Iron(III) Chloride/Dialkyl Diselenides-Promoted Cascade Cyclization of ortho-Diynyl Benzyl Chalcogenides

Article abstract of DOI:10.1002/adsc.201900086

Treatment of ortho-diynyl benzyl chalcogenides with a mixture of iron(III) chloride and diorganyl diselenides led to functionalized chalcogen isochromene-fused chalcogenophene derivatives. The reaction parameters were studied and the results indicated tha

Full text of DOI:10.1002/adsc.201900086

Title: Iron(III) Chloride/Dialkyl Diselenides-Promoted Cascade
Cyclization of ortho-Diynyl Benzyl Chalcogenides
Authors: Roberto Do carmo, Davi Back, and Gilson Zeni
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Iron(III) Chloride/Dialkyl Diselenides-Promoted Cascade
Cyclization of ortho-Diynyl Benzyl Chalcogenides
Roberto do Carmo Pinheiro,a Davi F. Backb and Gilson Zenia,*
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))
Abstract. Treatment of ortho-diynyl benzyl chalcogenides has a dual action, promoting the cyclization and introducing
with a mixture of iron(III) chloride and diorganyl diselenides
a
new functionalization at the 3-position of
led to functionalized chalcogen isochromene-fused isochalcogenochromenes. The methodology was highly
chalcogenophene derivatives. The reaction parameters were regioselective, giving the product via 6-endo-dig mode
studied and the results indicated that the reaction of ortho- followed by a second cyclization via 5-endo-dig mode.
diynyl benzyl chalcogenides (0.25 mmol) with iron(III)
chloride hexahydrate (2.0 equiv) and diorganyl diselenide (2
equiv) at reflux of dichloroethane was the best condition to
give the products in 40-83% yields. The results support the
idea that a mixture of iron salts and diorganyl diselenides
Keywords: cascade reactions; iron; diselenides;
isochromenes, selenides; heterocycles
iridium as catalysts.[8] Alternatively, isochromenes
can be also synthesized successfully using metal-
free conditions.[9] Conversely, the synthesis of
isochromene-fused chalcogenophenes is less
investigated.[10] Thus, the association of
isochromenes pharmacological potential, such as
Introduction
The challenge of synthetic organic chemists to
develop more efficient experimental protocols, that
combine atom economy, lower environmental
anticancer,[11]
anti-inflammatory,[12]
impact with a minimum number of reaction steps,
makes cascade reactions a powerful tool in the field
of organic synthesis. Cascade reactions involve a
one-pot protocol, in which multiple bonds are
formed from one or more substrates in a single
vessel. Transition metal-catalyzed cascade reactions
are one of the most common and efficient methods
for the synthesis of heterocycles.[1] Among those,
multiple C-C, C-H, C-N, C-O, C-S and C-P bonds
are formed to build heterocycles. Furthermore,
transition metal-catalyzed cascade reactions,
starting from alkynes, involving C-O bond
formation, have been successfully applied to the
synthesis of isochromenes.[2] Many transition
metals presented high efficiency to promote the
cyclization of acyclic substrates to isochromenes.
Most of these strategies involves, palladium,[3]
gold,[4] osmium,[5] ruthenium,[6] rhodium,[7] and
antimicrobial[13] and antibacterial activities,[14] with
the synthetic versatility and distinguished biological
activities of organochalcogens,[15] stimulated our
interest in joining these two classes of compounds
in the preparation of chalcogenisochromene-fused
chalcogenophene derivatives. Motivated by this
challenge, the main objective of this study was the
development of an efficient cascade synthesis of
chalcogenisochromene-fused
chalcogenophenes
between ortho-diynyl benzyl chalcogenides and
diorganyl dichalcogenides promoted by iron salts.
The use of iron salts in the organic synthesis has
been a subject of great interest in the recent year
because of their low cost, low toxicity,
compatibility with solvents, air and with a wide
range of functional groups.[16] Therefore, a number
of studies has been developed for the application of
1
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
Scheme 2. Retrosynthesis for preparation of ortho-
diynyl benzyl chalcogenides 1.
iron salts to promote not only the synthesis of
heterocycle compounds,[17] but also carbon-
heteroatom, heteroatom-heteroatom and carbon-
carbon bonds formation.[18] Thus, in this study we
demonstrate that the iron salt and diorganyl
dichalcogenides are a convenient tool to the
synthesis
of
chalcogenisochromene-fused
chalcogenophenes 2 from ortho-diynyl benzyl
chalcogenides 1 (Scheme 1).
