An Alternative Metal-Free Aerobic Oxidative Cross-Dehydrogenative Coupling of Sulfonyl Hydrazides with Secondary Phosphine Oxides

Article abstract of DOI:10.1055/s-0039-1690709

An alternative metal-free, efficient and practical approach for the preparation of phosphinothioates is established via the aerobic oxidative cross-dehydrogenative coupling (CDC) of sulfonyl hydrazides with secondary phosphine oxides catalyzed by tetrabutylammonium iodide (TBAI) in the presence of atmospheric oxygen. The strategy provides an array of diverse phosphinothioates in good to excellent yields. Furthermore, two representative bioactive molecules are synthesized on up to gram scale by utilizing this method.

Full text of DOI:10.1055/s-0039-1690709

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–J
paper
A
en
T. Liu et al.
Paper
Synthesis
An Alternative Metal-Free Aerobic Oxidative Cross-Dehydrogenative
Coupling of Sulfonyl Hydrazides with Secondary Phosphine Oxides
Teng Liu*
O
S
P
OEt
Yanqiong Zhang
Rong Yu
Ph
Inezin
S
TBAI
DMF
O
P
O
S
O
P
OEt
R
S
R1
Jianjun Liu
+
R1
H
R
NHNH2
P
OEt
O
O
R2
Feixiang Cheng*
R2
Cl
An anticholinesterase
1
3
2
4
Metal-free process
Air as safe and green oxidant
Broad substrate scope
Efficient and practical to prepare bioactive molecules
Center for Yunnan-Guizhou Plateau Chemical Functional
Materials and Pollution Control, Qujing Normal University,
Qujing, 655011, P. R. of China
15288404381@163.com
liut_yqzhin@mail.qjnu.edu.cn
Received: 06.08.2019
Accepted after revision: 20.09.2019
Published online: 17.10.2019
For the past few years, transition-metal-catalyzed cross-
coupling reactions of organosulfur compounds (diaryl di-
sulfides and sulfonyl chlorides) with secondary phosphine
oxides to construct S–P(O) bonds have been explored
(Scheme 1, B, Route 5).4e,5h,6 Very recently, the cross-dehy-
drogenative coupling (CDC) procedure has provided a
straightforward and atom-economic approach to access
phosphinothioates. However, many of the reported exam-
ples were highly dependent on the use of a stoichiometric
strong oxidant, such as peroxides (TBPB, DTBP) and DDQ
(Scheme 1, B, Route 6).7
DOI: 10.1055/s-0039-1690709; Art ID: ss-2019-f0440-op
Abstract An alternative metal-free, efficient and practical approach
for the preparation of phosphinothioates is established via the aerobic
oxidative cross-dehydrogenative coupling (CDC) of sulfonyl hydrazides
with secondary phosphine oxides catalyzed by tetrabutylammonium io-
dide (TBAI) in the presence of atmospheric oxygen. The strategy pro-
vides an array of diverse phosphinothioates in good to excellent yields.
Furthermore, two representative bioactive molecules are synthesized
on up to gram scale by utilizing this method.
Subsequently, Han et al. reported an oxidant-free, palla-
dium-catalyzed dehydrogenative phosphorylation of RSH
with R2P(O)H (Scheme 1, B, Route 6).8 Thereafter, Zhang and
co-workers developed two types of metal-free approaches
via oxidative dehydrogenative processes for the preparation
of phosphinothioates (Scheme 1, B, Route 6).1y,9 In recent
years, sulfonyl hydrazides, which are stable, non-corrosive,
readily accessible and odorless sulfur sources, have been
widely applied in organic synthesis.10 In 2014, Kumaras-
wamy and Raju developed an aerobic dehydrogenative
sulfenylation of secondary phosphine oxides with sulfonyl
hydrazides catalyzed by CuI for the preparation of phosphi-
nothioates (Scheme 1, B).11 However, despite these advanc-
es, the involved starting materials, R2P(O)X (X = Cl, Br) and
RSX (X = H, Cl, Br, CN, SAr), were often very odorous, toxic
or moisture-sensitive reagents.4–9 Furthermore, the afore-
mentioned methods frequently required transition-metal
catalysis and stoichiometric amounts of strong bases and
oxidants.4e,5h,6–8 Considering the importance of phosphi-
nothioates in organic chemistry and biological chemistry,
developing efficient, green and sustainable strategies to
avoid the restrictions mentioned above are highly desirable,
yet remain a formidable challenge.
Key words phosphinothioates, metal-free, cross-dehydrogenative
coupling, secondary phosphine oxides, sulfonyl hydrazides
Sulfur-containing organophosphorus derivatives have
received considerable attention in recent decades, and
many examples exhibit diverse biological activities as pesti-
cides, insecticides, anticholinesterases, curing accelerators,
antistatic agents and chemotherapeutic agents, etc.
(Scheme 1, A).1 Over the past decades, direct S–P cross-cou-
pling reactions have proven to be among the most import-
ant and effective strategies to access phosphinothioate
frameworks. In 1982, Michalski and co-workers reported
the reaction of a sulfonic acid with a phosphamidazole at –
60 °C to give, after oxidation, the corresponding phosphi-
nothioate (Scheme 1, B, Route 1).2 The groups of Kaboudin
and Zhao have described multicomponent reactions (MCRs)
for the preparation of phosphinothioates by utilizing dieth-
yl phosphite, sulfur and alkyl halides or aryl boronic acids,
respectively (Scheme 1, B, Route 2).3 In addition, general
methods for the preparation of phosphinothioates via nuc-
leophilic substitution reactions of the moisture-sensitive
and toxic halides [RSX, R2P(O)X]4 and base-promoted Ath-
erton–Todd type S–P(O) reactions5 have been reported
(Scheme 1, B, Routes 3 and 4).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
T. Liu et al.
Paper
Synthesis
A: Representative bioactive molecules
Me
N+
I–
O
O
P
OiPr
O
P
Me
Me
O
P
Me
S
S
OiPr
S
P
OEt
S
OEt
S
OEt
Ph
OEt
OEt
A: Inezin
B: Iprobenfos
C: Demeton
D: Echothiopate
OMe
OEt
OMe
OMe
OMe
OMe
OMe
S
S
S
S
P
P
O
P
O
P
OEt
OMe
O
O
Cl
Cl
tBu
Cl
E: A anticholinesterase
F: A curing accelerator
G: An antistatic agent
H: A pesticide
B: The strategies for the preparation of phosphinothioates
R1
O
N
R3SO3H
R1
P
R2
H
P
N
+
+
S (S8) + R3X or ArB(OH)2
R2
Route 2
Route 1
O
P
R2
O
P
R2
R1
R1
X
H
R1
R1
H
H
+
R3SH
(X = Cl, Br)
+
+
R3SX (X = SAr, O2Cl)
O
P
R3
S
R1
Route 3
Route 4
Route 5
Route 6
R2
O
P
O
P
phosphinothioates
+
R3SX
R3SH
R2
R2
(X = Cl, Br, CN)
Ref. 11
CuI
This work
TBAI, air
O
P
R1
H
+
R2SO2NHNH2
R2
Metal-free process
Air as a safe and green oxidant
Efficient and practical to prepare bioactive molecules
1
3
2
Broad substrate scope
4
Scheme 1 Representative bioactive molecules and the strategies for the preparation of phosphinothioates
Atmospheric oxygen is a renewable, safe and green oxi-
dant, which has been widely used in organic transforma-
tions. In continuation of our interest in constructing func-
tional molecules via green synthetic strategies,12 herein we
describe a metal-free procedure for the cross-dehydrogena-
tive coupling of secondary phosphine oxides with sulfonyl
hydrazides catalyzed by tetrabutylammonium iodide (TBAI)
in the presence of atmospheric oxygen (Scheme 1, B). Fur-
thermore, our strategy can be applied to the preparation of
representative bioactive molecules.
