Iron (III)-Promoted Synthesis of Substituted 4H-Chalcogenochromenes and Chemoselective Functionalization

Article abstract of DOI:10.1002/adsc.201900142

The iron(III)-promoted synthesis of densely-substituted 4H-chalcogenchromene from organochalcogen propargylamines in the presence of diaryl dichalcogenides is reported. Subsequent C2-functionalization with electrophiles and potassium trifluoroborate salts

Full text of DOI:10.1002/adsc.201900142

Title: Iron (III)-Promoted Synthesis of Substituted 4H-
Chalcogenochromenes and Chemoselective Functionalization
Authors: Helio Stefani, Isadora M Oliveira, Carlos Henrique Alves
Esteves, Mariana Pompilio Darbem, Daniel Carvalho
Pimenta, Julio Zukerman-Schpector, Antônio Ferreira, and
Flavia Manarin
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900142
Link to VoR: http://dx.doi.org/10.1002/adsc.201900142

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Iron (III)-Promoted Synthesis of Substituted 4H-
Chalcogenochromenes and Chemoselective Functionalization
Isadora M. de Oliveira,a C. Henrique A. Esteves,b Mariana P. Darbem,b Daniel C.
Pimenta,c Julio Zukerman-Schpector,d Antonio G. Ferreira,d Hélio A. Stefani,b* Flavia
Manarine*
a
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP – Brazil.
Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, SP – Brazil.
b
Phone (+55) 11 30913654; e-mail: hstefani@usp.br
Instituto Butantã, São Paulo, SP – Brazil.
Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP – Brazil.
Centro de Engenharias e Ciências Exatas – CECE, Universidade Estadual do Oeste do Paraná, Toledo, PR – Brazil.
c
d
e
Phone (+55) 45 33797073; e-mail: fgmanarin@gmail.com
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. The iron(III)-promoted synthesis of densely-
substituted 4H-chalcogenchromene from organochalcogen
propargylamines in the presence of diaryl dichalcogenides is
reported. Subsequent C2-functionalization with electrophiles
and potassium trifluoroborate salts via Suzuki-Miyaura
coupling reaction are also presented. A plausible mechanism
based on HRMS experiments is proposed and discussed.
Keywords: Chalcogen, 4H-Chalcogenochromenes,
Heterocycles, Iron, Propargylamines.
Introduction
Chromene derivatives are an important class of
compounds found in natural products and biologically
active molecules. Some of the activities described in
the literature include anticancer, antiprotozoal,
antibacterial, antiviral and insecticidal (Figure 1).[1]
Figure 2. Examples of chromenes.
Despite this scarcity, the potential of these
molecules cannot be ignored, as many organoselenium
and organotellurium compounds have demonstrated
pronounced biological activity in previous studies.[4]
With these considerations in mind, we set out to
design a useful and operationally simple route to 4H-
chalcogenochromenes. The proposed methodology
should be modular in order to accommodate a wide
variety of functional groups, based on simple starting
materials and at the same time allow the quick
functionalization of the final product. We believed that
a rapid cyclization process that at the same
incorporated organochalcogenide substituents would
meet these criteria as these groups are easily replaced
Figure 1. Biologically-relevant chromene derivatives.
The most common members of this family are 4H-
chromenes,
2H-chromenes,
2H-chromen-2-one
(coumarins) and 4H-chromen-4-one (chromones),
whose syntheses have been accomplished via many
different routes.[2] Other chalcogenochromenes, such
as 4H-seleno- and 4H-tellurochromenes, are rather
unusual, with only very few examples described in the
literature (Figure 2).[3]
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
by carbon-carbon, carbon-halogen and carbon-
heteroatom bonds.[5]
2a (Table 1). Reactions were followed by TLC in order
to ensure full conversion of 1.
These prerequisites led us to investigate iron(III)-
promoted cyclization methodologies in which pendant
alkynes are cyclized onto carbocyclic rings in the
presence of dichalcogenides. These transformations
have been explored as a way of introducing
organochalcogenide groups into cyclic structures[6]
using a non-toxic, environmentally friendly, Earth-
abundant element.[7] For example, Zeni and co-
workers reported the synthesis of 3-(organoselanyl)-
1,2-dihydroquinolines from arylpropargylamines
using FeCl3 in nitromethane (Scheme 1A),[8] while
Zhang and co-workers obtained functionalized 3-
selenylindoles from alkynylanilines in acetonitrile
(Scheme 1B)[9] using this approach. Both
methodologies rely on simple materials, are highly
modular and incorporate organochalcogenide groups
in the final heterocyclic product.
Table 1. Optimization of reaction conditions.
Inspired by these methods, we decided to
investigate the cyclization of organochalcogen
propargylamines (selected for being easily obtained
via A3-coupling chemistry)[10] in the presence of FeCl3
and dichalcogenides. We found that under certain
reaction conditions, densely substituted 4H-
chalcogenochromenes were obtained in a cascade
process that concomitantly forged 3 different C–C
bonds. Moreover, the organochalcogenide groups
installed by this sequence were easily functionalized
via coupling chemistry or by electrophilic quench of a
lithiated intermediate (Scheme 1C).
We began by using 1 equivalent of FeCl3, 2
equivalents of diphenyl diselenide 2a in DCE at 70 °C,
obtaining 3a in 71% yield (entry 1). Lower loadings of
FeCl3 were ineffective and no product 3a was observed
with 0.75 or 0.6 equivalents (entries 2 and 3). Next,
different amounts of diphenyl diselenide 2a were
screened, with 1.2 equivalents proving optimal (entries
4–6). An increase in the reaction yield was observed
when MeNO2 was used as solvent, while DCM, MeCN
and THF produced the opposite effect (entries 7–10).
The source of iron of choice proved crucial to the
reaction outcome, with Fe(NO3)3, Fe(acac)3, FeCl2
completely failing in delivering product 3a and FeBr3
giving 3a in only 49% yield (entries 11–14). The best
conditions found were tested under microwave
irradiation, however, a lower yield was obtained (entry
15). Finally, the effect of the leaving group R in the
organoselenium propargylamine 1 was surveyed:
pyrrolidinyl and morpholinyl were tested (entries 16
and 17), however, piperidinyl (entry 7) was confirmed
as the best among the amines. Surprisingly, acetyl and
methoxy group did not react in a similar way and the
starting materials were quickly decomposed under the
reaction conditions (entries 18 and 19). Interestingly,
a propargylamine containing a methyl group also
decomposed when exposed to FeCl3 and no starting
material was recovered from this reaction, as it was
initially expected (entry 20).
Scheme 1. Synthesis of cyclic chalcogenide species.
Results and Discussion
Our studies initiated with the screening of
conditions
for
the
formation
of
4H-
chalcogenochromene 3a from model substrates 1 and
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
With the optimized conditions in hand, we next
explored the scope of this reaction. The results are
summarized in Table 2.
Table 2. Scope of organochalcogen propargylamines.
Figure 3. ORTEP view of compound 3b.
