Metal-Free Catalytic Synthesis of Thiocarbamates Using Sodium Sulfinates as the Sulfur Source

Article abstract of DOI:10.1021/acs.joc.8b02844

A novel molecular iodine-catalyzed protocol for the construction of thiocarbamates from readily available sodium sulfinates, isocyanides, and water has been described. The present methodology offers a facile and practical route to a variety of thiocarbamates in moderate to good yields with favorable functional group tolerance by use odorless sodium sulfinates as the sulfur source. The mechanistic studies suggest the present transformation involves a radical process.

Full text of DOI:10.1021/acs.joc.8b02844

Note
pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Metal-Free Catalytic Synthesis of Thiocarbamates Using Sodium
Sulfinates as the Sulfur Source
Pengli Bao,† Leilei Wang,† Huilan Yue,‡ Yun Shao,‡ Jiangwei Wen,† Daoshan Yang,†,§ Xiaohui Zhao,‡
Hua Wang,† and Wei Wei*,†,§
†School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, China
‡Qinghai Provincial Key Laboratory of Tibetan Medicine Research and Key Laboratory of Tibetan Medicine Research, Northwest
Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, Qinghai, China
§College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, Shandong,
China
S
* Supporting Information
ABSTRACT: A novel molecular iodine-catalyzed protocol
for the construction of thiocarbamates from readily available
sodium sulfinates, isocyanides, and water has been described.
The present methodology offers a facile and practical route to
a variety of thiocarbamates in moderate to good yields with
favorable functional group tolerance by use odorless sodium
sulfinates as the sulfur source. The mechanistic studies suggest
the present transformation involves a radical process.
using of odorless and easy-to-handle sulfuration agents is still
hiocarbamates are recognized as an important class of
Tbiologically active molecules, with widespread use as an interesting and practical issue.
herbicides1 (e.g., molinate, thiobencarb, orbencarb), fungi-
cides,2 pesticides,3 anesthetics,4 and antiviral5 agents. In the
past decades, significant efforts have been made toward the
construction of substituted thiocarbamates in term of their
pharmacological effects and important biological activities.
Traditional synthetic methods mainly involve the two-step
operation reactions of amines with phosgene and thiols6 or the
reactions of amine with gaseous carbonyl sulfide followed by
alkylation with alkyl halides.7 Other strategies such as the
palladium-catalyzed thiocarboxylation of amines with CO and
S8 or ArSSAr8 and the reaction of thiols with isocyanates have
also been developed.9 However, multistep operations and the
utilization of hazardous phosgene, CO, or isocyanates as the
substrate limit their applications.10 Recently, some efficient
methods have been established to avoid the use of these
hazardous starting materials,11 including the Boc-Oxyma-
promoted coupling reaction of hydroxamic acid with
thiophenol,12 the reaction of CBZ(Boc)-protected amines
and thiophenols,13 and iodine-catalyzed synthesis of secondary
thiocarbamates from isocyanides and preformed thiosulfo-
nates.14 Very recently, the groups of He15 and Sawant16 and
our group17 also reported a strategy for direct one-pot
synthesis of thiocarbamates via cross-coupling of isocyanides
and thiols in the presence of water. Nevertheless, most of these
methods also suffer from some drawbacks such as the use of
metal reagents and air-sensitive, awful-smelling thiols or their
derivatives. This is particularly problematic for large-scale
synthesis in synthetic chemistry. Therefore, searching for
alternative metal-free methods to construct thiocarbamates by
Sodium sulfinates are stable, odorless, and readily accessible
reagents that have usually been employed as sulfone sources
for the construction of organic sulfone compounds.18 Recently,
sodium sulfinates have emerged as promising thiolating
reagents to construct the C−S bond through reductive
sulfenylation reactions.19−22 For example, Deng’ group
reported elegant methods for the synthesis of sulfenylated
indoles and phenols via direct sulfenylation of indoles and
phenols with sodium sulfinates.20 Wu and Jiang presented
copper-catalyzed oxysulfenylation of enolates with sodium
sulfinates leading to sulfenylated cyclic ethers.21 The Yi group
described sulfenylation strategies with sodium sulfinates via an
arylsulfenyl radical process using PPh3 as a reducing reagent.22
To the best of our knowledge, direct sulfenylation of
isocyanides with sodium sulfinates has not yet been reported.
In continuation of our ongoing research in the construction of
sulfur-containing compounds23 and green organic synthesis,24
herein, we report a novel and efficient molecular iodine-
catalyzed protocol for the direct synthesis of thiocarbamates
from sodium sulfinates, water, and isocyanides (Scheme 1).
This metal-free protocol, which simply utilizes readily available
sodium sulfinates as the thiolating reagent and HP(O)(OMe)2
as the reducing agent, provides an alternative and highly
attractive approach to a series of biologically important
thiocarbamate derivatives in moderate to good yields with
favorable functional group tolerance.
Received: November 7, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1, entry 6 vs entries 9−11). It should be noted that no reaction
occurred when the reaction was performed without reducing
agent, indicating that HP(O)(OMe)2 is essential for this
reaction (Table 1, entry 12). Subsequent investigation on the
effect of various solvents found that EtOAc was the optimized
reaction medium to give the corresponding product 4a in 88%
yield (Table 1, entry 15). The optimized reaction temperature
is 100 °C. A higher temperature (110 °C) or a lower
temperature (80 or 90 °C) led to a slightly lower yield (Table
1, entries 19−21). No conversion was observed when the
reaction was conducted at room temperature or 60 °C (Table
1, entries 22 and 23).
Scheme 1. Synthesis of Thiocarbamates Using Sodium
Sulfinates as the Sulfur Source
Initially, sodium benzenesulfinate (1a), ethyl 2-isocyanoa-
cetate (2a), and water were utilized as the model substrates to
optimize various reaction conditions. A series of iodide-
containing catalysts (5 mol %) were investigated using
HP(O)(OMe)2 as the reducing agent in DCE at 100 °C. As
a result, none of the desired product 4a was detected when KI,
TBAI, NaI, and I2O5 were screened (Table 1, entries 1−4). To
Under the established reaction conditions, we then
examined the scope of this transformation. As summarized in
Table 2, a series of substituted sodium benzenesulfinates
including some electron-rich groups or some electron-poor
groups were found to be suitable substrates for this reaction,
and the corresponding thiocarbamates (4b−h) were obtained
in moderate to good yields. Notably, halo substituents (F, Cl,
and Br), trifluoromethyl and nitro groups were also compatible
with this transformation, providing the chance for further
modification. It was found that the reaction efficiency was
significantly affected by the steric effect. The reaction failed to
yield the desired product 4i when sterically hindered sulfinate
such as sodium 2,6-diisopropylbenzenesulfinate was used in
this reaction system. When sodium 2-naphthalenesulfinate was
employed as the substrate, the desired product 4j was obtained
in 73% yield. It is noteworthy that heterocycle sodium sulfinate
such as sodium thiophene-2-sulfinate was also well tolerated in
this transformation leading to the expected product 4k in 67%
yield. Unfortunately, none of the desired products were
detected when alkyl sodium sulfinates such as sodium
methylsulfonate and sodium trifluoromethanesulfinate were
used as substrates. With respect to the isocyanides, in addition
to 2a, cyclohexyl isocyanide, tert-butyl isocyanide, and methyl
isocyanoacetate were all suitable substrates and generated the
corresponding products 4l−t in good yields. Moreover,
tosylmethyl isocyanide (TosMIC reagent) could also be
utilized in the process to give the desired products 4u and
4v in 70% and 78% yields, respectively. Unfortunately, when
an aromatic isocyanide such as 2,6-dimethylphenyl isocyanide
was investigated under the standard conditions, none of the
desired product 4w was detected.
