Selenomethoxylation of Alkenes Promoted by Oxone

Article abstract of DOI:10.1002/ejoc.201701775

We describe herein an alternative method for the selenomethoxylation of unactivated alkenes using Oxone as a stoichiometric oxidant. The electrophilic species of selenium were easily generated in situ by the reaction of diorganyl diselenides with Oxone. By this efficient and simple approach, β-methoxy-selenides were obtained in moderate to excellent yields at room temperature in an open flask, starting from alkenes by using methanol as both nucleophile and solvent. When a mixture of H₂O/CH₃CN was employed as the solvent, β-hydroxy-selenides were selectively obtained under mild conditions.

Full text of DOI:10.1002/ejoc.201701775

A Journal of
Accepted Article
Title: Selenomethoxylation of Alkenes Promoted by Oxone®
Authors: Gelson Perin, Paolo Santoni, Angelita M. Barcellos, Patrick C.
Nobre, Raquel G. Jacob, Eder Joao Lenardão, and Claudio
Santi
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using the Digital Object Identifier (DOI) given below. The VoR will be
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701775
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701775
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10.1002/ejoc.201701775
European Journal of Organic Chemistry
FULL PAPER
Selenomethoxylation of Alkenes Promoted by Oxone®
a
Gelson Perin,*, Paolo Santoni,b Angelita M. Barcellos,a Patrick C. Nobre,a Raquel G. Jacob,a Eder J.
b
Lenardão,a Claudio Santi*,
Abstract: We describe herein an alternative method for the
selenomethoxylation of unactivated alkenes using Oxone® as a
stoichiometric oxidant. The electrophilic species of selenium were
easily generated in situ by the reaction of diorganyl diselenides with
Oxone®. By this efficient and simple approach, β-methoxy-selenides
were obtained in moderate to excellent yields at room temperature in
an open flask, starting from alkenes and using methanol as both
nucleophile and solvent. When a mixture of H2O/CH3CN was the
solvent, β-hydroxy-selenides were selectively obtained under mild
conditions.
prepare symmetric thiosulfonates,17 3-arylthio indoles18 and 2-
aminobenzothiazoles.19
In parallel to the increasing number of applications of
Oxone®, studies on the synthesis, use as synthetic intermediate
and bioactivity of organoselenides has attracted continuous
interest, mainly due to their important role in biological systems.20
A common synthetic strategy to prepare new organoselenides is
the electrophilic addition of an organoselenium group into the
chemical structure. Among the alternatives to prepare
electrophilic selenium in situ, the oxidative cleavage of the Se-Se
bond of diorganyl diselenides is a usual approach. Stoichiometric
or over-stoichiometric amounts of KBr/m-CPBA,21 [PhI(OAc)2],22
I2/DMSO,23 (NH4)2S2O8 24 have been used with this aim.
Introduction
These reactive electrophiles are useful reagents in the
seleno-oxylation of alkenes by the anti-1,2-addition of an
organoseleno group to the double bond via the formation of a
seleniranium intermediate, that rapidly reacts with a nucleophilic
oxygen (HO or RO). In the literature, it was described the
selenoalkoxy- and hydroxylation of alkenes with diselenides
The use of potassium peroxymonosulfate as oxidizing
agent in organic synthesis presents many advantages, such as
simplicity in handling, stability under several conditions and an
environmentally safer disposal, once it is not toxic. Moreover, it is
commercially available as Oxone® in the form of a triple salt
(2KHSO5·KHSO4·K2SO4) containing about 50% of active
TsOH/m-CPBA,25
NH4I/m-CPBA,26
m-
−
promoted
by
oxidant/mol, i.e., the anion peroxymonosulfate (HSO5 ). The
nitrobenzenesulfonyl peroxide,27 I2/DMSO,23 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ),28 halide/electrolytic system,29
(NH4)2S2O830 and by ceric ammonium nitrate (CAN).31
active oxidant within the mixture has been efficiently used to
perform a great number of organic transformations in polar
solvents.1 More recently, Oxone® was applied in the direct
conversion of Baylis-Hillman alcohols to β-chloro aldehydes,2 the
α-amination of ketones through nitroso aldol reaction,3 the
oxidative chlorination of Csp3-H bonds,4 in Csp3-H hydroxylation5
and the direct oxidative cascade cyclization of 2-aminobenzoic
acid and arylaldehydes.6 Furthermore, Oxone® was used to
prepare different classes of organic compounds, such as
indenochromenes,7 β-fluoroporpholactones,8 α-bromo- and α-
azidoketones.9
Regarding its use in the synthesis of organochalcogen
compounds,10 Oxone® was used in the oxidation of sulfides to
sulfoxides and sulfones,11 oxidation of thiols to sulfonic acids,12
oxyhalogenation of thiols and disulfides,13 oxidative coupling of
thiols to disulfides,14 oxidation of selenides to selenones15 and in
the enantioselective oxidation of disulfides.16 Oxone® was used to
In continuation to our studies in the development of
efficient protocols to prepare functionalized organoselenides, we
report herein an alternative method for the selenomethoxy- and
selenohydroxylation of alkenes using Oxone® as an oxidant. This
method involves the reaction of alkenes 1 with electrophilic
selenium generated in situ, through the reaction of diorganoyl
diselenides 2 with Oxone® in methanol or aqueous medium under
mild conditions, to prepare β-methoxy-selenides 3 and β-hydroxy-
selenides 4, respectively (Scheme 1).
