New method for the synthesis of chromeno[4,3-b]chromene derivatives via multicomponent reaction promoted by niobium pentachloride

Article abstract of DOI:10.1016/j.tetlet.2017.01.062

Chromeno[4,3-b]chromene derivatives were synthesized from multicomponent reaction between 4-hydroxycoumarin, aryl aldehyde derivatives and 1,3-cyclohexanedione promoted by niobium pentachloride. This new method is simple, cost-effective, provides good yie

Full text of DOI:10.1016/j.tetlet.2017.01.062

Accepted Manuscript
New Method for the Synthesis of Chromeno[4,3-b]chromene Derivatives via
Multicomponent Reaction Promoted by Niobium Pentachloride
Willian Henrique dos Santos, Luiz Carlos da Silva-Filho
PII:
S0040-4039(17)30096-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.01.062
TETL 48565
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 December 2016
18 January 2017
20 January 2017
Please cite this article as: dos Santos, W.H., da Silva-Filho, L.C., New Method for the Synthesis of Chromeno[4,3-
b]chromene Derivatives via Multicomponent Reaction Promoted by Niobium Pentachloride, Tetrahedron Letters
(2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.01.062
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Willian Henrique dos Santos andLuiz Carlos da Silva-Filho

1
Tetrahedron Letters
New Method for the Synthesis of Chromeno[4,3-b]chromene Derivatives via
Multicomponent Reaction Promoted by Niobium Pentachloride
Willian Henrique dos Santosa, Luiz Carlos da Silva-Filhoa, 
a São Paulo State University (UNESP), School of Sciences, Department of Chemistry, Av. Eng. Luiz Edmundo Carrijo Coube, 14-01, Bairro: Vargem Limpa, Zip
Code 17033-360, Bauru, São Paulo, Brazil.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Chromeno[4,3-b]chromene derivatives were synthesized from multicomponent reaction between
4-hydroxycoumarin, aryl aldehyde derivatives and 1,3-cyclohexanedione promoted by niobium
pentachloride. This new method is simple, cost-effective, provides good yields with good
substrate generality and can be conducted in short reaction times.
Available online
2016 Elsevier Ltd. All rights reserved.
Keywords:
Niobium pentachloride
Lewis acid
Coumarin
Chromene
Multicomponent reactions
Introduction
functionally substituted chromenes have played an increasingly
important role in synthetic approaches in compounds with
Heterocyclic compounds of natural and synthetic occurrence
containing coumarin nuclei has aroused the interest of several
research groups around the world since, for this class of
compounds has a wide range of biological activities,1,2 such as:
antibacterial, anticoagulant, antiviral, antifungal, anticancer and
anti-inflammatory.3 The coumarins were isolated from clover
flowers (Melilotus officinalis) and Cumaru seeds for the first
time by Vogel in 1820, and the first synthesis was conducted in
1868 by Sir William Henry Perkin.4
potential application in the field of medicinal chemistry.16-18
Chromenes can occur in various natural extracts, such as
visnadine (1) used as coronary and peripheral vasodilator
extracted from the fruit of Ammi visnaga19 and Khellactone (2)
extracted from Phlojodicarpus sibiricus, which has vasodilatory
properties20 (Figure 1).
