Unusual Application for Phosphonium Salts and Phosphoranes: Synthesis of Chalcogenides

Article abstract of DOI:10.1021/acs.joc.1c00114

A novel strategy for the synthesis of sulfides and selenides from phosphonium salts and thio- or selenesulfonates, commercially available compounds, is described. When phosphoranes were used in the reaction, different products were obtained. The methodology does not require the use of metals, reactive species, or anhydrous conditions to be performed.

Full text of DOI:10.1021/acs.joc.1c00114

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Note
Unusual Application for Phosphonium Salts and Phosphoranes:
Synthesis of Chalcogenides
Igor M. R. Moura, Arisson Tranquilino, Barbara G. Sátiro, Ricardo O. Silva, Diogo de Oliveira-Silva,
Roberta A. Oliveira,* and Paulo H. Menezes*
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ABSTRACT: A novel strategy for the synthesis of sulfides and
selenides from phosphonium salts and thio- or selenesulfonates,
commercially available compounds, is described. When phosphor-
anes were used in the reaction, different products were obtained.
The methodology does not require the use of metals, reactive
species, or anhydrous conditions to be performed.
and chalcogenols14 or dichalcogenides15 promoted by different
transition metals, desulfurilative sulfonylthiolation of arenes,16
and the use of iodine and its derivatives17 have been also
described.
Despite several developments such as the use of different
catalysts, solvents, and reaction media, until recently, few
changes have been made for the use of new starting materials
to synthesize chalcogenides.18 In this context, chalcogenosul-
fonates appear as an alternative for the use of chalcogenols,19
since this class of compounds has high stability and some of
them are commercially available.
In this work, the synthesis of sulfur and selenium
compounds based on the reaction between thio- or
selenesulfonates and different phosphonium salts or phosphor-
anes is described. In the course of developing an optimal set
for the reaction conditions, we first examined the best base to
promote the reaction. Thus, S-(p-tolyl) p-toluenethiosulfo-
nate,20 1a (0.36 mmol), and benzyltriphenylphosphonium
bromide, 2a (0.43 mmol), both prepared according to the
literature procedures, were treated at room temperature using
different bases, and the progress of the reaction was monitored
by TLC. The results are presented in Table 1.
ince the discovery of the Wittig reaction,1 phosphonium
Ssalts and phosphoranes have been among the most
important chemicals for the stereoselective synthesis of
functionalized alkenes.2 In addition, the applications of these
reagents in the preparation of ionic liquids,3 sensors,4 and
catalysts5 and in separation processes6 were also described.
The large commercial availability, low cost, chemical stability,
and ease of handling also make these reagents interesting in the
development of new synthetic strategies.
Organosulfides and selenides are important not only from a
synthetic point of view, as they can be used as intermediates or
reagents for the preparation of molecules of high structural
complexity,7 but also because they can exhibit different
properties and biological/pharmacological activities.8 In
addition, these compounds have several applications in
materials chemistry9 and as ligands in asymmetric synthesis.10
There are several methods for the synthesis of sulfides and
selenides described in the literature. The most common
approach is based on the substitution reaction between alkyl
halides using thiols or selenols as nucleophiles.11 This strategy
has some inconveniences: thiols are known for their unpleasant
odor and difficult handling, while selenols usually need to be
generated and used in situ due to being prone to autoxidation
into the corresponding diselenides.12 The umpolung equiv-
alents, organoselenium halides (e.g., phenylselenyl bromide or
chloride), are stable and commercially available solids;
however, the use of phenylsulfenyl chloride has the
disadvantage of the need to be stored and manipulated
under argon.13 Other strategies for the synthesis of
chalcogenides based on the coupling reaction of aryl halides
Received: January 15, 2021
Published: March 31, 2021
https://doi.org/10.1021/acs.joc.1c00114
© 2021 American Chemical Society
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a
Table 1. Reaction Optimization
Scheme 1. Synthesis of Sulfides
b
entry
base (equiv)
solvent
time (h)
3a (%)
1
2
3
4
5
6
7
8
K2CO3 (2)
imidazole (2)
t-BuOK (2)
Et3N (2)
Et3N (10)
Et3N (20)
Et3N (20)
Et3N (20)
Et3N (20)
Et3N (20)
Et3N (20)
Et3N (20)
Et3N (20)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
DMSO
EtOH
H2O
THF
DCE
n-hexane
72
72
1
72
12
5
3
3
48
24
24
3
44
0
43
45
70
80
63
29
50
36
38
52
7
9
10
11
12
13
24
a
Reaction conditions: Reactions were performed using 1a (1 equiv)
and 2a (1.2 equiv) and the appropriate base and solvent (5 mL) at 25
°C for the time indicated. All data represent the average of two
b
experiments. Isolated yield.
According to Table 1, the use of 2 equiv of potassium
carbonate gave 3a in 44% yield after a long reaction time
(Table 1, entry 1). One reason for the yield observed in this
case could be attributed to the low solubility of the potassium
carbonate in dichloromethane, making the reaction slower or
less effective. When imidazole was used as base, 3a was not
observed even after 72 h (Table 1, entry 2). The use of a
stronger base such as potassium t-butoxide (2 equiv) led to the
formation of the desired product in 43% yield after only 1 h;
however, 3a was obtained with the corresponding disulfide as a
byproduct in the reaction (Table 1, entry 3). A similar yield
was obtained when triethylamine was used; however, the
reaction required 72 h for completion (Table 1, entry 4).
Higher yields and short reaction times were observed when the
amount of triethylamine was increased (Table 1, entries 5 and
6); the best result was observed when 20 equiv of triethylamine
was used, where the desired product 3a was obtained in 80%
yield after 5 h (Table 1, entry 6).
The influence of other solvents in the reaction yield was also
studied. Shorter reaction times for the formation of 3a were
observed when more polar solvents such as acetonitrile or
dimethyl sulfoxide were used as the reaction solvent (Table 1,
entries 7 and 8), possibly due to the better solubility of the
phosphonium salt 2a in these solvents; however, the yields
were lower when compared to the use of dichloromethane due
to the formation of higher quantities of the corresponding
disulfide. The use of ethanol or water as the reaction solvent
gave 3a in lower yields and required longer reaction times
(Table 1, entries 9 and 10). The use of dichloroethane gave 3a
in 52% yield after 3 h (Table 1, entry 12). Finally, the use of n-
hexane, a less polar solvent, gave 3a in only 7% yield after 24 h
(Table 1, entry 13).
Initially, the reactivity of different benzyltriphenylphospho-
nium halides was investigated. As described before, the use of
benzyltriphenylphosphonium bromide gave sulfide 3a in 80%
yield after 5 h. When benzyltriphenylphosphonium chloride
was used, the desired product 3a was obtained in 74% yield
after 24 h. A similar yield was observed when benzyltriphe-
nylphosphonium iodide was used; however, the reaction
proceeded faster when compared to the chloro derivative
since the desired product was observed after only 5 h. This
result could be attributed to the leaving group character of
halogen atoms in phosphonium salts. As the use of
benzyltriphenylphosphonium bromide led to a better yield,
other bromide phosphonium salts were chosen to expand the
scope of the reaction.
The use of a benzylic phosphonium salt containing the
electron-withdrawing nitro group in the aromatic ring 2b led to
the corresponding sulfide 3b in 65% yield after 0.5 h. A similar
result was observed when a cyano or an ester group was
present in the aromatic ring, where the corresponding sulfides
3c and 3d were obtained in 60% and 53% yield, respectively,
after only 1 h reaction. The presence of halogens such as
fluorine or chlorine atoms in the aromatic ring also led to the
corresponding sulfides 3e and 3f in good yields; however, both
reactions required 4 h.
The reaction is apparently sensitive to steric effects since the
use of a phosphonium salt containing a nitro group at the ortho
position led to the corresponding sulfide 3g in only 31% yield
after 1 h. This effect was further evidenced using a secondary
phosphonium salt where only traces of sulfide 3h were
observed.
When the reaction was carried out using S-phenyl
benzenethiosulfonate, 1b, the corresponding sulfide 3i was
obtained in 55% yield after 7 h, indicating that the method is
general and other thiosulfonates can be applied in the reaction.
On the other hand, when a benzylic phosphonium salt
containing an electron-donating group in the aromatic ring was
used, the corresponding sulfide 3j was not observed even after
Thus, the best conditions for the preparation of the sulfide
3a using S-(p-tolyl) p-toluenethiosulfonate, 1a, and benzyl-
triphenylphosphonium bromide, 2a, were observed when
triethylamine (20 equiv) in dichloromethane was used as the
solvent. These conditions were then applied to other
phosphonium salts, and the results are described in Scheme 1.
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24 h of reaction. The same behavior was observed for
phosphonium salts containing methyl and allyl groups, 2j and
2k, where the corresponding sulfides 3k and 3l were not
observed after a 24 h period.
Scheme 3. Synthesis of Selenides
Phosphonium salts containing electron-withdrawing groups
in the presence of a weak base such as triethylamine led to the
in situ formation of the corresponding stabilized phosphoranes
by deprotonation.21 In order to verify if the use of a
phosphonium salt that could in situ generate a nonstabilized
or reactive ylide could be used in the reaction, an attempt for
the synthesis of sulfide 3k was performed under anhydrous
conditions using methyltriphenylphosphonium bromide, 2k,
and sodium hydride as a base in dry THF at 0 °C. After half an
hour, S-(p-tolyl) p-toluenethiosulfonate, 1a, was then added,
and the reaction was monitored by TLC. Surprisingly, only the
corresponding disulfide 4 was observed as the reaction product
(Scheme 2).
Scheme 2. Reaction under Anhydrous Conditions
Thus, commercially available stabilized phosphoranes and S-
(p-tolyl) p-toluenethiosulfonate, 1a, or p-tolyl phenylselenyl
sulfone, 1c, were reacted under the standardized conditions.
Surprisingly, in most cases, new phosphoranes were obtained
as the reaction products (Scheme 4). The new thio- or
selenophosphoranes were obtained in similar yields; however,
the reaction was slightly faster for the synthesis of
selenophosphoranes.
In this way, under the conditions studied, the reaction led to
the corresponding sulfides only when benzylic phosphonium
salts that could generate stabilized or semistabilized phosphor-
anes were used.
Scheme 4. Synthesis of Thio- and Selenophosphoranes
The strategy was also extended for the synthesis of selenides.
In this case, p-tolyl phenylselenyl sulfone 1c, prepared
according to a literature procedure,22 was submitted to the
optimized conditions previously described. The corresponding
selenides 5a−g were obtained in lower yields when compared
to sulfides but in a shorter reaction time in all cases.