The scope for the diaryl diselenide was next
evaluated using 1a under the same reaction conditions
(Table 3).
Table 3. Scope of diaryl diselenides.
Organoselenium propargylamines bearing electron-
neutral (1e) and electron-donating substituents such as
methyl (1d) and methoxy (1a-c) smoothly afforded
products 3a-e in good to excellent yields. Reactions
involving substrates bearing electron-withdrawing
substituents, on the other hand, were sluggish: 1f gave
product 3f in only 22%, while 1g-h failed to deliver
products 3g-h. These examples suggest a preference
for strongly electron-donating rings with the ortho
position free. Substitution of the carbocyclic ring was
tolerated and product 3i was obtained in 67% yield.
When the strongly deactivating trifluoromethyl group
is present in the same position, however, the expected
product was not observed (3j). Interestingly,
phenyltelluryl and phenylthio propargylamines also
afforded 4H-thiochromene 3j and 4H-tellurochromene
3k in reasonable yields. A reaction between 1a and 2a
on a gram scale afforded 3a in comparable yield,
indicating that this protocol is suitable for large-scale
processes. Failed (3g-h, j) and low-yielding reactions
were accompanied by significant decomposition of the
starting materials. No relevant by-products or
unreacted substrate were isolated after the indicated
reaction time.
The reaction proceeded well with electron-rich
diselenides 2b and 2c, which allowed the isolation of
4b and 4c in 74% and 59%, respectively. Electron-
poor propargylamines 2d and 2e were also compatible
with this reaction, providing 4d and 4e in 61% and
54% yield. Gratifyingly, the reaction conditions also
tolerated phenyl disulfide 2f and ditelluride 2g with
products 4f and 4g being isolated in 73% and 47%,
respectively.
The structure of 3b was unambiguously confirmed
by single-crystal X-ray analysis. The ORTEP view of
this compound is shown in Figure 3.[11] All other
compounds were characterized by standard
spectroscopic techniques. In addition to that,
selenochromenes 3a and 3b were also characterized by
HMBC (77Se-1H) analysis (see Supporting
Information).
An interesting feature of C(sp2)-Se bonds is the ability
to undergo lithium exchange reactions with
organolithium reagents. This approach makes the
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
Table 5. Optimization of reaction conditions for the Suzuki-
Miyaura cross-coupling reaction.
formation of new carbon-carbon, carbon-metal,
carbon-halogen and carbon-heteroatom bonds
accessible via lithium intermediates.[12] With this
objective in mind, we treated 3a with n-butyllithium in
THF at -78 C, followed by the addition of
electrophiles (Table 4). The selectivity for the
phenylselenyl substituent at position 2 was confirmed
1
by the H NMR spectrum of 5a, which shows a
characteristic singlet signal at 3.80 ppm (see
supporting information for details). This result is in
line with the expected stabilization of the anionic
intermediate provided by the adjacent selenium atom.
Table 4. C2-functionalization of 3a with electrophiles.
Having established the optimized reaction
conditions, various potassium aryltrifluoroborate salts
6 were employed and the results are summarized in
Table 6.
Addition of the electrophiles indicated in Table 4
successfully installed hydrogen (5a), deuterium (5b),
a secondary alcohol (5c) and a TMS group (5d) at
position 2. These examples show the versatility of the
phenylselenyl group that is concomitantly installed
during the cyclization cascade.
Finally, we wanted to show one more example of
the flexibility of this substituent by replacing it by aryl
groups via Suzuki-Miyaura cross-coupling reaction, a
transformation still unprecedented for –SePh groups.
A screening of reaction conditions was carried out
The results shown above indicate that the electronic
nature of the potassium trifluoroborate salt directly
impacts the isolated yields. While electron-rich 6a
cleanly gave 8a in 80% yield, potassium aryl
trifluoroborate salts bearing electron-withdrawing
groups such as p–Cl (6b), p–CN (6c), m–CHO (6d)
and
p–COMe
(6e)
afforded
2-aryl-4H-
selenochromenes 7b-e in only low to modest yields.
In order to better understand the events leading to
the formation of chalcogenochromenes, a control
experiment involving propargylamine 1m containing a
methoxy group adjacent to the selenium atom was
carried out. Compound 8 bearing a fused 7-membered
ring was isolated as the sole product, suggesting a
different pathway in the cyclization cascade.
with
substrate
3a
and
4-methoxyphenyl-
trifluoroborate 6a (Table 5).
Initially, we used a set of conditions previously
described for the Suzuki-Miyaura cross-coupling
between
aryl
tellurides
and
potassium
aryltrifluoroborate salts,[13] obtaining 7a in
encouraging 41% yield (entry 1). Lowering the
amount of Ag2O and Et3N added increased the isolated
yield of 7a to 52% (entry 2). A survey of some
palladium catalysts and ligands showed that
Pd(dppf)Cl2 was the most active one (entries 3–7),
however, significant amounts of diarylated product
were also isolated, which led us to choose PEPPSI-iPr
to continue the screening, as this complex provided 7a
as the sole product. Lowering the reaction temperature
to 60 C significantly increased the reaction yield,
from 47% to 80% (entry 9). Variations in the additive
(entries 11 and 12) or the base (entries 12 and 13) were
not productive. Similar outcome was observed with
variations in the reaction solvent (entries 14–16).
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
Table 6. Scope for the Suzuki-Miyaura cross-coupling of 3a
with potassium aryl trifluoroborate salts.
and the experiments described above is illustrated in
Scheme 3. Activation of diphenyl selenide by FeCl3 in
MeNO2 generates the activated complex A (m/z:
454.8591, [M+Na]+), which is intercepted by 1a to
form seleniranium ion C (m/z: 542.0496, [M]+).[14]
Attack by phenylselenide leads to intermediate D,
which then expels the activated piperidinyl leaving
group to form the stabilized cation E. A quick
intramolecular cyclization follows to give F. In the
final step, the aromaticity is re-established by proton
abstraction, delivering product 3a (m/z: 614.9239
[M+H]+). In the case of compounds 3d-f, in which a
strong activating group is not present in the structure
of the starting materials 1d-f, we speculate that the
expulsion of the piperidinyl moiety and the cyclization
take place concomitantly (i.e. F forms directly from D).
Scheme 2. Control experiment.
A plausible mechanism for the cyclization of the
organochalcogen
propargylamines
based
on
information collected by high-resolution mass
spectrometry (see supporting information for details)
Scheme 3. Proposed mechanism for the formation of 4H-selenochromens.
This mechanism accounts for some of the
experimental observations: strongly electron-donating
groups in R1 (Table 2) facilitate the expulsion of the
piperidinyl leaving group in intermediate D, while
ortho-substituents in R1 introduce steric clash between
these groups, the phenyl selenide shown in red and the
piperidinyl moiety, making D more unstable (Scheme
3). Similarly, the significantly lower yield observed
when the piperidinyl moiety was replaced by a
morpholinyl group in substrate 1 (Table 1, entry 17)
may be due to competitive chelation of the Lewis acid
FeCl3 in intermediate D. The detection of complex A
indicates that a polar solvent is required in order to
stabilize iron-containing species, which is in
agreement with the results observed in entries 7–9
(Table 1). Finally, the control experiment shown in
Scheme 2 indicates the trapping of E by the o-methoxy
group adjacent to the selenium atom, strongly
suggesting the intermediacy of this species.
