Cu(II)/Proline-Catalyzed Reductive Coupling of Sulfuryl Chloride and P(O)-H for P-S-C Bond Formation

Article abstract of DOI:10.1021/acs.joc.7b02608

A considerably improved method for the Cu-catalyzed coupling of sulfuryl chloride with P(O)-H was described. Using commercially available l-proline as the ligand decreased the precatalyst loading, broadened the substrate scope and greatly promoted the efficiency of the coupling reaction. Moreover, gram-scale preparation, easy-to handle and recyclable catalyst featured this transformation.

Full text of DOI:10.1021/acs.joc.7b02608

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Note
Cu(II)/Proline Catalyzed Reductive-coupling of Sulfuryl
Chloride and P(O)-H for P-S-C Bond Formation
Xinghua Zhang, Dungai Wang, Duo An, Boshi Han, Xiang Song, Liang Li, Gaoqi Zhang, and Lixian Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02608 • Publication Date (Web): 09 Jan 2018
Downloaded from http://pubs.acs.org on January 10, 2018
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Cu(II)/Proline Catalyzed Reductive-coupling of Sulfuryl Chloride and
P(O)-H for P-S-C Bond Formation
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Xinghua Zhang,* Dungai Wang, Duo An, Boshi Han, Xiang Song, Liang Li, Gaoqi Zhang, and Lixian
Wang*
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Hai-Quan Road, Shanghai
201418, China
Supporting Information Placeholder
ABSTRACT: A considerably improved method for the Cu-catalyzed coupling of sulfuryl chloride with P(O)-H was described.
Using commercially available L-proline as the ligand decreased the pre-catalyst loading, broadened the substrate scope and greatly
promoted the efficiency of the coupling reaction. Moreover, gram-scale preparation, easy-to handle and recyclable catalyst featured
this transformation.
Compared with the traditional copper-mediated C-C and C-het-
eroatom bonds formation, increased activity and broadened
substrate scope have been achieved by using ligand-promoted
cross-coupling strategy.1 The enhanced solubility and stability
of copper complexes due to the use of these auxiliary ligands
was the key to accelerate these transformations. Recently, some
amino acide promoted,1a, 2 Cu-catalyzed C-X coupling have
been disclosed and caught more and more attention (Scheme 1,
eq 1).2a-2e
Scheme 1. L-Proline Promoted Cu-catalyzed C-X Bond
Formation
The P-S-C bond is also an important scaffold that have re-
ceived much attention within the biology and chemistry com-
munity.3 Among the existing methods for construction of P-S-
C bond,4-6 Cu-catalyzed coupling reactions of sulfonyl chlorides
with P(O)-H have become more and more attractive,4d mainly
because the coupling partners are readily commercially availa-
ble, and the reaction could proceed under base-free condition.
At the same time, avoiding use of foul-smelling materials, such
as aryl-SH and alkyl-SH, is also accord with the increased en-
vironmental requirements. Although significant advances have
been made in this transformation,6d further improvements are
still desirable. For example, how to reduce the loading of the
catalyst or P(O)-H reagent and further extend the scope to new
substrates. In particular, the development of reusability of the
catalyst, simple work-up and mild reaction condition remains a
formidable challenge.
chlorides under relatively mild conditions. In this respect, our
recent finding of Ligand-promoted Cu-catalyzed coupling reac-
tions has significantly expanded the substrate scope.
Initially, we chose tosyl chloride (1a) and P(O)-H, O-ethyl
phenylphosphinate (2a), as the model substrates. The influences
of different solvents, copper source, ligands, reactant molar ra-
tio and reaction temperature were screened to explore the opti-
mized condition. As shown in Table 1, Desired coupling prod-
uct 3a was obtained in 19% yield if the reaction mixture of 1a
(0.5 mmol) and 2a (2.0 mmol) was stirred in CH3CN at 80 oC
for 3 h (Table 1, entry 1). As expected, the yield of correspond-
ing product 3a increased obviously in the presence of copper
salts as catalyst (see the Supporting Information (SI)). A series
of copper salts and the amount of the catalyst loading were in-
vestigated under similar conditions, and the results showed that
Herein, we wish to disclose a considerably improved method
for the synthesis of S-aryl/alkyl phosphinothioates and phos-
phorothioates based on copper-catalyzed coupling of aryl/alkyl
sulfonyl chlorides with P(O)-H (Scheme 1, eq 2). The reaction
conditions allowed the use of 4.0 equiv. of P(O)-H compounds
in excess. Moreover, using commercially available L-proline as
the ligand greatly promoted the efficiency of the coupling reac-
tion, and a variety of P(O)-H coupled readily with sulfonyl
•
CuCl2 2H2O (5 mol%) was optimal (57% yield; Table 1, entry
2). Further investigations revealed that the choice of a suitable
ligand was the key factor increasing the reaction efficiency, a
promising yield of 75 % was obtained if the ligand, L-proline
(10 mol%), was added, which is more efficient than anyother
nitrogen ligands, including
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Table 1. Optimization of Reaction Conditiona Table 2. Reaction of 1 and 2 under Standard Conditionsa
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Entry
Catalyst
None
Ligand
None
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Dioxane
THF
Yield (%)b
19
1
2
•
CuCl2 2H2O
None
57
•
9
3
4
CuCl2 2H2O
L-pro
DMAP
py
75
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•
CuCl2 2H2O
52
•
5
CuCl2 2H2O
70
•
6
CuCl2 2H2O
bpy
32
•
7
CuCl2 2H2O
1,10-phen
TMEDA
L-pro
L-pro
L-pro
L-pro
L-pro
L-pro
L-pro
L-pro
19
•
8
CuCl2 2H2O
64
•
9
CuCl2 2H2O
72
•
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16
CuCl2 2H2O
78
•
CuCl2 2H2O
Toluene
THF
72
CuCl2 2H2O
27c
66d
74e
89f
69g
•
•
CuCl2 2H2O
Dioxane
THF
•
CuCl2 2H2O
•
CuCl2 2H2O
THF
•
CuCl2 2H2O
THF
aReaction conditions: 1a (0.5 mmol), 2a (2.0 mmol), catalyst
(0.025 mmol), ligand (0.05 mmol), solvent (1.5 mL), 80 °C, under
air, 3 h. Isolated yields based on 1a. 50 °C. 100 °C. THF (0.5
mL). fTHF (1.0 mL). gTHF (2.0 mL).
b
c
d
e
pyridine (py), bipyridine (bpy), phenanthroline (1,10-phen) and
tetramethylethylenediamine (TMEDA) (Table 1, entries 3-8).
