Organoselenium-catalyzed vicinal dichlorination of unsaturated phosphonates

Article abstract of DOI:10.1039/c6nj00658b

Diphenyl diselenide (PhSeSePh) was effective as a pre-catalyst for the vicinal dichlorination of α,β-unsaturated phosphonates with sulfuryl chloride. The reaction conditions were mild and the desired products were formed in up to 93% yield and moderate diastereoselectivity (10:1). The important diphenylselenium dichloride intermediate was obtained and characterized by X-ray crystallography.

Full text of DOI:10.1039/c6nj00658b

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Organoselenium-catalyzed vicinal dichlorination
of unsaturated phosphonates†
Cite this:DOI: 10.1039/c6nj00658b
a
a
a
ab
Xianghua Zeng,* Chunhua Gong, Junyong Zhang and Jingli Xie*
Diphenyl diselenide (PhSeSePh) was effective as
a pre-catalyst for the vicinal dichlorination of
Received (in Nottingham, UK)
2
9th February 2016,
a,b-unsaturated phosphonates with sulfuryl chloride. The reaction conditions were mild and the desired
products were formed in up to 93% yield and moderate diastereoselectivity (10 : 1). The important
diphenylselenium dichloride intermediate was obtained and characterized by X-ray crystallography.
Accepted 19th July 2016
DOI: 10.1039/c6nj00658b
www.rsc.org/njc
been reported. Herein we present an efficient procedure for the
selenium-catalyzed vicinal dichlorination of a,b-unsaturated
Introduction
The synthesis of a- and b-substituted phosphonic acids has been phosphonates.
an important area of research: phosphonic acid derivatives are
particularly useful natural products. They are widely found in
plants and exhibit excellent inhibitory activities including renin
Results and discussion
1
and HIV protease. The functionalization of olefins is a com-
monly employed strategy for the rapid construction of molecular The study began with unsaturated phosphonates 1a as a model
2
,3
complexity in organic synthesis. It is difficult to imagine a substrate and sulfuryl chloride as a source of ‘‘Cl’’ in a search for
more efficient means of causing the formation of a,b-substituted suitable conditions, as shown in Table 1. As might be expected,
phosphonates than simultaneously introducing two hetero- the reaction took place and produced the desired product 2a in
atoms into an olefin, especially if this transformation could also 70% isolated yield in dichloromethane at room temperature
4
be highly stereoselective when required. Recently, several kinds after 5 min, but the diastereoselectivity was very poor (entry 1).
5
of transformations such as aminohydroxylation, amino- Because the transformation was very quick, the reaction tem-
6
7
8
bromination, dihydroxylation, and bromohydroxylation of perature was tested, and the results showed that lowering the
a,b-unsaturated phosphonates have been reported. Surprisingly, reaction temperatures resulted in a significant decrease in the
however, these methods use the metal osmium as a catalyst, efficiency (entries 2 and 3). Guided by the literature indicating
which often causes low yields. Considering the rapid development that diphenyl diselenide was as good a candidate as the pre-
1
1
of the uses of olefins and the biological activity of a,b-substituted catalyst for the activation of chlorides, the addition of a series
phosphonic acids, developing highly efficient and operationally of aryl selenide compounds was tested in the current reaction
simple approaches to dihalogenation of a,b-unsaturated phos- (entries 4–6 and Table S1, ESI†). In 5% mol amount of diphenyl
phonates is still urgently desired. Meanwhile, because it is a diselenide the dichlorination product 2a was produced in excellent
stereodefined electrophile, the halogen substructure can be yield with moderate diastereoselectivity (entry 4). Variations in the
9
used to reconstruct C–N, C–S, C–O bonds and similar bonds.
solvents showed that the use of 1,2-dichloroethane gave a better
More recently, impressive progress in homogeneous catalysis diastereoselectivity of 2a than dichloromethane (entries 7–10).
1
0
has been made for dihalogenation of unsaturated compounds,
Further tuning of the reaction conditions demonstrated that a
but the dihalogenation of unsaturated phosphonates has never lower reaction temperature and catalyst loading could not main-
tain equal reactivity (entries 11 and 12). Other chloride sources
a
gave no better results in the reaction (entries 13 and 14). While the
gram-scale reaction of 1a gave 2a in comparable yield (entry 15),
diphenyl selenide was also isolated in 81% yield based on diphenyl
diselenide, which provided important insight into the mechanism
underlying the reaction.