Conclusion
In summary, we have described the synthesis of 4H-
chalcogenochromene prepared via the iron(III)-
promoted
cyclization
of
organochalcogen
propargylamines in the presence of diaryl
dichalcogenides. Products with variations in the
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
(hexane:ethyl acetate 95:5) as a yellow oil (200 mg, 67%).
carbocyclic ring and at positions 2, 3 and 4 were
obtained in moderate to excellent yields. In addition,
Reaction time 2h. IR max (cm-1): 2952, 2823, 2758, 1601,
1
1585, 1426, 1391, 989, 707, 666. H NMR (300 MHz,
we
demonstrated
the
chemoselective
C2-
CDCl3)  7.45 (d, J = 6.4 Hz, 2H), 7.38 (d, J = 6.6 Hz, 2H),
7.20 (dd, J = 13.8, 5.6 Hz, 7H), 7.09 (d, J = 7.3 Hz, 2H),
6.97 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.81 (d, J
= 8.8 Hz, 1H), 4.88 (s, 1H), 2.18 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 137.2, 136.7, 136.2, 133.8, 133.6, 132.0,
131.4, 130.5, 130.4, 129.7, 129.3, 129.2, 128.7, 128.4,
128.1, 127.9, 127.5, 127.4, 126.9, 120.4, 56.4, 21.0. HRMS
calcd for C28H22Se3 (ESI-TOF, [M]+): 597.9217. Found:
597.9235.
functionalization with four different electrophiles as
well as the arylation of the same position with
potassium aryl trifluoroborate salts via Suzuku-
Miyaura reaction, adding nine more examples to the
final scope.
Experimental Section
4-Phenyl-2,3-bis(phenylselanyl)-4H-selenochromene
(3e): Product 3e was isolated by column chromatography
(hexane:ethyl acetate 95:5) as a yellow oil (172 mg, 59%).
Reaction time 5h. IR max (cm-1): 2954, 1521, 1426, 1391,
989, 707, 666. 1H NMR (300 MHz, CDCl3)  7.55 (dd, J =
8.7, 6.4 Hz, 2H), 7.45 (d, J = 6.4 Hz, 2H), 7.38 (d, J = 7.8
Hz, 2H), 7.27 – 7.16 (m, 11H), 7.14 (s, 1H), 6.87 – 6.79 (m,
1H), 4.92 (s, 1H). 13C NMR (75 MHz, CDCl3)  139.7,
137.0, 133.8, 133.8, 133.6, 131.6, 130.4, 129.8, 129.3, 129.2,
129.2, 128.8, 128.4, 128.1, 128.0, 127.6, 127.5, 126.9, 126.6,
120.6, 56.7. HRMS calcd for C27H20Se3 (ESI-TOF, [M]+):
583.9061. Found: 583.9085.
General procedure for the iron-promoted cyclization of
organochalcogen
propargylamines
and
diaryl
dichalcogenides. A 10 mL-vial was charged with FeCl3 (81
mg, 0.5 mmol, 1.0 equiv.), the appropriate diaryl
dichalcogenide (0.6 mmol, 1.2 equiv.) and nitromethane (1
mL). The vial was then flushed with N2 and then the mixture
was stirred at room temperature for 15 min. The appropriate
organochalcogen propargylamine 1a-l (0.5 mmol, 1.0
equiv.) was then diluted in nitromethane (2 mL) and added
to the reaction vial via syringe. The mixture was stirred at
70 °C under a N2 flow until full consumption of the starting
material was observed by TLC. The mixture was
concentrated under reduced pressure and the residue was
purified by flash column chromatography using the mixture
of solvents indicated.
4-(4-Bromophenyl)-2,3-bis(phenylselanyl)-4H-
selenochromene (3f): Product 3f was isolated by column
chromatography (hexane:ethyl acetate 95:5) as a yellow oil
(73 mg, 22%). Reaction time 5h. IR max (cm-1): 2950, 2825,
1
1521, 1426, 1391, 978, 707, 666. H NMR (300 MHz,
CDCl3) δ 7.60 (dd, J = 6.3, 2.9 Hz, 3H), 7.53 (d, J = 7.5 Hz,
2H), 7.44 (d, J = 6.6 Hz, 2H), 7.34 – 7.29 (m, 5H), 7.20 –
7.15 (m, 3H), 6.99 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 7.4 Hz,
1H), 4.91 (s, 1H). 13C NMR (75 MHz, CDCl3) : 138.8,
136.6, 134.1, 134.1, 133.8, 132.3, 131.7, 131.2, 129.6, 129.5,
129.4, 129.3, 128.9, 128.6, 128.5, 128.3, 127.9, 127.7, 127.3,
120.7, 56.3. HRMS calcd for C27H19BrSe3 (ESI-TOF,
[M]+): 661.8166. Found: 661.8143.
4-(4-Methoxyphenyl)-2,3-bis(phenylselanyl)-4H-
selenochromene (3a): Product 3a was isolated by column
chromatography (hexane:ethyl acetate 95:5) as an orange oil
(288 mg, 94%). Reaction time 1h. IR max (cm-1): 2954,
2853, 2833, 2939, 1525, 1458, 1428, 1391, 1207, 1141, 989,
1
713, 668. H NMR (300 MHz, CDCl3)  7.56 – 7.49 (m,
2H), 7.46 – 7.41 (m, 2H), 7.26 (m, 7H), 7.18 – 7.11 (m, 2H),
7.06 (d, J = 8.5 Hz, 2H), 6.87 (dd, J = 7.1, 1.7 Hz, 1H), 6.70
(d, J = 8.8 Hz, 2H), 4.93 (s, 1H), 3.71 (s, 3H). 13C NMR (75
MHz, CDCl3)  158.3, 137.2, 133.8, 133.8, 132.0, 131.9,
131.5, 130.5, 130.3, 129.7, 129.3, 129.2, 128.7, 128.4, 128.1,
127.9, 127.5, 126.9, 120.2, 113.4, 56.1, 55.2. 77Se NMR (57
MHz, in CDCl3)  484.0, 475.1, 463.6 (d, JSe-H = 7.9 Hz).
HRMS calcd for C28H24OSe3 (ESI-TOF, [M + H]+):
614.9239. Found: 614.9258.
6-Fluoro-4-(4-methoxyphenyl)-2,3-bis(phenylselanyl)-
4H-selenochromene (3i): Product 3i was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a red
oil (211 mg, 67%). Reaction time 3h. IR max (cm-1): 2956,
2900, 2739, 1680, 1529, 1458, 1436, 1184, 1119, 709, 668.
