A Selectfluor-promoted oxidative reaction of disulfides and amines: access to sulfinamides

Article abstract of DOI:10.1039/d0ob00720j

An unprecedented transition-metal-free oxidative reaction of disulfides and amines with Selectfluor as a mild oxidant under aerobic conditions was developed. This reaction was conducted under mild conditions and tolerated a wide range of coupling partners including disulfides and amines, affording the corresponding sulfinamide products in good chemical yields. Furthermore, this reaction could be used in gram-scale synthesis. This reaction enriches the research content of Selectfluor and provides a valuable vista for the convenient synthesis of sulfinamides.

Full text of DOI:10.1039/d0ob00720j

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A Selectfluor-promoted oxidative reaction of
disulfides and amines: access to sulfinamides†
Cite this: DOI: 10.1039/d0ob00720j
Haibo Mei, a,b Jiang Liu,a Romana Pajkert,c Gerd-Volker Röschenthaler*c and
a
Jianlin Han
*
An unprecedented transition-metal-free oxidative reaction of disulfides and amines with Selectfluor as a
mild oxidant under aerobic conditions was developed. This reaction was conducted under mild conditions
and tolerated a wide range of coupling partners including disulfides and amines, affording the corres-
ponding sulfinamide products in good chemical yields. Furthermore, this reaction could be used in gram-
scale synthesis. This reaction enriches the research content of Selectfluor and provides a valuable vista for
the convenient synthesis of sulfinamides.
Received 6th April 2020,
Accepted 29th April 2020
DOI: 10.1039/d0ob00720j
rsc.li/obc
has the disadvantage of the formation of sulfonamides as the
by-product. In recent years, the Taniguchi group developed a
Introduction
Sulfinamides belong to an important class of organosulfur transition-metal-catalyzed oxidative coupling reaction between
compounds in drug research due to their fascinating role in thiols or disulfides with amines in the presence of NH4PF6
the design of bioactive molecules and new pharmaceuticals.1 under air to afford sulfinamides as the product (Scheme 1a).10
Also, sulfinamides exist widely in N–S bond-containing natural On the other hand, the Pd-catalyzed reactions of amino-substi-
products.2 Furthermore, sulfinamides represent a valuable syn- tuted iodoarenes have also been developed for the synthesis of
thetic block in organic synthesis for the construction of drugs sulfinamides with K2S2O5 as
a sulfur dioxide surrogate
and natural products,3 such as the anti-HIV drug maraviroc4 (Scheme 1a).11 Despite the fact that some progress has been
and the natural product (−)-vindoline.5 On the other hand,
chiral sulfinamides play unique roles in asymmetric synthesis,
and they can be used as chiral ligands or organocatalysts in
asymmetric catalysis, and as chiral auxiliaries in the synthesis
of chiral nitrogen-containing skeletons.6–8 Therefore, the
development of new methods for the preparation of sulfina-
mides is in great demand.
The traditional method for the synthesis of sulfonamides is
well developed by the condensation reaction of sulfonyl chlor-
ides and amines. In contrast, the N–S bond formation for the
preparation of sulfinamides remains much less explored. The
reaction between sulfonyl chlorides and amines has been
reported for the synthesis of sulfinamides.9 However, this reac-
tion requires the use of triphenylphosphine as a reductant and
aJiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest
Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing
210037, China. E-mail: hanjl@njfu.edu.cn
bShandong Key Laboratory of Biochemical Analysis, College of Chemistry and
Molecular Engineering, Qingdao University of Science and Technology, Qingdao
266042, PR China
cDepartment of Life Sciences and Chemistry, Jacobs University Bremen gGmbH,
Campus Ring 1, 28759 Bremen, Germany.
E-mail: g.roeschenthaler@jacobs-university.de
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
d0ob00720j
Scheme 1 Synthesis of sulfinamides and sulfonamides.
