One-Pot Synthesis of N-Iodo Sulfoximines from Sulfides

Article abstract of DOI:10.1021/acs.joc.1c00292

This is the first report on the synthesis and characterization of N-iodo sulfoximines. The synthesis was designed as a room temperature one-pot cascade reaction from readily available sulfides as starting compounds, converted into sulfoximines by reaction with ammonium carbonate and (diacetoxyiodo)benzene, followed by iodination with N-iodosuccinimide or iodine in situ, in up to 90% isolated yields, also at a multigram scale. Iodination of aryls with N-iodo sulfoximines, oxidation, and conversion to N-SCF3 congeners have been demonstrated.

Full text of DOI:10.1021/acs.joc.1c00292

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One-Pot Synthesis of N‑Iodo Sulfoximines from Sulfides
̌
Anze Zupanc and Marjan Jereb*
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ABSTRACT: This is the first report on the synthesis and
characterization of N-iodo sulfoximines. The synthesis was
designed as a room temperature one-pot cascade reaction from
readily available sulfides as starting compounds, converted into
sulfoximines by reaction with ammonium carbonate and
(diacetoxyiodo)benzene, followed by iodination with N-iodosucci-
nimide or iodine in situ, in up to 90% isolated yields, also at a
multigram scale. Iodination of aryls with N-iodo sulfoximines, oxidation, and conversion to N-SCF3 congeners have been
demonstrated.
he increasing interest in sulfoximines1−9 in drug
discovery,10−14 medicine,15−18 and agrochemistry19,20
sulfoximines, leading to dihydroisothiazole oxides (Figure
1f).50 Five decades ago, two N-iodo sulfoximines were
mentioned in the patent literature, but without any character-
ization data.52 All subsequent attempts to prepare these
compounds were unsuccessful.43,51 Our experience with
halogenations of organic compounds and green chemistry53−57
prompted us to develop a reliable method for the synthesis of
N-iodo sulfoximines. With simplicity and sustainability in
mind, we developed a one-pot cascade protocol using sulfides
as starting materials. Selected transformations were also
demonstrated.
T
has led to a rapidly growing number of publications21−34 in
these and other research areas.35 These compounds are of
great importance as ligands, auxiliaries, and catalysts, e.g., in
asymmetric synthesis and catalysis.36,37 Recently, a large
number of reports on their synthesis and transformations
have appeared in the literature,38−41 including halo- and
chalcogenations. Sulfoximines undergo chlorinations with NCS
(Figure 1a),42 brominations with NBS (Figure 1b),43
In initial screening experiments, PhSONHMe was reacted
with I2/K2CO3, giving supposedly 2a with 95% conversion in
MeCN and DCM. High conversion stimulated us to develop
the one-pot protocol from sulfides. Thioanisole (1a, 1 mmol)
was allowed to react with (NH4)2CO3 (1.5 equiv) and
(diacetoxyiodo)benzene (DIB, 2.3 equiv) in MeOH (10 mL)
to give PhSONHMe. Then the reaction solvent was replaced
by DCM (10 mL), followed by the addition of N-
iodosuccinimide (NIS, 1.2 equiv) for iodination. Although
complete conversion to a product tentatively identified as 2a
by 1H NMR (see below) was observed after 16 h of stirring at
room temperature, attempts to isolate the product failed.
Repeating both steps in MeOH (10 mL) as the sole reaction
solvent also resulted in complete conversion to the same
product, but with the same failure to isolate as described above
(Table 1, entry 1). Shortening the reaction time for the
iodination step proved to be beneficial. After 2 h, the
precipitate formed in the reaction mixture was collected by
Figure 1. (a−g) Transformations of sulfoximines with halo- and
chalcogenating agents, (h) this work.
trifluoromethylthiolations with AgSCF3 (Figure 1c),43 trifluor-
omethylations (Figure 1d),44−48 halocyclizations with
(diacetoxyiodo)benzene (DIB)/KI (Figure 1e),49 reactions
with (DIB)/I2 under visible light (Figure 1f),50 chlorinations
and N-sulfonylations in the presence of I2/H2O2 (Figure 1g),51
for example.
Received: February 5, 2021
Published: March 25, 2021
Surprisingly, unlike the halogen and chalcogenide deriva-
tives, the N-iodo sulfoximines remain elusive. These
compounds have been proposed as reactive intermediates in
̈
the iodine-mediated Hofmann−Loffler−Freytag reaction of
© 2021 The Authors. Published by
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https://doi.org/10.1021/acs.joc.1c00292
J. Org. Chem. 2021, 86, 5991−6000
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Note
a
Table 1. Optimization of the Reaction Conditions Using
NIS
Scheme 1. Substrate Scope
a
b
entry
MeOH (mL)
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
10
10
10
5
3
2
2
3
5
16
2
c
57
c
0.33
0.33
0.33
0.33
1
67
74
c
68
c
78
80
c
c
1
1
80
74
a
Conditions: 1a (1.0 mmol), (NH4)2CO3 (1.5 mmol), DIB (2.3
b
mmol), MeOH (mL), 1 h, rt, then NIS (1.1 equiv), time, rt. Yield.
c
NIS/succinimide accompanied the product in 3%/4% (entry 2), 9%/
7% (entry 3), 9%/9% (entry 5), 12%/12% (entry 6), 0%/6% along
with unidentified side products (entry 7), 0%/5% along with
unidentified side products (entry 8).
filtration, and NMR analysis showed the desired product 2a in
57% yield, accompanied by unreacted NIS and succinimide
(Table 1, entry 2).
Further reduction of the reaction time to 0.33 h yielded 67%
of impure 2a (Table 1, entry 3). Finally, halving the volume of
MeOH from 10 to 5 mL at this point allowed the isolation of
pure 2a in good 74% yield (Table 1, entry 4). Further
reduction in the volume of reaction solvent did not prove
beneficial (Table 1, entries 5−8). It is noteworthy that the
success of crystallization of 2a from the reaction mixture
depends strongly on the surface area of the reaction vessel, as
can be concluded from several successive repeating of the
above experiments. The best yields of the isolated product
were obtained when the reaction was carried out in a worn
(scratched) glass round-bottom flask, in a polyethylene vessel,
or in the presence of a glass frit that aided the nucleation
process (vide infra).
Product 2a showed a characteristic singlet resonance (δ =
3.33 ppm) for the S-CH3 group in 1H NMR spectra (CDCl3),
which was deshielded as compared to both thioanisole (1a, δ =
2.44 ppm) and PhSONHMe (δ = 3.12 ppm). HRMS analysis
in positive ESI+ mode confirmed the ion formula of
C7H9INOS+ for [M + H]+ (m/z calcd 281.9445, found for
[M + H]+ 281.9431). The molecular formula was corroborated
by CHN elemental analysis (calcd for C7H8INOS: C, 29.91; H,
2.87; N, 4.98. Found: C, 30.00; H, 2.70; N, 4.81.
a
Reaction conditions: (1) 1 (1 mmol), (NH4)2CO3 (1.5 equiv), DIB
b
(2.3 equiv), MeOH (5 mL), then (2) NIS (1.1 equiv). Yield.
c
(NH4)2CO3 (2.625 equiv) and DIB (4.025 equiv) were used.
d
e
(NH4)2CO3 (1.875 equiv) and DIB (2.875 equiv) were used. From
Having identified the optimal reaction conditions, we
focused on screening the substrate scope (Scheme 1). Mixed
phenyl alkyl sulfides 1b−1d gave the corresponding N-iodo
sulfoximines 2b−2d regardless of alkyl chain length or
branching. Electron-rich and electron-poor aryl alkyl sulfides
gave the desired products 2e−2o in good to high yields.