The use of a benzyltriphenylphosphonium bromide, 2a, gave
the corresponding selenide 5a in 60% yield after 0.5 h. Again,
the reaction was faster for phosphonium salts containing
electron-withdrawing groups in the aromatic ring. Selenide 5b
was obtained in 85% yield after only 0.1 h. When the cyano or
the ester group was present in the aromatic ring, the
corresponding selenides 5c and 5d were obtained in low
yields after 0.5 h. The use of phosphonium salts containing
halogens in the aromatic rings gave 5e and 5f in 15% and 34%
yield, respectively. The use of a phosphonium salt containing a
nitro group at the ortho position gave selenide 5g in 30% yield
after 0.5 h (Scheme 3). The observed lower yields can be
attributed to the high reactivity of p-tolyl phenylselenyl
sulfone, 1c, to form the respective diselenide, obtained as a
byproduct.
These experiments demonstrated that thio- or selenesulfo-
nates can be used as convenient precursors of both sulfides and
selenides but not of tellurides since an efficient method for the
synthesis of tellurosulfonates has not been described so far.23
Next, our attention was focused on the use of stabilized
phosphoranes, 6, rather than benzylic phosphonium salts in the
reaction. Generally, such compounds can be described as an
ylene or an ylide, two resonant structures, with the ylide
structure being the major contributor.24a This was later
confirmed by NMR studies24b (Scheme 1). Some authors,
however, describe ylides as phosphine-stabilized carbenes.25
Thiophosphoranes are versatile compounds and can be used,
for example, as ligands in coordination chemistry26 and in the
synthesis of alkynes.27 Selenophosphoranes were described to
be inert in Wittig-type reactions with carbonyl compounds.28
However, a latter report described the use of such compounds
for the stereoselective synthesis of vinylic selenides under
microwave irradiation.29
The only exception occurred when the reaction was
performed using a stabilized phosphorane derived from
Weinreb amide and 1a or 1c, where the corresponding
phosphoranes were not observed. In this case, only the
corresponding sulfide 3m or selenide 5h was obtained as the
reaction product in a similar yield as when phosphonium salts
were used (Scheme 5).
When the reactions are compared, it is clear that the nature
of the group present in the phosphonium salt or phosphorane
is important, since more or less stabilized carbanions can be
obtained and can lead to different products in the reaction.
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respectively. The presence of halogen atoms in the aromatic
rings also gave the corresponding phosphoranes 7h and 7i in
good yields.
Scheme 5. Use of Weinreb Amide Phosphorane
When the reaction was performed using p-tolyl phenyl-
selenyl sulfone, 1c, the corresponding phosphoranes 7j−n
were also obtained in good yields and in a shorter reaction
time when compared to the sulfur counterpart in all cases,
indicating the method is general for the synthesis of thio- and
selenophosphoranes.
In an attempt to explain this difference in reactivity, an
experiment using the phosphonium salt (cyanomethyl)-
triphenylphosphonium bromide, 2m, and its corresponding
phosphorane (triphenylphosphoranylidene)acetonitrile, 6b,
were performed. When the reaction was carried out with 1a
and phosphonium salt 2m using triethylamine (20 equiv) as a
base in dichloromethane, the resulting phosphorane 7b was
obtained as the sole product in 80% yield after 1 h. On the
other hand, when 1a and phosphorane 6b were used under the
same conditions, the desired product 7b was obtained in 60%
yield after 30 min (Scheme 7).
The reactivity of a phosphorane is related to its nucleophilic
character; consequently, the presence of an electron-with-
drawing group in its structure would increase its stability.30a It
is also possible to estimate the reactivity of a phosphorane
from the corresponding phosphonium salt pKa. Thus, the more
acidic the α-H in the phosphonium salt, the less reactive is the
phosphorane. This effect is attributed to the resonance
delocalization of the negative charge into the available 3d
vacant orbitals of phosphorus as well as to the Coulombic
effects of the positive charge on the phosphorus atom.30b
In this way, the reaction of 1a or 1c with phosphonium salts
that could generate highly stabilized phosphoranes would lead
to new thio- and selenophosphoranes. This fact was evidenced
by the use of phosphonium salts derived from substituted
acetophenones where in all cases the corresponding new
phosphoranes were obtained in good yields (Scheme 6).
Scheme 7. Competitive Experiments
Scheme 6. Synthesis of New Phosphoranes from
Phosphonium Salts Derived from Substituted
Acetophenones
Mechanistically, this result suggests that the phosphonium
salt 2m would initially lead to phosphorane 6b and its
subsequent reaction with 1a would lead to the desired product
7b. The presence of the base is somewhat important since
when the reaction was performed using 1a and 6b without
triethylamine; only the starting materials were recovered after
1 h (Scheme 7).
For a better understanding of the operating mechanism, the
progress of the reaction of 1a and phosphonium salt 2m was
monitored by 31P NMR in CDCl3 at different periods. At the
beginning of the reaction, 31P NMR shows only a singlet at δ =
21.5 attributed to phosphonium salt 2m (see the Supporting
Information). When treated with triethylamine, the disappear-
ance of this signal along with the appearance of two new
signals at δ = 23.2, attributed to the phosphorane 6b, and at δ
= 26, attributed to the phosphorane 7b, were immediately
observed. After 1 h, the complete disappearance of the signal at
δ = 23.2 attributed to 6b and an intense signal at δ = 26
attributed to 7b together with a small amount of
triphenylphosphine oxide could be observed.
The monitoring of the reaction using the phosphorane
derived from Weinreb amide, 6c, which led exclusively to the
formation of the corresponding selenide or sulfide, was also
carried out through 31P NMR. The phosphorane 6c appeared
as a singlet at δ 18, which completely disappeared after the
addition of triethylamine and thiosulfonate, 1a, with the
appearance of a new signal at δ 27.8, attributed to the
formation of a new phosphorus species, probably the Ph3P-
SO2p-Tol complex.
In an attempt to verify the formation of this complex, a
parallel experiment was carried out where sodium p-toluene-
sulfinate was added to an NMR tube containing a solution of
PPh3 in dichloromethane and the reaction was monitored by
According to Scheme 6, when the reaction was performed
using phenacyltriphenylphosphonium bromide and S-(p-tolyl)
p-toluenethiosulfonate, 1a, the new phosphorane 7e was
obtained in 86% yield after 4 h. The reaction does not appear
to be affected by electronic effects, since the use of
acetophenone-derived substrates containing electron-donating
or electron-withdrawing groups in the aromatic ring led to the
corresponding phosphoranes 7f and 7g in 95% and 97%,
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31P NMR. The NMR spectrum showed a signal at δ −5.7,
attributed to PPh3, and the appearance of a signal at δ 26,
attributed to the formation of Ph3P-SO2p-Tol complex. In
order to confirm the formation of such a complex, part of the
content of this tube was added to the content of the previous
reaction involving 6c where an increase in the value of the
integral for the signal at δ 26 was observed.
In conclusion, a new strategy for the synthesis of selenides
and sulfides based on the use of commercially available
phosphonium salts and thio- and selenosulfonates under basic
conditions was described. Using this strategy, the correspond-
ing sulfides and selenides were obtained in moderate to good
yields when benzylic phosphonium salts containing electron-
withdrawing groups were used. When stabilized phosphoranes
were used under the same reaction conditions, new thio- and
selenophosphoranes were obtained in moderate to good yields.
The method is simple, fast, and general, allowing further
applications in the synthesis of more complex compounds.
From these observations, a mechanistic proposal is shown in
Scheme 8. The reaction of phosphonium salt or phoshorane
Scheme 8. Plausible Reaction Mechanism
EXPERIMENTAL SECTION
■
General Information. All reagents and solvents used were
previously purified and dried in agreement with the literature.33
Sodium p-toluenesulfinate was purchased from Aldrich Chemical Co.
and was dried in vacuo at 60 °C before use. Reactions were monitored
by thin-layer chromatography on 0.25 mm E. Merck silica gel 60
plates (F254) using UV light, vanillin, and p-anisaldehyde as
visualizing agents. The GC/FID analysis was performed on a Varian
CP-3380 gas chromatograph system coupled with a flame ionization
detector. The chromatographic column was a Chrompack CP-
SPL5CB capillary column (30 m × 0.25 mm, 0.25 μm) using the
initial temperature of 60 °C, which was then increased to 220 °C at 10
°C min−1. 1H and 13C{1H} NMR data were recorded in CDCl3. The
chemical shifts are reported as delta (δ) units in parts per million
(ppm) relative to the solvent residual peak as the internal reference [δ
7.26 (1H NMR) and δ 77.16 (13C{1H} NMR)]. 77Se NMR (57 MHz)
and 31P NMR (121 MHz) spectra were also obtained in CDCl3.
Spectra were calibrated using diphenyl diselenide (δ 463.0) as
external reference in the case of 77Se NMR, and chemical shifts were
referenced to external H3PO4 (δ 0.0) in the case of 31P NMR.
Coupling constants (J) for all spectra are reported in Hertz (Hz).
HRMS analyses were performed on a micrOTOF-QII mass
spectrometer equipped with an Apollo II electrospray ion source
(Bruker, Billerica, USA) coupled to a UFLC Prominence binary liquid
chromatograph (Shimadzu, Kyoto, Japan). Samples were stored into
the SIL-30AC autosampler at 15 °C prior to analysis. The direct
injection (without column) of 1 μL of each sample was carried to the
analyzer by a 10 mmol/L ammonium formate (Sigma-Aldrich, St
Louis, USA) solution in methanol/water (1:1, v/v) at a flow rate of
200 μL/min. The HRMS data were acquired with the ESI source set
as follows: nebulizer gas at 2.0 bar, dry gas at 6.0 L/min, dry
temperature at 200 °C, and voltage at 4.0 kV. The mass/charge ratios
were scanned (m/z 50−800 Da) in positive ion mode (ESI+).
Sodium formate clusters in isopropyl alcohol within the m/z 50−800
Da range were used as the calibration standard.
and the thio- or selenesulfonate in the presence of triethyl-
amine would initially lead to the formation of the intermediary
8. When electron-withdrawing groups are present in the
structure, the subsequent abstraction of the acidic α-hydrogen
by the base would lead to the formation of the corresponding
phosphorane 7 (Scheme 8, path b). On the other hand, when
the benzyl group was present, the acidity of the α-hydrogen
would be reduced; therefore, the sulfonyl anion would attack
the phosphorus atom for the formation of the complex 9,
which was the driving force of the formation of a strong P−O
bond in the byproduct.31 The subsequent departure of the
sulfonyl-phosphonium species followed by protonation would
lead to the corresponding benzylic sulfides or selenides 3 or 5
(Scheme 8, path b).
Since the corresponding sulfides and selenides were not
obtained in some cases, an attempt for the conversion of
phosphorane 7b into the corresponding sulfide 3n was
performed using boron trifluoride diethyl etherate in THF
under reflux for 2 h.32 Using this strategy, the corresponding
sulfide 3n was obtained in 77% yield (Scheme 9).
General Procedures for the Preparation of Starting
Materials. Synthesis of S-(p-Tolyl) p-Toluenethiosulfonate (1a).