1H NMR (300 MHz, CDCl3)  7.51 (q, J = 3.0 Hz, 2H), 7.45
– 7.40 (m, 2H), 7.24 (d, J = 6.1 Hz, 4H), 7.13 – 7.04 (m,
4H), 6.99 – 6.88 (m, 3H), 6.68 (d, J = 8.3 Hz, 2H), 4.93 (s,
1H), 3.67 (s, 3H). 13C NMR (75 MHz, CDCl3)  164.8 (d, J
= 248.8 Hz), 158.5, 137.3, 136.6 (d, J = 8.0 Hz), 136.2 (d, J
= 8.0 Hz), 133.8 (d, J = 4.9 Hz), 133.6, 132.0, 131.7, 129.8,
129.5, 129.3, 128.7, 128.5, 128.0, 127.7, 127.0, 116.7 (d, J
= 21.7 Hz), 116.6 (d, J = 21.7 Hz), 113.6, 56.4, 55.2. HRMS
calcd for C28H21FOSe3 (ESI-TOF, [M]+): 631.9072. Found:
631.9093.
4-(2,6-Dimethoxyphenyl)-2,3-bis(phenylselanyl)-4H-
selenochromene (3b): Product 3b was isolated by column
chromatography (hexane:ethyl acetate 90:10) as a yellow
solid (196 mg, 61%). mp 162-164 °C. Reaction time 3h. IR

max (cm-1): 2892, 2831, 2738, 1521, 1423, 1387, 1197, 1071,
711, 668. 1H NMR (300 MHz, CDCl3)  7.74 (d, J = 7.4 Hz,
2H), 7.39 (d, J = 17.0 Hz, 6H), 7.19 (s, 3H), 7.01 (s, 1H),
6.96 – 6.84 (m, 3H), 6.48 (d, J = 8.3 Hz, 2H), 5.76 (s, 1H),
3.68 (s, 6H). 13C NMR (75 MHz, CDCl3)  158.4, 136.6,
136.1, 132.6, 131.6, 130.6, 129.9, 129.4, 128.9, 128.9, 128.8,
128.3, 127.2, 126.5, 126.3, 126.2, 126.1, 123.4, 120.7, 104.0,
55.6, 46.6. 77Se NMR (57 MHz, in CDCl3)  519.1, 423.7,
415.7 (d, JSe-H = 9.8 Hz). HRMS calcd for C29H24O2Se3
(ESI-TOF, [M]+): 643.9272. Found: 643.9256.
4-(4-Methoxyphenyl)-2,3-bis(phenylselanyl)-4H-
thiochromene (3k): Product 3k was isolated by column
chromatography (hexane:ethyl acetate 95:5) as a yellow oil
(144 mg, 51%). Reaction time 3h. IR max (cm-1): 2954,
2739, 1527, 1458, 1393, 1207, 991, 713, 666. 1H NMR (300
MHz, CDCl3) δ 7.55 (d, J = 6.1 Hz, 1H), 7.32 – 7.23 (m,
9H), 7.19 – 7.08 (m, 5H), 6.96 (d, J = 3.4 Hz, 1H), 6.73 (d,
J = 8.0 Hz, 2H), 4.81 (s, 1H), 3.72 (s, 3H). 13C NMR (75
MHz, CDCl3)  157.5, 134.8, 133.5, 132.8, 132.3, 131.6,
129.9, 129.7, 129.4, 128.5, 128.1, 128.0, 127.5, 127.4, 126.4,
125.8, 125.7, 124.6, 112.7, 112.6, 54.1, 51.2. HRMS calcd
for C28H22OSSe2 (ESI-TOF, [M]+): 565.9722. Found:
565.9740.
4-(2,5-Dimethoxyphenyl)-2,3-bis(phenylselanyl)-4H-
selenochromene (3c): Product 3c was isolated by column
chromatography (hexane: ethyl acetate 95:5) as a brown oil
(167 mg, 52%). Reaction time 3h. IR max (cm-1): 2956,
1
2831, 2738, 1497, 1443, 1391, 1173, 989, 709, 668. H
NMR (300 MHz, CDCl3) δ 7.67 (d, J = 7.7 Hz, 2H), 7.35
(dd, J = 19.3, 6.8 Hz, 5H), 7.19 (dd, J = 15.2, 7.5 Hz, 6H),
7.09 – 6.96 (m, 2H), 6.63 (s, 2H), 5.55 (s, 1H), 3.67 (s, 3H),
3.60 (s, 3H). 13C NMR (75 MHz, CDCl3)  153.5, 150.4,
136.8, 135.2, 134.6, 133.5, 130.8, 130.7, 130.2, 129.8, 129.6,
129.3, 129.0, 128.7, 127.9, 127.5, 127.3, 126.7, 122.2, 115.0,
112.8, 111.7, 55.8, 55.7, 51.0. HRMS calcd for
C29H24O2Se3 (ESI-TOF, [M]+): 643.9272. Found: 643.9298.
(4-(4-Methoxyphenyl)-4H-tellurochromene-2,3-
diyl)bis(phenylselane) (3l): Product 3l was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a
brown oil (186 mg, 56%). Reaction time 4h. IR max (cm-1):
1
2952, 2739, 1527, 1458, 1391, 1207, 989, 709, 666. H
NMR (300 MHz, CDCl3) δ 7.52 (d, J = 6.0 Hz, 2H), 7.44
(d, J = 6.1 Hz, 2H), 7.33 – 7.20 (m, 7H), 7.14 (t, J = 6.0 Hz,
2H), 7.06 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 7.0 Hz, 1H), 6.69
2,3-bis(Phenylselanyl)-4-(p-tolyl)-4H-selenochromene
(3d): Product 3d was isolated by column chromatography
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
(d, J = 8.7 Hz, 2H), 4.93 (s, 1H), 3.71 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 158.4, 137.3, 133.8, 133.8, 132.0, 131.9,
131.5, 130.5, 130.4, 129.7, 129.4, 129.3, 128.7, 128.4,
128.2, 127.9, 127.5, 126.9, 120.2, 113.4, 56.1, 55.2. HRMS
calcd for C28H22OSe2Te (ESI-TOF, [M]+): 663.9063.
Found: 663.9053.
2H), 4.82 (s, 1H), 3.73 (s, 3H). 13C NMR (75 MHz, CDCl3)
 158.5, 135.4, 135.0, 133.8, 133.6, 133.3, 132.0, 131.6,
129.3, 129.2, 129.0, 128.5, 127.9, 127.8, 127.3, 126.7, 125.7,
123.6, 113.6, 113.4, 55.2, 53.2. HRMS calcd for
C28H22OS2Se (ESI-TOF, [M]+): 518.0277. Found: 518.0293.