Phenyl alkyl and pentafluorophenyl alkyl sulfides 1p−1s
reacted smoothly and gave the expected products 2p−2s in
up to 90% yields. The C6F5 motif in product 2r is notable for
its intrinsic properties that allow molecular recognition and
improved structural ordering.58,59 Relatively challenging
substrates, diphenyl sulfide 1t and dibenzothiophene 1u,
afforded the corresponding products 2t and 2u in reasonable
yields. Benzyl methyl-, symmetric and unsymmetric dialkyl
DMSO as starting compound, with (NH4)2CO3 (1.5 equiv), DIB (1.3
equiv) and I2 (1.1 equiv) in MeOH (2 mL).
sulfides 1v−1y afforded products 2v−2y in moderate yields.
The method was also suitable for heteroaromatic sulfides, as
shown by the formation of the product 2z formation in 66%
yield. In some cases, those of 2d, 2e, 2g, 2j−2s, 2v, 2x, and 2y,
the product did not precipitate from the reaction mixture as
described above for 2a. Since attempts to precipitate pure
products by addition of a co-solvent (EtOAc, Et2O, DCM,
AcOH, PE, or hexanes) failed, MeOH was evaporated and the
residue was subjected to rapid flash chromatography through a
short silica gel plug with DCM as eluent. Prolonged contact
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Note
a
with SiO2, Al2O3 (neutral or basic), activated carbon, or
extractive workup was detrimental to the N-iodo sulfoximines.
The scalability of the protocol was tested using sulfide 1a as
a model substrate. A mixture of 1a (10 mmol), (NH4)2CO3
(15 mmol), and DIB (23 mmol) in MeOH (50 mL) was
stirred in a used polyethylene flask for 1 h at room
temperature. After addition of NIS (11 mmol) and further
stirring of the reaction mixture for 1 h, the precipitate was
collected by filtration to afford pure 2a in 78% yield. Repeating
the above procedure in a new round-bottom glass flask gave 2a
in only a modest 44% yield, consistently indicating the
importance of the surface area of the reaction vessel for
nucleation.
Scheme 2. N-Bromo and N-Chloro Sulfoximines
a
Reaction conditions: (1) 1a (1 mmol), MeOH (5 mL), (NH4)2CO3
(1.5 mmol), DIB (2.3 mmol), then (2) NBS or NCS (equiv), rt.
b
Yield (%).
a
Table 3. Iodination and Oxidation with 2a
In addition to NIS, I2 was tested as an iodinating agent.
Under the same reaction conditions as in Scheme 1, sulfide 1a
was reacted in situ to give PhSONHMe and then treated with
I2 to give 2a. The iodination proceeded smoothly without the
need for a catalyst or promoter. The optimization process of
the reaction conditions is summarized in Table 2.
a
Table 2. Optimization and Scale-Up by Using I2
b
entry
MeOH (mL)
I2 (equiv)
time (h)
yield (%)
1
2
3
4
5
6
5
5
1
2
2
2
20
50
1.1
1.1
1.1
1.5
1.1
1.25
1.1
1.1
1
16
1
1
1
1
1
1
44
52
62
79
75
77
74
75
c
d
7
e
8
a
Reaction conditions: (1) 1a (1 mmol), (NH4)2CO3 (1.5 mmol),
a
DIB (2.3 mmol), MeOH (mL), 1 h, rt, then (2) I2 (equiv), time, rt,
Reaction conditions: 5−13 (1 mmol), AcOH (5 mL), 2a (equiv).
b
c
1
then filtration of precipitate, washing with a small amount of MeOH
Yield. Full conversion according to H NMR analysis; the product
b
c
d
d
e
and an excess of n-hexane. Yield. Impure product. The reaction
was not isolated. Starting 5 remined unconsumed. Slow addition of
2a and additional stirring: entry 7, 2 h and 0.5 h; entry 9, 1 h and 0.25
h.
e
was conducted with 10 mmol of 1a. The reaction was conducted
with 25 mmol of 1a.
Reaction of the sulfoximines generated in situ from 1a with
I2 (1.1 equiv) in MeOH (5 mL) gave 2a in moderate yield
(Table 2, entries 1 and 2). Reducing the amount of reaction
solvent to 1 mL gave impure 2a (Table 2, entry 3). Optimal
results were obtained with 2 mL of MeOH and 1.1−1.25 equiv
of I2 (Table 2, entries 5 and 6). On a larger scale, experiments
using I2 as the iodinating agent were performed with 10 and 25
mmol amounts of 1a to give pure 2a in consistent 74% (2.09
g) and 75% (5.31 g) yields, respectively (Table 2, entries 7 and
8).
Having in hand the one-pot protocol for the N-iodination of
sulfoximines formed in situ, we decided to briefly extend it to
the preparation of N-bromo sulfoximine 3 and N-chloro
sulfoximine 4 (Scheme 2). The reactions were carried out with
1a (1 mmol) in MeOH (5 mL) at room temperature with
variable amounts of N-bromosuccinimide (NBS) and N-
chlorosuccinimide (NCS). The yields of products 3 and 4
depended strongly on the amount of halogenating agent.
Finally, to demonstrate the applicability of the N-iodo
sulfoximines, we decided to test their potential in the
electrophilic aromatic substitution reaction with activated
benzene derivatives (Table 3). Treatment of 5 with 2a in
AcOH for 1.5 h at 22 °C resulted in full conversion to 4-
iodoanisole (6, entry 1). At elevated temperature (60 °C),
product 6 formed in 1.5 h and was isolated in 86% yield (entry
2). No reaction was observed in DCM, MeOH, or MeCN as
reaction solvent, with unconsumed 5 being regenerated
(entries 3−5). This is in sharp contrast to NIS, which proved
to work best in MeCN60 and TFA,61 suggesting potential
orthogonality of these two reagents in iodinations. Phenol (7)
was triiodinated with 2a at room temperature to give 8 (entry
6), while 1-methoxynaphthalene (9) gave the 4-iodo derivative
10 (entry 7). Iodination also proceeded with less activated 4-
nitrophenol (11) to give the diiodinated derivative 12 in
excellent yield (entry 8). Thiophenol (13), on the other hand,
gave diphenyl disulfide quantitatively (14, entry 9). After
completion of the reactions from Table 3, the resulting
PhSONHMe was simply removed by extractive workup
(HClaq/DCM), yielding a pure product that required no
further purification.
We also tested the reactivity of N-iodo sulfoximines toward
silver(I) trifluoromethanethiolate (AgSCF3). The desired N-
SCF3-substituted sulfoximines 15 were obtained in good to
excellent yields (Table 4). This is complementary to the
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Note
a
In the case of 1r (1 mmol), 2.625 equiv of (NH4)2CO3 (2.625
mmol, 252 mg) and 4.025 equiv of DIB (4.025 mmol, 1296 mg) were
used.
Table 4. Synthesis of N-SCF3-Substituted Sulfoximines
In the case of 1u (1 mmol), 1.875 equiv of (NH4)2CO3 (1.875
mmol, 180 mg) and 2.875 equiv of DIB (2.875 mmol, 926 mg) were
used.
Then, 1.1 equiv of NIS (1.1 mmol, 248 mg) was added, and the
stirring was continued for another hour.
The method of isolation was chosen depending on whether the
product 2 precipitated or not.
a
Reaction conditions: 2 (0.3−1 mmol), AgSCF3 (1.2 equiv), Ar,
b
MeCN (5 mL/1 mmol of 2), 0.33−1 h, rt. Yield.
Method A for products 2 that precipitated from the reaction
mixture (2a−2c, 2f, 2h, 2i, 2t, 2u, 2z).
The precipitate was collected by vacuum filtration using a Buchner
̈
procedure of Bohnen and Bolm,43 who developed the synthesis
of N-trifluoromethylthiolated sulfoximines from sulfoximines
via the corresponding N−Br derivatives, and will add to the
chemistry of this specific type of compounds.43
funnel, washed with a small amount of MeOH, and dried under
reduced pressure (vacuum pump) to obtain pure product 2.
