Iron-Mediated Cyclization of 1,3-Diynyl Propargyl Aryl Ethers with Dibutyl Diselenide: Synthesis of Selenophene-Fused Chromenes

Article abstract of DOI:10.1002/adsc.201901410

The synthesis of selenophene-fused chromene derivatives starting from 1,3-diynyl propargyl aryl ethers is reported herein. The method is based on carbon-carbon, carbon-selenium, selenium-carbon and carbon-selenium bonds formation in a one-pot protocol, using iron(III) chloride and dibutyl diselenide as promoters. The same reaction conditions were applied to propargyl anilines leading to the formation of 1-(butylselanyl)-selenophene quinolines. The results showed that the dilution and temperature of substrate addition had a crucial influence in the products obtained. When the substrates were added at room temperature, in the absence of a solvent, a mixture of products was obtained, whereas the slowly addition (15 min) of starting materials, as a dichloromethane solution, at 0 °C led to the product formation in good yields. The mechanistic study indicates that the cooperative action between iron(III) chloride and dibutyl diselenide was essential to promote the cyclization, whereas separately none of them was effective in promoting the cyclization. We proved the synthetic utility of heterocycles obtained in the Suzuki cross coupling reaction, giving the corresponding cross-coupled products in good yields. In addition, the organoselenium moiety was removed from the structures of products by using n-butyllithium. (Figure presented.).

Full text of DOI:10.1002/adsc.201901410

Title: Iron-Mediated Cyclization of 1,3-Diynyl Propargyl Aryl Ethers with
Dibutyl Diselenide: Synthesis of Selenophene-Fused Chromenes
Authors: Guilherme Lutz, Davi Back, and Gilson Zeni
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201901410
Iron-Mediated Cyclization of 1,3-Diynyl Propargyl Aryl Ethers
with Dibutyl Diselenide: Synthesis of Selenophene-Fused
Chromenes
Guilherme Lutz a, Davi F. Back b and Gilson Zeni a,*
a
Laboratꢀrio de Síntese, Reatividade, Avaliaꢁꢂo Farmacolꢀgica e Toxicolꢀgica de Organocalcogꢃnios CCNE, UFSM,
Santa Maria, Rio Grande do Sul, Brazil 97105-900.
E-mail: gzeni@ufsm.br; Fax: (+55)55-3220-8978; Tel: (+55)55-3220-9611.
b
Laboratꢀrio de Materiais Inorgꢄnicos, Departamento de Química, UFSM, Santa Maria, Rio Grande do Sul, Brazil 97105-
900.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
o
Abstract. The synthesis of selenophene-fused chromene of starting materials, as a dichloromethane solution, at 0 C
derivatives starting from 1,3-diynyl propargyl aryl ethers is led to the product formation in good yields.
The
reported herein. The method is based on carbon-carbon, mechanistic study indicates that the cooperative action
carbon-selenium, selenium-carbon and carbon-selenium between iron(III) chloride and dibutyl diselenide was
bonds formation in a one-pot protocol, using iron(III) essential to promote the cyclization, whereas separately
chloride and dibutyl diselenide as promoters. The same none of them was effective in promoting the cyclization.
reaction conditions were applied to propargyl anilines We proved the synthetic utility of heterocycles obtained in
leading to the formation of 1-(butylselanyl)-selenophene the Suzuki cross coupling reaction, giving the
quinolines. The results showed that the dilution and corresponding cross-coupled products in good yields. In
temperature of substrate addition had a crucial influence in addition, the organoselenium moiety was removed from the
the products obtained. When the substrates were added at structures of products by using n-butyllithium.
room temperature, in the absence of a solvent, a mixture of
products was obtained, whereas the slowly addition (15 min)
Keywords:
chromenes;
selenophenes;
diselenides;
selenides; heterocycles; iron.
developed for their preparation.[7]
methods, such as the addition of selenium
nucleophilic[8] or electrophilic[9] species to alkynes,
have been frequently used for the synthesis of
Classical
Introduction
Although the development of heterocycle-related
field merges with that of chemistry, there are
continuous improvements in their synthesis.[1] This
is because heterocycle derivatives have displayed
broad spectrum applications in medicine,
agriculture, industry, and chemistry.[2] In this
context, selenium-containing heterocycles,[3] even
though not present in natural products, have been
widely used in material science, as intermediaries
in organic synthesis, and also searched for different
biological activities.[4] Among selenium-containing
heterocycles, selenophene derivatives are synthetic
compounds, which have impressive biological,[5]
optical, and electronic properties.[6] Consequently,
a number of synthetic methods have been
functionalized selenophenes.
Furthermore, the
electrophilic cyclization of alkynes is also an
efficient alternative to their synthesis.[10] Recently,
Koketsu and co-workers successfully combined the
green chemistry principles of iron-based reactions
with the peculiar properties of the organoselenium
chemistry in the preparation of selenophene-fused
quinolines via an intramolecular cascade
cyclization of 1,3-diyne and 1,3,5-triyne.[11] Based
on the results reported in the literature, which
demonstrate that the cooperative action between
iron(III) salts and diorganyl dichalcogenides is a
useful tool to promote the cyclization of
unsaturated substrates,[12] we hypothesized that this
1
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
system could be an alternative to the cyclization anticipate that the use of an alkyl diselenide is an
and functionalization of 1,3-diynyl propargyl aryl indispensable requirement for the reaction to
ethers. Thus, we reported, in the present study, a proceed sequentially.
Thus, we began our
route to obtain selenophene-fused chromene investigation with the addition of 1a (0.25 mmol),
derivatives 2 through the cascade cyclization of at room temperature, under argon atmosphere, to a
1,3-diynyl propargyl aryl ethers 1 promoted by solution of FeCl3 (2.5 equiv) and dibutyl diselenide
iron(III) salt and diorganyl diselenides (Scheme 1). (1.1 equiv) in dichloroethane (4 mL), which was
Particularly, the selenophene-fused chromenes have prepared 10 min before. The reaction was stirred
attracted our attention because of their cytotoxic for 0.5 h at room temperature. These reaction
activity against various tumor cell lines, in vitro and conditions resulted in the formation of an
in vivo anti-angiogenic, antioxidant, and prooxidant inseparable 1:1 mixture of 2a and hydrogenated
properties.[13] Whereas the synthesis of furan-fused products 3 in 60% yield (Table 1, entry 1). To
chromenes[14] and thiophene-fused chromenes[15] is avoid the formation of the by-product 3, we
widespread in the literature, the preparation of 1- performed the addition of starting material 1a as a
(organoselenyl)-selenophene-fused chromenes is dichloromethane
solution;
however,
no
not reported. The advantages of this methodology improvement in the selectivity or yield was
are the formation of carbon-carbon, carbon- observed (Table 1, entry 2). The desired 2a was
selenium, selenium-carbon, and carbon-selenium obtained in good yield (74%), as a sole product,
bonds sequence in a one-pot protocol and the when the reaction was carried out by slowly adding
preparation
of
fused-heterocycles
with (15 min) the starting material 1a, as
a
simultaneous functionalization. Another feature of dichloroethane solution in the mixture of iron salt
o
our methodology is the introduction of an and dibutyl diselenide at 0 C (Table 1, entry 3).
organoselenium group in the heterocycles, which The screening of promoters revealed that none of
becomes the final product attractive as a substrate them showed higher efficiency than iron(III)
for new organic transformations[16] and for chloride, although iron(III) chloride hexahydrate
biological studies.[17]
gave the product 2a in moderate yield (Table 1,
entries 4-9). Thus, we chose iron(III) chloride as
the promoter to study the other parameters.
A
screening of the promoter amount indicated that the
use of 3 equivalents of iron(III) chloride did not
improve the yield of 2a, whereas 2.0 and 1.5
equivalents resulted in a decrease of yields (Table 1,
entries 10-12). We found that increasing the
amount of dibutyl diselenide to 1.5 and 2.1
equivalents did not result in an improvement in the
yields (Table 1, entries 13 and 14). Next, we
screened other solvents, such as dichlormethane,
dioxane, toluene, acetonitrile, and nitromethane.
