Catalytic chalcogenylation under greener conditions: A solvent-free sulfur- and seleno-functionalization of olefins via I2/DMSO oxidant system

Article abstract of DOI:10.1021/jo502621a

Herein, we report a solvent- and metal-free methodology for the alkoxy-chalcogenylation of styrenes, using molecular iodine as a catalyst, DMSO as a stoichiometric oxidant, and different nucleophiles under microwave irradiation. This eco-friendly approach afforded the desired products in good to excellent yields in only 10 min. In addition, using the same protocol, we carried out the cyclization reaction of relevant molecules, such as lapachol derivatives.

Full text of DOI:10.1021/jo502621a

Article
pubs.acs.org/joc
Catalytic Chalcogenylation under Greener Conditions: A Solvent-Free
Sulfur- and Seleno-functionalization of Olefins via I2/DMSO Oxidant
System
Andre A. Vieira,‡ Juliano B. Azeredo,† Marcelo Godoi,§ Claudio Santi,∥ Eufranio N. da Silva Junior,⊥
́
̂
́
and Antonio L. Braga*,†
†Departamento de Química, Universidade Federal de Santa Catarina, Florianop
‡Instituto de Química, Departamento de Química Organ
ica, Universidade Federal da Bahia, Campus de Ondina, Salvador, 40170-290,
Brazil
§Escola de Química e Alimentos, Universidade Federal do Rio Grande − Campus Santo Anto
∥Dipartimento di Scienze Farmaceutiche, Universita
di Perugia, Via del Liceo 1, 06134, Perugia, Italy
⊥Universidade Federal de Minas Gerais, Instituto de Cien
cias Exatas, Departamento de Química, Av. Anto
́
olis, SC, Brazil
̂
̂
nio da Patrulha, RS, Brazil
̀
̂
̂
nio Carlos, 6627 - Belo
Horizonte, MG − Brazil
S
* Supporting Information
ABSTRACT: Herein, we report a solvent- and metal-free methodology
for the alkoxy-chalcogenylation of styrenes, using molecular iodine as a
catalyst, DMSO as a stoichiometric oxidant, and different nucleophiles
under microwave irradiation. This eco-friendly approach afforded the
desired products in good to excellent yields in only 10 min. In addition,
using the same protocol, we carried out the cyclization reaction of relevant molecules, such as lapachol derivatives.
reagents, such as KNO3,10 CuSO4,11 Ce(NH4)2(NO2)6,12 and
INTRODUCTION
■
Mn(OAc)2.13 Similarly, the electrophilic sulfur species is also
well-established in relation to the oxysulfenylation of alkenes
through the use of several sulfenylation agents, such as
sulfenamides,14 sulfenate esters,15 disulfides,16 sulfenyl hal-
ides,17 sulfonium salts,18 and, more recently, sulfonyl
hydrazides.19
Organoselenium compounds continue to be extensively studied
due to their recognized biological activities.1 The antioxidant
properties and mimetic activity of some enzymes are well-
established, making these compounds interesting synthetic
targets.2 Particularly relevant is the fact that organoselenium
compounds have been widely used as versatile reagents in
organic synthesis, playing an important role in a wide range of
transformations.3
In this regard, the electrophilic addition of sulfur or selenium
species (RYX, where X = a halide or other anion) to double
bonds with the formation of a thiiranium or a seleniranium
intermediate that rapidly reacts with a number of nucleophiles
is one of the most common methodologies for the formation of
new C−S or C−Se bonds.4 In this context, alkoxy-
chalcogenylation processes have been reported and several
electrophilic selenium or sulfur reagents have been employed
for this purpose.5 The electrophilic selenium species either are
commercially available (for instance, chloride, bromide, and N-
phenylselenophthalimide6) or can be conveniently prepared
through the reaction of diorganoyl diselenides with stoichio-
metric amounts of halogens.7 However, in this kind of
transformation, the halide anion generated in the reaction
medium can give rise to undesirable side processes due to the
nucleophilicity of the halide anions.
Although several methodologies have been reported for
reactions involving the addition of an electrophilic chalcogenide
specie to alkenes, all of these methods have some particular
disadvantages, such as long reaction times and the use of large
amounts of metals and/or solvents. Thus, the development of a
new environmentally friendly approach for alkoxy-selenylation
and related reactions remains an important challenge in organic
synthesis.
In this context, molecular iodine (I2) has emerged as a
convenient catalyst in several organic transformations, because
it is a nontoxic, nonmetallic, and low-cost reagent.20 We
recently reported a protocol that involves the use of a
stoichiometric amount of DMSO in the presence of a catalytic
loading of molecular iodine to generate in situ RYI.21 Using this
methodology, the preparation of 3-selenyl- and sulfenyl-indoles
under solvent-free conditions can be easily carried out.22 As a
continuation of this project, herein, we describe a new and fast
method for the alkoxy-chalcogenylation of olefins in the
absence of solvent, under microwave irradiation (Scheme 1).
Alternatively, electrophilic selenium species can also be
generated in situ through the oxidation of diorganoyl
diselenides with several oxidants, such as ammonium
persulfate,8 hypervalent iodine species,9 and metallic inorganic
Received: November 17, 2014
© XXXX American Chemical Society
A
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Article
a
Scheme 1. Molecular Iodine-Catalyzed Alkoxy-selenylation
Table 2. Optimization of Reaction Conditions
of Olefins under Solvent-Free Conditions
b
entry
MeOH (equiv )
oxidant (equiv )
I2 (mol %)
yield (%)
1
2
1.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
DMSO (1)
DMSO (1)
DMSO (1)
TBHP (1)
H2O2 (1)
air
20
20
20
20
20
20
20
20
10
5
79
86
RESULTS AND DISCUSSION
■
c
3
96 (94)
90
The reaction conditions were optimized for styrene 1a and
diphenyl diselenide 2a in the presence of dimethyl sulfoxide
(DMSO), methanol, and iodine as the catalyst (Table 1). When
4
5
77
6
56
7
DMSO (2)
DMSO (1.5)
DMSO (1)
DMSO (1)
DMSO (1)
93
a
Table 1. Optimization of Microwave Parameters
8
87
9
85
10
11
56
b
a
entry
MW (W)
T (°C)
time (min)
yield (%)
Reaction conditions: styrene 1a (0.5 mmol), (PhSe)2 2a (0.25
mmol). Conversion yields. Isolated yield.
b
c
1
2
3
4
5
6
7
8
9
100
100
100
100
100
150
50
50
50
50
80
40
50
50
50
r.t
3
55
78
5
c
10
10
10
10
10
10 h
24 h
96 (94)
89
The effect of the oxidant was then studied (entries 3−8). In
this regard, a number of oxidants (DMSO, TBHP, H2O2, and
air) were evaluated, and DMSO provided the best results when
used in stoichiometric excess (entry 3). A slight decrease in the
yield was observed on increasing the DMSO loading to 1.5 and
2.0 equiv (entries 7 and 8).