Furthermore, several control experiments were carried out to
gain some insights into the possible reaction mechanism.
Initially, when TEMPO (well-known radical-capturing species)
was added into the reaction system of 1b and 2a under the
standard conditions, the present reaction was completely
inhibited and TEMPO-trapped thiyl radical complex was
detected by LC−MS analysis. The above result suggested that
the present transformation might proceed via a radical process
(Scheme 2, (a)). When sodium benzenesulfinate (1a) was
added independently in this reaction system, only a trace
amount of PhSSPh was detected (Scheme 2, (b)).
Furthermore, treatment of 1,2-diphenyl disulfide with 2a
under standard conditions did not give the desired product 4a
(Scheme 2, (c)). These results indicated that the disulfide
should not be the intermediate in this reaction. When the
model reaction was carried out in the absence of water, only a
trace amount of product 4a was detected (Scheme 2, (d)).
Moreover, isotope-labeling experiments using H218O revealed
that the oxygen atom of thiocarbamates originated from water
(Scheme 2, (e)). In addition, when the model reaction was
a
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
reducing agent
solvent
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
CH3CN
1,4-dioxane
EtOAc
DMSO
DMF
EtOH
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
T (°C) yield (%)
1
2
3
4
5
6
7
8
KI (5)
P1
P1
P1
P1
P1
P1
P1
P1
P2
P3
P4
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
110
90
0
0
0
TBAI (5)
NaI (5)
I2O5 (5)
I2 (5)
I2 (10)
I2 (15)
0
70
85
75
0
76
60
9
9
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
0
P1
P1
P1
P1
P1
P1
P1
P1
P1
P1
P1
83
73
88
trace
0
0
68
81
59
0
80
60
25
0
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), H2O (0.6
mmol), catalyst (5−15 mol %), reducing agent (0.4 mmol), solvent
b
(1.5 mL), 25−100 °C, 6 h. Isolated yields based on 1a.
our delight, molecular iodine could catalyze efficiently the
reaction to give the desired product 4a in 70% yield (Table 1,
entry 5). The reaction efficiency was further improved with an
increase of the loading of molecular iodine to 10 mol % (Table
1, entries 6 and 7). No transformation was observed in the
absence of molecular iodine catalyst (Table 1, entry 8). Among
various reducing agents such as HP(O)(OMe)2, HP(O)-
(OEt)2, HP(O)(OiPr)2, and PPh3 examined, HP(O)(OMe)2
was found to be the best one to promote this reaction (Table
B
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a,b
Table 2. Substrate Scope
a
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), 3 (0.6 mmol), I2 (10 mol %), HP(O)(OMe)2 (0.4 mmol), EtOAc (1.5 mL), air, 100 °C, 6 h.
b
c
Isolated yields based on 1. 1 (2 mmol), 2 (4 mmol), 3 (6 mmol).
conducted under N2, the reaction was dramatically inhibited
radical intermediate 7.14,16,17 The interaction of C-radical
intermediate 7 with iodine radical gave intermediate 8, which
was attacked by water leading to the desired product 4 with the
release of HI.16,26 Finally, the generated HI would be oxidized
by air (O2) into I2 to complete the catalytic cycle.27
In summary, we have developed a facile and efficient metal-
free protocol for the preparation of thiocarbamates from
sodium sulfinates, isocyanides, and water. Control experiments
suggest that the present transformation proceeds via a radical
process. The present protocol opens up a new door to
construct various thiocarbamates by using stable and odorless
and only 9% yield of the desired product 4a was isolated,
which suggested air (oxygen) is necessary for this reaction
(Scheme 2, (f)).
Based on the above experiments and previous related
reports,15−17,20−22 the possible reaction pathway is described
in Scheme 3. Initially, sodium sulfinate 1 was converted into
sulfenyl iodide 5 by a combination of I2−HP(O)(OMe)2.20,22
Subsequently, sulfenyl iodide 5 might undergo homolytic
cleavage to form sulfenyl radical 6 andiodine radical.22,25 Then,
the addition of sulfenyl radical 6 to isocyanide 2 produced C-
C
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Column chromatography was performed on silica gel (200−300
mesh).
Scheme 2. Control Experiments
General Experimental Procedure. In a tube (25 mL), sodium
sulfinate 1 (0.2 mmol), isocyanide 2 (0.4 mmol), H2O 3 (0.6 mmol,
10.8 μL), I2 (0.02 mmol, 5 mg), HP(O)(OMe)2 (0.4 mmol, 36.7 μL),
and EtOAc(1.5 mL) were added. Then the tube was sealed, and the
reaction vessel was allowed to stir at 100 °C (oil bath) for 6 h. After
completion of the reaction, 3 mL of water was added to the reaction
system. The mixture was extracted by ethyl acetate. The combined
organic layers were concentrated under reduced pressure, and the
crude mixtures were purified by flash column chromatography using a
mixture of petroleum ether and ethyl acetate as eluent to give the
desired product 4.
Experimental Procedure for Model Reaction (2 mmol). In a
tube (50 mL), sodium benzenesulfinate 1 (2 mmol), ethyl 2-
isocyanoacetate 2 (4 mmol), H2O 3 (6 mmol, 108 μL), I2 (0.2 mmol,
50 mg), HP(O)(OMe)2 (4 mmol, 367 μL), and EtOAc (10 mL) were
added. Then the tube was sealed, and the reaction vessel was allowed
to stir at 100 °C (oil bath) for 6 h. After completion of the reaction, 5
mL of water was added to the reaction system. The mixture was
extracted by ethyl acetate. The combined organic layers were
concentrated under reduced pressure, and the crude mixtures were
purified by flash column chromatography using a mixture of
petroleum ether and ethyl acetate as eluent (PE/EtOAc = 5:1) to
give the desired product 4a in 78% yield (0.37g).
Radical-Trapping Experiment with TEMPO. In a tube (25
mL), sodium 4-methylbenzenesulfinate 1a (35.6 mg), ethyl 2-
isocyanoacetate 2a (43.5 μL), H2O 3 (0.6 mmol, 10.8 μL), I2 (0.02
mmol, 5 mg), HP(O)(OMe)2 (0.4 mmol, 36.7 μL), TEMPO (31.2
mg), and EtOAc(1.5 mL) were added. Then the tube was sealed, and
the reaction vessel was allowed to stir at 100 °C (oil bath) for 6 h.