Our initial studies were directed toward investigation of
the coupling of sulfonyl hydrazide 1a and secondary phos-
phine oxide 2a, as model substrates, at 75 °C in DMF under
atmospheric oxygen (Table 1). In order to avoid metal io-
dide salts, TBAI was selected as the iodine source to catalyze
this reaction. To our delight, the anticipated product 3a was
obtained in 81% yield, however, the dimerized compounds
4a and 4b were also isolated in 13% and 15% yield, respec-
tively (Table 1, entry 1). The relative configuration of 3a was
determined by X-ray crystallographic analysis (Scheme 2).13
In order to further improve the yield of the desired product
3a and reduce the formation of dimerized compounds, oth-
er iodine sources were screened (NaI, KI, NIS), resulting in
product 3a being obtained in yields of 25–45% (Table 1, en-
tries 2–4). Remarkably, no trace of the desired product 3a
was observed when using molecular iodine as the catalyst;
instead, the dimerized compounds 4a and 4b were isolated
in yields of 23% and 25%, respectively (Table 1, entry 5).
Next, different solvents were screened, including toluene,
CH3CN, NMP, DMSO and 1,4-dioxane, and the results
showed that DMF was the best reaction medium (Table 1,
compare entries 1 and 6–10).
Furthermore, increasing or lowering the reaction tem-
perature had adverse effects on the yield, with product 3a
being obtained in yields of 55% and 72% at temperatures of
65 °C and 85 °C, respectively (Table 1, entries 11 and 12).
Ultimately, the optimum conditions for this coupling reac-
tion required 20 mol% of TBAI as the catalyst, a temperature
of 75 °C and DMF as the solvent, with 3a being obtained in
81% yield.
Having optimized the conditions for the cross-dehydro-
genative coupling process between secondary phosphine
oxides and sulfonyl hydrazides, we next sought to explore
the generality of this reaction. Firstly, aromatic sulfonyl hy-
t
drazides 1 with electron-rich [Me, OMe, Bu, Ph, 2,4,6-
(Me)3] or electron-withdrawing (F, Cl, Br) substituents re-
acted with diphenylphosphine oxide (2a) to give the corre-
sponding products in excellent yields (70–85%). Sterically
hindered mesitylenesulfonyl hydrazide (1f) also reacted ef-
ficiently to give the desired product in a satisfactory 77%
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J

C
T. Liu et al.
Paper
Synthesis
Table 1 Optimization of the Reaction Conditionsa
Me
Me
S
S
Me
Me
O
O
O
4a
conditions
Me
S
P
Ph
Me
S
NHNH2
+
Ph
P
H
O
S
75 °C, 4 h, air
Ph
O
Ph
2a
S
1a
3a
O
4b
Entry
Catalyst
Solvent
Yield (%)b
1
2
TBAI
NaI
DMF
81
45
28
25
–
DMF
3
KI
DMF
4
NIS
DMF
5
I2
DMF
6
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
toluene
CH3CN
NMP
61
50
65
44
51
55
72
7
8
9
DMSO
10
11c
12d
1,4-dioxane
DMF
DMF
a Reaction conditions: 1a (1.1 mmol), 2a (1.0 mmol), catalyst (20 mol%), solvent (5.0 mL), air, 75 °C, 4 h.
b Yield of isolated product based on 2a.
c Reaction temperature: 65 °C, reaction time: 5 h.
d Reaction temperature: 85 °C, reaction time: 2 h.
yield (Scheme 2). Furthermore, -naphthylsulfonyl hydra-
zide (1g) was also compatible with this transformation, de-
livering the corresponding phosphinothioate 3g in 76%
yield. In addition, a sulfonyl hydrazide bearing an electron-
donating methoxy substituent and an electron-withdraw-
ing chlorine group on the aromatic nucleus provided the
target product 3k in 80% yield. More importantly, various
aliphatic sulfonyl hydrazides containing straight-chain and
O
O
S
O
TBAI (20 mol%)
R
S
P
Ph
Ph
R
NHNH2
+
Ph
P
H
DMF, 75 °C, air
1–4 h
O
Ph
2a
1
3a–p
R = Aryl
O
O
O
Me
S
P
Ph
S
P
Ph
MeO
S
P
Ph
Ph
Ph
Ph
3a, 81%
3b, 80%
3c, 85%
(CCDC 1941646)
O
Me
S
O
P
O
O
Me
Ph
tBu
S
P
Ph
Ph
Cl
S
P
Ph
S
P
Ph
Ph
Ph
Ph
Ph
Ph
Me
3f, 77%
3d, 83%
3e, 80%
3g, 76%
OMe
S
O
P
O
O
P
O
F
S
Ph
S
P
Ph
Br
S
Ph
P
Ph
Ph
Ph
Ph
Cl
3h, 77%
3i, 78%
3j, 70%
3k, 80%
R = Alkyl
O
O
O
O
O
Me
Me
Bn
S
P
Ph
nBu
S
P
Ph
Et
S
P
Ph
S
P
Ph
S
P
Ph
Ph
Ph
Ph
Ph
Ph
3l, 75%
3m, 79%
3n, 73%
3o, 77%
3p, 70%
Scheme 2 Synthesis of phosphinothioates 3a–p
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J

D
T. Liu et al.
Paper
Synthesis
branched alkyl substituents also proved to be suitable sub-
strates in this transformation, giving the corresponding
phosphinothioates 3l–p in yields of 70–79% (Scheme 2).
Under the optimized conditions, the substrate scope of
various secondary phosphine oxides 2 was examined
(Scheme 3). Diaryl-substituted phosphorus oxides with
electron-donating substituents (R1/R2 = 4-Me-C6H4, -
naphthyl) or sterically hindered groups [R1/R2 = 3,5-(Me)2-
C6H3] reacted with 4-methylbenzenesulfonyl hydrazide
(1a) to give the corresponding products 5a–c in yields of
82–88%. In addition, diaryl-substituted phosphorus oxides
with electron-withdrawing groups (4-F, 4-Cl), and even
with both electron-donating (Me) and electron-withdraw-
ing (F) groups, on the aromatic rings provided the corre-
sponding products 5d–f with 74–80% yields. Notably, a di-
heteroarylphosphine oxide was also well tolerated in this
transformation, providing the desired product 5g in a satis-
factory 82% yield.