Scheme 1
[a]
[b]
Prof. G. Perin, A.M. Barcellos, P. C. Nobre, Prof. E. J. Lenardão,
Laboratório de Síntese Orgânica Limpa – LASOL
Federal University of Pelotas – UFPel
P.O. Box 354, 96010-900, Pelotas – RS, Brazil.
E-mail: gelson_perin@ufpel.edu.br
Results and Discussion
Preliminary experiments were carried out on styrene 1a
and diphenyl diselenide 2a in order to optimize the reaction
http://lattes.cnpq.br/5962449538872950
P. Santoni, Prof. C. Santi.
Department of Pharmaceutical Sciences
University of Perugia
Via del Liceo, 1, Perugia (PG), Italy.
conditions,
in
the
synthesis
of
(2-methoxy-2-
phenylethyl)(phenyl)selane 3a, the results are summarized in
Table 1. When a mixture of styrene 1a (0.5 mmol), diphenyl
diselenide 2a (0.25 mmol) and Oxone® (0.125 mmol) in methanol
(3.0 mL) was stirred at room temperature for 8.0 h, the desired
product 3a was obtained in 30% yield (Table 1, entry 1). Aiming
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201701775
European Journal of Organic Chemistry
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to improve this result, the amount of Oxone® was increased to
0.25 mmol and fortunately, yield increased to 93% in 3.5 h (Table
1, entry 2). A decrease in the yield of 3a was observed when 0.50
mmol of Oxone® was used, probably due to the oxidation of the β-
methoxy-selenides under these conditions, as previously
reported15 (Table 1, entry 3). Additionally, if no oxidizing agent is
present, no product 3a is formed, as indicated by GC/MS analysis
(Table 1, entry 4). Regarding the influence of the reaction time, it
was observed that 3.5 h gave the best result, almost no difference
in the yield was observed after 5 hours (Table 1, entries 2 vs 5
and 6). A small amount of 1-phenyl-2-(phenylseleno)ethanol 4a
(< 3%), formed by the attack of OH as nucleophile in the
seleniranium intermediate, was observed in all the tested
reactions. To avoid the formation of side products, the reaction
was carried out using dry Oxone® and methanol in a closed flask.
However, similar yields, as well as the presence of trace amounts
of 4a were observed (Table 1, entry 7).
hindered dimesityl diselenide 2e. The performance of the reaction
was very good using the aliphatic dibutyl diselenide 2f, with the
product of interest 3f (R1 = C4H9) being isolated in 89% yield after
3.5 h.
Table 2. Synthesis of β-alkoxy-selenides 3a-l promoted by Oxone®.[a],[b]
Table 1. Optimization of selenomethoxylation of olefins by Oxone®.[a]
Entry
Oxone® (mmol)
0.125
Time (h)
8.0
Yield of 3a (%)[b],[c]
1
2
3
4
5
6
7
30
93
0.250
3.5
0.500
3.5
52
-
3.5
nr
0.250
2.5
79
0.250
5.0
92
85[d]
0.250
3.5
[a] Reactions performed using styrene 1a (0.5 mmol), (C6H5Se)2 2a (0.25 mmol)
and Oxone® in methanol (3.0 mL) in an open flask at room temperature. [b]
Isolated yields. [c] Observed the presence of 1-phenyl-2-(phenylseleno)ethanol
4a in trace amounts (< 3%), determined by CG-MS. [d] Performed using dry
Oxone® in a closed flask. nr = no reaction.
[a]Reactions performed in the presence of alkene 1a-f (0.5 mmol), diorganyl
diselenide 2a-f (0.25 mmol), CH3OH (3.0 mL), Oxone® (0.25 mmol) under
open flask at room temperature for 3.5 h. [b] Isolated yields. [c] CH3OH/THF
(2:1) under reflux for 20 h. [d] Under 50 °C. [e] A 4:1 mixture of isomers
(Markovnikov)/(anti-Markovnikov adduct) was isolated. [f] C2H5OH (3.0 mL)
was used instead CH3OH.
From the results collected in Table 1, the best reaction
conditions were defined as the stirring of a mixture of styrene 1a
(0.5 mmol), diphenyl diselenide 2a (0.25 mmol) and Oxone® (0.25
mmol) in methanol (3.0 mL) for 3.5 h at room temperature (Table
1, entry 2).