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made in the synthesis of sulfinamides, the development/ acetonitrile as a solvent under air after 30 min (entry 1).
design of highly efficient new synthetic procedures, especially Subsequently, the loading amount of Selectfluor was varied to
from inexpensive and commercially available reagents, still improve the reaction yield. No improvement was observed
remains a great challenge.12
upon switching the amount of Selectfluor from 4.0 equiv. to
Selectfluor is a safe, commercially available, and highly 3.0 or 5.0 equiv. (entries 2 and 3). When the reaction was
reactive compound,13 which has been widely used as an stopped at 15 min, the yield increased to 75% (entry 4).
efficient electrophilic fluorinating reagent14 and a mild chemi- However, the yield decreased markedly to 52% when the reac-
cal oxidant.15 Notably, the synthesis of functionalized hetero- tion was prolonged to 60 min (entry 5), which is mainly
cyclic compounds has been achieved successfully using because of the over oxidation of product 3a by Selectfluor. On
Selectfluor as a mild oxidant.16 On the other hand, Selectfluor the other hand, the loading amount of amine 2a was found to
has been used in the synthesis of thiosulfonates via oxidation be crucial for this reaction, and decreasing the amount of
of disulfides.17 Very recently, the Noël group reported an amine 2a to 5 equiv. led to a poor yield of product 3a (23%,
elegant work on the electrochemical reaction between thiols entry 6). Solvents were found to be important for this trans-
and amines, which afforded sulfonamides as the product formation, as evidenced by almost no desired product
(Scheme 1b).18 However, to the best of our knowledge, oxi- obtained when using THF or CH2Cl2 as the reaction medium
dation of easily available thiols or disulfides using Selectfluor (0% yield, entries 7 and 8). It should be mentioned that almost
to obtain sulfinamides has never been explored to date. all the starting disulfide 1a remained in these two reactions.
Herein, we report an unprecedented one-pot oxidative reaction Further evaluation of the reaction conditions showed that the
of disulfides and amines promoted by Selectfluor under reaction could not proceed without the use of Selectfluor as an
aerobic conditions (Scheme 1c). Furthermore, this process oxidant, and no desired product was observed when the reac-
demonstrates a new oxidative transformation reaction of disul- tion was conducted under a nitrogen atmosphere (entries 9
fides and also provides a new strategy for the synthesis of and 10).
sulfinamides.
Then, the substrate generality of this Selectfluor-promoted
oxidative reaction of diphenyl disulfide (1a) with various
amines was explored under the optimized reaction conditions
(Scheme 2).
Results and discussion
Initially, we started our investigation of the conditions for this
envisioned oxidative reaction between 1,2-diphenyldisulfide
(1a) and methylpropylamine (2a) (Table 1). It was pleasing to
note that the reaction could proceed at room temperature and
the desired sulfinamide product 3a was obtained in 65% iso-
lated yield with 4.0 equiv. of Selectfluor as an oxidant and
Table 1 Optimization of reaction conditionsa
2a
Selectfluor
Solvent (equiv.)
Time
(min)
Yieldb
(%)
Entry (equiv.)
1
2
3
4
5
6
7
8
10
10
10
10
10
5
10
10
10
10
CH3CN 4.0
CH3CN 5.0
CH3CN 3.0
CH3CN 4.0
CH3CN 4.0
CH3CN 4.0
30
30
30
15
60
15
15
15
15
15
65
32
53
75
52
23
0
THF
CH2Cl2 4.0
CH3CN
CH3CN 4.0
4.0
0
9
0
nrc
0
10d
Scheme 2 Substrate study with variation of amine 2. Reaction con-
ditions: Diphenyl disulfide (1a) (0.2 mmol) and Selectfluor (4.0 equiv.) in
acetonitrile (3 mL) were stirred at room temperature for 5 minutes.
Then, amine 2 (10 equiv.) in CH3CN (2 mL) was added to the mixture
over 30 minutes and stirred for an additional 15 minutes. Isolated yields.
a Determined by 1H NMR.
a Reaction conditions: Diphenyl disulfide (0.2 mmol), Selectfluor and
solvent (3 mL) were stirred at room temperature for 5 minutes. Then,
amine 2a in CH3CN (2 mL) was added to the mixture over 30 minutes
and stirred at room temperature. b Isolated yield. c No reaction. d Under
nitrogen.