The coupling reaction also proceeded smoothly in other sol-
vents, such as toluene, dioxane and THF, and THF was the ideal
solvent (78% yield; Table 1, entry 10). Unfortunately, the P-S-
C bond transformation was not accelerated by elevating the re-
action temperature to 100 °C (66% yield; Table 1, entry 13) or
reducing to 50 oC (27% yield; Table 1, entry 12). Interestingly,
using 1.0 mL THF as solvent provided 3a in a 89% yield (Table
1, entry 15) as opposed to 69%, 74% (Table 1, entries 14, 16)
employing 0.5 and 2.0 mL of THF, respectively. These results
indicated that the efficiency of the coupling should be con-
trolled by the reactant concentration. Therefore, the optimum
reaction condition was set as 1a (0.5 mmol) and 2a (2.0 mmol)
in the presence of CuCl2 2H2O (5 mol%) in THF (1.0 mL), pro-
moted by L-proline (10 mol%), at 80 °C for 3 h (Table 1, entry
15).
Next, we conducted a survey of the reaction scope, and the
results are summarized in Table 2. A variety of sulfonyl chlo-
rides readily coupled with P(O)-H compound, O-ethyl phe-
nylphosphinate (2a), under the relatively mild reaction condi-
tion to produce the corresponding phosphinothioates 3 in good
to excellent yields. For para-substituted aryl sulfonyl chlorides,
both electron-rich (with methyl, tert-butyl or methoxyl group)
•
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DOPO (2c), were also suitable substrates and did not signifi-
1
cantly affect this transformation, afforded the desired S-aryl or
-alkyl phosphinothioates 3m-3t in 77-92% yield (Table 2, 3m-
3t), respectively. Moreover, the configuration of compound 3s
was clearly identified by X-ray diffraction (See SI). It is worth
noting that our previous protocol was not applicable to the syn-
thesis of compound 3r,6d however, it could be achieved in 89%
yield under the current reaction condition (Table 2, 3r). Simi-
larly, by using the present Pro/Cu-catalyzed coupling strategy,
compound 3t was synthesized in high yield (81%; Table 2, 3t),
which is enhanced from 32% under the previous method for the
coupling of 1-butanesulfonyl chloride (1t) with DOPO (2c).6d
Encouraged by the findings described above, we then ex-
tended the modifed reaction condition to the coupling of aryl
sulfonyl chlorides with dialkyl phosphonate, including diethyl
phosphonate (2d), dimethyl phosphonate (2e) and diisopropyl
phosphonate (2f). S-aryl phosphonothioates can be efficiently
synthesized under relatively mild condition (80 oC, 12 h), and
substituted aryl sulfonyl chlorides with electron-donating
groups (Table 2, entries 3u-3w) or electron-withdrawing groups
(Table 2, entries 3x-3aa) did not change the yields significantly,
affording the corresponding products in 60-75% yields.
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Scheme 2. Recycling Experiment of Pro/Cu.
100
90
80
70
60
50
40
30
20
10
0
a
•
Reaction conditions: 1 (0.5 mmol), 2 (2.0 mmol), CuCl2 2H2O (5
mol%), L-proline (10 mol%), THF(1.0 mL), 80 °C, air, 3 h. Isolated
yields based on 1. bReaction conditions: 12 h.
and -deficient (chloro, bromo or trifluoromet-hyl group) sub-
strates worked well, providing aryl phosphinothioates 3a-3f in
74-90% yields. Morever, this method also can be applied to
gram-scale preparation, O-ethyl S-(p-tolyl) phenylphosphono-
thioate, 3a was successfully achieved in 86% yield (Table 2,
1.25 g, 5 mmol). As for the sterically hindered substrate, the
ortho-substituted steric hindrance did not significantly affect
the reaction efficiency, the corresponding product 3g was ob-
tained in 82% yield from 2,4,6-trimethylphenyl sulfonyl chlo-
ride (Table 2, 3g). To our delight, the present method is also
suitable for 2-naphthalenesulfonyl chloride and 2-thiophenesul-
fonyl chloride, leading to the desired products 3h, 3i in 88% and
77% yield, respectively (Table 2, 3h, 3i). Notably, under the
current reaction condition, the alkyl sulfonyl chlorides could be
readily transformed to the corresponding alkyl phosphinothio-
ates 3j-3l in 52-83% yield (Table 2, 3j-3l), further expanding
the substrate scope of this approach. The steric hindrance of
P(O)-H compound, such as isopropyl phenylphosphinate (2b),
1
2 3 4 5 6 7 8 9 10
Run time
Further investigations were also conducted to assess the po-
tential for recycling of Pro/Cu catalyst in the model reaction.
After completion of the reaction, the catalyst was easily recov-
ered by centrifugalization, which was washed with ethyl ether,
vacuumed and reused directly for the next run. The results indi-
cated that the easy-to handle Pro/Cu catalyst was able to be re-
used in multiple consecutive catalytic runs (up to 10 runs) with-
out loss of high reactivity (Scheme 2).
To further identify the role of L-Proline in this transformation,
some controlled experiments were performed. As illustrated in
Scheme 3, the desired product 3a was not observed under the
standard condition when 4.0 equiv of radical trapping agent,
2,2,6,6-tetramethylpiperidinooxy (TEMPO), was involved. But
3
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a tosyl radical, generated from tosyl chloride 1a, was success-
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fully captured and the byproduct 4a was obtained in 48% yield,
thus suggesting the generation of a sulfonyl radical during the
reaction (Scheme 3a). The model reaction was also readily car-
ried out under a nitrogen atmosphere (85% yield, Scheme 3b),
which indicated that the oxygen molecule was not the key factor
in achieving the radical intermediate.4d Further studies were
performed to shed light on the source of the radical, as showed
in Scheme 3c, the reaction was almost completely quenched and
the corresponding product 3a was not detected under the stand-
ard condition at room temperature, while 30% yield was af-
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o
forded only in THF at 80 C (Scheme 3d). These results illus-
trated that the reaction might proceed via a radical pathway and
the temperature played a critical role in this Pro/Cu catalyzed
coupling.
Scheme 3. Mechanistic Studies.
Based on the above-mentioned experiments and the literature
precedents,4d,6d,7 a plausible mechanism for the Pro/Cu cata-
lyzed P-S-C bond formation is shown in Scheme 4. Initially,
CuCl2 and L-proline may form a complex 4b at 80 oC. Then, the
active catalytic species, R-sulfonyl radical and chloro radical,
were generated from R-sulfonyl chloride induced by the exter-
nally-provided energy. Nextly, the newly formed (CuII) inter-
mediate A, which was achieved from ligand exchange reaction
between 4b and P(O)-H, could act as an active catalyst under-
going the initial single electron transfer (SET) with the R-sul-
fonyl radical to generate (CuIII) intermediate B. At the same
time, P-centered radical, phosphonic chloride radical C was
generated via a radical transfer process between P(O)-H and the
chloro radical. Finally, the in situ formed intermediate B was
attacked by phosphonic chloride radical C, undergoes reductive
elimination of an oxygen atom to afford the target product,
along with the regeneration of the chloro radical and LCuI spe-
cies E. Subsequently, the latter rapidly acted with chloro radical
and L-Proline, affording the complex 4b to fulfill the catalytic
cycle.