Afterward, the possibility of performing these reactions
with different alkenes 1b-e was also investigated. Differently of
the observed in the aromatic diselenides, the presence of
electron-withdrawing group 4-Cl in the styryl derivative 1d did not
influence negatively the reaction and the desired β-methoxy-
selenide 3i (R = 4-ClC6H4) was obtained in 88% yield. This
outcome is like that observed for neutral 1a and discreetly
electron-rich 4-tolylstyrene 1b, that afforded the respective β-
methoxy-selenides 3a (R = C6H5) and 3g (R = 4-CH3C6H4) in 92%
and 72% yields, respectively. The presence of the strong electron-
donor CH3O group however, like in 4-methoxystyrene 1c caused
a drastic reduction in the reaction yield, and β-methoxy-selenide
3h (R = 4-CH3OC6H4) was obtained in only 37% yield, even if the
reaction temperature was increased to 50 °C. This moderate yield
could probably be associated with the low solubility of 1c in the
reaction medium. The low reactivity of 4-methoxystyrene in the
presence of Oxone® was already observed before, by Parida and
Moorthy,32 during their studies on the cleavage of olefins to
Once the best reaction conditions were determined for the
synthesis of 3a, the scope and limitations of the methodology
were explored by reacting a variety of alkenes 1a-e with a range
of diorganyl diselenides 2a-f (Table 2). The results showed in
Table 2 reveal that our protocol is general, working well for most
of the employed substrates. The reaction showed to be sensitive
to electronic effects in the aryl moiety of the diorganyl diselenides
2a-d. The presence of electron-releasing and electron-neutral
substituents in the aromatic ring of the diaryl diselenides 2a-c (R1
= C6H5, 4-CH3C6H4 or 4-CH3OC6H4) positively influenced the
reactivity, compared to the electron-poor diselenide 2d (R1 = 4-
ClC6H4). Further, to obtain compound 3d in satisfactory yield, a
mixture MeOH/THF (2:1) was necessary to homogenizing the
mixture and accelerate the reaction. In a similar way, the same
mixture of solvents under reflux was used to give a good yield of
β-methoxy-selenide 3e (R1 = mesityl), derived from the sterically
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10.1002/ejoc.201701775
European Journal of Organic Chemistry
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carboxylic acids. A number of unidentified by-products derived
from parallel reactions were observed.
only 21% yield. Unfortunately, the product of the reaction with
hept-1-ene 1f (R = C5H11) could not be obtained in isolable
amount using our method.
Not only styrene derivatives were reactive under our
conditions, but also the common alkene hept-1-ene 1e furnished
3j (R = C5H11) as a 4:1 mixture of Markovnikov and anti-
Markovnikov adducts in 75% yield. We also examined the
reaction of cyclohexene 1f, affording the respective β-methoxy-
selenide 3k [R = -(CH2)4-] in 77% yield. The reaction performed
with ethanol as nucleophile and solvent instead methanol
furnished the expected β-ethoxy-selenide 3l (R2 = C2H5) in poor
yield (35%) after 3.5 h. Additional reactions were conducted
aiming to obtain higher yields of 3l, however even after 20 h under
reflux, the isolated yield was the same.
In order to extend the scope of the present methodology,
we attempted to synthesize β-hydroxy-selenides by using
aqueous medium (Table 3). In a first assay, the reaction of styrene
1a, diphenyl diselenide 2a and Oxone® in a 2:1 mixture of
H2O/CH3CN (3.0 mL) as the solvent, provided 1-phenyl-2-
(phenylseleno)ethanol 4a (R = C6H5) in 53% yield after 5 h at room
temperature. To our delight, when the temperature was increased
to 50 oC, the desired β-hydroxy-selenide 4a was obtained in 75%
yield after 20 h. This optimal reaction conditions extended to
substituted styrenes 1b-d. Similar to the observed in the
selenomethoxylation reactions (Table 2), the presence of a CH3
group in the aromatic ring (4-tolylstyrene 1b) did not considerably
affect the reaction, and the respective β-hydroxy-selenide 4b (R
= 4-CH3C6H4) was isolated in 83% yield after 20 h at 50 oC.