To a 50 mL flask containing sodium p-toluenesulfinate (1.0 equiv, 5.6
mmol, 1.0 g) [previously dried under vacuum for 1 h at 100 °C] and
CuI (0.25 equiv, 1.4 mmol, 265 mg) was added CH2Cl2 (15 mL)
followed by H2SO4 (7.5 equiv, 42 mmol, 4.12 g, 2.25 mL). The
mixture was stirred for 13 min and then quenched with a NaHCO3
saturated solution. The mixture was diluted with CH2Cl2 (20 mL),
transferred to a separation funnel, and then washed with water (2 ×
20 mL). The organic phase was separated, dried over anhydrous
Na2SO4, and filtrated. The solvent was removed in vacuo. The crude
compound was crystallized in hot hexanes to yield 600 mg (77%) of
1
the title compound as a white solid. H NMR (300 MHz, CDCl3) δ
7.49 (d, J = 9 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.24 (d, J = 9 Hz, 2H),
7.17 (d, J = 9 Hz, 2H), 2.45 (s, 3H), 2.41 (s, 3H); 13C{1H} NMR (75
MHz, CDCl3) δ 144.6, 142.0, 140.4, 136.5, 130.2, 129.3, 127.6, 124.6,
21.6, 21.5. The data match with the previously described
compound.20
Scheme 9. Synthesis of Sulfides from Thiophosphoranes
Synthesis of S-Phenyl Benzenesulfonothioate (1b). To a 50 mL
flask containing sodium benzenesulfinate (1.0 equiv, 5.6 mmol, 920
mg) [previously dried under vacuum for 1 h at 100 °C] and CuI (0.25
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equiv, 1.4 mmol, 265 mg) was added CH2Cl2 (15 mL) followed by
H2SO4 (7.5 equiv, 42 mmol, 4.12 g, 2.25 mL). The mixture was
stirred for 13 min and then quenched with a NaHCO3 saturated
solution. The mixture was diluted with CH2Cl2 (20 mL), transferred
to a separation funnel, and then washed with water (2 × 20 mL). The
organic phase was separated, dried over anhydrous Na2SO4, and
filtrated. The solvent was removed in vacuo. The crude compound was
crystallized in hot hexanes to yield 420 mg (60%) of the title
NMR (400 MHz, CDCl3) δ 7.20−7.17 (m, 4H), 7.05 (dt, J = 8, 0.7
Hz, 2H), 6.93 (t, J = 8 Hz, 2H), 4.01 (s, 2H), 2.30 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.8 (d, J = 240 Hz), 136.8, 133.5 (d, J
= 3 Hz), 130.9, 130.3 (d, J = 8 Hz), 129.6, 115.1 (d, J = 21 Hz), 39.0,
21.0; 19F NMR (376 MHz, CDCl3) δ −115.53 The data match with
the previously described compound.38
(4-Chlorobenzyl)(p-tolyl)sulfane (3f). 67 mg (75%) of 3f was
obtained was as a white solid after column chromatography [hexanes].
1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8 Hz, 2H), 7.19 (d, J = 8
Hz, 2H), 7.16 (d, J = 8 Hz, 2H), 7.07 (d, J = 8 Hz, 2H), 4.01 (s, 2H),
2.32 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 136.9, 136.4,
132.8, 131.7, 131.1, 130.1, 129.7, 128.5, 39.2, 21.0. The data match
with the previously described compound.38
1
compound as a white solid. H NMR (400 MHz, CDCl3) δ 7.61−
7.52 (m, 3H), 7.49−7.38 (m, 3H), 7.37−7.29 (m, 4H); 13C{1H}
NMR (100 MHz, CDCl3) δ 142.8, 136.5, 133.6, 131.4, 129.4, 128.7,
127.7, 127.4. The data match with the previously described
compound.20
Synthesis of p-Tolyl Phenylselenyl Sulfone (1c). To a 50 mL flask
containing sodium p-toluenesulfinate (4.0 equiv, 6.4 mmol, 1.15 g),
diphenyl diselenide (1.0 equiv, 1.6 mmol, 500 mg), and N-
bromosuccinimide (2.0 equiv, 3.2 mmol, 570 mg) was added
MeCN (20 mL). The reaction was monitored by TLC, and after 2
h, it was diluted with EtOAc (20 mL), transferred to a separation
funnel, and then washed with water (2 × 20 mL). The organic phase
was separated, dried over anhydrous Na2SO4, and filtrated. The
solvent was removed in vacuo. The crude compound was purified by
column chromatography [hexanes/EtOAc (9:1)] to yield 550 mg
(2-Nitrobenzyl)(p-tolyl)sulfane (3g). 29 mg (31%) of 3g was
obtained as a yellow oil after column chromatography [hexanes]. H
1
NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8 Hz, 1H), 7.40 (m, 2H),
7.21 (d, J = 8 Hz, 1H), 7.17 (d, J = 8 Hz, 2H), 7.17 (d, J = 8 Hz, 2H),
7.05 (d, J = 8 Hz, 2H), 4.38 (s, 2H), 2.31 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ137.7, 133.8, 132.9, 132.5, 131.9, 130.8, 129.7,
128.1, 125.2, 37.8, 21.1. HRMS (ESI) m/z: [M + H]+ Calcd for
C14H14NO2S+ 260.0740; Found 260.0756.
Benzyl(phenyl)sulfane (3i). 44 mg (55%) of 3i was obtained as a
1
white solid after column chromatography [hexanes]. H NMR (400
1
MHz, CDCl3) δ 7.31−7.14 (m, 10H), 4.10 (s, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 137.5, 136.4, 129.8, 128.9, 128.8, 128.5, 127.2,
126.4, 137.5, 136.4, 129.8, 128.9, 128.8, 128.5, 127.2, 126.4, 39.0. The
data match with the previously described compound.39
(55%) of the title compound as a yellow solid. H NMR (400 MHz,
CDCl3) δ 7.52−7.32 (m, 7H), 7.18 (d, J = 8 Hz, 2H), 2.41 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 144.5, 142.7, 137.2, 130.8,
129.5, 129.2, 128.0, 127.0, 21.6; 77Se NMR (76 MHz, CDCl3) δ
970.4. The data match with the previously described compound.22,34
General Procedure for the Synthesis of Sulfides (3a−m). To
a 25 mL flask containing 1a (1.0 equiv, 0.36 mmol, 100 mg) and the
appropriate phosphonium salt (1.2 equiv, 0.432 mmol) was added
CH2Cl2 (5.0 mL). The mixture was stirred until a solution was
observed (approximately 5 min); then, Et3N (20.0 equiv, 7.2 mmol,
1.0 mL) was added. The reaction was monitored by TLC and, after
consumption of the starting material, diluted with CH2Cl2 (20 mL),
transferred to a separation funnel, and then washed with a NH4Cl
saturated solution (2 × 20 mL). The organic phase was separated,
dried over anhydrous Na2SO4, and filtrated. The solvent was removed
in vacuo. The crude compound was purified by column chromatog-
raphy.
N-Methoxy-N-methyl-2-(p-tolylthio)acetamide (3m). 77 mg
(95%) of 3m was obtained as a white solid after column
chromatography [hexanes/EtOAc (7:3)]. 1H NMR (300 MHz,
CDCl3) δ 7.30 (d, J = 9 Hz, 2H), 7.03 (d, J = 9 Hz, 2H), 3.70 (s,
2H), 3.62 (s, 3H), 3.12 (s, 3H), 2.24 (s, 3H); 13C{1H} NMR (75
MHz, CDCl3) δ 169.4, 136.1, 130.8, 129.9, 128.8, 60.5, 35.1, 31.5,
20.0. HRMS (ESI) m/z: [M + H]+ Calcd for C11H16NO2S+ 226.0896;
Found 226.0893.
General Procedure for the Synthesis of Selenides (5a−h).
To a 25 mL flask containing 1b (1.0 equiv, 0.32 mmol, 100 mg) and
the appropriate phosphonium salt (1.2 equiv, 0.384 mmol) was added
CH2Cl2 (5.0 mL). The mixture was stirred until a solution was
observed (approximately 5 min); then, Et3N (20.0 equiv, 6.4 mmol,
0.9 mL) was added. The reaction was monitored by TLC and, after
consumption of the starting material, diluted with CH2Cl2 (20 mL),
transferred to a separation funnel, and then washed with a NH4Cl
saturated solution (2 × 20 mL). The organic phase was separated,
dried over anhydrous Na2SO4, and filtrated. The solvent was removed
in vacuo. The crude compounds were purified by column
chromatography.
Benzyl(p-tolyl)sulfane (3a). 61 mg (80%) of 3a was obtained as a
1
white solid after column chromatography [hexanes]. H NMR (300
MHz, CDCl3) δ 7.27−7.23 (m, 5H), 7.21 (d, J = 9 Hz, 2H), 7.06 (d, J
= 9 Hz, 2H), 4.06 (s, 2H), 2.30 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3) δ 137.8, 136.5, 132.4, 130.7, 129.6, 128.8, 128.4, 127.0, 39.8,
21.0. The data match with the previously described compound.35
(4-Nitrobenzyl)(p-tolyl)sulfane (3b). 60 mg (65%) of 3b was
obtained as a yellow solid after column chromatography [hexanes/
EtOAc (8:2)]. 1H NMR (300 MHz, CDCl3) δ 8.09 (d, J = 8 Hz, 2H),
7.33 (d, J = 8 Hz, 2H), 7.17 (d, J = 8 Hz, 2H), 7.05 (d, J = 8 Hz, 2H),
4.07 (s, 2H), 2.30 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 146.9,
145.8, 137.6, 131.7, 130.6, 129.8, 129.5, 123.5, 39.5, 21.0. The data
match with the previously described compound.36
4-((p-Tolylthio)methyl)benzonitrile (3c). 52 mg (60%) of 3c was
obtained as white solid after column chromatography [hexanes/
EtOAc (8:2)]. 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8 Hz, 2H),
7.20 (d, J = 8 Hz, 2H), 7.17 (d, J = 8 Hz, 2H), 6.97 (d, J = 8 Hz, 2H),
3.95 (s, 2H), 2.22 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
143.6, 137.4, 132.1, 131.6, 130.7, 129.7, 129.4, 118.7, 110.7, 39.7,
21.0. The data match with the previously described compound.37
Methyl 4-((p-Tolylthio)methyl)benzoate (3d). 52 mg (53%) of 3d
was obtained as a white solid after column chromatography [hexanes].