Concerning the amount of catalyst (iodine), it was observed
that the best results were obtained using 20 mol % (entry 3),
since a decrease in the yield was observed when the iodine
loading decreased (entries 9 and 10). Moreover, we observed
that the catalyst has a substantial influence on this reaction,
because no product formation was observed in the absence of
iodine (entry 11).
80
86
74
d
76
ec
,
80
a
Reaction conditions: styrene 1a (0.5 mmol), (PhSe)2, 2a (0.25
b
c
d
mmol). Conversion yields. Isolated yield. Conventional heating.
e
Reaction performed at room temperature without microwave
irradiation.
the reaction was carried out for 3 min, the desired product was
obtained in only 55% yield (entry 1). However, a significant
improvement in the yield of the product 3a was achieved when
the reaction time was increased to 5 min (entry 2). Notably,
carrying out the reaction for 10 min afforded the desired
product in almost quantitative yield (entry 3).
In order to demonstrate the synthetic utility of this
methodology, a scale-up reaction of 10 mmol was carried out
under the optimized conditions (Scheme 2). Thereby, the
reaction between styrene 1a and diphenyl diselenide 2a
provided the product 3a in 81% yield after 1 h of reaction time.
In the next step, we evaluated the effect of temperature on
the reaction system (entries 3−5). Screening of this parameter
revealed that 50 °C was the best choice, affording the product
3a in 96% yield.
Scheme 2. Scale-Up Reaction between 1a and 2a
The influence of the radiation power of the microwave
equipment was also studied, using different levels of power.
However, employing either 50 or 150 W provided the desired
product 3a in lower yields (entries 6 and 7). Thus, 100 W was
selected as the irradiation power for all subsequent experiments.
Additionally, the reaction was tested under conventional
heating using a preheated oil bath. Under these conditions, the
reaction provided acceptable yield but required a very long
reaction time (entry 8). Similarly, the reaction was performed at
room temperature for 24 h, providing the desired product in
80% yield (entry 9).
In a second step of the investigation, we considered the
influence of several reaction parameters, including the oxidant,
the methanol loading, and the catalyst (Table 2). First, we
examined the influence of the nucleophile loading, carrying out
the reaction with different amounts of methanol, and a
significant improvement in the chemical yield was observed
when the amount of methanol was increased from 1.0 to 2.0
(entries 1−3). Thus, 2 equiv of methanol were found to be the
most appropriate, affording the desired product in very high
yield.
More importantly, the formation of the undesirable side
product derived from the competition between the iodide
nucleophile formed in the reaction medium and the nucleophile
used was not observed. This is probably a consequence of the
low concentration of iodide formed, since it is continuously
oxidized by the DMSO to iodine, as shown in the plausible
reaction pathway in Scheme 6.
After the determination of the optimized conditions, the
scope and limitations of the proposed protocol were further
investigated. First, a variety of diorganyl diselenides were
reacted with methanol in order to prepare different β-methoxy-
selenides (Table 3).
Electronic effects seem to have a significant influence on the
reaction course. In general, diaryl diselenides with electron-
releasing groups gave the products (3e−f) in better yields than
those with electron-withdrawing groups, with the exception of
para-chlorophenyl diselenide, which afforded the product 3d in
B
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Article
a b c
, ,
Table 3. Synthesis of β-Methoxy-selenides 3a−l
Table 4. Synthesis of Compounds 3m−u Using the Styrene
1a, Diphenyl Diselenide 2a, and Different Nucleophile
Species
a b c
, ,
a
Reaction conditions: styrene (0.5 mmol), diphenyl diselenide (0.25
mmol), I2 (20 mol %), Nu (2 equiv), and DMSO (1 equiv), MW (100
b
c
W), 10 min, 50 °C. Isolated yields. Determined by CG−MS.
we turned our attention to their preparation applying our
protocol (Table 5). In general, all the reactions proceeded
a
Reaction conditions: styrene (0.5 mmol), diorganoyl diselenide (0.25
mmol), I2 (20 mol %), MeOH (2 equiv), and DMSO (1 equiv), MW
b
c
Table 5. Synthesis of Compounds 5a−f Using the Styrene 1a,
(100 W), 10 min, 50 °C. Isolated yields. Determined by CG−MS.
a b
,
Diorganoyl Dichalcogenides, and Different Nucleophiles
89% yield. Notably, when we employed para-methoxyphenyl
diselenide as a selenium source, the corresponding product 3f
was achieved in 96% yield, suggesting that aromatic diselenides
with electron-donating groups are favored substrates for this
transformation.
Moreover, the reaction was also effective when a less reactive
organoyl diselenide, such as dibutyl diselenide, was employed,
giving the respective product in satisfactory yield.
The reactions of various styrenes with diphenyl diselenide
were also examined under optimized conditions. Para-
substituted styrenes were suitable substrates, affording the
expected products (3h−j) in reasonable yields. It is noteworthy
that, when we employed 4-tert-butoxystyrene, the respective
product 3j was achieved in 90% yield. Furthermore, the
protocol was also applicable to α-methylstyrene, affording the
desired product 3k in good yield. However, when 1-pentene
was employed as substrate in the optimized conditions, the
corresponding methoxy-selenilation product 3l was not
obtained.