Based on our results and those from the literature,23,25,33
a
plausible mechanism for the selenomethoxylation of styrene 1a
with (C6H5Se)2 2a promoted by Oxone® in methanol or aqueous
medium is proposed in Scheme 2. We believe that Oxone® at first
reacts with diphenyl diselenide 2a to generate intermediates A
and B. 77Se-NMR analysis and MS were used to confirm the
formation of these intermediates. When equivalent amounts of 2a
and Oxone® were mixed in a NMR tube (CD3OD), the reaction
started and after few minutes, the signal at 457.54 ppm in the
77Se-NMR spectra, characteristic of starting (C6H5Se)2 2a,
disappeared and the only observed signal was a peak at 993.05
ppm, attributed to intermediate B.34 Intermediate A was not
noticeable in NMR, but its presence was detected by MS. Once
the electrophilic selenium species A is formed, it reacts with the
carbon-carbon double bond of the alkene 1 to produce the
carbocation C, which can be stabilized by the organoselenium
group, via the seleniranium intermediate D. When aryl alkenes
were used, the carbocation C undergoes a nucleophilic attack by
R1OH (R1 = CH3, C2H5 or H) to give the respective product 3 or 4,
via a SN1 mechanism.26 From alkyl alkenes, the formation of
seleniranium species D is favored, which is nucleophilically
opened by R1OH (R1 = CH3 or H) to give a mixture of Markovnikov
and anti-Markovnikov adducts 3 or 4.26
Table 3. Synthesis of β-hydroxy-selenides 4a-f promoted by Oxone®.[a],[b]
[a] Reactions performed in the presence of alkene 1a-f (0.5 mmol), diphenyl
diselenide 2a (0.25 mmol), H2O/CH3CN (1:2, 3.0 mL), Oxone® (0.25 mmol)
under open flask at 50 °C for 20 h. [b] Isolated yields. [c] Under room
temperature for 5 h.
Scheme 2
The presence of the strongly electron-donating OCH3 (4-
methoxy-styrene 1c), however, negatively affected the reaction,
affording the expected 4c (R = 4-CH3OC6H4) in only 22% yield.
The reaction was considerably faster using 4-chloro-styrene 1d,
with β-hydroxy-selenide 4d (R = 4-ClC6H4) being obtained in 95%
yield at room temperature after only 5 h. The protocol was applied
Conclusions
An efficient methodology to prepare β-methoxy-selenides
and β-hydroxy-selenides by selenomethoxylation and
selenohydroxylation of alkenes using the Oxone® as
stoichiometric oxidant was developed. The electrophilic species
of selenium was generated in situ from easily available diorganyl
diselenides in the presence of oxidizing agent. The reactions
a
to
cyclohexene
1e,
however
the
desired
2-
(phenylselanyl)cyclohexan-1-ol 4e [R = -(CH2)4-] was obtained in
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10.1002/ejoc.201701775
European Journal of Organic Chemistry
FULL PAPER
[23]
0.151 g (94%); yellow oil.
1H NMR (CDCl3, 400 MHz) δ
proceeded at room temperature or gentle heating at 50 °C for few
hours, affording the corresponding compounds in moderate to
excellent yields. The protocol is versatile and was successfully
applied to aromatic and aliphatic diselenides and alkenes.
(ppm) = 7.44 (d, J = 8.9 Hz, 2H), 7.35-7.25 (m, 5H), 6.78 (d, J
= 8.9 Hz, 2H), 4.29 (dd, J = 8.3 and 5.1 Hz, 1H), 3.77 (s, 3H),
3.23 (dd, J = 12.3 and 8.3, 1H), 3.23 (s, 3H), 3.00 (dd, J = 12.3
and 5.1 Hz, 1H). 13C NMR (CDCl3, 100 MHz) δ (ppm) = 159.2,
141.0, 135.5, 128.4, 127.9, 126.6, 120.3, 114.7, 83.1, 56.9,
55.2, 36.3. MS (rel. int) m/z: 77 (12.7), 91 (10.4), 121 (100.0),
187 (3.9), 322 (13.3).
Experimental Section
The reactions were monitored by thin layer chromatography
(TLC) was performed using Merck silica gel (60 F254), 0.25 mm
thickness. For visualization, TLC plates were either placed
under UV light, or stained with iodine vapor, or and 5% vanillin
in 10% H2SO4 and heat. Column chromatography was
performed using Merck Silica Gel (230-400 mesh). High
resolution mass spectra (HRMS) were recorded on a Bruker
Micro TOF-QII spectrometer 10416. Low-resolution mass
spectra (MS) were measured on a Shimadzu GC-MS-QP2010
mass spectrometer. NMR spectra were recorded with Bruker
DPX (1H NMR = 400 and 500 MHz; 13C NMR = 100 and 125
MHz; 77Se NMR = 76 MHz) instruments using, were otherwise
4-Chlorophenyl(2-methoxy-2-phenylethyl)selane 3d: Yield:
0.072 g (44%); yellow oil.
[23]
1H NMR (CDCl3, 400 MHz) δ
(ppm) = 7.37 (d, J = 8.7 Hz, 2H), 7.27-7.36 (m, 5H), 7.18 (d, J
= 8.7 Hz, 2H), 4.33 (dd, J = 8.3 and 5.1 Hz, 1H), 3.29 (dd, J =
12.3 and 8.3 Hz, 1H), 3.23 (s, 3H), 3.07 (dd, J = 12.3 and 5.1
Hz, 1H). 13C NMR (CDCl3, 100 MHz) δ (ppm) = 140.7, 134.0,
133.0, 129.1, 128.9, 128.5, 128.1, 126.6, 83.1, 57.0, 35.7. MS
(rel. int) m/z: 77 (11.2), 91 (9.1), 121 (100.0), 191 (1.6), 326
(5.0).