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Amines with different alkyl chains were well tolerated in
this reaction, leading to the formation of the corresponding
sulfinamides in moderate to good chemical yields (40–75%,
3a–d). Extending the length of the alkyl chains on amines
showed an obvious effect on the reaction performance.
N-Methyl-substituted sulfinamide (3a) was obtained in the
best yield (75%), while only 47% yield (3d) was obtained when
dibutylamine was used as the substrate. Then, amines with
cycloalkyl substituents on the nitrogen atom were used for this
reaction. Fortunately, these amines performed equally well in
this reaction, and the desired products 3e and 3f were
obtained in good yields (67 and 71%, respectively). Besides
linear amines, cyclic amines, including piperidines and pyrro-
lidines, were also suitable substrates, which reacted smoothly
with disulfides to furnish the corresponding products 3g and
3h in 58 and 37% yields, respectively. To further demonstrate
the utility of this Selectfluor-promoted oxidative coupling reac-
tion, we used bioactive amines as substrates for this reaction.
For example, 1-methyl-piperazin-2-one could react well with
diphenyl disulfide (1a) under the standard conditions, giving
the expected sulfonamide 3i in 49% yield. Furthermore, an
antidepressant drug, sertraline hydrochloride, was also
employed in this reaction, which provided the desired product
3j in 46% yield with 60 : 40 diastereoselectivity. Other amines,
including 2,2-dimethylthiazolidine and cytisine, were exam-
ined in this system, which were demonstrated to be unsuitable
substrates.
To further probe the applicability of this oxidative reaction,
the coupling reaction of a series of substituted diaryl disul-
fides 1 with N-methylpropylamine (2a) was carried out under
the standard reaction conditions (Scheme 3).
Scheme 3 Substrate study with variation of disulfide 1. Reaction con-
ditions: Disulfide 1 (0.2 mmol) and Selectfluor (4.0 equiv.) in acetonitrile
(3 mL) were stirred at room temperature for 5 minutes. Then, amine 2
(10 equiv.) in CH3CN (2 mL) was added to the mixture over 30 minutes
and stirred at room temperature for an additional 15 minutes. Isolated
yield.
We found that the reactions of disulfide substrates bearing
electron-donating groups (methyl and methoxyl) or electron-
withdrawing groups (chloro and fluoro) could all proceed
smoothly, resulting in the formation of the corresponding sul-
finamides 3 in good yields (41–74%, 3k–3n). Notably, methyl-
and chloro-substituted diphenyl sulfides could also participate
well in the reaction with N-cycloalkyl amines to form the
desired products in 47–79% yields (3o–3r). In the cases of
dibenzyl disulfide and dibutyl disulfide, the reaction did not
occur and almost no desired products 3s and 3t were obtained,
which is presumably due to the instability of the cation inter-
mediate. We also used 1,2-diphenyldiselane as the substrate
for this reaction. However, no desired product 3u was obtained
with the starting material used. Finally, several diheteroaryl
Scheme 4 Large-scale synthesis.
To gain insight into this oxidative reaction, a mixture of
disulfides were examined in this system. Unfortunately, almost diphenyl disulfide (1a) and Selectfluor in acetonitrile was
no desired products (3v–3y) were detected. It should be men- stirred at room temperature for 30 minutes under air. After
tioned that these pure sulfinamide products are not very stable careful isolation of the reaction mixture, S-phenyl benzenesul-
when they are stored in a flask at room temperature.
fonothioate (4) was obtained in 33% yield (Scheme 5a). Then,
In order to further demonstrate the scale applicability of we used it as the starting material to perform the reaction
this newly explored oxidative reaction, we conducted the reac- under the standard reaction conditions. However, no reaction
tion of disulfide 1a and N-ethylcyclohexanamine (2f) on a occurred and no desired product 3a was obtained (Scheme 5b).
gram scale under the optimized reaction conditions. The for- Thus, compound 4 may not be the intermediate or the cap-
mation of sulfonamide 3f in 47% yield (951.4 mg) from this tured intermediate of this oxidative coupling procedure. On
large-scale synthesis was observed, which discloses the practi- the other hand, Selectfluor and amine 2a were stirred in aceto-
cal application of the current system (Scheme 4).
nitrile for 30 min, followed by the addition of disulfide 1a.