Scheme 1. Cyclization of ortho-diynyl benzyl
chalcogenides promoted by iron salt and diorganyl
diselenides.
Results and Discussion
The studies started with the preparation of ortho-
diynyl benzyl chalcogenides 1 following the routes
presented in Scheme 2.
The 2-bromo-
benzylchalcogenides II were considered the key
intermediary for the preparation of all starting
materials. The strategy for the preparation of II
involved the reaction of 2-bromobenzyl bromide
with a nucleophilic species of chalcogen. The
reaction of methanol with sodium metal was used
to generate the methoxy anion.[19] The reaction of
ethanethiol with cesium carbonate led to the
formation of thiolate.[20] For the preparation of
selenolate anion, we chose the reaction of diorganyl
diselenides with sodium borohydride.[21] Thus,
Scheme 3. Synthesis of ortho-diynyl benzyl
chalcogenides 1.
ortho-diynyl benzyl chalcogenides
1
were
The main challenge in this work was not only to
promote a double cyclization in the ortho-diynyl
benzyl chalcogenides 1 but also to add a
functionalization at the 3-position of the
selenophene ring, in a one-pot procedure. To
achieve the goal we need a reagent that has double
function; to act as a cyclizing agent as well as to be
able to introduce the functionalization at the 3-
position of selenophene ring. Our research group
and other have reported the application of iron salts
in combination with diorganyl diselenides, as
cyclizing agents, in the preparation of
heterocyles.[25] The main feature of these protocols
is the effectiveness of diorganyl diselenides to
incorporate the two equal portions (2 RSe) in the
final product, thus becoming a more useful and
valuable method in terms of atom economy. This
particularity of diorganyl diselenides is possible
only because one portion of molecule reacts as a
nucleophilic whereas the other behaves as an
electrophilic species. For this reason, we believe
synthesized in three steps from 2-bromo-
benzylchalcogenides II, previously prepared. In
the first step the terminal alkynes I were prepared
via a classical Sonogashira reaction[22] followed by
the retro-Favorskii reactions.[23]
The Cadiot-
Chodkiewicz coupling[24] of terminal alkynes I with
alkynyl iodide led to ortho-diynyl benzyl
chalcogenides 1. As shown in Scheme 3, the
formation of ortho-diynyl benzyl chalcogenides 1
was efficient in all cases, giving the products in
moderate to good yields.
2
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
that applying the combination of diorganyl (Table 1, entries 10-12). For further optimization
diselenides with iron salts could be a useful tool for of the reaction conditions, decreasing the amount of
the preparation of chalcogenisochromene-fused dibutyl diselenide resulted in a decrease in the yield
chalcogenophenes 2 from ortho-diynyl benzyl of product 2a (Table 1, entry 13). The optimization
chalcogenides 1. Because of the first step of this of iron loading from a range of 2 equiv to catalytic
reaction involves the removal of the group, directly amount was found to be unsuccessful to improve
bonded to the selenium atom, via a nucleophilic the yield of 2a (Table 1, entries 14-16). We believe
substitution (See mechanism discussion, Scheme 6), that the large amount of iron(III) chloride required
the first requirement for the success of this in this cyclization proved to be necessary because
cyclization is the use of diorganyl diselenides of iron salt has strong affinity for chalcogen atoms
having a Csp3 directly bonded to the selenium
atom. Thus, we began the optimization of the
reaction conditions using dibutyl diselenide, as
selenium source, by varying some reaction
parameters, such as solvent, temperature, iron
source, amount of diorganyl diselenide and the
reaction time that could affect the cyclization of
ortho- diynyl benzyl chalcogenides 1. Thus, the
influence of iron species was examined by the
addition of 1a (0.25 mmol), at room temperature,
under argon atmosphere, to a solution of FeCl3 (2.0
equiv) and dibutyl diselenide (2.0 equiv) in
dichloroethane (3 mL), which was prepared 10 min
before. Using this condition, all starting material
was consumed in 30 min; however, the product was
obtained only in 55% yield (Table 1, entry 1).
Changing the solvent to toluene, the product 2a was
obtained in a very poor yield (Table 1, entry 2).