These studies showed that all solvents tested led to
Scheme 1. Cyclization of 1,3-diynyl propargyl aryl
ethers 1 promoted by iron(III) salt and diorganyl
diselenides.
Results and Discussion
the
product
2a
formation;
however,
For the preparation of 1,3-diynyl propargyl aryl
ethers 1 we chose the reaction of phenol with
propargyl bromide in the presence of K2CO3 in
acetone at reflux for 24 h.[18] After that, we
installed the bromine in the alkyne using N-
dichloromethane was the solvent that gave the
highest yield. Thus, we selected dichloromethane,
the best solvent, for the next studies (Table 1,
entries 15-19). We also observed that the reaction
did not proceed without iron(III) chloride (Table 1,
entry 20). After these series of experiments, we
established the optimal reaction conditions as the
slowly addition (15 min) at 0 oC of starting material
1a (0.25 mmol), as a dichloromethane solution (2
mL), to a mixture of iron (III) chloride (2.5 equiv)
bromosuccinimide and silver nitrate.[19]
The
copper-catalyzed cross-coupling of bromoacetylene
with terminal alkynes led to 1,3-diynyl propargyl
aryl ethers 1.[20] The examples prepared, yields,
identification data, and NMR spectra are listed in
the Supporting Information.
After that, we
and
dibutyl
diselenide
(1.1
equiv)
in
attempted to determine the best reaction conditions
to the cyclization of 1,3-diynyl propargyl aryl ether
1a (Table 1). Because the second step of the
reaction mechanism involves the release of the
group directly attached to the selenium atom (See
mechanism discussion, Scheme 6), we can
dichloromethane (4 mL) which was prepared 10
min before. After that, the reaction was stirred for
0.5 h at room temperature (Table 1, entry 15).
2
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
Table 1. Effects of different reaction parameters on the
during the purification process.
When the
substituents were alkyl, propargyl alcohol, and
hydrogen no reaction took place and the starting
materials decomposed. Next, we evaluated the
influence of substituents in the aromatic ring
directly bonded to the oxygen atom. We supposed
that increasing the electron density of the aromatic
ring would increase the nucleophilicity of the
aromatic, consequently, electron donating groups
should lead to products in higher yields than
electron withdrawing groups.[21] Contrary to our
expectations, the results obtained did not indicate
any relationship between the yields and electronic
effects of substituents on the aromatic ring (Table
2, 2i-2r). We also studied the regioselectivity of
the nucleophilic attack of the aromatic ring on the
alkynes by adding a chlorine substituent at the
meta-position of the aryl group directly bonded to
the oxygen atom. In this case, as ortho-carbons
behave as nucleophiles, they may lead to a mixture
of products. We observed that the reaction was
moderately regioselective giving a 3:1 mixture
(determined by GCMS) of 2p and 2p’ in 70%
yields (Table 2, 2p and 2p’). The regioselectivity
in favor of 2p may be influenced by the steric
hindrance caused by the chlorine atom in the 2p'
regioisomer. The results demonstrated that the
yields of cyclized products were influenced by the
chalcogen atom, because 1,3-diynyl propargyl aryl
thioether gave low yields of thiochromene
derivative 2s, whereas the corresponding
selenoether and telluroether did not give the
products (Table 2, 2s). Finally, for products 2f, 2g,
2j and 2s, which were obtained in moderate yields,
we observed the total consumption of the starting
material and the presence of unidentified by-
products.
preparation of 1-(butylselanyl)-selenophene chromene
]
2a.[a
entry
1
2
3
4
5
promoter (equiv)
FeCl3 (2.5)
FeCl3 (2.5)
FeCl3 (2.5)
FeSO4·7H2O (2.5)
Fe0 (2.5)
solvent
DCE
DCE
DCE
DCE
yield[b] (%)
2a:3 (1:1)
2a:3 (1:1)[c]
74[d]
-
DCE
-
6
7
8
9
Fe(acac)3 (2.5)
FeCl3·6H2O (2.5)
BF3·OEt2 (2.5)
CuI (2.5)
DCE
DCE
DCE
DCE
-
54
trace
-
10
11
12
13
14
15
16
17
18
19
20
FeCl3 (2)
FeCl3 (1.5)
FeCl3 (3)
DCE
DCE
DCE
DCE
67
64
73
56[e]
53[f]
78
37
49
30
37
-
FeCl3 (2.5)
FeCl3 (2.5)
FeCl3 (2.5)
FeCl3 (2.5)
FeCl3 (2.5)
FeCl3 (2.5)
FeCl3 (2.5)
-
DCE
CH2Cl2
dioxane
toluene
CH3CN
CH3NO2
CH2Cl2
[a]
The reaction was performed by the addition of 1a (0.25
mmol), at room temperature, under argon atmosphere, to a
solution of FeCl3 (2.5 equiv) and dibutyl diselenide (1.1
equiv) in dichloroethane (4 mL), which was prepared 10
min before. The reaction was stirred for 0.5 h at room
temperature.
[b] Isolated yield after column chromatography.
[c] 1a was added as a dichloroethane solution (2 mL).
[d] 1a was added at 0 oC as a dichloroethane solution (2 mL).
[e] Dibutyl diselenide (1.5 equiv) was added.
[f] Dibutyl diselenide (2.1 equiv) was added.
The generality of optimized conditions utilizing
propargyl anilines rather than propargyl aryl ethers
After the optimum conditions for the cyclization
being determined, we applied them to other 1,3- as the substrate was further studied (Table 3). In
diynyl propargyl aryl ethers 1, to investigate the
effects of different substituents on the structure of moderate to good yields. We concluded that there
general, all examples prepared were obtained in
starting material. The results of the cyclization
reactions are summarized in Table 2. We started
was no relationship between substituents present in
the substrate and achieved yields, thus an extensive
these studies investigating the influence of discussion on the yields obtained would make it
substituents directly bonded to the alkyne.
Generally, electron rich aryl groups led to the made conserning the aromatic ring directly bonded
speculative. However, simple observation can be
formation
of
1-(butylselanyl)-selenophene
to the oxygen atom, which once again showed that
the electron withdrawing groups gave the products
chromene products in better yields than electron
poor aryl groups (Table 2, 2b-g). It was observed in good yields. These results, similar to those
that hindered 2-naphthyl substituents in the alkynes
had no steric influence in the reaction (Table 2, 2h). expectation that the product should be obtained;
found with propargyl aryl ethers, contradict our
Furthermore, 1,3-diynyl propargyl aryl ethers
having the aromatic ring with para-fluoro, meta-
methoxy, ortho-amino, and 3-pyridyl afforded the
desired products; however, they decomposed
however, in lower yields than electron rich
aromatic groups. Thus, we can conclude that in
addition to aromatic nucleophilicity, steric effects,
the characteristics of the electrophile, and the
3
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
Table 3. Synthesis of 1-(butylselanyl)-selenophene
quinolines 2t-y.[a], [b]
reactivity of carbon-carbon triple bond, among
others, can influence the yields of this cyclization
reaction.
Table 2. Synthesis of 1-(butylselanyl)-selenophene
chromenes 2a-s.[a], [b]
[a] The reaction was performed by slowly addition (15
o
min) at 0 C of 1,3-diynyl propargyl anilines 1 (0.25
mmol), as a dichloromethane solution (2 mL), to a
mixture of iron (III) chloride (2.5 equiv) and dibutyl
diselenide (1.1 equiv) in dichloromethane (4 mL), which
was prepared 10 min before. After that, the reaction was
stirred at room temperature for the time indicated in
Table 3.
[b] Isolated yield after column chromatography.
