DCDMH-promoted synthesis of thiophosphates by coupling of H-phosphonates with thiols

Article abstract of DOI:10.1016/j.tet.2015.12.020

DCDMH-mediated phosphorylation of versatile thiols with H-phosphonates for the preparation of synthetically and biologically important thiophosphates was demonstrated. Without metal catalysts and other additives, phosphorylation occurred to give the desired products with good to excellent yields within 10 min at ambient temperature in the air.

Full text of DOI:10.1016/j.tet.2015.12.020

Tetrahedron xxx (2015) 1e6
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
DCDMH-promoted synthesis of thiophosphates by coupling
of H-phosphonates with thiols
*
Xiaojing Bi, Junchen Li, Fanhua Meng, Hongmei Wang, Junhua Xiao
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
DCDMH-mediated phosphorylation of versatile thiols with H-phosphonates for the preparation of syn-
thetically and biologically important thiophosphates was demonstrated. Without metal catalysts and
other additives, phosphorylation occurred to give the desired products with good to excellent yields
within 10 min at ambient temperature in the air.
Received 10 August 2015
Received in revised form 6 December 2015
Accepted 10 December 2015
Available online xxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Thiophosphate
DCDMH
H-Phosphonate
Thiol
Phosphorylation
1. Introduction
The synthesis of thiophosphates has attracted much attention,
and multifarious synthetic methods have been reported in recent
Thiophosphates are common and useful scaffolds in a variety
of biologically active molecules,1 most of which are well known
as pesticides (Fig. 1),2 and recently, several thiophosphates have
been reported to be used as potential HIV-1 and AChE inhibitors.3
Moreover, thiophosphates are also powerful precursors for se-
lective introduction of other functional groups in organic
synthesis.4
years (Fig. 2).5 Jensen reported a convenient method to obtain
thiophosphates through coupling of H-phosphonates with disul-
fides in the presence of NaH as base.6 Whereas, the employment of
base restricts its functional group compatibility. Yokomatsu
exploited the synthesis of thiophosphates by coupling of H-
phosphonates with benzenethiols using copper(I) iodide as cata-
lyst in DMF at room temperature in the air.7 Notably, Lee de-
veloped an efficient two-step procedure, which treated thiols
directly with N-chlorosuccinimide for the first time. Both aryl and
aliphatic thiols reacted well in these conditions.8 Very recently,
Wu reported a copper-catalyzed reductive coupling of arylsulfonyl
chlorides with H-phosphonates to afford S-aryl thiophosphates.9
Whereas, 7 equiv of H-phosphonates were employed and long
reaction time and high temperature were required to obtain ideal
yields. Though different substrates and reagents have been used
in the preparation of thiophosphates,10 several disadvantages still
exist in current protocols, for example, toxic reagents, excess
amounts of substrates, strong bases, long reaction time, or addi-
tional catalysts were required. Therefore, development of an ef-
ficient and convenient strategy for the preparation of
thiophosphates is still needed. Herein, we describe a simple and
efficient access to thiophosphates in one step by coupling of H-
phosphonates with thiols employing DCDMH (1, 3-Dichloro-5,
5-dimethylhydantoin) as a mediator.
Fig. 1. Selected examples of thiophosphates used as pesticides.
* Corresponding author. E-mail address: xiao.junhua@pku.edu.cn (J. Xiao).
http://dx.doi.org/10.1016/j.tet.2015.12.020
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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2
X. Bi et al. / Tetrahedron xxx (2015) 1e6
Table 1
Optimization studies on phosphorylation of 2, 4-dimethylthiophenol 2aa
Entry
DCDMH (equiv.)
Solvent
Ratio (3a:4a)b
Yield (%)b
1
2
0.75
0.50
0.25
0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
EtOAc
MeCN
THF
61:39
98: 2
0:49
d
61
98
0
3d
4e
5
0
99:1
99:1
0:100
33:67
73:27
15:85
63:37
99:1
95:5
99
99 (92)c
0
33
73
15
63
99
95
6
7f
8
9
10
11
12
13
DMF
CHCl3
DCE
a
Reaction conditions: Entries 1e3: 1a (0.5 mmol) and DCDMH in 1.5 mL CH2Cl2,
were stirred at room temperature for 10 min, then 2a (0.5 mmol) was added and
stirred for another 10 min. Entry 5: 2a (0.5 mmol), DCDMH, 1.5 mL CH2Cl2, rt,
10 min, then 1a (0.5 mmol) was added and stirred for another 10 min. Entries 6e13:
1a (0.5 mmol), 2a (0.5 mmol), DCDMH (0.5 equiv), 1.5 mL solvent, rt, 10 min.