Even using different solvents under reflux, the
results were not satisfactory, although with
dichloroethane, the product was obtained in 61%
yield (Table 1, entries 2-7). Under these conditions,
the starting material was fully consumed in the
reaction time indicated in Table 1; however, many
by-products were also detected by TLC. In
addition, in the course of 1a addition, we observed
that the reactions were exothermic, changing the
color from yellow to black, with release of gas,
as well as for the carbon-carbon triple bond,[26] iron
was required to complex with these groups and to
promote the cyclization and the incorporation of
BuSe in the final product. We also studied the
effect of other iron salts under similar reaction
conditions; however, we did not observe any
improvement in the yield of 2a (Table 1, entries 17-
21). An additional experiment using Lewis acids,
such as PdCl2, BF3·OEt2, ZnCl2 and CuI, or
Brønsted acids, such as H3PO4 and p-
toluenesulfonic acid, was carried out and did not
result in the formation of 2a (These results are
shown in the Supporting Information). We believe
that these promoters were ineffective because they
are unable to cleave the selenium-selenium bond
(202 KJmol-1) to form the complex iron-selenium
intermediary required to the carbon-carbon triple
bond activation and to promote the cyclization.
Table 1. Effects of different reaction parameters on the
preparation
of
chalcogenisochromene-fused
chalcogenophene 2a.[a]
entry
iron salt (equiv)
solvent
T (°C)
reaction
time (h)
0.5
1
2
18
18
2
18
yield
(%)[b]
55
32
53
N.R.
43
N.R.
61
1
2
3
4
5
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
DCE
toluene
toluene
1,4-dioxane
CH2Cl2
CH3NO2
DCE
r.t.
r.t.
110
101
36
100
85
probably HCl liberation.
To investigate the
hypothesis that the starting material could
decompose in contact with the iron/diselenide
mixture, we carried out the experiment in the
absence of dibutyl diselenide (Table 1, entry 8).
This reaction condition showed the same
characteristics described above and the TLC
analysis indicated that all starting material was
consumed after 5 min, with formation of many
spots. To confirm this assumption, we carried out
the reaction described in Table 1, entry 1 by
changing temperature for the addition of 1a to 0 0C
and after 5 min, at this temperature, the reaction
mixture was refluxed. Under this condition, after
30 min, the selenoisochromene-fused selenophene
2a was obtained in 73% yield (Table 1, entry 9).
The progress of the reactions was monitored and
we observed that 1 h was the required time taken
for the reactions to be completed in good yields
6
7
FeCl3 (2)
FeCl3 (2)
[c]
8
9
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
FeCl3 (2)
FeCl3 (1.5)
FeCl3 (1)
FeCl3 (20mol%)
FeCl2.4H2O (2)
FeCl3.6H2O (2)
Fe(acac)3 (2)
Fe (2)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
r.t.
0.5
0.5
1h
2h
3h
1h
1h
1h
1h
1h
1h
18
18
-
73
77
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
0 - 85
10
11
12
13
14
15
16
17
18
19
20
21
58
75
48[d]
62
traces
traces
39
55
n.r.
n.r.
n.r.
ferrocene (2)
18
[a] The reaction was performed by the addition of 1a (0.25 mmol),
at room temperature, under argon atmosphere, to a solution of
FeCl3 (2.0 equiv) and dibutyl diselenide (2.0 equiv) in
dichloroethane (3 mL), which was prepared 10 min before. The
reaction was stirred for 0.5 h at room temperature.
[b] Isolated yield after column chromatography.
3
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
[c] The reaction was carried out in the absence of BuSeSeBu.
[d] The reaction was carried out with BuSeSeBu (1.5 equiv).
Subsequently, the substrate benzyl methyl thioether
was applied as nucleophile source; however, it did
not react even after adjustments in the standard
condition (Table 2, 2x). This probably occurred
because sulfur compounds are usually less
nucleophilic than the corresponding selenium ones
for the cyclization step.
We next evaluated the scope of this cyclization
regarding the use of dibutyl ditelluride instead of
diselenides. The reaction conditions were efficient
for the cyclization of unsubstituted and methyl
substituted benzyl selenide derivatives, giving the
selenocromene-fused tellurophenes 2y and 2z in
moderate yields of 52% and 57%, respectively.
However, we did not observe any amount of
product with benzyl selenide having a para-chloro-
substituent (Scheme 4).