After completion of the reaction, none of the desired product 4b was
detected and TEMPO-trapped thiyl radical complex (p-MePhS−
TEMPO) was detected by LC−MS experiment (see the Supporting
Information).
Scheme 3. Possible Reaction Pathway
Reaction of PhSSPh with Isocyanide under Standard
Conditions. In a tube (25 mL), PhSSPh 1a′(43.6 mg), ethyl 2-
isocyanoacetate 2a(43.5 μL), H2O 3 (0.6 mmol, 10.8 μL), I2 (0.02
mmol, 5 mg), HP(O)(OMe)2 (0.4 mmol, 36.7 μL), and EtOAc(1.5
mL) were added. Then the tube was sealed, and the reaction vessel
was allowed to stir at 100 °C (oil bath) for 6 h. After completion of
the reaction, none of the desired product 4a was detected.
The model reaction was carried out in the absence of water. In a
tube (25 mL), sodium 4-methylbenzenesulfinate 1a (35.6 mg), ethyl
2-isocyanoacetate 2a (43.5 μL), 4 Å molecular sieves (20 mg), I2
(0.02 mmol, 5 mg), HP(O)(OMe)2 (0.4 mmol, 36.7 μL), and EtOAc
(1.5 mL) were added. Then the tube was sealed, and the reaction
vessel was allowed to stir at 100 °C (oil bath) for 6 h. After
completion of the reaction, only a trace amount of the desired product
4a was detected.
sodium sulfinates as the sulfur source, in which molecular
iodine and HP(O)(OMe)2 was simply employed as the
catalyst and reducing agent, respectively.
Isotope Labeling Experiment Using H218O. In a tube (25 mL),
sodium 4-methylbenzenesulfinate 1a (35.6 mg), ethyl 2-isocyanoace-
tate 2a (43.5 μL), H2O18 (0.6 mmol, 12 μL), I2 (0.02 mmol, 5 mg),
HP(O)(OMe)2 (0.4 mmol, 36.7 μL), and EtOAc (1.5 mL) were
added. Then the tube was sealed, and the reaction vessel was allowed
to stir at 100 °C (oil bath) for 6 h. After completion of the reaction,
the desired product O18-4a was obtained in 81% yield (38.7 mg).
The model reaction was carried out under N2. In a tube (25 mL),
sodium 4-methylbenzenesulfinate 1a (35.6 mg), ethyl 2-isocyanoace-
tate 2a (43.5 μL), H2O 3 (0.6 mmol, 10.8 μL), I2 (0.02 mmol, 5 mg),
HP(O)(OMe)2 (0.4 mmol, 36.7 μL), and EtOAc (1.5 mL) were
added. Then the tube was sealed, and the reaction vessel was allowed
to stir at 100 °C (oil bath) for 6 h. After completion of the reaction, 3
mL of water was added to the reaction system. The mixture was
extracted with ethyl acetate. The combined organic layers were
concentrated under reduced pressure and the crude mixtures were
purified by flash column chromatography using a mixture of
petroleum ether and ethyl acetate (PE/EtOAc = 5:1) as eluent to
give the desired product 4a in 9% yield (4.3 mg).
EXPERIMENTAL SECTION
■
General Information. All commercially available reagent-grade
chemicals were purchased from Aldrich, Acros, Alfa Aesar, and Energy
Chemical Co. and used as received without further purification unless
otherwise stated. 1H NMR and 13C{1H} NMR were recorded in
CDCl3 on a Bruker Avance III spectrometer with TMS as internal
1
standard (500 MHz H, 125 MHz 13C) at room temperature, the
chemical shifts (δ) were expressed in ppm, and J values were given in
Hz. The following abbreviations are used to indicate the multiplicity:
singlet (s), doublet (d), triplet (t), quartet (q), doublet of doublets
(dd), doublet of triplets (dt), and multiplet (m). All first-order
splitting patterns were assigned on the basis of the appearance of the
multiplet. Splitting patterns that could not be easily interpreted were
designated as multiplet (m). Mass analyses and HRMS were obtained
on a Finnigan-LCQDECA mass spectrometer and a Bruker Daltonics
Bio-TOF-Q mass spectrometer by the ESI method, respectively.
D
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Ethyl 2-(Phenylthiocarbonylamino)acetate. Compound 4a was
obtained in 88% yield (42.1 mg) according to the general procedure
(0.2 mmol, eluent: PE/EtOAc = 5:1): white solid; mp = 101.2−101.5
124.2, 62.0, 43.0, 14.1; HRMS calcd for C11H13N2O5S (M + H)+
285.0545, found 285.0547.
Ethyl 2-((Naphthalen-2-ylthio)carbonylamino)acetate. Com-
pound 4j was obtained in 73% yield (42.2 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
mp = 104.8−106.0 °C; 1H NMR (500 MHz, CDCl3) δ 8.09 (s, 1H),
7.87−7.83 (m, 3H), 7.61−7.60 (m, 1H), 7.55−7.49 (m, 2H), 6.05 (s,
1H), 4.19−4.11 (m, 2H), 4.00 (d, J = 5.2 Hz, 2H), 1.24 (t, J = 7.1 Hz,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.3, 167.0, 135.6, 133.6,
133.5, 131.7, 129.3, 128.1, 127.8, 127.5, 126.8, 125.2, 61.7, 42.7, 14.1;
HRMS calcd for C15H16NO3S (M + H)+ 290.0851, found 290.0855.
Ethyl 2-((Thiophene-2-ylthio)carbonylamino)acetate. Com-
pound 4k was obtained in 67% yield (31.5 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 7:1): white solid;
1
°C; H NMR (500 MHz, CDCl3) δ 7.61−7.59 (m, 2H), 7.47−7.42
(m, 3H), 6.00 (s, 1H), 4.21 (q, J = 7.2 Hz, 2H), 4.04 (d, J = 5.1 Hz,
2H), 1.28 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
169.3, 166.9, 135.6, 130.0, 129.6, 128.0, 61.7, 42.7, 14.1; HRMS calcd
for C11H14NO3S (M + H)+ 240.0694, found 240.0697.
Ethyl 2-(p-Tolylthiocarbonylamino)acetate. Compound 4b was
obtained in 86% yield (43.5 mg) according to the general procedure
(0.2 mmol, eluent: PE/EtOAc = 5:1): white solid; mp = 72.8−73.3
°C; 1H NMR (500 MHz, CDCl3) δ 7.46 (d, J = 8.0 Hz, 2H), 7.23 (d,
J = 7.9 Hz, 2H), 5.96 (s, 1H), 4.18 (d, J = 7.1 Hz, 2H), 4.01 (d, J =
5.2 Hz, 2H), 2.38 (s, 3H), 1.26 (t, J = 7.1 Hz, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 169.3, 167.4, 140.4, 135.6, 130.4, 124.5, 61.7,
42.7, 21.4, 14.1; HRMS calcd for C12H16NO3S (M + H)+ 254.0851,
found 254.0852.
