ed lower activities and gave the desired products 5h and 5i
in 70 and 72% yield, respectively, as a result of steric effects.
To further expand the scope of the reaction, the aliphatic
amines benzylamine, butylamine, and propylamine were
chosen to react with 4-hydroxy-6-methyl-2H-pyran-2-one
(1) and 2,2-dihydroxy-1H-indene-1,3(2H)-dione (4). To our
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

C
C. Li et al.
Letter
Synlett
O
O
O
O
O
O
2 RNH2
2
HO
R
OH
OH
R
N
O
N
OH
NH
R
CSO3H, H2O
80 °C
4
OH
N
3
R
1
5
O
O
O
O
F
O
O
O
O
HO
HO
HO
HO
N
N
N
N
OH
OH
OH
OH
N
N
N
N
F
5a, 81%
5b, 75%
5c, 74%
5d, 83%
O
O
O
O
Cl
Br
F3C
O
O
O
O
HO
HO
HO
HO
N
N
N
N
OH
F
OH
OH
OH
N
N
N
N
F
Cl
Br
CF3
5e, 87%
5f, 84%
5g, 80%
5h, 70%
O
O
O
O
O
O
O
O
HO
HO
HO
HO
N
Cl
N
N
N
OH
OH
OH
OH
N
N
N
N
Cl
5i, 72%
5j, 83%
5k, 81%
5l, 80%
Scheme 2 The synthesis of compounds 5a–l. Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), CSO3H (10 mg), H2O (3.0 mL), sealed tube, 2 h, 80 °;
then, 4 (0.5 mmol), 80 °C, 4 h. Isolated yields are reported.
1
delight, the corresponding products 5j–l were obtained in
yields of 80–83%, probably due to the high reactivities of
these amines.
of the products were determined by means of H and 13C
NMR spectroscopy and high-resolution mass spectro-
metry.17,18
Having explored the diversity of the fused indanone
scaffolds, we then turned our attention to investigating the
three-component reaction of 4-hydroxy-6-methyl-2H-pyran-
2-one (1), aryl amines 2, and 2,2-dihydroxy-1H-indene-
1,3(2H)-dione (3).16 Initially, none of the desired product 7
was obtained when the three-component two-step reac-
tion was carried out under the above conditions. However,
various substituted 5-aryl-5a,10a-dihydroxy-3-methyl-
5a,10a-dihydro-1H-indeno[1,2-b]pyrano[3,4-d]pyrrole-
1,10(5H)-diones 7 were obtained after a series of optimiza-
tions of the reaction conditions (Scheme 3). The reactions
of substituted amines bearing electron-withdrawing
groups, such as fluoro, chloro, or bromo, or electron-donat-
ing groups, such as methoxy, all worked well to give the
corresponding products 7a–d in yields of 64–72%. We also
noted that aromatic amines bearing electron-withdrawing
groups exhibited slightly higher reactivities than those
bearing electron-donating groups.
O
O
O
O
O
ArNH2
2
OH
OH
HO
O
O
O
CSO3H, H2O
r.t.
NH
Ar
OH
4
OH
O
O
N
6
1
Ar
80 °C
7
O
O
O
O
O
O
O
HO
HO
HO
HO
O
O
O
O
OH
OH
OH
OH
N
N
N
N
Br
Cl
7c, 72%
OMe
F
7a, 64%
7b, 69%
7d, 66%
Scheme 3 Synthesis of compounds 7 by the three-component
reaction
O
O
O
O
HO
In all cases, the reactions occurred rapidly. Water was
almost the only byproduct, which made the workup green
and convenient. Furthermore, increasing the reaction times
did not lead to the elimination of the OH groups. However,
the addition of homogeneous acids, such as acetic acid, led
to the dehydration products (e.g., Scheme 4). The structures
HOAc
N
N
OH
N
N
H2O, 80 °C
5a
8a, 73%
Scheme 4 The elimination reaction of compound 5a
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Letter
Synlett
Subsequently, we examined the recyclability of the solid-
acid catalyst by using the model substrates 4-hydroxy-6-
methyl-2H-pyran-2-one (1), aniline, and 2,2-dihydroxy-1H-
indene-1,3(2H)-dione (4). After the completion of the mod-
el reaction, the catalyst was recovered by filtration and
washed with 95% EtOH and water. The solid-acid catalyst
could be reused easily after drying in a vacuum oven at
120 °C for four hours. The recovered catalyst was used re-
petitively ten times, and the results are shown in Figure 2.