To test the generality of this cyclization reaction,
other ortho-diynyl benzyl chalcogenide derivatives
1 were subjected to the optimized reaction
conditions and the results are summarized in Table
2. From the results in Table 2, it is apparent that
substrates, which contain an unsubstituted aryl
group on the terminal alkyne, gave higher yields of
products in relatively shorter reaction times,
whereas the reaction gave the products in poor
yields with aryl having electron-donating, electron
withdrawing and bulky groups (Table 2, entries 2a-
2i). Because alkynes rich in electrons should be
more reactive toward the electrophilic chalcogen
species, favoring the formation of products, these
results exclude any attempt to relate the structure of
substrates to the reaction yields (See mechanism
discussion, Scheme 6). Regarding the substrates
having substituent groups at the benzyl aryl ring,
we found additional limitations in this methodology.
For example, no reaction was observed with
dioxole, naphthyl, chloro, methyl and methoxy
groups and any change in the reaction conditions
was found to be ineffective to give the products
(Table 2, 2j and 2k). Other examples tested that
did not give the products are shown in Scheme S1,
in the Supporting Information. The generalization
of the optimized reaction conditions was also
verified using oxygen as nucleophile instead of the
selenium atom. Although less nucleophilic than
selenium derivatives, the benzyl methyl ethers
presented similar results to those of benzyl
selenides because the highly (Lewis) acidic
character of iron(III), together with its oxophilic
character, probably supports the nucleophilic
substitution step allowing the cyclization. The
compound with an unsubstituted aryl group in the
alkyne proceeded smoothly and led to the formation
of the desired product in good yield, although by
using more prolonged reaction time (Table 2, 2l).
Whereas the nature of substituent on the aromatic
ring influenced on the yields of the products,
electron-donating and electron withdrawing groups
provided products with a slightly lower yields
(Table 2, 2m-u). In the case of substrate having a
heteroaryl group, such as 3-thienyl, the
corresponding product 2v was obtained in 62%
yield (Table 2, 2v). When an alkyl group was
introduced at the carbon-carbon triple bond of the
benzyl methyl ethers, we did not observe the
formation of product and the benzyl methyl ether
and dibutyl diselenide were recovered even under
various reaction conditions (Table 2, 2w). In this
case, the reactivity of the triple bond is reduced by
the absence of pi (π) bonds next to the alkyne.
The next step in this study was to test the
optimized
reaction
conditions
with
disulfides/iron(III) chloride, as the promoter
system, in the preparation of thiocromene-fused
selenophenes. However, no reaction occurred with
any disulfides (diethyl disulfide and butyl disulfide)
tested even whether different ortho-diynyl benzyl
selenides were used as substrate. From these
experiments, it can be concluded that the strength
of the sulfur-sulfur bond prevents its cleavage by
iron salt hampering the formation of desired
products. All the compounds were characterized by
1H and 13C NMR spectroscopy. Furthermore, the 6-
endo-dig followed by a 5-endo-dig cyclization
sequence was confirmed by X-ray analysis of the
crystalline sample (Supporting Information, Figure
1, CCDC 1891005 and 1891009 for compounds 2g
and 2u, respectively).[27]
Table 2. Synthesis of chalcogenochromene-fused
chalcogenophenes 2.[a]
4
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
unidentified products (Scheme 5, eq 1). As
previously reported, in the reactions promoted by
iron(III) chloride, occasionally a radical process
may be operating on the cyclizations.[29] Thus, we
subjected the substrate 1a to the standard reaction
condition in the presence of a radical inhibitor
(hydroquinone) and a radical scavenger (TEMPO).
The reaction with hydroquinone gave the product
2a in 66% yield, whereas TEMPO afforded the
decomposition of the starting material and dibutyl
diselenide was recovered. These results suggest
that a free-radical mechanism may be excluded
(Scheme 5, eq 2 and 3). We also investigated
whether the selenium functionalization could be
occurring after
a
previous cyclization step
promoted by the iron(III) chloride alone via a Csp2-
Fe intermediated.[30] As a result, the product 2a
was not obtained when dibutyl diselenide was
added to a solution of iron(III) chloride and 1a,
maintained for 1 h under optimized conditions
(Scheme 5, eq 4).
[a] The reaction was performed by the addition of 1 (0.25
0
mmol), at 0 C, under argon atmosphere, to a solution of
FeCl3 (2.0 equiv) and dibutyl diselenide (2.0 equiv) in
dichloroethane (3 mL), which was prepared 10 min
before. The reaction mixture was stirred under reflux
conditions for the time indicated in Table 2.