Mechanistic Considerations
Next, a series of control experiments were
conducted to gain insights into the mechanism for
this cyclization.
In the first experiment,
hydroquinone was used as a radical scavenger.
Thus, the reaction of 1,3-diynyl propargyl aryl
ethers, under the optimized conditions, in the
presence of hydroquinone led to the formation of 1-
(butylselanyl)-selenophene chromene 2a in 78%
yield. This result weakens the hypothesis that the
reaction occurs via selenium radical species
prepared in situ by the reaction of dibutyl
diselenide with iron(III) chloride (Scheme 2, eq 1).
In the next set of experiments, we carried out the
cyclization by using a selenium electrophilic
species, prepared via the reaction of dibutyl
diselenide with NBS (Scheme 2, eq 2) and with
iron(III) chloride in the absence of dibutyl
diselenide (Scheme 2, eq 3). The purpose of this
experiment was to determine if the products were
formed via an electrophilic cyclization reaction
with an electrophilic selenium species acting as a
promoter without the participation of iron(III)
chloride. In either case, the product 2a was not
[a]
The reaction was performed by slowly addition (15
o
min) at 0 C of 1,3-diynyl propargyl aryl ethers 1 (0.25
mmol), as a dichloromethane solution (2 mL), to a
mixture of iron (III) chloride (2.5 equiv) and dibutyl
diselenide (1.1 equiv), in dichloromethane (4 mL), which
was prepared 10 min before. After that, the reaction was
stirred at room temperature for the time indicated in
Table 2.
[b] Isolated yield after column chromatography.
formed under these conditions.
Thus, we
4
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
concluded that a cooperative action between dibutyl carbon-halogen bond, became these compounds an
diselenide and iron(III) chloride is essential for the impressive choice for the carbon-carbon bond
outcome of the cyclization. When 1,3-diynyl construction.[23] In a last set of experiments, we
propargyl aryl ether 1a was reacted under the
standard reaction in the presence of gaseous HCl
and the absence of iron(III) chloride, the product 2a
was not formed (Scheme 2, eq 4). This result
shows that the gaseous HCl, formed in situ by
decomposition of iron(III) chloride, was not the
cyclization promoter. In order to isolate and
identify the intermediate 2b’ (Scheme 2, eq 5), we
carried out the reactions under low temperature (-78
oC) and reduced amounts of dibutyl diselenide (0.5
equiv); however, in none of these experiments this
intermediate was obtained. In these cases, the
product 2b was always obtained, although in low
yields. Thus, it seems that the reaction mechanism
for the cyclization of 1,3-diynyl propargyl aryl
ethers 1 promoted by iron(III) salt and diorganyl
diselenide involves an initial formation of
seleniranium ion I through activation of the carbon-
carbon triple bond promoted by an organoselenium
iron complex. The attack of the electron cloud
from the aromatic ring at the activated intermediate
I gives the cyclized species II. The removal of a
hydrogen from intermediate III restores the
aromatic ring, giving the 3-(butylselanyl)-2H-
chromene IV. The organoselenium iron complex
promoted the activation of the second alkynes for
the selenium nucleophilic attack, generating the
selenophene cation VI. The removal of the butyl
group bonded to the selenium atom via SN2
displacement by the chloride ion, present in the
reaction mixture, affords the selenophene chromene
derivatives 2 and butyl chloride, which was
detected by CGMS. Because of the last step of the
reaction mechanism involves a SN2 type reaction,
the substrates must have a group with a Csp3
directly bonded to the selenium atom. Therefore,
the reactions with diaryl diselenide derivatives
would not lead to the product formation.
study.
Scheme 2. Control experiments for the mechanistic
The formation of a carbon-carbon bond by using
explored the potential of these selenophene
palladium catalysts is one of the most important
discovery of organic chemistry. The aryl or vinyl
halides are frequently used as substrates, although
chromene derivatives 2 towards Suzuki cross-
coupling reactions catalyzed by palladium salts.
Thus, the reaction of selenophene chromene 2b
triflate, tosylate, phosphonate, and sulfonate can be
with different boronic acids under Suzuki
conditions[24] gave the corresponding products 4a
and 4b in 82% and 72% yields, respectively
(Scheme 4, eq 1). When the same conditions were
applied to the reaction of selenophene quinoline 2u
with 4-methoxyphenylboronic acid, the cross-
coupled product 4c was obtained in 43% yield
(Scheme 4, eq 2).
a good alternative.
Recently, the use of
organochalcogens as an electrophile in the
palladium cross-coupling has emerged as a
powerful substitutes to these substrates.[22] The
simple
and
easy
preparation
of
organochalcogenides associated with their chemo-,
regio- and stereoselective reactions and the fact that
the oxidative addition of organoselenides on
palladium is faster than organohalides, because the
carbon-selenium bond is more labile than the
The structures containing selenium atoms may
contain important biological activities as previously
5
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
0
justified; however, in some cases, the selenium a solution of 2b in THF (3 mL) at 78 C, followed
chemistry can be used as a tool for the construction by 24 h at room temperature, gave the 4-alkynyl
of new structures. For this reason and to expand coumarin 5 in 80% yield (Scheme 5). 4-Alkynyl
the synthetic application of the compounds coumarin is an important class of compounds
prepared, we carried out the reaction of because some of them have found applications in
selenophene chromene 2b with n-buthyllithium to medicinal, pharmaceutical[25] and advanced optical
promote the opening of selenophene ring and, materials.[26]
consequently, eliminate the butyl selenolate anion.
Thus, the addition of n-buthyllithium (1.0 equiv) to
.
Scheme 3. Proposed reaction mechanism.
Conclusions
In summary, we demonstrate the synthesis of
several 1,3-diynyl propargyl aryl ethers and 1,3-
diynyl propargyl anilines, which were used as the
starting materials in the cyclization reactions
promoted by iron(III) chloride and dibutyl
diselenide, establishing an efficient route to obtain
selenophene-fused chromenes and 1-(butylselanyl)-
selenophene quinolines. The results showed that
both dilution and temperature of substrate addition
had a fundamental influence on the reaction
outcome. When the substrates were added at room
temperature, in the absence of a solvent, a mixture
of products was obtained, whereas the slow
addition (15 min) of the starting materials, as a
Scheme 4. Reactivity of 2b and 2u towards
o
dichloromethane solution, at 0 C led to the desired
palladium-catalyzed
reactions.
Suzuki
cross-coupling
products in good yields. The reaction mechanism
indicates that the cooperative action between
iron(III) chloride and dibutyl diselenide was
essential to promote cyclization. We also found
that electronic and steric effects of substituents did
not directly affect the yields, indicating that besides
the nucleophilicity of aromatic ring other factors,
such as the nature of the electrophilic source and
polarization of the carbon-carbon triple bond can
also significantly influence the yields. All the
compounds were characterized by 1H and 13C NMR
Scheme 5. Reactivity of 2b towards n-
buthyllithium reaction.
spectroscopy.
Furthermore, the 6-endo-dig
6
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
= 8.0 Hz, J =1.3 Hz, 1H), 5.19 (s, 2H), 2.43 (t, J = 7.4
Hz, 2H), 2.39 (s, 3H), 1.30 (quint, J = 7.4 Hz, 2H), 1.10
(sex, J = 7.4 Hz, 2H), 0.67 (t, J = 7.4 Hz, 3H). 13C {1H}
NMR (100 MHz, CDCl3): δ (ppm) 153.6, 151.0, 138.0,
135.8, 134.9, 133.8, 130.2, 128.8, 128.2, 126.1, 124.1,
123.6, 121.7, 116.8, 66.7, 31.5, 29.5, 22.4, 21.2, 13.3.