In summary, we have described a copper catalysed coupling
of P(O)-H with sulfuryl chlorides under relatively mild condi-
tions. Using natural product L-proline as the ligand greatly
broadened the substrate scope, and provided S-aryl/alkyl phos-
phinothioates or phosphorothioates in good to excellent yields.
In addition, the easy-to handle and recyclable Pro/Cu catalyst
make this reaction practical and highly attractive. Further de-
tailed mechanistic studies and applications based on this effi-
cient transformation are underway in our laboratory.
Notably, the complex 4b, CuII(L-Proline)2, can be successfully
o
obtained in THF at 80 C and conformed by HRMS (Scheme
3e). Furthermore, using 5 mol% 4b as the catalyst, this cross-
coupling reaction can be readily performed in 80% yield
(Scheme 3f), which showed that the catalyst CuII(L-Proline)2
(4b) plays an important role in the formation of P-S-C bond.
Additionally, the byproduct 4c in the reaction system was also
examined by HRMS under the standard condition (Scheme 3g),
further corroborated that the oxygen atom in sulfonyl chloride
was reduced by excessive P(O)-H.
■ EXPERIMENTAL SECTION
General Methods. All chemicals were obtained from commer-
1
cial suppliers and used directly without further purification. H
NMR (500 MHz) and 13C NMR (125 MHz) spectras were recorded
on Bruker AVANCE III (500 MHz) spectrometer with CDCl3,
DMSO-d6 or MeOD as solvents. The chemical shifts δ are reported
in ppm relative to tetra-methylsilane. Reference peaks for chloro-
1
form in H NMR and 13C NMR spectra were set at 7.26 ppm and
Scheme 4. Proposed Mechanism.
4
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77.0 ppm, and for DMSO-d6 (1H NMR: TMS at 0.00 ppm, DMSO
(202 MHz, CDCl3): δ 40.3; HRMS (ESI): m/z [M+H]+ calcd for
C14H15ClO2PS+: 313.0213, found: 313.0213.
at 2.50 ppm; 13C NMR: DMSO at 40.0 ppm), MeOD (1H NMR:
TMS at 0.00 ppm, MeOD at 3.3 ppm; 13C NMR: MeOD at 48.8
ppm), High resolution mass spectras (HRMS) were obtained on Ul-
tra-high Resolution Hybrid Qh-Fourier Transform Mass Spectrom-
eter, SolariX70 FT-ICR MS (Bruker, Switzerland) with ESI. Melt-
ing points were determined on a WRS-1B melting point apparatus
and were uncorrected.
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S-(4-bromophenyl) O-ethyl phenylphosphonothioate (3e). Col-
orless oil, 139 mg, 78%; 1H NMR (500 MHz, CDCl3): δ 7.69-7.64
(m, 2H), 7.52-7.48 (m, 1H), 7.40-7.36 (m, 2H), 7.34-7.31 (m, 2H),
7.17-7.15 (m, 2H), 4.37-4.28 (m, 2H), 1.39 (t, J = 7.0 Hz, 3H); 13
C
NMR (125 MHz, CDCl3): δ 136.6 (d, J = 4.2 Hz), 132.5 (d, J = 3.2
Hz), 132.0 (d, J = 2.2 Hz), 131.2 (d, J = 10.6 Hz), 131.0 (d, J =
149.5 Hz), 128.1 (d, J = 15.0 Hz), 125.6 (d, J = 5.4 Hz), 123.5 (d,
J = 3.5 Hz), 62.5 (d, J = 7.1 Hz), 16.1 (d, J = 6.6 Hz); 31P NMR
(202 MHz, CDCl3): δ 39.5; HRMS (ESI): m/z [M+H]+ calcd for
C14H15BrO2PS+: 356.9708, found: 356.9706.
General Experimental Procedure.
9
Compound 1, aryl/alkyl sulfonyl chlorides (0.5 mmol) and 2, P(O)-
H (2.0 mmol), CuCl2•2H2O (0.025 mmol) and L-proline (0.05
mmol) were added to a glass tube, and then 1.0 mL of THF was
added. The reaction mixture was stirred at 80 oC for 3-12 h. After
completion of the reaction, the mixture was concentrated under re-
duced pressure and extracted with Et2O (10.0 mL x 3). Then the
organic phases were combined and dried with anhydrous MgSO4,
purified by silica gel column chromatography (petroleum
ether/ethyl acetate as the eluent) to afford the corresponding prod-
uct 3. After washed with Et2O and dried in an oven at 60 °C for 2
h, the residue (catalyst) can be reused directly for the next run
without further purification.
O-ethyl S-(p-tolyl)phenylphosphonothioate (3a)6c. Colorless oil,
130 mg, 89% (1.25 g, 86%, 5 mmol); 1H NMR (500 MHz, CDCl3):
δ 7.68-7.64 (m, 2H), 7.50-7.47 (m, 1H), 7.38-7.34 (m, 2H), 7.17-
7.15 (m, 2H), 7.02-7.00 (m, 2H), 4.38-4.29 (m, 2H), 2.28 (s, 3H),
1.39 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 139.1 (d,
J = 3.0 Hz), 135.3 (d, J = 4.2 Hz), 132.3 (d, J = 3.2 Hz), 131.6 (d,
J = 149.8 Hz), 131.3 (d, J = 10.5 Hz), 129.8 (d, J = 2.3 Hz), 128.0
(d, J = 14.8 Hz), 122.8 (d, J = 5.5 Hz), 62.3 (d, J = 6.9 Hz), 21.0,
16.2 (d, J = 6.7 Hz); 31P NMR (202 MHz, CDCl3): δ 41.8.
S-(4-(tert-butyl)phenyl) O-ethyl phenylphosphonothioate (3b)5.