Fig. 2. Approaches towards the synthesis of thiophosphates.
b
Determined by GCeMS using n-dodecane as internal standard.
Isolated yield.
No desired product 3a but by-product 4a was generated in 49% yield.
No reaction.
c
d
2. Results and discussion
e
f
No desired product 3a but by-product 4a was generated in 100% yield.
Preliminary optimization experiments were carried out with
model substrates dipropyl phosphonate 1a and 2,4-
dimethylthiophenol 2a (Table 1). Our initial investigations fo-
cused on the influence of the dose of DCDMH in two-step pro-
cedures at ambient temperature in the air (Table 1, entries 1e4).
Reducing the amount of DCDMH from 0.75 equiv to 0.5 equiv led to
the ratio of PeS coupling product 3a to by-product disulfide 4a
increasing from 61:39 to 98:2 (entry 1e2), whereas further re-
ducing the amount of DCDMH to 0.25 equiv resulted in complete
inhibition of the PeS coupling (entry 3). No reaction occurred in the
absence of DCDMH (entry 4). Gratifyingly, change the addition
sequences of the substrates (entries 2, 5e6), no obvious difference
was observed. These results promoted us to explore the reaction
conditions in one step (entries 6e13). Solvent screening indicated
that MeCN, DMF, EtOAc, toluene, and THF were not suitable for the
reaction (entries 7e11), whereas haloalkanes, such as CH2Cl2, DCE
and CHCl3 exhibited comparable results (entries 6, 12e13). For its
lower boiling point and relatively environmental benefits, CH2Cl2
was selected as the solvent.
As described in Table 2, we first applied the optimal conditions
to aryl thiols to examine the substrate scope. Aryl thiols with both
electron-donating and electron-withdrawing groups performed
well under optimal reaction conditions (Table 2). It was worth
mentioning that ortho-substituents of aryl ring did not affect the
reaction markedly and gave the desired products in good yields (3a,
3b, 3je3o). The reactive functional groups, such as bromo and nitro
group were also tolerated well in current reaction system (3de3h).
Due to their poor solubility in CH2Cl2, the phosphorylation of 4-
nitrothiophenol and 2-naphthalenethiol were carried out in DME
for 30 min and ideal yields were obtained (3h and 3i).
2,4-dimethylthiophenol (2a) as coupling partner. As shown in Table
2, both linear and branched H-phosphonates performed well in this
coupling (3je3p).
With the encouraging results in Table 2, we then paid attention
to the coupling of aliphatic thiols with dipropyl H-phosphonates
(1a) in above optimal conditions (Table 3). As expected, benzylthiol
occurred well with 1a in a yield of 85% (3q). Cyclohexanethiol and
cyclopentanethiol showed relatively lower reactivity in comparison
with aryl thiols (3r and 3s). Much more by-products disulfide 4
were generated because of the active properties of cycloalkane
thiols. On the contrary, straight-chain paraffin thiols with ester
groups gave a relatively small amount of by-products 4. Aliphatic
thiols containing branched chain at a-position (3v, 3w) tended to
give higher ratios of by-products 4. On the whole, the reactions
performed well (3qe3w) and gave the desired products within
10 min at ambient temperature with good to excellent yields. We
then changed the substrates from aliphatic thiols to cysteine (3x,
3y) in the optimal conditions. Frustratingly, the coupling reactions
failed, possibly due to the poor solubility of these substrates in the
solvents used in the reaction.12
On the basis of preliminary results, a proposed mechanism of
this coupling reaction was shown in Fig. 3. Different addition se-
quences of the substrates might have different mechanisms. In
mechanism A, the reaction of H-phosphonates 1 with DCDMH gave
chlorophosphates I, which could be observed on GCeMS. Then,
chlorophosphates I reacted with thiols 2 to form the desired
products 3. In mechanism B, the reaction between thiols 2 and
DCDMH resulted in the formation of intermediates II.8 Then, in-
termediates II reacted with H-phosphonates 1 to give the corre-
sponding products 3. At the same time, the reaction of II and thiols
To determine the substrate scope and limitations of this
DCDMH-mediated metal-free phosphorylation of thiols, we then
test the reactivity of various H-phosphonates using
2
resulted in the formation of by-products disulfide 4.11
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X. Bi et al. / Tetrahedron xxx (2015) 1e6
3
Table 2
Table 3
Coupling of H-phosphonates with aryl thiolsa,b,c
Coupling of different aliphatic thiols with 1aa,b,c
thiols reacted well in the optimal conditions. Aromatic thiols
bearing fluoro, chloro, bromo, and nitro group were compatible in
this coupling. ortho-Substitutes and electro-withdrawing group
substituted aliphatic thiols were also well tolerated. Compared
with reported approaches, there are several advantages when
DCDMH was used as a mediator. First, the reaction is very fast and
proceeded completely in one step within 10 min with good to ex-
cellent yields. Second, the reaction was carried out under mild
conditions at room temperature in the air without heating or
cooling. Third, only DCDMH was required for the reaction without
any other metal catalysts or additives.