MS (EI, 70 eV. m/z (relative intensity)): 462 (16), 405
(3), 325 (61), 245 (100), 202 (19). HRMS: calcd for
C22H23OSe2 (ESI-TOF, [M + H]+): 463.079, found:
463.0086.
followed by
a
5-endo-dig cyclization was
confirmed by X-ray analyses of the crystalline
sample (Supporting Information, Figure S1 and S2,
CCDC 1961007, and 1961008 for compounds 2o
and 2u, respectively).[27]
Experimental Section
General procedure for 1-(butylselanyl)-selenophene 1-(Butylselanyl)-2-(4-methoxyphenyl)-4H-
chromenes/quinolines 2a-2y: The reaction was
selenopheno[2,3-c]chromene (2d): The product was
performed by the dropwise addition of dichloroethane (2 isolated by column chromatography (hexane/ethyl
mL) solution containing 1,3-diynyl propargyl aryl acetate 99:1 as eluent) as a yellow oil. Yield: 0.073 g
0
ethers/propargyl anilines 1 (0.25 mmol), at 0 C, under (61%). 1H NMR (CDCl3, 400 MHz): δ (ppm) 8.82 (dd, J
argon atmosphere, to a solution of FeCl3 (0.625 mmol, = 7.8, J = 1.6 Hz, 1H), 7.42 (d, J = 8.7 Hz, 2H), 7.19 (td,
2.5 equiv) and diorganoyl dichalcogenide (0.275 mmol,
1.1 equiv) in dichloroethane (4 mL), which was prepared
J = 7.7, J = 1.7 Hz, 1H), 7.06 (td, J = 7.6, J = 1.4 Hz,
1H), 7.01 (dd, J = 8.0, J = 1.3 Hz, 1H), 6.94 (d, J = 8.7
10 min before. The reaction mixture was stirred under Hz, 2H), 5.19 (s, 2H), 3.85 (s, 3H), 2.43 (t, J = 7.4 Hz,
room temperature for the time indicated in Tables 2 and 2H), 1.30 (quint, J = 7.4 Hz, 2H), 1.10 (sex, J = 7.4 Hz,
3. The organic phase was separated, dried with MgSO4 2H), 0.68 (t, J = 7.4 Hz. 3H). 13C {1H} NMR (100 MHz,
and concentrated under vacuum. The residue was CDCl3): δ (ppm) 159.5, 153.6, 150.7, 135.5, 134.8,
purified by flash chromatography. 1-(Butylselanyl)-8-
methyl-2-phenyl-4H-selenopheno[2,3-c]chromene
131.5, 129.0, 128.1, 124.1, 123.6, 121.7, 118.4, 116.8,
113.5, 66.7, 55.3, 31.4, 29.4, 22.4, 13.3. MS (EI, 70 eV.
(2a): The product was isolated by column m/z (relative intensity)): 478 (36), 418 (7), 341 (100),
chromatography (hexane as eluent) as a yellow oil. 261 (72), 218 (28). HRMS: calcd for C22H23O2Se2 (ESI-
1
Yield: 0.09 g (78%). H NMR (CDCl3, 400 MHz): δ TOF, [M + H]+): 479.028, found: 479.0037.
(ppm) 8.65 (d, J = 2.1 Hz, 1H), 7.54-7.35 (m, 5H), 7.01
(dd, J = 8.2 Hz, J = 2.1 Hz, 1H), 6.92 (d, J = 8.1 Hz,
1-(Butylselanyl)-2-(2-methoxyphenyl)-4H-
selenopheno[2,3-c]chromene (2e): The product was
1H), 5.17 (s, 2H), 2.45 (t, J = 7.4 Hz, 2H), 2.36 (s, 3H), isolated by column chromatography (hexane/ethyl
1.32 (quint, J = 7.4 Hz, 2H), 1.11 (sex, J = 7.4 Hz, 2H), acetate 99:1 as eluent) as a yellow oil. Yield: 0.087 g
0.68 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (CDCl3, 100 (73%). 1H NMR (CDCl3, 400 MHz): δ (ppm) 8.90 (dd, J
MHz): δ (ppm) 151.4, 150.5, 136.7, 136.2, 134.9, 130.9, = 7.9 Hz, 1.6 Hz, 1H), 7.37 (td, J = 7.4 Hz, J = 1.8 Hz,
130.3, 128.6, 128.0, 124.5, 123.2, 118.9, 116.5, 66.6, 1H), 7.31 (dd, J = 7.5 Hz, J = 1.7 Hz, 1H), 7.18 (td, J =
31.4, 29.5, 22.4, 21.0, 13.3. MS (EI, 70 eV. m/z (relative
7.4 Hz, J = 1.7 Hz, 1H), 7.07-6.98 (m, 3H), 6.96 (dd, J =
intensity)): 462 (22), 325 (73), 246 (22), 245 (100), 207 8.3 Hz, J = 1.0 Hz, 1H), 5.21 (s, 2H), 3.82 (s, 3H), 2.43
(23). HRMS: calcd for C22H23OSe2 (ESI-TOF, [M + (t, J = 7.4 Hz. 2H), 1.31 (quint, J = 7.4 Hz. 2H), 1.10
H]+): 463.0079, found: 463.0085.
1-(Butylselanyl)-2-phenyl-4H-selenopheno[2,3-
c]chromene (2b): The product was isolated by column
(sex, J = 7.4 Hz, 2H), 0.68 (t. J = 7.4 Hz, 3H). 13C {1H}
NMR (100 MHz, CDCl3): δ (ppm) 156.9, 153.4, 146.3,
136.59, 133.9, 132.3, 129.8, 128.0, 125.6, 123.9, 123.5.
121.6, 121.1, 120.1, 116.8, 110.8, 66.7, 55.4, 31.5, 28.7,
chromatography (hexane as eluent) as a yellow oil.
1
Yield: 0.086 g (80%). H NMR (CDCl3, 400 MHz): δ 22.5, 13.3. MS (EI, 70 eV. m/z (relative intensity)): 478
(ppm) 8.83 (dd, J = 7.8 Hz, J = 1.6 Hz, 1H), 7.52-7.36 (46), 241 (13), 341 (100), 325 (44), 261 (60), 207 (45).
(m, 5H), 7.21 (td, J = 7.9 Hz, J = 1.6 Hz, 1H), 7.07 (td, J HRMS: calcd for C22H23O2Se2 (ESI-TOF, [M + H]+):
= 7.7 Hz, J = 1.4 Hz, 1H), 7.03 (dd, J = 8.0 Hz, J = 1.2 479.0028, found: 479.0036.
Hz, 1H), 5.20 (s, 2H), 2.42 (t, J = 7.4 Hz, 2H), 1.28
1-(Butylselanyl)-2-(4-chlorophenyl)-4H-
(quint, J = 7.4 Hz, 2H), 1.07 (sex, J = 7.4 Hz, 2H), 0.66 selenopheno[2,3-c]chromene (2f): The product was
(t, J = 7.4 Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz): δ isolated by column chromatography (hexane as eluent)
(ppm) 153.5, 150.6, 136.5, 136.0, 134.8, 130.3, 128.2, as a orange oil. Yield: 0.049 g (40%). 1H NMR (CDCl3,
128.0, 126.1, 124.0, 123.4, 121.7, 118.7, 116.8, 66.6, 400 MHz): δ (ppm) 8.82 (dd, J = 7.8 Hz, J =1.6 Hz, 1H),
31.3, 29.4, 22.4, 13.3. 77Se NMR (77 MHz, in CDCl3 7.46-7.34 (m, 4H), 7.20 (td, J = 7.2 Hz, J = 1.6 Hz, 1H),
with diphenyl diselenide as internal reference): δ (ppm)
7.06 (td, J = 7.6 Hz, J = 1.3 Hz, 1H), 7.02 (dd, J = 8.0
644.3, 192.6. MS (EI, 70 eV. m/z (relative intensity)): Hz, J = 1.3 Hz, 1H), 5.19 (s, 2H), 2.43 (t, J = 7.4 Hz,
446 (15), 311 (53), 231 (100), 202 (62). HRMS: calcd 2H), 1.29 (quint, J = 7.4 Hz, 2H), 1.09 (sex, J = 7.4 Hz,
for C21H21OSe2 (ESI-TOF, [M + H]+): 448.9923, found: 2H), 0.68 (t. J = 7.4 Hz, 3H). 13C {1H} NMR (100 MHz,
448.9939.