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8 Hz, 2H), 7.28 (d, J = 8
Hz, 2H), 7.17 (d, J = 8 Hz, 2H), 7.05 (d, J = 8 Hz, 2H), 4.06 (s, 2H),
3.90 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
166.9, 143.3, 137.1, 131.5, 131.4, 129.8, 129.7, 128.9, 128.8, 52.0,
39.8, 21.0. The data match with the previously described
compound.37
Benzyl(phenyl)selane (5a). 47 mg (60%) of 5a was obtained as a
1
dark yellow/orange oil after column chromatography [hexanes]. H
NMR (300 MHz, CDCl3) δ 7.48−7.44 (m, 2H), 7.27−7.18 (m, 8H),
4.12 (s, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 138.6, 133.5, 130.4,
128.9, 128.8, 128.4, 127.2, 126.8, 32.2; 77Se NMR (57 MHz, CDCl3)
δ 369.7. The data match with the previously described compound.40
(4-Nitrobenzyl)(phenyl)selane (5b). 79 mg (85%) of 5b was
obtained as a yellow solid after column chromatography [hexanes/
EtOAc (95:5)]. 1H NMR (300 MHz, CDCl3) 8.05 (d, J = 8 Hz, 2H),
7.40 (d, J = 8 Hz, 2H), 7.30−7.19 (m, 5H), 4.08 (s, 2H); 13C{1H}
NMR (75 MHz, CDCl3) 148.9, 146.8, 134.9, 134.4, 129.4, 129.1,
128.1, 123.5, 31.3; 77Se NMR (57 MHz, CDCl3) δ 398.0. The data
match with the previously described compound.41
4-((Phenylselanyl)methyl)benzonitrile (5c). 9 mg (10%) of 5c was
obtained as a yellow solid after column chromatography [hexanes/
EtOAc (95:5)]. 1H NMR (400 MHz, CDCl3) 7.49 (d, J = 8 Hz, 2H),
7.39 (d, J = 8 Hz, 2H), 7.30−7.18 (m, 5H), 4.05 (s, 2H); 13C{1H}
NMR (100 MHz, CDCl3) 144.7, 135.0, 134.4, 132.1, 129.4, 129.1,
129.0, 128.0, 118.8, 110.4, 31.7; 77Se NMR (76 MHz, CDCl3) δ
398.5. The data match with the previously described compound.42
Methyl 4-((Phenylselanyl)methyl)benzoate (5d). 12 mg (12%) of
5d was obtained was as a yellow liquid after column chromatography
[hexanes/EtOAc (95:5)]. 1H NMR (400 MHz, CDCl3) 7.89 (d, J = 8
(4-Fluorobenzyl)(p-tolyl)sulfane (3e). 64 mg (76%) of 3e was
obtained as a white solid after column chromatography [hexanes]. 1H
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Note
Hz 2H), 7.43−7.40 (m, 2H), 7.27−7.23 (m, 3H), 7.20 (d, J = 8 Hz,
2H), 4.09 (s, 2H), 3.89 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
166.9, 144.3, 137.0, 134.1, 131.5, 129.7, 129.0, 128.8, 127.7, 52.0,
31.9; 77Se NMR (77 MHz, CDCl3) δ 388.9. The data match with the
previously described compound.43
Hz, 2H), 6.91 (d, J = 8.2 Hz, 2H), 2.25 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 138.4, 134.6, 133.6 (d, J = 9.7 Hz), 132.9 (d, J = 2.4
Hz), 128.9 (d, J = 12.2 Hz), 126.1, 124.8 (d, J = 91.5 Hz), 20.9; 31P
NMR (162 MHz, CDCl3) δ 25.8. HRMS (ESI) m/z: [M + H]+ Calcd
for C27H23NPS+ 424.1283; Found 424.1285.
1-Phenyl-2-(p-tolylthio)-2-(triphenylphosphaneylidene)ethan-1-
one (7e). 156 mg (86%) of 7e was obtained as a white solid after
column chromatography [hexanes/EtOAc (7:3)]. 1H NMR (400
MHz, CDCl3) δ 7.82 (dd, J = 7.9, 1.7 Hz, 2H), 7.60 (ddd, J = 12.2,
8.3, 1.3 Hz, 6H), 7.51 (dd, J = 7.5, 1.8 Hz, 3H), 7.40 (ddd, J = 8.7,
5.4, 2.4 Hz, 6H), 7.33−7.24 (m, 3H), 7.08 (d, J = 8.2 Hz, 2H), 6.95
(d, J = 8.0 Hz, 2H), 2.26 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 192.2 (d, J = 14.0 Hz), 140.7 (d, J = 10.9 Hz), 140.5 (d, J = 2.2 Hz),
133.8, 133.7 (d, J = 9.4 Hz), 131.7 (d, J = 3.0 Hz), 129.1, 129.0, 128.3
(d, J = 12.1 Hz), 128.1, 127.3, 126.6 (d, J = 90.0 Hz), 124.8, 57.4 (d, J
= 101.4 Hz), 20.8; 31P NMR (162 MHz, CDCl3) δ 26.2. HRMS
(ESI) m/z: [M + H]+ Calcd for C33H28OPS+ 503.1593; Found
503.1604.
1-(4-Methoxyphenyl)-2-(p-tolylthio)-2-(triphenylphosphaneyl-
idene)ethan-1-one (7f). 186 mg (97%) of 7f was obtained as a white
solid after column chromatography [hexanes/EtOAc (7:3)]. 1H NMR
(400 MHz, CDCl3) δ 0.87 (d, J = 8.8 Hz, 2H), 7.57 (ddd, J = 12.1,
8.4, 1.3 Hz, 6H), 7.48 (td, J = 7.4, 1.8 Hz, 3H), 7.37 (td, J = 7.7, 3.0
Hz, 6H), 7.08 (d, J = 8.2 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H), 6.78 (d, J
= 8.9 Hz, 2H), 3.76 (s, 3H), 2.25 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 190.9 (d, J = 13.6 Hz), 160.5, 140.6 (d, J = 2.0 Hz), 133.8,
133.6 (d, J = 9.3 Hz), 132.9 (d, J = 10.9 Hz), 131.6 (d, J = 2.7 Hz),
130.1, 129.0, 128.3 (d, J = 12.0 Hz), 126.9 (d, J = 90.1 Hz), 124.8,
112.6, 56.6 (d, J = 103.0 Hz), 55.2, 20.8; 31P NMR (162 MHz,
CDCl3) δ 26.0. HRMS (ESI) m/z: [M + H]+ Calcd for C34H30O2PS+
533.1699; Found 533.1707.
1-(4-Nitrophenyl)-2-(p-tolylthio)-2-(triphenylphosphaneylidene)-
ethan-1-one (7g). 187 mg (95%) of 7g was obtained as an orange
solid after column chromatography [hexanes/EtOAc (7:3)]. 1H NMR
(400 MHz, CDCl3) δ 8.11 (d, J = 8.9 Hz, 2H), 7.83 (d, J = 8.8 Hz,
2H), 7.64−7.52 (m, 9H), 7.47−7.38 (m, 6H), 7.00 (d, J = 8.3 Hz,
2H), 6.94 (d, J = 8.1 Hz, 2H), 2.25 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 190.3 (d, J = 15.1 Hz), 147.8, 147.7 (d, J = 11.2 Hz),
139.5 (d, J = 2.0 Hz), 134.3, 133.7 (d, J = 9.5 Hz), 132.2 (d, J = 2.8
Hz), 129.3, 128.8, 128.6 (d, J = 12.2 Hz), 125.6 (d, J = 90.3 Hz),
124.6, 122.7, 59.0 (d, J = 99.9 Hz), 20.8; 31P NMR (162 MHz,
CDCl3) δ 26.3. HRMS (ESI) m/z: [M + H]+ Calcd for
C33H27NO3PS+ 548.1444; Found 548.1453.
(4-Fluorobenzyl)(phenyl)selane (5e). 13 mg (15%) of 5e was
obtained as a yellow liquid after column chromatography [hexanes/
1
EtOAc (95:5)]. H NMR (400 MHz, CDCl3) 7.46−7.39 (m, 2H),
7.31−7.20 (m, 3H), 7.13 (dd, J = 8.7, 5.3 Hz, 2H), 6.91 (t, J = 8.7 Hz,
2H), 4.06 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) 161.7 (d, J =
245.3 Hz), 134.4 (d, J = 3.1 Hz), 133.8, 130.3 (d, J = 8.0 Hz), 129.9,
129.0, 127.5, 115.2 (d, J = 21.5 Hz), 31.4; 77Se NMR (76 MHz,
CDCl3) δ 380.3. The data match with the previously described
compound.44
(4-Chlorobenzyl)(phenyl)selane (5f). 31 mg (34%) of 5f was
obtained as a light yellow solid after column chromatography
1
[hexanes/EtOAc (95:5)]. H NMR (400 MHz, CDCl3) 7.44−7.41
(m, 2H), 7.26−7.23 (m, 3H), 7.19 (d, J = 8 Hz, 2H), 7.09 (d, J = 8
Hz, 2H), 4.03 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) 137.3,
133.9, 132.6, 130.1, 129.0, 128.5, 127.6, 31.4; 77Se NMR (77 MHz,
CDCl3) δ 383.2. The data match with the previously described
compound.42
(2-Nitrobenzyl)(phenyl)selane (5g). 28 mg (30%) of 5g was
obtained as a yellow liquid after column chromatography [hexanes/
EtOAc (95:5)]. 1H NMR (400 MHz, CDCl3) 8.01 (dd, J1 = 8 Hz, J2
= 1.8 Hz, 1H), 7.44−7.21 (m, 7H), 7.00 (dd, J1 = 8 Hz, J2 = 1.8 Hz,
1H), 4.36 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) 135.4, 135.2,
133.0, 131.9, 129.0, 128.1, 127.8, 125.5, 29.8; 77Se NMR (76 MHz,
CDCl3) δ 404.0. The data match with the previously described
compound.45
N-Methoxy-N-methyl-2-(phenylselanyl)acetamide (5h). 57 mg
(70%) of 5h was obtained as a yellow oil after column
chromatography [hexanes/EtOAc (8:2)]. 1H NMR (300 MHz,
CDCl3) δ 7.56−7.51 (m 2H), 7.23−7.18 (m, 3H), 3.65 (s, 2H),
3.59 (s, 3H), 3.11 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 170.4,
132.3, 130.5, 128.9, 128.1, 126.6, 60.3, 31.6, 25.7; 77Se NMR (57
MHz, CDCl3) δ 316.2. HRMS (ESI) m/z: [M + H]+ Calcd for
C10H14NO2Se+ 260.0184; Found 260.0186.
General Procedure for the Synthesis of Phosphoranes.
Synthesis of Thiophosphoranes (7a−b, 7e−i). To a 25 mL flask
containing 1a (1.0 equiv, 0.36 mmol, 100 mg) and the appropriate
phosphorus ylene (1.2 equiv, 0.432 mmol) was added CH2Cl2 (5.0
mL). The mixture was stirred until a solution was observed
(approximately 5 min); then, Et3N (20.0 equiv, 7.2 mmol, 1.0 mL)
was added. The reaction was monitored by TLC and, after
consumption of the starting material, diluted with CH2Cl2 (20 mL),
transferred to a separation funnel, and then washed with a NH4Cl
saturated solution (2 × 20 mL). The organic phase was separated,
dried over anhydrous Na2SO4, and filtrated. The solvent was removed
in vacuo. The crude compounds were purified by column
chromatography.
1-(4-Bromophenyl)-2-(p-tolylthio)-2-(triphenylphosphaneyl-
idene)ethan-1-one (7h). 195 mg (93%) of 7h was obtained as a pale
yellow solid after column chromatography [hexanes/EtOAc (7:3)].