Thiophosphates 3 are the main products because that the forma-
tion of II was very fast, there were little thiols left to give the cor-
responding by-products 4. When all of the substrates were mixed
in one pot at the same time, the reactions proceeded as mechanism
B, proved by the real-time monitoring of the reaction via 31P NMR,
and no intermediates I was observed during the reaction.
In summary, we have developed a novel one-pot protocol for
synthesis of thiophosphates employing DCDMH as the mediator to
promote the reaction for the first time. Both aryl thiols and aliphatic
Fig. 3. Proposed mechanism.
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X. Bi et al. / Tetrahedron xxx (2015) 1e6
3. Experimental section
(121 MHz, CDCl3) d 22.74; MS (70 eV, EI) m/z: 292 (26), 250 (13), 208
(100), 128 (34), 114 (44).
3.1. Materials and methods
3.2.6. S-(4-Chlorophenyl) O,O-dipropyl thiophosphate (3f). Colorless
NMR spectra were recorded on Bruker Advance 300 MHz
spectroscope in CDCl3. GCeMS spectra were measured on Thermo
Polaris Q GCeMS instrument. All the chemicals were commercially
available and used without further purification.
oil. Yield: 89%. 1H NMR (300 MHz, CDCl3)
d 7.54e7.47 (m, 2H),
7.35e7.29 (m, 2H), 4.07 (qdt, J¼9.9, 8.2, 6.6 Hz, 4H), 1.74e1.61 (m,
4H), 0.92 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 135.9 (d,
J¼5.3 Hz), 135.6(d, J¼3.4 Hz), 129.7 (d, J¼2.2 Hz), 69.8 (d, J¼6.8 Hz),
23.7 (d, J¼7.2 Hz), 10.1; 31P NMR (121 MHz, CDCl3)
d 22.31; MS
(70 eV, EI) m/z: 308 (34), 266 (58), 224 (100), 144 (36), 128 (46), 108
(18).
3.2. General procedure
3.2.7. S-(4-Bromophenyl)
O,O-dipropyl
thiophosphate
The corresponding H-Phosphonates (0.5 mmol) and thiols
(0.5 mmol) were added into the mixture of DCDMH (0.5 equiv) in
solvent (1.5 mL). The mixture was stirred at room temperature for
10 min. Then the mixture was filtered off and the filtrate was
evaporated under reduced pressure. The crude product was purified
by column chromatography (silica gel, n-hexane-EtOAc, 9:1 to 4:1).
(3g). Colorless oil. Yield: 91%. 1H NMR (300 MHz, CDCl3)
d
7.52e7.39 (m, 4H), 4.17e3.97 (m, 4H), 1.75e1.62 (m, 4H), 0.92 (t,
J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
136.1 (d, J¼5.3 Hz), 132.6
d
(d, J¼2.2 Hz), 126.1 (d, J¼7.3 Hz), 123.7 (d, J¼0.5 Hz), 69.9 (d,
J¼6.8 Hz), 23.7 (d, J¼7.2 Hz), 10.1; 31P NMR(121 MHz, CDCl3)
d
22.04; MS (70 eV, EI) m/z: 354 (18), 311 (64), 270 (100), 187 (32),
174 (30), 123 (23), 108 (52).
3.2.1. S-(2,4-Dimethylphenyl)
O,O-dipropyl
thiophosphate
7.47 (dd,
(3a). Colorless oil. Yield: 92%. 1H NMR (300 MHz, CDCl3)
d
3.2.8. S-(4-Nitrophenyl) O,O-dipropyl thiophosphate (3h). Colorless
J¼7.9, 2.3 Hz, 1H), 7.07 (s, 1H), 6.98 (d, J¼7.9 Hz, 1H), 4.12e3.94 (m,
oil. Yield: 52%. 1H NMR (300 MHz, CDCl3):
d 8.21e8.16 (m, 2H),
4H), 2.48 (s, 3H), 2.30 (d, J¼2.1 Hz, 3H), 1.66 (dt, J¼13.7, 6.9 Hz, 4H),
7.80e7.72 (m, 2H), 4.21e4.01 (m, 4H), 1.77e1.63 (m, 4H), 0.93 (t,
0.92 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d
142.2 (d,
J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3):
134.1 (d, J¼6.0 Hz),126.5,
d
J¼5.4 Hz),139.7 (d, J¼3.3 Hz),136.4 (d, J¼4.2 Hz),131.8 (d, J¼2.8 Hz),
127.7 (d, J¼2.8 Hz), 122.2 (d, J¼7.4 Hz), 69.6 (d, J¼7.1 Hz), 23.7 (d,
J¼7.2 Hz), 21.4 (d, J¼17.7 Hz), 10.1; 31P NMR (121 MHz, CDCl3):
124.6, 124.2 (d, J¼Hz), 70.3 (d, J¼6.8 Hz), 23.7 (d, J¼7.1 Hz), 10.1; 31
P
NMR (121 MHz, CDCl3):
d 20.27; MS (70 eV, EI) m/z: 319 (4), 277
(15), 236 (100), 207 (5), 155 (12), 123 (21), 105 (8).