The slight decline in catalytic activity after each run might
be due to minor losses in the recovery process. Therefore,
the solid-acid catalyst has good reusability.
In conclusion, we have established a new four-component,
one-pot, two-step reaction that provides an efficient syn-
thesis of 5a,10a-dihydroxy-3-methyl-2,5,5a,10a-tetrahy-
droindeno[2′,1′:4,5]pyrrolo[3,2-c]pyridine-1,10-diones, and a
three-component one-pot, two-step reaction that gives
5a,10a-dihydroxy-3-methyl-5a,10a-dihydro-1H-indeno[1,2-
b]pyrano[3,4-d]pyrrole-1,10(5H)-diones in good yields. Both
reaction processes employ readily available 4-hydroxy-6-
methyl-2H-pyran-2-one, an amine, and 2,2-dihydroxy-1H-
indene-1,3(2H)-dione as starting materials. The one-pot
operational simplicity, the environmentally friendly reac-
tion media, and the recyclable solid-supported catalyst
make this synthetic strategy highly attractive for accessing
compounds of potential biological and pharmacological in-
terest.
Funding Information
We are grateful for financial support from the Open Research Founda-
tion of Zhejiang Key Laboratory of Alternative Technologies for Fine
Chemicals Process.()
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609655.
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References and Notes
Figure 2 Study on the recyclability of the solid acid in the synthesis of
5a
(1) (a) Shah, S.; Lee, C.; Choi, H.; Gautam, J.; Jang, H.; Kim, G. J.; Lee,
Y.-J.; Chaudhary, C. L.; Park, S. W.; Nam, T.-G.; Kim, J.-A.; Jeong,
B.-S. Org. Biomol. Chem. 2016, 14, 4829. (b) Zhang, J.; Shen, W.;
Li, X.; Chai, Y.; Li, S.; Lv, K.; Guo, H.; Liu, M. Molecules 2016, 21,
1674. (c) Wang, M.; Ye, C.; Liu, M.; Wu, Z.; Li, L.; Wang, C.; Liu,
X.; Guo, H. Bioorg. Med. Chem. Lett. 2015, 25, 2782. (d) Chu, W.;
Zhou, D.; Gaba, V.; Liu, J.; Li, S.; Peng, X.; Xu, J.; Dhavale, D.;
Bagchi, D. P.; Avignon, A.; Shakerdge, N. B.; Bacskai, B. J.; Tu, Z.;
Kotzbauer, P. T.; Mach, R. H. J. Med. Chem. 2015, 58, 6002.
(e) Chen, G.; Weng, Q.; Fu, L.; Wang, Z.; Yu, P.; Liu, Z.; Li, X.;
Zhang, H.; Liang, G. Bioorg. Med. Chem. 2014, 22, 6953.
(f) Yamagishi, H.; Shirakami, S.; Nakajima, Y.; Tanaka, A.;
Takahashi, F.; Hamaguchi, H.; Hatanaka, K.; Moritomo, A.;
Inami, M.; Higashi, Y.; Inoue, T. Bioorg. Med. Chem. 2015, 23,
4846.
The plausible mechanism for the one-pot reaction was
proposed and is shown in Scheme 5. The initial nucleophilic
addition of 2 to activated 1 gives intermediate A, which can
be separated from the mixture. Compound 3 is then formed
by nucleophilic substitution of 2 with intermediate A in the
presence of the solid acid. Finally, the target product 5 is
obtained after nucleophilic substitution of substrate 3 with
protonated 2,2-dihydroxy-1H-indene-1,3(2H)-dione 4, and
the subsequent intramolecular cyclization.
CSO3
O
CSO3H
O
O
H
RNH2
2
O
RNH2
2
R
(2) Combs, A. P.; Maduskuie, T. P. J.; Falahatpisheh, N. US
2015307493, 2015.