CDCl3): δ (ppm) 153.5, 149.2, 136.3, 135.1, 135.0,
134.1, 131.5, 129.1, 128.3, 128.3, 124.0, 123.3, 121.7,
116.9, 66.5, 31.4, 29.6, 22.4, 13.3. MS (EI, 70 eV. m/z
1-(Butylselanyl)-2-(p-tolyl)-4H-selenopheno[2,3-
c]chromene (2c): The product was isolated by column
chromatography (hexane as eluent) as a yellow oil. (relative intensity)): 482 (56), 425 (16), 344 (100), 265
1
Yield: 0.086 g (74%). H NMR (CDCl3, 400 MHz): δ (95), 202 (39). HRMS: calcd for C21H20ClOSe2 (ESI-
(ppm) 8.83 (dd, J = 7.9 Hz, J = 1.6 Hz, 1H), 7.42-7.13 TOF, [M + H]+): 482.9533, found 482.9539.
(m, 5H), 7.05 (td, J = 7.6 Hz, J = 1.3 Hz, 1H), 7.01 (dd, J
7
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
124.5, 123.3, 118.7, 116.5, 66.6, 31.4, 29.4, 22.4, 21.3,
2-(2-Bromophenyl)-1-(butylselanyl)-4H-
selenopheno[2,3-c]chromene (2g): The product was 21.0, 13.3. MS (EI, 70 eV. m/z (relative intensity)): 476
isolated by column chromatography (hexane as eluent) (36), 417 (9), 339 (87), 259 (100), 215 (25), 207 (29).
1
as a yellow oil. Yield: 0.063 g (48%). H NMR (CDCl3, HRMS: cald for C23H25OSe2 (ESI-TOF, [M + H]+):
400 MHz): δ (ppm) 8.91 (dd, J = 7.8 Hz, J = 1.6 Hz, 477.0236, found: 477.0230.
1H), 7.70-7.65 (m, 1H), 7.39-7.31 (m, 2H), 7.28-7.22
6-(Tert-butyl)-1-(butylselanyl)-2-phenyl-4H-
(m, 1H), 7.20 (td, J = 7.4 Hz, J = 1.6 Hz, 1H), 7.06 (td. J selenopheno[2,3-c]chromene (2k): The product was
= 7.4 Hz, J = 1.4 Hz, 1H), 7.02 (dd, J = 8.0 Hz, J = 1.3 isolated by column chromatography (hexane as eluent)
Hz, 1H), 5.23 (s, 2H), 2.51 (t, J = 7.4 Hz, 2H), 1.37 as a yellow solid. Yield: 0.072 g (57%); mp 97-98 °C. 1H
(quint, J = 7.4 Hz, 2H), 1.14 (sex, J = 7.4 Hz, 2H), 0.72 NMR (CDCl3, 400 MHz): δ (ppm): 8.60 (dd, J = 7.8 Hz,
(t, J = 7.4 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ J = 1.6 Hz, 1H), 7.59-7.34 (m, 5H), 7.24 (dd, J = 7.8 Hz,
(ppm) 153.4, 149.0, 137.6, 137.0, 133.7, 132.7, 132.6, J = 1.4 Hz, 1H), 7.02 (t, J = 7.8 Hz, 1H), 5.13 (s, 2H),
129.7, 128.3, 126.8, 125.2, 123.7, 123.3, 121.8, 121.7, 2.41 (t, J = 7.4 Hz, 2H), 1.42 (s, 9H), 1.28 (quint, J = 7.4
116.8, 66.5, 31.7, 29.1, 22.5, 13.3. MS (EI, 70 eV. m/z Hz, 2H). 1.07 (sex. J = 7.4 Hz, 2H), 0.65 (t, J = 7.4 Hz,
(relative intensity)): 525 (2), 447 (39), 389 (100), 309 3H). 13C {1H} NMR (100 MHz, CDCl3): δ (ppm) 152.2,
(52), 281 (21), 202 (63). HRMS: calcd for C21H20BrOSe2 150.1, 138.6, 136.8, 135.8, 135.8, 130.3, 128.0, 128.0,
(ESI-TOF, [M + H]+): 526.9028, found: 526.9036.
1-(Butylselanyl)-2-(naphthalen-2-yl)-4H-
125.7, 124.5, 122.5, 121.0, 119.2, 65.7, 34.7, 31.4, 29.9,
29.4, 22.4, 13.3. 77Se NMR (77 MHz, in CDCl3 with
selenopheno[2,3-c]chromene (2h): The product was diphenyl diselenide as internal reference): δ (ppm) 617.0,
isolated by column chromatography (hexane as eluent) 203.7. MS (EI, 70 eV. m/z (relative intensity)): 504 (17),
1
as a yellow oil. Yield: 0.082 g (66%). H NMR (CDCl3, 367 (100), 365 (48), 287 (27), 231 (12) 57 (26). HRMS:
400 MHz): δ (ppm) 8.91 (dd, J = 7.8 Hz, J = 1.3 Hz, cald for C25H29OSe2 (ESI-TOF, [M + H]+): 505.0549,
1H), 7.90-7.85 (m, 2H), 7.82 (dd, J = 8.5 Hz, J = 1.3 Hz, found: 505.0555.
1H), 7.50 - 7.40 (m, 4H), 7.19 (td, J = 8.0 Hz, J = 1.6
1-(Butylselanyl)-2,8-diphenyl-4H-selenopheno[2,3-
Hz, 1H), 7.08 - 7.01 (m, 2H), 5.24 (s, 2H), 2.39 (q, J = c]chromene (2l): The product was isolated by column
6.9 Hz, 2H), 1.25 (quint, J = 7.4 Hz, 2H), 1.00 (sex, J = chromatography (hexane as eluent) as a yellow oil.
7.4 Hz, 2H), 0.61 (t, J = 7.3 Hz, 3H). 13C {1H} NMR Yield: 0.065 g (50%). H1 NMR (CDCl3, 400 MHz): δ
(100 MHz, CDCl3): δ (ppm) 153.6, 148.4, 136.9, 134.2, (ppm) 9.17 (d, J = 2.3 Hz, 1H), 7.64 (dd, J = 7.2 Hz, J =
134.1, 133.5, 132.6, 128.9, 128.8, 128.3, 128.1, 126.3, 1.2 Hz, 1H), 7.53-7.26 (m, 10H), 7.08 (d, J = 8.4 Hz,
126.1, 126.0, 124.8, 123.9, 123.5, 122.0, 121.7, 116.9, 1H), 5.23 (s, 2H), 2.46 (t, J = 7.4 Hz, 2H), 1.28 (quint, J
66.6, 31.6, 29.4, 22.4, 13.2. MS (EI, 70 eV. m/z (relative = 7.4 Hz, 2H), 1.05 (sex, J = 7.4 Hz, 2H), 0.61 (t, J = 7.4
intensity)): 498 (29), 441 (36), 361 (39), 281 (100), 252 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ (ppm)
(46), 207 (76). HRMS: calcd for C25H20OSe2 (ESI-TOF, 153.2, 151.1, 141.0, 136.6, 136.3, 134.9, 134.6, 130.4,
[M + H]+): 499.0079, found: 499.0085.
1-(Butylselanyl)-6-methyl-2-phenyl-4H-
128.8, 128.1, 128.1, 126.8, 126.8, 126.7, 123.7, 122.9,
118.9, 117.2, 66.8, 31.5, 29.7, 22.5, 13.3. MS (EI, 70 eV.
selenopheno[2,3-c]chromene (2i): The product was m/z (relative intensity)): 524 (26), 388 (61), 307 (100),
isolated by column chromatography (hexane as eluent) 230 (50), 215 (33) HRMS: calcd for C27H25OSe2 (ESI-
1
as a yellow oil. Yield: 0.064 g (55%). H NMR (CDCl3, TOF, [M + H]+): 525.0236, found: 525.0230.