Colorless oil, 151 mg, 90%; 1H NMR (500 MHz, CDCl3): δ 7.66-
7.62 (m, 2H), 7.48-7.45 (m, 1H), 7.35-7.31 (m, 2H), 7.21 (s, 4H),
4.40-4.29 (m, 2H), 1.38 (t, J = 7.0 Hz, 3H), 1.25 (s, 9H); 13C NMR
(125 MHz, CDCl3): δ 152.1 (d, J = 2.9 Hz), 134.9 (d, J = 4.1 Hz),
132.2 (d, J = 3.0 Hz), 131.4 (d, J = 148.9 Hz), 131.2 (d, J = 10.5
Hz), 127.9 (d, J = 15.1 Hz), 126.0 (d, J = 2.0 Hz), 122.7 (d, J = 5.9
Hz), 62.1 (d, J = 6.9 Hz), 34.3, 30.9, 16.1 (d, J = 6.8 Hz); 31P NMR
(202 MHz, CDCl3): δ 40.4.
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O-ethyl
S-(4-(trifluoromethyl)phenyl)phenylphosphonothioate
1
(3f). Colorless oil, 128 mg, 74%; H NMR (500 MHz, CDCl3): δ
7.71-7.67 (m, 2H), 7.54-7.51 (m, 1H), 7.47 (s, 4H), 7.42-7.38 (m,
2H), 4.42-4.30 (m, 2H), 1.42 (t, J = 7.0 Hz, 3H); 13C NMR (125
MHz, CDCl3): δ 135.3 (d, J = 4.3 Hz), 132.8 (d, J = 2.9 Hz), 131.3
(d, J = 10.8 Hz), 131.2 (d, J = 149.3 Hz), 131.0 (d, J = 2.3 Hz),
130.8 (d, J = 2.6 Hz), 128.3 (d, J = 15.0 Hz), 123.7 (q, J = 270.3
Hz), 125.8 (d, J = 3.3 Hz), 62.9 (d, J = 7.1 Hz), 16.3 (d, J = 6.6 Hz);
31P NMR (202 MHz, CDCl3): δ 42.1; HRMS (ESI): m/z [M+H]+
calcd for C15H15F3O2PS+: 347.0477, found: 347.0475.
O-ethyl S-mesityl phenylphosphonothioate (3g). Colorless oil,
1
131 mg, 82%; H NMR (500 MHz, CDCl3): δ 7.67-7.63 (m, 2H),
7.49-7.46 (m, 1H), 7.37-7.33 (m, 2H), 6.84 (s, 2H), 4.27-4.20 (m,
2H), 2.25 (s, 6H), 2.21 (s, 3H), 1.35 (t, J = 7.0 Hz, 3H); 13C NMR
(125 MHz, CDCl3): δ 143.9 (d, J = 3.9 Hz), 138.9 (d, J = 2.8 Hz),
132.6 (d, J = 144.7 Hz), 132.1, 130.9 (d, J = 10.6 Hz), 129.1 (d, J
= 2.4 Hz), 128.0 (d, J = 14.5 Hz), 121.2 (d, J = 6.5 Hz), 62.3 (d, J
= 7.2 Hz), 22.0, 20.7, 16.2 (d, J = 6.6 Hz); 31P NMR (202 MHz,
CDCl3): δ 38.9; HRMS (ESI): m/z [M+H]+ calcd for C17H22O2PS+:
321.1073, found: 321.1071..
O-ethyl S-(naphthalen-2-yl)phenylphosphonothioate (3h). Col-
orless oil, 144 mg, 88%; 1H NMR (500 MHz, CDCl3): δ 7.77-7.76
(m, 1H), 7.73-7.72 (m, 1H), 7.67-7.61 (m, 4H), 7.45-7.39 (m, 3H),
7.33-7.27 (m, 3H), 4.40-4.32 (m, 2H), 1.37 (t, J = 7.0 Hz, 3H); 13
C
NMR (125 MHz, CDCl3): δ 135.3 (d, J = 5.3 Hz), 133.2 (d, J = 2.4
Hz), 132.7 (d, J = 1.9 Hz), 132.3 (d, J = 3.0 Hz), 131.4 (d, J = 3.2
Hz), 131.2 (d, J = 148.4 Hz), 131.2 (d, J = 10.7 Hz), 130.5 (d, J =
11.3 Hz), 128.5, 128.2 (d, J = 13.3 Hz), 128.0 (d, J = 14.9 Hz),
127.4 (d, J = 3.3 Hz), 126.8, 126.3, 62.3 (d, J = 6.9 Hz), 16.1 (d, J
= 6.8 Hz); 31P NMR (202 MHz, CDCl3): δ 41.7; HRMS (ESI): m/z
[M+H]+ calcd for C18H17O2PS+: 329.0760, found: 329.0758.
O-ethyl S-(thiophen-2-yl)phenylphosphonothioate (3i). Color-
O-ethyl S-(4-methoxyphenyl)phenylphosphonothioate (3c). Col-
orless oil, 132 mg, 86%; 1H NMR (500 MHz, CDCl3): δ 7.66-7.62
(m, 2H), 7.50-7.47 (m, 1H), 7.38-7.34 (m, 2H), 7.18-7.16 (m, 2H),
6.74-6.72 (m, 2H), 4.39-4.27 (m, 2H), 3.74 (s, 3H), 1.39 (t, J = 7.0
Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 160.3 (d, J = 2.5 Hz),
136.8 (d, J = 3.8 Hz), 132.2 (d, J = 2.9 Hz), 131.5 (d, J = 148.3 Hz)
131.3 (d, J = 10.5 Hz), 128.0 (d, J = 14.8 Hz), 116.6 (d, J = 5.0 Hz),
114.6 (d, J = 2.2 Hz), 62.2 (d, J = 7.0 Hz), 55.1, 16.2 (d, J = 6.7
Hz); 31P NMR (202 MHz, CDCl3): δ 40.6; HRMS (ESI): m/z
[M+H]+ calcd for C15H18O3PS+: 309.0709, found: 309.0708.
S-(4-chlorophenyl) O-ethyl phenylphosphonothioate (3d). Col-
orless oil, 133 mg, 85%; 1H NMR (500 MHz, CDCl3): δ 7.69-7.64
(m, 2H), 7.53-7.49 (m, 1H), 7.41-7.37 (m, 2H), 7.24-7.21 (m, 2H),
1
less oil, 109 mg, 77%; H NMR (500 MHz, CDCl3): δ 7.67-7.63
(m, 2H), 7.52-7.49 (m, 1H), 7.38-7.37 (m, 2H), 7.32-7.31 (m, 1H),
6.86 (s, 2H), 4.44-4.35 (m, 2H), 1.43 (t, J = 7.0 Hz, 3H); 13C NMR
(125 MHz, CDCl3): δ 136.3 (d, J = 5.4 Hz), 132.5 (d, J = 2.8 Hz),
131.3 (d, J = 10.5 Hz), 131.0 (d, J = 3.6 Hz), 130.2 (d, J = 151.7
Hz), 128.0 (d, J = 15.0 Hz), 127.5 (d, J = 3.3 Hz), 123.3 (d, J = 7.3
Hz), 62.4 (d, J = 6.9 Hz), 16.1 (d, J = 6.8 Hz); 31P NMR (202 MHz,
CDCl3): δ 39.5; HRMS (ESI): m/z [M+H]+ calcd for C12H14O2PS2+:
285.0167, found: 285.0166.