Mesityl(2-methoxy-2-phenylethyl)selane 3e: Yield: 0.142 g
(85%); yellow oil. 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.24-
7.33 (m, 5H), 6.91 (s, 2H), 4.21 (dd, J = 8.8 and 4.7 Hz, 1H),
3.21 (s, 3H), 3.05 (dd, J = 12.1 and 8.8 Hz, 1H), 2.79 (dd, J =
12.1 and 4.7 Hz, 1H), 2.51 (s, 6H), 2.25 (s, 3H). 13C NMR
(CDCl3, 100 MHz) δ (ppm) = 143.0, 141.2, 138.0, 128.4,
128.36, 128.1, 128.0, 126.5, 83.4, 56.9, 35.0, 24.4, 20.9. 77Se
NMR (76 MHz, CDCl3): δ = 155 ppm. MS (rel. int) m/z: 77 (9.9),
91 (12.0), 121 (100.0), 135 (12.3), 334 (12.2). HRMS:
Calculated mass for C18H22OSe [M + Na]+: 357.0734, found:
357.0747.
indicated,
CDCl3 as solvent and calibrated using
tetramethylsilane (TMS) for H and 13C NMR and (PhSe)2 for
77Se-NMR as internal standard. Coupling constants (J) are
reported in Hertz and chemical shift (δ) in ppm. The reagents
(alkenes and Oxone®) were purchased from Sigma-Aldrich.
1
General Procedure for the Synthesis of β-alkoxy-selenides
3a-l: To a 10 mL glass tube containing a mixture of alkene 1
(0.5 mmol) and an appropriate diorganyl diselenide 2 (0.25
mmol) in methanol (3.0 mL), Oxone® (0.25 mmol, 0.077 g) was
added. The resulting mixture was stirred for the time indicated
in Table 2 at room temperature (r.t.; 25 °C) in open flask. The
reactions were monitored by TLC until total disappearance of
the starting materials. After that, the reaction mixture was
received in water (50.0 mL), extracted with ethyl acetate (3x
15.0 mL), dried over MgSO4 and concentrated under vacuum.
The residue was purified by column chromatography on silica
gel using hexane as the eluent. All the compounds were
Butyl(2-methoxy-2-phenylethyl)selane 3f: Yield: 0.121
(89%); yellow oil.
g
[23]
1H NMR (CDCl3, 400 MHz) δ (ppm) =
7.26-7.37 (m, 5H), 4.32 (dd, J = 7.8 and 5.5 Hz, 1H); 3.24 (s,
3H), 2.97 (dd, J = 12.3 and 7.8 Hz, 1H); 2.73 (dd, J = 12.3 and
5.5 Hz, 1H); 2.48 (t, J = 7.3 Hz, 2H); 1.58 (quint, J = 7.3 Hz,
2H); 1.35 (sex, J = 7.3, 2H); 0.89 (t, J = 7.3 Hz, 3H). 13C NMR
(CDCl3, 100 MHz) δ (ppm) = 141.2, 128.4, 127.9, 126.6, 84.4,
56.8, 32.6, 31.0, 24.5, 22.9, 13.5. MS (rel. int) m/z: 77 (9.6),
91 (8.7), 121 (100.0), 272 (6.8).
1
properly characterized by MS, H NMR and 13C NMR.
(2-Methoxy-2-phenylethyl)(phenyl)selane 3a: Yield: 0.134 g
(92%); yellow oil.[23] 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.45-
7.49 (m, 2H), 7.20-7.37 (m, 8H), 3.34 (dd, J = 8.4 and 5.0 Hz,
1H), 3.32 (dd, J = 12.3 and 8.4 Hz, 1H), 3.24 (s, 3H), 3.10 (dd,
J = 12.3 and 5.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz) δ (ppm)
= 140.9, 132.6, 130.6, 129.0, 128.5, 128.1, 126.8, 126.6, 83.2,
57.0, 35.3. MS (rel. int) m/z: 77 (16.6), 91 (13.0), 121 (100.0),
135 (1.9), 157 (2.3), 292 (6.9).
2-Methoxy-2-(4-tolyl)ethyl(phenyl)selane 3g: Yield: 0.110 g
(72%); yellow oil.
[23]
1H NMR (CDCl3, 400 MHz) δ (ppm) =
7.45-7.49 (m, 2H), 7.13-7.26 (m, 7H), 4.31 (dd, J = 8.4 and 5.1
Hz, 1H), 3.32 (dd, J = 12.2 and 8.4 Hz, 1H), 3.23 (s, 3H), 3.09
(dd, J = 12.2 and 5.1 Hz, 1H), 2.34 (s, 3H). 13C NMR (CDCl3,
100 MHz) δ (ppm) = 137.82, 137.8, 132.5, 130.7, 129.2, 129.0,
126.7, 126.6, 82.9, 56.9, 35.3, 21.2. MS (rel. int) m/z: 77 (3.5),
105 (4.6), 119 (5.0), 135 (100.0), 306 (6.2).