1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.5 Hz, 2H), 7.62−7.53
(m, 6H), 7.50 (td, J = 7.3, 1.6 Hz, 3H), 7.38 (td, J = 8.0, 2.4 Hz, 8H),
7.03 (d, J = 8.2 Hz, 2H), 6.92 (d, J = 8.1 Hz, 2H), 2.24 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 190.9 (d, J = 14.2 Hz), 140.0 (d,
J = 2.2 Hz), 139.6 (d, J = 11.1 Hz), 134.0, 133.6 (d, J = 9.4 Hz), 131.8
(d, J = 3.0 Hz), 130.4, 129.8, 129.1, 128.4 (d, J = 12.1 Hz), 126.2 (d, J
= 90.2 Hz), 124.6, 123.3, 57.6 (d, J = 101.4 Hz), 20.8; 31P NMR (162
MHz, CDCl3) δ 26.4. HRMS (ESI) m/z: [M + H]+ Calcd for
C33H27BrOPS+ 581.0698; Found 581.0694.
1-(p-Tolylthio)-1-(triphenylphosphoraneylidene)propan-2-one
(7a). 126 mg (80%) of 7a was obtained as a pale yellow solid after
column chromatography [hexanes/EtOAc (7:3)]. 1H NMR (400
MHz, CDCl3) δ 7.47−7.39 (m, 9H), 7.33−7.27 (m, 6H), 6.97 (d, J =
8 Hz, 2H), 6.87 (d, J = 8 Hz, 2H), 2.27 (s, 3H), 2.17 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 196.8 (d, J = 14.1 Hz), 140.1,
133.7, 133.6 (d, J = 9.5 Hz), 131.7 (d, J = 2.5 Hz), 129.0, 128.2 (d, J =
12.1 Hz), 126.7 (d, J = 90.0 Hz), 124.5, 55.9 (d, J = 103.6 Hz), 25.5
(d, J = 7.6 Hz), 20.7; 31P NMR (162 MHz, CDCl3) δ 25.6. HRMS
(ESI) m/z: [M + H]+ Calcd for C28H26OPS+ 441.1436; Found
441.1441.
When the reaction was carried out on a larger scale by employing
1a (2.9 mmol, 800 mg) and the phosphorus ylene 6a (3.5 mmol, 1.12
g) in CH2Cl2 (40 mL) using Et3N (58 mmol, 8 mL), the indicated
product (7a) was obtained in 70% yield (900 mg).
2-(p-Tolylthio)-2-(triphenylphosphaneylidene)acetonitrile (7b).
91 mg (60%) of 7b was obtained as a white solid after column
chromatography [hexanes/EtOAc (7:3)]. 1H NMR (400 MHz,
CDCl3) δ 7.65−7.55 (m, 9H), 7.49−7.43 (m, 6H), 7.12 (d, J = 8.1
1-(4-Fluorphenyl)-2-(p-tolylthio)-2-(triphenylphosphaneylidene)-
ethan-1-one (7i). 180 mg (96%) of 7i was obtained as a pale yellow
solid after column chromatography [hexanes/EtOAc (7:3)]. 1H NMR
(400 MHz, CDCl3) δ 7.78 (dd, J = 8.7, 5.7 Hz, 2H), 7.52 (ddd, J =
12.1, 8.3, 1.3 Hz, 6H), 7.45 (dd, J = 7.6, 1.8 Hz, 3H), 7.34 (td, J = 7.6,
3.1 Hz, 6H), 7.00 (d, J = 8.2 Hz, 2H), 6.92−6.84 (m, 4H), 2.20 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 190.7 (d, J = 14.1 Hz),
163.2 (d, J = 247.9 Hz), 140.1 (d, J = 2.2 Hz), 136.7 (dd, J = 11.1, 3.0
Hz), 133.9, 133.6 (d, J = 9.5 Hz), 131.7 (d, J = 2.9 Hz), 130.3 (d, J =
8.3 Hz), 129.0, 128.3 (d, J = 12.1 Hz), 126.4 (d, J = 90.1 Hz), 124.6,
114.0 (d, J = 21.2 Hz), 57.2 (d, J = 101.9 Hz), 20.7; 31P NMR (162
MHz, CDCl3) δ 26.3. 19F NMR (376 MHz, CDCl3) δ −112.07 (t, J =
8.0 Hz). HRMS (ESI) m/z: [M + H]+ Calcd for C33H27FOPS+
521.1499; Found 521.1510.
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Synthesis of Selenophosphoranes (7c,d, 7j−n). To a 25 mL flask
containing 1c (1.0 equiv, 0.32 mmol, 100 mg) and the appropriate
phosphorus ylene (1.2 equiv, 0.384 mmol) was added CH2Cl2 (5.0
mL). The mixture was stirred until a solution was observed
(approximately 5 min); then, Et3N (20.0 equiv, 6.4 mmol, 0.9 mL)
was added. The reaction was monitored by TLC and, after
consumption of the starting material, diluted with CH2Cl2 (20 mL),
transferred to a separation funnel, and then washed with a NH4Cl
saturated solution (2 × 20 mL). The organic phase was separated,
dried over anhydrous Na2SO4, and filtrated. The solvent was removed
in vacuo. The crude compounds were purified by column
chromatography.
1-(Phenylselanyl)-1-(triphenylphosphoranylidene)propan-2-one
(7c). 121 mg (80%) of 7c was obtained as a yellow solid after column
chromatography [hexanes/EtOAc (8:2)]. 1H NMR (400 MHz,
CDCl3) δ 7.57−7.44 (m, 9H), 7.37 (dd, J = 7.5, 3.1 Hz, 6H), 7.29
(d, J = 7.1 Hz, 2H), 7.12 (t, J = 7.1 Hz, 2H), 7.07 (t, J = 7.1 Hz, 1H),
2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.06 (d, J = 10.3
Hz), 138.13 (d, J = 2.1 Hz), 133.59 (d, J = 9.4 Hz), 131.60 (d, J = 2.9
Hz), 128.44, 128.22 (d, J = 12.2 Hz), 127.41, 127.24 (d, J = 90.6 Hz),
125.07, 52.29 (d, J = 96.2 Hz), 26.73 (d, J = 8.0 Hz); 77Se NMR (76
MHz, CDCl3) δ 338.9; 31P NMR (162 MHz, CDCl3) δ 25.7. HRMS
(ESI) m/z: [M + H]+ Calcd for C27H24OPSe+ 475.0725; Found
475.0725.
2-(Phenylselanyl)-2-(triphenylphosphoranylidene)acetonitrile
(7d). 105 mg (72%) of 7d was obtained as a yellow oil after column
chromatography [hexanes/EtOAc (6:4)]. 1H NMR (300 MHz,
CDCl3) δ 77.63−7.33 (m, 15H), 7.28−7.23 (m, 2H), 7.05−6.97
(m, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 135.4, 132.7 (d, J = 9.6
Hz), 131.8 (d, J = 3.0 Hz), 128.1, 127.9 (d, J = 12.3 Hz), 127.4, 124.9,
124.6 (d, J = 91.9 Hz); 77Se NMR (57 MHz, CDCl3) δ 339.0; 31P
NMR (121 MHz, CDCl3) δ 28.8. HRMS (ESI) m/z: [M + H]+ Calcd
for C26H21NPSe+ 458.0571; Found 458.0574.
1-Phenyl-2-(phenylselanyl)-2-(triphenylphosphaneylidene)-
ethan-1-one (7j). 161 mg (94%) of 7j was obtained as a pale yellow
solid after column chromatography [hexanes/EtOAc (7:3)]. 1H NMR
(400 MHz, CDCl3) δ 7.73 (dd, J = 8.0, 1.7 Hz, 2H), 7.59 (ddd, J =
12.2, 7.1, 1.7 Hz, 6H), 7.48 (td, J = 7.3, 1.6 Hz, 3H), 7.37 (td, J = 7.7,
3.0 Hz, 6H), 7.30−7.22 (m, 5H), 7.12−7.01 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 192.6 (d, J = 10.5 Hz), 141.7 (d, J = 11.1 Hz),
138.6 (d, J = 2.0 Hz), 133.7 (d, J = 9.4 Hz), 131.7 (d, J = 3.0 Hz),
128.9, 128.4, 128.3 (d, J = 12.2 Hz), 127.6 (d, J = 89.5 Hz), 127.5,
127.5, 126.6, 125.1, 52.8 (d, J = 93.2 Hz); 31P NMR (162 MHz,
CDCl3) δ 25.8; 77Se NMR (76 MHz, CDCl3) δ 343.6. The data
match with the previously described compound.46
1-(4-Bromophenyl)-2-(phenylselanyl)-2-(triphenylphosphaneyl-
idene)ethan-1-one (7m). 183 mg (93%) of 7m was obtained as a
pale yellow solid after column chromatography [hexanes/EtOAc
(7:3)]. 1H NMR (400 MHz, CDCl3) δ 7.63−7.53 (m, 8H), 7.48 (td,
J = 7.4, 1.7 Hz, 3H), 7.36 (ddd, J = 8.7, 6.7, 3.4 Hz, 8H), 7.26−7.21
(m, 2H), 7.11−7.01 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
191.2 (d, J = 10.8 Hz), 140.6 (d, J = 11.4 Hz), 138.2 (d, J = 1.9 Hz),
133.6 (d, J = 9.5 Hz), 131.8 (d, J = 2.8 Hz), 130.2, 129.8, 128.5, 128.3
(d, J = 12.2 Hz), 127.3, 126.6 (d, J = 90.6 Hz), 125.2, 123.0, 52.9 (d, J
= 93.0 Hz); 31P NMR (162 MHz, CDCl3) δ 23.5; 77Se NMR (77
MHz, CDCl3) δ 342.9. HRMS (ESI) m/z: [M + H]+ Calcd for
C32H25BrOPSe+ 614.9986; Found 614.9991.
1-(4-Fluorphenyl)-2-(phenylselanyl)-2-(triphenylphosphaneyl-
idene)ethan-1-one (7n). 152 mg (86%) of 7n was obtained as a pale
yellow solid after column chromatography [hexanes/EtOAc (7:3)].
1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 8.5, 5.7 Hz, 2H), 7.62
(dt, J = 12.2, 8.0 Hz, 6H), 7.55−7.47 (m, 3H), 7.40 (td, J = 7.7, 3.0
Hz, 6H), 7.30 (d, J = 7.4 Hz, 2H), 7.11 (dt, J = 12.8, 6.8 Hz, 3H),
6.95 (t, J = 8.7 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 191.1
(d, J = 10.7 Hz), 163.1 (d, J = 247.9 Hz), 138.3 (d, J = 1.9 Hz), 137.7
(dd, J = 11.5, 3.5 Hz), 133.6 (d, J = 9.5 Hz), 131.7 (d, J = 2.9 Hz),
130.2 (d, J = 8.3 Hz), 128.5, 128.3 (d, J = 12.0 Hz), 127.3, 126.8 (d, J
= 90.7 Hz), 125.2, 113.9 (d, J = 21.3 Hz), 52.5 (d, J = 93.5 Hz); 31P
NMR (162 MHz, CDCl3) δ 23.5; 77Se NMR (77 MHz, CDCl3) δ
343.6; 19F NMR (376 MHz, CDCl3) δ −112.2. HRMS (ESI) m/z:
[M + H]+ Calcd for C32H25FOPSe+ 555.0787; Found 555.0795.