S-butyl O-ethyl phenylphosphonothioate (3j). Colorless oil, 83
mg, 64%; 1H NMR (500 MHz, CDCl3): δ 7.90-7.86 (m, 2H), 7.56-
7.53 (m, 1H), 7.50-7.46 (m, 2H), 4.29-4.22 (m, 2H), 2.76-2.70 (m,
2H), 1.58-1.52 (m, 2H), 1.39 (t, J = 7.0 Hz, 3H), 1.35-1.31 (m, 2H),
7.19-7.17 (m, 2H), 4.40-4.27 (m, 2H), 1.40 (t, J = 7.0 Hz, 3H); 13
C
NMR (125 MHz, CDCl3): δ 136.5 (d, J = 4.0 Hz), 135.4 (d, J = 3.2
Hz), 132.6 (d, J = 3.2 Hz), 131.3 (d, J = 10.6 Hz), 131.1 (d, J =
148.8 Hz), 129.2 (d, J = 2.1 Hz), 128.2 (d, J = 15.0 Hz), 125.0 (d,
J = 5.3 Hz), 62.5 (d, J = 7.0 Hz), 16.2 (d, J = 6.8 Hz); 31P NMR
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0.83 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 132.6 (d,
7.66 (m, 2H), 7.50-7.47 (m, 1H), 7.40-7.37 (m, 2H), 7.33-7.31 (m,
2H), 7.19-7.17 (m, 2H), 5.01-4.94 (m, 1H), 1.41-1.36 (m, 6H); 13
1
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3
4
5
6
7
8
J = 148 Hz), 132.2 (d, J = 3.2 Hz), 130.9 (d, J = 10.7 Hz), 128.3 (d,
J = 14.5 Hz), 61.8 (d, J = 6.8 Hz), 32.4 (d, J = 5.1 Hz), 29.9 (d, J =
2.8 Hz), 21.4, 16.2 (d, J = 6.8 Hz), 13.2; 31P NMR (202 MHz,
CDCl3): δ 43.4; HRMS (ESI): m/z [M+H]+ calcd for C12H20O2PS+:
259.0916, found: 259.0915.
C
NMR (125 MHz, CDCl3): δ 136.7 (d, J = 4.2 Hz), 132.5 (d, J = 3.1
Hz), 132.1 (d, J = 2.0 Hz), 132.0 (d, J = 147.4 Hz), 131.4 (d, J =
10.7 Hz), 128.2 (d, J = 15.0 Hz), 126.0 (d, J = 5.3 Hz), 123.6 (d, J
= 3.3 Hz), 72.5 (d, J = 7.2 Hz), 24.2 (d, J = 3.7 Hz), 24.0 (d, J = 5.1
Hz); 31P NMR (202 MHz, CDCl3): δ 38.5; HRMS (ESI): m/z
[M+H]+ calcd for C15H17BrO2PS+: 370.9865, found: 370.9861.
S-butyl O-isopropyl phenylphosphonothioate (3q). Colorless oil,
S-(2-chloroethyl) O-ethy phenylphosphonothioate (3k). Color-
1
less oil, 110 mg, 83%; H NMR (500 MHz, CDCl3): δ 7.89-7.85
(m, 2H), 7.60-7.56 (m, 1H), 7.52-7.48 (m, 2H), 4.30-4.24 (m, 2H),
3.64-3.57 (m, 2H), 3.13-3.04 (m, 2H), 1.40 (t, J = 7.5 Hz, 3H); 13
C
105 mg, 77%; H NMR (500 MHz, CDCl3): δ 7.89-7.85 (m, 2H),
9
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13
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15
16
17
18
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27
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31
32
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42
43
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45
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51
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NMR (125 MHz, CDCl3): δ 132.8 (d, J = 3.3 Hz), 132.3 (d, J =
149.5 Hz), 131.1 (d, J = 10.9 Hz), 128.6 (d, J = 15.0 Hz), 62.6 (d,
J = 6.9 Hz), 43.3 (d, J = 3.1 Hz), 31.9 (d, J = 2.6 Hz), 16.3 (d, J =
6.8 Hz); 31P NMR (202 MHz, CDCl3): δ 42.1; HRMS (ESI): m/z
[M+H]+ calcd for C10H15ClO2PS+: 265.0213, found: 265.0211.
S-cyclopropyl O-ethyl phenylphosphonothioate (3l). Colorless
oil, 63 mg, 52%; 1H NMR (500 MHz, CDCl3): δ 7.84-7.80 (m, 2H),
7.50-7.47 (m, 1H), 7.42-7.38 (m, 2H), 4.27-74.15 (m, 2H), 1.76-
1.71 (m, 1H), 1.34 (t, J = 7.1 Hz, 3H), 0.72-0.70 (m, 2H), 0.43-0.40
(m, 1H), 0.39-0.36 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 132.7
(d, J = 146.4 Hz), 132.4 (d, J = 3.1 Hz), 131.3 (d, J = 10.9 Hz),
128.3 (d, J = 14.7 Hz), 62.0 (d, J = 6.8 Hz), 16.3 (d, J = 6.7 Hz),
9.9 (d, J = 2.6 Hz), 7.9 (d, J = 5.8 Hz), 7.8 (d, J = 6.6 Hz); 31P NMR
(202 MHz, CDCl3): δ 42.8; HRMS (ESI): m/z [M+Na]+ calcd for
C11H15O2PSNa+: 265.0423, found: 265.0423.
7.55-7.52 (m, 1H), 7.49-7.45 (m, 2H), 4.95-4.88 (m, 1H), 2.75-2.70
(m, 2H), 1.57-1.51 (m, 2H), 1.42-1.40 (m, 3H), 1.38-1.36 (m, 3H),
1.34-1.28 (m, 2H), 0.83 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz,
CDCl3): δ 133.4 (d, J = 149.6 Hz), 132.1 (d, J = 2.7 Hz), 131.0 (d,
J = 10.8 Hz), 128.3 (d, J = 14.7 Hz), 71.3 (d, J = 6.9 Hz), 32.5 (d,
J = 5.4 Hz), 30.0 (d, J = 2.5 Hz), 24.2 (d, J = 3.6 Hz), 24.0 (d, J =
5.0 Hz), 21.5, 13.3; 31P NMR (202 MHz, CDCl3): δ 42.2; HRMS
(ESI): m/z [M+H]+ calcd for C13H22O2PS+: 273.1073, found:
273.1072.