d
23.54; GCeMS (70 eV, EI) m/z: 302 (40), 260 (43), 218 (79), 185
(40), 147 (21), 137 (10), 105 (100), 91 (9).
3.2.9. S-(Naphthalene-2-yl) O,O-dipropyl thiophosphate (3i). White
solid. Yield: 85%. 1H NMR (300 MHz, CDCl3)
d
8.09 (t, J¼2.2 Hz, 1H),
3.2.2. S-(o-Tolyl) O,O-dipropyl thiophosphate (3b). Colorless oil.
7.87e7.75 (m, 3H), 7.65e7.58 (m, 1H), 7.55e7.47 (m, 2H),4.28e3.94
(m, 4H), 1.82e1.53 (m, 4H), 0.91 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz,
Yield: 88%. 1H NMR (300 MHz, CDCl3)
d 7.66e7.60 (m, 1H), 7.28 (m,
2H), 7.22e7.14 (m, 1H), 4.14e3.96 (m, 4H), 2.54 (d, J¼1.3 Hz, 3H),
CDCl3)
d
134.5 (d, J¼6.8 Hz), 133.8 (d, J¼2.3 Hz), 133.2 (d, J¼1.8 Hz),
1.68 (dd, J¼14.0, 7.3 Hz, 4H), 0.92 (t, J¼7.4 Hz, 6H); 13C NMR
131.1 (d, J¼4.2 Hz), 129.1 (d, J¼1.6 Hz), 127.9 (dd, J¼3.6, 1.1 Hz), 127.2
(d, J¼1.0 Hz), 126.9 (d, J¼0.7 Hz), 124.0 (d, J¼7.3 Hz), 69.7 (d,
J¼6.8 Hz), 23.7 (d, J¼7.2 Hz), 10.2; 31P NMR(121 MHz, CDCl3)
(75 MHz, CDCl3)
d
142.3 (d, J¼5.7 Hz), 136.3 (d, J¼4.2 Hz), 131.0 (d,
J¼2.6 Hz), 129.5 (d, J¼3.0 Hz), 126.9 (d, J¼2.7 Hz), 126.0 (d,
J¼7.4 Hz), 69.7 (d, J¼7.1 Hz), 23.7 (d, J¼7.2 Hz), 21.6, 10.1; 31P NMR
d
22.91; MS (70 eV, EI) m/z: 324 (45), 282 (48), 240 (100), 160 (56),
(121 MHz, CDCl3)
d
23.09; MS (70 eV, EI) m/z (EI): 288 (7), 246 (23),
144 (31), 115 (57).
204 (100), 171 (90), 123 (30), 91 (87), 77 (8).