(2-Methoxy-2-phenylethyl)(4-tolyl)selane 3b: Yield: 0.125 g
(82%); yellow oil. [23] 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.38
(d, J = 8.3 Hz, 2H), 7.25-7.36 (m, 5H), 7.05 (d, J = 8.3 Hz, 2H),
4.32 (dd, J = 8.4 and 5.1 Hz, 1H), 3.28 (dd, J = 12.3 and 8.4
Hz, 1H), 3.24 (s, 3H), 3.05 (dd, J = 12.3 and 5.1 Hz, 1H), 2.31
(s, 3H). 13C NMR (CDCl3, 100 MHz) δ (ppm) = 141.0, 136.9,
133.1, 129.8, 128.5, 128.0, 126.7, 83.1, 57.0, 35.7, 21.0. MS
(rel. int) m/z: 77 (12.6), 91 (16.0), 121 (100.0), 171 (1.7), 306
(8.6).
2-Methoxy-2-(4-methoxyphenyl)ethyl(phenyl)selane 3h: Yield:
0.060 g (37%); yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm)
1
= 7.44-7.48 (m, 2H), 7.19-7.24 (m, 5H), 6.85-6.89 (m, 2H),
4.30 (dd, J = 8.2 and 5.4 Hz, 1H), 3.79 (s, 3H), 3.32 (dd, J =
12.2 and 8.2 Hz, 1H), 3.21 (s, 3H), 3.08 (dd, J = 12.2 and 5.4
Hz, 1H). 13C NMR (CDCl3, 100 MHz) δ (ppm) = 159.4, 132.8,
132.5, 130.7, 128.9, 127.8, 126.7, 113.9, 82.7, 56.7, 55.2,
35.3. 77Se NMR (76 MHz, CDCl3): δ = 275 ppm. MS (rel. int)
m/z: 77 (5.0), 91 (8.8), 119 (4.0), 135 (8.7), 151 (100.0), 322
(2.8). HRMS: Calculated mass for C16H18O2Se [M]+: 322.0467,
2-Methoxy-2-phenylethyl(4-methoxyphenyl)selane 3c: Yield:
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10.1002/ejoc.201701775
European Journal of Organic Chemistry
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found: 322.0477.
1-Phenyl-2-(phenylseleno)ethanol 4a: Yield: 0.104 g (75%);
yellow oil. [27] 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.42-7.44
(m, 2H), 7.22-7.23 (m, 4H), 7.15-7.20 (m, 4H), 4.64 (dd, J =
9.4 and 3.7 Hz, 1H), 3.18 (dd, J = 12.8 and 3.7 Hz, 1H), 3.01
(dd, J = 12.8 and 9.4 Hz, 1H), 2.84 (brs, 1H). 13C NMR (CDCl3,
100 MHz) δ (ppm) = 142.4, 133.1, 129.2, 129.1, 128.5, 127.9,
127.4, 125.8, 72.2, 38.4. MS (rel. int) m/z: 77 (58.4), 91 (45.2),
107 (58.9), 157 (16.6), 172 (100.0), 278 (33.0).
2-(4-Chlorophenyl)-2-methoxyethyl(phenyl)selane 3i: Yield:
0.143 g (88%); yellow oil.[23] 1H NMR (CDCl3, 400 MHz) δ
(ppm) = 7.36-7.38 (m, 2H), 7.20-7.23 (m, 2H), 7.13-7.16 (m,
5H), 4.23 (dd, J = 7.9, 5.4 Hz, 1H), 3.20 (dd, J = 12.4, 7.9 Hz,
1H), 3.14 (s, 3H), 2.97 (dd, J = 12.4, 5.4 Hz, 1H). 13C NMR
(CDCl3, 125 MHz) δ (ppm) = 139.3, 133.7, 132.7, 130.3, 129.0,
128.6, 128.0, 126.9, 82.5, 57.0, 35.1. MS (rel. int) m/z: 77
(10.3), 91 (23.1), 111 (2.3), 125 (3.8), 155 (100.0), 326 (6.8).
1-(4-Tolyl)-2-(phenylseleno)ethanol 4b: Yield: 0.121 g (83%);
yellow oil.[23] 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.50-7.53
(m, 2H), 7.20-7.25 (m, 5H), 7.11-7.13 (m, 2H), 4.71 (dd, J =
9.2 and 4.0 Hz, 1H), 3.26 (dd, J = 12.7 and 4.0 Hz, 1H), 3.13
(dd, J = 12.7 and 9.2 Hz, 1H), 2.75 (brs, 1H), 2.32 (s, 3H). 13C
NMR (CDCl3, 100 MHz) δ (ppm) = 139.6, 137.6, 133.0, 129.3,
129.15, 129.1, 127.2, 125.7, 72.1, 38.3, 21.1. MS (rel. int) m/z:
77 (59.3), 91 (100.0), 115 (36.0), 157 (11.1), 172 (80.5), 292
(13.5).