400 MHz): δ (ppm) 8.65 (dd, J = 7.9 Hz, J = 1.7 Hz,
1-(Butylselanyl)-8-methoxy-2-phenyl-4H-
1H), 7.54-7.34 (m, 5H), 7.07 (dq, J = 7.5 Hz, J = 0.9 Hz, selenopheno[2,3-c]chromene (2m): The product was
1H), 6.97 (t, J = 7.7 Hz, 1H), 5.19 (s, 2H), 2.41 (t, J = isolated by column chromatography (hexane/ethyl
7.4 Hz, 2H), 2.29 (s, 3H), 1.28 (quint, J = 7.4 Hz, 2H), acetate 99:1 as eluent) as a yellow oil. Yield: 0.102 g
1.07 (sex, J = 7.4 Hz, 2H), 0.66 (t, J = 7.4 Hz, 3H). 13C (85%). 1H NMR (CDCl3, 400 MHz): δ (ppm) 8.55 (d, J =
{1H} NMR (100 MHz, CDCl3): δ (ppm) 151.6, 150.4, 3.0 Hz, 1H), 7.53-7.36 (m, 5H), 6.95 (d, J = 8.7 Hz, 1H),
136.7, 135.8, 135.3, 130.3, 129.9, 128.0, 128.0, 126.1, 6.77 (dd, J = 8.8 Hz, J = 3.0 Hz, 1H), 5.16 (s, 2H), 3.83
123.0, 121.8, 120.9, 119.0, 66.4, 31.4, 29.4, 22.4, 16.3, (s, 3H), 2.46 (t, J = 7.4 Hz. 2H), 1.30 (quint, J = 7.4 Hz,
13.3. MS (EI, 70 eV. m/z (relative intensity)): 462 (23), 2H), 1.10 (sex, J = 7.4 Hz, 2H), 0.68 (t, J = 7.4 Hz, 3H).
325 (81), 323 (41), 245 (100), 207 (64), 202 (23). 13C {1H} NMR (CDCl3, 100 MHz): δ (ppm) 154.3,
HRMS: cald for C22H23OSe2 (ESI-TOF, [M + H]+): 150.9, 147.5, 137.0, 136.6, 134.7, 130.3, 128.1, 128.0,
463.0079, found: 463.0083.
124.1, 118.8, 117.3, 113.9, 109.1, 66.7, 55.8, 31.5, 29.6,
22.4, 13.3. MS (EI, 70 eV. m/z (relative intensity)): 479
1-(Butylselanyl)-8-methyl-2-(m-tolyl)-4H-
selenopheno[2,3-c]chromene (2j): The product was (23), 341 (54), 261 (100), 207 (79). HRMS: calcd for
isolated by column chromatography (hexane as eluent) C22H23O2Se2 (ESI-TOF, [M + H]+): 479.0028, found:
1
as a yellow oil. Yield: 0.056 g (47%), H NMR (CDCl3, 479.0033.
400 MHz): δ (ppm) 8.65 (d, J = 2.1 Hz, 1H), 7.29 (d, J =
1-(Butylselanyl)-8-iodo-2-phenyl-4H-selenopheno[2,3-
4.8 Hz, 3H), 7.18 (td, J = 4.3 Hz, J = 2.4 Hz, 1H), 6.99 c]chromene (2n): The product was isolated by column
(dd, J = 8.2 Hz, J = 2.1 Hz, 1H), 6.91 (d, J = 8.1 Hz, chromatography (hexane as eluent) as a yellow oil.
1
1H), 5.15 (s, 2H), 2.46 (t, J = 7.4 Hz, 2H), 2.40 (s, 3H), Yield: 0.106 g (74%). H NMR (CDCl3, 400 MHz): δ
2.35 (s, 3H), 1.32 (quint, J = 7.4 Hz, 2H), 1.12 (sex, J = (ppm) 9.22 (d, J = 2.2 Hz, 1H), 7.51-7.38 (m, 6H), 6.77
7.4 Hz, 2H), 0.69 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (d, J = 8.5 Hz, 1H), 5.21 (s, 2H), 2.46 (t, J = 7.4 Hz, 2H),
(100 MHz, CDCl3): δ (ppm) 151.4, 150.7, 137.6, 136.6, 1.35 (quint, J = 7.4 Hz, 2H), 1.15 (sex, J = 7.4 Hz, 2H),
136.0, 134.9, 130.9, 130.8, 128.8, 128.6, 127.9, 127.4, 0.71 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (CDCl3,100
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901410
Advanced Synthesis & Catalysis
MHz): δ (ppm) 153.3, 151.4, 136.8, 136.7, 136.3, 132.5, 2H), 0.99 (sex, J = 7.4 Hz. 2H), 0.62 (t, J = 7.4 Hz. 3H).
130.3, 129.0, 128.2, 128.1, 126.1, 125.6, 119.0, 84.4, 13C {1H} NMR (100 MHz. CDCl3): δ (ppm) 148.1,
66.6, 31.4, 29.7, 22.5, 13.4. MS (EI, 70 eV. m/z (relative 140.0, 138.3, 136.9, 133.3, 132.8, 130.2, 128.4, 128.1,
intensity)): 574 (100), 515 (25), 437 (96), 389 (28), 357 127.9, 126.8, 126.8, 125.6, 120.5, 31.2, 29.3, 29.1, 22.3,
(97), 202 (51). HRMS: calcd for C21H20IOSe2 (ESI-TOF, 13.3. MS (EI. 70 eV. m/z (relative intensity)): 464 (24),
[M + H]+): 574.8889, found: 574.8894.
1-(Butylselanyl)-6-iodo-2-phenyl-4H-selenopheno[2,3-
405 (13), 325 (47), 247 (100), 215 (34), 207 (49).
HRMS: cald for C21H21SSe2 (ESI-TOF, [M + H]+):
c]chromene (2o): The product was isolated by column 464.9694, found 464.9694.
chromatography (hexane as eluent) as a white solid.
1-(Butylselanyl)-2-phenyl-5-tosyl-4,5-
Yield: 0.103 g (72%); mp 102-103 °C. 1H NMR (CDCl3, dihydroselenopheno[2,3-c]quinolone (2t): The product
400 MHz): δ (ppm) 8.82 (dd, J = 7.6 Hz, J =1.2 Hz, 1H), was isolated by column chromatography (hexane as
1
7.64 (dd, J = 7.8 Hz, J = 1.5 Hz, 1H), 7.51-7.37 (m, 5H), eluent) as a yellow oil. Yield: 0.084 g (56%), H NMR
6.83 (t, J = 7.9 Hz, 1H), 5.28 (s, 2H), 2.38 (t, J = 7.4 Hz, (CDCl3, 400 MHz): δ (ppm) 8.64-8.59 (m, 1H), 7.86-
2H), 1.26 (quint, J = 7.4 Hz, 2H), 1.06 (sex, J = 7.4 Hz, 7.81 (m, 1H), 7.43-7.32 (m, 7H), 7.24-7.19 (m, 2H), 6.93
2H), 0.66 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (100 MHz, (dd, J = 8.5 Hz, J = 0.8 Hz, 2H), 4.96 (s, 2H), 2.27 (s,
CDCl3): δ (ppm) 152.7, 151.2, 137.8, 136.4, 136.3, 3H), 2.13 (t, J = 7.4 Hz, 2H), 1.29 (quint, J = 7.4 Hz,
134.4, 130.2, 128.1, 128.0, 124.1, 124.0, 123.3, 118.5, 2H), 1.13 (sex, J = 7.4 Hz, 2H), 0.73 (t, J = 7.4 Hz, 3H).