Scheme 5. Control experiments for mechanism proposal.
Considering these experimental results and the
concept that iron salts react with diorganyl
diselenides via selenium-selenium bond heterolytic
cleavage to form an organoselenyl cation and an
organoselenyl anion,[31] a tentative mechanism,
shown in Scheme 6, was proposed. The addition of
the electrophilic portion of diphenyl diselenide to
the carbon-carbon triple bond generates the three-
membered cyclic selenonium cation I, which is
subsequently attacked by the selenium atom from
benzylic position to give the isoselenochromene
intermediate II and a selenolate species. The
elimination of the butyl group bonded to the
selenium atom via SN2 reaction gave 4-
Scheme 4. The use of dibutyl ditelluride and iron(III)
chloride for the cyclization of ortho-diynyl benzyl
chalcogenide derivatives 1.
To gain further insight into the mechanism, we
carried out additional experiments using the
substrate 1a.
For example, to eliminate the
hypothesis that BuSeCl, a selenium electrophilic
species, that could be generated in situ via
reduction of dibutyl diselenide by iron(II) chloride,
could be the promoter of the cyclization, we
performed the reaction of 1a with BuSeCl,[28] under
optimized conditions, in the absence of iron salt and
dibutyl diselenide. This reaction gave trace amount
of product 2a together with a complex mixture of
(butylselanyl)-isoselenochromene III.
This
intermediary reacts with iron(III) chloride and
diselenide, in the same way, to give the product 2
(Scheme 6).
5
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
(ESI-TOF) m/z calcd for C21H21Se3 [M + H]+: 512.9139.
Found: 512.9145.
3-(Butylselanyl)-2-(o-tolyl)-5H-selenopheno[3,2-
c]isoselenochromene (2b). The product was isolated by
column chromatography (hexane as eluent) as a yellow
1
oil. Yield: 0.063 g (48%). H NMR (CDCl3, 400 MHz):
δ (ppm) 7.33-7.27 (m, 4H), 7.25-7.18 (m, 4H), 3.99 (s,
2H), 2.60 (t, J = 7.4 Hz, 2H), 2.31 (s, 3H), 1.46 (quin, J
= 7.5 Hz, 2H), 1.22 (sex, J = 7.4 Hz, 2H), 0.78 (t, J = 7.4
Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz): δ (ppm)
149.3, 137.9, 137.2, 135.6, 134.2, 133.7, 130.8, 130.1,
130.0, 128.6, 128.1, 127.9, 127.7, 127.5, 125.3, 125.2,
32.2, 29.0, 25.6, 22.6, 20.6, 13.4. MS (EI, 70 eV. m/z
(relative intensity)): 527 (16), 521 (64), 308 (83), 228
(100), 115 (23). HRMS (ESI-TOF) m/z calcd for
C22H23Se3 [M + H]+: 526.9295. Found: 526.9291.
Scheme 6. Proposed reaction mechanism.
Conclusions
In summary, we establish a protocol for the
synthesis of functionalized chalcogenisochromene-
fused chalcogenophene derivatives using ortho-
diynyl benzyl chalcogenides as substrate and a
mixture of iron(III) chloride and diorganyl
dichalcogenides to promote de cyclization. The
methodology was highly regioselective, giving the
products exclusively via 6-endo-dig mode followed
by a 5-endo-dig mode. The advantages of this
protocol are that the two portions of
dichalcogenides were incorporated in the final
products, the use of iron salts, which are easily
available commercially, less expensive and
relatively non-toxic. Moreover, the products were
formed in a cascade process, conducted in a one-pot
protocol, in which three new carbon-chalcogen
bonds are formed consecutively.
3-(Butylselanyl)-2-(m-tolyl)-5H-selenopheno[3,2-
c]isoselenochromene (2c). The product was isolated by
column chromatography (hexane as eluent) as a brown
1
oil. Yield: 0.074 g (56%). H NMR (CDCl3, 400 MHz):
δ (ppm) 7.45-7.41 (m, 2H), 7.32-7.26 (m, 2H), 7.26-7.16
(m, 4H), 3.98 (s, 2H), 2.67 (t, J = 7.3 Hz, 2H), 2.41 (s,
3H), 1.44 (quin, J = 7.3 Hz, 2H), 1.21 (sex, J = 7.3 Hz,
2H), 0.76 (t, J = 7.3 Hz, 3H). 13C {1H} NMR (CDCl3,
100 MHz): δ (ppm) 150.3, 137.9, 137.2, 135.9, 135.3,
134.3, 130.3, 130.1, 129.0, 128.1, 128.1, 127.9, 127.7,
127.5, 126.7, 123.2, 40.0, 29.6, 25.7, 22.6, 21.4, 13.5.