(S)-6-(mesitylthio)dibenzo[c,e][1,2]oxaphosphinine 6-oxide (3r).
o
1
White solid,163 mg, 89%, m.p. 149.2-150.1 C; H NMR (500
MHz, CDCl3): δ 7.84-7.80 (m, 2H), 7.73-7.71 (m, 1H), 7.67-7.64
(m, 1H), 7.46-7.42 (m, 1H), 7.30-7.26 (m, 1H), 7.16-7.11 (m, 2H),
6.64 (s, 2H), 2.14 (s, 6H), 2.11 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ 150.2 (d, J = 9.7 Hz), 144.0 (d, J = 4.1 Hz), 139.5 (d, J
= 3.5 Hz), 135.9 (d, J = 7.6 Hz), 133.5 , 130.5 (d, J = 10.1 Hz),
130.2, 129.1 (d, J = 3.0 Hz), 128.4 (d, J = 14.5 Hz), 125.7 (d, J =
129.8 Hz), 124.5, 124.1, 123.2 (d, J = 11.1 Hz), 121.5 (d, J = 11.2
Hz), 119.6 (d, J = 6.9 Hz), 119.2 (d, J = 9.2 Hz), 21.9 , 20.8; 31P
NMR (202 MHz, CDCl3): δ 32.8; HRMS (ESI): m/z [M+H]+ calcd
for C21H20O2PS+: 367.0916, found: 367.0912.
O-isopropyl S-(p-tolyl)phenylphosphonothioate (3m). Colorless
1
oil, 138 mg, 90%; H NMR (500 MHz, CDCl3): δ 7.70-7.66 (m,
2H), 7.50-7.47 (m, 1H), 7.39-7.35 (m, 2H), 7.19-7.18 (m, 2H),
7.01-7.00 (m, 2H), 5.03-.94 (m, 1H), 2.28 (s, 3H), 1.41-1.36 (m,
6H); 13C NMR (125 MHz, CDCl3): δ 138.9 (d, J = 2.9 Hz), 135.3
(d, J = 4.1 Hz), 132.4 (d, J = 148.4 Hz), 132.2 (d, J = 2.9 Hz), 131.4
(d, J = 10.5 Hz), 129.7 (d, J = 2.0 Hz), 128.0 (d, J = 14.9 Hz), 123.0
(d, J = 6.0 Hz), 72.0 (d, J = 7.3 Hz), 24.2(d, J = 3.4 Hz), 24.0 (d, J
= 5.2 Hz), 21.1; 31P NMR (202 MHz, CDCl3): δ 38.8; HRMS (ESI):
m/z [M+H]+ calcd for C16H20O2PS+: 307.0916, found: 307.0915.
S-(4-(tert-butyl)phenyl) O-isopropyl phenylphosphonothioate
(3n). Colorless oil, 160 mg, 92%; 1H NMR (500 MHz, CDCl3): δ
7.69-7.65 (m, 2H), 7.48-7.46 (m, 1H), 7.37-7.33 (m, 2H), 7.25-7.20
(m, 4H), 5.02-4.95 (m, 1H), 1.40-1.37 (m, 6H), 1.26 (s, 9H); 13C
NMR (125 MHz, CDCl3): δ 152.1 (d, J = 3.0 Hz), 135.0 (d, J = 4.1
Hz), 132.4 (d, J = 149.0 Hz), 132.1 (d, J = 2.9 Hz), 131.3 (d, J =
10.6 Hz), 128.0 (d, J = 14.9 Hz), 126.0, 123.0 (d, J = 5.4 Hz), 72.0
(d, J = 7.2 Hz), 34.5, 31.1, 24.2 (d, J = 3.5 Hz), 24.0 (d, J = 5.2 Hz);
31P NMR (202 MHz, CDCl3): δ 39.1; HRMS (ESI): m/z [M+H]+
calcd for C19H26O2PS+: 349.1386, found: 349.1385.
(S)-6-(naphthalen-2-ylthio)dibenzo[c,e][1,2]oxaphosphinine 6-
oxide (3s)6i. White solid, 153 mg, 82%, 168.3-169.6 C; 1H NMR
o
(500 MHz, DMSO-d6): δ 8.07-8.05 (m, 1H), 7.94 -7.90 (m, 1H),
7.85-7.80 (m, 4H), 7.72-7.70 (m, 2H), 7.64 (s, 1H), 7.55-7.51 (m,
2H), 7.43-7.40 (m, 1H), 7.34-7.33 (m, 1H), 7.25-7.24 (m, 1H),
7.15-7.12 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 150.4 (d, J =
9.7 Hz), 136.3 (d, J = 5.4 Hz), 136.3 (d, J = 7.3 Hz), 133.7 (d, J =
2.6 Hz), 133.1 (d, J = 2.9 Hz), 132.9 (d, J = 2.2 Hz), 131.7 (d, J =
3.2 Hz), 130.6 (d, J = 10.3 Hz), 130.3, 128.5 (d, J = 2.1 Hz), 128.4
(d, J = 14.8 Hz), 127.6, 127.3, 127.1, 126.4, 124.6 (d, J = 133.1 Hz),
124.6, 124.3, 123.1 (d, J = 11.4 Hz), 121.5 (d, J = 11.6 Hz), 121.1
(d, J = 6.3 Hz), 119.7 (d, J = 7.1 Hz); 31P NMR (202 MHz, CDCl3)
δ 32.6.
(S)-6-(butylthio)dibenzo[c,e][1,2]oxaphosphinine 6-oxide (3t)6d.
Colorless oil, 123 mg, 81%; 1H NMR (500 MHz, CDCl3): δ 7.91-
7.86 (m, 1H), 7.82-7.77 (m, 2H), 7.58-7.55 (m, 1H), 7.41-7.38 (m,
1H), 7.28-7.24 (m, 1H), 7.16-7.10 (m, 2H), 2.84-2.68 (m, 2H),
S-(4-chlorophenyl) O-isopropyl phenylphosphonothioate (3o).
Colorless oil, 135 mg, 83%; 1H NMR (500 MHz, CDCl3): δ 7.70-
7.66 (m, 2H), 7.51-7.48 (m, 1H), 7.41-7.37 (m, 2H), 7.26-7.24 (m,
2H), 7.18-7.17 (m, 2H), 5.01-4.95 (m, 1H), 1.42-1.36 (m, 6H); 13
C
1.55-1.48 (m, 2H), 1.26-1.19 (m, 2H), 0.74 (t, J = 7.5 Hz, 3H); 13
C
NMR (125 MHz, CDCl3): δ 136.4 (d, J = 4.1 Hz), 135.3 (d, J = 3.2
Hz), 132.4 (d, J = 2.7 Hz), 131.9 (d, J = 145.9 Hz), 131.3 (d, J =
10.6 Hz), 129.1 (d, J = 1.7 Hz), 128.2 (d, J = 15.0 Hz), 125.3 (d, J
= 4.6 Hz), 72.4 (d, J = 7.2 Hz), 24.1 (d, J = 3.6 Hz), 24.0 (d, J = 5.1
Hz); 31P NMR (202 MHz, CDCl3): δ 38.4; HRMS (ESI): m/z
[M+H]+ calcd for C15H17ClO2PS+: 327.0370, found: 327.0371.