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sequent oxidation to give the corresponding sulfinamide may
not be possible for the current reaction.20
Experimental section
General information
All the commercial reagents including solvents were used
directly without further purification. All the experiments were
monitored by thin layer chromatography (TLC) with UV light
using 0.25 mm silica gel coated on glass plates. Column
chromatography was performed with silica gel 60
(300–400 mesh). NMR spectra were recorded using Bruker
600 MHz and 400 MHz spectrometers. High-resolution mass
spectra (HRMS) were recorded using an Agilent 6210 ESI/TOF
MS instrument.
Scheme 5 Control experiments.
Typical procedure of the reaction of disulfides and amines
Almost no desired sulfinamide 3a was obtained (Scheme 5c).
In addition, the oxidative reaction process was detected by 19F
NMR, which indicated that a fluorine-containing intermedi-
ate17 was formed in the initial step and disappeared along
with the formation of product 3a (see the ESI†).
Into a 10 mL vial were taken disulfide 1 (0.2 mmol),
Selectfluor (4 equiv.) and acetonitrile (3 mL). The mixture was
stirred at room temperature for 5 minutes. Then, amine 2 (10
equiv.) dissolved in acetonitrile (2 mL) was added dropwise
within 30 minutes. After stirring for another 15 minutes, the
mixture was concentrated in vacuo. The residue was purified by
column chromatography using hexane/EtOAc (4 : 1, v/v) as an
eluent to afford the desired product 3.
On the basis of the above experimental results and previous
reports,17–19 an oxidative cross-coupling pathway via a disulfox-
ide intermediate was proposed for this reaction (Scheme 6).
Initially, the reaction between Selectfluor and diphenyl di-
sulfide (1a) affords the active sulfonium intermediate A,17
which undergoes the oxidation reaction with oxygen to give
thiosulfinate (B).18,19 Thiosulfinate (B) is subsequently oxi-
dized into an unstable disulfoxide (C) via a similar two-step
process. The formation of the by-product thiosulfonate 4 is
probably due to the rearrangement of the unstable disulfoxide
(C).17 Then, the substitution reaction of disulfoxide (C) with
amine occurs to form the final product 3a and intermediate D.
Intermediate D reacts with Selectfluor to give benzenesulfinic
fluoride (E), which finally reacts with amine to afford product
3a again. It should be mentioned that the pathway including
the initial generation of N-fluoro amine, reaction with di-
sulfide to generate phenyl sulfamate (PhSNHR) and sub-
1
Compound 3a. Colorless oil, 75% yield. H NMR (600 MHz,
CDCl3): δ = 7.67–7.65 (m, 2H), 7.52–7.48 (m, 3H), 3.19–3.14 (m,
1H), 3.07–3.02 (m, 1H), 3.27 (s, 3H), 1.67–1.59 (m, 2H), 0.94 (t,
J = 7.35 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ = 144.0, 130.7,
128.8, 126.2, 54.3, 32.3, 21.4, 11.3. HRMS (ESI): calculated for
C10H15NNaOS+ [M + Na]+ 220.0767, found 220.0769.
1
Compound 3b. Colorless oil, 50% yield. H NMR (600 MHz,
CDCl3): δ = 7.67–7.65 (m, 2H), 7.50–7.44 (m, 3H), 3.03–2.95 (m,
4H), 1.61–1.55 (m, 2H), 1.50–1.44 (m, 2H), 0.82 (t, J = 7.38 Hz,
6H). HRMS (ESI): calculated for C12H19NNaOS+ [M + Na]+
248.1080, found 248.1083.
1
Compound 3c. Colorless oil, 40% yield. H NMR (600 MHz,
CDCl3): δ = 7.67–7.65 (m, 2H), 7.50–7.47 (m, 2H), 7.45–7.43 (m,
1H), 3.60–3.53 (m, 2H), 1.42 (d, J = 6.72 Hz, 6H), 1.13 (d, J =
6.84 Hz, 6H). HRMS (ESI): calculated for C12H19NNaOS+ [M +
Na]+ 248.1080, found 248.1084.