MS (EI, 70 eV. m/z (relative intensity)): 527 (11), 386
(46), 310 (100), 229 (79), 202 (16). HRMS (ESI-TOF)
m/z calcd for C22H23Se3 [M + H]+: 526.9295. Found:
526.9288.
3-(Butylselanyl)-2-(p-tolyl)-5H-selenopheno[3,2-
Experimental Section
c]isoselenochromene (2d). The product was isolated by
column chromatography (hexane as eluent) as a yellow
solid. Yield: 0.072 g (55%); 75-78 °C. 1H NMR (CDCl3,
400 MHz): δ (ppm) 7.54-7.50 (m, 2H), 7.31-7.26 (m,
1H), 7.25-7.19 (m, 5H), 3.97 (s, 2H), 2.66 (t, J = 7.3 Hz,
2H), 2.39 (s, 3H), 1.45 (quin, J = 7.5 Hz, 2H), 1.22 (sex,
J = 7.5 Hz, 2H), 0.75 (t, J = 7.3 Hz, 3H). 13C {1H} NMR
(CDCl3, 100 MHz): δ (ppm) 150.3, 138.2, 137.0, 135.3,
134.2, 133.1, 130.0, 129.4, 128.9, 128.1, 127.9, 127.6,
127.4, 122.9, 31.9, 29.6, 25.7, 22.6, 21.3, 13.5. MS (EI,
70 eV. m/z (relative intensity)): 527 (12), 522 (48), 388
(49), 310 (100), 229 (69). HRMS (ESI-TOF) m/z calcd
for C22H23Se3 [M + H]+: 526.9295. Found: 526.9289.
General Procedure for the Synthesis chalcogen
isochromene-fused chalcogenophenes 2: The reaction
was performed by the addition of ortho-diynyl benzyl
chalcogenide 1 (0.25 mmol), at 0 0C, under argon
atmosphere, to a solution of FeCl3 (2.0 equiv) and
diorganoyl dichalcogenide (2.0 equiv) in dichloroethane
(3 mL), which was prepared 10 min before. The reaction
mixture was stirred under reflux conditions for the time
indicated in Table 2.The mixture was concentrated in
vacuum and residue was purified by column
chromatography over silica gel to provide the products 2.
3-(Butylselanyl)-2-phenyl-5H-selenopheno[3,2-
c]isoselenochromene (2a). The product was isolated by
column chromatography (hexane as eluent) as a brown
oil. Yield: 0.098 g (77%). H NMR (CDCl3, 400 MHz):
3-(Butylselanyl)-2-(4-methoxyphenyl)-5H-
selenopheno[3,2-c]isoselenochromene
(2e).
The
1
product was isolated by column chromatography (hexane
as eluent) as a yellow oil. Yield: 0.073 g (54%). H
1
δ (ppm) 7.65-7.59 (m, 2H), 7.43-7.28 (m, 4H), 7.25-7.19
(m, 3H), 3.97 (s, 2H), 2.65 (t, J = 7.3 Hz, 2H), 1.44 (quin,
J = 7.4 Hz, 2H), 1.19 (sex, J = 7.3 Hz, 2H), 0.75 (t, J =
7.3 Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz): δ (ppm)
150.0, 137.3, 136.0, 135.4, 134.2, 132.4, 130.1, 129.6,
128.2, 128.2, 127.9, 127.7, 127.4, 123.3, 31.9, 29.6, 25.7,
22.5, 13.4. 77Se NMR (CDCl3, 77 MHz) δ (ppm) 672.5,
225.3, 204.8. MS (EI, 70 eV. m/z (relative intensity)):
513 (11), 373 (33), 295 (80), 215 (100), 207 (56). HRMS
NMR (CDCl3, 400 MHz): δ (ppm) 7.57 (d, J = 8.8 Hz,
2H), 7.31-7.26 (m, 1H), 7.26-7.19 (m, 3H), 6.93 (d, J =
8.8 Hz, 2H), 3.97 (s, 2H), 3.85 (s, 3H), 2.66 (t, J = 7.3
Hz, 2H), 1.45 (quin, J = 7.3 Hz, 2H), 1.23 (sex, J = 7.4
Hz, 2H), 0.76 (t, J = 7.3 Hz, 3H). 13C {1H} NMR
(CDCl3, 100 MHz): δ (ppm) 159.6, 150.1, 136.6, 135.3,
134.2, 130.8, 130.0, 128.5, 128.0, 127.9, 127.6, 127.4,
122.6, 113.6, 55.3, 32.0, 29.5, 25.7, 22.6, 13.5. MS (EI,
70 eV. m/z (relative intensity)): 543 (15), 329 (36), 213
6
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10.1002/adsc.201900086
Advanced Synthesis & Catalysis
(44), 207 (100), 73 (24). HRMS (ESI-TOF) m/z calcd Chem. 2004, 69, 5139-5142; f) S. Mondal, T. Nogami, N.