84.9, 67.2, 31.3, 29.5, 22.3, 13.3. MS (EI, 70 eV. m/z 13C {1H} NMR (100 MHz, CDCl3): δ (ppm) 150.0,
(relative intensity)): 572 (5), 437 (73), 435 (19), 357 142.8, 137.3, 136.6, 135.9, 135.5, 134.8, 130.1, 130.0,
(70), 202 (100). HRMS: cald for C21H20IOSe2 (ESI-TOF, 128.7, 128.1, 128.1, 128.0, 127.4, 127.1, 126.6, 124.6,
[M + H]+): 574.8889, found: 574.8893.
6-Bromo-1-(butylselanyl)-8-methyl-2-phenyl-4H-
119.0, 47.6, 31.3, 29.4, 22.6, 21.5, 13.4. HRMS: cald for
C28H28NO2SSe2 (ESI-TOF, [M + H]+): 602.0171, found:
selenopheno[2,3-c]chromene (2q): The product was 602.0177.
isolated by column chromatography (hexane as eluent)
1-(Butylselanyl)-8-methyl-2-phenyl-5-tosyl-4,5-
1
as a yellow oil. Yield: 0.097 g (72%). H NMR (CDCl3, dihydroselenopheno[2,3-c]quinolone (2u): The product
400 MHz): δ (ppm) 8.62 (dd, J = 2.0 Hz, J = 0.9 Hz, was isolated by column chromatography (hexane/ethyl
1H), 7.51-7.36 (m, 5H), 7.27-7.25 (m, 1H), 5.25 (s, 2H), acetate 98:2 as eluent) as a yellow solid. Yield: 0.075 g
0
2.41 (t, J = 7.4 Hz. 2H), 2.34 (s, 3H), 1.28 (quint, J = 7.4 (49%); mp 96-97 C. 1H NMR (CDCl3, 400 MHz): δ
Hz, 2H), 1.09 (sex, J = 7.4 Hz, 2H), 0.68 (t, J = 7.4 Hz, (ppm) 8.44 (dd, J = 1.5 Hz, J = 0.6 Hz, 1H), 7.71 (d, J =
3H). 13C {1H} NMR (100 MHz, CDCl3): δ (ppm) 151.0, 8.1 Hz, 1H), 7.43-7.31 (m, 5H), 7.24-7.20 (m, 2H), 7.17
148.1, 136.6, 136.4, 134.4, 132.0, 132.0, 130.2, 128.1, (ddd, J = 8.1 Hz, J = 2.0 Hz, J = 0.8 Hz, 1H), 6.93 (dd, J
128.1, 124.4, 123.7, 118.6, 110.5, 67.1, 31.3, 29.5, 22.4, = 8.6 Hz, J = 0.7 Hz, 2H), 4.94 (s, 2H), 2.41 (s, 3H),
20.7, 13.3. MS (EI, 70 eV. m/z (relative intensity)): 541 2.27 (s, 3H), 2.12 (t, J = 7.4 Hz, 2H), 1.31 (quint, J = 7.4
(16), 405 (75), 403 (100), 401 (50), 325 (79), 323 (84), Hz, 2H), 1.16 (sex. J = 7.4 Hz, 2H), 0.75 (t, J = 7.4 Hz,
215 (93). HRMS: calcd for C22H22BrOSe2 (ESI-TOF, [M 3H). 13C {1H} NMR (100 MHz. CDCl3): δ (ppm) 149.9,
+ H]+): 540.9184, found: 540.9189.
6-Bromo-1-(butylselanyl)-8-fluoro-2-phenyl-4H-
142.7, 137.2, 136.7, 136.4, 136.0, 135.6, 132.3, 130.0,
129.8, 128.7, 128.2, 128.0, 127.9, 127.1, 125.1, 119.1,
selenopheno[2,3-c]chromene (2r): The product was 77.3, 77.0, 76.6, 47.7, 31.3, 29.4, 22.6, 21.5, 21.4, 13.4.
isolated by column chromatography (hexane as eluent) 77Se NMR (77 MHz, in CDCl3 with diphenyl diselenide
1
as a yellow oil. Yield: 0.093 g (68%). H NMR (CDCl3, as internal reference): δ (ppm) 649.8, 194.7. HRMS: cald
400 MHz): δ (ppm) 8.73 (dd, J = 10.3 Hz, J = 2.9 Hz, for C29H30NO2SSe2 (ESI-TOF, [M + H]+): 616.0328,
1H), 7.51-7.35 (m, 5H), 7.18 (dd, J = 7.5 Hz, J = 2.9 Hz, found: 616.0335.
1H), 5.28 (s, 2H), 2.42 (t, J = 7.4 Hz, 2H), 1.28 (quint, J
= 7.4 Hz, 2H), 1.10 (sex, J = 7.4 Hz, 2H), 0.69 (t, J = 7.4
1-(Butylselanyl)-2-(4-methoxyphenyl)-8-methyl-5-
tosyl-4,5-dihydroselenopheno[2,3-c]quinoline (2v):
Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ (ppm) The product was isolated by column chromatography
156.9 (d, J = 242.0 Hz), 151.8, 146.8 (d, J = 3.0 (hexane/ethyl acetate 95:5 as eluent) as a yellow solid.
Hz),137.7, 136.2, 133.5, 130.3, 128.3, 128.1, 125.3, Yield: 0.100 g (62%); mp 105-106 °C. 1H NMR (CDCl3,
125.2, 118.7, 118.4 (d, J = 26.3 Hz), 110.7 (d, J = 11.0 400 MHz): δ (ppm) 8.48 (dd, J = 1.5 Hz, J = 0.6 Hz,
Hz), 110.1 (d, J = 26.4 Hz) 67.2, 31.4, 29.8, 22.4, 13.3. 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.35-7.27 (m, 2H), 7.30-
MS (EI, 70 eV. m/z (relative intensity)): 546 (30), 544 7.21 (m, 2H), 7.19 (ddd, J = 8.1 Hz, J = 2.1 Hz, J = 0.7
(45), 542 (36), 488 (19), 409 (71), 407 (98), 329 (88), Hz, 1H), 7.00-6.91 (m. 4H), 4.95 (s, 2H), 3.89 (s, 3H),
327 (100), 220 (67). HRMS: calcd for C21H19BrFOSe2 2.43 (s, 3H), 2.29 (s, 3H), 2.15 (t, J = 7.4 Hz. 2H), 1.35
(ESI-TOF, [M + H]+): 544.8934, found: 544,8940.
1-(Butylselanyl)-2-phenyl-4H-selenopheno[2.3-
(quint, J = 7.4 Hz, 2H), 1.20 (sex, J = 7.4 Hz, 2H), 0.79
(t, J = 7.4 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
c]thiochromene (2s): The product was isolated by (ppm) 159.5, 149.9, 142.6, 136.7, 136.3, 135.9, 135.6,
column chromatography (hexane as eluent) as a yellow 132.2, 131.1, 129.8, 129.0, 128.7, 128.1, 127.8, 127.1,
1
oil. Yield: 0.039 g (33%). H NMR (CDCl3, 400 MHz): 125.1, 118.7, 113.5, 55.3, 47.6, 31.3, 29.3, 22.6, 21.4,
δ (ppm) 8.44 (dd, J = 7.8 Hz, J = 1.5 Hz, 1H), 7.54 (dd, J 21.4, 13.4. HRMS: cald for C30H32NO3SSe2 (ESI-TOF,
= 8.1 Hz, J = 1.5 Hz, 2H), 7.48 (dd, J = 7.7 Hz, J = 1.5 [M + H]+): 646.0433, found 646.0440.