Subsequently, we turned our attention to phosphite di-
ester substrates. To our delight, phosphite diesters such as
diethyl phosphite, diisopropyl phosphite and dibutyl phos-
phite survived in this transformation, delivering the corre-
sponding products 5h–k in satisfactory yields of 78–85%
(Scheme 3). Furthermore, a dialkyl-substituted phosphorus
oxide was also compatible with this transformation, afford-
ing the desired product 5l in 78% yield. To further demon-
strate the potential utility of our strategy, two bioactive
molecules, including the pesticide inezin (5m) and the anti-
cholinesterase agent 5n, were synthesized via this metal-
free, aerobic cross-dehydrogenative coupling reaction.
These reactions could also be scaled-up to gram level.
Additionally, to confirm that this reaction is an aerobic
oxidative cross-dehydrogenative coupling process, several
investigations were conducted. Indeed, under the standard
conditions, the coupling reaction between 1a and 2a pro-
ceeded smoothly in the presence of an oxygen (O2) atmo-
sphere, but was sluggish when performed under a nitrogen
(N2) atmosphere (Scheme 4).
Based on the aforementioned results and previous re-
ports, a plausible mechanism is proposed by analogy with
cross-dehydrogenative coupling reactions.11,14 Initially, io-
dine ions from TBAI react with oxygen to generate an io-
dine(I) peroxo species, which then dissociates in the pres-
ence of the sulfonyl hydrazide resulting in organic peroxide
Int-A and hypoiodous acid (HOI). Next, sequential removal
of hydrogen and oxygen atoms from putative Int-A could
lead to thiodiazonium salt Int-B. Subsequently, the phos-
phorus atom of 2′ (i.e., the tautomer of 2) attacks Int-B to
form the desired phosphinothioates 3 or 5, accompanied by
release of nitrogen and hypoiodic acid (HOI). In these pro-
cedures, iodine ions are converted into the iodine(I) peroxo
species, which then dissociates into HOI and HOOI, both of
which react to give water and regenerate the iodine(I) per-
oxo species to continue the catalytic cycle (Scheme 5).
O
O
S
O
P
TBAI (20 mol%)
R1
+
R1
H
Me
S
P
Me
NHNH2
DMF, 75 °C, 1–4 h
R2
R2
O
1a
2
5a–k
R1, R2 = Aryl, (Het)Aryl
O
Me
O
Me
S
P
Me
O
P
Me
S
P
Me
S
Me
Me
Me
Me
5a, 88%
5b, 82%
5c, 84%
O
P
O
F
O
P
O
P
Me
S
F Me
S
P
Cl
S
Me
S
Me
Me
S
S
Me
F
F
Cl
5e, 77%
5f, 80%
5g, 82%
5d, 74%
R1, R2 = Aryl, Alkyl, O-alkyl
O
O
O
O
Me
S
P
OEt
Me
S
P
OiPr
OiPr
Me
S
P
OnBu
OnBu
Me
S
P
OEt
OEt
Ph
5h, 85%
5i, 82%
5j, 84%
5k, 78%
OEt
O
S
O
P
P
S
P
OEt
OEt
Me
S
O
Ph
Cl
5m: Inezin, 68%
gram-level, 65%
5n: An anticholinesterase, 77%
5l, 78%
gram-level, 76%
Scheme 3 Synthesis of phosphorus-containing thioates 5a–n
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J

E
T. Liu et al.
Paper
Synthesis
O
O
O
TBAI (20 mol%)
Me
Me
S
S
P
Ph trace
Me
S
NHNH2
NHNH2
+
+
Ph
Ph
P
H
H
DMF, N2, 75 °C, 3 h
Ph
O
Ph
2a
1a
1a
3a
3a
O
O
S
O
TBAI (20 mol%)
P
Ph
85%
Me
P
DMF, O2, 75 °C, 2 h
Ph
O
Ph
2a
Scheme 4 Confirmation of the aerobic oxidative cross-dehydrogenative coupling process
I–
R
+
O2
N
I-O-O-I
O
I-O-O-I
O
O-I
N
OI–#
O
H
H
O
S
H
H
S
N
H
R
S
N
N
R
N
H
R
S
N
N
H
O
O
O-I
Int-A
– H-O-O-I
– HOI
– H-O-O-I
H
I-O-O-I
O
tautomerization
P
R2
R1
2
O
R1
2'
R
S N N
R S
P
R2
3, 5
OI–
– N2, – HOI
+ H2O
Int-B
I-O-O-I
HOI
+
H-O-O-I
Scheme 5 Proposed reaction mechanism
In summary, an alternative metal-free, efficient and
practical approach for the preparation of phosphinothio-
ates has been established. The aerobic oxidative cross-de-
hydrogenative coupling (CDC) of sulfonyl hydrazides with
secondary phosphine oxides catalyzed by TBAI in the pres-
ence of atmospheric oxygen provides an array of diverse
phosphinothioates in good to excellent yields. Furthermore,
several bioactive molecules could be prepared on up to
gram scale via this method. Studies on the potential biolog-
ical activity of the other compounds prepared in this work
are currently under investigation in our laboratory.
and brine (2 × 5 mL) and then dried over anhydrous Na2SO4. The sol-
vent was evaporated under reduced pressure to give the correspond-
ing sulfonyl hydrazide 1.
Secondary Phosphine Oxides 2; General Procedure12c
A mixture of magnesium turnings (3.3 mmol, 3.3 equiv), a small
amount of iodine (ca. 3 pieces) and a small amount of 1-bromo-4-bu-
tylbenzene (ca. 5 drops) in THF (20 mL) was vigorously stirred under
N2. The flask was heated until the reaction was initiated (the solution
became colorless). A solution of the corresponding aryl bromide (30.0
mmol, 3.0 equiv) in THF (30 mL) was added dropwise and the mixture
stirred for 1 h. The flask was cooled to 0 °C using an ice bath and di-
ethyl phosphite (1.30 mL, 10.0 mmol, 1.0 equiv) in THF (10 mL) was
added over 30 min. After stirring for a further 2 h at room tempera-
ture, the reaction was quenched by the addition of 2 M HCl (20 mL) at
0 °C, and stirred for 15 min. The mixture was filtered through a Celite
pad and the filtrate was extracted with EtOAc (×3). The combined or-
ganic layer was washed with brine and dried over Na2SO4. After evap-
oration of the solvent, the residue was purified by flash column chro-
matography on silica gel (PE/EtOAc, 1:1) to afford the corresponding
secondary phosphine oxide 2.
All commercial reagents and solvents were used without further pu-
rification unless otherwise stated. Column chromatography was per-
formed using Greagent silica gel (200–300 mesh). Melting points
were determined on an XT-4A melting point apparatus and are uncor-
rected. NMR spectra were recorded on a Bruker 400 spectrometer (1H,
400 MHz; 13C, 100 MHz) with CDCl3 as the solvent. The chemical
shifts () are expressed in parts per million relative to the residual
deuterated solvent signal and coupling constants (J) are given in
hertz. High-resolution mass spectrometry (ESI) was performed on an
Agilent LC/MSD TOF instrument.