In the next step, we evaluated the effect of several
nucleophiles on the reaction (Table 4). The influence of the
nucleophilic species was investigated initially by evaluating
different alcohols (3m−q). Ethanol and iso-propanol proved to
be very good nucleophiles for this transformation, affording the
corresponding products (3m−n) in very high yields. However,
when tert-butanol was used as nucleophile, there was no
formation of the corresponding product 3u. Notably, when we
employed a benzylic alcohol as the nucleophile source, the
respective product 3o was achieved in 95% yield. In contrast,
the protocol was not efficient for phenol derivatives since only
trace levels of the corresponding products were observed.
However, other nucleophiles, such as acetic acid and water,
afforded the corresponding products in moderate yields (3q−
s). In addition, our protocol was also useful for the preparation
of a selenium azide derivative (3t), which was obtained in
reasonable yield using sodium azide as the nucleophile source.
Encouraged by these results and considering the particular
relevance of the functionalization of olefins with sulfur atoms,23
a
Reaction conditions: styrene (0.5 mmol), diorganoyl dichalcogenides
(0.25 mmol), I2 (20 mol %), R3-OH (2 equiv), and DMSO (1 equiv),
MW (100 W), 10 min, 50 °C. Isolated yields.
b
smoothly, allowing the preparation of sulfur derivatives in very
good yields (5a−e). For instance, when we employed p-toluyl
disulfide as a sulfur source, the respective product 5b was
obtained in 81% yield.
Similarly, ethanol proves to be an effective alcohol in the
alkoxy-sulfenylation reaction. When p-tolyl disulfide and
diphenyl disulfide were used, the corresponding products 5c
and 5d were obtained in 77% and 79% yield, respectively.
Acetic acid also showed good activity as a nucleophile with
diphenyl disulfide, furnishing the product 5e in good yield.
In addition, the reaction of methoxy-tellurenylation was also
performed using the same methodology. However, diphenyl
ditelluride was less reactive than its selenium and sulfur
analogues under the same reaction conditions, providing the
respective product 5f in lower yield.
The well-known functionalization of alkenes reaction with
electrophilic reagents of selenium via the cyclization reaction
has attracted considerable attention in organic synthesis.24
Therefore, in order to extend the scope of the present
methodology, we attempted to extend our protocol to
unsaturated substrates containing internal nucleophiles. Using
C
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the reagent 4-penten-1-ol 6 as a substrate, we observed the
formation of a seleno tetrahydrofuran derivative 6a in 81% yield
via the 5-exo-trig pathway.25 Similarly, when 4-pentenoic acid 7
was employed as substrate, the corresponding seleno-lactone 7a
was achieved in excellent yield (95%) (Scheme 3).
previously reported compounds.31 The others signals corre-
sponding to the aromatic rings are totally in accordance with
those expected for 8a. Compound 9a presented chemical shifts
among δ 2.9−3.4 related to methylenic hydrogens. A multiplet
signal (methynic H-2) was observed at δ 5.2−5.3. In a similar
way, the signals corresponding to the aromatic rings are
consistent.
Scheme 3. Seleno-cyclofunctionalization of Olefins
As observed with other electrophiles, two pathways (β- or α-
cyclizations) are possible in the reaction with lapachol 8.
Initially, the selenonium ion was formed and the carbon atom
with a partial positive charge was better stabilized. The C−Se
bond was weakened and suffered an internal nucleophilic
attack, β-cyclization occurred, and the preferential kinetic
product was formed under the pre-established conditions. In
general, β-lapachone derivatives are preferentially formed in
reactions without heating and in a shorter reaction time
compared with α-lapachone derivatives (thermodynamic
product) (Scheme 5).
Containing an Internal Nucleophile
Scheme 5. Pathways for the Formation of β- or α-Lapachone
Analogues from Lapachol (8)
Recently, Jacob and co-workers described quinoidal com-
pounds containing selenium or tellurium as multifunctional
redox agents. These compounds present important activity
against cancer cell lines with low cytotoxity in normal cell
lines.26 Lapachol, a naturally occurring naphthoquinone, is
important due to its biological activities, for instance,
trypanocidal,27 leishmanicidal,28 and antitumoral.29−31 Based
on the potential activity of lapachol, a quinonoid compound
containing an unsaturated system with an internal nucleophile,
in this study, we also selected some lapachol derivatives for the
application of the methodology described herein.
Lapachol 8, C-allyl lawsone 9, and nor-lapachol 10 were
employed as substrates for the seleno-functionalization. Using
compound 8, the respective 3-selenophenyl-β-lapachone 8a was
obtained in good yield (65%) in a 6-endo-trig fashion (Scheme
4).
When this chalcogenylation method was applied to the C-
allyl lawsone 9, the selenium product 9a was obtained in
excellent yield (80%) (Scheme 4).
Finally, nor-lapachol 10, the inferior homologue of lapachol
(8), was synthesized by Hooker oxidation32 and used under the
same reaction conditions, but no reaction was observed.
On the basis of previous reports,33 a plausible reaction
pathway for the chalcogen functionalization of styrenes is
illustrated in Scheme 6. First, the electrophilic species in the
The chemical shifts of the hydrogens belonging to the
pyranic ring of 3-phenylselanyl-β-lapachone 8a appear among δ
2.6−3.4. The diastereotopic methyl groups showed chemical
shifts at δ 1.68 and 1.54 as singlets and are in accordance with
Scheme 6. Plausible Reaction Pathway
Scheme 4. Seleno-cyclofunctionalization of Lapachol
Derivatives
form of RYI (Y = S, Se) would be generated through the
reaction of diorganyl dichalcogenide with the catalyst. Next, the
RYI undergoes nucleophilic attack of the double bond of
styrene, leading to the formation of the intermediate
chalcogeniranium ion. Subsequently, this intermediate under-
goes attack by the nucleophile to furnish the desired β-
methoxy-selenide with the concomitant formation of HI. Two
equivalents of HI would then react with DMSO, affording an
intermediate of the protonated sulfur species, which is rapidly
converted to the iodine-dimethyl sulfide adduct.34 Finally, the
iododimethylsulfonium iodide species is converted to water and
dimethyl sulfide, and the catalyst is regenerated in the reaction
D
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MHz) δ: = 140.5; 135.5; 132.0; 131.5 (q, J = 32.2 Hz); 129.1; 128.8
(q, J = 3.84 Hz), 128.3; 126.0, 126.4 (q, J = 272 Hz); 123.4 (q. J 3.84
Hz); 83.2; 57.0; 35.4. (APPI+) m/z: calculated for C16H15F3OSe
[M]+: 360.0240; found 360.0234. IR (film): 3061, 3028, 2985, 2933,
2822, 1579, 1492, 1453, 1421, 1321, 1270, 1166, 1127, 796, 695 cm−1.