2-Methoxyheptyl(phenyl)selane 3j: Yield: 0.107 g (75%);
yellow oil, (4:1 mixture of regioisomers). Markovnikov adduct
1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.42-7.50 (m, 2H), 7.14-
7.20 (m, 3H), 3.25 (s, 3H), 3.01 (dd, J = 12.2 and 5.5 Hz, 1H),
2.92 (dd, J = 12.2 and 6.1 Hz, 1H), 1.42-1.61 (m, 3H), 1.12-
1.40 (m, 5H), 0.80 (t, J = 7.0 Hz, 3H). 77Se NMR (76 MHz,
CDCl3): δ = 257 ppm. MS (rel. int) m/z: 55 (71.0), 83 (100.0),
115 (86.1), 157 (11.5), 286 (25.6). anti-Markovnikov adduct 1H
NMR (CDCl3, 400 MHz) δ (ppm) = 7.42-7.50 (m, 2H), 7.14-
7.20 (m, 3H), 3.39-3.49 (m, 1 H), 3.27-3.32 (m, 1H), 3.24 (s,
3H), 1.42-1.61 (m, 3H), 1.12-1.40 (m, 5H), 0.80 (t, J = 7.0 Hz,
3H). 77Se NMR (76 MHz, CDCl3): δ = 343 ppm. MS (rel. int)
m/z: 55 (100.0), 97 (69.1),129 (9.7), 157 (7.7), 286 (30.3).
Regioisomers 13C NMR (CDCl3, 100 MHz) δ (ppm) = 134.7,
132.6, 130.7, 129.0, 128.9, 127.4, 126.7, 58.6, 56.9, 44.9,
33.8, 32.2, 32.0, 31.8, 31.6, 27.3, 24.9, 22.5, 22.47, 14.0.
HRMS: Calculated mass for C15H22OSe [M]+: 286.0831, found:
286.0840.
1-(4-Methoxyphenyl)-2-(phenylseleno)ethanol 4c: Yield: 0.034
g (22%); yellow oil. 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.50-
7.53 (m, 2H), 7.23-7.26 (m, 5H), 6.84-6.86 (m, 2H), 4.71 (dd,
J = 9.1 and 4.1 Hz, 1H), 3.78 (s, 3H), 3.26 (dd, J = 12.7 and
4.1 Hz, 1H), 3.14 (dd, J = 12.7 and 9.1 Hz, 1H), 2.75 (brs, 1H).
13C NMR (CDCl3, 100 MHz) δ (ppm) = 159.3, 134.7, 133.0,
129.3, 129.2, 127.2, 127.0, 113.9, 72.0, 55.2, 38.3. 77Se NMR
(76 MHz, CDCl3): δ = 250 ppm. MS (rel. int) m/z: 77 (56.1), 91
(46.9), 137 (100.0), 172 (66.1), 210 (26.5), 308 (6.6). HRMS:
Calculated mass for C15H16O2Se [M]+: 308.0311, found:
308.0321.
2-Methoxycyclohexyl(phenyl)selane 3k: Yield: 0.104 g (77%);
colorless oil.[26] 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.57-7.60
(m, 2H), 7.23-7.28 (m, 3H), 3.37 (s, 3H), 3.24-3.29 (m, 1H),
3.15-3.19 (m, 1H), 2.12-2.16 (m, 1H), 1.97-2.03 (m, 1H), 1.67-
1.74 (m, 1H), 1.57-1.62 (m, 1H), 1.45-1.53 (m, 1H), 1.21-1.36
(m, 3H). 13C NMR (CDCl3, 125 MHz) δ (ppm) = 135.2, 128.9,
128.7, 127.3, 82.1, 56.3, 47.3, 32.1, 30.2, 25.7, 23.4. MS (rel.
int) m/z: 77 (5.2), 81 (100.0), 113 (33.1), 157 (3.1), 270 (14.4).
1-(4-Chlorophenyl)-2-(phenylseleno)ethanol 4d: Yield: 0.148 g
(95%); yellow oil.[27] 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.48-
7.51 (m, 2H), 7.20-7.27 (m, 7H), 4.68 (dd, J = 9.1 and 4.0 Hz,
1H), 3.22 (dd, J = 12.8 and 4.0 Hz, 1H), 3.06 (dd, J = 12.8 and
9.1 Hz, 1H) 2.93 (brs, 1H). 13C NMR (CDCl3, 100 MHz) δ (ppm)
= 140.9, 133.5, 133.1, 129.2, 128.9, 128.5, 127.4, 127.1, 71.5,
38.2. MS (rel. int) m/z: 77 (85.0), 91 (55.8), 113 (25.4), 157
(17.5), 172 (100.0), 312 (27.8).