1
Compound 3d. Colorless oil, 47% yield. H NMR (600 MHz,
CDCl3): δ = 7.67–7.66 (m, 2H), 7.51–7.45 (m, 3H), 3.05 (t, J =
7.59 Hz, 4H), 1.58–1.51 (m, 2H), 1.47–1.39 (m, 2H), 1.29–1.19
(m, 4H), 0.85 (t, J = 7.41 Hz, 6H). HRMS (ESI): calculated for
C14H23NNaOS+ [M + Na]+ 276.1393, found 276.1397.
1
Compound 3e. Colorless oil, 67% yield. H NMR (600 MHz,
CDCl3): δ = 7.63–7.62 (m, 2H), 7.49–7.43 (m, 3H), 3.29–3.23 (m,
1H), 2.40 (s, 3H), 2.04–2.00 (m, 1H), 1.97–1.94 (m, 1H),
1.87–1.80 (m, 2H), 1.66–1.63 (m, 1H), 1.62–1.50 (m, 2H),
1.37–1.27 (m, 2H), 1.16–1.08 (m, 1H). HRMS (ESI): calculated
for C13H19NNaOS+ [M + Na]+ 260.1080, found 260.1082.
1
Compound 3f. Colorless oil, 70% yield. H NMR (600 MHz,
CDCl3): δ = 7.65–7.64 (m, 2H), 7.47–7.42 (m, 3H), 3.12–3.07 (m,
2H), 2.92–2.86 (m, 1H), 2.15–2.11 (m, 1H), 1.84–1.78 (m, 3H),
Scheme 6 Possible mechanism.
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1.66–1.57 (m, 3H), 1.29–1.22 (m, 2H), 1.16–1.09 (m, 1H), 0.89 1H), 7.18–7.14 (m, 1H), 3.18–3.13 (m, 1H), 3.06–3.01 (m, 1H),
(t, J = 7.14 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ = 144.7, 2.53 (s, 3H), 1.67–1.60 (m, 2H), 0.93 (t, J = 7.38 Hz, 3H). 13C
130.3, 128.5, 126.4, 59.8, 37.9, 33.7, 33.2, 26.3, 26.2, 25.6, 15.8. NMR (150 MHz, CDCl3): δ = 163.7 (d, J = 249.3 Hz), 146.8 (d, J
HRMS (ESI): calculated for C14H21NNaOS+ [M + Na]+ 274.1236, = 5.8 Hz), 130.4 (d, J = 7.7 Hz), 121.9 (d, J = 3.4 Hz), 117.9 (d, J
found 274.1239.
= 21.4 Hz), 113.5 (d, J = 23.6 Hz), 54.4, 32.4, 21.4, 11.3. 19F
Compound 3g. White solid, 58% yield, mp 78–79 °C. 1H NMR (565 MHz, CDCl3): δ = −110.9. HRMS (ESI): calculated for
NMR (600 MHz, CDCl3): δ = 7.67–7.66 (m, 2H), 7.51–7.47 (m, C10H14FNNaOS+ [M + Na]+ 238.0672, found 238.0675.
1
3H), 3.14–3.10 (m, 2H), 2.98–2.94 (m, 2H), 1.66–1.57 (m, 4H),
Compound 3o. Colorless oil, 45% yield. H NMR (600 MHz,
1.55–1.51 (m, 2H). HRMS (ESI): calculated for C11H15NNaOS+ CDCl3): δ = 7.51 (d, J = 8.28 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H),
[M + Na]+ 232.0767, found 232.0770.
3.28–3.23 (m, 1H), 2.40 (s, 6H), 2.03–2.00 (m, 1H), 1.97–1.94
1
Compound 3h. Colorless oil, 37% yield. H NMR (600 MHz, (m, 1H), 1.87–1.80 (m, 2H), 1.67–1.63 (m, 1H), 1.62–1.50
CDCl3): δ = 7.69–7.67 (m, 2H), 7.50–7.45 (m, 3H), 3.37–3.33 (m, (m, 2H), 1.37–1.28 (m, 2H), 1.16–1.09 (m, 1H). HRMS (ESI): cal-
2H), 3.03–2.99 (m, 2H), 1.87–1.84 (m, 4H). HRMS (ESI): calcu- culated for C14H21NNaOS+ [M
+
Na]+ 274.1236, found
lated for C10H13NNaOS+ [M + Na]+ 218.0610, found 218.0614.