Method B for products 2, not precipitating from the reaction
mixture (2d, 2e, 2g, 2j−2s, 2v, 2x, 2y).
In summary, we have developed a one-pot telescoped
synthesis of N-iodo sulfoximines from sulfides using NIS or I2.
The reaction proceeds via sulfoximines as reaction inter-
mediates. The protocol is simple and suitable for obtaining a
series of structurally diverse (hetero)aryl-, alkyl-, and benzyl-
substituted products that can be easily isolated as stable
compounds in pure form and in high yields. A multigram scale
synthesis was also demonstrated. The reactivity of N-iodo
sulfoximines was preliminarily investigated, revealing interest-
ing properties as iodinating and oxidizing agents. For example,
unlike NIS, which performs best in MeCN, no iodination of
activated anisole occurs with 2a. In contrast, iodination in
acetic acid is readily possible, even with 4-nitrophenol as an
example of a deactivated substrate. N-Iodo sulfoximines were
also found to be valuable intermediates in the synthesis of N-
SCF3-substituted sulfoximines. An in-depth study of the
chemistry of N-iodo sulfoximines is underway.
The reaction solvent was removed under reduced pressure; the
residue was redissolved in small amounts of DCM and subjected to
flash chromatography under pressure (nitrogen gas) through a short
plug of SiO2 as a stationary phase and DCM as eluant. The elution
was performed in less than 3 min to avoid decomposition of the
product. The progress of separation was monitored visually and, if
necessary, by TLC analysis. Pink-colored fractions that eluted first
contained I2 and PhI and were disposed of. Orange-colored fractions
containing product 2 were collected into 50−100 mL flasks, and the
solvent was removed under reduced pressure to obtain a brown-
orange semisolid. It was redissolved in small amounts of DCM,
triturated with large amounts of PE (or hexane) to induce
solidification (for solid products), and evaporated to dryness under
reduced pressure. The process was repeated 2−3 times to remove any
residual I2 or PhI, resulting in pure product 2.
Synthesis of 2w. A mixture of DMSO (78 mg, 1 mmol), 2 mL of
MeOH, 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), and 1.3 equiv
of DIB (1.3 mmol, 419 mg) were charged into a 10 mL round-bottom
flask equipped with a magnetic stirrer. The flask was closed with a
glass stopper, and the reaction mixture was let to stir vigorously for 1
h. Then, 1.1 equiv of I2 (1.1 mmol, 279 mg) was added, and stirring
was continued for another hour. The reaction mixture was cooled to
−5 °C (using an ice/NaCl cooling bath); the precipitate was collected
EXPERIMENTAL SECTION
■
General Considerations. Chemicals and solvents were obtained
from commercial sources. TLC was performed on Merck-60-F254
plates using mixtures of petroleum ether (PE), hexane, dichloro-
methane (DCM), diethyl ether, ethyl acetate, and methanol. For flash
chromatography, silica gel (63−200 μm, 70−230 mesh ASTM; Fluka)
by vacuum filtration using a Buchner funnel and washed with small
̈
amounts of cold (−5 °C) MeOH, followed by large amounts of
hexane. The product was dried under reduced pressure (vacuum
pump) to obtain an orange-brown solid of 2w (68 mg, 0.31 mmol,
31%).
was used. The glass frit MPLC Buchi was utilized for induction of
̈
nucleation of the products. Products were characterized by H, 13C,
and 19F NMR spectroscopy, IR spectroscopy, HRMS, and melting
points of solids. All NMR spectra were recorded in CDCl3 using
Me4Si as an internal standard. Chemical shifts are reported in δ
1
Synthesis of 2a Using NIS (10 mmol Scale). A mixture of
methyl phenyl sulfide (1a, 10 mmol, 1242 mg), 50 mL of MeOH, 1.5
equiv of (NH4)2CO3 (15 mmol, 1440 mg), and 2.3 equiv of DIB (23
mmol, 7410 mg) was charged into a 250 mL polyethylene container
equipped with a large magnetic stirrer. The container was closed with
a plastic screw top, and the reaction mixture was let to stir vigorously
for 1 h. Then, 1.1 equiv of NIS (11 mmol, 2480 mg) was added, and
the stirring was continued for another hour. The precipitate was
1
(ppm) values relative to δ = 0.00 ppm (Me4Si) for H NMR, and to
the central line of CDCl3 (δ = 77.16 ppm) for 13C NMR. 19F spectra
were referenced to CFCl3 as an external standard at δ = 0.00 ppm. 1H,
13C, and 19F NMR spectra were recorded with a Bruker Avance III
500 instrument at 500, 126, and 471 MHz, respectively. IR spectra
were recorded with a Bruker FTIR Alpha Platinum spectropho-
tometer. LC-HRMS analyses were performed on a Shimadzu LCMS-
IT-TOF system (Kyoto, Japan), composed of a liquid chromatograph
Nexera XR hyphenated to a mass spectrometer with an ion trap and
time-of-flight tube equipped with an electrospray ionization (ESI)
source. The melting points were determined with an OptiMelt
MPA100. By heating, all N-iodo sulfoximines first changed color from
orange or yellow to brown and then melted into brown oily liquids. A
change of color could imply partial degradation. Elemental
combustion analyses were performed with a PerkinElmer analyzer
2400 CHN.
collected by vacuum filtration using a Buchner funnel, was washed
̈
with small amounts of MeOH, and dried under reduced pressure
(vacuum pump) to obtain a pale yellow solid of 2a (2182 mg, 7.8
mmol, 78%).
Repeating the synthesis under the same reaction conditions in a
flawless 250 mL round-bottom flask, equipped with a magnetic stirrer,
afforded 2a in 44% yield (1244 mg, 4.4 mmol).
Synthesis of 2a Using I2 (10 mmol Scale). A mixture of methyl
phenyl sulfide (1a, 10 mmol, 1242 mg), 20 mL of MeOH, 1.5 equiv of
(NH4)2CO3 (15 mmol, 1440 mg), and 2.3 equiv of DIB (23 mmol,
7410 mg) was charged into a 250 mL polyethylene container
equipped with a large magnetic stirrer. The container was sealed with
a plastic screw top, and the reaction mixture was let to stir vigorously
for 1 h. Then, 1.1 equiv of I2 (11 mmol, 2794 mg) was added, and the
stirring was continued for another hour. The precipitate was collected
Synthesis of N-Iodo Sulfoximines. A mixture of organic sulfide
(1a−q, 1s, 1t, 1v, 1x−z, 1 mmol), 5 mL of MeOH, 1.5 equiv of
(NH4)2CO3 (1.5 mmol, 144 mg), and 2.3 equiv of PhI(OAc)2 (DIB,
2.3 mmol, 741 mg) was charged into a 10 mL round-bottom flask
equipped with a magnetic stirrer. The flask was sealed with a glass
stopper, and the reaction mixture was let to stir vigorously for 1 h.
by vacuum filtration using a Buchner funnel, was washed with small
̈
amounts of MeOH and large amounts of hexane, and dried under
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Note
reduced pressure (vacuum pump) to obtain 2a (2090 mg, 7.4 mmol,
74%) as an orange solid.
1143, 1054, 989, 943, 824, 757, 621 cm−1. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C9H12INOS 309.9757; Found 309.9757. Mp =
115.9−116.8 °C.