(4-Chlorophenyl)(2-methoxy-2-phenylethyl)selane (Compound
medium, completing the cycle. It is important to mention that,
in this process, the amount of iodide anions in the reaction
medium is low, since they are continuously converted to I2 by
reaction with DMSO. This is important in order to avoid
nucleophilic competition of the iodide with the nucleophile.
1
3d). 0.1444 g, yield 89%, yellow oil. H NMR (CDCl3, 200 MHz)
CONCLUSIONS
δ: = 7.38 (d, J = 8.0 Hz, 2H); 7.33−7.29 (m, 5H); 7.18 (d, J = 8.0 Hz,
2H); 4.33 (dd, 1H, J1 = 4.0 Hz; J2 = 8.0 Hz); 3.32 (dd, J1 = 8.0 Hz; J2 =
11.4 Hz, 1H); 3.24 (s, 3H); 3.07 (dd, 1H, J1 = 4.0 Hz, J2 = 12.0 Hz,
1H). 13C NMR (CDCl3, 50 MHz) δ: = 140.7; 134.0; 133.0; 129.1;
128.9; 128.5; 128.1; 126.6; 83.1; 57.0; 35.7. IR (film): 3028, 2983,
2930, 2821, 1473, 1453, 1386, 1106, 1089, 1010, 814, 766, 729, 701
cm−1. HRMS (APPI+) m/z: calculated for C15H15ClOSe [M]+:
325.9977; found: 325.9970.
■
In conclusion, we have developed a fast and sustainable
approach for the alkoxy-selenylation of styrenes, employing an
oxidant catalytic system composed of I2/DMSO. This new
regioselectivity method afforded the desired products in good
to excellent yields in only 10 min, in solvent- and metal-free
reaction media. Another important advance associated with this
methodology is the applicability of different nucleophiles, such
as alcohols, carboxylic acid, azide, and water, which allows the
preparation of β-substituted aryl selenides with different
functionalities. Furthermore, the present methodology was
satisfactorily applied to the reaction of the styrene with
diorganoyl disulfides. One important advantage of this method
is the fact that the side product derived from the competition
between the iodide generated in the reaction medium and the
nucleophile used was not observed. We also extended our
protocol to the seleno-cyclofunctionalization reactions, using a
nucleophile containing olefins. In this regard, lapachol and C-
allyl-lawsone selenium derivatives, which are compounds with
potential biological activity, were prepared in good yields.
(2-Methoxy-2-phenylethyl)(p-tolyl)selane (Compound 3e). 0.1094
g, yield 72%. 1NMR (CDCl3, 200 MHz) δ: = 7.43 (d, J = 8,0 Hz, 2H);
7.38−7.29 (m, 5H); 7.09 (d, J = 8.0 Hz, 2H); 4.37 (1H, J1 = 4.0 Hz; J2
= 8.0 Hz, 1H); 3.33 (dd, J1 = 8.0 Hz, J2 = 12.0 Hz, 1H); 3.28 (s, 3H);
3.10 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H); 2.35 (s, 3H). 13C NMR
(CDCl3, 50 MHz) δ: 140.8; 136.8; 133.0; 129.7; 128.4; 127.9; 126.6;
83.0; 56.9; 35.6; 21.0. IR (film): 3060, 3026, 2978, 2963, 2819, 1489,
1453, 1352, 1106, 1089, 1016, 803, 766, 701 cm−1. HRMS (APPI+)
m/z: calculated for C16H18OSe [M]+: 306.0523; found: 306.0518.
(2-Methoxy-2-phenylethyl)(4-methoxyphenyl)selane (Compound
1
3f). 0.1535 g, yield 96%, yellow oil. H NMR (CDCl3, 200 MHz) δ:
7.46 (d, J = 8.0 Hz, 2H); 7.37−7.29 (m, 5H); 6.81 (d, J = 8.0 Hz, 2H);
4.31 (dd, J1 = 4.0 Hz; J2 = 8.0 Hz, 1H); 3.80 (s, 3H), 3.31−3.20 (m,
1H); 3.25 (s, 3H); 3.02 (dd, 1H, J1 = 4.0 Hz; J2 = 12.0 Hz). 13C NMR
(CDCl3, 50 MHz) δ: 159.1; 140.8; 135.5; 128.4; 127.9; 126.6; 114.6;
83.0; 56.9; 55.2; 36.3. IR (film): 3060, 3026, 2998, 2932, 2833, 2820,
1590, 1571, 1490, 1454, 1284, 1247, 1173, 1071, 1030, 1006, 824, 766,
702 cm−1. HRMS (APPI+) m/z: calculated for C16H18O2Se [M]+:
322.0472; found: 322.0468.
EXPERIMENTAL SECTION
■
1H and 13C NMR spectra were recorded in CDCl3 at 400 and 200
MHz or at 100 and 50 MHz, respectively. Chemical shifts (δ) are
reported (ppm) relative to the TMS (1H NMR) and the solvent (13C
NMR). APPI-Q-TOFMS measurements were taken on a mass
spectrometer equipped with an automatic syringe pump for sample
injection. Infrared spectra were recorded on a commercial Fourier
transformer spectrometer. The styrenes were obtained from
commercial sources and used without further purification. All reactions
were performed in 10 mL sealed glass tubes in a commercially
available microwave monomode CEM reactor with IR monitoring and
a noninvasive pressure transducer. The yields are based on isolated
compounds after purification.