College of Biological, Chemical Sciences and Engineering, Jiaxing University,
Jiaxing 314001, China. E-mail: xianghuazeng@mail.zjxu.edu.cn,
jlxie@mail.zjxu.edu.cn
b
State Key Laboratory of Coordination Chemistry, Nanjing University,
Nanjing 210093, China
1
13
31
†
Electronic supplementary information (ESI) available: H, C, P NMR spectra.
The scope of unsaturated phosphonates was examined under
these optimized conditions. First, the effects of the olefin group
CCDC 1448837 (5) and 1448838 (2s). For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c6nj00658b
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a
a
Table 1 Screening of reaction conditions
Table 2 Substrate scope of a,b-unsaturated phosphonates
‘
‘Cl’’ sources Cat.
dr
b
c
Entry (eq.)
(mol%) T (1C) Solvent Yield (%) (anti/syn)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
SO
SO
SO
SO
SO
SO
SO
SO
SO
SO
SO
SO
2
2
2
2
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
2
2
2
(1.1)
(1.1)
(1.1)
—
—
—
CH
CH
CH
CH
CH
CH
THF
CHCl
CCl
DCE
DCE
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
25
0
70
58
Trace
91
90
85
Trace
82
Trace
92
87
1 : 1
2 : 1
—
4 : 1
4 : 1
4 : 1
—
5 : 1
—
5 : 1
5 : 1
5 : 1
3 : 1
—
À20
À20
À20
À20
À20
À20
À20
À20
À25
À20
À20
À20
À20
(1.1) C1(5)
(1.1) C2(5)
(1.1) C3(5)
(1.1) C1(5)
(1.1) C1(5)
(1.1) C1(5)
(1.1) C1(5)
(1.1) C1(5)
3
4
d
0
1
2
3
4
5
(1.1) C1(2.5) DCE
79
45
Trace
90
NCS (2.2)
SOCl (1.1)
SO Cl
C1(5)
C1(5)
DCE
DCE
DCE
2
e
2
2
(1.1) C1(5)
5 : 1
a
Except where otherwise noted, the reactions were carried out by using
1
a (0.20 mmol) and sources of ‘‘Cl’’ with a catalyst in solvent (1.5 mL)
a
under an N
flash chromatography on SiO
spectroscopy analysis of the integral area of a-H or b-H. DCE = 1,2- no reaction. Determined by H NMR spectroscopy analysis of the
2
atmosphere for 5 min in a sealed reaction tube, followed by
Reaction conditions: 1 (0.20 mmol), SO Cl2 (0.22 mol), PhSeSePh
2
b
c
1
b
2
.
Isolated yield. Determined by H NMR (5 mol%), ClCH CH Cl (1.5 mL), À20 1C, 5 min, isolated yield. NR =
2
2
d
c
1
e
dichloroethane. Reaction was performed with 6 mmol of the 1a.
integral area of a-H or b-H.
were investigated. As illustrated in Table 2, a series of aryl-
substituted alkenes with electron-donating and -accepting
groups on the phenyl ring gave the desired products in excellent
yields and moderate diastereoselectivities (2a–2k) except for the
strong electron-acceptor of nitro (2l). Reactions with alkyl alkyne
such as benzyl except for strong electron-donating substituent
groups such as cyclohexyl (2p) also worked well (2o). Unfortu-
nately, typical heteroaryl-substituted substrates did not produce
the corresponding products (2m, 2n). For example, the 2-thienyl
substituted group underwent a,b- and a-substitution reactions
a
Table 3 Dichlorination of other unsaturated phosphonates
b
c
Entry Substrate
Product
Yield (%) dr
d
1
87
8 : 1
2
86
91
3 : 1
7 : 1
1
2
3
readily (2m), and 2-furanyl only gave a trace amount of the
target molecule (2n). Next, with regard to the phosphonate
a
Except where otherwise noted, the reactions were carried out with 3a–c
group, diisopropyl (2q), dibutyl (2r), and alkenylphosphine oxide (0.20 mmol), SO Cl2 (0.22 mol), PhSeSePh (5 mol%) and ClCH CH Cl
2
2
2
b
c
1
(
1.5 mL) at À20 1C for 5 min. Isolated yields. Determined by H NMR.