for C22H23OSe3 [M + H]+: 542.9245. Found: 542.9251.
Asao, Y. Yamamoto, J. Org. Chem. 2003, 68, 9496-9498.
[3] B. Gabriele, G. Salerno, A. Fazio, R. Pittelli,
3-(Butylselanyl)-2-(2-chlorophenyl)-5H-
selenopheno[3,2-c]isoselenochromene
(2f).
The Tetrahedron 2003, 59, 6251-6259.
product was isolated by column chromatography
(hexane/ethyl acetate 99:1 as eluent) as a green oil.
Yield: 0.055 g (40%). H NMR (CDCl3, 400 MHz): δ
[4] Y. Feng, X. Jiang, J. K. D. Brabander, J. Am. Chem.
Soc. 2012, 134, 17083-17093.
1
(ppm) 7.49-7.44 (m, 1H), 7.44-7.40 (m, 1H), 7.36-7.26
(m, 3H), 7.26-7.19 (m, 3H), 3.98 (s, 2H), 2.66 (t, J = 7.4
Hz, 2H), 1.47 (quin, J = 7.5 Hz, 2H), 1.21 (sex, J = 7.5
Hz, 2H), 0.78 (t, J = 7.4 Hz, 3H). 13C {1H} NMR
(CDCl3, 100 MHz): δ (ppm) 146.1, 138.8, 135.2, 134.2,
134.1, 133.6, 132.6, 130.1, 129.7, 129.7, 128.3, 127.9,
127.7, 127.5, 126.7, 126.3, 32.2, 29.1, 25.6, 22.6, 13.4.
77Se NMR (CDCl3, 77 MHz) δ (ppm) 687.4, 224.8,
214.0. MS (EI, 70 eV. m/z (relative intensity)): 547 (17),
410 (22), 330 (95), 213 (100), 187 (23). HRMS (ESI-
TOF) m/z calcd for C21H20ClSe3 [M + H]+: 546.8749.
Found: 546.8755.
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3-(Butylselanyl)-2-(4-chlorophenyl)-5H-
selenopheno[3,2-c]isoselenochromene
(2g).
The
product was isolated by column chromatography (hexane
as eluent) as a yellow solid. Yield: 0.089 g (65%); mp
94-97 °C. H NMR (CDCl3, 400 MHz): δ (ppm) 7.58-
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2006, 71, 3381-3388; b) S. Mondal, T. Nogami, N. Asao,
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1
7.55 (m, 2H), 7.39-7.36 (m, 2H), 7.33-7.22 (m, 4H), 3.98
(s, 2H), 2.66 (t, J = 7.3 Hz, 2H), 1.44 (quin, J = 7.3 Hz,
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127.9, 127.7, 127.5, 123.8, 31.9, 29.7, 25.7, 22.5, 13.4.
MS (EI, 70 eV. m/z (relative intensity)): 547 (5), 346
(19), 265 (100), 207 (11), 132 (10). HRMS (ESI-TOF)
m/z calcd for C21H20ClSe3 [M + H]+: 546.8749. Found:
546.8755.
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Acknowledgements
We are grateful to FAPERGs, CAPES and CNPq for the
financial support. CNPq is also acknowledged for the
fellowships.
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FULL PAPER
Iron(III) Chloride/Dialkyl Diselenides-Promoted
Cascade Cyclization of ortho-Dyinyl Benzyl
Chalcogenides
Adv. Synth. Catal. Year, Volume, Page – Page
Roberto do Carmo Pinheiro,a Davi F. Backb and
Gilson Zenia,*
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