Butyl(2-methoxy-2-phenylethyl)selane (Compound 3g). 0.0769 g,
1
yield: 57%, yellow oil. H NMR (CDCl3, 200 MHz) δ: = 7.34 (m,
5H); 4.33 (dd, J1 = 6.0 Hz; J2 = 8.0 Hz, 1H); 3.26 (s, 3H); 2.98 (dd, J1
= 12.0 Hz; J2 = 8.0 Hz, 1H); 2.75 (dd, 1H, J1 = 6.0 Hz, 12.0 Hz, 1H);
2.49 (t, J = 7.3 Hz, 2H); 1.60 (m, 2H); 1.42−1.27 (m, 2H); 0.89 (t, J =
7.38 Hz, 3H). 13C NMR (CDCl3, 50 MHz) δ: 141.3; 128.4; 127.9;
126.6; 84.5; 56.8; 32.6; 30.9; 24.5; 22.9; 13.5. IR (film): 2954, 2925,
2869, 2856, 2818, 1463, 1453, 1106, 1090, 1070, 955, 765, 701 cm−1.
HRMS (APPI+) m/z: calculated for C13H20OSe [M]+: 272.0679;
found: 272.0679.
General Procedure for the Synthesis of the Aryl Chalcoge-
nides. The styrene (0.5 mmol), diorganyl chalcogenide (0.25 mmol),
iodine (20% mol), respective nucleophile (2 equiv), and DMSO (1
equiv) were placed in a dry microwave glass tube. The tube was sealed
and placed into a CEM Discover microwave apparatus. Initially, an
irradiation power of 100 W was applied. After the temperature reached
50 °C, the instrument was automatically adjusted to maintain a
constant temperature. After 10 min, the reaction was quenched with a
solution of sodium thiosulfate 10% and the aqueous layer was
extracted with ethyl acetate. The organic phase was dried over MgSO4
and filtered, and the solvent was completely removed under vacuum to
give the crude product. Purification was carried out by flash
chromatography with a mixture of hexane/ethyl acetate (96:4),
affording the desired product.
Characterization. (2-Methoxy-2-phenylethyl)(phenyl)selane
(Compound 3a). 0.1363 g, Yield: 94%, yellow oil,35 1H NMR
(CDCl3, 200 MHz) δ: = 7.49−7.44 (m, 2H); 7.38−7.19 (m, 8H); 4.34
(dd, J1 = 4.0 Hz; J2 = 8.4 Hz, 1H); 3.32 (dd, J1 = 8.4 Hz, J2 = 12.0 Hz,
1H); 3.23 (s, 3H); 3.09 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H). 13C NMR
(CDCl3, 50 MHz) δ: = 140.8; 132.5; 130.6; 128.9; 128.4; 127.9; 126.7;
126.6; 83.1; 56.9; 35.3. IR (film): 3057, 3026, 2980, 2929, 2819, 1578,
1477, 1436, 1105, 1090, 1022, 765, 736, 701, 691 cm−1.
(2-(4-Chlorophenyl)-2-methoxyethyl)(phenyl)selane (Compound
3h). 0.0908 g, yield: 56%, yellow oil.1H NMR (CDCl3, 200 MHz) δ: =
7.47−7.41 (m, 2H); 7.32−7.20 (m, 8H); 4.30 (dd, J1 = 6.0 Hz; J2 = 8.0
Hz, 1H); 3.28 (dd, J1 = 8.0 Hz, J2 = 12.0 Hz, 1H); 3.22 (s, 3H); 3.05
(dd, J1 =6.0 Hz, J2 = 12.0 Hz, 1H). 13C NMR (CDCl3, 50 MHz) δ: =
139.3; 133.7, 132.6; 130.3; 128.9; 128.6; 128.0; 126.9; 82.5; 56.9; 35.0.
IR (film): 3054, 2983, 2929, 2819, 1595, 1578, 1488, 1436, 1099,
1088, 827, 736, 690 cm−1. HRMS (APPI+) m/z: calculated for
C15H15ClOSe [M]+: 325.9977; found: 325.9967.
(2-Methoxy-2-(p-tolyl)ethyl)(phenyl)selane (Compound 3i).
1
0.0577 g, yield 38%, yellow oil. H NMR (CDCl3, 200 MHz) δ: =
7.64−7.59 (m, 2H); 7.37−7.31 (m, 8H); 4.46 (dd, J1 = 4.8 Hz; J2 = 8.0
Hz, 1H); 3.47 (dd, J1 = 8.0 Hz, J2 = 12.0 Hz, 1H); 3.37 (s, 3H); 3.23
(dd, J1 = 4.8 Hz, J2 = 12.0 Hz, 1H); 2.48 (s, 3H). 13C NMR (CDCl3,
50 MHz) δ: = 137.8; 137.7; 132.4; 130.6; 129.2; 128.9; 126.7; 126.5;
82.8; 56.8; 35.3; 21.1. IR (film): 2975, 2929, 2818, 1604, 1578, 1504,
1477, 1365, 1236, 1161, 1105, 897, 736, 691 cm−1. HRMS (APPI+)
m/z: calculated for C16H18OSe [M]+: 306.0518; found: 306.0523
(2-(4-tert-Butoxyphenyl)-2-methoxyethyl)(phenyl)selane (Com-
1
pound 3j). 0.1629 g, yield 90%. H NMR (CDCl3, 200 MHz) δ: =
7.47 (d, J = 7.0 Hz, 2H); 7.25−7.18 (m, 5H); 6.96 (d, J = 7.0 Hz, 2H);
4.32 (dd, J1 = 4.0 Hz; J2 = 8.0 Hz, 1H); 3.32 (dd, J1 = 8.0 Hz, J2 = 12.0
Hz, 1H); 3.23 (s, 3H); 3.09 (dd, J1 = 4.0 Hz, J2 =12.0 Hz, 1H); 1.34 (s,
9H). 13C NMR (CDCl3, 50 MHz) δ: = 155.2; 135.5; 132.5; 130.7;
128.9; 127.1; 126.7, 124.0, 82.7; 56.9; 35.4; 28.8. IR (film): 2981,
2928, 2818, 1578, 1511, 1477, 1436, 1102, 1022, 818, 736, 691 cm−1.
(2-Methoxy-2-phenylethyl)(3-(trifluoromethyl)phenyl)selane
1
(Compound 3b). 0.0376 g, yield 21%, yellow oil. H NMR (CDCl3,
200 MHz) δ: = 7.49−7.44 (m, 2H); 7.38−7.19 (m, 8H); 4.34 (dd, J1 =
4.0 Hz; J2 = 8.0 Hz, 1H); 3.32 (dd, J1 = 8.0 Hz, J2 = 11.0 Hz 1H); 3.23
(s, 3H); 3.09 (dd, J1 =4.0 Hz, J2 = 11.1 Hz 1H). 13C NMR (CDCl3, 50
E
DOI: 10.1021/jo502621a
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
HRMS (APPI+) m/z: calculated for C19H23O2Se [M − H]+:
363.0859; found: 363.0862.