Synthesis of 2a Using I2 (25 mmol Scale). A mixture of methyl
phenyl sulfide (1a, 25 mmol, 3105 mg), 50 mL of MeOH, 1.5 equiv of
(NH4)2CO3 (37.5 mmol, 3603 mg), and 2.3 equiv of DIB (57.5
mmol, 18521 mg) was charged into a 250 mL polyethylene container
equipped with a large magnetic stirrer. The container was sealed with
a plastic screw top, and the reaction mixture was let to stir vigorously
for 1 h. Then, 1.1 equiv of I2 (27.5 mmol, 6980 mg) was added, and
the stirring was continued for another hour. The precipitate was
N-Iodo-S-(3,5-dimethylphenyl)-S-methyl Sulfoximine (2f). 1f (1
mmol, 152 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method A: pale yellow solid (189 mg, 61%). 1H NMR
(500 MHz, CDCl3): δ 7.45 (s, 2H), 7.28 (s, 1H), 3.30 (s, 3H), 2.43
(s, 6H). 13C{1H} NMR (126 MHz, CDCl3): δ 139.8, 139.4, 135.5,
125.8, 42.9, 21.4. IR (neat): 2918, 1605, 1451, 1194, 1107, 1003, 972,
959, 866, 848, 746, 684 cm−1. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C9H12INOS 309.9757; Found 309.9756. Mp = 116.2−116.7
°C.
collected by vacuum filtration using a Buchner funnel, was washed
̈
with small amounts of MeOH and large amounts of hexane, and dried
under reduced pressure (vacuum pump) to obtain 2a (5305 mg,
18.75 mmol, 75%) as an orange solid.
N-Iodo-S-(4-methoxyphenyl)-S-methyl Sulfoximine (2g). 1g (1
mmol, 154 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: yellow solid (272 mg, 87%). 1H NMR (500
MHz, CDCl3): δ 7.74−7.79 (m, 2H), 7.03−7.08 (m, 2H), 3.91 (s,
3H), 3.32 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 163.9,
131.1, 130.6, 114.9, 55.9, 43.0. IR (neat): 3000, 2913, 1590, 1574,
1491, 1257, 1199, 1088, 1005, 969, 951, 938, 837, 800, 735, 706
cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C8H10INO2S
311.9550; Found 311.9546. Mp = 118.6−118.9 °C.
N-Iodo-S-methyl-S-phenyl Sulfoximine (2a). 1a (1 mmol, 124
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
method A: yellow solid (208 mg, 74%). 1H NMR (500 MHz,
CDCl3): δ 7.82−7.89 (m, 2H), 7.66−7.71 (m, 1H), 7.57−7.64 (m,
2H), 3.33 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 140.0,
133.8, 129.8, 128.5, 42.9. IR (neat): 3019, 2917, 1445, 1198, 1088,
971, 949, 774, 738, 685 cm−1. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C7H8INOS 281.9445; Found 281.9431. Mp = 125.3−125.6
°C. CHN analysis: Calcd for C7H8INOS: C, 29.91; H, 2.87; N, 4.98.
Found: C, 30.00; H, 2.70; N, 4.81.
N-Iodo-S-ethyl-S-phenyl Sulfoximine (2b). 1b (1 mmol, 138 mg),
1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB (2.3
mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
method A: yellow solid (136 mg, 46%). 1H NMR (500 MHz,
CDCl3): δ 7.76−7.84 (m, 2H), 7.65−7.70 (m, 1H), 7.57−7.64 (m,
2H), 3.36−3.53 (m, 2H), 1.25−1.30 (m, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 138.1, 133.7, 129.6, 129.1, 49.6, 8.7. IR (neat):
2993, 2958, 1676, 1441, 1409, 1372, 1277, 1231, 1203, 1171, 1088,
1041, 956, 766, 719, 687, 674 cm−1. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C8H10INOS 295.9601; Found 295.9598. Mp = 118.2−
118.6 °C.
N-Iodo-S-(3-methoxyphenyl)-S-methyl Sulfoximine (2h). 1h (1
mmol, 154 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
1
mg), isolation method A: yellowish solid (152 mg, 49%). H NMR
(500 MHz, CDCl3): δ 7.47−7.53 (m, 1H), 7.41 (ddd, J = 7.8, 1.8, 1.0
Hz, 1H), 7.34 (dd, J = 2.6, 1.8 Hz, 1H), 7.19 (ddd, J = 8.2, 2.6, 1.0
Hz, 1H), 3.90 (s, 3H), 3.32 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 160.5, 141.2, 130.8, 120.4, 120.4, 112.8, 55.9, 42.8. IR
(neat): 3023, 2921, 1676, 1594, 1479, 1243, 1201, 998, 971, 751
cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C8H10INO2S
311.9550; Found 311.9554. Mp = 125.1−125.5 °C.
N-Iodo-S-(2-methoxyphenyl)-S-methyl Sulfoximine (2i). 1i (1
mmol, 154 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method A: pale yellow solid (213 mg, 68%). 1H NMR
(500 MHz, CDCl3): δ 7.95 (dd, J = 8.0, 1.8 Hz, 1H), 7.63 (ddd, J =
8.4, 7.5, 1.8 Hz, 1H), 7.15 (ddd, J = 8.0, 7.5, 1.0 Hz, 1H), 7.07 (dd, J
= 8.4, 1.0 Hz, 1H), 3.99 (s, 3H), 3.49 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 156.9, 135.7, 131.7, 127.3, 120.9, 112.8, 56.7, 41.0.
IR (neat): 3097, 3041, 3013, 2968, 2928, 2832, 1589, 1477, 1280,
1192, 1065, 990, 958, 760 cm−1. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C8H10INO2S 311.9550; Found 311.9543. Mp = 127.8−
129.3 °C.
N-Iodo-S-(1-dodecyl)-S-phenyl Sulfoximine (2c). 1c (1 mmol, 278
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
1
method A: pale yellow solid (369 mg, 85%). H NMR (500 MHz,
CDCl3): δ 7.77−7.83 (m, 2H), 7.65−7.70 (m, 1H), 7.57−7.64 (m,
2H), 3.44 (ddd, J = 14.0, 11.4, 5.1 Hz, 1H), 3.33 (ddd, J = 14.0, 11.3,
5.0 Hz, 1H), 1.74−1.85 (m, 1H), 1.57−1.68 (m, 1H), 1.15−1.35 (m,
18H), 0.88 (t, J = 6.9 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
138.9, 133.6, 129.6, 129.0, 55.2, 31.9, 29.6, 29.6, 29.5, 29.4, 29.3, 29.0,
28.1, 23.8, 22.7, 14.2. IR (neat): 2911, 2849, 1472, 1444, 1220, 1206,
1175, 1092, 1011, 967, 756, 749, 713, 686 cm−1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C18H30INOS 436.1166; Found 436.1171.
Mp = 93.1−93.5 °C.
N-Iodo-S-(4-fluorophenyl)-S-methyl Sulfoximine (2j). 1j (1 mmol,
156 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of
DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg),
isolation method B: yellow solid (272 mg, 87%). 1H NMR (500 MHz,
CDCl3): δ 7.79−7.86 (m, 2H), 7.26−7.32 (m, 2H), 3.36−3.53 (m,
2H), 1.25−1.31 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 165.7
(C-F, 1JC‑F = 256.4 Hz), 133.9 (s), 131.8 (C-F, 3JC‑F = 9.5 Hz), 116.8
N-Iodo-S-(2-butyl)-S-phenyl Sulfoximine (2d). 1d (1 mmol, 166
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
method B: yellow solid (282 mg, 87%), a mixture of diastereoisomers.
1H NMR (500 MHz, CDCl3): δ 7.72−7.81 (m, 4H), 7.64−7.70 (m,
2H), 7.55−7.63 (m, 4H), 3.28−3.41 (m, 2H), 2.19−2.29 (m, 1H),
1.92−2.02 (m, 1H), 1.38−1.53 (m, 2H), 1.37 (d, J = 6.9 Hz, 3H),
1.23 (d, J = 6.9 Hz, 3H), 0.98 (t, J = 7.5 Hz, 3H), 0.92 (t, J = 7.5 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 137.4, 137.3, 133.6, 133.6,
130.0, 130.0, 129.5 (2C), 62.2, 62.0, 24.4, 23.3, 14.4, 13.3, 11.3, 11.3.