4-(4-Methoxyphenyl)-2,3-bis((4-
4-(4-Methoxyphenyl)-2,3-bis(naphthalen-2-ylselanyl)-
4H-selenochromene (4b): Product 4b was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a
brown solid (264 mg, 74%); mp: 104-107 °C. Reaction time
5h. IR max (cm-1): 2944, 2887, 2743, 1456, 1205, 1141,
1000, 782, 715, 670. 1H NMR (300 MHz, CDCl3) δ 7.95 (s,
1H), 7.73 (t, J = 7.9 Hz, 2H), 7.59 (dd, J = 14.4, 8.5 Hz, 2H),
7.54 – 7.37 (m, 7H), 7.33 – 7.23 (m, 4H), 7.04 (d, J = 8.5
Hz, 2H), 6.91 (d, J = 8.6 Hz, 1H), 6.78 – 6.70 (m, 1H), 6.63
(d, J = 8.5 Hz, 2H), 5.96 (s, 1H), 3.65 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 158.3, 134.5, 134.1, 133.8, 133.3, 133.2,
133.1, 132.8, 132.8, 132.0, 131.8, 131.1, 130.9, 130.7,
129.7, 129.3, 129.2, 128.9, 128.6, 128.0, 127.7, 127.7,
127.6, 127.3, 126.6, 126.5, 126.3, 125.4, 125.4, 122.3,
119.9, 113.4, 55.1, 49.4. HRMS calcd for C36H26OSe3 (ESI-
TOF, [M]+): 713.9479. Found: 713.9265.
(trifluoromethyl)phenyl)tellanyl)-4H-selenochromene
(4g): Product 4g was isolated by column chromatography
(hexane:ethyl acetate 95:5) as a brown oil (200 mg, 47%).
Reaction time 3h. IR max (cm-1): 2952, 2739, 1458, 1391,
1
1205, 1140, 989, 709, 606. H NMR (300 MHz, CDCl3) 
7.52 (d, J = 6.7 Hz, 2H), 7.44 (d, J = 7.1 Hz, 2H), 7.34 –
7.22 (m, 5H), 7.15 (s, 2H), 7.06 (d, J = 8.2 Hz, 2H), 6.88 (d,
J = 6.5 Hz, 1H), 6.70 (d, J = 8.4 Hz, 2H), 4.93 (s, 1H), 3.73
(s, 3H). 13C NMR (75 MHz, CDCl3)  158.4, 137.3, 134.6,
133.8, 133.8, 132.0, 131.9, 131.5, 130.4 (q, J = 32 Hz),
130.4, 129.7, 129.5, 129.4, 129.3, 128.7, 128.4, 128.2,
127.9, 127.4 (q, J = 2.3 Hz), 126.9 (q, J = 284 Hz), 120.2 (q,
J = 284 Hz), 113.4, 56.1, 55.2. HRMS calcd for
C30H22F6OSeTe2 (ESI-TOF, [M + H]+): 850.8781. Found:
850.8778.
General Procedure for the reaction addition of
elecrophiles to C-2. A solution of 3a (0.1 mmol, 1.0 equiv.)
in THF (1 mL) was added to a 10 mL pre-flushed flask under
nitrogen flow via syringe. The solution was cooled to –78 °C
and then n-butyllithium 2 M (60 L, 0.12 mmol, 1.2 equiv.)
was added dropwise. The solution was stirred at this
temperature for one hour and then the indicated electrophile
(0.12 mmol, 1.2 equiv.) was slowly added. The mixture was
warmed to RT and stirred for 1 h. The reaction was then
diluted with ethyl acetate and the solvent was in sequence
4-(4-Methoxyphenyl)-2,3-bis(o-tolylselanyl)-4H-
selenochromene (4c): Product 4c was isolated by column
chromatography (hexane:ethyl acetate 95:5) as an orange oil
(189 mg, 59%). Reaction time 6h. IR max (cm-1): 2950,
1
2739, 1458, 1413, 1393, 1207, 1140, 1000, 709, 668. H
NMR (300 MHz CDCl3)  7.43 – 7.35 (m, 2H), 7.20 – 7.10
(m, 6H), 7.04 – 6.93 (m, 6H), 6.61 (s, 2H), 4.71 (s, 1H), 3.61
(s, 3H), 2.18 (s, 3H), 2.11 (s, 3H). 13C NMR (75 MHz,
CDCl3)  158.4, 141.3, 137.0, 136.1, 135.3, 133.6, 133.2,
131.9, 130.9, 130.5, 129.4, 129.3, 128.7, 128.6, 128.0, 127.9, removed under reduced pressure. The residue was purified
127.4, 127.3, 126.9, 126.8, 126.7, 118.3, 113.5, 113.4, 55.9,
55.2, 22.8, 21.7. HRMS calcd for C30H27OSe3 (ESI-TOF,
[M + H]+): 642.9552. Found: 642.9563.
by flash column chromatography using the indicated
mixture of solvents as eluent.
4-(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
2,3-bis((4-Fluorophenyl)selanyl)-4-(4-methoxyphenyl)-
4H-selenochromene (4d): Product 4d was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a
brown oil (198 mg, 61%). Reaction time 5h. IR max (cm-1):
2959, 2741, 1529, 1458, 1436, 1182, 1119, 981, 799, 711.
1H NMR (300 MHz, CDCl3) δ 7.57 – 7.51 (m, 2H), 7.46 –
7.41 (m, 2H), 7.31 – 7.24 (m, 2H), 7.18 – 7.13 (m, 3H), 7.04
- 6.95 (m, 5H), 6.70 (d, J = 7.6 Hz, 2H), 4.87 (s, 1H), 3.72
(s, 3H). 13C NMR (75 MHz, CDCl3) δ 163.5 (d, J = 248 Hz),
161.2 (d, J = 248 Hz), 158.4, 137.1, 136.5 (d, J = 8.0 Hz),
136.0 (d, J = 8.0 Hz), 133.6 (d, J = 18.0 Hz), 131.6 (d, J =
17.7 Hz), 130.4, 129.6, 129.3, 128.5, 128.4, 128.2, 127.6,
127.0, 120.7, 116.6 (d, J = 5.1 Hz), 116.3 (d, J = 5.1 Hz),
113.5, 56.2, 55.2. HRMS calcd for C28H20F2OSe3 (ESI-TOF,
[M]+): 649.8978. Found: 649.8953.
selenochromene (5a): Product 5a was isolated by column
chromatography (hexane:ethyl acetate 95:5) as a yellow oil
(36 mg, 79%). IR max (cm-1): 2833, 2739, 1458, 1207, 1140,
1
998, 711, 668. H NMR (300 MHz, CDCl3)  7.57 – 7.49
(m, 2H), 7.42 (d, J = 7.3 Hz, 1H), 7.29 (d, J = 5.2 Hz, 5H),
7.18 (d, J = 13.4 Hz, 2H), 7.03 (s, 1H), 6.78 (d, J = 8.5 Hz,
2H), 4.90 (s, 1H), 3.80 (s, 1H), 3.77 (s, 3H). 13C NMR (75
MHz, CDCl3)  158.6, 137.0, 133.6, 132.9, 130.3, 129.7,
129.4, 129.1, 128.8, 127.8, 127.5, 127.4, 127.1, 126.9, 117.4,
113.7, 55.2, 54.5. HRMS calcd for C22H17OSe2 (ESI-TOF,
[M - H]+): 456.9610. Found: 456.9636.