Ethyl 2-((4-Methoxyphenylthio)carbonylamino)acetate. Com-
pound 4c was obtained in 58% yield (31.2 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
mp = 60.2−61.1 °C; 1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 8.6
Hz, 2H), 6.96−6.93 (d, J = 8.6 Hz, 2H), 5.91 (s, 1H), 4.19 (m, J = 7.1
Hz, 2H), 4.01 (d, J = 5.1 Hz, 2H), 3.83 (s, 3H), 1.26 (t, J = 7.1 Hz,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.3, 167.8, 161.1, 137.4,
118.6, 115.2, 61.7, 55.4, 42.6, 14.1; HRMS calcd for C12H16NO4S (M
+ H)+ 270.0800, found 270.0803.
1
mp = 64.1−64.9 °C; H NMR (500 MHz, CDCl3) δ 7.61−7.59 (m,
1H), 7.35−7.33 (m, 1H), 7.15−7.12 (m, 1H), 6.04 (s, 1H), 4.21 (q, J
= 7.1 Hz, 2H), 4.02 (d, J = 5.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 169.1, 166.4, 137.9, 133.4,
128.5, 125.6, 61.8, 42.7, 14.1; HRMS calcd for C9H12NO3S2 (M +
H)+ 246.0259, found 246.0263.
S-Phenyl Cyclohexylcarbamothioate. Compound 4l was obtained
in 71% yield (33.4 mg) according to the general procedure (0.2
mmol, eluent: PE/EtOAc = 7:1): white solid; mp = 56.6−57.8 °C; 1H
NMR (500 MHz, DMSO) δ 8.21 (d, J = 7.4 Hz, 1H), 7.45−7.42 (m,
2H), 7.40−7.38 (m, 3H), 3.51−3.49 (m, 1H), 1.69−1.66 (m, 2H),
1.55−1.53 (m, 1H), 1.26−1.17 (m, 4H), 1.13−1.07 (m, 1H);
13C{1H} NMR (125 MHz, DMSO) δ 162.9, 135.4, 129.5, 129.3,
129.1, 50.8, 32.8, 25.5, 25.0; HRMS calcd for C13H18NOS (M + H)+
236.1109, found 236.1112.
Ethyl 2-((4-Fluorophenylthio)carbonylamino)acetate,. Com-
pound 4d was obtained in 52% yield (26.7 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
1
mp = 79.7−80.9 °C, H NMR (500 MHz, CDCl3) 7.57−7.52 (m,
S-4-Chlorophenyl Cyclohexylcarbamothioate. Compound 4m
was obtained in 70% yield (37.7 mg) according to the general
procedure (0.2 mmol, eluent: PE/EtOAc = 7:1): white solid; mp =
2H), 7.14−7.07 (m, 2H), 5.92 (s, 1H), 4.22 (q, J = 7.1 Hz, 2H), 4.04
(d, J = 5.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 169.3, 166.5, 163.7 (d, J = 248.8 Hz), 137.7 (d, J =
8.8 Hz), 123.2, 116.7 (d, J = 21.3 Hz), 61.8, 42.8, 14.1; HRMS calcd
for C11H13FNO3S (M + H)+ 258.0600, found 258.0603.
1
60.0−61.8 °C; H NMR (500 MHz, DMSO) δ 8.29 (d, J = 7.4 Hz,
1H), 7.45 (s, 4H), 3.51−3.50 (m, 1H), 1.78−1.76 (m, 2H), 1.69−
1.66 (m, 2H), 1.55−1.53 (m, 1H), 1.27−1.18 (m, 4H), 1.13−1.08
(m, 1H); 13C{1H} NMR (125 MHz, DMSO) δ 162.4, 137.0, 134.1,
129.3, 128.6, 50.9, 32.8, 25.5, 25.0; HRMS calcd for C13H17ClNOS
(M + H)+ 270.0719, found 270.0721.
Ethyl 2-((4-Chlorophenylthio)carbonylamino)acetate. Com-
pound 4e was obtained in 68% yield (37.1 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
mp = 86.0−86.3 °C; 1H NMR (500 MHz, CDCl3) δ 7.49 (d, J = 8.4
Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 5.98 (s, 1H), 4.21 (q, J = 7.2 Hz,
2H), 4.04 (d, J = 5.1 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 169.2, 166.0, 136.7, 136.3, 129.6, 126.4,
61.8, 42.8, 14.1; HRMS calcd for C11H13ClNO3S (M + H)+ 274.0305,
found 274.0309.
Ethyl 2-((4-Bromophenylthio)carbonylamino)acetate. Com-
pound 4f was obtained in 71% yield (44.9 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
mp = 67.6−68.7 °C; 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J = 8.4
Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 6.02 (s, 1H), 4.22 (q, J = 7.2 Hz,
2H), 4.04 (d, J = 5.1 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 169.3, 165.9, 136.9, 132.6, 127.0, 124.5,
61.8, 42.8, 14.1; HRMS calcd for C11H13BrNO3S (M + H)+ 317.9800,
found 317.9801.
S-p-Tolyl Cyclohexylcarbamothioate. Compound 4n was ob-
tained in 64% yield (31.9 mg) according to the general procedure (0.2
mmol, eluent: PE/EtOAc = 7:1): white solid; mp = 61.6−62.3 °C; 1H
NMR (500 MHz, CDCl3) δ 7.43 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 7.9
Hz, 2H), 5.28 (s, 1H), 3.73−3.71 (m, 1H), 2.37 (s, 3H), 1.88−1.86
(m, 2H), 1.63−1.54 (m, 3H), 1.35−1.26 (m, 2H), 1.16−1.05 (m,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 165.5, 139.9, 135.4, 130.3,
125.4, 50.4, 32.9, 25.4, 24.6, 21.3; HRMS calcd for C14H20NOS (M +
H)+ 250.1266, found 250.1267.
S-2-(Trifluoromethyl)phenyl 2-Oxopropylcarbamothioate. Com-
pound 4o was obtained in 80% yield (44.3 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
1
mp = 121.5−122.1 °C, H NMR (500 MHz, CDCl3) δ 7.78 (d, J =
7.8 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.61 (t, J = 7.2 Hz, 1H), 7.55
(t, J = 7.6 Hz, 1H), 5.94 (s, 1H), 4.07 (d, J = 5.1 Hz, 2H), 3.77 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.6, 165.2, 139.9, 133.7,
133.5 (d, J = 12.5 Hz), 132.4, 130.1, 127.2 (q, J = 6.3 Hz), 123.2 (d, J
= 272.5 Hz), 52.6, 42.8; HRMS calcd for C11H11F3NO2S (M + H)+
278.0463, found 278.0465.
Ethyl 2-((2-(Trifluoromethyl)phenylthio)carbonylamino)acetate.