(2s, 2t) compounds were also compatible with this reaction with
d
Reaction carried out using 2.2 eq. of SO
2 2
Cl
at À20 1C for 1 h.
good yields and moderate diastereoselectivities. The solid state
structure of 2s was unambiguously characterized by single-
1
3
crystal X-ray crystallographic analysis (see the ESI†). It illus-
trated that the formation of anti-products was preferred in this ESI†) inspired by the isolation of diphenyl selenide in gram-
reaction system. scale reaction were performed to gain insight into the reaction
A series of additional experiments (Scheme 1 and Table S2,
To further demonstrate the power of this method, this mechanism. There was only a trace of 2a when 1a reacted with
chlorination method was applied to a,b,g,d-unsaturated phos- sulfuryl chloride and tetrabutylammonium chloride in the absence
phonate 3a, and alkynyl phosphonate 3b, and alkynyl phos- of the selenium catalyst. Additionally, there was only a trace of
phine oxide 3c were successfully produced in excellent yields product that could be obtained when using cyclohexene as the
with moderate diastereoselectivities as shown in Table 3. The substrate without adding the selenium catalyst (see Table S2,
1
0f
relative configuration of product 4a is syn. The products 4b ESI†). As shown in Scheme 1, intermediate 5 was produced
and 4c are E-selective, with E/Z ratios larger than 3 : 1. in excellent yields when diphenyl diselenide and diphenyl
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On the basis of experimental results and those reported in
previous work, here the plausible reaction mechanism shown
in Scheme 2 is proposed. First, PhSeSePh reacts with SO Cl to
2
2
generate (Ph) SeCl 5. Then (Ph) SeCl may add to the alkene,
2
2
2
2
+
possibly via the loss of chloride to generate (Ph) SeCl 6 as the
active electrophile,
form a seleniranium ion intermediate species 7. The nucleo-
philic ring-opening of 7 by a chloride ion would then furnish the
2
1
1b,15,17
which can then intercept the alkene to
1
8
(b-chloroalkyl)diphenylselenium chloride species 8. And the
subsequent invertive displacement of the Se(IV) nucleofuge with
the chloride ion would produce the anti-dichloride product,
1
9
releasing the selenium catalyst as PhSePh. To complete the
next catalytic cycle, the oxidation of PhSePh by Cl2 could
2 2 2
regenerate the (Ph) SeCl 5 catalyst. The amounts of Cl could
1
5,20
2 2
be generated from SO Cl .
Conclusions
In summary, the vicinal dichlorination of a,b-unsaturated phos-
phonates was developed using simple sulfuryl chloride as a source
of chloride and green diphenyl diselenide as a pre-catalyst.
A series of unsaturated phosphonates were smoothly trans-
formed to the corresponding products. Mechanistic studies
Scheme 1 Preliminary mechanistic studies.
2 2
suggested that the (Ph) SeCl intermediate may play a key role
selenide were reacted with sulfuryl chloride at room temperature
for 10 min (I, II). These results exclude the possible route for
the generation of PhSeCl as the active catalyst. When 5 and
3
diphenyl selenide were used as the catalysts, the dichlorination
products were obtained in good yields under standard conditions
in the diastereoselectivity of the product. Studies of asymmetric
catalysis and dichlorination of other type alkenes are currently
in progress in our group.
14
(
III, IV), respectively. In addition, the reaction also proceeded well
Experimental
General information
when only 5 was used as the chloride source (V). Furthermore,
the (Ph) SeCl species was detected in the reaction mixture
+
2
7
7
All non-aqueous reactions and manipulations were performed
by using standard Schlenk techniques. All solvents were dried
and degassed before use using standard methods and were
stored under a nitrogen atmosphere. NMR spectra were recorded
on Varian (400 MHz) and Bruker (600 MHz) spectrometers.