O
N
R
O
N
OH
OH+
– H2O
OH
CSO3H
– H2O
4
OH
NH
R
(3) Menichincheri, M.; Bargiotti, A.; Berthelsen, J.; Bertrand, J. A.;
Bossi, R.; Ciavolella, A.; Cirla, A.; Cristiani, C.; Croci, V.; D'Alessio,
R.; Fasolini, M.; Fiorentini, F.; Forte, B.; Isacchi, A.; Martina, K.;
Molinari, A.; Montagnoli, A.; Orsini, P.; Orzi, F.; Pesenti, E.;
Pezzetta, D.; Pillan, A.; Poggesi, I.; Roletto, F.; Scolaro, A.; Tato,
M.; Tibolla, M.; Valsasina, B.; Varasi, M.; Volpi, D.; Santocanale,
C.; Vanotti, E. J. Med. Chem. 2009, 52, 293.
1
A
– H2O
3
O
O
O
O
HO
OH
R
R
N
intramolecular cyclization
N
OH
HN
R
B
N
OH
R
5
(4) Adler, M.; Burdick, D. J.; Crawford, T.; Duplessis, M.; Magnuson,
S.; Nasveschuk, C. G.; Romero, F. A.; Tang, Y.; Tsui, V. H.-W.;
Wang, S. US 2018009805, 2018.
Scheme 5 Probable mechanism for the formation of the indenopyrro-
lo[3,2-c]pyridinones
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

E
C. Li et al.
Letter
Synlett
(5) Smith, R. A.; Fathi, Z.; Brown, S.-E.; Choi, S.; Fan, J.; Jenkins, S.;
Kluender, H. C. E.; Konkar, A.; Lavoie, R.; Mays, R.; Natoli, J.;
O'Connor, S. J.; Ortiz, A. A.; Podlogar, B.; Taing, C.; Tomlinson, S.;
Tritto, T.; Zhang, Z. Bioorg. Med. Chem. Lett. 2007, 17, 673.
(6) (a) Davis, T.; Rokicki, M. J.; Bagley, M. C.; Kipling, D. Chem. Cent.
J. 2013, 7, 18. (b) Caruso, M.; Valsasina, B.; Ballinari, D.;
Bertrand, J.; Brasca, M. G.; Caldarelli, M.; Cappella, P.; Fiorentini,
F.; Gianellini, L. M.; Scolaro, A.; Beria, I. Bioorg. Med. Chem. Lett.
2012, 22, 96. (c) Vanotti, E. A.; Bargiotti, R. A.; Berthelsen, J.;
Bosotti, R.; Ciavolella, A.; Cirla, A.; Cristiani, C.; D’Alessio, R.; Forte,
B.; Isacchi, A.; Martina, K.; Menichincheri, M.; Molinari, A.;
Montagnoli, A.; Orsini, P.; Pillan, A.; Roletto, F.; Scolaro, A.; Tibolla,
M.; Valsasina, B.; Varasi, M.; Volpi, D.; Santocanale, C. J. Med. Chem.
2008, 51, 487.
(7) (a) Croix, C.; Massip, S.; Viaud-Massuard, M.-C. Chem. Commun.
2018, 54, 5538. (b) Zhang, Z.; Gao, X.; Wan, Y.; Huang, Y.;
Huang, G.; Zhang, G. ACS Omega 2017, 2, 6844. (c) Li, Y.; Lin, Z.
Organometallics 2015, 34, 3538. (d) Li, Z.; Kumar, A.; Sharma, S.
K.; Parmar, V. S.; Van der Eycken, E. V. Tetrahedron 2015, 71,
3333. (e) Deguest, G.; Devineau, A.; Bischoff, L.; Fruit, C.;
Marsais, F. Org. Lett. 2006, 8, 5889.
Chem. Lett. 2011, 21, 2341. (c) Weng, Y.; Zhou, H.; Sun, C.; Xie,
Y.; Su, W. J. Org. Chem. 2017, 82, 9047. (d) Balalas, T.; Abdul-
Sada, A.; Hadjipavlou-Litina, D. J.; Litinas, K. E. Synthesis 2017,
49, 2575.