Compound 4g was obtained in 53% yield (32.5 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
1
mp = 83.4−84.8 °C; H NMR (500 MHz, CDCl3) δ 7.79−7.75 (m,
2H), 7.60 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 6.04 (s, 1H),
4.22 (q, J = 7.1 Hz, 2H), 4.05 (d, J = 5.1 Hz, 2H), 1.28 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.2, 165.1, 139.9, 133.8
(q, J = 30.0 Hz), 132.4, 130.1, 127.1 (q, J = 5.5 Hz), 126.5, 121.06 (q,
J = 272.5 Hz), 61.9, 42.9, 14.1; HRMS calcd for C12H13F3NO3S (M +
H)+ 308.0568, found 308.0571.
Methyl 2-((Naphthalen-2-ylthio)carbonylamino)acetate. Com-
pound 4p was obtained in 83% yield (45.7 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
1
mp = 102.7−103.2 °C; H NMR (500 MHz, DMSO) δ 8.81 (t, J =
5.8 Hz, 1H), 8.12 (s, 1H), 7.97−7.93 (m, 3H), 7.61−7.55 (m, 2H),
7.54−7.52 (m, 1H), 3.95 (d, J = 5.9 Hz, 2H), 3.65 (s, 3H); 13C{1H}
NMR (125 MHz, DMSO) δ 170.3, 165.7, 134.9, 133.5, 133.1, 132.3,
128.8, 128.2, 128.1, 127.6, 127.1, 126.2, 52.3, 42.7; HRMS calcd for
C14H14NO3S (M + H)+ 276.0694, found 276.0697.
Ethyl 2-((3-Nitrophenylthio)carbonylamino)acetate. Compound
4h was obtained in 56% yield (31.8 mg) according to the general
procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): yellow oil; 1H NMR
(500 MHz, CDCl3) δ 8.40 (s, 1H), 8.26 (d, J = 8.3 Hz, 1H), 7.86 (d, J
= 7.7 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 6.15 (s, 1H), 4.25 (q, J = 7.2
Hz, 2H), 4.09 (d, J = 5.1 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 169.1, 164.5, 148.3, 141.0, 130.3, 129.8,
S-p-Tolyl tert-Butylcarbamothioate. Compound 4q was obtained
in 70% yield (31.2 mg) according to the general procedure (0.2
mmol, eluent: PE/EtOAc = 5:1): white solid; mp = 119.0−119.6 °C;,
1H NMR (500 MHz, CDCl3) δ 7.41 (d, J = 8.1 Hz, 2H), 7.20 (d, J =
E
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
8.1 Hz, 2H), 5.19 (s, 1H), 2.36 (s, 3H), 1.31 (s, 9H); 13C{1H} NMR
(125 MHz, CDCl3) δ 164.5, 139.7, 135.4, 130.1, 125.7, 53.4, 28.8,
21.3; HRMS calcd for C12H18NOS (M + H)+ 224.1109, found
224.1113.
Tibetan Medicine Research (2017-ZJ-Y11), and the National
Natural Science Foundation of China (Nos. 21302109 and
21302110).
Methyl 2-((4-Chlorophenylthio)carbonylamino)acetate. Com-
pound 4r was obtained in 67% yield (34.7 mg) according to the
general procedure (0.2 mmol, eluent: PE/EtOAc = 5:1): white solid;
mp = 98.6−99.9 °C; 1H NMR (500 MHz, CDCl3) δ 7.49 (d, J = 8.5
Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 5.97 (s, 1H), 4.06 (d, J = 5.2 Hz,
2H), 3.76 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.7, 166.1,
136.7, 136.3, 129.7, 126.3, 52.6, 42.6; HRMS calcd for
C10H11ClNO3S (M + H)+ 260.0148, found 260.0151.
REFERENCES
■
(1) Chen, Y. S.; Schuphan, I.; Casida, J. E. S-Chloroallyl
Thiocarbamate Herbicides: Mouse Hepatic Microsomal Oxygenase
and Rat Metabolism of cis- and trans-[14C = 0]Diallate. J. Agric. Food
Chem. 1979, 27, 709−712.
(2) (a) Heyns, A. J.; Carter, G. A.; Rothwell, K.; Wain, R. L.
Investigations on fungicides: The systemic fungicidal activity of
certain N-carboxymethyl dithiocarbamic acid derivatives. Ann. Appl.
Biol. 1966, 57, 33−51. (b) Erian, A. W.; Sherif, S. M. The chemistry
of thiocyanic esters. Tetrahedron 1999, 55, 7957−8024.
(3) (a) The Pesticide Manual, 9th ed.; Worthing, C. R., Ed.; British
Crop Protection Council: London, 1991. (b) Wang, C.-H. Phase-
transfer-catalysed preparation of S-alkyl thiocarbamates. Synthesis
1981, 1981, 622−623.
(4) Goel, A.; Mazur, S. J.; Fattah, R. J.; Hartman, T. L.; Turpin, J. A.;
Huang, M.; Rice, W. G.; Appella, E.; Inman, J. K. Benzamide-Based
Thiolcarbamates: A New Class of HIV-1 NCp7 Inhibitors. Bioorg.
Med. Chem. Lett. 2002, 12, 767−770.
(5) Wood, T. F.; Gardner, J. H. The Synthesis of Some
Dialkylaminoalkyl Arylthiourethans and Thioureas. J. Am. Chem.
Soc. 1941, 63, 2741−2742.
(6) (a) Evans, T. W.; Dehn, W. M. Some new derivatives of
diphenylcarbamine chloride. J. Am. Chem. Soc. 1930, 52, 3645−3647.
(b) Weijlard, J.; Tishler, M. Some New Choline Type Thiols. J. Am.
S-Phenyl tert-Butylcarbamothioate. Compound 4s was obtained
in 72% yield (30.1 mg) according to the general procedure (0.2
mmol, eluent: PE/EtOAc = 10:1): white solid; mp = 110.3−110.8
1
°C; H NMR (500 MHz, CDCl3) δ 7.58−7.50 (m, 2H), 7.43−7.36
(m, 3H), 5.22 (s, 1H), 1.32 (s, 9H); 13C{1H} NMR (125 MHz,
CDCl3) δ 164.0, 135.4, 129.3, 129.3, 129.1, 53.5, 28.9; HRMS calcd
for C11H16NOS (M + H)+ 210.0953, found 210.0955.
S-Naphthalen-2-yl tert-Butylcarbamothioate. Compound 4t was
obtained in 70% yield (36.3 mg) according to the general procedure
(0.2 mmol, eluent: PE/EtOAc = 10:1): white solid; mp = 110.3−
1
110.8 °C; H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.90−7.77
(m, 3H), 7.58−7.56 (m, 1H), 7.54−7.47 (m, 2H), 5.27 (s, 1H), 1.33
(s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ 164.1, 135.2, 133.6,
133.3, 131.8, 128.9, 128.0, 127.8, 127.2, 126.6, 126.4, 53.6, 28.9;
HRMS calcd for C15H18NOS (M + H)+,260.1109, found 260.1106.