(2-Methoxy-2-phenylethyl)(p-tolyl)sulfane (Compound 5b).
0.1044 g, yield 74%, colorless oil.38 1H NMR (CDCl3, 200 MHz) δ:
= 7.38−7.25 (m, 7H); 7.10 (d, J1 = 8.0 Hz, 2H); 4.28 (dd, J1 = 4.0 Hz;
J2 = 8.0 Hz, 1H); 3.29−3.26 (m, 1H); 3.26 (s, 3H); 3.10 (dd, J1 = 8.0
Hz; J2 = 12.0 Hz, 1H); 2.33 (s, 3H). 13C NMR (CDCl3, 50 MHz) δ: =
140.5; 136.2; 132.6; 130.1; 129.6; 128.5; 128.0; 126.7; 82.4; 57.0; 42.2;
21.0. IR (film): 3058, 3023, 2981, 2922, 2866, 2820, 1492, 1453, 1352,
1106, 1098, 1091, 804, 699 cm−1.
(2-Ethoxy-2-phenylethyl)(p-tolyl)sulfane (Compound 5c). 0.1048
g , yield 77%, colorless oil.19 1H NMR (CDCl3, 400 MHz) δ: = 7.37−
7.02 (m, 9H); 4.38 (dd, J1 = 5.08 Hz, J2 = 3.03 Hz, 1H), 3.48−3.27
(m, 3H), 3.08 (dd, J1 = 5.08; J2 = 8.21, 1H); 2.31 (s, 3H); 1.18 (t, J =
7.31, 3H). 13C NMR (CDCl3, 100 MHz) δ: = 141.3; 136.0; 133.3;
130.0; 129.6; 128.3; 127;9; 126.6; 80.6; 64.6; 42.2; 20.9; 15.2.
(2-Ethoxy-2-phenylethyl)(phenyl)sulfane (Compound 5d). 0.1015
g, yield 79%, colorless oil.19 1H NMR (CDCl3, 400 MHz) δ: = 7.33−
7.14 (m, 10H); 4.40 (dd, J1 = 5.08 Hz; J2 = 2.74 Hz, 1H); 3.42−3.30
(m, 3H); 3.11 (dd, J1 = 5.08 Hz; J2 = 8.21 Hz, 1H); 1.17 (t, J = 7.03
Hz, 3H).13C NMR (CDCl3, 100 MHz) δ: = 141.2; 136.7; 132.8;
129.2; 128.7; 128.5; 127.9; 126.6; 80.6; 64.6; 41.6; 15.2.
(2-Ethoxy-2-phenylethyl)(p-tolyl)sulfane (Compound 5d). 0.1048
g, yield 77%, colorless oil.19 1H NMR (CDCl3, 400 MHz) δ: = 7.37−
7.02 (m, 9H); 4.38 (dd, J1 = 5.08 Hz, J2 = 3.03 Hz, 1H), 3.48−3.27
(m, 3H), 3.08 (dd, J1 = 5.08; J2 = 8.21, 1H); 2.31 (s, 3H); 1.18 (t, J =
7.31, 3H). 13C NMR (CDCl3, 100 MHz) δ: = 141.3; 136.0; 133.3;
130.0; 129.6; 128.3; 127;9; 126.6; 80.6; 64.6; 42.2; 20.9; 15.2.
1-Phenyl-2-(phenylthio)ethyl Acetate (Compound 5e). 0.102 g,
yield 75%, colorless oil.16a 1H NMR (CDCl3, 200 MHz) δ: = 7.40−
7.18 (m, 10H); 5.88 (dd, J1 = 6.0 Hz; J2 = 8.0 Hz, 1H); 3.42 (dd, J1 =
8.0 Hz, J2 = 12.0 Hz, 1H); 3.23 (dd, J1 = 6.0 Hz, J2 = 12.0 Hz, 1H);
2.01 (s, 3H). 13C NMR (CDCl3, 50 MHz) δ: = 170.0; 139.0, 135.6;
130.1; 129.0; 128.5; 128.4; 126.6; 76.4; 74.6; 40.1; 21.0. IR (film):
3058, 3029, 2923, 1742, 1582, 1493, 1480, 1438, 1370, 1238, 1230,
1024, 739, 697 cm−1.
(2-Methoxy-2-phenylpropyl)(phenyl)selane (Compound 3k).
1
0.0957 g, Yield 63%, yellow oil. H NMR (CDCl3, 200 MHz) δ: =
7.44−7.24 (m, 8H); 7.19−7.16 (m, 2H); AB system (J = 12.0 Hz);
3.12 (s, 3H); 1.72 (s, 3H). 13C NMR (CDCl3, 50 MHz) δ: = 143.6;
132.6; 131.3; 128.8; 128.2; 127.3; 126.6; 126.2; 78.9; 50.9; 42.2; 23.1.
IR (film): 3055, 2977, 2931, 2822, 1578, 1476, 1444, 1436, 1369,
1072, 1022, 764, 737, 701, 691 cm−1. HRMS (APPI+) m/z: calculated
for C16H18OSe [M]+: 306.0518; found: 306.0514.
(2-Ethoxy-2-phenylethyl)(phenyl)selane (Compound 3m). 0.1352
g, yield 89%, yellow oil.36 1H NMR (CDCl3, 200 MHz) δ: = 7.50−
7.49 (m, 2H); 7.35−7.23 (m, 8H); 4.47 (dd, J1 = 5.0 Hz; J2 = 8.0 Hz,
1H); 3.43−3.32 (m, 3H); 3.10 (dd, J1 = 5.0 Hz, J2 = 12.0 Hz, 1H);
1.19 (t, J = 7.0 Hz, 3H). 13C NMR (CDCl3, 50 MHz) δ: = 141.6;
132.5; 130.8; 128.9; 128.4; 127.9; 126.7; 126.5; 81.3; 64.6; 35.5; 15.2.