4-(4-Methoxyphenyl)-3-(phenylselanyl)-2-deuterium-
4H-selenochromene (5b): Product 5b was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a
yellow oil (32 mg, 70%). IR max (cm-1): 2952, 2739, 2501,
1
4-(4-Methoxyphenyl)-2,3-bis((4-
1458, 1205, 1140, 1000, 713, 670. H NMR (300 MHz,
(trifluoromethyl)phenyl)selanyl)-4H-selenochromene
(4e): Product 4e was isolated by column chromatography
(hexane:ethyl acetate 95:5) as a brown oil (202 mg, 54%).
Reaction time 6h. IR max (cm-1): 2959, 2743, 1549, 1460,
CDCl3)  7.49 (d, J = 3.6 Hz, 2H), 7.40 (d, J = 6.5 Hz, 1H),
7.31 – 7.19 (m, 6H), 7.13 (d, J = 7.8 Hz, 2H), 6.80 – 6.71
(m, 2H), 4.88 (s, 1H), 3.74 (s, 3H). 13C NMR (75 MHz,
CDCl3)  158.5, 137.0, 133.6, 132.9, 130.3, 129.7, 129.4,
129.0, 128.7, 127.8, 127.4, 127.4, 126.9, 126.8, 113.7, 55.2,
54.4. HRMS calcd for C22H19DOSe2 (ESI-TOF, [M + H]+):
459.9824. Found: 459.9845.
1
1277, 1084, 1039, 979, 799, 709. H NMR (300 MHz,
CDCl3)  7.56 – 7.34 (m, 8H), 7.27 (d, J = 6.9 Hz, 1H), 7.14
(t, J = 6.9 Hz, 2H), 7.01 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 7.1
Hz, 1H), 6.64 (d, J = 8.5 Hz, 2H), 4.90 (s, 1H), 3.65 (s, 3H).
13C NMR (75 MHz, CDCl3)  158.8, 136.9, 135.9, 135.4,
135.2, 134.7, 133.1, 132.7, 131.9, 131.6, 131.6, 131.4,
129.8, 128.7 (q, J = 32 Hz), 128.5, 128.2, 127.5, 126.2 (q, J
= 2.3 Hz), 125.9 (q, J = 284 Hz), 122.3 (q, J = 284 Hz),
113.7, 113.5, 57.1, 55.3. HRMS calcd for C30H22F6OSe3
(ESI-TOF, [M + H]+): 750.8987. Found: 750.8965.
(4-(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
selenochromen-2-yl)(4-nitrophenyl)metha-nol
(5c):
Product 5c was isolated by column chromatography
(hexane:ethyl acetate 95:5) as a yellow solid (30 mg, 49%);
MP 151-153 °C. IR max (cm-1): 3416, 2831, 1458, 1296,
1
1208, 1143, 991, 720, 676. H NMR (300 MHz, CDCl3) δ
8.20 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.42 (d, J
= 7.3 Hz, 3H), 7.32 – 7.24 (m, 3H), 7.22 – 7.16 (m, 2H),
7.02 (d, J = 8.6 Hz, 2H), 6.93 (d, J = 6.6 Hz, 1H), 6.67 (d, J
= 8.7 Hz, 2H), 6.51 (s, 1H), 5.02 (s, 1H), 3.72 (s, 3H), 2.74
(s, 1H). 13C NMR (75 MHz, CDCl3)  158.5, 148.2, 147.6,
139.9, 138.0, 133.1, 131.6, 129.6, 129.6, 129.4, 128.8, 128.4,
128.0, 127.7, 127.4, 127.1, 126.9, 126.4, 123.7, 113.5, 75.0,
56.7, 55.2. HRMS calcd for C29H21NO2Se2 (ESI-TOF, [M -
OH]+): 591.9930. Found: 591.9946.
(4-(4-Methoxyphenyl)-4H-selenochromene-2,3-
diyl)bis(phenylsulfane) (4f): Product 4f was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a
brown oil (189 mg, 73%). Reaction time 3h. IR max (cm-1):
1
2952, 2739, 1458, 1426, 1391, 1207, 989, 709, 666. H
NMR (300 MHz, CDCl3) δ 7.50 (d, J = 7.2 Hz, 2H), 7.44
(d, J = 5.7 Hz, 2H), 7.29 – 7.25 (m, 7H), 7.16 (s, 2H), 7.06
(d, J = 8.1 Hz, 2H), 6.91 – 6.87 (m, 1H), 6.71 (d, J = 8.3 Hz,
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
(4-(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
2H), 7.52 (d, J = 7.8 Hz, 2H), 7.49 – 7.44 (m, 1H), 7.33 (d,
J = 7.1 Hz, 2H), 7.25 – 7.17 (m, 7H), 6.94 (q, J = 4.2 Hz,
1H), 6.80 – 6.73 (m, 2H), 5.04 (s, 1H), 3.74 (s, 3H), 2.60 (s,
3H). 13C NMR (75 MHz, CDCl3)  197.4, 158.4, 144.8,
137.7, 136.9, 133.6, 133.0, 132.0, 130.8, 130.0, 129.8, 129.7,
129.2, 128.8, 128.6, 128.3, 127.8, 127.5, 127.0, 125.2, 113.6,
55.8, 55.2, 26.7. HRMS calcd for C30H24O2Se2 (ESI-TOF,
[M]+): 576.0107. Found: 576.0124.
selenochromen-2-yl)trimethylsilane (5d): Product 5d was
isolated by column chromatography (hexane:ethyl acetate
95:5) as a yellow oil (37 mg, 70%). IR max (cm-1): 2956,
1
2851, 2831, 1458, 1205, 1140, 1002, 806, 711, 668. H
NMR (300 MHz, CDCl3) δ 7.47 – 7.40 (m, 1H), 7.33 (dd, J
= 5.5, 2.0 Hz, 2H), 7.25 (d, J = 2.1 Hz, 1H), 7.21 – 7.15 (m,
4H), 7.13 – 7.08 (m, 2H), 6.94 – 6.89 (m, 1H), 6.74 – 6.63
(m, 2H), 5.02 (s, 1H), 3.71 (s, 3H), 0.39 (s, 9H). 13C NMR
(75 MHz, CDCl3)  157.9, 137.5, 133.3, 133.2, 131.5,
131.2, 131.1, 129.9, 128.9, 128.8, 128.2, 126.9, 126.7,
126.2, 113.3, 113.0, 57.9, 54.7, 0.0. HRMS calcd for
C25H27OSe2Si (ESI-TOF, [M + H]+): 531.0156. Found:
531.0138.