3.2.10. S-(2,4-Dimethylphenyl)
O,O-dimethyl
thiophosphate
3.2.3. S-(m-Tolyl) O,O-dipropyl thiophosphate (3c). Colorless oil.
(3j). Colorless oil. Yield: 88%. 1H NMR (300 MHz, CDCl3)
d 7.45 (dd,
Yield: 90%. 1H NMR (300 MHz, CDCl3)
d
7.36 (dd, J¼5.5, 5.0 Hz, 2H),
J¼7.9, 2.3 Hz, 1H), 7.08 (s, 1H), 7.01e6.96 (m, 1H), 3.81 (s, 3H), 3.77
(s, 3H), 2.49 (d, J¼0.9 Hz, 3H), 2.31 (d, J¼2.2 Hz, 3H); 13C NMR
7.22 (t, J¼7.5 Hz, 1H), 7.15 (dd, J¼7.6, 0.6 Hz, 1H), 4.28e3.85 (m, 4H),
2.33 (s, 3H), 1.79e1.50 (m, 4H), 0.91 (t, J¼7.4 Hz, 6H).13C NMR
(75 MHz, CDCl3)
d
142.2 (d, J¼5.4 Hz), 139.9 (d, J¼3.5 Hz), 136.3 (d,
(75 MHz, CDCl3)
d
139.3 (d, J¼2.3 Hz), 135.3 (d, J¼5.3 Hz), 131.7 (d,
J¼4.2 Hz), 131.9 (d, J¼2.8 Hz), 127.8 (d, J¼2.9 Hz), 121.5 (d, J¼7.4 Hz),
J¼5.3 Hz),129.9 (d, J¼2.8 Hz),129.2 (d, J¼2.2 Hz),126.3 (d, J¼7.1 Hz),
54.3 (d, J¼6.6 Hz), 21.2 (d, J¼13.8 Hz); 31P NMR (121 MHz, CDCl3)
69.6 (d, J¼6.7 Hz), 23.7 (d, J¼7.3 Hz), 21.4, 10.1. 31P NMR(121 MHz,
d
26.54; MS (70 eV, EI) m/z: 246 (100), 213 (98), 135 (60), 105 (59),
CDCl3)
d
23.17; MS (70 eV, EI) m/z: 288 (26), 246 (13), 204 (100), 124
91 (43), 77 (29).
(29), 108 (32), 91 (26), 77 (5).
3.2.11. S-(2,4-Dimethylphenyl)
O,O-diethyl
thiophosphate
3.2.4. S-(4-Methoxyphenyl)
O,O-dipropyl
thiophosphate
(3k). Colorless oil. Yield: 89%. 1H NMR (300 MHz, CDCl3)
d 7.47 (dd,
(3d). Colorless oil. Yield: 93%. 1H NMR (300 MHz, CDCl3)
J¼7.9, 2.3 Hz, 1H), 7.08 (s, 1H), 6.99 (d, J¼7.9 Hz, 1H), 4.24e4.08 (m,
4H), 2.48 (s, 3H), 2.30 (d, J¼2.1 Hz, 3H), 1.30 (td, J¼7.1, 0.8 Hz, 6H);
d
7.50e7.44 (m, 2H), 6.90e6.84 (m, 2H), 4.14e3.97 (m, 4H), 3.80 (s,
3H), 1.74e1.61 (m, 4H), 0.92 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz,
13C NMR (75 MHz, CDCl3)
d
142.2 (d, J¼5.4 Hz), 139.7 (d, J¼3.4 Hz),
CDCl3)
d
160.6 (d, J¼2.8 Hz), 136.5 (d, J¼4.8 Hz), 116.8 (d, J¼7.5 Hz),
136.3 (d, J¼4.2 Hz), 131.8 (d, J¼2.8 Hz), 127.7 (d, J¼2.8 Hz), 122.1 (d,
J¼7.4 Hz), 64.1 (d, J¼6.7 Hz), 21.3 (d, J¼14.6 Hz), 16.1 (d, J¼7.1 Hz);
115.1 (d, J¼2.5 Hz), 69.6 (d, J¼6.7 Hz), 55.5, 23.7 (d, J¼7.2 Hz), 10.2;
31P NMR(121 MHz, CDCl3)
23.59; MS (70 eV, EI) m/z: 304 (41), 262
(36), 220 (100), 140 (55), 124 (35), 95 (9), 77 (6).
d
31P NMR (121 MHz, CDCl3)
d 23.46; MS (70 eV, EI) m/z: 274 (100),
239 (8), 137 (77), 91 (51), 77 (28).