S-Phenyl Tosylmethylcarbamothioate. Compound 4u was
obtained in 70% yield (44.9 mg) according to the general procedure
(0.2 mmol, eluent: PE/EtOAc = 10:1): white solid; mp = 98.2−98.9
1
1
Chem. Soc. 1951, 73, 1497−1500. (c) Riemschneider, R.; Ku
Thiocarbamate and verwandte Verbindungen. Mitteilung IX: N-
substituierte Monothiocarbamidsaure-S-R1-ester. Monatsh. Chem.
1953, 84, 1238−1240.
(7) (a) Tilles, H. Thiolcarbamates. Preparation and Molar
Refractions. J. Am. Chem. Soc. 1959, 81, 714−727. (b) Reddy, T. I.;
Bhawal, B. M.; Rajappa, S. A facile general method for the preparation
of s-methyl thiolcarbamates using zeolite catalysts. Tetrahedron Lett.
1992, 33, 2857−2860.
̈
hl, A.
°C; H NMR (500 MHz, CDCl3): H NMR (500 MHz, CDCl3) δ
7.79 (d, J = 8.1 Hz, 2H), 7.42−7.36 (m, 6H), 6.35 (t, J = 6.3 Hz, 1H),
4.62 (d, J = 6.7 Hz, 2H), 2.45 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 166.6, 145.7, 135.4, 133.6, 130.2, 130.1, 129.6, 129.0, 126.9,
61.3, 21.8; HRMS calcd for C15H16NO3S2 (M + H)+ 322.0572, found
322.0575.
̈
S-p-Tolyl Tosylmethylcarbamothioate. Compound 4v was
obtained in 78% yield (52.3 mg) according to the general procedure
(0.2 mmol, eluent: PE/EtOAc = 5:1): white solid; mp = 91.3−92.4
°C; 1H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz, 2H), 7.37 (d,
J = 8.1 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H),
6.06 (t, J = 6.3 Hz, 1H), 4.59 (d, J = 6.7 Hz, 2H), 2.47 (s, 3H), 2.38
(s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 167.0, 145.7, 141.0,
135.5, 133.5, 130.6, 130.1, 129.0, 61.1, 21.6, 21.4; HRMS calcd for
C16H18NO3S2 (M + H)+ 336.0728, found 336.0731.
(8) (a) Smith, J. F.; Friedrich, E. C. Urethans of 2-Mercaptoethanol.
J. Am. Chem. Soc. 1959, 81, 161−163. (b) Yamaguchi, T.; Harada, N.;
Ozaki, K.; Hayashi, M.; Arakawa, H.; Hashiyama, T. Synthesis of
taxoids 4. Novel and versatile methods for preparation of new taxoids
by employing cis-or trans-phenyl glycidic acid. Tetrahedron 1999, 55,
1005−1016. (c) Movassagh, B.; Soleiman-Beigi, M. Synthesis of
thiocarbamates from thiols and isocyanates under catalyst-and
solvent-free conditions. Monatsh. Chem. 2008, 139, 137−140.
(9) (a) Sugiyama, H. J. Development of paddy field herbicide
″Benthiocarb agent″. Yuki Gosei Kagaku Kyokaishi 1980, 38, 555−
563. (b) Mizuno, T.; Nishiguchi, I.; Sonoda, N. Novel synthesis of S-
alkyl thiocarbamates from amines, carbon monoxide, elemental sulfur,
and alkyl halides in the presence of a selenium catalyst. Tetrahedron
1994, 50, 5669−5680. (c) Mizuno, T.; Iwai, T.; Ito, T. Practical
synthesis of S-alkyl thiocarbamate herbicides by carbonylation of
amines with carbon monoxide and sulfur. Tetrahedron 2004, 60,
2869−2873. (d) Mizuno, T.; Iwai, T.; Ishino, Y. Solvent-assisted
thiocarboxylation of amines and alcohols with carbon monoxide and
sulfur under mild conditions. Tetrahedron 2005, 61, 9157−9163.
(e) Zhang, X. P.; Lu, S. W. A new and facile route for the synthesis of
thiocarbamates from aniline, carbon monoxide, and thiols mediated
by selenium. Chem. Lett. 2005, 34, 606−607. (f) Nishiyama, Y.;
Kawamatsu, H.; Sonoda, N. A Facile Method for the Synthesis of
Thiocarbamates: Palladium-Catalyzed Reaction of Disulfide, Amine,
and Carbon Monoxide. J. Org. Chem. 2005, 70, 2551−2554.
(10) Health (H) rating of CO (H = 3), COCl2 (H = 4), and
isocyanates (e.g., tBuNCO (H = 3)) shows high toxicity. Scale from 0
(low) to 4 (high).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.8b02844.
■
S
1H and 13C{1H}NMR spectra for all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
* E-mail: weiweiqfnu@163.com.
■
ORCID
Daoshan Yang: 0000-0002-3047-5416
Wei Wei: 0000-0002-0015-7636
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Natural Science Foundation
of Shandong Province (ZR2018MB009 and ZR2016JL012),
the International Cooperation Project of Qinghai Province
(2018-HZ-806 and 2018-HZ-815), Qinghai Key Laboratory of
̈
(11) (a) Knolker, H.-J.; Braxmeier, T.; Schlechtingen, G. A novel
method for the synthesis of isocyanates under mild conditions. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2497−2500. (b) Padiya, K. J.; Gavade,
F
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
S.; Kardile, B.; Tiwari, M.; Bajare, S.; Man, M.; Gaware, V.; Varghese,
S.; Hare, D.; Kurhade, S. Unprecedented “in water” imidazole
carbonylation: paradigm shift for preparation of urea and carbamate.
Org. Lett. 2012, 14, 2814−2817. (c) Deng, J.-C.; Zhuang, S.-B.; Liu,
Q.-Z.; Lin, Z.-W.; Su, Y.-L.; Chen, J.-H.; Tang, R.-Y. Metal-free direct
thiocarbamation of imidazopyridines with carbamoyl chloride and
elemental sulfur. RSC Adv. 2017, 7, 54013−54016. (d) Wynne, J. H
S.; Jensen, D.; Snow, A. W. Facile one-pot synthesis of S-alkyl
thiocarbamates. J. Org. Chem. 2003, 68, 3733−3735. (e) Díaz, D. D.;
Finn, M. G. Expanded chemistry of formamidine ureas. Org. Lett.
2004, 6, 43−46. (f) Artuso, E.; Carvoli, G.; Degani, I.; Fochi, R.;
Magistris, C. Controllable synthesis and magnetic properties of cubic
and hexagonal phase nickel nanocrystals. Synthesis 2007, 2007, 1096−
1100. (g) Wu, S.; Lei, X.; Fan, E.; Sun, Z. Thermolysis-Induced Two-
or Multicomponent Tandem Reactions Involving Isocyanides and
Sulfenic-Acid-Generating Sulfoxides: Access to Diverse Sulfur-
Containing Functional Scaffolds. Org. Lett. 2018, 20, 522−525.