Phosphorus-Containing Thioates 3 and 5; General Procedure14
A 10 mL round-bottomed flask was charged with sulfonyl hydrazide 1
(1.1 mmol, 1.1 equiv), secondary phosphine oxide 2 (1.0 mmol, 1.0
equiv) and TBAI (0.2 mmol, 0.2 equiv) in DMF (5 mL). The resulting
solution was stirred for 1–4 h at 75 °C until the secondary phosphine
oxide 2 had been completely consumed, as indicated by TLC. After,
cooling, the reaction mixture was extracted with EtOAc (2 × 20 mL).
The combined organic layers were washed with H2O (2 × 10 mL) and
brine (2 × 5 mL) and then dried over anhydrous Na2SO4. The solvent
was evaporated under reduced pressure and the residue purified by
flash column chromatography on silica gel (PE/EtOAc, 10:1 to 2:1) to
afford the desired product 3 or 5.
Sulfonyl Hydrazides 1; General Procedure10
To a stirred solution of the corresponding sulfonyl chloride (10 mmol,
1.0 equiv) in THF (20 mL) at 0 °C, hydrazine hydrate (11 mmol, 1.1
equiv) was added slowly. The reaction mixture was allowed to warm
to ambient temperature and was stirred for over 1 h, with the prog-
ress monitored by TLC analysis. After the sulfonyl chloride had been
completely consumed, the residue was extracted with EtOAc (2 × 20
mL). The combined organic layers were washed with H2O (2 × 10 mL)
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J

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T. Liu et al.
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Synthesis
S-p-Tolyl Diphenylphosphinothioate (3a)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H19OPSNa: 409.0786;
found: 409.0785.
Yield: 262 mg (81%); yellow-white solid; mp 114–116 °C.
1H NMR (400 MHz, CDCl3):  = 7.82–7.87 (m, 4 H, ArH), 7.49–7.53 (m,
2 H, ArH), 7.42–7.46 (m, 4 H, ArH), 7.31–7.33 (m, 2 H, ArH), 7.01 (d, J =
8.0 Hz, 2 H, ArH), 2.25 (s, 3 H, ArCH3).
S-Mesityl Diphenylphosphinothioate (3f)
Yield: 271 mg (77%); yellow-white solid; mp 74–76 °C.
1H NMR (400 MHz, CDCl3):  = 7.74–7.79 (m, 4 H, ArH), 7.50–7.54 (m,
2 H, ArH), 7.40–7.45 (m, 4 H, ArH), 6.84 (s, 2 H, ArH), 2.24 (s, 6 H,
ArCH3), 2.23 (s, 3 H, ArCH3).
13C NMR (100 MHz, CDCl3):  = 139.2 (d, J = 3.7 Hz), 135.4 (d, J = 5.9
Hz), 133.2, 132.3, 132.2, 132.1, 130.0 (d, J = 3.0 Hz), 122.3 (d, J = 8.3
Hz), 122.2, 21.2.
13C NMR (100 MHz, CDCl3):  = 144.8 (d, J = 5.1 Hz), 139.4 (d, J = 4.5
Hz), 139.3, 133.8, 132.8, 132.2, 131.4, 131.3, 129.4, 129.3, 128.5,
128.3, 120.8 (d, J = 9.6 Hz), 22.4, 21.1.
31P NMR (160 MHz, CDCl3):  = 41.3.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H17OPSNa: 347.0630;
found: 347.0630.
31P NMR (160 MHz, CDCl3):  = 39.6.
S-Phenyl Diphenylphosphinothioate (3b)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H21OPSNa: 375.0943;
found: 375.0943.
Yield: 247 mg (80%); yellow-white solid; mp 108–110 °C.
1H NMR (400 MHz, CDCl3):  = 7.75–7.78 (m, 4 H, ArH), 7.42–7.47 (m,
2 H, ArH), 7.34–7.39 (m, 6 H, ArH), 7.10–7.20 (m, 3 H, ArH).
S-(Naphthalen-2-yl) Diphenylphosphinothioate (3g)
Yield: 273 mg (76%); yellow-white solid; mp 142–144 °C.
1H NMR (400 MHz, CDCl3):  = 7.99 (s, 1 H, ArH), 7.85–7.90 (m, 4 H,
ArH), 7.65–7.76 (m, 3 H, ArH), 7.41–7.53 (m, 9 H, ArH).
13C NMR (100 MHz, CDCl3):  = 135.4 (d, J = 6.1 Hz), 133.1, 132.3 (d, J =
4.6 Hz), 131.7 (d, J = 16.3 Hz), 129.1 (d, J = 2.2 Hz), 129.0 (d, J = 3.4 Hz),
128.6, 126.2, 126.1 (d, J = 8.2 Hz).
13C NMR (100 MHz, CDCl3):  = 135.4 (d, J = 8.0 Hz), 133.5, 133.1 (d, J =
11.8 Hz), 132.4 (d, J = 4.6 Hz), 132.0, 131.7, 131.6 (d, J = 5.3 Hz), 128.7,
128.6, 128.5, 127.8, 127.6, 126.9, 126.5, 123.5, 123.4 (d, J = 9.0 Hz).
31P NMR (160 MHz, CDCl3):  = 41.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H15OPSNa: 333.0473;
found: 333.0472.
31P NMR (160 MHz, CDCl3):  = 41.5.
S-(4-Methoxyphenyl) Diphenylphosphinothioate (3c)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H17OPSNa: 383.0630;
found: 383.0628.
Yield: 289 mg (85%); yellow-white solid; mp 112–114 °C.
1H NMR (400 MHz, CDCl3):  = 7.81–7.83 (m, 4 H, ArH), 7.49–7.53 (m,
2 H, ArH), 7.42–7.47 (m, 4 H, ArH), 7.32–7.34 (m, 2 H, ArH), 6.73 (d, J =
8.4 Hz, 2 H, ArH), 3.74 (s, 3 H, ArCH3).
S-(4-Fluorophenyl) Diphenylphosphinothioate (3h)
Yield: 252 mg (77%); yellow-white solid; mp 78–80 °C.
1H NMR (400 MHz, CDCl3):  = 7.81–7.86 (m, 4 H, ArH), 7.39–7.55 (m,
8 H, ArH), 6.88–6.92 (m, 2 H, ArH).
13C NMR (100 MHz, CDCl3):  = 160.5 (d, J = 3.2 Hz), 137.1 (d, J = 5.6
Hz), 133.2, 132.3, 132.2, 132.1, 131.7, 131.6, 128.6, 116.0 (d, J = 8.2
Hz), 114.8 (d, J = 2.6 Hz), 55.3.
31P NMR (160 MHz, CDCl3):  = 41.3.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H17O2PSNa: 363.0579;
13C NMR (100 MHz, CDCl3):  = 164.7, 162.2, 137.5 (d, J = 5.8), 137.4
(d, J = 5.8 Hz), 132.5, 132.4, 121.1, 116.5 (d, J = 2.2 Hz), 116.2 (d, J = 2.2
Hz), 116.3, 116.2.