3.2.5. S-(4-Fluorophenyl)
O,O-dipropyl
thiophosphate
3.2.12. S-(2,4-Dimethylphenyl)
O,O-diisopropyl
thiophosphate
7.52 (dd,
(3e). Colorless oil. Yield: 82%. 1H NMR (300 MHz, CDCl3)
(3l). Colorless oil. Yield: 90%. 1H NMR (300 MHz, CDCl3)
d
d
7.64e7.45 (m, 2H), 7.09e7.00 (m, 2H), 4.07 (qdt, J¼9.9, 8.2, 6.6 Hz,
J¼7.9, 2.3 Hz, 1H), 7.06 (s, 1H), 7.00e6.94 (m, 1H), 4.72 (m, 2H), 2.47
4H), 1.75e1.58 (m, 4H), 0.92 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz,
(d, J¼0.8 Hz, 3H), 2.29 (d, J¼2.0 Hz, 3H), 1.31 (d, J¼6.2 Hz, 6H), 1.24
CDCl3)
d
136.8 (dd, J¼8.4, 5.1 Hz), 116.8 (d, J¼2.3 Hz), 116.5 (d,
(d, J¼6.2 Hz, 6H). 13C NMR (75 MHz, CDCl3)
d
142.0 (d, J¼5.6 Hz),
J¼2.3 Hz), 69.8 (d, J¼6.8 Hz), 23.7 (d, J¼7.2 Hz), 10.1; 31P NMR
139.4 (d, J¼3.3 Hz), 136.0 (d, J¼4.2 Hz), 131.7 (d, J¼2.7 Hz), 127.6 (d,
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5
J¼2.7 Hz), 122.9 (d, J¼7.3 Hz), 73.3 (d, J¼7.2 Hz), 24.0 (d, J¼4.2 Hz),
23.7 (d, J¼5.6 Hz), 21.4 (d, J¼20.3 Hz). 31P NMR (121 MHz, CDCl3)
3.56e3.42 (m, 1H), 2.19e2.05 (m, 2H), 1.79e1.68 (m, 6H), 1.68e1.57
(m, 4H), 0.97 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 69.0 (d,
d
21.44. MS (70 eV, EI) m/z: 302 (26), 260 (31), 218 (82),185 (51), 138
J¼6.5 Hz), 44.8 (d, J¼3.7 Hz), 35.5 (d, J¼6.8 Hz), 24.5 (s), 23.7 (d,
(11), 105 (100), 77 (13).
J¼7.4 Hz), 10.2; 31P NMR (121 MHz, CDCl3)
d 27.63. MS (70 eV, EI) m/
z: 267 (5), 225 (3), 182 (11), 157 (22), 125 (10), 115 (100), 97 (31), 83
3.2.13. S-(2,4-Dimethylphenyl)
O,O-dibutyl
thiophosphate
7.47 (dd,
(38), 67 (18).
(3m). Colorless oil. Yield: 93%. 1H NMR (300 MHz, CDCl3)
d
J¼7.9, 2.2 Hz, 1H), 7.07 (s, 1H), 6.97 (d, J¼7.9 Hz, 1H), 4.16e3.98 (m,
4H), 2.48 (s, 3H), 2.30 (d, J¼2.0 Hz, 3H), 1.61 (dt, J¼14.7, 6.6 Hz, 4H),
1.35 (dq, J¼14.5, 7.3 Hz, 4H), 0.90 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz,
3.2.20. S-(2-Methoxycarbonyl-ethyl) O,O-dipropyl thiophosphate
(3t). Colorless oil. Yield: 92%. 1H NMR (300 MHz, CDCl3)
d
4.14e3.94 (m, 4H), 3.70 (s, 3H), 3.07 (dt, J¼16.5, 7.1 Hz, 2H), 2.76 (t,
CDCl3)
d
142.2 (d, J¼5.4 Hz), 139.7 (d, J¼3.3 Hz), 136.3 (d, J¼4.2 Hz),
J¼7.1 Hz, 2H), 1.80e1.65 (m, 4H), 0.97 (t, J¼7.4 Hz, 6H); 13C NMR
131.8 (d, J¼2.7 Hz), 127.7 (d, J¼2.8 Hz), 122.2 (d, J¼7.4 Hz), 77.6, 77.2,
(75 MHz, CDCl3)
d
171.8, 69.3 (d, J¼6.5 Hz), 52.0, 35.6 (d, J¼3.9 Hz),
76.7, 67.9 (d, J¼7.1 Hz), 32.3 (d, J¼7.0 Hz), 21.3 (dd, J¼18.5, 0.8 Hz),
25.7 (d, J¼4.1 Hz), 23.7 (d, J¼7.4 Hz), 10.2; 31P NMR (121 MHz,
18.8,13.7; 31P NMR (121 MHz, CDCl3)
d
23.56. MS (70 eV, EI) m/z: 330
CDCl3) d 27.27; MS (70 eV, EI) m/z: 285 (100), 253 (11), 243 (18), 211
(32), 274 (78), 218 (85),185 (45),137 (34),105 (100), 91 (18), 77 (13).
(12), 201 (29), 169 (30), 141 (39), 115 (54), 87 (33), 71 (49); HRMS
(ESI): calcd for C10H21O5PS [Mþ]: 285.0920, found: 285.0927.