IR (film): 3057, 3026, 2971, 2926, 2865, 1578, 1490, 1477, 1454,
1436, 1115, 1091, 1022, 763, 735, 701 cm−1.
(2-Isopropoxy-2-phenylethyl)(phenyl)selane (Compound 3n).
1
0.1272 g, yield 80%, yellow oil. H NMR (CDCl3, 200 MHz) δ: =
7.50−7.47 (m, 2H); 7.35−7.22 (m, 8H); 4.59 (dd, J1 = 4.0 Hz; J2 = 8.0
Hz, 1H); 3.51 (m, 1H); 3.30 (dd, J1 = 8.0 Hz, J2 = 12.0 Hz, 1H); 3.08
(dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H); 1.17 (d, J = 6.0 Hz, 3H); 1.09 (d, J
= 6.0 Hz, 3H). 13C NMR (CDCl3, 50 MHz) δ: = 142.4; 132.2; 131.0;
128.9; 128.4; 127.8; 126.6; 126.5; 78.7; 69.7; 35.9; 23.3; 21.3. IR
(film): 3057, 3026, 2968, 2928, 2876, 1578, 1491, 1462, 1452, 1436,
1120, 1084, 1022, 763, 735, 701 cm−1. HRMS (APPI+) m/z:
calculated for C17H20OSe [M]+: 320.0679; found: 320.0678.
(2-(Benzyloxy)-2-phenylethyl)(phenyl)selane (Compound 3o).
1
0.1738 g, yield 95%, yellow oil. H NMR (CDCl3, 200 MHz) δ: =
7.49−7.44 (m, 2H), 7.38−7.19 (m, 8H), 4.34 (dd, J1 = 4.0 Hz; J2 = 8.0
Hz, 1H); 3.32 (dd, J1 = 8.0 Hz, J2 = 11.5 Hz, 1H); 3.23 (s, 3H); 3.09
(dd, J1 = 4.0 Hz, J2 = 11.5 Hz, 1H). 13C NMR (CDCl3, 50 MHz) δ: =
140.9; 137.9; 133.0; 132.4; 130.8; 129.7; 128.9; 128.5; 128.3; 128.3;
128.1; 127.8; 127.6; 126.8; 126.7; 80.7; 70.8; 66.6; 35.5. IR (film):
3059, 3028, 2930, 2862, 1720, 1578, 1494, 1477, 1453, 1436, 13.46,
1270, 1095, 1072, 1022, 735, 700 cm−1. HRMS (APPI+) m/z:
calculated for C21H20OSe [M]+: 368.0679; found: 368.0673.
(2-Methoxy-2-phenylethyl)(phenyl)tellane (Compound 5f).
1
0.0237 g, yield 14%, yellow oil. H NMR (CDCl3, 200 MHz) δ: =
7.6 (d, 2H, J = 8.0, 2H); 7.38−7.11 (m, 8H); 4.44 (dd, J1 = 6.0 Hz; J2
= 9.0 Hz, 1H); 3.43 (dd, J1 = 9.0 Hz, J2 = 12.0 Hz, 1H); 3.24 (s, 3H);
3.10 (dd, J1 = 6.0, J2 = 12.0, 1H). 13C NMR (CDCl3, 50 MHz) δ: =
141.8; 138.2; 129.1; 128.7; 128.5; 128.0; 127.4; 126.4; 84.2; 57.0; 17.4.
IR (film): 3060, 3025, 2979, 2924, 2851, 2819, 1574, 1491, 1473,
1453, 1432, 1221, 1100, 1018, 763, 731, 700 cm−1. HRMS (APPI+)
m/z: calculated for C15H16OTe [M]+: 342.0263; found: 342.0253.
2-((Phenylselanyl)methyl)tetrahydrofuran (Compound 6a).
0.0972 g, yield 81%, yellow oil.39 1H NMR (400 MHz, CDCl3) δ: =
7.53−7.51 (m, 2H); 7.27−7.20 (m, 3H); 4.09 (qui, J = 6.9 Hz, 1H),
3.93−3.88 (m, 1H), 3.79−3.73(m, 1H); 3.12 (dd, J1 = 5.8 Hz ; J2 =
12.0 Hz, 1H); 2.97 (dd, J1 = 6.9 Hz, J2 = 12.0 Hz, 1H); 2.10−2.02 (m,
1H); 1.96−1.88 (m, 2H); 1.66−1.67 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ: = 132.4; 130.2; 128.9; 126.7; 78.2; 68.3; 32.9; 31.4; 25.9.
Dihydro-[(phenylseleno)methyl]-2(3H)-furanone (Compound
7a). 0.1243 g, yield 95%, yellow oil.39 1H NMR (400 MHz, CDCl3)
δ: 7.6−7.5 (m, 2H), 7.30−7.25 (m, 3H), 4.68−4.41 (m, 1H), 3.27 (dd,
J1 = 4.9; J2 = 12.8 Hz, 1H), 3.01 (dd, J1 = 7.8; J2 = 12.8 Hz, 1H), 2.63−
2.35 (m, 3H), 1.99−1.89 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:
176.5; 133.0; 129.2; 128.7; 127.5; 79.2; 31.7; 28.6; 27.5.
1-Phenyl-2-(phenylselanyl)ethanol (Compound 3r). 0.0386 g,
yield 28%, yellow oil.1H NMR (CDCl3, 200 MHz) δ: = 7.57−7.52
(m, 2H); 7.35−7.25 (m, 8H); 4.77 (dd, J1 = 4.0 Hz; J2 = 8.4 Hz, 1H);
3.30 (dd, J1 = 4.0 Hz, J2 = 13.0 Hz, 1H); 3.11 (dd, J1 = 8.4 Hz, J2 =
13.0 Hz, 1H); 2.81 (s, 1H). 13C NMR (CDCl3, 50 MHz) δ: = 142.5;
133.1; 129.2; 128.5; 127.9; 127.4; 125.8; 72.2; 38.4. IR (film):
3451(OH), 3057, 3027, 2926, 2851, 2358, 2336, 1578, 1491, 1443,
1193, 1084, 1022, 765, 700 cm−1. HRMS (APPI+) m/z: calculated for
C14H14OSe [M]: 278.0205; found: 278.0206.