Chemical shifts were reported in parts per million (ppm) down-
field from TMS with the solvent resonance as the internal
standard. High resolution mass spectra (HRMS) were recorded
on Bruker solariX FT-ICR (ESI) and Waters LCT Premier XE (TOF)
mass spectrometers. X-ray crystallographic data were collected
on a Gemini diffractometer under graphite-monochromated
Mo Ka radiation (l = 0.71073 Å) at 293 K. Aldehyde, tetraethyl
methylenebis(phosphonate), organoselenium, solvents and other
materials were purchased from Energy Chemical. Sulfuryl chloride
(1a/SO Cl /PhSeSePh) by Se NMR and HRMS spectra (Fig. S2
2 2
1
5
and S3, ESI†). Therefore, these results may indicate that the
active catalyst in this reaction system was compound 5, which
was also characterized by X-ray crystallography.
1
6
21
was purchased from Xiya Reagent. Unsaturated phosphonates
and selenide compounds were synthesized according to the
literature procedure.
2
2
General procedure for the synthesis of products 2 and 4.
Unsaturated phosphonates 1 or 3 (0.2 mmol), PhSeSePh
(
0.01 mmol, 5 mol%), and ClCH CH Cl (1.5 mL) were added
2 2
to a 10 mL flask tube at À20 1C under a nitrogen atmosphere.
Then SO Cl (0.22 mmol) was added to the mixture and
2
2
stirred at À20 1C for 5 min. The solvent was evaporated
Scheme 2 Plausible reaction mechanism.
under reduced pressure and the residue was purified by flash
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chromatography on silica gel (petroleum ether/ethyl acetate = 4/1) 131.6, 129.6, 123.1, 64.6 (d, J = 6 Hz), 63.2 (d, J = 7 Hz),
to afford the products.
61.7 (d, J = 3 Hz), 58.6, 57.1, 16.2 (dd, J
1
= 6 Hz, J
2
= 27 Hz).
3
1
General procedure for the synthesis of diphenylselenium
dichloride (5). To a stirred solution of PhSeSePh or PhSePh C H Cl PO ([M + H] ): 344.9975, found 344.9978.
P NMR (CDCl , 162 MHz) d = 15.16. HRMS m/z (ESI): calcd for
3
+
1
2
17
3
3
(
1 mmol) in ClCH CH Cl (5 mL) at room temperature under a
(trans)-Diethyl(1,2-dichloro-2-(3,4-dichlorophenyl)ethyl)phos-
2
2
1
nitrogen atmosphere was added SO
resulting mixture was stirred for 10 min. The solvent was (CDCl
removed under reduced pressure and the crude product was 1H), 7.32 (q, J
recrystallized in MeCN as a light yellow crystal. 4.19–4.31 (m, 3H), 3.97–4.10 (m, 2H), 1.33 (t, J = 7.0 Hz, 3H), 1.21
trans)-Diethyl(1,2-dichloro-2-phenylethyl)phosphonate (2a). (t, J = 7.2 Hz, 3H). C NMR (CDCl
2
Cl
2
(1.1 mmol). Then the phonate (2f). Colorless oil (69 mg, 91%, dr = 5 : 1). H NMR
, 400 MHz) d = 7.59 (d, J = 2.0 Hz, 1H), 7.45 (d, J = 8.4 Hz,
= 2.4 Hz, J = 6.4 Hz, 1H), 5.40 (t, J = 5.2 Hz, 1H),
3
1
2
1
3
(
3
, 100 MHz) d = 137.8 (d, J =
1
Colorless oil (57 mg, 92%, dr = 5 : 1). H NMR (CDCl , 400 MHz) 8 Hz), 133.2, 132.6, 130.3, 129.9, 127.2, 64.7 (d, J = 7 Hz), 63.3
3
d = 7.47–7.49 (m, 2H), 7.34–7.38 (m, 3H), 5.46 (t, J = 5.4 Hz, 1H), (d, J = 7 Hz), 60.7 (d, J = 2 Hz), 58.4, 56.9, 16.2 (dd, J = 6 Hz,
1
3
1
4
.20–4.23 (m, 3H), 3.97–4.08 (m, 1H), 3.86–3.96 (m, 1H), 1.31 (t, J2 = 27 Hz). P NMR (CDCl , 162 MHz) d = 14.88. HRMS m/z (ESI):
3
1
3
+
J = 7.2 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H). C NMR (CDCl
3
, 100 MHz) calcd for C12
4 3
H16Cl PO ([M + H] ): 378.9586, found 378.9585.