3.2.14. S-(2,4-Dimethylphenyl)
O,O-diisobutyl
thiophosphate
7.47 (dd,
(3n). Colorless oil. Yield: 93%. 1H NMR (300 MHz, CDCl3)
d
3.2.21. S-(1-Methoxycarbonyl-methyl) O,O-dipropyl thiophosphate
J¼7.9, 2.3 Hz,1H), 7.06 (s,1H), 6.99e6.93 (m,1H), 3.92e3.75 (m, 4H),
(3u). Colorless oil. Yield: 95%. 1H NMR (300 MHz, CDCl3)
2.48 (s, 3H), 2.29 (d, J¼2.1 Hz, 3H), 1.91 (dp, J¼13.3, 6.7 Hz, 2H), 0.90
d
4.17e4.00 (m, 4H), 3.76 (s, 3H), 3.61 (d, J¼15.2 Hz, 2H), 1.80e1.67
(d, J¼6.7 Hz, 12H); 13C NMR (75 MHz, CDCl3)
d
142.2 (d, J¼5.4 Hz),
(m, 4H), 0.97 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 169.4 (d,
139.7 (d, J¼3.4 Hz), 136.4 (d, J¼4.2 Hz), 131.8 (d, J¼2.8 Hz), 127.7 (d,
J¼2.8 Hz), 122.2 (d, J¼7.4 Hz), 73.9 (d, J¼7.6 Hz), 29.2 (d, J¼7.3 Hz),
J¼5.1 Hz), 69.6 (d, J¼6.3 Hz), 53.0, 32.3 (d, J¼3.8 Hz), 23.6 (d,
J¼7.4 Hz),10.2; 31P NMR (121 MHz, CDCl3)
d 25.46; MS (70 eV, EI) m/
21.50, 21.2, 18.8; 31P NMR (121 MHz, CDCl3)
d
23.38; MS (70 eV, EI)
z: 271 (100), 22 9(36), 197 (12), 187 (76), 155 (78), 127 (19); HRMS
m/z: 330 (22), 274 (9), 218 (100), 185 (44), 137 (9), 105 (94), 77 (10).
(ESI): calcd for C9H19O5PS [Mþ]: 271.0764, found: 271.0773.
3.2.15. S-(2,4-Dimethylphenyl) O,O-bis (2-methoxyethyl) thio-
3.2.22. S-(1-Ethoxycarbonyl-ethyl)
O,O-dipropyl
thiophosphate
4.20 (q,
phosphate (3o). Colorless oil. Yield: 83%. 1H NMR (300 MHz, CDCl3)
(3v). Colorless oil. Yield: 87%. 1H NMR (300 MHz, CDCl3)
d
d
7.52 (dd, J¼7.9, 2.4 Hz, 1H), 7.07 (s, 1H), 6.98 (d, J¼7.9 Hz, 1H),
J¼7.1 Hz, 2H), 4.14e3.98 (m, 4H), 3.94 (dd, J¼13.3, 7.2 Hz, 1H),
4.28e4.12 (m, 4H), 3.58e3.51 (m, 4H), 3.35 (s, 6H), 2.48 (d, J¼0.9 Hz,
1.79e1.66 (m, 4H), 1.60 (d, J¼7.2 Hz, 3H), 1.29 (t, J¼7.1 Hz, 3H), 0.97
3H), 2.30 (d, J¼2.2 Hz, 3H).13C NMR (75 MHz, CDCl3)
d
142.4 (d,
(td, J¼7.4, 1.2 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 172.1 (d,
J¼5.5 Hz),139.9 (d, J¼3.5 Hz),136.6 (d, J¼4.3 Hz),131.9 (d, J¼2.9 Hz),
127.8 (d, J¼2.9 Hz), 121.6 (d, J¼7.5 Hz), 71.3 (d, J¼7.3 Hz), 66.8 (d,
J¼7.0 Hz), 59.1, 21.4 (d, J¼17.6 Hz). 31P NMR (121 MHz, CDCl3)
J¼5.9 Hz), 69.5 (dd, J¼6.4, 4.6 Hz), 61.9, 42.7 (d, J¼3.4 Hz), 23.6 (dd,
J¼7.4, 1.5 Hz), 20.2 (d, J¼6.0 Hz), 14.2, 10.2 (d, J¼0.8 Hz); 31P NMR
(121 MHz, CDCl3):
d 25.14; MS (70 eV, EI) m/z: 299 (100), 253 (18),
d
24.72. MS (70 eV, EI) m/z: 335 (3), 197 (79), 139 (100), 113 (45), 105
239 (8), 211 (24), 169 (58), 141 (63), 99 (19); HRMS (ESI): calcd for
(17), 91 (12), 77 (10).
C
11H23O5PS [Mþ]: 299.1077, found: 299.1081.