2-Ethoxy-2-phenylethyl(phenyl)selane 3l: Yield: 0.054
g
(35%); colorless oil.[26] 1H NMR (CDCl3, 400 MHz) δ (ppm) =
7.46-7.49 (m, 2H), 7.20-7.35 (m, 8H), 4.46 (dd, J = 8.4 and 5.1
Hz, 1H), 3.30-3.43 (m, 3H), 3.09 (dd, J = 12.2 and 5.1 Hz, 1H),
1.17 (t, J = 7.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ (ppm) =
141.7, 132.6, 130.9, 128.9, 128.5, 127.9, 126.7, 126.6, 81.4,
64.7, 35.6, 15.2. MS (rel. int) m/z: 77 (14.7), 107 (59.7), 135
(100.0), 157 (3.8), 306 (6.4).
2-(Phenylselanyl)cyclohexanol 4e: Yield: 0.027 g (21%);
yellow oil.[27] 1H NMR (CDCl3, 400 MHz) δ (ppm) = 7.58-7.61
(m, 2H), 7.26-7.34 (m, 3H), 3.33 (ddd, J = 10.0, 10.0 and 4.2
Hz, 1H), 2.90 (ddd, J = 11.2, 10.0 and 3.9 Hz, 1H), 2.11-2.22
(m, 2H), 1.71-1.75 (m, 1H), 1.60-1.66 (m, 1H), 1.16-1.48 (m,
5H). 13C NMR (CDCl3, 100 MHz) δ (ppm) = 136.1, 129.0,
128.1, 126.7, 72.3, 53.6, 33.9, 33.4, 26.9, 24.5. MS (rel. int)
m/z: 77 (23.3), 81 (100.0), 99 (14.3), 156 (42.7), 256 (35.6).
General Procedure for the Synthesis of β-hydroxy-selenides
4a-e: To a 10 mL glass tube containing a mixture of alkene 1 (0.5
mmol) and an appropriate diorganyl diselenide 2 (0.25 mmol) in
H2O/CH3CN (1:2, 3.0 mL), Oxone® (0.25 mmol, 0.077 g) was
added. The resulting mixture was stirred for the time indicated in
Table 2 at room temperature (r.t.; 25 °C) in open flask. After that,
the reaction mixture was received in water (50.0 mL), extracted
with ethyl acetate (3x 15.0 mL), dried over MgSO4, and
concentrated under vacuum. The residue was purified by column
chromatography on silica gel using hexane as the eluent. All the
Mechanism experiments
Procedure to Prepare Intermediate A: To a 10 mL glass tube
containing diphenyl diselenide 2a (0.25 mmol) in methanol (3.0
mL), Oxone® was added. The resulting mixture was stirred for
1 h at room temperature in the open flask. The diphenyl
diselenide oxidative cleavage was accompanied by a change
in the reaction’s solution color, from yellow to white, and the
formation of a precipitate. The solvent was separated from the
precipitate by decantation and removed with a Pasteur pipette.
The resulting solid was dried under vacuum and characterized
by MS.
compounds were properly characterized by MS, 1H NMR and 13
NMR.
C
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10.1002/ejoc.201701775
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Procedure to Prepare Intermediate B: To a NMR tube
containing styrene 1a and diphenyl diselenide 2a (0.25 mmol)
in methanol (3.0 mL), Oxone® was added. The resulting
mixture was used to collect the 77Se NMR data.
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(a) Barcellos, A.; Abenante, L.; Sarro, M.; Leo, I.; Lenardão,
E. J.; Perin, G.; Santi, C. Curr. Org. Chem. 2017, 21, 2044-
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Acknowledgements
The authors thank FAPERGS, CNPq, and CAPES for financial
support. CNPq is also acknowledged for the fellowship for G.P.,
R.G.J. and E.J.L. University of Perugia is acknowledged for
fellowship “accordi quadro” P.S. and financial support “Ricerca di
Base 2017” C.S. This manuscript is part of the scientific activity of
the international multidisciplinary “SeS Redox and Catalysis”
network.
Keywords: oxone, β-methoxy-selenides, β-hydroxy-selenides,
organochalcogen compounds.
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Gelson Perin,* Paolo Santoni, Angelita
M. Barcellos, Patrick C. Nobre, Raquel
G. Jacob, Eder J. Lenardão, Claudio
Santi*
Page No. – Page No.
Selenomethoxylation of Alkenes
Promoted by Oxone®
We describe herein an alternative method for the selenomethoxylation of unactivated
alkenes using Oxone® as a stoichiometric oxidant. By this efficient and simple
approach, β-methoxy-selenides were obtained in moderate to excellent yields in an
open flask, starting from alkenes and using methanol as both nucleophile and
solvent. When a mixture of H2O/CH3CN was the solvent, β-hydroxy-selenides were
selectively obtained under mild conditions.
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