(12) Manne, S. R.; Thalluri, K.; Giri, R. S.; Chandra, J.; Mandal, B.
Ethyl 2-tert-Butoxycarbonyloxyimino)-2-cyanoacetate (Boc-Oxyma):
An Efficient Reagent for the Racemization Free Synthesis of Ureas,
Carbamates and Thiocarbamates via Lossen Rearrangement. Adv.
Synth. Catal. 2017, 359, 168−176.
(13) (a) Kim, H.-K.; Lee, A. One-pot synthesis of carbamates and
thiocarbamates from Boc-protected amines. Tetrahedron Lett. 2016,
57, 4890−4892. (b) Kim, H.-K.; Lee, A. Facile one-pot synthesis of
unsymmetrical ureas, carbamates, and thiocarbamates from Cbz-
protected amines. Org. Biomol. Chem. 2016, 14, 7345−7353.
(14) Mampuys, P.; Zhu, Y.; Sergeyev, S.; Ruijter, E.; Orru, R. V. A.;
Van Doorslaer, S.; Maes, B. U. W. Iodide-Catalyzed Synthesis of
Secondary Thiocarbamates from Isocyanides and Thiosulfonates. Org.
Lett. 2016, 18, 2808−2811.
1517−1520. (i) Xie, L.-Y.; Peng, S.; Liu, F.; Chen, G.-R.; Xia, W.; Yu,
X.; Li, W.-F.; Cao, Z.; He, W.-M. Metal-free deoxygenative
sulfonylation of quinoline N-oxides with sodium sulfinates via a
dual radical coupling process. Org. Chem. Front. 2018, 5, 2604−2609.
(19) (a) Wang, D.; Zhang, R.; Lin, S.; Yan, Z.; Guo, S. Iodine-
mediated thiolation of phenol/phenylamine derivatives and sodium
arylsulfinates in neat water. RSC Adv. 2015, 5, 108030−108033.
(b) Wang, C.; Jia, H.; Li, Z.; Zhang, H.; Zhao, B. Palladium-catalyzed
C-3 desulfitative arylation of indolizines with sodium arylsulfinates
and arylsulfonyl hydrazides. RSC Adv. 2016, 6, 21814−21821.
(c) Guo, Y.-J.; Lu, S.; Tian, L.-L.; Huang, E.-L.; Hao, X.-Q.; Zhu,
X.; Shao, T.; Song, M.-P. Iodine-Mediated Difunctionalization of
Imidazopyridines with Sodium Sulfinates: Synthesis of Sulfones and
Sulfides. J. Org. Chem. 2018, 83, 338−349. (d) Katrun, P.;
Hongthong, S.; Hlekhlai, S.; Pohmakotr, M.; Reutrakul, V.;
Soorukram, D.; Jaipetch, T.; Kuhakarn, C. Iodine−PPh 3-mediated
C3-sulfenylation of indoles with sodium sulfinates. RSC Adv. 2014, 4,
18933−18938. (e) Rao, H.; Wang, P.; Wang, J.; Li, Z.; Sun, X.; Cao,
S. K2S2O8/arenesulfinate: an unprecedented thiolating system
enabling selective sulfenylation of indoles under metal-free conditions.
RSC Adv. 2014, 4, 49165−49169. (f) Huang, X.; Wang, S.; Li, B.;
Wang, X.; Ge, Z.; Li, R. Iodine−triphenylphosphine mediated
sulfenylation of imidazoheterocycles with sodium sulfinates. RSC
Adv. 2015, 5, 22654−22657. (g) Ding, Y.; Wu, W.; Zhao, W.; Li, Y.;
Xie, P.; Huang, Y.; Liu, Y.; Zhou, A. Generation of thioethers via
direct C−H functionalization with sodium benzenesulfinate as a sulfur
source. Org. Biomol. Chem. 2016, 14, 1428−1431.
(20) (a) Xiao, F. H.; Xie, H.; Liu, S.; Deng, G. J. Iodine Catalyzed
Regioselective Sulfenylation of Indoles with Sodium Sulfinates. Adv.
Synth. Catal. 2014, 356, 364−368. (b) Chen, Y.; Xiao, F.; Chen, H.;
Liu, S.; Deng, G.-J. Iodine-promoted 2-arylsulfanylphenol formation
using cyclohexanones as phenol source. RSC Adv. 2014, 4, 44621−
44628. (c) Xiao, F.; Chen, S.; Tian, J.; Huang, H.; Liu, Y.; Deng, G.-J.
Chemoselective cross-coupling reaction of sodium sulfinates with
phenols under aqueous conditions. Green Chem. 2016, 18, 1538−
1546.
(21) (a) Gao, Y.; Gao, Y.; Tang, X.; Peng, J.; Hu, M.; Wu, W.; Jiang,
H. Copper-catalyzed oxysulfenylation of enolates with sodium
sulfinates: a strategy to construct sulfenylated cyclic ether. Org. Lett.
2016, 18, 1158−1161. (b) Wu, W.; An, Y.; Li, J.; Yang, S.; Zhu, Z.;
Jiang, H. Iodine-catalyzed cascade annulation of alkynes with sodium
arylsulfinates: assembly of 3-sulfenylcoumarin and 3-sulfenylquinoli-
none derivatives. Org. Chem. Front. 2017, 4, 1751−1756.
(15) Bao, W.-H.; Wu, C.; Wang, J.-T.; Xia, W.; Chen, P.; Tang, Z.;
Xu, X.; He, W.-M. Molecular iodine-mediated synthesis of
thiocarbamates from thiols, isocyanides and water under metal-free
conditions. Org. Biomol. Chem. 2018, 16, 8403−8407.
(16) Pathare, R. S.; Patil, V.; Kaur, H.; Maurya, A. K.; Agnihotri, V.
K.; Khan, S.; Devunuri, N.; Sharon, A.; Sawant, D. M. Iodine-
catalyzed cross-coupling of isocyanides and thiols for the synthesis of
S-thiocarbamates. Org. Biomol. Chem. 2018, 16, 8263−8266.
(17) Wei, W.; Bao, P.; Yue, H.; Liu, S.; Wang, L.; Li, Y.; Yang, D.
Visible-Light-Enabled Construction of Thiocarbamates from Iso-
cyanides, Thiols, and Water at Room Temperature. Org. Lett. 2018,
20, 5291−5295.
(18) (a) Xiao, F. H.; Chen, S.; Chen, Y.; Huang, H.; Deng, G.-J.
Efficient 2-sulfolmethyl quinoline formation from 2-methylquinolines
and sodium sulfinates under transition-metal free conditions. Chem.