3.2.16. S-(2,4-Dimethylphenyl) O,O-bis (2-chloroethyl) thiophosphate
3.2.23. S-(3-Oxobutan-2-yl)
O,O-dipropyl
thiophosphate
(3p). Colorless oil. Yield: 30%. 1H NMR (300 MHz, CDCl3)
d 7.50 (dd,
(3w). Colorless oil. Yield: 79%. 1H NMR (300 MHz, CDCl3)
J¼7.9, 2.5 Hz, 1H), 7.10 (s, 1H), 7.01 (d, J¼7.9 Hz, 1H), 4.38e4.20 (m,
d
4.14e3.96 (m, 5H), 2.33 (s, 3H), 1.80e1.66 (m, 4H), 1.52 (dd, J¼7.2,
4H), 3.64 (t, J¼5.9 Hz, 4H), 2.49 (d, J¼1.2 Hz, 3H), 2.32 (d, J¼2.4 Hz,
0.5 Hz, 3H), 0.97 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 205.2
3H); 13C NMR (75 MHz, CDCl3)
d
142.6 (d, J¼5.5 Hz), 140.5 (d,
(d, J¼5.2 Hz), 69.6 (dd, J¼6.8, 3.3 Hz), 49.2 (d, J¼3.3 Hz), 27.4, 23.7
J¼3.6 Hz),136.7 (d, J¼4.3 Hz),132.1 (d, J¼3.1 Hz),128.0 (d, J¼3.0 Hz),
(dd, J¼7.5, 0.6 Hz), 18.7 (d, J¼6.4 Hz), 10.2; 31P NMR (121 MHz,
120.8 (d, J¼7.8 Hz), 77.6, 77.2, 76.7, 67.3 (d, J¼6.7 Hz), 42.3 (d,
CDCl3)
d 25.44. MS (70 eV, EI) m/z: 268 (8), 227 (3), 185 (43), 143
J¼7.5 Hz), 21.4 (d, J¼17.7 Hz); 31P NMR (121 MHz, CDCl3)
d
24.87;
(100), 115 (19), 83 (20), 71 (5); HRMS (ESI): calcd for C10H21O4PS
MS (70 eV, EI) m/z: 342 (52), 307 (25), 280 (61), 263 (32), 247 (24),
[Mþ]: 269.0971, found: 269.0969.
218 (61), 185 (38), 163 (25), 137 (41), 105 (100), 91 (30), 71 (21).
3.2.24. 1,2-Bis(2,4-dimethylphenyl) disulfide (4a). Yellow oil. 1H
3.2.17. S-Benzyl O,O-dipropyl thiophosphate (3q). Colorless oil.
NMR (300 MHz, CDCl3)
d
7.37 (d, J¼7.9 Hz, 2H), 6.98 (s, 2H), 6.92 (d,
Yield: 85%. 1H NMR (300 MHz, CDCl3)
d
7.39e7.26 (m, 5H),
J¼8.4 Hz, 2H), 2.36 (s, 6H), 2.28 (s, 6H); 13C NMR (75 MHz, CDCl3)
4.07e3.87 (m, 6H), 1.72e1.59 (m, 4H), 0.93 (t, J¼7.4 Hz, 6H); 13C
d 138.4, 138.0, 132.5, 131.4, 130.6, 127.5, 21.1, 20.3; MS (70 eV, EI) m/
z: 274 (83), 137 (100), 91 (59), 77 (33).
NMR (75 MHz, CDCl3)
d
137.7 (d, J¼5.6 Hz), 129.1, 128.8, 127.7, 69.1
(d, J¼6.2 Hz), 35.1 (d, J¼3.8 Hz), 23.6 (d, J¼7.5 Hz), 10.2; 31P NMR
(121 MHz, CDCl3)
d 26.86; MS (70 eV, EI) m/z: 288 (25), 246 (34),
Supplementary data
204 (10), 171 (25), 123 (11), 107 (22), 91 (100), 65 (24).
Supplementary data (1H and 13C NMR spectra for all products)
associated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2015.12.020. These data include MOL
files and InChiKeys of the most important compounds described in
this article.
3.2.18. S-Cyclohexyl O,O-dipropyl thiophosphate (3r). Colorless oil.
Yield: 80%. 1H NMR (300 MHz, CDCl3)
d 4.12e3.94 (m, 4H),
3.35e3.21 (m, 1H), 1.81e1.66 (m, 6H), 1.61e1.22 (m, 8H), 0.97 (t,
J¼7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3)
69.0 (d, J¼6.6 Hz), 45.7 (d,
d
J¼3.5 Hz), 35.5 (d, J¼6.0 Hz), 26.1, 25.4, 23.7 (d, J¼7.4 Hz), 10.2; 31
P
NMR (121 MHz, CDCl3) d 27.78; MS (70 eV, EI) m/z: 281 (19), 231 (7),
References and notes
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d
Please cite this article in press as: Bi, X.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.12.020

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Please cite this article in press as: Bi, X.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.12.020