(17) 2,5-Disubstituted
5a,10a-Dihydroxy-3-methyl-2,5,5a,10a-
tetrahydroindeno[2′,1′:4,5]pyrrolo[3,2-c]pyridine-1,10-
diones 5a–l; General Method
A mixture of pyranone 1 (0.5 mmol), the appropriate amine 2
(1.0 mmol), and solid acid (10 mg) in H2O (3.0 mL) in sealed
tube was heated at 80 °C until starting material was completely
converted (~2 h; TLC). Indenedione 4 (0.5 mmol) was then
added and the mixture was heated at 80 °C for another 4 h. The
mixture was cooled to r.t. and the solid product was collected by
filtration and washed with H2O. The crude product and solid
acid were treated with hot 95% EtOH. The catalyst was removed
by filtration, and the pure product 5 was obtained from the
mother liquor.
5a,10a-Dihydroxy-3-methyl-2,5-diphenyl-2,5,5a,10a-tetra-
hydroindeno[2′,1′:4,5]pyrrolo[3,2-c]pyridine-1,10-dione (5a)
Yellow crystals; yield: 177.0 mg (81%); mp 238–240 °C. IR (KBr):
3403, 1721, 1638, 1487, 1454, 1357, 1197, 1021, 943, 870, 772
(8) (a) Tierney, M. T.; Grinstaff, M. W. J. Org. Chem. 2000, 65, 5355.
(b) Rochais, C.; Dallemagne, P.; Rault, S. Anti-Cancer Agents Med.
Chem. 2009, 9, 369. (c) Diana, P.; Stagno, A.; Barraja, P.;
Montalbano, A.; Carbone, A.; Parrino, B.; Cirrincione, G. Tetrahe-
dron 2011, 67, 3374. (d) Hemmerling, H.-J.; Reiss, G. Synthesis
2009, 985.
cm–1 1H NMR (400 MHz, CDCl3): δ = 7.85–7.86 (m, 1 H, ArH),
.
7.39–7.52 (m, 10 H, ArH), 7.20–7.23 (m, 1 H, ArH), 7.11–7.14
(m, 1 H, ArH), 6.78 (dd, J = 5.6, 2.8 Hz, 1 H, ArH), 6.41 (br s, 1 H,
OH), 5.63 (s, 1 H, CH), 5.36 (s, 1 H, OH), 1.83 (s, 3 H, CH3). 13C
NMR (100 MHz, CDCl3): δ = 197.3, 161.2, 155.9, 150.7, 147.7,
138.3 (2 C), 136.9, 135.2 (2 C), 135.0, 129.9, 129.4, 128.8, 128.7,
(9) Brown, D. W.; Graupner, P. R.; Sainsbury, M.; Shertzer, H. G. Tet-
rahedron 1991, 47, 4383.
(10) Butera, J. A.; Antane, S. A.; Hirth, B.; Lennox, J. R.; Sheldon, J. H.;
Norton, N. W.; Warga, D.; Argentieri, T. M. Bioorg. Med. Chem.
Lett. 2001, 11, 2093.
128.5, 128.4, 127.8 (2 C), 124.9, 124.5, 100.2, 96.2, 93.4, 82.7,
77.3, 22.5. HRMS (ESI): m/z [M + H]+ calcd for C27H21N2O4
437.1496; found: 437.1495..
:
+
(18) 5-Aryl-5a,10a-dihydroxy-3-methyl-5a,10a-dihydro-1H-
indeno[1,2-b] pyrano[3,4-d]pyrrole-1,10(5H)-diones 7a–d;
General Procedure
(11) Bal, C.; Baldeyrou, B.; Moz, F.; Lansiaux, A.; Colson, P.; Kraus-
Berthier, L.; Léonce, S.; Pierre, A.; Boussard, M.-F.; Rousseau, A.;
Wierzbicki, M.; Bailly, C. Biochem. Pharmacol. 2004, 68, 1911.
(12) (a) Wang, S.; Yang, Q.; Dong, J.; Li, C.; Sun, L.; Song, C.; Chang, J.
Eur. J. Org. Chem. 2013, 7631. (b) Chang, J.; Sun, L.; Dong, J.;
Shen, Z.; Zhang, Y.; Wu, J.; Wang, R.; Wang, J.; Song, C. Synlett.