274.1239.
1
1
Compound 3i. Colorless oil, 49% yield. H NMR (600 MHz,
Compound 3p. Colorless oil, 79% yield. H NMR (600 MHz,
CDCl3): δ = 7.65–7.63 (m, 2H), 7.52–7.50 (m, 3H), 3.76 (d, J = CDCl3): δ = 7.53 (d, J = 8.16 Hz, 2H), 7.26 (d, J = 7.92 Hz, 2H),
16.8 Hz, 1H), 3.52–3.45 (m, 2H), 3.38–3.32 (m, 3H), 2.95 (s, 3.12–3.05 (m, 2H), 2.92–2.86 (m, 1H), 2.39 (s, 3H), 2.14–2.11
3H). 13C NMR (150 MHz, CDCl3): δ = 165.3, 141.7, 131.5, 129.1, (m, 1H), 1.84–1.78 (m, 3H), 1.66–1.55 (m, 3H), 1.29–1.22 (m,
125.9, 48.9, 46.6, 44.7, 34.2. HRMS (ESI): calculated for 2H), 1.17–1.09 (m, 1H), 0.91 (t, J = 7.17 Hz, 3H). 13C NMR
C11H14N2NaO2S+ [M + Na]+ 261.0668, found 261.0670.
Compound 3j. Colorless oil, 48% yield (dr = 3 : 2). H NMR 33.7, 33.3, 26.3, 26.2, 25.6, 21.3, 15.8. HRMS (ESI): calculated
(600 MHz, CDCl3): δ = 7.80–7.78 (m, 0.8H), 7.73–7.72 (m, for C15H23NNaOS+ [M + Na]+ 288.1393, found 288.1395.
(150 MHz, CDCl3): δ = 141.5, 140.5, 129.3, 126.4, 59.7, 37.8,
1
1.8H), 7.69–7.67 (m, 0.4H), 7.58–7.47 (m, 3H), 7.36–7.32 (m,
Compound 3q. White solid, 54% yield, mp 59–60 °C. 1H
2H), 7.24–7.20 (m, 1H), 7.14–7.13 (m, 0.6H), 7.09–7.08 (m, NMR (600 MHz, CDCl3): δ = 7.57–7.55 (m, 2H), 7.46–7.44 (m,
0.4H), 6.97–6.94 (m, 1H), 6.87–6.85 (m, 0.6H), 6.84–6.82 (m, 2H), 3.27–3.22 (m, 1H), 2.40 (s, 3H), 2.02–1.99 (m, 1H),
0.4H), 4.91–4.88 (m, 0.4H), 4.85–4.83 (m, 0.6H), 4.18–4.12 (m, 1.95–1.92 (m, 1H), 1.87–1.80 (m, 2H), 1.67–1.63 (m, 1H),
1H), 2.42 (s, 1.8H), 2.39 (m, 1.2H), 2.31–2.21 (m, 1H), 1.61–1.49 (m, 2H), 1.36–1.27 (m, 2H), 1.16–1.08 (m, 1H).
2.16–2.07 (m, 1H), 2.04–1.89 (m, 2H). 13C NMR (150 MHz, HRMS (ESI): calculated for C13H18ClNNaOS+ [M
+
Na]+
CDCl3): δ = 146.9, 146.8, 144.2, 144.1, 138.6, 138.5, 136.1, 294.0690, found 294.0693.
1
135.8, 132.3, 132.2, 130.9, 130.8, 130.73, 130.70, 130.6, 130.5,
Compound 3r. Colorless oil, 47% yield. H NMR (600 MHz,
130.2, 130.1, 129.1, 129.0, 128.9, 128.4, 128.1, 128.0, 127.9, CDCl3): δ = 7.60–7.58 (m, 2H), 7.46–7.43 (m, 2H), 3.12–3.05 (m,
127.8, 127.6, 127.4, 126.2, 126.1, 61.9, 61.7, 60.4, 43.4, 43.2, 2H), 2.94–2.88 (m, 1H), 2.15–2.11 (m, 1H), 1.86–1.80 (m, 3H),
29.9, 29.8, 28.0, 27.1, 24.3, 23.4, 14.2. HRMS (ESI): calculated 1.66–1.55 (m, 3H), 1.31–1.23 (m, 2H), 1.18–1.12 (m, 1H), 0.93
for C23H21Cl2NNaOS+ [M + Na]+ 452.0613, found 452.0615.