S-(4-bromophenyl) O-isopropyl phenylphosphonothioate (3p).
Colorless oil, 144 mg, 78%; 1H NMR (500 MHz, CDCl3): δ 7.70-
NMR (125 MHz, CDCl3): δ 149.3 (d, J = 9.5 Hz), 135.7 (d, J = 7.5
Hz), 133.5 (d, J = 2.8 Hz), 130.4 , 130.1 (d, J = 10.7 Hz), 128.3 (d,
J = 14.8 Hz), 125.7 (d, J = 135.8 Hz), 124.9 , 124.7, 123.6 (d, J =
11.0 Hz), 122.0 (d, J = 11.8 Hz), 120.1 (d, J = 6.6 Hz), 32.6 (d, J =
4.8 Hz), 29.6 (d, J = 3.5 Hz), 21.3, 13.1; 31P NMR (202 MHz,
CDCl3): δ 37.6.
O,O-diethyl S-(p-tolyl)phosphorothioate (3u)4d. Colorless oil, 98
mg, 75%; 1H NMR (500 MHz, CDCl3): δ7.44 (d, J = 7.0 Hz,2H),
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7.15 (d, J = 8.0 Hz, 2H), 4.25-4.12 (m, 4H), 2.34 (s, 3H), 1.31 (t, J
The Supporting Information is available free of charge on the ACS
Publications website.
= 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 139.1 (d, J = 1.9
Hz), 134.4 (d, J = 5.0 Hz), 130 (d, J = 2.3 Hz), 122.6 (d, J = 7.5
Hz), 63.8 (d, J = 6.1 Hz), 21.0, 15.9 (d, J = 7.3 Hz); 31P NMR (202
MHz, CDCl3): δ 23.3.
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1H NMR, 13C NMR and 31P NMR spectra for all products (PDF)
Crystallographic data for the compound 3s (CIF).
O,O-diethyl S-(4-methoxyphenyl) phosphorothioate (3v)4e. Col-
■ AUTHOR INFORMATION
1
orless oil, 94 mg, 68%; H NMR (500 MHz, CDCl3): δ 7.48-7.46
Corresponding Author
*E-mail: xhzhang@sit.edu.cn.
*E-mail: wlx@sit.edu.cn
(m ,2H), 6.88 (d, J = 9.0 Hz ,2H), 4.24-4.12 (m, 4H), 3.80 (s, 3H),
1.31 (t, J = 7.0 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 160.3 (d,
J = 3.0 Hz), 136.2 (d, J = 5.0 Hz), 116.4 (d, J = 7.4 Hz), 114.8 (d,
J = 2.6 Hz), 63.8 (d, J = 6.3 Hz), 55.2, 15.9 (d, J = 7.1 Hz); 31P
NMR (202 MHz, CDCl3): δ 23.5.
9
Notes
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The authors declare no competing financial interest.
O,O-diethyl S-mesityl phosphorothioate (3w). Colorless oil, 92
mg, 64%; H NMR (500 MHz, CDCl3): δ 6.94 (s, 2H), 4.17-4.05
■ ACKNOWLEDGMENTS
1
(m, 4H), 2.53 (s, 6H), 2.25 (d, J = 2.0 Hz, 3H), 1.28 (t, J = 7.0
Hz ,6H); 13C NMR (125 MHz, CDCl3): δ 143.7 (d, J = 4.8 Hz),
139.2 (d, J = 3.9 Hz), 129.2 (d, J = 3.6 Hz), 121.0 (d, J = 7.9 Hz),
63.9 (d, J = 7.3 Hz), 22.2, 20.8, 15.9 (d, J = 6.8 Hz); 31P NMR (202
MHz, CDCl3): δ 23.5; HRMS (ESI): m/z [M+H]+ calcd for
C13H22O3PS+: 289.1022, found: 289.1020.
This work was supported by the NSF of China (21302127,
21502116), and the collaborative innovation funding of Shanghai
Institute of Technology (XTCX2016-7).
■ REFERENCES
O,O-diethyl S-(3-nitrophenyl) phosphorothioate (3x)4e. Colorless
oil, 100 mg, 69%; 1H NMR (500 MHz, CDCl3): δ 8.45-8.44
(m ,1H), 8.23 (d, J = 8.0 Hz ,1H), 7.94 (d, J = 8.0 Hz ,1H), 7.57 (t,
(1) (a) Ma, D.; Cai. Q. Acc. Chem. Res. 2008, 41, 1450–1460. (b) Surry, D. S.;
Buchwald, S. L. Chem. Sci. 2010, 1, 13-31. (c) Creutz, S. E.; Lotito, K. J.; Fu, G.
C.; Peters, J. C. Science 2012, 338, 647-651. (d) Casitas, A.; Ribas. X. Chem.
Sci. 2013, 4, 2301-2318. (e) Xia, S.; Gan, L.; Wang, K.; Li, Z.; Ma, D. J. Am.
Chem. Soc. 2016, 138, 13493-13496.
J = 8.0 Hz ,1H), 4.31-4.19 (m, 4H), 1.36 (t, J = 7.0 Hz, 6H); 13
C
NMR (125 MHz, CDCl3): δ 148.3, 140.11 (d, J = 5.1 Hz), 130.0 ,
129.5 (d, J = 7.3 Hz), 128.9 (d, J = 5.5 Hz), 123.7, 64.5 (d, J = 6.5
Hz), 15.9 (d, J = 7.2 Hz); 31P NMR (202 MHz, CDCl3): δ 20.8.