Synthesis of 2-(p-Tolylthio)acetonitrile (3n) from 7b Using a
Boron Trifluoride Diethyl Etherate Complex. To a 25 mL dried flask
under argon containing 7b (1.0 equiv, 0.227 mmol, 100 mg) was
added THF (5.0 mL). The mixture was stirred at room temperature
for 5 min, and BF3·Et2O (2.0 equiv, 0.45 mmol, 56 μL) was added.
The mixture was heated to reflux in an oil bath, and the reaction was
monitored by TLC. After consumption of the starting material, it was
diluted with CH2Cl2 (20 mL), transferred to a separation funnel, and
then washed with a NaHCO3 saturated solution (2 × 20 mL). The
organic phase was separated, dried over anhydrous Na2SO4, and
filtrated. The solvent was removed in vacuo. The crude compound was
purified by column chromatography [hexanes/EtOAc (9:1)] to yield
1
29 mg (77%) of 3n as a white solid. H NMR (300 MHz, CDCl3) δ
7.39 (d, J = 6 Hz, 2H), 7.12 (d, J = 6 Hz, 2H), 3.43 (s, 2H), 2.29 (s,
3H); 13C{1H} NMR (75 MHz, CDCl3): 169.4, 136.1, 130.8, 129.9,
128.8, 60.5; 35.1, 31.5, 20.0. The data match with the previously
described compound.47
ASSOCIATED CONTENT
■
1-(4-Methoxyphenyl)-2-(phenylselanyl)-2-(triphenylphos-
phaneylidene)ethan-1-one (7k). 150 mg (83%) of 7k was obtained
as a pale yellow solid after column chromatography [hexanes/EtOAc
(7:3)]. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.7 Hz, 2H), 7.59
(ddd, J = 12.1, 8.4, 1.3 Hz, 6H), 7.51−7.44 (m, 3H), 7.41−7.33 (m,
6H), 7.29 (d, J = 6.9 Hz, 2H), 7.14−7.02 (m, 3H), 6.77 (d, J = 8.8
Hz, 2H), 3.76 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 191.5 (d,
J = 10.3 Hz), 160.5, 138.8 (d, J = 1.9 Hz), 133.9 (d, J = 11.2 Hz),
133.7 (d, J = 9.4 Hz), 131.7 (d, J = 2.9 Hz), 130.2, 128.5, 128.4 (d, J =
12.2 Hz), 127.4, 127.4 (d, J = 90.7 Hz), 125.2, 112.5, 55.2, 51.9 (d, J
= 94.4 Hz); 31P NMR (162 MHz, CDCl3) δ 25.8; 77Se NMR (77
MHz, CDCl3) δ 344.6. The data match with the previously described
compound.46
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00114.
FAIR data, including the primary NMR FID files, for
compounds 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3i, 3m, 3n, 5a, 5b,
5c, 5d, 5e, 5f, 5g, 5h, 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h, 7i, 7j,
7k, 7l, 7m, and 7n (ZIP)
1
Copies of H, 13C, 31P, and 77Se NMR spectra (PDF)
1-(4-Nitrophenyl)-2-(phenylselanyl)-2-(triphenylphosphaneyl-
idene)ethan-1-one (7l). 180 mg (97%) of 7l was obtained as a pale
yellow solid after column chromatography [hexanes/EtOAc (7:3)].
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.7 Hz, 2H), 7.77 (d, J =
8.7 Hz, 2H), 7.60 (ddd, J = 12.3, 8.4, 1.3 Hz, 6H), 7.54−7.48 (m,
3H), 7.40 (td, J = 7.8, 3.2 Hz, 6H), 7.20 (dd, J = 8.0, 1.6 Hz, 2H),
7.13−7.04 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 190.4 (d, J
= 11.5 Hz), 148.8 (d, J = 11.8 Hz), 147.5, 137.6 (d, J = 1.9 Hz), 133.6
(d, J = 9.5 Hz), 132.1 (d, J = 3.0 Hz), 128.6, 128.6, 128.4 (d, J = 12.2
Hz), 127.2, 126.0 (d, J = 90.7 Hz), 125.4, 122.5, 54.2 (d, J = 91.7 Hz);
31P NMR (162 MHz, CDCl3) δ 23.6; 77Se NMR (76 MHz, CDCl3) δ
340.0. The data match with the previously described compound.46
AUTHOR INFORMATION
■
Corresponding Authors
Paulo H. Menezes − Depto. de Química Fundamental,
Universidade Federal de Pernambuco, 50740-560 Recife,
Pernambuco, Brazil; orcid.org/0000-0002-0327-6032;
Email: pauloh.menezes@ufpe.br
Roberta A. Oliveira − Depto. de Química Fundamental,
Universidade Federal de Pernambuco, 50740-560 Recife,
Pernambuco, Brazil; orcid.org/0000-0001-7905-2433;
Email: roberta.aoliveira@ufpe.br
5961
https://doi.org/10.1021/acs.joc.1c00114
J. Org. Chem. 2021, 86, 5954−5964

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Agents. Nucl. Med. Mol. Imaging 2016, 50, 185−195. (c) Kim, D. Y.;
Kim, H. S.; Le, U. N.; Jiang, S. N.; Kim, H. J.; Lee, K. C.; Woo, S. K.;
Chung, J.; Kim, H. S.; Bom, H. S.; et al. Evaluation of a mitochondrial
voltage sensor, (18F-fluoropentyl)triphenylphosphonium cation, in a
rat myocardial infarction model. J. Nucl. Med. 2012, 53, 1779−1785.
(d) Chen, L. D.; Mandal, D.; Gladysz, J. A.; Buhlmann, P. Chemical
stability and application of a fluorophilic tetraalkylphosphonium salt
in fluorous membrane anion-selective electrodes. New J. Chem. 2010,
34, 1867−1874. (e) Lee, C. W.; Gong, M. S. Resistive humidity
sensor using phosphonium salt-containing polyelectrolytes based on
the mutually cross-linkable copolymers. Macromol. Res. 2003, 11,
322−327.
(5) (a) Toda, Y.; Komiyama, Y.; Esaki, H.; Fukushima, K.; Suga, H.
Methoxy Groups Increase Reactivity of Bifunctional Tetraarylphos-
phonium Salt Catalysts for Carbon Dioxide Fixation: A Mechanistic
Study. J. Org. Chem. 2019, 84, 15578−15589. (b) Wu, J.-H.; Pan, J.;
Wang, T. Dipeptide-Based Phosphonium Salt Catalysis: Application
to Enantioselective Synthesis of Fused Tri- and Tetrasubstituted
Aziridines. Synlett 2019, 30, 2101−2106. (c) Zhang, S.; Yu, X. J.; Pan,
J. K.; Jiang, C. H.; Zhang, H. S.; Wang, T. L. Asymmetric synthesis of
spiro-structural 2,3-dihydrobenzofurans via the bifunctional phospho-
nium salt-promoted [4 + 1] cyclization of ortho-quinone methides
with α-bromoketones. Org. Chem. Front. 2019, 6, 3799−3803.
(d) Zhang, X.; McNally, A. Cobalt-Catalyzed Alkylation of Drug-
Like Molecules and Pharmaceuticals Using Heterocyclic Phospho-
nium Salts. ACS Catal. 2019, 9, 4862−4866. (e) Toda, Y.; Tanaka, S.;
Gomyou, S.; Kikuchi, A.; Suga, H. 4-Hydroxymethyl-substituted
oxazolidinone synthesis by tetraarylphosphonium salt-catalyzed
reactions of glycidols with isocyanates. Chem. Commun. 2019, 55,
5761−5764. (f) Chen, L.; Xiao, B.-X.; Du, W.; Chen, Y.-C.
Quaternary Phosphonium Salts as Active Brønsted Acid Catalysts
for Friedel−Crafts Reactions. Org. Lett. 2019, 21, 5733−5736.
(g) Golandaj, A.; Ahmad, A.; Ramjugernath, D. Phosphonium Salts
in Asymmetric Catalysis: A Journey in a Decade’s Extensive Research
Work. Adv. Synth. Catal. 2017, 359, 3676−3706.
(6) (a) Reyhanitash, E.; Fufachev, E.; van Munster, K. D.; van Beek,
M. B. M.; Sprakel, L. M. J.; Edelijn, C. N.; Weckhuysen, B. M.;
Kersten, S. R. A.; Bruijnincx, P. C. A.; Schuur, B. Recovery and
conversion of acetic acid from a phosphonium phosphinate ionic
liquid to enable valorization of fermented wastewater. Green Chem.
2019, 21, 2023−2034. (b) Firmansyah, M. L.; Kubota, F.; Masahiro,
G. Solvent extraction of Pt(IV), Pd(II), and Rh(III) with the ionic
liquid trioctyl(dodecyl) phosphonium chloride. J. Chem. Technol.
Biotechnol. 2018, 93, 1714−1721. (c) Pereira, M. M.; Pedro, S. N.;
Quental, M. V.; Lima, A. S.; Coutinho, J. A. P.; Freire, M. G.
Enhanced extraction of bovine serum albumin with aqueous biphasic
systems of phosphonium- and ammonium-based ionic liquids. J.
Biotechnol. 2015, 206, 17−25.
(7) (a) Heravi, M. M.; Ghanbarian, M.; Zadsirjan, V.; Alimadadi, J.
B. Recent advances in the applications of Wittig reaction in the total
synthesis of natural products containing lactone, pyrone, and lactam
as a scaffold. Monatsh. Chem. 2019, 150, 1365−1407. (b) Rocha, D.
H. A.; Pinto, D. C. G. A.; Silva, A. M. S. Applications of the Wittig
Reaction on the Synthesis of Natural and Natural Analogue
Heterocyclic Compounds. Eur. J. Org. Chem. 2018, 2018, 2443−
2457. (c) Lao, Z.; Toy, P. H. Catalytic Wittig and aza-Wittig
reactions. Beilstein J. Org. Chem. 2016, 12, 2577−2587.
Authors
Igor M. R. Moura − Depto. de Química Fundamental,
Universidade Federal de Pernambuco, 50740-560 Recife,
Pernambuco, Brazil; orcid.org/0000-0003-3279-6894
Arisson Tranquilino − Depto. de Química Fundamental,
Universidade Federal de Pernambuco, 50740-560 Recife,
Pernambuco, Brazil; orcid.org/0000-0002-6312-8461
Barbara G. Sátiro − Depto. de Química Fundamental,
Universidade Federal de Pernambuco, 50740-560 Recife,
Pernambuco, Brazil; orcid.org/0000-0001-6697-0921
Ricardo O. Silva − Depto. de Química Fundamental,
Universidade Federal de Pernambuco, 50740-560 Recife,
Pernambuco, Brazil; orcid.org/0000-0001-8090-7320
Diogo de Oliveira-Silva − Depto. de Química, Instituto de
̂
̂
Ciencias Ambientais, Químicas e Farmaceuticas,
Universidade Federal de Sao Paulo, 09972-270 Diadema,
Sao Paulo, Brazil; orcid.org/0000-0002-0046-3502
̃
̃
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00114
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work was provided by CNPq,
CAPES, and FACEPE. I.M.R.M. and B.G.S. are thankful for
their FACEPE-CNPq fellowships. P.H.M is also thankful for
his CNPq fellowship.