Commun. 2015, 51, 652−654. (b) Xiao, F. H.; Chen, H.; Xie, H.;
Chen, S.; Yang, L.; Deng, G.-J. Iodine-catalyzed regioselective 2-
sulfonylation of indoles with sodium sulfinates. Org. Lett. 2014, 16,
50−53. (c) Xu, Y.; Tang, X.; Hu, W.; Wu, W.; Jiang, H. F. Transition-
metal-free synthesis of vinyl sulfones via tandem cross-decarbox-
ylative/coupling reactions of sodium sulfinates and cinnamic acids.
Green Chem. 2014, 16, 3720−3723. (d) Tang, X. D.; Huang, L. B.;
Xu, Y. L.; Yang, J. D.; Wu, W. Q.; Jiang, H. F. Copper-Catalyzed
Coupling of Oxime Acetates with Sodium Sulfinates: An Efficient
Synthesis of Sulfone Derivatives. Angew. Chem., Int. Ed. 2014, 53,
4205−4208. (e) Wei, W.; Liu, C.; Yang, D.; Wen, J.; You, J.; Wang,
H. Metal-Free Direct Construction of Sulfonamides via Iodine-
Mediated Coupling Reaction of Sodium Sulfinates and Amines at
Room Temperature. Adv. Synth. Catal. 2015, 357, 987−992. (f) Wei,
W.; Cui, H.; Yang, D.; Liu, X.; He, C.; Dai, S.; Wang, H. Metal-free
molecular iodine-catalyzed direct sulfonylation of pyrazolones with
sodium sulfinates leading to sulfonated pyrazoles at room temper-
ature. Org. Chem. Front. 2017, 4, 26−30. (g) Li, W.; Yin, G.; Huang,
L.; Xiao, Y.; Fu, Z.; Xin, X.; Liu, F.; Li, Z.; He, W. Regioselective and
stereoselective sulfonylation of alkynylcarbonyl compounds in water.
Green Chem. 2016, 18, 4879−4883. (h) Li, L.-X.; Dong, D.-Q.; Hao,
S.-H.; Wang, Z.-L. Direct sulfonylation of pyrazolones with sodium
sulfinates catalyzed by TBAI in water. Tetrahedron Lett. 2018, 59,
(22) (a) Lin, Y.-m.; Lu, G.-p.; Cai, C.; Yi, W.-b. Odorless, One-Pot
Regio- and Stereoselective Iodothiolation of Alkynes with Sodium
Arenesulfinates under Metal-Free Conditions in Water. Org. Lett.
2015, 17, 3310−3313. (b) Lin, Y.-m.; Lu, G.-p.; Wang, G.-x; Yi, W.-b.
Odorless, Regioselective Synthesis of Diaryl Sulfides and α-Thioaryl
Carbonyls from Sodium Arylsulfinates via a Metal-Free Radical
Strategy in Water. Adv. Synth. Catal. 2016, 358, 4100−4105. (c) Lin,
Y.-m.; Lu, G.-p.; Wang, G.-x.; Yi, W.-b. Acid/Phosphide-Induced
Radical Route to Alkyl and Alkenyl Sulfides and Phosphonothioates
from Sodium Arylsulfinates in Water. J. Org. Chem. 2017, 82, 382−
389.
(23) (a) Wen, J.; Wei, W.; Xue, S.; Yang, D.; Lou, Y.; Gao, C.;
Wang, H. Metal-free Oxidative Spirocyclization of Alkynes with
Sulfonylhydrazides leading to 3-Sulfonated Azaspiro[4,5]trienones. J.
Org. Chem. 2015, 80, 4966−4972. (b) Cui, H.; Liu, X.; Wei, W.; Yang,
D.; He, C.; Zhang, T.; Wang, H. Molecular Iodine-Mediated
Difunctionalization of Alkenes with Nitriles and Thiols Leading to
β-Acetamido Sulfides. J. Org. Chem. 2016, 81, 2252−2260. (c) Wei,
W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.; Wang, H. Direct
and metal-free arylsulfonylation of alkynes with sulfonylhydrazides for
the construction of 3-sulfonated coumarins. Chem. Commun. 2015,
51, 768−771. (d) Bao, P.; Wang, L.; Liu, Q.; Yang, D.; Wang, H.;
Zhao, X.; Yue, H.; Wei, W. Direct coupling of haloquinolines and
sulfonyl chlorides leading to sulfonylated quinolines in water.
Tetrahedron Lett. 2019, 60, 214−218.
G
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(24) (a) Cui, H.; Wei, W.; Yang, D.; Zhang, Y.; Zhao, H.; Wang, L.;
Wang, H. Visible-light-induced selective synthesis of sulfoxides from
alkenes and thiols using air as the oxidant. Green Chem. 2017, 19,
3520−3524. (b) Wei, W.; Cui, H.; Yang, D.; Yue, H.; He, C.; Zhang,
Y.; Wang, H. Visible-light-enabled spirocyclization of alkynes leading
to 3-sulfonyl and 3-sulfenyl azaspiro[4,5]trienones. Green Chem. 2017,
19, 5608−5613. (c) Wei, W.; Wang, L.; Yue, H.; Bao, P.; Liu, W.; Hu,
C.; Yang, D.; Wang, H. ACS Sustainable Chem. Eng. 2018, 6, 17252−
17257. (d) Wei, W.; Wang, L.; Bao, P.; Shao, Y.; Yue, H.; Yang, D.;
Yang, X.; Zhao, X.; Wang, H. Org. Lett. 2018, 20, 7125−7130.
(25) (a) Katrun, P.; Mueangkaew, C.; Pohmakotr, M.; Reutrakul, V.;
Jaipetch, T.; Soorukram, D.; Kuhakarn, C. Regioselective C 2
Sulfonylation of Indoles Mediated by Molecular Iodine. J. Org.
Chem. 2014, 79, 1778−1785. (b) Larsen, A. G.; Holm, A. H.;
Roberson, M.; Daasbjerg, K. Substituent effects on the oxidation and
reduction potentials of phenylthiyl radicals in acetonitrile. J. Am.
Chem. Soc. 2001, 123, 1723−1729. (c) Ji, C.; Ahmida, M.; Chahma,
M.; Houmam, A. Radical/ion pair formation in the electrochemical
reduction of arene sulfenyl chlorides. J. Am. Chem. Soc. 2006, 128,
15423−15431.
(26) He, Y.; Wang, Y.-C.; Hu, K.; Xu, X.-L.; Wang, H.-S.; Pan, Y.-M.
Palladium-Catalyzed Synthesis of 5-Iminopyrrolones through Iso-
cyanide Double Insertion Reaction with Terminal Alkynes and Water.
J. Org. Chem. 2016, 81, 11813−11818.
(27) Liu, X.; Cui, H.; Yang, D.; Dai, S.; Zhang, G.; Wei, W.; Wang,
H. Iodine-catalyzed Direct Thiolation of Indoles with Thiols Leading
to 3-Thioindoles Using Air as the Oxidant. Catal. Lett. 2016, 146,
1743−1748.
H
DOI: 10.1021/acs.joc.8b02844
J. Org. Chem. XXXX, XXX, XXX−XXX