d = 144.9 (d, J = 16 Hz), 137.8 (d, J = 7 Hz), 129.0, 128.4, 127.8, 64.5
(trans)-Diethyl(1,2-dichloro-2-(2-chlorophenyl)ethyl)phos-
1
(
d, J = 6 Hz), 63.2 (d, J = 7 Hz), 62.4 (d, J = 3 Hz), 58.9, 57.4, 16.2 phonate (2g). Colorless oil (63 mg, 92%, dr = 10 : 1). H NMR
31
(dd, J
1
= 6 Hz, J
2
= 24 Hz). P NMR (CDCl
3
, 162 MHz) d = 15.46. (CDCl
3
, 400 MHz) d = 7.71 (q, J
1
= 1.6 Hz, J
2
= 6.0 Hz, 1H), 7.24–7.27
= 1.6 Hz, J = 14.0 Hz,
1H), 4.14–4.17 (m, 4H), 1.32 (m, 6H). C NMR (CDCl , 100 MHz)
+
HRMS m/z (ESI): calcd for C12
H17Cl
2
NaPO
3
([M + Na] ): 333.0185, (m, 3H), 6.03 (t, J = 4.4 Hz, 1H), 4.40 (dd, J
1
2
13
found 333.0198.
3
(
trans)-Diethyl(1,2-dichloro-2-(p-tolyl)ethyl)phosphonate (2b). d = 134.9 (d, J = 4.4 Hz), 131.7, 131.0, 130.0, 129.5, 126.9, 64.3 (d,
1
Colorless oil (60 mg, 92%, dr = 5 : 1). H NMR (CDCl , 400 MHz) J = 7 Hz), 63.7 (d, J = 7 Hz), 60.8 (d, J = 2 Hz), 56.9, 55.3, 16.3 (dd, J =
3
1
3
1
d = 7.35 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.43 (t, J = 6 Hz, J
2
= 27 Hz). P NMR (CDCl
.2 Hz, 1H), 4.16–4.30 (m, 3H), 3.99–4.06 (m, 1H), 3.88–3.94 (m, (ESI): calcd for C12 PO ([M + H] ): 344.9975, found 344.9988.
H), 2.35 (s, 3H), 1.31 (t, J = 7.2 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H). (trans)-Diethyl (2-(4-bromophenyl)-1,2-dichloroethyl)phos-
3
, 162 MHz) d = 15.35. HRMS m/z
+
5
1
H
17Cl
3
3
1
3
1
C NMR (CDCl
3
, 100 MHz) d = 139.0, 135.0, 129.1, 127.7, 64.4 (d, phonate (2h). Colorless oil (70 mg, 90%, dr = 5 : 1). H NMR
, 400 MHz) d = 7.47 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.4 Hz,
dd, J = 6 Hz, J = 20 Hz). P NMR (CDCl , 162 MHz) d = 15.57. 2H), 5.37 (t, J = 5.6 Hz, 1H), 4.17–4.24 (m, 3H), 3.95–4.02 (m,
J = 7 Hz), 63.1 (d, J = 7 Hz), 62.3 (d, J = 3 Hz), 59.0, 57.4, 21.5, 16.2 (CDCl
3
3
1
(
1
2
3
+
HRMS m/z (ESI): calcd for C H Cl NaPO ([M + Na] ): 347.0341, 1H), 3.91–3.93 (m, 1H), 1.29 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.2 Hz,
found 347.0346.