Currently, more than 1400 species of coumarin were described
in the literature. They are found in many different families of the
plant kingdom, such as Papilonaceae (Fabaceae), Lamiaceae,
Asteraceae, Solanaceae, Poaceae, Umbelliferae, and especially
Apiaceaee Rutaceae, which are more abundant.5,6 The coumarins
strongly absorb in the visible light region, which makes this class
of compounds promising molecules which can potentially be
used in Dye Sensitized Solar Cells (DSSCs).7-14
On the other hand, bicyclic heterocyclic compounds, with
oxygen as heteroatom, that present in its structure the fusion of
the benzene ring with the 2H-pyran or 4H-pyran rings are
designated 2H-chromene (2H-1-benzopyran) and 4H-chromene
(4H-1-benzopyran).15 Chromene derivatives often appear as
important structural components on biologically active natural
compounds. Chromene fragments can occur in alkaloids,
Fig. 1. Visnadine 1 and Khellactone 2 structures
Due to the large application of chromene derivatives, several
methods of preparation were described in the literature, of which
we can mention: copper-catalyzed intramolecular coupling of
aryl bromides with 1,3-dicarbonyls,21 cycloaddition reaction
between propargylic alcohols with 2-naphthols or phenols
flavonoids, tocopherols, and anthocyanins. In addition,
———
 Corresponding author. Tel.: + 55-14-3103-6088; Fax: +55-14-3103-6099; E-mail: lcsilva@fc.unesp.br

2
Tetrahedron Letters
derivatives (6a-n) via multicomponent reaction between 4-
bearing
electron-donating
groups,
via
allenylidene
hydroxycoumarin (3), 1,3-cyclohexanedione (4) and different
aryl aldehydes (5a-n) promoted by niobium pentachloride
(scheme 1). NbCl5 is highly electrophilic, making possible act as
a Lewis acid, have a low-cost commercial, and has been used by
our group and other researchers as an effective catalyst in
synthetic methodologies in a variety of reactions, obtaining
excellent results. 50-57
intermediates, leading to the formation of the respective 1H-
naphtho[2,1-b]pyrans and 4H-1-benzopyrans,22 cyclization
reaction between different substituted α,α-dicyanoolefins with β-
naphthol in the presence of efficient bifunctional thiourea
catalyst,23 among others.24-33
As part of our research interest on synthetic methodologies by
using niobium pentachloride,34-49 we wish to present in this work
a new method for the synthesis of chromeno[4,3-b]chromene
Scheme 1. MCR of 4-hydroxycoumarin (3), 1,3-cyclohexanedione (4) and aryl aldehydes (5a-n) promoted by NbCl5
Results and discussion
Firstly, the multicomponent reaction between 4-
hydroxycoumarin (3) (1.0 equiv.), 1,3-cyclohexanedione (4) (1.0
equiv.) and benzaldehyde (5a) (1.0 equiv.) in the presence of
different concentrations (0.0, 10, 25 and 50 mol%) of niobium
Table 1. Optimization of multicomponent reaction between 4-
hydroxycoumarin
(3),
1,3-cyclohexanedione
(4)
and
benzaldehyde (5a) promoted by NbCl5.a
NbCl5
(mol %)
Time
(h)
24
2
2
2
24
2
2
2
24
2
Yieldb
(%)
-
15
21
18
-
18
29
20
-
pentachloride
and
different
solvents
(acetonitrile,
Entry
Solvent
dichloromethane and 1,2-dichloroethane), was used as a model in
order to develop a protocol for the optimization of the reaction
conditions. The reaction was performed under N2 atmosphere.
The results are summarized in Table 1.
0
DCM
DCM
DCM
DCM
DCE
DCE
DCE
DCE
1
2
3
4
5
6
7
8
9
10
25
50
0
10
25
50
0
As shown in Table 1, we were unable to obtain the expected
product by using 0.0 mol% of NbCl5, independent of the solvent.
The use of 25 mol% of NbCl5 produced the best results for the
tested solvents, in which the mixture of DCE/CH3CN (70:30)
presented the best yield (74% in 2 hours) (entry 15, Table 1).
With 50 mol % of NbCl5, degradation of the product and
formation of by-products were observed, resulting in a reduction
in yielding. Based on these results, it was established that Entry
15 (Table 1) presents the best reaction conditions to be applied in
the reactions with the other studied aldehydes (5b-n). We
hypothesize that the low solubility of the same aldehydes and
reactive intermediates may explain the differences in the product
yields when the solvent mixtures varied (entries 13-20, Table 1).
CH3CN
CH3CN
CH3CN
CH3CN
DCE/CH3CN
50:50
DCE/CH3CN
60:40
DCE/CH3CN
70:30
10
25
50
10
15
Trace
10
11
12
2
2
25
25
25
25
25
25
25
25
2
2
2
2
2
2
2
2
53
59
74
58
18
35
41
38
13
14
15
16
17
18
19
20
We investigated the reaction profile of this reaction by using
other aldehydes (5b-n) containing electron-donating and
electron-withdrawing groups obtaining the chromeno[4,3-
b]chromene derivatives (6b-n) in analogous yields. The results
are summarized in Table 2. The products were purified by
recrystallization in two steps; the first recrystallization was done
from ethanol and the second recrystallization from ethyl acetate.