2
(C-F, JC‑F = 22.7 Hz), 49.7 (s), 8.7 (s). 19F NMR (471 MHz,
CDCl3): δ −104.3 (s, 1F). IR (neat): 3095, 3063, 2974, 1922, 1581,
1486, 1221, 1193, 1154, 1085, 986, 954, 843, 816, 768, 724, 694
cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C8H9FINOS
313.9506; Found 313.9499. Mp = 96.1−97.2 °C.
N-Iodo-S-(3,4-dichlorophenyl)-S-methyl Sulfoximine (2k). 1k (1
mmol, 193 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: pale orange solid (290 mg, 83%). 1H NMR
(500 MHz, CDCl3): δ 7.94 (d, J = 2.1 Hz, 1H), 7.64−7.70 (m, 2H),
3.34 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 139.9, 138.9,
134.5, 131.8, 130.4, 127.4, 42.9. IR (neat): 3078, 3002, 1567, 1449,
1368, 1206, 1141, 1093, 1033, 984, 959, 893, 812, 746, 673 cm−1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C7H6Cl2INOS
349.8665; Found 349.8665. Mp = 117.4−118.2 °C.
IR (neat): 2972, 2934, 1442, 1192, 1086, 969, 789, 761, 731 cm−1
.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C10H14INOS 323.9914;
Found 323.9917. Mp = 90.2−91.5 °C.
N-Iodo-S-(2,4-dimethylphenyl)-S-methyl Sulfoximine (2e). 1e (1
mmol, 152 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: yellow solid (272 mg, 88%). 1H NMR (500
MHz, CDCl3): δ 7.86 (d, J = 8.2 Hz, 1H), 7.21 (dd, J = 8.2, 1.8 Hz,
1H), 7.16 (d, J = 1.8 Hz, 1H), 3.32 (s, 3H), 2.61 (s, 3H), 2.41 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.7, 137.7, 134.9, 134.0,
131.0, 127.7, 41.6, 21.5, 19.9. IR (neat): 2919, 1599, 1449, 1198,
N-Iodo-S-(4-bromophenyl)-S-methyl Sulfoximine (2l). 1l (1
mmol, 203 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
5995
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Note
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: yellow solid (310 mg, 86%). 1H NMR (500
MHz, CDCl3): δ 7.73−7.77 (m, 2H), 7.68−7.73 (m, 2H), 3.32 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 139.1, 133.1, 130.0, 129.2,
42.9. IR (neat): 3074, 3017, 2920, 1566, 1466, 1404, 1200, 1085,
1062, 1017, 975, 953, 824, 758, 715 cm−1. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C7H7BrINOS 359.8549; Found 359.8559. Mp =
95.9−96.8 °C.
N-Iodo-S-(4-cyanophenyl)-S-methyl Sulfoximine (2m). 1m (1
mmol, 149 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: yellow solid (205 mg, 67%). 1H NMR (500
MHz, CDCl3): δ 7.95−8.00 (m, 2H), 7.89−7.93 (m, 2H), 3.36 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.5, 133.5, 129.2, 117.6,
117.3, 42.7. IR (neat): 3090, 2992, 2911, 2231, 1396, 1206, 1178,
1087, 1027, 1006, 964, 845, 833, 785, 748 cm−1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C8H7IN2OS 306.9397; Found 306.9407.
Mp = 100.8−102.4 °C.
N-Iodo-S-pentafluorophenyl-S-phenethyl Sulfoximine (2r). 1r (1
mmol, 304 mg), 2.625 equiv of (NH4)2CO3 (2.625 mmol, 252 mg),
4.025 equiv of DIB (4.025 mmol, 1296 mg), 1.1 equiv of NIS (1.1
mmol, 248 mg), isolation method B: yellow solid (369 mg, 80%). 1H
NMR (500 MHz, CDCl3): δ 7.21−7.28 (m, 2H), 7.11−7.21 (m, 3H),
3.77−4.01 (m, 2H), 3.12−3.34 (m, 2H). 13C{1H} NMR (126 MHz,
CDCl3): δ 143.7−146.3 (m), 143.0−145.6 (m), 136.6−139.1 (m),
136.2, 128.9, 128.6, 127.3, 115.2−116.7 (m), 57.5, 29.6. 19F NMR
(471 MHz, CDCl3): δ −135.8 (d, J = 23.3 Hz, 2F), −143.8 (t, J =
20.8 Hz, 1F), −158.1 (t, J = 20.5 Hz, 2F). IR (neat): 2926, 1639,
1517, 1482, 1230, 1208, 1093, 1026, 980, 743, 691 cm−1. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C14H9F5INOS 461.9443;
Found 461.9451. Mp = 103.0−104.1 °C.
N-Iodo-S-phenyl-S-(3-phenylpropyl) Sulfoximine (2s). 1s (1
mmol, 228 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: light yellow solid (256 mg, 66%). 1H NMR
(500 MHz, CDCl3): δ 7.75−7.80 (m, 2H), 7.64−7.70 (m, 1H),
7.56−7.61 (m, 2H), 7.23−7.27 (m, 2H), 7.16−7.21 (m, 1H), 7.05−
7.09 (m, 2H), 3.44 (ddd, J = 14.0, 11.0, 5.3 Hz, 1H), 3.32 (ddd, J =
14.0, 10.9, 5.1 Hz, 1H), 2.62−2.69 (m, 2H), 2.08−2.19 (m, 1H),
1.92−2.02 (m, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 139.7,
138.7, 133.7, 129.7, 129.0, 128.7, 128.4, 126.5, 54.3, 34.0, 25.3. IR
(neat): 3052, 2983, 2944, 1605, 1579, 1495, 1445, 1206, 1092, 987,
745, 686 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C15H16INOS 386.0070; Found 386.0087. Mp = 99.3−100.4 °C.
N-Iodo-S,S-diphenyl Sulfoximine (2t). 1t (1 mmol, 186 mg), 1.5
equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB (2.3
mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
method A: yellow solid (180 mg, 53%). 1H NMR (500 MHz,
CDCl3): δ 7.90−7.98 (m, 4H), 7.54−7.60 (m, 2H), 7.46−7.54 (m,
4H). 13C{1H} NMR (126 MHz, CDCl3): δ 139.4, 133.2, 129.5, 128.4.
IR (neat): 3062, 1445, 1219, 1088, 976, 757, 722, 685 cm−1. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C12H10INOS 343.9601; Found
343.9598. Mp = 114.2−114.9 °C.
N-Iodo-S-methyl-S-(4-nitrophenyl) Sulfoximine (2n). 1n (1
mmol, 169 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3
equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248
mg), isolation method B: yellow solid (280 mg, 86%). 1H NMR (500
MHz, CDCl3): δ 8.43−8.47 (m, 2H), 8.03−8.10 (m, 2H), 3.38 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 150.9, 146.1, 129.9, 124.9,
42.9. IR (neat): 3099, 3004, 2918, 1605, 1520, 1343, 1209, 1185,
1088, 1021, 1004, 961, 853, 767, 739, 716, 679 cm−1. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C7H7IN2O3S 326.9295; Found
326.9306. Mp = 97.2−100.7 °C.
N-Iodo-S-methyl-S-(2-naphthyl) Sulfoximine (2o). 1o (1 mmol,
174 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of
DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg),
1
isolation method B: pale yellow solid (162 mg, 49%). H NMR (500
MHz, CDCl3): δ 8.47 (d, J = 1.9 Hz, 1H), 8.00−8.06 (m, 2H), 7.93−
7.98 (m, 1H), 7.76 (dd, J = 8.7, 1.9 Hz, 1H), 7.70 (ddd, J = 8.2, 6.9,
1.4 Hz, 1H), 7.65 (ddd, J = 8.0, 6.8, 1.4 Hz, 1H), 3.39 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 136.8, 135.4, 132.5, 130.6,
130.2, 129.6, 129.5, 128.1, 127.9, 122.8, 42.9. IR (neat): 3003, 2921,
1624, 1590, 1504, 1346, 1267, 1208, 1070, 985, 954, 938, 811, 753,
637 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C11H10INOS
331.9601; Found 331.9601. Mp = 93.4−94.9 °C.