1
3
19
2
3
1
3
3H). C NMR (CDCl , 100 MHz) d = 136.8 (d, J = 7 Hz), 131.6,
3
(
trans)-Diethyl(1,2-dichloro-2-(m-tolyl)ethyl)phosphonate (2c). 129.6, 123.1, 64.7 (d, J = 7 Hz), 63.3 (d, J = 7 Hz), 61.6 (d, J =
1
31
Colorless oil (61 mg, 93%, dr = 4 : 1). H NMR (CDCl
d = 7.19–7.27 (m, 3H), 7.11 (d, J = 6.4 Hz, 1H), 5.39 (t, J = 5.2 Hz, 162 MHz) d = 15.14. HRMS m/z (ESI): calcd for C12
H), 4.13–4.28 (m, 3H), 3.96–4.05 (m, 1H), 3.83–3.90 (m, 1H), 2.32 ([M + H] ): 388.9470, found 388.9472.
s, 3H), 1.27 (t, J = 7.2 Hz, 3H), 1.14 (t, J = 7.2 Hz, 3H). C NMR
3
, 400 MHz) 2 Hz), 58.6, 57.1, 16.2 (dd, J
1
= 6 Hz, J
2
= 27 Hz). P NMR (CDCl
BrPO
3
,
H
17Cl
2
3
+
1
(
(
13
(trans)-Diethyl (2-(3-bromophenyl)-1,2-dichloroethyl)phos-
1
CDCl , 100 MHz) d = 138.1, 137.8 (d, J = 7 Hz), 129.7, 128.4, 128.3, phonate (2i). Colorless oil (71 mg, 91%, dr = 5 : 1). H NMR
3
1
5
1
24.9, 64.5 (d, J = 6 Hz), 63.2 (d, J = 7 Hz), 62.3 (d, J = 3 Hz), 58.9, (CDCl , 400 MHz) d = 7.60 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.38
3
3
1
7.3, 21.3, 16.2 (dd, J = 6 Hz, J = 25 Hz). P NMR (CDCl3, (d, J = 8.0 Hz, 1H), 7.20–7.24 (m, 1H), 5.37 (t, J = 5.6 Hz, 1H),
1
2
62 MHz) d = 15.55. HRMS m/z (ESI): calcd for C13
H
19Cl
2
NaPO
3
4.15–4.24 (m, 3H), 3.99–4.06 (m, 1H), 3.90–3.97 (m, 1H), 1.29
(t, J = 7.2 Hz, 3H), 1.17 (t, J = 6.8 Hz, 3H). C NMR (CDCl ,
3
+
13
([M + Na] ): 347.0341, found 347.0358.
(
trans)-Diethyl(1,2-dichloro-2-(o-tolyl)ethyl)phosphonate (2d). 100 MHz) d = 139.9 (d, J = 7 Hz), 132.1, 130.9, 129.9, 126.6,
1
Colorless oil (59 mg, 90%, dr = 5 : 1). H NMR (CDCl
d = 7.52–7.58 (m, 1H), 7.20–7.21 (m, 2H), 7.12–7.19 (m, 1H),5.65 57.0, 16.2 (dd, J
3
, 400 MHz) 122.3, 64.6 (d, J = 7 Hz), 63.3 (d, J = 7 Hz), 61.3 (d, J = 3 Hz), 58.6,
3
1
1
= 6 Hz, J
2 3
= 24 Hz). P NMR (CDCl , 162 MHz)
(
t, J = 6.0 Hz, 1H), 4.29–4.34 (m, 1H),4.13–4.22 (m, 2H), 3.91–3.96 d = 15.09. HRMS m/z (ESI): calcd for C H Cl BrNaPO
1
2
16
2
3
+
(m, 1H), 3.73–3.90 (m, 1H), 2.41 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), ([M + Na] ): 410.9290, found 410.9301.
1
3
1
.10 (t, J = 7.2 Hz, 3H). C NMR (CDCl , 100 MHz) d = 144.0 (d,
(trans)-Diethyl(1,2-dichloro-2-(naphthalen-1-yl)ethyl)phos-
3
1
J = 16 Hz), 136.1 (d, J = 6 Hz), 135.0, 130.6, 128.7 (d, J = 17 Hz), phonate (2j). Colorless oil (65 mg, 90%, dr = 5 : 1). H NMR
1
5
1
3
26.2, 64.5 (d, J = 7 Hz), 63.1 (d, J = 7 Hz), 59.0 (d, J = 4 Hz), 58.0, (CDCl , 400 MHz) d = 8.04 (d, J = 8.4 Hz, 1H), 7.82–7.88 (m, 3H),
3
1
6.4, 19.3, 16.2 (dd, J
62 MHz) d = 15.72. HRMS m/z (ESI): calcd for C13
1
= 6 Hz, J
2
= 26 Hz). P NMR (CDCl
NaPO
3
,
7.55–7.62 (m, 1H), 7.48–7.50 (m, 2H), 6.38 (s, 1H), 4.49–4.52 (m,
H
19Cl
2
3
1H), 4.17–4.29 (m, 2H), 3.92–4.02 (m, 2H), 1.28 (t, J = 7.0 Hz,
+
13
([M + Na] ): 347.0341, found 347.0354.