Hz, 1H), 7.44 -7.34 (m, 3H), 7.27 (td, J = 7.4 Hz, J = 1.5
1-(Butylselanyl)-2-(4-chlorophenyl)-8-methyl-5-tosyl-
Hz, 1H), 7.18 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 3.93 (s. 4.5-dihydroselenopheno[2,3-c]quinoline (2w): The
2H), 2.23 (t, J = 7.4 Hz. 2H), 1.17 (quint, J = 7.4 Hz, product was isolated by column chromatography
9
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10.1002/adsc.201901410
Advanced Synthesis & Catalysis
(hexane/ethyl acetate 98:2 as eluent) as a orange solid. [3] a) S. Fukuno, M. Ninomiya, M. Koketsu, Synlett
Yield: 0.108 g (66%); mp 117-118 °C. 1H NMR (CDCl3,
400 MHz): δ (ppm) 8.44 (dd, J = 1.5 Hz J = 0.5 Hz, 1H),
7.71 (d, J = 8.2 Hz, 1H), 7.40 - 7.25 (m, 4H), 7.24-7.20
(m, 2H), 7.17 (ddd, J = 8.1 Hz, J = 2.1 Hz, J = 0.7 Hz,
1H), 6.92 (dd, J = 8.6 Hz, J = 0.7 Hz, 2H), 4.93 (s, 2H),
2.40 (s, 3H), 2.26 (s, 3H), 2.13 (t, J = 7.4 Hz, 2H), 1.32
(quint, J = 7.4 Hz, 2H), 1.18 (sex, J = 7.4 Hz, 2H), 0.77
(t, J = 7.4 Hz. 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
(ppm) 148.4, 142.7, 137.6, 136.4, 136.1, 135.7, 135.1,
134.2, 132.3, 131.2, 129.6, 128.7, 128.3, 127.8, 127.2,
125.1, 119.7, 47.6, 31.3, 29.5, 22.6, 21.4, 21.4, 13.4.
HRMS: cald for C29H29ClNO2SSe2 (ESI-TOF, [M +
H]+): 649.9938, found: 649.9944.
2017, 28, 831; b) D. R. Garud, M. Koketsu, Org. Lett.
2008, 10, 3319; c) D. R. Garud, H. Ando, Y. Kawai,
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Coord. Chem. Rev. 2017, 330, 110; b) M. Jeffries-EL,
B. M. Kobilka, B. J. Hale, Macromolecules 2014, 47,
7253; c) S. H. Abdel-Hafez, Eur. J. Med. Chem.
2008, 43, 1971.
[5] a) E. A. Wilhelm, B. M. Gai, A. C. G. Souza, C. F.
Bortolatto, J. A. Roehrs, C. W. Nogueira, Mol. Cell.
Biochem. 2012, 365, 175; b) E. A. Wilhelm, A. C. G.
Souza, B. M. Gai, P. M. Chagas, J. A. Roehrs, C. W.
Nogueira, Life Sci. 2012, 90, 666.
1-(Butylselanyl)-8-methoxy-2-phenyl-5-tosyl-4,5-
dihydroselenopheno[2,3-c]quinoline (2x): The product
was isolated by column chromatography (hexane/ethyl
acetate 95:5 as eluent) as a yellow solid. Yield: 0.084g
[6] a) W. Xu, M. Wang, Z. Ma, Z. Shan, C. Li, H. Wang,
J. Org. Chem. 2018, 83, 12154; b) D. Meng, D. Sun,
C. Zhong, T. Liu, B. Fan, L. Huo, Y. Li, W. Jiang, H.
Choi, T. Kim, J. Am. Chem. Soc. 2015, 138, 375; c) J.
Hollinger, A. A. Jahnke, N. Coombs, D. S. Seferos, J.
Am. Chem. Soc. 2010, 132, 8546; d) T. Okamoto, K.
Kudoh, A. Wakamiya, S. Yamaguchi, Org. Lett.
2005, 7, 5301.
1
(53%); mp 137-138 °C. H NMR (CDCl3, 400 MHz): δ
(ppm) 8.30 (d, J = 2.9 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H),
7.41-7.31 (m, 5H), 7.23-7.19 (m, 2H), 6.97-6.86 (m,
3H), 4.94 (s, 2H), 3.85 (s, 3H), 2.28 (s, 3H), 2.13 (t, J =
7.4 Hz, 2H), 1.29 (quint,J = 7.4 Hz, 2H), 1.13 (sex, J =
7.4 Hz, 2H), 0.73 (t, J = 7.4 Hz, 3H). 13C {1H} NMR
(100 MHz. CDCl3): δ (ppm) 158.0, 150.1, 142.7, 137.8,
136.5, 135.6, 135.3, 131.0, 130.0, 129.2, 128.7, 128.1,
128.0, 127.6, 127.1, 118.9, 113.1, 109.6, 55.5, 47.7,
31.3, 29.4, 22.6, 21.5, 13.4. HRMS: cald for
C29H30NO3SSe2 (ESI-TOF, [M + H]+): 632.0277, found:
632.0281.
[7] A. D. Sonawane, D. R. Garud, T. Udagawa, M.
Koketsu, Org. Biomol. Chem. 2018, 16, 245.
[8] a) S. Ahmad, K. K. Yadav, S. Bhattacharya, P.
Chauhan, S. Chauhan, J. Org. Chem. 2015, 80, 3880;
b)T. Kashiki, S. Shinamura, M. Kohara, E. Miyazaki,
K. Takimiya, M. Ikeda, H. Kuwabara, Org. Lett.
2009, 11, 2473; c) V. Potapov, S. Amosova, I.
Doron'kina, S. Zinchenko, Sulfur Lett. 2001, 24, 275.
1-(Butylselanyl)-8-chloro-2-phenyl-5-tosyl-4,5-
dihydroselenopheno[2,3-c]quinoline (2y): The product
was isolated by column chromatography (hexane/ethyl
acetate 98:2 as eluent) as a orange solid. Yield: 0.124g
(78%); mp 143-144 °C. 1H NMR (CDCl3, 400 MHz): δ
(ppm) 8.73 (d, J = 2.4 Hz, 1H), 7.77 (d, J = 8.6 Hz, 1H),
7.45-7.30 (m, 6H), 7.23 -7.19 (m, 2H), 7.04-6.85 (m,
2H), 4.96 (s, 2H), 2.28 (s, 3H), 2.12 (t, J = 7.4 Hz, 2H),
1.33 (quint, J = 7.4 Hz, 2H), 1.17 (sex, J = 7.4 Hz, 2H),
0.76 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (100 MHz,
CDCl3): δ (ppm) 150.6, 143.1, 138.3, 136.2, 134.9,
134.5, 133.0, 132.5, 131.3, 130.0, 129.3, 128.8, 128.2,
128.1, 127.3, 127.0, 124.4, 118.7, 47.5, 31.2, 29.5, 22.6,
21.5, 13.4. HRMS: cald for C28H27ClNO2SSe2 (ESI-
TOF, [M + H]+): 635.9781, found: 635.9785.
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I. Kanepe-Lapsa, I. Shestakova, Eur. J. Med. Chem.
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Worlikar, R. C. Larock, J.Org. Chem. 2006, 71, 2307.
Acknowledgements
[11] A. D. Sonawane, Y. Kubota, M. Koketsu, J. Org.
Chem. 2019, 84, 8602.
We are grateful to FAPERGs, CAPES and CNPq for the
financial support. CNPq is also acknowledged for the
fellowships.
[12] a) M. Mishra, S. Mohapatra, N. P. Mishra, B. K.
Jena, P. Panda and S. Nayak, Tetrahedron Letters,
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Advanced Synthesis & Catalysis
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11
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Advanced Synthesis & Catalysis
FULL PAPER
Iron-Mediated
Cyclization
of
1,3-Diynyl
Propargyl Aryl Ethers with Dibutyl Diselenide:
Synthesis of Selenophene-Fused Chromenes
Adv. Synth. Catal. Year, Volume, Page-Page
Guilherme Lutza, Davi F. Backb and Gilson Zeni a, *
12
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