3-(4-(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
selenochromen-2-yl)benzaldehyde (7e): Product 7e was
isolated by column chromatography (hexane:ethyl acetate
95:5) as a yellow oil (48 mg, 43%). Reaction time 7h. IR

max (cm-1): 2954, 2739, 2635, 1643, 1458, 1207, 1141, 756,
713, 670. 1H NMR (300 MHz, CDCl3) δ 10.01 (s, 1H), 7.91
(s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 7.7 Hz, 1H),
7.54 (d, J = 7.6 Hz, 1H), 7.48 (dd, J = 6.7, 2.7 Hz, 1H), 7.31
(d, J = 6.6 Hz, 2H), 7.27 – 7.16 (m, 7H), 6.95 (dd, J = 5.8,
3.2 Hz, 1H), 6.77 (d, J = 8.7 Hz, 2H), 5.06 (s, 1H), 3.75 (s,
3H). 13C NMR (75 MHz, CDCl3) δ 191.7, 158.4, 141.1,
137.6, 136.4, 135.5, 133.5, 132.8, 131.9, 130.9, 130.7,
130.0, 129.7, 129.5, 129.2, 129.0, 128.6, 128.6, 127.7,
127.5, 127.0, 125.4, 113.6, 55.9, 55.2. HRMS calcd for
C29H23O2Se2 (ESI-TOF, [M + H]+): 563.0023. Found:
563.0046.
General procedure for the Suzuki Coupling Reaction. To
a 10 mL vial were added in sequence 3a (122 mg, 0.2 mmol,
1.0 equiv.), potassium organotrifluoroborate (0.4 mmol, 2.0
equiv.), PEPPSI-iPr (14 mg, 20 mol, 10 mol%), silver (I)
oxide (46 mg, 0.2 mmol, 1.0 equiv.), MeOH/DMF (1:3) (4
mL) and triethylamine (56 L, 0.4 mmol, 2.0 equiv.). The
mixture was stirred at 60 °C until total consumption of 3a
was observed by TLC. After cooling to RT, the reaction was
diluted with EtOAc and washed with saturated of NH4Cl,
dried over MgSO4 and concentrated under reduced pressure.
The residue was then purified by flash column
chromatography.
5-(4-methoxyphenyl)-2,3-bis(phenylselanyl)-5H-
benzo[e][1,4]oxaselenepine (8): Product 8 was isolated by
column chromatography (hexane:ethyl acetate 95:5) as a
yellow oil (132 mg, 42%). Reaction time 3h. IR max (cm-1):
2952, 2803, 2738, 1458, 1391, 1205, 1140, 989, 709, 666.
1H NMR (300 MHz, CDCl3) 7.52 (2H, d, J = 7.4 Hz), 7.44
(2H, d, J = 6.2 Hz), 7.33 – 7.20 (6H, m), 7.18 – 7.10 (2H,
m), 7.06 (2H, d, J = 8.6 Hz), 6.90 – 6.84 (1H, m), 6.70 (2H,
d, J = 8.7 Hz), 4.93 (1H, s), 3,71 (3H, s). 13C NMR (75
MHz, CDCl3) δ 158.4, 137.3, 133.8, 133.8, 132.0, 131.9,
131.5, 130.5, 130.4, 129.7, 129.4, 129.3, 128.7, 128.4,
128.2, 127.9, 127.5, 126.9, 120.3, 113.4, 56.1, 55.2. HRMS
2,4-bis(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
selenochromene (7a): Product 7a was isolated by column
chromatography (hexane:ethyl acetate 95:5) as a yellow oil
(90 mg, 80%). Reaction time 8h. IR max (cm-1): 2956, 2741,
1553, 1456, 1205, 1136, 998, 879, 804, 706. 1H NMR (300
MHz, CDCl3) δ 7.45 – 7.40 (m, 1H), 7.38 (d, J = 8.5 Hz,
2H), 7.33 (d, J = 6.2 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.18
– 7.11 (m, 5H), 6.87 (d, J = 8.6 Hz, 3H), 6.73 (d, J = 8.7 Hz,
2H), 5.00 (s, 1H), 3.74 (s, 3H), 3.67 (s, 3H). 13C NMR (75
MHz, CDCl3)  160.0, 158.3, 138.1, 134.3, 133.5, 132.3,
132.3, 131.3, 131.0, 130.6, 129.6, 129.1, 128.7, 128.6, 127.5, calcd for C28H23O2Se3 (ESI-TOF, [M + H]+): 630.9188 .
127.3, 126.9, 122.8, 113.7, 113.5, 55.7, 55.3, 55.2. HRMS
calcd for C29H25O2Se2 (ESI-TOF, [M + H]+): 565.0180.
Found: 565.0162.
Found: 630.9152.
Acknowledgements
2-(4-Chlorophenyl)-4-(4-methoxyphenyl)-3-
(phenylselanyl)-4H-selenochromene (7b): Product 7b was
isolated by column chromatography (hexane:ethyl acetate
95:5) as a yellow oil (61 mg, 54%). Reaction time 10h. IR
The authors gratefully thank the São Paulo Research Foundation
(FAPESP grant 2017/24821-4 to HAS, FAPESP 2016/04289-3 to
IMO, 2017/26673-2 to CHAE, 2016/24396-9 to MPD) and The
National Council for Scientific and Technological Development
(CNPq) for fellowships (306119/2014-5 to HAS, 303207/2017–5
to JZ-S). The Araucária Foundation for a fellowship (FGM-
Unioeste 003/2017). We thank Professor Regina H. A. Santos from
IQSC-USP for the X-ray data collection.

max (cm-1): 2956, 2739, 1680, 1458, 1207, 1140, 981, 715,
1
668. H NMR (300 MHz, CDCl3) δ 7.45 (dd, J = 9.1, 5.4
Hz, 2H), 7.35 – 7.32 (m, 3H), 7.25 – 7.17 (m, 9H), 6.96 –
6.89 (m, 1H), 6.75 (d, J = 8.6 Hz, 2H), 5.02 (s, 1H), 3.72 (s,
3H). 13C NMR (75 MHz, CDCl3)  158.4, 138.4, 137.7,
134.6, 134.0, 133.6, 132.1, 130.9, 130.2, 129.7, 129.2, 129.1,
128.6, 128.4, 127.7, 127.4, 126.9, 124.5, 113.7, 113.6, 55.7,
55.2. HRMS calcd for C28H21ClOSe2 (ESI-TOF, [M]+):
567.9611. Found: 567.9640.
References
4-(4-(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
[1] a) D. Kumar, P. Sharma, H. Singh, K. Nepali, G. K.
Gupta, S. K. Jain, F. Ntie-Kang, RSC Adv. 2017, 7,
36977-36999; b) D. Harel, D. Schepmann, H. Prinz, R.
Brun, T. J. Schmidt, B. Wünsch, J. Med. Chem. 2013,
56, 7442-7448; c) N. F. L. Machado, M. P. M. Marques,
Curr. Bioact. Compd. 2010, 6, 76-89; d) B. Godoi, A.
Sperança, D. F. Back, R. Brandão, C. W. Nogueira, G.
Zeni, J. Org. Chem. 2009, 74, 3469-3477; e) W. A. L.
van Otterlo, E. L. Ngidi, S. Kuzvidza, G. L. Morgans, S.