3
3H), 1.13 (t, J = 6.0 Hz, 3H). C NMR (CDCl , 100 MHz) d = 133.7,
(
trans)-Diethyl (1,2-dichloro-2-(4-chlorophenyl)ethyl)phos- 132.8 (d, J = 9 Hz), 129.7, 129.3, 127.5, 127.0, 125.9, 125.1, 122.1,
1
phonate (2e). Colorless oil (61 mg, 88%, dr = 5 : 1). H NMR 64.5 (d, J = 7 Hz), 63.4 (d, J = 7 Hz), 57.8, 56.3, 16.2 (dd, J = 7 Hz, J =
CDCl , 400 MHz) d = 7.50 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 27 Hz). P NMR (CDCl , 162 MHz) d = 15.84. HRMS m/z (ESI): calcd
H), 5.40 (t, J = 5.6 Hz, 1H), 4.20–4.27 (m, 3H), 4.01–4.07 (m, for C16H19Cl NaPO ([M + Na] ): 383.0141, found 383.0149.
2 3
H), 3.92–4.00 (m, 1H), 1.32 (t, J = 7.2 Hz, 3H), 1.19 (t, J = 7.2 Hz,
1
2
31
(
3
3
+
2
1
3
(trans)-Diethyl(1,2-dichloro-2-(naphthalen-2-yl)ethyl)phos-
, 100 MHz) d = 136.8 (d, J = 7 Hz), phonate (2k). Colorless oil (61 mg, 85%, dr = 4 : 1). H NMR
1
3
1
H). C NMR (CDCl
3
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CDCl
Paper
1
(
3
, 400 MHz) d = 7.90 (s, 1H), 7.83 (d, J = 9.2 Hz, 3H), 7.55–
.58 (m, 1H), 7.49 (dd, J = 3.2 Hz, J
.6 Hz, 1H), 4.38 (dd, J = 6.4 Hz, J = 13.2 Hz, 1H), 4.17–4.24 (m, 4H), 7.24–7.27 (m, 3H), 5.92 (t, J = 4.0 Hz, 1H), 4.78 (dd, J =
H NMR (CDCl
3
, 400 MHz) d = 7.95–8.00 (m, 2H), 7.73–7.78
7
5
2
3
1
1
1
2
= 6.4 Hz, 2H), 5.60 (t, J = (m, 2H), 7.56–7.58 (m, 1H), 7.47–7.51 (m, 3H), 7.38–7.43 (m,
1
2
1
1
3
H), 3.90–3.94 (m, 1H), 3.74–3.80 (m, 1H), 1.26 (t, J = 7.2 Hz, 3.6 Hz, J = 7.2 Hz, 1H). C NMR (CDCl , 100 MHz) d = 138.1
H), 1.00 (t, J = 7.2 Hz, 3H). C NMR (CDCl , 100 MHz) d = (d, J = 7 Hz), 133.0 (d, J = 9 Hz), 132.3 (d, J = 17 Hz), 131.0 (d,
35.0 (d, J = 8 Hz), 133.4, 132.8, 128.3, 128.2, 127.6, 127.4, 126.8, J = 9 Hz), 128.9, 128.7, 128.6, 128.4, 128.2, 128.1, 127.8, 61.3,
3
26.6, 124.9, 64.5, 63.1 (d, J = 7 Hz), 62.8, 58.8, 57.3, 16.1 (dd, 60.4. P NMR (CDCl , 162 MHz) d = 28.93. HRMS m/z (ESI):
2
3
1
3
3
3
1
3
1
+
1 2 3 2
J = 6 Hz, J = 40 Hz). P NMR (CDCl , 162 MHz) d = 15.46. calcd for C20H17Cl PNaO ([M + Na] ): 397.0286, found 397.0291.