1-Phenyl-2-(phenylselanyl)ethyl acetate (Compound 3s). 0.0667
g, yield 42%, yellow oil.16a 1H NMR (CDCl3, 200 MHz) δ: = 7.46−
7.39 (m, 2H); 7.24−7.17 (m, 8H); 5.88 (dd, J1 = 4.0 Hz; J2 = 6.0 Hz,
1H); 3.32 (dd, J1 = 6.0 Hz, J2 = 12.0 Hz, 1H); 3.16 (dd, J1 = 4.0 Hz, J2
= 12.0 Hz 1H); 1.95 (s, 3H). 13C NMR (CDCl3, 50 MHz) δ: = 170.0;
139.3; 133.0; 129.1; 128.5; 128.3; 127.2; 126.5; 75.2; 33.3; 21.0. IR
(film): 3058, 3029, 2998, 2928, 2851, 1737, 1578, 1493, 1477, 1453,
1436, 1370, 1236, 1021, 762, 737, 699 cm−1.
(2-Azido-2-phenylethyl)(phenyl)selane (Compound 3t). 0.0316 g,
21%, yellow oil.37 1H NMR (CDCl3, 200 MHz) δ: = 7.52−7.48 (m,
2H); 7.37−7.24 (m, 8H); 4.62 (t, J = 7.0 Hz, 1H); 3.23 (d, J1 = 4.0 Hz,
J2 =12.0 Hz 1H); 3.20 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H). 13C NMR
(CDCl3, 50 MHz) δ: = 138.7; 133.3; 129.3; 128.9; 128.7; 127.5; 126.8;
66.0; 34.0. IR (film): 3059, 3028, 2926, 2101, 1578, 1492, 1476, 1453,
1436, 1248, 1209, 1022, 737, 700 cm−1.
(2-Methoxy-2-phenylethyl)(phenyl)sulfane (Compound 5a).
0.0988 g, 81%, colorless oil.38 1H NMR (CDCl3, 200 MHz) δ: =
7.38−7.25 (m, 10H); 4.30 (dd, J1 = 4.0 Hz; J1 = 8.0 Hz, 1H); 3.32 (dd,
J1 = 8.0 Hz, J2 = 12.0 Hz, 1H); 3.25 (s, 3H); 3.13 (dd, J1 = 8.0 Hz, J2 =
12.0 Hz, 1H). 13C NMR (CDCl3, 50 MHz) δ: = 13C NMR (CDCl3, 50
MHz) δ = 140.4; 136.5; 129.3; 128.9; 128.5; 128.1; 126.7; 126.0; 82.4;
57.0; 41.5. IR (film): 3059, 3027, 2924, 2853, 2821, 1742, 1582, 1480,
1454, 1438, 1239, 1106, 1090, 1025, 738, 699, 692 cm−1.
2,2-Dimethyl-3-(phenylselanyl)-3,4-dihydro-2H-benzo[h]-
1
chromene-5,6-dione (Compound 8a). 0,1296 g, 65%, yellow oil. H
NMR (CDCl3, 200 MHz) δ: = 8.06 (d, J = 8.0 Hz, 1H), 7.78 (d, J =
8.0 Hz, 1H), 7.69−7.47 (m, 5H), 7.28 (d, J = 4.0, 2H), 3.41 (dd, J1 =
5.6 Hz, J2 = 9.6 Hz, 1H), 3.10 (dd, J1 = 5.6 Hz, J2 = 18.0 Hz, 1H), 2.73
(dd, J = 9.6, J = 18.0, 1H), 1.68 (s, 3H), 1.54 (s, 3H). 13C NMR
(CDCl3, 50 MHz) δ: = 179.4, 178.0, 161.4, 135.1, 134.8, 132.1, 130.8,
130.1, 129.3, 128.7, 128.5, 128.3, 124.1, 112.5, 82.9, 45.7, 27.7, 25.3,
23.2. IR (film): 2974, 2927, 2851, 1693, 1658, 1611, 1590, 1572, 1454,
1370, 1286, 1264, 1227, 1154, 1111, 1091, 777, 746 cm−1. HRMS
(APPI+) m/z: calculated for C21H19O3Se [M + H]+: 399.0495; found:
399.0493.
2-((Phenylselanyl)methyl)-2,3-dihydronaphtho[1,2-b]furan-4,5-
dione (Compound 9a). 0,1484 g, 80%, yellow oil.1H NMR (CDCl3,
F
DOI: 10.1021/jo502621a
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
200 MHz) δ: = 8.04 (d, J = 8.0, 1H), 7.61−7.54 (m, 4H), 7.44 (d, J =
8.0, 1H), 7.29−7.24 (m, 1H), 5.29 (m, 1H), 3.74 (dd, 1H, J = 8.0, J =
16.0), 3.27−3.17 (m, 2H), 2.96 (dd, 1H, J1 = 8.0 Hz, J2 = 16.0 Hz).
13C NMR (CDCl3, 50 MHz) δ: = 180.9, 175.2, 169.3, 134.4, 133.4,
131.8, 130.5, 129.3, 129.2, 128.6, 127.6, 127.2, 124.5, 114.9, 86.6, 40.8,
32.3, 32.1. IR (film): 3045, 2982, 2959, 2922, 2854, 1697, 1646, 1613,
1587, 1572, 1489, 1405, 1246, 1146, 1080, 891, 734 cm−1. HRMS
(APPI+) m/z: calculated for C19H15O3Se [M + H]+: 371.0182; found:
371.0187.
(d) Schmid, G. H.; Garratt, D. G. In The Chemistry of Double-bonded
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ASSOCIATED CONTENT
* Supporting Information
Spectral data for all compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*Fax: 55 48 3721 6427. Tel: 55 48 37216427. E-mail: braga.
antonio@ufsc.br (A.L.B.).
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors gratefully acknowledge CAPES, CNPq, FAPERGS,
FAPESP-GSK, FAPEMIG, INCT-Catal
■
́
ise, and FAPESC-
Pronex for financial support. CNPq is also acknowledged for
the doctorate fellowship received by J.B.A. The authors are also
thankful to CEBIME for the HRMS analysis. This research is
part of the scientific activity of the international multi-
disciplinary group “SeS redox and catalysis”.
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