REFERENCES
■
(1) (a) Wittig, G.; Schöllkopf, U. Uber Triphenyl-Phosphin-
methylene Als Olefinbildende Reagenzien 0.1. Chem. Ber. 1954, 87,
1318. (b) Wittig, G.; Haag, W. Uber Triphenyl-Phosphin-Methylene
Als Olefinbildende Reagenzien 0.2. Chem. Ber. 1955, 88, 1654.
(c) Vedejs, E.; Peterson, M. J. Stereochemistry and Mechanism in the
Wittig Reaction. In Topics in Stereochemistry; Eliel, E. L., Wilen, S. H.,
Eds.; John. Wiley & Sons: New York, 1994; Vol. 21, pp 412−432.
(2) (a) Thiemann, T. Wittig- and Horner-Wadsworth-Emmons
Olefination in Aqueous Media with and without Phase Transfer
Catalysis. Mini-Rev. Org. Chem. 2018, 15, 412−432. (b) Lao, Z.; Toy,
P. H. Catalytic Wittig and aza-Wittig reactions. Beilstein J. Org. Chem.
2016, 12, 2577−2587. (c) Jasem, Y. A.; El-Esawi, R.; Thiemann, T.
Wittig- and Horner-Wadsworth-Emmons-olefination reactions with
stabilised and semi-stabilised phosphoranes and phosphonates under
non-classical conditions. J. Chem. Res. 2014, 38, 453−463. (d) Byrne,
P. A.; Gilheany, D. G. The modern interpretation of the Wittig
reaction mechanism. Chem. Soc. Rev. 2013, 42, 6670−6696. (e) Gu,
Y.; Tian, S.-K. Olefination reactions of phosphorus-stabilized carbon
nucleophiles. Top. Curr. Chem. 2012, 327, 197−238. (f) Siau, W.-Y.;
Zhang, Y.; Zhao, Y. Stereoselective synthesis of Z-alkenes. Top. Curr.
Chem. 2012, 327, 33−58. (g) Guenin, E.; Meziane, D. Microwave
Assisted Phosphorus Organic Chemistry: A Review. Curr. Org. Chem.
2011, 15, 3465−3485.
(3) (a) Macarie, L.; Simulescu, V.; Ilia, G. Phosphonium-Based Ionic
Liquids Used as Reagents or Catalysts. ChemistrySelect 2019, 4,
9285−9299. (b) Langer, J.; Meyer, S.; Dundar, F.; Schowtka, B.;
Gorls, H.; Westerhausen, M. Dppm-derived phosphonium salts and
ylides as ligand precursors for s-block organometallics. ARKIVOC
2012, 2012, 210−225. (c) Fraser, K. J.; MacFarlane, D. R.
Phosphonium-Based Ionic Liquids: An Overview. Aust. J. Chem.
2009, 62, 309−321.
(4) (a) McNeel, K. E.; Siraj, N.; Bhattarai, N.; Warner, I. M.
Fluorescence-Based Ratiometric Nanosensor for Selective Imaging of
Cancer Cells. ACS Omega 2019, 4, 1592−1600. (b) Kim, D.-Y.; Min,
J.-J. Radiolabeled Phosphonium Salts as Mitochondrial Voltage
Sensors for Positron Emission Tomography Myocardial Imaging
(8) For some examples, see: (a) Surur, A. S.; Schulig, L.; Link, A.
Interconnection of sulfides and sulfoxides in medicinal chemistry.
Arch Pharm. 2019, 352, No. e1800248. (b) Noguchi, N. Ebselen, a
useful tool for understanding cellular redox biology and a promising
drug candidate for use in human diseases. Arch. Biochem. Biophys.
2016, 595, 109−112. (c) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T.
Organoselenium and organotellurium compounds: toxicology and
pharmacology. Chem. Rev. 2004, 104, 6255−6286. (d) Mugesh, G.;
Singh, H. B. Synthetic organoselenium compounds as antioxidants:
glutathione peroxidase activity. Chem. Soc. Rev. 2000, 29, 347−357.
5962
https://doi.org/10.1021/acs.joc.1c00114
J. Org. Chem. 2021, 86, 5954−5964

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(9) Wang, D.-Y.; Guo, W.; Fu, Y. Organosulfides: An Emerging
Class of Cathode Materials for Rechargeable Lithium Batteries. Acc.
Chem. Res. 2019, 52, 2290−2300.
Preparation of Diaryl Chalcogenides. J. Org. Chem. 2006, 71, 5400−
5403.
(16) Kanemoto, K.; Furuhashi, K.; Morita, Y.; Komatsu, T.;
Fukuzawa, S.-I. Acid-Mediated Sulfonylthiolation of Arenes via
Selective Activation of SS-Morpholino Dithiosulfonate. Org. Lett.
2021, 23, 1582−1587.
(17) Zhang, H.; Wang, H.; Jiang, Y.; Cao, F.; Gao, W.; Zhu, L.;
Yang, Y.; Wang, X.; Wang, Y.; Chen, Y.; Feng, Y.; Deng, X.; Lu, Y.;
Hu, X.; Li, X.; Zhang, J.; Shi, T.; Wang, Z. Recent Advances in Iodine-
Promoted C-S/N-S Bonds Formation. Chem. - Eur. J. 2020, 26,
17289−17317.
(18) (a) Firouzabadi, H.; Iranpoor, N.; Gholinejad, M.; Samadi, A.
Copper(I) Iodide Catalyzes Odorless Thioarylation of Phenolic
Esters with Alkyl Derivatives Using Thiourea in Wet Polyethylene
Glycol (PEG 200). J. Mol. Catal. A: Chem. 2013, 377, 190−196.
(b) Pan, X.; Curran, D. P. Neutral Sulfur Nucleophiles: Synthesis of
Thioethers and Thioesters by Substitution Reactions of N-
Heterocyclic Carbene Boryl Sulfides and Thioamides. Org. Lett.
2014, 16, 2728−2731. (c) Zhang, Y.; Li, Y.; Zhang, X.; Jiang, X.
Sulfide Synthesis through Copper-Catalyzed C-S Bond Formation
under Biomolecule-Compatible Conditions. Chem. Commun. 2015,
51, 941−944. (d) Rostami, A.; Rostami, A.; Iranpoor, N.; Zolfigol, M.
A. Efficient Cu-Catalyzed One-Pot Odorless Synthesis of Sulfides
from Triphenyltin Chloride, Aryl Halides and S8 in PEG. Tetrahedron
Lett. 2016, 57, 192−195.
(19) Mampuys, P.; McElroy, C. R.; Clark, J. H.; Orru, R. V. A.;
Maes, B. U. W. Thiosulfonates as Emerging Reactants: Synthesis and
Applications. Adv. Synth. Catal. 2020, 362, 3−64.
(20) Tranquilino, A.; Andrade, S. R. C. P.; da Silva, A. P. M.;
Menezes, P. H.; Oliveira, R. A. Non-expensive, open-flask and
selective catalytic systems for the synthesis of sulfinate esters and
thiosulfonates. Tetrahedron Lett. 2017, 58, 1265−1268.
(21) Bordwell, F. G. Equilibrium acidities in dimethyl sulfoxide
solution. Acc. Chem. Res. 1988, 21, 456−463.
(22) Fang, Y.; Rogge, T.; Ackermann, L.; Wang, S.-Y.; Ji, S.-J. Nickel-
catalyzed reductive thiolation and selenylation of unactivated alkyl
bromides. Nat. Commun. 2018, 9, 2240.
(23) Back, T. G.; Collins, S.; Krishn, M. V. Reactions of
sulfonhydrazides with benzeneseleninic acid, selenium halides, and
sulfur halides. A convenient preparation of selenosulfonates and
thiosulfonates. Can. J. Chem. 1987, 65, 38−42.
(24) (a) Kolodiazhnyi, O. In Phosphorus Ylides: Chemistry and
Application in Organic Synthesis; Wiley Online Books: Weinheim,
2007. (b) Schlosser, M.; Jenny, T.; Schaub, B. About the Structure of
Phosphorus Ylids: Electron Distribution and Geometry. Heteroat.
Chem. 1990, 1 (2), 151−156.
(10) (a) Han, J.; Soloshonok, V. A.; Klika, K. D.; Drabowicz, J.;
Wzorek, A. Chiral sulfoxides: advances in asymmetric synthesis and
problems with the accurate determination of the stereochemical
outcome. Chem. Soc. Rev. 2018, 47, 1307−1350. (b) Otocka, S.;
́
Kwiatkowska, M.; Madalinska, L.; Kielbasinski, P. Chiral Organosulfur
Ligands/Catalysts with a Stereogenic Sulfur Atom: Applications in
Asymmetric Synthesis. Chem. Rev. 2017, 117, 4147−4181. (c) Mu-
kherjee, A. J.; Zade, S. S.; Singh, H. B.; Sunoj, R. B. Organoselenium
Chemistry: Role of Intramolecular Interactions. Chem. Rev. 2010, 110,
4357−4416.
(11) Rayner, C. M. Synthesis of thiols, selenols, sulfides, selenides,
sulfoxides, selenoxides, sulfones and selenones. Contemp. Org. Synth.
1996, 3, 499−533.
(12) Uemura, S. in Comprehensive Organic Synthesis 1991, 7 (1991),
757−787.
(13) Petrovic, G.; Saicic, R. N.; Cekovic, Z. Phenylsulfenylation Of
Nonactivated−Carbon Atom By Photolysis Of Alkyl Benzenesulfen-
ates: Preparation Of 2-Phenylthio-5-Heptanol (Heptane, 2-phenyl-
thio-5-hydroxy). Org. Synth. 2005, 81, 244−253.
(14) (a) Senol, E.; Scattolin, T.; Schoenebeck, F. Selenolation of
Aryl Iodides and Bromides Enabled by a Bench Stable PdI Dimer.
Chem. - Eur. J. 2019, 25, 9419−9422. (b) Junquera, L. B.; Fernández,
F. E.; Puerta, M. C.; Valerga, P. Nickel(II) N-Heterocyclic Carbene
Complexes: Versatile Catalysts for C−C, C−S and C−N Coupling
Reactions. Eur. J. Inorg. Chem. 2017, 2017, 2547−2556. (c) Guzmán-
Percástegui, E.; Hernández, D. J.; Castillo, I. Calix[8]arene nano-
reactor for Cu(I)-catalysed C−S coupling. Chem. Commun. 2016, 52,
3111−3114. (d) Zhang, X.-Y.; Zhang, X.-Y.; Guo, S.-R. Efficient
copper(I)-catalyzed C−S cross-coupling of thiols with aryl halides in
an aqueous two-phase system. J. Sulfur Chem. 2011, 32, 23−35.