The products were characterized by spectroscopic and
spectrometric methods.58
DCE/CH3CN
80:20
DCM/CH3CN
50:50
DCM/CH3CN
60:40
DCM/CH3CN
70:30
DCM/CH3CN
80:20
a) Reaction conditions: 4-hydroxycoumarin (3) (1.0 mmol), 1,3-
cyclohexanedione (4) (1.0 mmol), benzaldehyde (5a) (1.0 mmol) and NbCl5
(0–50 mol %) in DCM (4.0 ml), DCE (4.0 ml), CH3CN (4.0 ml), mixture
DCE/CH3CN (4.0 ml) (50:50, 60:40, 70:30, 80:20) in NbCl5 25 mol % and
mixture DCM/CH3CN (4.0 ml) (50:50, 60:40, 70:30, 80:20) in NbCl5 25 mol
%at reflux, under N2 atmosphere. b) isolated yields.

3
Table 2. Results for the synthesis of chromeno[4,3-b]chromene
derivatives (6a-n)
Table 3. Comparison between different Lewis acids in the
synthesis of chromeno[4,3-b]chromene derivatives.
Aryl aldehyde
R
C6H5
Yield (%)*
74 (6a)29,30
67 (6b)29,31
70 (6c)
68 (6d)29,31,32
60 (6e)31,32
75 (6f)29,30
58 (6g)29,31,32
56 (6h)31,32
53 (6i)31,32
55 (6j)33
Lewis acid
Solvent
DCE/CH3CN
70:30
Time (h)
Yield (%)
-
5a
None
24
5b
4-CH3C6H4
4-COOHC6H4
4-OCH3C6H4
2-OCH3C6H4
4-OH-3-OCH3C6H3
4-NO2C6H4
4-BrC6H4
5c
DCE/CH3CN
70:30
NbCl5*
2
58
5d
5e
NbCl5*
FeCl3**
MgCl2**
ZnCl2**
CH3CN
2
6
6
6
10
40
20
20
5f
CH3CN
5g
CH3CN
5h
CH3CN
*
Reaction conditions: 4-hydroxycoumarin (3) (1.0 mmol), 1,3-
cyclohexanedione (4) (1.0 mmol), 4-nitrobenzaldehyde (5g) (1.0 mmol) and
25 mol % of NbCl5, at reflux, under N2 atmosphere.
** Reaction conditions: 4-hydroxycoumarin (3) (1.0 mmol), 1,3-
cyclohexanedione (4) (1.0 mmol), 4-nitrobenzaldehyde (5g) (1.0 mmol) and
10 mol % FeCl3 or MgCl2 or ZnCl2, at reflux.
5i
2-BrC6H4
5j
4-C6H5C6H4
C4H3S
5k
71 (6k)30
5l
5m
4-(CH3)2NC6H4
CH3
62 (6l)
63 (6m)
When compared with other Lewis acids,29 niobium
pentachloride is more effective, requiring shorter reaction times
and providing better yields. These notable features make this
procedure a useful and attractive process for the synthesis of
chromeno[4,3-b]chromene derivatives, compounds with high
biological interest.
5n
CH=CHC6H5
55 (6n)
* Isolated yields.
The results in Table 2 show that by using 1.0 equivalent of
NbCl5 and a reaction time of 2 hours, it was possible to obtain
chromeno[4,3-b]chromene derivatives (6a-n) with good yields
(53-75%), under N2 atmosphere and reflux. Large yield
differences were not observed by changing the benzaldehyde
derivative. Besides, these methodology was applied successfully
on aliphatic aldehyde and corresponding chromeno[4,3-
b]chromene derivatives were obtained in good yields.
In a recently published study by our research group, we
described a new synthetic method for xanthenedione derivatives
in the presence of NbCl5 between 1,3-cyclohexanedione (4) and
aryl-aldehydes.54 Based on this work and our experimental results
we proposed a plausible mechanism that begins with the
Knoevenagel condensation reaction between the enol form of
1,3-cyclohexanedione (4) and aldehydes activated by NbCl5
followed by the elimination of H2O, producing, as intermediate,
the -dicarbonyl enone (I), which can act as Michael acceptors.
The -dicarbonyl enone (I) forms a complex with NbCl5, and can
be attacked by 4-hydroxycoumarin (4) via Michael addition,
giving rise to a novel intermediate II that can be readily
converted into the product by an intramolecular hemiketalization
followed by loss of water in the presence of NbCl5, leading to 6a-
n products.
For comparison, our results for the multicomponent reaction
between
4-hydroxycoumarin
(3)
(1.0
mmol),
1,3-
cyclohexanedione (4) (1.0 mmol) and 4-nitrobenzaldehyde (5g)
(1.0 mmol) were compared with other studies described in the
literature (Table 3).29

4
Tetrahedron
(3)
Venugopala, K. N.; Rashmi, V.; Odhav, B.;
Venugopala, K. N.; Rashmi, V.; Odhav, B. BioMed Res. Int.