N-Iodo-dibenzothiophene Sulfoximine (2u). 1u (1 mmol, 184
mg), 1.875 equiv of (NH4)2CO3 (1.875 mmol, 180 mg), 2.875 equiv
of DIB (2.875 mmol, 926 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg),
isolation method A: yellow solid (252 mg, 74%). 1H NMR (500
MHz, CDCl3): δ 7.95−8.00 (m, 2H), 7.79−7.83 (m, 2H), 7.63−7.68
(m, 2H), 7.53−7.59 (m, 2H). 13C{1H} NMR (126 MHz, CDCl3): δ
137.9, 134.0, 132.3, 130.1, 123.2, 121.8. IR (neat): 2987, 1587, 1444,
1195, 1195, 1122, 1066, 978, 948, 753, 709 cm−1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C12H8INOS 341.9444; Found 341.9457.
Mp = 180.0−181.3 °C.
N-Iodo-S-phenethyl-S-phenyl Sulfoximine (2p). 1p (1 mmol, 214
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
1
method B: orange oil (334 mg, 90%). H NMR (500 MHz, CDCl3):
δ 7.81−7.87 (m, 2H), 7.64−7.70 (m, 1H), 7.56−7.63 (m, 2H), 7.22−
7.27 (m, 2H), 7.17−7.22 (m, 1H), 7.07−7.11 (m, 2H), 3.72 (ddd, J =
14.0, 12.2, 5.0 Hz, 1H), 3.56 (ddd, J = 14.0, 12.0, 4.9 Hz, 1H), 3.13
(ddd, J = 13.9, 12.0, 5.0 Hz, 1H), 2.96 (ddd, J = 13.9, 12.2, 4.9 Hz,
1H). 13C{1H} NMR (126 MHz, CDCl3): δ 138.7, 137.1, 133.8, 129.7,
129.0, 128.9, 128.4, 127.1, 56.3, 29.8. IR (neat): 3059, 3026, 2924,
1602, 1581, 1495, 1445, 1398, 1196, 1088, 1003, 981, 730, 685 cm−1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H14INOS 371.9914;
Found 371.9919.
N-Iodo-S-benzyl-S-methyl Sulfoximine (2v). 1v (1 mmol, 138
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
method B: brown solid (176 mg, 60%). 1H NMR (500 MHz,
CDCl3): δ 7.42 (app. as s, 5H), 4.47−4.56 (m, 2H), 2.89 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 130.6, 129.4, 129.3, 129.2, 60.9,
38.0. IR (neat): 3001, 2969, 2920, 1493, 1454, 1411, 1210, 1198, 981,
945, 778, 697 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C8H10INOS 295.9601; Found 295.9595. Mp = 81.2−83.8 °C.
N-Iodo-S,S-dimethyl Sulfoximine (2w). DMSO (1 mmol, 78 mg),
1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 1.3 equiv of DIB (1.3
mmol, 419 mg), 1.1 equiv of I2 (1.1 mmol, 279 mg), isolation: orange-
N-Iodo-S-(2-pentafluorophenyethyl)-S-phenyl Sulfoximine (2q).
1q (1 mmol, 304 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg),
2.3 equiv of DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol,
1
1
248 mg), isolation method B: pale yellow solid (379 mg, 82%). H
brown solid (68 mg, 31%). H NMR (500 MHz, CDCl3): δ 3.21 (s,
6H). 13C{1H} NMR (126 MHz, CDCl3): δ 42.1. IR (neat): 2999,
2918, 1409, 1301, 1167, 1016, 970, 930, 754, 682 cm−1. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C2H6INOS 219.9288; Found
219.9286. Mp = 118.4−119.0 °C.
NMR (500 MHz, CDCl3): δ 7.78−7.88 (m, 2H), 7.67−7.74 (m, 1H),
7.56−7.66 (m, 2H), 3.66−3.79 (m, 1H), 3.52−3.64 (m, 1H), 3.14−
3.25 (m, 1H), 3.01−3.14 (m, 1H). 13C{1H} NMR (126 MHz,
1
2
3
CDCl3): δ 145.0 (C-F, JC‑F = 247.3 Hz, JC‑F = 11.9 Hz, JC‑F = 7.9
4
1
2
Hz, JC‑F = 3.8 Hz), 140.4 (C-F, JC‑F = 253.9 Hz, JC‑F = 13.3 Hz,
3JC‑F = 5.3 Hz), 138.0 (s), 136.3−138.7 (m), 134.0 (s), 129.7 (s),
128.8 (s), 110.5 (C-F, 2JC‑F = 18.1 Hz, 3JC‑F = 4.0 Hz), 52.7 (s), 17.3
(s). 19F NMR (471 MHz, CDCl3): δ −143.0 − (−142.9) (m, 2F),
−155.5 (t, J = 20.7 Hz, 1F), −162.2 − (−162.0) (m, 2F). IR (neat):
2987, 1520, 1505, 1208, 1089, 982, 962, 938, 748, 721, 682 cm−1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H9F5INOS
461.9443; Found 461.9446. Mp = 115.3−116.4 °C.
N-Iodo-S-(1-dodecyl)-S-methyl Sulfoximine (2x). 1x (1 mmol,
216 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of
DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg),
1
isolation method B: brown-red solid (156 mg, 42%). H NMR (500
MHz, CDCl3): δ 3.18−3.34 (m, 2H), 3.07 (s, 3H), 1.77−1.86 (m,
2H), 1.40−1.48 (m, 2H), 1.22−1.38 (m, 16H), 0.88 (t, J = 6.8 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 54.6, 40.2, 32.0, 29.7,
29.7, 29.6, 29.4, 29.3, 29.1, 28.3, 23.9, 22.8, 14.2. IR (neat): 2916,
5996
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Note
2849, 1468, 1184, 998, 929, 719 cm−1. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C13H28INOS 374.1009; Found 374.1009. Mp = 51.5−
51.9 °C.
NaHSO3 or Na2S2O3 solution, 10% aqueous solution of HCl, and
water, respectively, and dried over anhydrous MgSO4 or Na2SO4.
Solvent was removed under reduced pressure to afford pure products
6, 8, 10, 12, or 14.
N-Iodo-S,S-(di-1-octyl) Sulfoximine (2y). 1y (1 mmol, 259 mg),
1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB (2.3
mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg), isolation
method B: brown oil (211 mg, 51%). 1H NMR (500 MHz, CDCl3): δ
2.85−3.33 (m, 4H), 1.70−1.85 (m, 4H), 1.38−1.47 (m, 4H), 1.21−
1.38 (m, 16H), 0.86−0.91 (m, 6H). 13C{1H} NMR (126 MHz,
CDCl3): δ 52.4, 31.7, 29.0, 29.0, 28.3, 23.2, 22.6, 14.1. IR (neat):
2954, 2922, 2854, 1630, 1461, 1188, 982, 756, 722 cm−1. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C16H34INOS 416.1479; Found
416.1469.
4-Iodoanisole62 (6). 5 (1 mmol, 108 mg), 1.1 equiv of 2a in one
portion (1.1 mmol, 309 mg), extraction: white solid (202 mg, 86%).