2012, 23, 2704. (c) Lobo, G.; Monasterios, M.; Rodrigues, J.;
Gamboa, N.; Capparelli, M. V.; Martínez-Cuevas, J.; Lein, M.;
Jung, K.; Abramjuk, C.; Charris, J. Eur. J. Med. Chem. 2015, 96,
281. (d) Pathak, S.; Das, D.; Kundu, A.; Maity, S.; Guchhait, N.;
Pramanik, A. RSC Adv. 2015, 5, 17308. (e) Jiang, B.; Wang, X.; Xu,
H.-W.; Tu, M.-S.; Tu, S.-J.; Li, G. Org. Lett. 2013, 15, 1540.
(13) Vekariya, R. H.; Patel, K. D.; Patel, H. D. RSC Adv. 2015, 5, 90819.
(14) (a) Vekariya, R. H.; Prajapati, N. P.; Patel, H. D. Synth. Commun.
2016, 46, 1713. (b) Ziarani, G. M.; Lashgari, N.; Badiei, A. J. Mol.
Catal. A: Chem. 2015, 397, 166. (c) Gholamzadeh, P.; Ziarani, G.
M.; Lashgari, N.; Badiei, A. J. Mol. Catal. A: Chem. 2014, 391, 208.
(d) Vekariya, R. H.; Patel, H. D. ARKIVOC 2015, (i), 136.
A mixture of pyranone 1 (0.5 mmol), the appropriate amine 2
(0.5 mmol), and solid acid (10 mg) in water (3.0 mL) in a sealed
tube was stirred at r.t. until the starting material was com-
pletely converted (~12 h; TLC). Indenedione 4 (0.5 mmol) was
then added and the mixture was heated at 80 °C for another 4 h.
The mixture was cooled to r.t. and the solid product was col-
lected by filtration and washed with H2O. The crude product
and the solid acid were treated with hot 95% EtOH and water.
The catalyst was removed by filtration, and the pure product 7
was obtained from the mother liquor.
5a,10a-Dihydroxy-5-(4-methoxyphenyl)-3-methyl-5a,10a-
dihydro-1H-indeno[1,2-b]pyrano[3,4-d]pyrrole-1,10(5H)-
dione (7a)
Gray solid; yield: 147.2 mg (75%); mp 286–288 °C. IR (KBr):
3401, 1720, 1637, 1488, 1451, 1356, 1149, 1028, 875, 758 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 7.60 (d, J = 7.2 Hz, 1 H, ArH),
7.53–7.63 (m, 2 H, ArH), 7.38 (s, 1 H, OH), 7.20 (d, J = 8.0 Hz, 2 H,
ArH), 7.07 (d, J = 8.8 Hz, 2 H, ArH), 6.73 (d, J = 7.6 Hz, 1 H, ArH),
6.36 (s, 1 H, OH), 5.59 (s, 1 H, CH), 3.83 (s, 3 H, OMe), 2.06 (s, 3
H, CH3). 13C NMR (100 MHz, DMSO-d6): δ = 197.4, 167.4, 159.4,
158.5, 158.2, 147.7, 135.7 (2 C), 135.0, 130.8, 128.4 (2 C), 125.6
(2 C), 123.8, 114.9, 97.1, 93.1, 91.4, 83.1, 55.8, 20.4. HRMS (ESI):
m/z [M + H]+ calcd for C22H18NO6+: 392.1129; found: 392.1131.
(15) (a) Li, C.; Liang, X.; Zhang, F.; Qi, C. Catal. Commun. 2015, 62, 6.
(b) Chen, Z.; Shi, Y.; Shen, Q.; Xu, H.; Zhang, F. Tetrahedron Lett.
2015, 56, 4749. (c) Zhang, F.; Li, C.; Liang, X. Green Chem. 2018,
20, 2057.
(16) (a) Kraus, G. A.; Wanninayake, U. K.; Bottoms, J. Tetrahedron
Lett. 2016, 57, 1293. (b) Dong, Y.; Nakagawa-Goto, K.; Lai, C.-Y.;
Morris-Natschke, S. L.; Bastow, K. F.; Lee, K.-H. Bioorg. Med.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E