31P NMR (160 MHz, CDCl3):  = 41.7.
19F NMR (160 MHz, CDCl3):  = –111.7.
found: 363.0580.
S-[4-(tert-Butyl)phenyl] Diphenylphosphinothioate (3d)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H14FOPSNa: 351.0379;
Yield: 366 mg (83%); yellow-white solid; mp 112–114 °C.
found: 351.0377.
1H NMR (400 MHz, CDCl3):  = 7.82–7.87 (m, 4 H, ArH), 7.50–7.54 (m,
2 H, ArH), 7.42–7.47 (m, 4 H, ArH), 7.34–7.36 (m, 2 H, ArH), 7.21–7.23
(m, 2 H, ArH), 1.24 (s, 9 H, ArCH3).
S-(4-Chlorophenyl) Diphenylphosphinothioate (3i)
Yield: 268 mg (78%); yellow-white solid; mp 86–88 °C.
13C NMR (100 MHz, CDCl3):  = 152.3 (d, J = 3.8 Hz), 135.3 (d, J = 6.1
Hz), 135.2, 133.2, 132.3 (d, J = 4.8 Hz), 132.1, 131.7, 131.6, 128.6,
128.4, 126.3, 122.2 (d, J = 8.3 Hz), 34.6. 31.1.
31P NMR (160 MHz, CDCl3):  = 41.7.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H23OPSNa: 389.1099;
1H NMR (400 MHz, CDCl3):  = 7.81–7.87 (m, 4 H, ArH), 7.52–7.56 (m,
2 H, ArH), 7.44–7.49 (m, 4 H, ArH), 7.36–7.39 (m, 2 H, ArH), 7.16–7.20
(m, 2 H, ArH).
13C NMR (100 MHz, CDCl3):  = 136.6 (d, J = 6.2 Hz), 135.6 (d, J = 4.0
Hz), 135.5, 132.7, 132.6, 132.5, 129.4, 129.3, 124.7 (d, J = 8.3 Hz).
31P NMR (160 MHz, CDCl3):  = 41.7.
found: 389.1096.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H14ClOPSNa: 367.0084;
found: 367.0080.
S-([1,1′-Biphenyl]-4-yl) Diphenylphosphinothioate (3e)
Yield: 308 mg (80%); yellow-white solid; mp 100–102 °C.
1H NMR (400 MHz, CDCl3):  = 7.85–7.91 (m, 4 H, ArH), 7.39–7.55 (m,
S-(4-Bromophenyl) Diphenylphosphinothioate (3j)
14 H, ArH), 7.31–7.36 (m, 1 H, ArH).
Yield: 271 mg (70%); yellow-white solid; mp 140–142 °C.
13C NMR (100 MHz, CDCl3):  = 141.8 (d, J = 3.5 Hz), 140.0 (d, J = 6.2
Hz), 135.8, 135.7, 133.1, 132.4, 132.3, 132.0, 131.7, 131.6, 128.8,
128.7, 128.5, 127.8, 127.7, 127.1, 125.0, 124.9 (d, J = 8.6 Hz).
1H NMR (400 MHz, CDCl3):  = 7.81–8.05 (m, 4 H, ArH), 7.60–7.77 (m,
3 H, ArH), 7.52–7.55 (m, 2 H, ArH), 7.42–7.48 (m, 4 H, ArH), 7.35–7.39
(m, 1 H, ArH).
31P NMR (160 MHz, CDCl3):  = 41.5.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J

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13C NMR (100 MHz, CDCl3):  = 136.8 (d, J = 5.9 Hz), 132.7, 132.5,
132.3, 132.2, 131.6, 131.3, 131.2, 129.4, 128.7, 128.6, 128.2, 128.0,
125.4 (d, J = 9.6 Hz), 123.8 (d, J = 7.7 Hz).
1H NMR (400 MHz, CDCl3):  = 7.86–7.91 (m, 4 H, ArH), 7.46–7.55 (m,
6 H, ArH), 3.38–3.47 (m, 1 H, CH), 1.36 (s, 3 H, CH3), 1.35 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3):  = 134.3, 133.2, 132.2, 132.1, 131.6,
131.4, 128.7, 128.6, 37.0 (d, J = 3.8 Hz), 25.8 (d, J = 7.2 Hz).
31P NMR (160 MHz, CDCl3):  = 41.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H14BrOPSNa: 410.9579;
31P NMR (160 MHz, CDCl3):  = 41.9.
found: 410.9578.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H17OPSNa: 299.0630;
found: 299.0631.
S-(5-Chloro-2-methoxyphenyl) Diphenylphosphinothioate (3k)
Yield: 299 mg (80%); yellow-white solid; mp 112–114 °C.
S-Cyclopropyl Diphenylphosphinothioate (3p)
1H NMR (400 MHz, CDCl3):  = 7.85–7.90 (m, 4 H, ArH), 7.61–7.62 (m,
1 H, ArH), 7.50–7.54 (m, 2 H, ArH), 7.42–7.47 (m, 4 H, ArH), 7.17–7.20
(m, 1 H, ArH), 6.64 (d, J = 8.8 Hz, 1 H, ArH), 3.61 (s, 3 H, ArOCH3).
13C NMR (100 MHz, CDCl3):  = 158.3 (d, J = 5.6 Hz), 136.8 (d, J = 6.4
Hz), 133.2, 132.4, 132.3, 132.2, 130.5, 125.6 (d, J = 3.0 Hz), 115.9 (d, J =
8.2 Hz), 112.0 (d, J = 2.7 Hz), 55.9.
Yield: 191 mg (70%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.83–7.92 (m, 4 H, ArH), 7.55–7.58 (m,
6 H, ArH), 1.92–1.99 (m, 1 H, CH), 0.78–0.83 (m, 2 H, CH2), 0.67–0.69
(m, 2 H, CH2).
13C NMR (100 MHz, CDCl3):  = 133.8, 132.7, 132.3 (d, J = 4.8 Hz),
131.6, 131.5, 129.5, 128.7, 128.6, 128.1, 126.4, 115.4, 31.1, 9.39 (d, J =
4.5 Hz), 7.73 (d, J = 8.6 Hz).
31P NMR (160 MHz, CDCl3):  = 41.6.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H16ClO2PSNa: 397.0189;
31P NMR (160 MHz, CDCl3):  = 42.9.
found: 397.0189.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H15OPSNa: 297.0473;
found: 297.0475.
S-Benzyl Diphenylphosphinothioate (3l)
Yield: 243 mg (75%); yellow-white oil.
S-(p-Tolyl) Di-p-tolylphosphinothioate (5a)
1H NMR (400 MHz, CDCl3):  = 7.84–7.89 (m, 4 H, ArH), 7.52–7.56 (m,
2 H, ArH), 7.36–7.49 (m, 4 H, ArH), 7.18–7.22 (m, 5 H, ArH), 4.03 (d, J =
8.8 Hz, 2 H, ArCH2).
13C NMR (100 MHz, CDCl3):  = 136.8, 133.5, 132.4, 132.3, 131.6,
131.5, 129.1, 128.8, 128.6 (d, J = 5.4 Hz), 127.5, 33.2.