2013, 2013, e963248.
(4)
Ribeiro, C. V. C.; Kaplan, M. A. C. Quim. Nova 2002,
25, 533-538.
(5)
Audisio, D.; Messaoudi, S.; Brion, J.-D.; Alami, M.
Eur. J. Org. Chem. 2010, 2010, 1046–1051.
(6)
Trost, B. M.; Toste, F. D.; Greenman, K. J. Am. Chem.
Soc. 2003, 125, 4518–4526.
(7)
Liu, X.; Cole, J. M.; Waddell, P. G.; Lin, T.-C.; Radia,
J.; Zeidler, A. J. Phys. Chem. A 2012, 116, 727–737.
(8)
Hu, Y.; Zhong, Y.; Li, J.; Cai, L.; Li, H. Color.
Technol. 2011, 127, 335–339.
(9)
Takizawa, S.; Pérez-Bolívar, C.; Anzenbacher, P.;
Murata, S. Eur. J. Inorg. Chem. 2012, 2012, 3975–3979.
(10)
Barooah, N.; Mohanty, J.; Pal, H.; Bhasikuttan, A. C.
Org. Biomol. Chem. 2012, 10, 5055–5062.
(11)
Ghatak, C.; Rao, V. G.; Mandal, S.; Sarkar, N. Phys.
Chem. Chem. Phys. 2012, 14, 8925–8935.
(12)
Liu, B.; Wang, R.; Mi, W.; Li, X.; Yu, H. J. Mater.
Chem. 2012, 22, 15379–15387.
(13)
Anufrik, S. S.; Tarkovsky, V. V.; Sazonko, G. G.;
Asimov, M. M. J. Appl. Spectrosc. 2012, 79, 46–52.
Scheme 2. Mechanistic proposal for multicomponent reaction
promoted by NbCl5.
(14)
Chen, L.; Hu, T.-S.; Yao, Z.-J. Eur. J. Org. Chem.
2008, 2008, 6175–6182.
Finally, we can conclude that the use of niobium
pentachloride as a promoter agent in the multicomponent reaction
between 4-hydroxycoumarin (3), 1,3-cyclohexanedione (4) and
aryl aldehydes (5a-n), produces chromeno[4,3-b]chromene
derivatives (6a-n) with good-yielding, good substrate generality
and in short reaction times.
(15)
10526.
Pratap, R.; Ram, V. J. Chem. Rev. 2014, 114, 10476–
(16)
Elinson, M. N.; Dorofeev, A. S.; Feducovich, S. K.;
Gorbunov, S. V.; Nasybullin, R. F.; Stepanov, N. O.; Nikishin,
G. I. Tetrahedron Lett. 2006, 47, 7629–7633.
(17)
Sun, W.; Cama, L. D.; Birzin, E. T.; Warrier, S.; Locco,
L.; Mosley, R.; Hammond, M. L.; Rohrer, S. P. Bioorg. Med.
Chem. Lett. 2006, 16, 1468–1472.
Acknowledgments
The authors would like to thank Fundação de Amparo à
Pesquisa do Estado de São Paulo (FAPESP 16/01599-1),
Conselho Nacional de Desenvolvimento Científico e Tecnológico
(18)
Stachulski, A. V.; Berry, N. G.; Lilian Low, A. C.;
Moores, S. L.; Row, E.; Warhurst, D. C.; Adagu, I. S.; Rossignol,
J.-F. J. Med. Chem. 2006, 49, 1450–1454.
(CNPq)
(Proc.
302753/2015-0),
Coordenadoria
de
Aperfeiçoamento de Pessoal do Nível Superior (CAPES), and
Pró-Reitoria de Pesquisa da UNESP (PROPe-UNESP) for their
financial support. The authors would also like to thank CBMM –
Companhia Brasileira de Metalurgia e Mineração for the NbCl5
samples.
(19)
Iranshahi, M.; Askari, M.; Sahebkar, A.; Hadjipavlou-
Litina, D. DARU J. Pharm. Sci. 2009, 17, 99–103.
(20)
Gantimur, D.; Syrchina, A. I.; Semenov, A. A. Chem.
Nat. Compd. 1986, 22, 103–104.
(21)
(22)
Fang, Y.; Li, C. J. Org. Chem. 2006, 71, 6427–6431.
Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J.
References and notes
(1)
Musa, M. A.; Cooperwood, J. S.; Khan, M. O. F. Curr.
Am. Chem. Soc. 2002, 124, 7900–7901.
Med. Chem. 2008, 15, 2664–2679.
(23)
Wang, X.-S.; Yang, G.-S.; Zhao, G. Tetrahedron
(2)
Neyts, J.; Clercq, E. D.; Singha, R.; Chang, Y. H.; Das,
Asymmetry 2008, 19, 709–714.
A. R.; Chakraborty, S. K.; Hong, S. C.; Tsay, S.-C.; Hsu, M.-H.;
Hwu, J. R. J. Med. Chem. 2009, 52, 1486–1490.
(24)
Zhang, G.; Zhang, Y.; Yan, J.; Chen, R.; Wang, S.; Ma,
Y.; Wang, R. J. Org. Chem. 2012, 77, 878–888.

5
(25)
Xie, J.-W.; Huang, X.; Fan, L.-P.; Xu, D.-C.; Li, X.-S.;
(47)
Oshiro, P. B.; Lima, P. S. S. G.; Menezes, L. M.; da
Su, H.; Wen, Y.-H. Adv. Synth. Catal. 2009, 351, 3077–3082.
Silva-Filho, L. C. Tetrahedron Lett. 2015, 56, 4476-4479.
(26)
Du, Z.; Siau, W.-Y.; Wang, J. Tetrahedron Lett. 2011,
(48)
Santos, W. H.; da Silva-Filho, L. C. Chem. Pap. 2016,
52, 6137–6141.
70, 1658–1664.
(27)
Gao, Y.; Yang, W.; Du, D.-M. Tetrahedron Asymmetry
(49)
Siqueira, M. S.; Silva-Filho, L. C. Tetrahedron Lett.
2012, 23, 339–344.
2016, 57, 5050–5052
(28)
Hu, K.; Lu, A.; Wang, Y.; Zhou, Z.; Tang, C.
(50)
Andrade, C. K. Z. Curr. Org. Synth. 2004, 1, 333–353.
Tetrahedron Asymmetry 2013, 24, 953–957.
(51)
Andrade, C. K. Z.; Rocha, R. Mini-Rev. Org. Chem.
(29)
Pradhan, K.; Paul, S.; Das, A. R. Tetrahedron Lett.
2006, 3, 271–280.
2013, 54, 3105–3110.
(52)
Hou, J.-T.; Gao, J.-W.; Zhang, Z.-H. Appl. Organomet.
(30)
Chen, Z.; Zhu, Q.; Su, W. Tetrahedron Lett. 2011, 52,
Chem. 2011, 25, 47–53.
2601-2604.
(53)
Hou, J.-T.; Liu, Y.-H.; Zhang, Z.-H. J. Heterocycl.
(31)
Shafiee, A.; Motamedi, R.; Firuzi, O.; Meili, S.;
Chem. 2010, 47, 703–706.
Mehdipour, A. R.; Miri, R. Med. Chem. Res. 2011, 20, 466-474.
(54)
Hou, J.-T.; Chen, H.-L.; Zhang, Z.-H. Phosphorus
(32)
Motamedi, R.; Baghbani, S.; Bamoharram, F. F. Synth.
Sulfur Silicon Relat. Elem. 2010, 186, 88–93.
Commun. 2012, 42, 1604-1612.
(55)
Hou, J.-T.; Gao, J.-W.; Zhang, Z.-H. Monatshefte Für
(33)
Iniyaran, P.; Sarveswari, S.; Vijayakumar, V. Res.
Chem. - Chem. Mon. 2011, 142, 495–499.
Chem. Intermed 2015, 41, 7413-7426.
(56)
Lacerda Jr, V.; Santos, D. A.; da Silva-Filho, L. C.;
(34)
Constantino, M. G.; Lacerda Jr, V.; da Silva-Filho, L.
Greco, S. J.; Santos, R. B. Aldrichimica Acta 2012, 19–27.
C.; da Silva, G. V. J. Lett. Org. Chem. 2004, 1, 360–364.
(57)
Arpini, B.; Andrade Bartolomeu, A.; Andrade, C.; da
(35)
Constantino, M. G.; da Silva Filho, L. C.; Neto, A. C.;
Silva-Filho, L.; Lacerda, V. Curr. Org. Synth. 2015, 12, 570–
Heleno, V. C. G.; da Silva, G. V. J.; Lopes, J. L. C. Spectrochim.