(t, J = 7.17 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ = 143.3,
1
Compound 3k. Colorless oil, 74% yield. H NMR (600 MHz, 136.6, 128.8, 127.9, 59.8, 38.0, 33.7, 33.2, 26.2, 26.1, 25.5, 15.8.
CDCl3): δ = 7.53–7.51 (m, 2H), 7.30–7.28 (m, 2H), 3.15–3.11 (m, HRMS (ESI): calculated for C18H20ClNNaOS+ [M
1H), 3.04–2.99 (m, 1H), 2.50 (s, 3H), 2.40 (s, 3H), 1.66–1.56 (m, 308.0846, found 308.0847.
+
Na]+
2H), 0.92 (t, J = 7.38 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ =
Compound 4. Yellow oil, 33% yield. 1H NMR (400 MHz,
141.0, 140.9, 129.4, 126.1, 54.1, 32.2, 21.4, 21.3, 11.3. HRMS CDCl3): δ = 7.61–7.56 (m, 3H), 7.50–7.46 (m, 1H), 7.45–7.41
(ESI): calculated for C11H17NNaOS+ [M + Na]+ 234.0923, found (m, 2H), 7.37–7.32 (m, 4H). 13C NMR (100 MHz, CDCl3): δ =
234.0925.
142.9, 136.6, 133.8, 131.5, 129.5, 128.9, 127.8, 127.6. HRMS
1
+
Compound 3l. Colorless oil, 53% yield. H NMR (600 MHz, (ESI): calculated for C12H11O2S2 [M + H]+ 251.0195, found
CDCl3): δ = 7.60–7.57 (m, 2H), 7.48–7.46 (m, 2H), 3.16–3.12 (m, 251.0196.
1H), 3.05–3.00 (m, 1H), 2.52 (s, 3H), 1.67–1.57 (m, 2H), 0.93 (t,
J = 7.38 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ = 142.6, 137.0,
129.0, 127.6, 54.3, 32.3, 21.4, 11.3. HRMS (ESI): calculated for
C10H14ClNNaOS+ [M + Na]+ 254.0377, found 254.0381.
Conclusions
Compound 3m. Colorless oil, 41% yield. 1H NMR (600 MHz,
CDCl3): δ = 7.57–7.54 (m, 2H), 7.01–6.98 (m, 2H), 3.85 (s, 3H), In summary, we have developed a new two-fold coupling reac-
3.14–3.09 (m, 1H), 3.03–2.98 (m, 1H), 2.50 (s, 3H), 1.65–1.56 tion of disulfides and amines with Selectfluor as a mild
(m, 2H), 0.92 (t, J = 7.38 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ oxidant. The reaction was carried out under mild conditions
= 161.6, 135.3, 127.7, 114.2, 55.5, 53.9, 32.1, 21.4, 11.3. HRMS and tolerated a wide range of amine substrates, resulting in
(ESI): calculated for C11H18NO2S+ [M + H]+ 228.1053, found the formation of sulfinamides in good yields. This reaction
228.1056.
does not require any metal catalyst and uses easily available
1
Compound 3n. Colorless oil, 41% yield. H NMR (600 MHz, reagents as starting materials, and provides a new and efficient
CDCl3): δ = 7.49–7.46 (m, 1H), 7.44–7.42 (m, 1H), 7.39–7.37 (m, strategy for the preparation of sulfinamides.
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Organic & Biomolecular Chemistry
11 H. Konishi, H. Tanaka and K. Manabe, Org. Lett., 2017, 19,
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
We gratefully acknowledge the financial supports from the
National Natural Science Foundation of China (No.
21761132021), the German Research Foundation (Grant RO
362/74-1) and the open project of Chemistry Department of
Qingdao
University
of
Science
and
Technology
(QUSTHX202005).
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