31P NMR (160 MHz, CDCl3):  = 42.9.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H17OPSNa: 347.0630;
Yield: 310 mg (88%); yellow-white solid; mp 102–104 °C.
1H NMR (400 MHz, CDCl3):  = 7.69–7.75 (m, 4 H, ArH), 7.32–7.33 (m,
2 H, ArH), 7.22–7.26 (m, 4 H, ArH), 7.01 (d, J = 8.0 Hz, 2 H, ArH), 2.38
(s, 6 H, ArCH3), 2.26 (s, 3 H, ArCH3).
13C NMR (100 MHz, CDCl3):  = 142.8 (d, J = 4.6 Hz), 139.0 (d, J = 3.5
Hz), 138.9, 135.3 (d, J = 5.6 Hz), 131.7, 131.6, 130.2, 130.0, 129.9,
129.3, 129.2, 129.1, 122.8, 122.7, 21.7, 21.2.
found: 347.0631.
31P NMR (160 MHz, CDCl3):  = 41.9.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H21OPSNa: 375.0943;
found: 375.0945.
S-Butyl Diphenylphosphinothioate (3m)
Yield: 229 mg (79%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.86–7.91 (m, 4 H, ArH), 7.46–7.56 (m,
6 H, ArH), 2.77–2.83 (m, 2 H, CH2), 1.57–1.64 (m, 2 H, CH2), 1.31–1.43
(m, 2 H, CH2), 0.84 (t, J = 7.2 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3):  = 133.9, 132.9, 132.3, 132.2,
131.5,131.4, 128.7, 128.6, 32.6 (d, J = 8.0Hz), 32.5, 29.7, 29.0 (d, J = 3.4
Hz), 21.8, 13.5.
S-(p-Tolyl) Bis(3,5-dimethylphenyl)phosphinothioate (5b)
Yield: 311 mg (82%); yellow-white solid; mp 118–120 °C.
1H NMR (400 MHz, CDCl3):  = 7.42–7.46 (m, 4 H, ArH), 7.32–7.33 (m,
2 H, ArH), 7.12 (s, 2 H, ArH), 7.02 (d, J = 7.6 Hz, 2 H, ArH), 2.32 (s, 12 H,
ArCH3), 2.27 (s, 3 H, ArCH3).
13C NMR (100 MHz, CDCl3):  = 139.0 (d, J = 3.8 Hz), 138.3, 138.1,
135.4 (d, J = 5.9 Hz), 134.0 (d, J = 4.8 Hz), 133.0, 131.9, 129.9 (d, J = 2.1
Hz), 122.7 (d, J = 8.5 Hz), 21.3, 21.2.
31P NMR (160 MHz, CDCl3):  = 43.3.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H19OPSNa: 313.0786;
found: 313.0785.
31P NMR (160 MHz, CDCl3):  = 42.6.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C23H25OPSNa: 403.1256;
found: 403.1253.
S-Ethyl Diphenylphosphinothioate (3n)
Yield: 191 mg (73%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.86–7.91 (m, 4 H, ArH), 7.46–7.57 (m,
6 H, ArH), 2.79–2.87 (m, 2 H, CH2), 1.30 (t, J = 7.2 Hz, 3 H, CH3).
S-(p-Tolyl) Di(naphthalen-1-yl)phosphinothioate (5c)
Yield: 356 mg (84%); yellow-white solid; mp 128–130 °C.
13C NMR (100 MHz, CDCl3):  = 133.8, 132.8, 132.3, 132.2, 131.6,
131.5, 129.5, 128.8, 128.6, 115.4, 23.9 (d, J = 4.2 Hz), 16.3 (d, J = 8.5
Hz).
1H NMR (400 MHz, CDCl3):  = 8.84–8.87 (m, 2 H, ArH), 8.06–8.08 (m,
1 H, ArH), 8.00–8.03 (s, 3 H, ArH), 7.88–7.90 (m, 2 H, ArH), 7.51–7.54
(m, 4 H, ArH), 7.42–7.50 (m, 2 H, ArH), 7.34–7.37 (m, 2 H, ArH), 6.97
(d, J = 8.0 Hz, 2 H, ArH), 2.23 (s, 3 H, ArCH3).
31P NMR (160 MHz, CDCl3):  = 43.4.
13C NMR (100 MHz, CDCl3):  = 139.1 (d, J = 3.8 Hz), 135.4 (d, J = 6.1
Hz), 134.0, 133.9, 133.7 (d, J = 5.3 Hz), 133.5, 133.3, 133.2, 129.9 (d, J =
2.9 Hz),129.6 (d, J = 4.3 Hz), 128.8, 128.5, 127.3 (d, J = 7.8 Hz), 126.5,
126.0, 124.5, 124.3, 123.0 (d, J = 8.5 Hz), 21.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H15OPSNa: 285.0473;
found: 285.0474.
S-Isopropyl Diphenylphosphinothioate (3o)
31P NMR (160 MHz, CDCl3):  = 45.3.
Yield: 212 mg (77%); yellow-white oil.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J

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HRMS (ESI-TOF): m/z [M + Na]+ calcd for C27H21OPSNa: 447.0943;
O,O-Diethyl S-(p-Tolyl) Phosphorothioate (5h)
found: 447.0940.
Yield: 221 mg (85%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.43–7.45 (m, 2 H, ArH), 7.15–7.17 (m,
2 H, ArH), 4.16–4.27 (m, 4 H, CH2), 2.35 (s, 3 H, ArCH3), 1.31 (t, J = 7.2
Hz, 6 H, CH3).
S-(p-Tolyl) Bis(4-fluorophenyl)phosphinothioate (5d)
Yield: 266 mg (74%); yellow-white solid; mp 123–125 °C.
1H NMR (400 MHz, CDCl3):  = 7.80–7.87 (m, 4 H, ArH), 7.29–7.31 (m,
2 H, ArH), 7.12–7.17 (s, 4 H, ArH), 7.03–7.05 (m, 2 H, ArH), 2.28 (s, 3 H,
ArCH3).
13C NMR (100 MHz, CDCl3):  = 139.4, 134.7 (d, J = 7.7 Hz), 130.2 (d, J =
3.5 Hz), 122.8 (d, J = 11.4 Hz), 64.0 (d, J = 9.0Hz), 21.2, 16.1 (d, J = 11.7
Hz).
13C NMR (100 MHz, CDCl3):  = 166.6, 164.0, 139.5, 135.3 (d, J = 6.1
Hz), 134.3 (d, J = 3.5 Hz), 134.2 (d, J = 14.1 Hz), 130.2 (d, J = 2.7 Hz),
127.8, 121.7, 116.2, 116.1, 116.0, 115.9, 21.2.
31P NMR (160 MHz, CDCl3):  = 39.3.
19F NMR (160 MHz, CDCl3):  = –105.7.
31P NMR (160 MHz, CDCl3):  = 23.4.