1H NMR (500 MHz, CDCl3): δ 7.52−7.58 (m, 2H), 6.64−6.71 (m,
2H), 3.77 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 159.6,
138.3, 116.5, 82.8, 55.4. IR (neat): 3005, 2967, 2938, 2838, 1584,
1567, 1484, 1454, 1285, 1241, 1175, 1102, 1025, 997, 829, 807, 784
cm−1.
2,4,6-Triiodophenol63 (8). 7 (1 mmol, 94 mg), 3.3 equiv of 2a in
one portion (3.3 mmol, 927 mg), extraction: pale white solid (465
mg, 99%). 1H NMR (500 MHz, CDCl3): δ 7.93 (s, 2H), 5.77 (s, 1H,
OH). 13C{1H} NMR (126 MHz, CDCl3): δ 153.9, 146.5, 83.5, 83.5.
IR (neat): 3428, 3049, 1539, 1432, 1369, 1293, 1258, 1229, 1170,
1133, 858, 697, 629 cm−1.
N-Iodo-S-methyl-S-(2-pyridine) Sulfoximine (2z). 1z (1 mmol,
125 mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of
DIB (2.3 mmol, 741 mg), 1.1 equiv of NIS (1.1 mmol, 248 mg),
isolation method A: yellow solid (187 mg, 66%). 1H NMR (500
MHz, CDCl3): δ 8.77 (ddd, J = 4.7, 1.8, 0.9 Hz, 1H), 8.12−8.17 (m,
1H), 7.97−8.03 (m, 1H), 7.57 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 3.50 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 157.6, 150.6, 138.1, 127.4,
123.4, 39.5. IR (neat): 3017, 2915, 1577, 1560, 1421, 1206, 1082,
984, 785, 752 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C6H7IN2OS 282.9397; Found 282.9384. Mp = 103.0−105.4 °C.
One-Pot Synthesis of N-Bromo and N-Chloro Sulfoximines
3 and 4. This procedure is similar to the one-pot synthesis of N-iodo
sulfoximines. A mixture of methyl phenyl sulfide (1a, 1 mmol, 124
mg), 5 mL of MeOH, 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg),
and 2.3 equiv of DIB (2.3 mmol, 741 mg) was charged into a 10 mL
round-bottom flask equipped with a magnetic stirrer. The flask was
sealed with a glass stopper, and the reaction mixture was let to stir
vigorously for 1 h. Then, 1.75 equiv of NBS (1.75 mmol, 312 mg) or
1.75 equiv of NCS (1.75 mmol, 235 mg) was added, and the stirring
was continued for another hour. The reaction solvent was removed
under reduced pressure; the residue was redissolved in small amounts
of DCM and subjected to flash chromatography under pressure
(nitrogen gas) through a short plug of SiO2 as a stationary phase and
DCM as eluant. The progress of separation was monitored by TLC
analysis. Fractions containing product 3 or 4 were collected into 50−
100 mL flasks, and the solvent was removed under reduced pressure
to obtain a lightly colored semisolid. It was redissolved in small
amounts of DCM, triturated with large amounts of PE (or hexane),
and evaporated to dryness under reduced pressure. The process was
repeated 2−3 times to remove any residual PhI, resulting in pure
products 3 (194 mg, 0.83 mmol, 83%) as a colorless solid, and 4 (120
mg, 0.63 mmol, 63%) as a colorless solid.
1-Iodo-4-methoxynaphthalene62 (10). 9 (1 mmol, 158 mg), 1.1
equiv of 2a in portions over 2 h (1.1 mmol, 309 mg), extraction: pale
1
yellow solid (276 mg, 97%). H NMR (500 MHz, CDCl3): δ 8.20−
8.27 (m, 1H), 8.00−8.06 (m, 1H), 7.95 (d, J = 8.2 Hz, 1H), 7.56−
7.63 (m, 1H), 7.48−7.55 (m, 1H), 6.59 (d, J = 8.1 Hz, 1H), 3.99 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 156.3, 137.0, 134.7, 131.8,
128.2, 126.7, 126.1, 122.6, 105.7, 88.3, 55.8. IR (neat): 2932, 2837,
1828, 1584, 1503, 1454, 1416, 1364, 1315, 1258, 1238, 1155, 1082,
1027, 989, 807, 757, 712, 614 cm−1.
2,6-Diiodo-4-nitro-phenol63 (12). 11 (1 mmol, 139 mg), 2.2 equiv
of 2a in one portion (2.2 mmol, 618 mg), extraction: yellow solid
(384 mg, 98%). 1H NMR (500 MHz, CDCl3): δ 8.60 (s, 2H).
13C{1H} NMR (126 MHz, CDCl3): δ 159.1, 142.3, 134.9, 80.9. IR
(neat): 3368, 3068, 1576, 1502, 1441, 1398, 1312, 1228, 1114, 898,
739, 675 cm−1.
Diphenyl Disulfide64 (14). 13 (1 mmol, 110 mg), 1.1 equiv of 2a in
portions over 1 h (1.1 mmol, 309 mg), extraction: white solid (109
1
mg, 100%). H NMR (500 MHz, CDCl3): δ 7.45−7.52 (m, 4H),
7.24−7.31 (m, 4H), 7.18−7.24 (m, 2H). 13C{1H} NMR (126 MHz,
CDCl3): δ 137.1, 129.2, 127.6, 127.3. IR (neat): 3066, 2976, 2915,
1573, 1473, 1435, 1232, 1071, 1020, 995, 733, 684 cm−1.
Synthesis of N-(Trifluoromethanesulfenyl) Sulfoximines 15
from N-Iodo Sulfoximines 2. The method is similar to the known
procedure.43 AgSCF3 was prepared according to the literature
procedure.65
A mixture of 2a, 2g, 2n, or 2t (0.304−1 mmol) in dry MeCN (2
mL per 1 mmol of 2) was charged into a 10 mL flask equipped with a
magnetic stirrer. The flask was sealed with a septum under an argon
atmosphere, and a solution of AgSCF3 (1.2 equiv, 3 mL of MeCN per
1.2 mmol of AgSCF3) was added. The reaction mixture was let to stir
in the dark for a specified time (20−60 min) as judged by TLC
analysis. After completion, MeCN was removed under reduced
pressure; the crude residue was redissolved in small amounts of DCM
and subjected to flash chromatography under pressure (nitrogen gas)
through a short plug of SiO2 as stationary phase and DCM as eluant.
Fractions containing product 15 were collected, and solvent was
removed under reduced pressure to afford products 15a, 15g, 15n, or
15t as white solids.
N-Bromo-S-methyl-S-phenyl Sulfoximine43 (3). 1a (1 mmol, 124
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.75 equiv of NBS (1.75 mmol, 312 mg),
1
isolation method B: colorless solid (194 mg, 83%). H NMR (500
MHz, CDCl3): δ 7.87−7.95 (m, 2H), 7.66−7.72 (m, 1H), 7.58−7.65
(m, 2H), 3.30 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 137.9,
134.1, 129.8, 128.8, 42.7. IR (neat): 3004, 2913, 1446, 1415, 1222,
1088, 981, 964, 940, 777, 738, 683 cm−1.