S-(4-chlorophenyl) O,O-diethyl phosphorothioate (3y)4e. Color-
less oil, 99 mg, 71%; 1H NMR (500 MHz, CDCl3): δ7.52-7.49 (m,
2H), 7.33-7.32 (m, 2H), 4.26-4.14 (m, 4H), 1.32 (t, J = 7.0 Hz, 6H);
13C NMR (125 MHz, CDCl3): δ 135.6 (d, J = 5.1 Hz), 135.3 (d, J
= 3.5 Hz), 129.4 (d, J = 2.3 Hz), 124.9 (d, J = 7.1 Hz), 64.1 (d, J =
6.3 Hz), 15.9 (d, J = 7.1 Hz); 31P NMR (202 MHz, CDCl3): δ 22.1.
S-(4-chlorophenyl) O,O-dimethyl phosphorothioate (3z)4d. Col-
orless oil, 76 mg, 60%; 1H NMR (500 MHz, CDCl3): δ 7.50 (d, J =
(2) (a) Xie, X.; Cai, G.; Ma. D. Org. Lett. 2005, 7, 4693-4695. (b) Yang, T.; Lin,
C.; Fu, H.; Jiang, Y.; Zhao, Y. Org. Lett. 2005, 7, 4781-4784. (c) Zhu, W.; Ma,
D. J. Org. Chem. 2005, 70, 2696-2700. (d) Huang, C.; Tang, X.; Fu, H.; Jiang,
Y.; Zhao, Y. J. Org. Chem. 2006, 71, 5020-5022. (e) Ma, D.; Cai, Q. Org. Lett.
2003, 5, 3799-3802.
(3) (a) Li, N.-S.; Frederiksen, J. K.; Piccirilli, J. A. Acc. Chem. Res. 2011, 44,
1257-1269. (b) Kumar, T. S.; Yang, T.; Mishra, S.; Cronin, C.; Chakraborty, S.;
Shen, J.-B.; Liang, B. T.; Jacobson, K. A. J. Med. Chem. 2013, 56, 902-914. (c)
Jahns, H.; Roos, M.; Imig, J.; Baumann, F.; Wang, Y.; Gilmour, R.; Hall, J. Nat.
Commun. 2015, 6, 6317-6325. (d) Zhang, A.; Sun, J.; Lin, C.; Hu, X.; Liu, W. J.
Agric. Food Chem. 2014, 62, 1477-1481. (e) Robertson, F. J.; Wu, J. J. Am.
Chem. Soc. 2012, 134, 2775-2780.
7.0 Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H), 3.84 (s, 3H), 3.81 (s, 3H);13
C
NMR (125 MHz, CDCl3): δ 135.7 (d, J = 5.1 Hz), 135.6 (d, J = 3.6
Hz), 129.6 (d, J = 2.4 Hz), 124.4 (d, J = 7.4 Hz), 54.3 (d, J = 6.2
Hz); 31P NMR (202 MHz, CDCl3): δ 24.0.
(4) For selected examples of Cu-catalyzed P-S-C bond formation: (a) Gao, Y.;
Tang, G.; Cao, Y.; Zhao, Y. Synthesis 2009, 1081-1086. (b) Kaboudin, B.; Abedi,
Y.; Kato, J.; Yokomatsu, T. Synthesis 2013, 45, 2323-2327. (c) Kumaraswamy,
G.; Raju, R. Adv. Synth. Catal. 2014, 356, 2591-2598. (d) Bai, J.; Cui, X.; Wang,
H.; Wu, Y. Chem. Commun. 2014, 50, 8860-8863. (e) Xu, J.; Zhang, L.; Li, X.;
Gao, Y.; Tang, G.; Zhao, Y. Org. Lett. 2016, 18, 1266-1269.
S-(4-chlorophenyl) O,O-diisopropyl phosphorothioate (3aa).
Colorless oil, 114 mg, 74%; 1H NMR (500 MHz, CDCl3): δ 7.54-
7.52 (m, 2H), 7.31 (d, J = 8.5 Hz, 2H), 4.80-4.73 (m, 2H), 1.33 (d,
J = 6.5 Hz, 6H), 1.27 (d, J = 6.5 Hz, 6H); 13C NMR (125 MHz,
CDCl3): δ 135.3 (d, J = 5.4 Hz), 134.9 (d, J = 3.3 Hz), 129.2 (d, J
= 2.2 Hz), 125.7 (d, J = 7.1 Hz), 73.4 (d, J = 6.8 Hz), 23.7 (d, J =
4.3 Hz), 23.4 (d, J = 5.6 Hz); 31P NMR (202 MHz, CDCl3): δ 18.5;
HRMS (ESI): m/z [M+H]+ calcd for C12H19ClO3PS+: 309.0476,
found: 309.0474.
2,2,6,6-tetramethylpiperidin-1-yl 4-methylbenzenesulfonate (4a).
White solid, 75 mg, 48%; 1H NMR (500 MHz, MeOD): δ 7.70 (s,
2H), 7.23 (s, 2H), 2.37 (s, 3H), 1.75-1.63 (m, 6H), 1.40 (s, 12H),
13C NMR (125 MHz, MeOD): δ 143.4 (d, J = 6.1Hz), 141.5 (d, J =
2.8Hz), 129.6, 126.7, 57.6, 35.6, 27.4, 21.1, 16.9.
(5) For selected example of Pd-catalyzed P-S-C bond formation: Zhu, Y.; Chen,
T.; Li, S.; Shimada, S.; Han, L.-B. J. Am. Chem. Soc. 2016, 138, 5825-5828.
(6) For other P-S-C bond formation under metal-free condition: (a) Harvey, R.
G.; Jacobson, H. I.; Jensen, E. V. J. Am. Chem. Soc. 1963, 85, 1618-1623. (b)
Liu, Y.-C.; Lee, C.-F. Green Chem. 2014, 16, 357-364. (c) Sun, J.-G.; Yang, H.;
Li, P.; Zhang, B. Org. Lett. 2016, 18, 5114-5117. (d) Wang, D.; Zhao, J.; Xu, W.;
Shao, C.; Shi, Z.; Li, L.; Zhang, X. Org. Biomol. Chem. 2017, 15, 545-549. (e)
Zhang, X.; Shi, Z.; Shao, C.; Zhao, J.; Wang, D.; Zhang, G.; Li, L. Eur. J. Org.
Chem. 2017, 1884-1888. (f) Song, S.; Zhang, Y.; Yeerlan, A.; Zhu, B.; Liu, J.;
Jiao, N. Angew. Chem. Int. Ed. 2017, 56, 2487-2491.
(7) For mechanistic considerations, see the following leading references: (a)
Wang, F.; Wang, D.; Mu, X.; Chen, P.; Liu, G. J. Am. Chem. Soc. 2014, 136,
10202-10205. (b) Chikkade, P. K.; Kuninobu, Y.; Kanai, M. Chem. Sci. 2015, 6,
3195-3200. (c) Zhang, W.; Wang, F.; McCann, S. D.; Wang, D.; Chen, P.; Stahl,
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S. S.; Liu, G. Science 2016, 353, 1014-1018. (d) Vasilopoulos, A.; Zultanski, S.
L.; Stahl, S. S. J. Am. Chem. Soc. 2017, 139, 7705-7708.
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