583.
Acta. A. Mol. Biomol. Spec.. 2005, 61, 171–176.
(58)
General procedure for synthesis of chromeno[4,3-
(36)
da Silva Filho, L. C.; Lacerda Jr, V.; Constantino, M.
b]chromene derivatives (6a-n): To a solution of NbCl5 (67.5 mg,
0.25 mmol) dissolved in 1.0 mL of the mixture of anhydrous
solvents DCE/CH3CN (0.7:0.3 mL), were added a solution of 4-
hydroxycoumarin (3) (162.0 mg, 1.0 mmol), 1,3-
cyclohexanedione (4) (112.0 mg, 1.0 mmol) and the respective
aldehyde (5a–n) (1.0 mmol) in 3.0 mL of anhydrous
DCE/CH3CN (2.1:0.9 mL), under N2 atmosphere. The reaction
mixture was stirred at reflux for 2 hours. After this time, the
reaction was poured into water and the product was extracted
with dichloromethane. The organic layer was concentrated under
reduced pressure. The products (6a-n) were obtained by
recrystallization in two steps, the first recrystallization was done
from ethanol and a second recrystallization from ethyl acetate. 7-
phenyl-7,9,10,11-tetrahydro-6H,8H-chromeno[4,3-b]chromene-
G.; da Silva, G. V. J.; Invernize, P. R. Beilstein J. Org. Chem.
2005, 1, 14.
(37)
Constantino, M. G.; Lacerda Jr, V.; Invernize, P. R.; da
Silva-Filho, L. C.; da Silva, G. V. J. Synth. Commun. 2007, 37,
3529–3539.
(38)
daꢀSilva-Filho, L. C; LacerdaꢀJr, V.; Constantino, M.
G.; daꢀSilva, G. V. J. Synthesis 2008, 16, 2527–2536.
(39)
Polo, E. C.; da Silva-Filho, L. C.; da Silva, G. V. J.;
Constantino, M. G. Quim. Nova 2008, 31, 763–766.
1
(40)
da Silva-Filho, L. C.; Frenhe, M. Orbital - Electron. J.
6,8-dione (6a): White solid. NMR H (CDCl3, 400 MHz, 25°C,
Chem. 2011, 3, 1–14.
TMS): δ = 7.89 (dd, J = 8.1; 1.5 Hz, 1H); 7.60-7.54 (m, 1H);
7.40-7.37 (m, 2H); 7.35-7.29 (m, 2H); 7.26-7.25 (m, 1H); 7.23-
7.13 (m, 2H); 5.00 (s, 1H); 2.93-2.84 (m, 1H); 2.84-2.72 (m, 1H);
2.70-2.52 (m, 2H); 2.48-2.39 (m, 2H) ppm. NMR 13C (CDCl3,
100 MHz, 25°C, TMS): δ = 196.9; 163.5; 160.3; 153.6; 152.3;
144.0; 131.9; 128.3; 127.8; 126.8; 126.1; 123.9; 116.6; 115.4;
113.3; 105.3; 36.6; 33.0; 26.8; 19.9 ppm.
(41)
da Silva, B. H, S. T.; Martins, L. M.; da Silva-Filho, L.
C. Synlett 2012, 23, 1973–1977.
(42)
3361–3365.
Santos, W. H.; da Silva-Filho, L. C. Synthesis 2012, 44,
(43)
Martins, L. M.; Silva, B. H. S. T.; Menezes, M. L.; da
Silva-Filho, L. C. Heterocycl. Lett. 2013, 3, 307–317.
Supplementary Material
(44)
Santos, W. H.; Siqueira, M. S.; da Silva-Filho, L. C.
Quim. Nova 2013, 36, 1303–1307.
Supplementary data associated with this article can be found in
(45)
Andrade, A.; Santos, G. C.; da Silva-Filho, L. C. J.
the
online
version.
Heterocycl. Chem. 2015, 52, 273–277.
(46)
Bartolomeu, A. A.; Menezes, M. L.; da Silva-Filho, L.
C. Synth. Commun. 2015, 45, 1114–1126.

6
Tetrahedron
- Chromeno[4,3-b]chromene derivatives are
Highlights
an important class of organic compounds
- Synthesis of Chromeno[4,3-b]chromene
derivatives by MCR promoted by NbCl5
- Synthesis of Chromeno[4,3-b]chromene
derivatives in mild reaction conditions