HRMS (ESI-TOF): m/z calcd for C11H17O3PSNa: 283.0528; found:
283.0525.
O,O-Diisopropyl S-(p-Tolyl) Phosphorothioate (5i)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H15F2OPSNa: 383.0441;
Yield: 236 mg (82%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.46–7.48 (m, 2 H, ArH), 7.14–7.16 (m,
2 H, ArH), 4.72–4.80 (m, 2 H, CH), 2.34 (s, 3 H, ArCH3), 1.33 (d, J = 6.0
Hz, 6 H, CH3), 1.27 (d, J = 6.4 Hz, 6 H, CH3).
found: 383.0440.
S-(p-Tolyl) Bis(4-chlorophenyl)phosphinothioate (5e)
13C NMR (100 MHz, CDCl3):  = 139.0 (d, J = 4.6 Hz), 134.4 (d, J = 8.3
Hz), 130.1 (d, J = 3.5 Hz), 123.5 (d, J = 11.0 Hz), 73.3 (d, J = 10.7 Hz),
23.9 (d, J = 6.7 Hz), 23.6 (d, J = 9.1 Hz), 21.2.
Yield: 301 mg (77%); yellow-white solid; mp 102–104 °C.
1H NMR (400 MHz, CDCl3):  = 7.73–7.78 (m, 4 H, ArH), 7.42–7.44 (m,
4 H, ArH), 7.29–7.32 (m, 2 H, ArH), 7.04 (d, J = 8.0 Hz, 2 H, ArH), 2.28
(s, 3 H, ArCH3).
31P NMR (160 MHz, CDCl3):  = 21.0.
13C NMR (100 MHz, CDCl3):  = 139.7 (d, J = 3.5 Hz), 139.2 (d, J = 5.8
Hz), 135.4 (d, J = 6.2 Hz), 133.0, 132.9, 131.4, 130.3 (d, J = 13.1 Hz),
130.2, 129.1, 129.0, 121.5, 121.4 (d, J = 7.0 Hz), 21.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H21O3PSNa: 311.0841;
found: 311.0840.
31P NMR (160 MHz, CDCl3):  = 39.2.
O,O-Dibutyl S-(p-Tolyl) Phosphorothioate (5j)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H15Cl2OPSNa: 414.9850;
Yield: 265 mg (84%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.43–7.45 (m, 2 H, ArH), 7.14–7.16 (m,
2 H, ArH), 4.04–4.18 (m, 4 H, CH2), 2.34 (s, 3 H, ArCH3), 1.61–1.66 (m,
4 H, CH2), 1.31–1.40 (m, 4 H, CH2), 0.90 (t, J = 7.2 Hz, 6 H, CH3).
found: 414.9851.
S-(p-Tolyl) Bis(3-fluoro-5-methylphenyl)phosphinothioate (5f)
13C NMR (100 MHz, CDCl3):  = 139.3 (d, J = 4.8 Hz), 134.6 (d, J = 8.2
Hz), 130.2 (d, J = 3.8 Hz), 122.9 (d, J = 11.5 Hz), 67.8 (d, J = 10.4 Hz),
32.2 (d, J = 11.5 Hz), 21.2, 18.7, 13.6.
Yield: 310 mg (80%); yellow-white solid; mp 108–110 °C.
1H NMR (400 MHz, CDCl3):  = 7.42–7.46 (m, 2 H, ArH), 7.28–7.35 (m,
4 H, ArH), 7.02–7.06 (m, 4 H, ArH), 2.37 (s, 6 H, ArCH3), 2.28 (s, 3 H,
ArCH3).
31P NMR (160 MHz, CDCl3):  = 23.5.
13C NMR (100 MHz, CDCl3):  = 163.7 (d, Jc-F= 32.0 Hz), 161.2 (d, Jc-F
=
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H25O3PSNa: 339.1154;
31.7 Hz), 141.6 (d, J = 11.5 Hz), 141.5 (d, J = 11.7 Hz), 139.7 (d, J = 4.2
Hz), 135.5, 135.4, 134.8 (d, J = 10.1 Hz), 133.7 (d, J = 10.1 Hz), 130.2,
130.1, 128.1 (d, J = 4.5 Hz), 127.9 (d, J = 4.0 Hz), 121.4 (d, J = 8.8 Hz),
120.4 (d, J = 4.3 Hz), 120.2 (d, J = 4.3 Hz), 115.5, 115.4, 115.3, 115.1,
21.3 (d, J = 20.8 Hz).
31P NMR (160 MHz, CDCl3):  = 39.2.
19F NMR (160 MHz, CDCl3):  = –112.0.
found: 339.1150.
(S)-O-Ethyl S-(p-Tolyl) Phenylphosphonothioate (5k)
Yield: 227 mg (78%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.63–7.69 (m, 2 H, ArH), 7.49–7.52 (m,
1 H, ArH), 7.36–7.41 (m, 2 H, ArH), 7.15–7.17 (m, 2 H, ArH), 7.01–7.03
(m, 2 H, ArH), 4.27–4.42 (m, 2 H, ArH), 2.30 (s, 3 H, ArCH3), 1.40 (t, J =
7.2 Hz, 3 H, CH3).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H19F2OPSNa: 411.0754;
13C NMR (100 MHz, CDCl3):  = 139.3 (d, J = 4.5 Hz), 135.5 (d, J = 6.7
Hz), 132.5 (d, J = 5.1 Hz), 131.6 (d, J = 17.0 Hz), 130.0 (d, J = 3.5 Hz),
128.3, 128.1, 62.4 (d, J = 10.9 Hz), 21.2, 16.4 (d, J = 10.9 Hz).
found: 411.0750.
S-(p-Tolyl) Di(thiophen-2-yl)phosphinothioate (5g)
31P NMR (160 MHz, CDCl3):  = 41.9.
Yield: 274 mg (82%); yellow-white solid; mp 99–101 °C.
1H NMR (400 MHz, CDCl3):  = 7.72–7.75 (m, 2 H, ArH), 7.64–7.67 (m,
2 H, ArH), 7.38–7.40 (m, 2 H, ArH), 7.15–7.17 (m, 2 H, ArH), 7.07 (d, J =
8.0 Hz, 2 H, ArH), 2.29 (s, 3 H, ArCH3).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H17O2PSNa: 315.0579;
found: 315.0577.
13C NMR (100 MHz, CDCl3):  = 139.5, 136.9 (d, J = 17.4 Hz), 136.8,
135.3 (d, J = 6.9 Hz), 134.6, 134.5 (d, J = 9.3 Hz), 133.4, 130.1 (d, J = 3.4
Hz), 128.4, 128.2, 122.3 (d, J = 8.8 Hz), 21.2.
31P NMR (160 MHz, CDCl3):  = 23.1.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H13OPS3Na: 358.9758;
S-(p-Tolyl) Dicyclohexylphosphinothioate (5l)
Yield: 262 mg (78%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.47 (d, J = 7.2 Hz, 2 H, ArH), 7.13 (d, J =
8.0 Hz, 2 H, ArH), 2.33 (s, 3 H, ArCH3), 1.92–2.03 (m, 6 H, CH, CH2),
1.82–1.83 (m, 4 H, CH2), 1.69–1.74 (m, 3 H, CH2), 1.38–1.52 (m, 4 H,
CH2), 1.20–1.22 (m, 5 H, CH2).
found: 358.9756.