S. Moleele, C. B. de Koning, Tetrahedron 2005, 61,
9996-10006. f) D. Joulain, R. Tabacchi, Phytochemistry
1994, 37, 1769-1770.
selenochromen-2-yl)benzonitrile (7c): Product 7c was
isolated by column chromatography (hexane:ethyl acetate
95:5) as a yellow oil (44 mg, 39%). Reaction time 8h. IR

max (cm-1): 2956, 2741, 2155, 1458, 1393, 1207, 1140, 806,
709, 670. 1H NMR (300 MHz, CDCl3) δ 7.63 (d, J = 8.3 Hz,
2H), 7.55 – 7.45 (m, 3H), 7.31 – 7.17 (m, 9H), 6.98 – 6.92
(m, 1H), 6.76 (d, J = 8.7 Hz, 2H), 5.06 (s, 1H), 3.74 (d, J =
3.4 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 158.5, 144.7,
137.5, 134.0, 133.6, 132.1, 131.8, 130.5, 130.3, 129.8,
129.3, 129.2, 128.5, 128.6, 127.9, 127.6, 127.1, 126.2,
118.6, 113.8, 112.1, 56.0, 55.2. HRMS calcd for
C29H22NOSe2 (ESI-TOF, [M + H]+): 560.0026. Found:
560.0013.
1-(4-(4-(4-Methoxyphenyl)-3-(phenylselanyl)-4H-
selenochromen-2-yl)phenyl)ethanone (7d): Product 7d
was isolated by column chromatography (hexane:ethyl
acetate 95:5) as a yellow oil (47 mg, 41%). Reaction time
8h. IR max (cm-1): 2954, 2741, 1626, 1458, 1207, 1141, 802,
715, 670. 1H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 7.8 Hz,
[2] R. Pratap, V. J. Ram. Chem. Rev. 2014, 114, 10476-
10526.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
[3] a) H. Sashida, M. Yoshida, H. Minamida, M. Teranishi,
J. Heterocyclic Chem. 2002, 39, 405-409. b) H. Sashida,
H. Minamida, J. Chem. Soc. Perkin Trans. 1999, 12,
1665-1670.
11, 2113-2116; f) G. Cantagrel, B. de Carné-Carnavalet,
C. Mayer, J. Cossy, Org. Lett. 2009, 11, 4262-4265.
[8] T. A. C. Goulart, J. A. G. Kazmirski, D. F. Back, G. Zeni,
Adv. Synth. Catal. 2019, 361, 96-104.
[4] a) J. Sayers, R. J. Payne, N. Winssinger, Chem. Sci. 2018,
9, 896-903; b) S. Shaaban, F. Sasse, T. Burkholz, C.
Jacob, Bioorg. Med. Chem. 2014, 22, 3610-3619; c) L.
Engman, J. Persson, T. K. Vessman, M. Ekstrom, M.
Berglund, C.-M. Andersson, Free Radical Biol. Med.
1995, 19, 441-452; (d) A. Nyska, T. Waner, M. Pirak, M.
Albeck, M. Sredni, Arch. Toxicol. 1989, 63, 386-393.
[9] H.-A. Du, R.-Y. Tang, C.-L. Deng, Y. Liu, J.-H. Li, X.-
G. Zhang, Adv. Synth. Catal. 2011, 353, 2739-2748.
[10] I. M. De Oliveira, D. C. Pimenta, J. Zukerman-
Schpector, H. A. Stefani, F. Manarin, New J. Chem.
2018, 42, 10118-10123.
[11] CCDC 1903966 (3b) contains the supplementary
crystallographic data for this paper. These data can
obtained free of charge from The Cambridge
[5] a) R. Mousa, R. N. Dardashti, N. Metanis, Angew. Chem.
Int. Ed. 2017, 56, 15818-15827; b) I. M. De Oliveira, S.
S. N. Vasconcelos, C. S. Barbeiro, T. C. Correra, A.
Shamim, D. C. Pimenta, I. Caracelli, J. Zukerman-
Schpector, H. A. Stefani, F. Manarin, New J. Chem.
2017, 41, 9884-9888; c) C. M. Weekley, H. H. Harris,
Chem. Soc. Rev. 2013, 42, 8870-8894; d) I. P.
Beletskaya, V. P. Ananikov, Chem. Rev. 2011, 111,
1596-1636; e) J. V. J. Comasseto, Braz. Chem. Soc.
2010, 21, 2027-2031.
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
[12] a) C. R. B. Rhoden, G. Zeni, Org. Biomol. Chem. 2011,
9, 1301-1313; b) M. Nakamura, L. Ilies, S. Otsubo, E.
Nakamura, Org. Lett. 2006, 8, 2803-2805; c) M.
Nakamura, L. Ilies, S. Otsubo, E. Nakamura, Angew.
Chem. Int. Ed. 2006, 45, 944-947; d) H. J. Reich, M. J.
Bevan, B. Ö. Gudmundsson, C. L. Puckett, Angew.
Chem. Int. Ed. 2002, 41, 3436-3439; e) H. J. Reich, M.
D. Bowe, J. Am. Chem. Soc. 1990, 112, 8994-8995.
[6] a) A. M. S. Recchi, D. F. Back, G. Zeni, J. Org. Chem.
2017, 82, 2713-2723; b) B. Godoi, A. Sperança, C. A.
Bruning, D. F. Back, P. H. Menezes, C. W. Nogueira, G.
Zeni, Adv. Synth. Catal. 2011, 353, 2042-2050; c) B.
Godoi, A. Sperança, C. A. Bruning, D. F. Back, P. H.
Menezes, C. W. Nogueira, G. Zeni, Adv. Synth. Catal.
2011, 353, 2042-2050.
[13] R. Cella, R. L. O. R. Cunha, A. E. S. Reis, D. C.
Pimenta, C. F. Klitzke, H. A. Stefani, J. Org. Chem.
2006, 71, 244-250.
[14] S. E. Denmark, W. R. Collins, M. D. Cullen, J. Am.
Chem. Soc. 2009, 131, 3490-3492.
[7] a) X. He, H. Wang, X. Cai, Q. Li, J. Tao, Y. Shang, Org.
Biomol. Chem. 2018, 16, 7191-7202; b) A. Fürstner,
ACS Cent. Sci. 2016, 2, 778-789; c) I. Bauer, H.-J
Knölker,. Chem. Rev. 2015, 115, 3170-3387; d) M.
Wang, K. Ren, L. Wang, Adv. Synth. Catal. 2009, 351,
1586-1594; e) T. Xu, Z. Yu, L. Wang, Org. Lett. 2009,
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900142
Advanced Synthesis & Catalysis
FULL PAPER
Iron (III)-Promoted Synthesis of Substituted 4H-
Chalcogenochromenes and Chemoselective
Functionalization
Adv. Synth. Catal. Year, Volume, Page – Page

Isadora M. de Oliveira,a C. Henrique A. Esteves,
Mariana P. Darbem, Daniel C. Pimenta, Julio
Zukerman-Schpector, Antonio G. Ferreira, Hélio
A. Stefani,* Flavia Manarin*



10
This article is protected by copyright. All rights reserved.