(e) Yuan, Y.; Thomé, I.; Kim, S. H.; Chen, D.; Beyer, A.; Bonnamour,
J.; Zuidema, E.; Chang, S.; Bolm, C. DMSO/KOH: A Superbase for
the Transition Metal-free Preparation of Cross-Coupling Products.
Adv. Synth. Catal. 2010, 352, 2892−2898. (f) Eichman, C. C.;
Stambuli, J. P. Zinc-Mediated Palladium-Catalyzed Formation of
Carbon−Sulfur Bonds. J. Org. Chem. 2009, 74, 4005−4008.
(g) Mispelaere-Canivet, C.; Spindler, J. F.; Perrio, S.; Beslin, P.
Pd2(dba)3/Xantphos-catalyzed cross-coupling of thiols and aryl
bromides/triflates. Tetrahedron 2005, 61, 5253−5259. (h) Cristau,
H. J.; Chabaud, B.; Labaudiniere, R.; Christol, H. Synthesis of aryl
phenyl and heteroaryl phenyl selenides by nickel(II)-catalyzed
arylation of sodium benzeneselenolate. Organometallics 1985, 4,
657−661.
(15) (a) Verma, A.; Jana, S.; Durga Prasad, C.; Yadav, A.; Kumar, S.
Organoselenium and DMAP co-catalysis: regioselective synthesis of
medium-sized halolactones and bromooxepanes from unactivated
alkenes. Chem. Commun. 2016, 52, 4179−4182. (b) Wen, M.; Shen,
C.; Wang, L.; Zhang, P.; Jin, J. An efficient d-glucosamine-based
copper catalyst for C−X couplings and its application in the synthesis
of nilotinib intermediate. RSC Adv. 2015, 5, 1522−1528.
(c) Chatterjee, T.; Ranu, B. C. Solvent-Controlled Halo-Selective
Selenylation of Aryl Halides Catalyzed by Cu(II) Supported on Al2O3.
A General Protocol for the Synthesis of Unsymmetrical Organo
Mono- and Bis-Selenides. J. Org. Chem. 2013, 78, 7145−7153.
(d) Kumar, A.; Bhakuni, B. S.; Prasad, C. D.; Kumar, S.; Kumar, S.
Potassium tert-butoxide-mediated synthesis of unsymmetrical diaryl
ethers, sulfides and selenides from aryl bromides. Tetrahedron 2013,
69, 5383−5392. (e) Swapna, K.; Murthy, S. N.; Nageswar, Y. V. D.
Magnetically Separable and Reusable Copper Ferrite Nanoparticles
for Cross Coupling of Aryl Halides with Diphenyl Diselenide. Eur. J.
Org. Chem. 2011, 2011, 1940−1946. (f) Singh, D.; Alberto, E. E.;
Rodrigues, O. E. D.; Braga, A. L. Eco-friendly cross-coupling of diaryl
diselenides with aryl and alkyl bromides catalyzed by CuO
nanopowder in ionic liquid. Green Chem. 2009, 11, 1521−1524.
(g) Kumar, S.; Engman, L. Microwave-Assisted Copper-Catalyzed
(25) (a) Scharf, L. T.; Gessner, V. H. Metalated Ylides: A New Class
of Strong Donor Ligands with Unique Electronic Properties. Inorg.
Chem. 2017, 56, 8599−8607. (b) Schmidbaur, H. Phosphorus Ylides
in the Coordination Sphere of Transition Metals: An Inventory.
Angew. Chem., Int. Ed. Engl. 1983, 22, 907−927.
(26) (a) Leung, W. P.; Chan, Y. C.; Choi, T. H.; Lee, H. K.
Synthesis and Structural Characterization of Mono and Bimetallic
Rhodium(I), Iridium(I) and Gold(I) Methanide and Methandiide
Complexes from 2-Quinolyl Linked (Thiophosphoranyl)methane.
Eur. J. Inorg. Chem. 2016, 2016, 3859−3867. (b) Kuhn, N.; Winter,
̋
M. Synthese und Reaktivitat von Dienylmetall-Verbindungen: IX.
Thiophosphorane als Liganden in Cyclopentadienylnickel-Komplex-
en. J. Organomet. Chem. 1982, 239, C31−C34.
(27) Braga, A. L.; Comasseto, J. V.; Petragnani, N. Pyrolysis of α-
acyl, α,-thio phosphoranes → thioacetylenes. Tetrahedron Lett. 1984,
25, 1111−1114.
(28) Petragnani, N.; Rodrigues, R.; Comasseto, J. V. The reaction of
selenenyl halides with wittig reagents. J. Organomet. Chem. 1976, 114,
281−292.
(29) Silveira, C. C.; Nunes, M. R. S.; Wendling, E.; Braga, A. L.
Synthesis of α-phenylseleno-α,β-unsaturated esters by Wittig-type
reactions. Studies on the Diels−Alder reaction. J. Organomet. Chem.
2001, 623, 131−136.
5963
https://doi.org/10.1021/acs.joc.1c00114
J. Org. Chem. 2021, 86, 5954−5964

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(30) (a) Blakemore, P. R. Olefination of Carbonyl Compounds by
Main-Group Element Mediators; Elsevier Ltd., 2014; Vol. 1, pp 516−
608. (b) Zhang, X. M.; Fry, A. J.; Bordwell, F. G. Equilibrium
Acidities and Homolytic Bond Dissociation Enthalpies of the Acidic
C-H Bonds in P-(Para-Substituted Benzyl)Triphenylphosphonium
Cations and Related Cations. J. Org. Chem. 1996, 61 (12), 4101−
4106.
(47) Ramirez, N. P.; König, B.; Gonzalez-Gomez, J. C.
Decarboxylative Cyanation of Aliphatic Carboxylic Acids via Visible-
Light Flavin Photocatalysis. Org. Lett. 2019, 21 (5), 1368−1373.
(31) (a) Adam, W.; Narita, N.; Nishizawa, Y. On the Mechanism of
the Triphenylphosphine-Azodicarboxylate (Mitsunobu Reaction)
Esterification. J. Am. Chem. Soc. 1984, 106 (4), 1843−1845.
(b) Camp, D.; Jenkins, I. D. Mechanism of the Mitsunobu
Esterification Reaction. 1. The Involvement of Phosphoranes and
Oxyphosphonium Salts. J. Org. Chem. 1989, 54 (13), 3045−3049.
(32) McAllister, T.; Mackle, H. Bonding in Triphenylphosphine
Borane and Related Molecules. Trans. Faraday Soc. 1969, 65, 1734−
1735.
(33) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals; Butterworth-Heinemann: Oxford, UK, 1997.
(34) Zhang, X.; Cui, T.; Zhang, Y.; Gu, W.; Liu, P.; Sun, P.
Electrochemical Oxidative Cross-Coupling Reaction to Access
Unsymmetrical Thiosulfonates and Selenosulfonates. Adv. Synth.
Catal. 2019, 361 (9), 2014−2019.
(35) Zhao, X.; Zheng, X.; Yang, B.; Sheng, J.; Lu, K. Deoxygenation
of Sulfoxides to Sulphides with Trichlorophosphane. Org. Biomol.
Chem. 2018, 16 (7), 1200−1204.
(36) Yang, Y.; Ye, Z.; Zhang, X.; Zhou, Y.; Ma, X.; Cao, H.; Li, H.;
Yu, L.; Xu, Q. Efficient Dehydrative Alkylation of Thiols with
Alcohols Catalyzed by Alkyl Halides. Org. Biomol. Chem. 2017, 15
(45), 9638−9642.
(37) Santoni, G.; Mba, M.; Bonchio, M.; Nugent, W.; Zonta, C.;
Licini, G. Stereoselective Control by Face-to-Face Versus Edge-to-
Face Aromatic Interactions: The Case of C3-TiIV Amino Trialkolate
Sulfoxidation Catalysts. Chem. - Eur. J. 2010, 16, 645−654.
(38) Yang, Y.; Ye, Z.; Zhang, X.; Zhou, Y.; Ma, X.; Cao, H.; Li, H.;
Yu, L.; Xu, Q. Efficient Dehydrative Alkylation of Thiols with
Alcohols Catalyzed by Alkyl Halides. Org. Biomol. Chem. 2017, 15
(45), 9638−9642.
(39) Thomas, A. M.; Sherin, D. R.; Asha, S.; Manojkumar, T. K.;
Anilkumar, G. Exploration of the Mechanism and Scope of the CuI/
DABCO Catalysed CS Coupling Reaction. Polyhedron 2020, 176,
114269.
(40) Narayanaperumal, S.; Alberto, E. E.; Gul, K.; Kawasoko, C. Y.;
Dornelles, L.; Rodrigues, O. E. D.; Braga, A. L. Zn in Ionic Liquid: An
Efficient Reaction Media for the Synthesis of Diorganyl Chalcoge-
nides and Chalcogenoesters. Tetrahedron 2011, 67 (25), 4723−4730.
(41) Ranu, B. C.; Mandal, T. Indium(I) Iodide-Promoted Cleavage
of Diaryl Diselenides and Disulfides and Subsequent Condensation
with Alkyl or Acyl Halides. One-Pot Efficient Synthesis of Diorganyl
Selenides, Sulfides, Selenoesters, and Thioesters. J. Org. Chem. 2004,
69 (17), 5793−5795.
(42) Chen, Q.; Wang, P.; Yan, T.; Cai, M. A Highly Efficient Heter-
ogeneous Ruthenium(III)-Catalyzed Reaction of Diaryl Diselenides
with Alkyl Halides Leading to Unsymmetrical Diorganyl Selenides. J.
Organomet. Chem. 2017, 840, 38−46.
(43) Higuchi, H.; Sakata, Y.; Misumi, S.; Otsubo, T.; Ogura, F.;
Yamaguchi, H. NEW Synthetic Method Of [2.2]Paracyclophane,
Benzocyclobutene, And Lepidopterene: Pyrolysis Of Arylmethyl
Phenyl Selenides. Chem. Lett. 1981, 10 (5), 627−630.
(44) Li, F.; Wang, D.; Chen, H.; He, Z.; Zhou, L.; Zeng, Q. Transi-
tion Metal-Free Coupling Reactions of Benzylic Trime-thylammo-
nium Salts with Di(Hetero)Aryl Disulfides and Diselenides. Chem.
Commun. 2020, 56 (85), 13029−13032.
(45) Pandey, G.; Tiwari, S. K.; Singh, B. α-Alkylation of Tertiary
Amines by C(Sp3)−C(Sp3) Cross-Coupling under Redox Neu-tral
Photocatalysis. Tetrahedron Lett. 2016, 57 (40), 4480−4483.
(46) Braga, A. L.; Comasseto, J. V.; Petragnani, N. An Intra-
molecular Wittig Reaction Leading to Protected Terminal Acetylenes.
Synthesis 1984, 1984, 240−243.
5964
https://doi.org/10.1021/acs.joc.1c00114
J. Org. Chem. 2021, 86, 5954−5964