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T. Liu et al.
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13C NMR (100 MHz, CDCl3):  = 138.7, 135.5 (d, J = 4.8 Hz), 130.0,
123.0 (d, J = 8.0 Hz), 40.4, 39.7, 26.6, 26.5, 26.4, 26.3, 26.2, 26.0, 25.9,
25.8, 21.2.
31P NMR (160 MHz, CDCl3):  = 67.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H29OPSNa: 359.1569;
(h) Elzagheid, M. I.; Mattila, K.; Oivanen, M.; Jones, B. C. N. M.;
Cosstick, R.; Lonnberg, H. Eur. J. Org. Chem. 2000, 1987. (i) Quin,
L. D. A Guide to Organophosphorus Chemistry; John Wiley &
Sons: New York, 2000. (j) Murphy, P. J. Organophosphorus
Reagents; Oxford University Press: Oxford, 2004. (k) Reddy, E.
P.; Reddy, M. V. R.; Bell, S. C. WO2005089269A2, 2005. (l) Carta,
P.; Puljic, N.; Robert, C.; Dhimane, A.-L.; Fensterbank, L.; Lacôte,
E.; Malacria, M. Org. Lett. 2007, 9, 1061. (m) Pandey, V. K.;
Dwivedi, A.; Pandey, O. P.; Sengupta, S. K. J. Agric. Food Chem.
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2011. (q) Hoshi, N.; Kashiwabara, T.; Tanaka, M. Tetrahedron
Lett. 2012, 53, 2078. (r) Leisvuori, A.; Ahmed, Z.; Ora, M.;
Beigelman, L.; Blatt, L.; Lönnberg, H. Helv. Chim. Acta 2012, 95,
1512. (s) Noro, M.; Fujita, S.; Wada, T. Org. Lett. 2013, 15, 5948.
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Shen, J.-B.; Liang, B. T.; Jacobson, K. A. J. Med. Chem. 2013, 56,
902. (u) Loranger, M. W.; Beaton, S. A.; Lines, K. L.; Jakeman, D.
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Fang, J.; Mei, X.; Ning, J.; Tang, Y. Bioorg. Med. Chem. 2013, 21,
278. (w) Zhang, A.; Sun, J.; Lin, C.; Hu, X.; Liu, W. J. Agric. Food
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found: 359.1570.
(S)-S-Benzyl O-Ethyl Phenylphosphonothioate (5m)
Yield: 198 mg (68%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.79–7.82 (m, 2 H, ArH), 7.52–7.57 (m,
1 H, ArH), 7.43–7.48 (m, 3 H, ArH), 7.20–7.25 (m, 4 H, ArH), 4.08–4.29
(m, 2H, CH2), 3.87–4.02 (m, 2H, CH2), 1.34 (t, J = 7.2 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3):  = 148.2, 137.2 (d, J = 8.5 Hz), 132.6 (d, J =
5.0 Hz), 131.7 (d, J = 17.6 Hz), 131.3 (d, J = 17.6 Hz), 130.9 (d, J = 14.9
Hz), 129.0 (d, J = 11.0 Hz), 128.5 (d, J = 19.8 Hz), 127.5 (d, J = 4.6 Hz),
34.5 (d, J = 4.2 Hz), 16.3 (d, J = 11.2 Hz).
31P NMR (160 MHz, CDCl3):  = 43.7.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H17O2PSNa: 315.0579;
found: 315.0575.
S-(4-Chlorophenyl) O,O-Diethyl Phosphorothioate (5n)
Yield: 215 mg (77%); yellow-white oil.
1H NMR (400 MHz, CDCl3):  = 7.49–7.52 (m, 2 H, ArH), 7.32–7.34 (m,
2 H, ArH), 4.12–4.27 (m, 4 H, CH2), 1.30–1.34 (m, 6 H, CH3).
13C NMR (100 MHz, CDCl3):  = 135.8 (d, J = 8.3 Hz), 135.5 (d, J = 5.3
Hz), 129.6 (d, J = 3.5 Hz), 125.2 (d, J = 11.5 Hz), 64.3 (d, J = 10.1 Hz),
16.1 (d, J = 11.5 Hz).
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1266.
31P NMR (160 MHz, CDCl3):  = 22.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C10H14ClO3PSNa: 302.9982;
found: 302.9980.
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Malacria, M. Org. Lett. 2007, 9, 1061. (h) Carta, P.; Puljic, N.;
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E.; Malacria, M. Tetrahedron 2008, 64, 11865. (i) Gao, Y.-X.; Tang,
G.; Cao, Y.; Zhao, Y.-F. Synthesis 2009, 1081. (j) Ouyang, Y.-J.; Li,
Y.-Y.; Li, N.-B.; Xu, X.-H. Chin. Chem. Lett. 2013, 24, 1103. (k) Bai,
J.; Cui, X.-L.; Wang, H.; Wu, Y.-J. Chem. Commun. 2014, 50, 8860.
(l) Liu, Y.-C.; Lee, C.-F. Green Chem. 2014, 16, 357. (m) Bi, X.; Li,
J.; Meng, F.; Wang, H.; Xiao, J. Tetrahedron 2016, 72, 706.
(n) Wang, W.-M.; Liu, L.-J.; Yao, L.; Meng, F.-J.; Sun, Y.-M.; Zhao,
C.-Q.; Xu, Q.; Han, L.-B. J. Org. Chem. 2016, 81, 6843. (o) Moon,
Y.; Moon, Y.; Choi, H.; Hong, S. Green Chem. 2017, 19, 1005.
(5) (a) Atherton, F. R.; Todd, A. R. J. Chem. Soc. 1947, 674. (b) Renard,
P.-Y.; Schwebel, H.; Vayron, P.; Josien, L.; Valleix, A.; Mioskowski,
C. Chem. Eur. J. 2002, 8, 2910. (c) Gao, Y.-X.; Tang, G.; Cao, Y.;
Zhao, Y.-F. Synthesis 2009, 1081. (d) Wang, G.; Shen, R.; Xu, Q.;
Goto, M.; Zhao, Y.; Han, L.-B. J. Org. Chem. 2010, 75, 3890.
(e) Xiong, B.; Zhou, Y.; Zhao, C.; Goto, M.; Yin, S.-F.; Han, L.-B.
Tetrahedron 2013, 69, 9373. (f) Ouyang, Y.-J.; Li, Y.-Y.; Li, N.-B.;
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Funding Information
This work was supported by the Program for the Application of Fun-
damental Research of Yunnan Province (Grant No. 2018FB019), the
Opening Foundation of the Key Laboratory of Natural Resources and
Pharmaceutical Chemistry, Ministry of Education, Yunnan University,
and the National Natural Science Foundation of China (Grant No.
21961030).
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690709.
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References
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© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–J