N-Chloro-S-methyl-S-phenyl Sulfoximine43 (4). 1a (1 mmol, 124
mg), 1.5 equiv of (NH4)2CO3 (1.5 mmol, 144 mg), 2.3 equiv of DIB
(2.3 mmol, 741 mg), 1.75 equiv of NCS (1.75 mmol, 235 mg),
N-(Trifluoromethanesulfenyl)-S-methyl-S-phenyl Sulfoximine43
(15a). 2a (1 mmol, 281 mg), 1.2 equiv of AgSCF3 (1.2 mmol, 251
1
isolation method B: colorless solid (120 mg, 63%). H NMR (500
1
MHz, CDCl3): δ 7.92−7.98 (m, 2H), 7.69−7.74 (m, 1H), 7.60−7.67
(m, 2H), 3.27 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 136.5,
134.3, 129.9, 129.2, 42.2. IR (neat): 3016, 2994, 2915, 1709, 1447,
1215, 1088, 1006, 990, 968, 936, 742, 682, 644 cm−1.
mg), 60 min, flash (SiO2/DCM): white solid (195 mg, 76%). H
NMR (500 MHz, CDCl3): δ 7.87−7.97 (m, 2H), 7.68−7.75 (m, 1H),
7.59−7.66 (m, 2H), 3.29 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3):
1
δ 137.9, 134.4, 130.5 (C-F, JC‑F = 312.4 Hz), 129.8, 128.4, 43.7. 19F
Reactions with 2a: Iodination and Oxidation Procedures. A
mixture of 2a (1.1−3.3 mmol), 5 mL of AcOH, and compound 5, 7,
9, 11, or 13 (1 mmol) was charged into a 10 mL round-bottom flask
equipped with a magnetic stirrer. The flask was sealed with a glass
stopper, and the reaction mixture was let to stir for a specific time (t)
at a specific temperature (T) and monitored by TLC analysis. After
completion, the reaction mixture was diluted with DCM and 10%
aqueous solution HCl was added. Products were extracted with DCM
three times; the organic phase was washed with 10% aqueous
NMR (471 MHz, CDCl3): δ −50.7 (s, 3F). IR (neat): 3062, 3028,
3006, 2926, 1581, 1449, 1209, 1111, 1087, 986, 960, 785, 747, 718,
687 cm−1.
N-(Trifluoromethanesulfenyl)-S-(4-methoxyphenyl)-S-methyl
Sulfoximine43 (15g). 2g (1 mmol, 311 mg), 1.2 equiv of AgSCF3 (1.2
mmol, 251 mg), 60 min, flash (SiO2/DCM): white solid (267 mg,
1
94%). H NMR (500 MHz, CDCl3): δ 7.79−7.85 (m, 2H), 7.03−
7.09 (m, 2H), 3.90 (s, 3H), 3.25 (s, 3H). 13C{1H} NMR (126 MHz,
1
CDCl3): δ 164.2, 130.5 (C-F, JC‑F = 312.5 Hz), 130.4, 128.4, 114.9,
5997
https://doi.org/10.1021/acs.joc.1c00292
J. Org. Chem. 2021, 86, 5991−6000

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
55.8, 43.8. 19F NMR (471 MHz, CDCl3): δ −50.7 (s, 3F). IR (neat):
3017, 2932, 2844, 1592, 1497, 1263, 1219, 1088, 1009, 978, 833, 803,
766, 705 cm−1.
AUTHOR INFORMATION
Corresponding Author
■
Marjan Jereb − Faculty of Chemistry and Chemical
Technology, University of Ljubljana, 1000 Ljubljana,
Slovenia; orcid.org/0000-0002-1318-0560;
Email: marjan.jereb@fkkt.uni-lj.si
N-(Trifluoromethanesulfenyl)-S-(4-nitrophenyl)-S-methyl Sulfox-
imine43 (15n). 2n (0.304 mmol, 99 mg), 1.2 equiv of AgSCF3 (0.365
mmol, 76 mg), 20 min, flash (SiO2/DCM): white solid (62 mg, 68%).
1H NMR (500 MHz, CDCl3): δ 8.44−8.50 (m, 2H), 8.10−8.16 (m,
2H), 3.36 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 151.2,
1
143.9, 130.3 (C-F, JC‑F = 312.4 Hz), 130.0, 124.9, 43.6. 19F NMR
Author
Anze Zupanc − Faculty of Chemistry and Chemical
̌
Technology, University of Ljubljana, 1000 Ljubljana,
Slovenia
(471 MHz, CDCl3): δ −50.4 (s, 3F). IR (neat): 3109, 3053, 3022,
2926, 1604, 1527, 1345, 1226, 1136, 1105, 1087, 990, 963, 739, 728
cm−1.
N-(Trifluoromethanesulfenyl)-S,S-diphenyl Sulfoximine43 (15t).
2t (0.515 mmol, 147 mg), 1.2 equiv of AgSCF3 (0.515 mmol, 108
mg), 20 min, flash (SiO2/DCM): white solid (88 mg, 65%). 1H NMR
(500 MHz, CDCl3): δ 7.92−8.01 (m, 4H), 7.58−7.64 (m, 2H),
7.50−7.58 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3): δ 139.0,
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00292
Notes
1
133.8, 130.5 (C-F, JC‑F = 312.5 Hz), 129.6, 128.5. 19F NMR (471
The authors declare no competing financial interest.
MHz, CDCl3): δ −50.4 (s, 3F). IR (neat): 3066, 1580, 1475, 1446,
1221, 1151, 1107, 1081, 953, 761, 730, 683 cm−1.
ACKNOWLEDGMENTS
■
Preparation of Other Sulfides. Synthesis of 1p. A mixture of
thiophenol (2.200 g, 20 mmol) and styrene (2.184 g, 21 mmol) was
charged into a 100 mL round-bottom flask. The flask was sealed with
a glass stopper, equipped with a magnetic stirrer, and let to stir
overnight at 60 °C. After completion of the reaction as determined by
TLC analysis, the crude product was purified by vacuum distillation,
furnishing 1p as a yellow oil in 90% yield.
The authors acknowledge the financial support from the
Slovenian Research Agency (Research Core Funding Grant
P1-0230, Young Researcher Grant to A.Z., and Projects J1-
8147 and J1-9166). The authors thank M. Sc. Anja Kristl for
HRMS analyses.
Synthesis of 1q. A mixture of thiophenol (1.533 g, 13.9 mmol) and
pentafluorostyrene (2.980 g, 15.35 mmol) was charged into a 100 mL
round-bottom flask. The flask was sealed with a glass stopper,
equipped with a magnetic stirrer, and let to stir overnight at 60 °C.
After completion of the reaction as determined by TLC analysis, the
crude product was purified by vacuum distillation, furnishing 1q as a
yellow oil in 85% yield.
Synthesis of 1r. A mixture of pentafluorothiophenol (4.000 g, 20
mmol) and styrene (2.080 g, 20 mmol) was charged into a 100 mL
round-bottom flask. The flask was sealed with a glass stopper,
equipped with a magnetic stirrer, and let to stir overnight at 60 °C.
After completion of the reaction as determined by TLC analysis, the
crude product was purified by vacuum distillation, furnishing 1r as a
yellow oil in 92% yield.
Synthesis of 1s. To a solution of thiophenol (2.200 g, 20 mmol) in
80 mL of MeCN, K2CO3 (3.312 g, 24 mmol) and 1-bromo-3-
phenylpropane (4.179 g, 21 mmol) were consecutively added, and the
mixture was let to stir overnight at room temperature. After
completion, as determined by TLC analysis, the reaction solvent
was evaporated, and the residue was partitioned three times between
DCM and water. The combined organic phase was dried over
anhydrous MgSO4, and solvent was removed. The oily residue was
purified by vacuum distillation, furnishing 1s as a yellow oil in 94%
yield.
Synthesis of 1y. A mixture of 1-octanethiol (2.926 g, 20 mmol)
and 1-octene (2.244 g, 20 mmol) was charged into a 100 mL round-
bottom flask equipped with a magnetic stirrer. The flask was sealed
with a glass stopper, and the reaction mixture was let to stir overnight
at 60 °C. After completion, as determined by TLC analysis, the crude
product was purified by vacuum distillation, furnishing 1y as a yellow
oil in 92% yield.
DEDICATION
■
This paper is dedicated to Professor Antonio Togni, ETH
Zurich, on the occasion of his 65th anniversary and his lifetime
research and pedagogical achievements.
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00292.
Experimental procedures and analytic data for the
compounds described and copies of NMR spectra
(PDF)
5998
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J. Org. Chem. 2021, 86, 5991−6000

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
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