HRMS m/z (ESI): calcd for C16
+
H
20Cl
2
PO
3
([M + H] ): 361.0522,
(trans)-(1,2-Dichloro-2-(4-chlorophenyl)ethyl)diphenylphos-
found 361.0536.
phine oxide (2t). White solid (74 mg, 90%, dr = 4 : 1), mp 125–
1
(
E)-Diethyl(1,2-dichloro-2-(thiophen-2-yl)vinyl)phosphonate 127 1C. H NMR (CDCl , 400 MHz) d = 7.93 (dd, J = 8.0 Hz, J =
3
1
2
(
2m ) and (Z)-diethyl(1-chloro-2-(thiophen-2-yl)vinyl)phosphonate 11.6 Hz, 2H), 7.68–7.78 (m, 3H), 7.55–7.59 (m, 1H), 7.48–7.51
1
(
2m ). Inseparable mixtures (m /m = 1/1), colorless oil (52 mg, (m, 3H), 7.38–7.41 (m, 3H), 7.33 (d, J = 8.4 Hz, 2H), 7.17 (d, J =
2 1 2
1
13
8
7
4
4
1
1
6
7%). H NMR (CDCl
.76 (d, J = 13.6 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 7.16 (d, J = (CDCl
.0 Hz, 1H), 7.10 (t, J = 4.4 Hz, 1H), 6.92 (d, J = 4.0 Hz, 1H), 134.9, 132.7 (d, J = 9 Hz), 132.5, 131.9, 131.0 (d, J = 9 Hz), 129.3,
3
, 400 MHz) d = 7.91 (d, J = 14.0 Hz, 1H), 8.0 Hz, 1H), 5.83 (t, J = 4.0 Hz, 1H), 4.76–4.78 (m, 1H). C NMR
3
, 100 MHz) d = 146.3 (d, J = 9 Hz), 136.3 (d, J = 7 Hz),
1
3
31
.07–4.29 (m, 8H), 1.34 (t, J = 7.2 Hz, 12H). C NMR (CDCl
00 MHz) d = 135.3, 135.1, 135.0, 134.8, 133.7, 133.0, 130.7, d = 29.12. HRMS m/z (ESI): calcd for C20
26.8, 126.6, 126.0, 63.1 (dd, J = 5 Hz, J = 10 Hz), 16.2 (d, J = 409.0077, found 409.0089.
3
,
128.7, 128.6, 128.5, 128.2, 61.0, 60.3. P NMR (CDCl
3
, 162 MHz)
+
H17Cl
3
PO ([M + H] ):
1
2
3
1
Hz). P NMR (CDCl , 162 MHz) d = 10.94, 10.37. {HRMS(2m )
(syn)-Diethyl(1,2,3,4-tetrachloro-4-phenylbutyl)phosphonate
3
1
+
1
m/z (ESI): calcd for C H Cl PSO ([M + H] ): 314.9773, found (4a). Colorless oil (71 mg, 87%, dr = 8 : 1). H NMR (CDCl3,
3
2
1
0
14
2
3
+
14.9776}, {HRMS(2m
81.0163, found 281.0163}.
trans)-Diethyl(1,2-dichloro-3-phenylpropyl)phosphonate (2o).
2
) m/z (ESI): calcd for C10
H
15ClPSO
3
([M + H] ): 400 MHz) d = 7.46 (d, J = 7.6 Hz, 2H), 7.30–7.40 (m, 3H), 5.87 (s,
1H), 5.10 (d, J = 10.0 Hz, 1H), 4.86 (d, J = 14.0 Hz, 1H), 4.57 (dd,
(
J
1
= 10.0 Hz, J
, 400 MHz) 1H), 1.31–1.38 (m, 6H). C NMR (CDCl
d = 7.34–7.43 (m, 5H), 5.34 (d, J = 3.6 Hz, 0.6H), 5.13 (d, J = 6.8 Hz, 128.4, 128.3, 127.7, 66.8, 64.8 (d, J = 3 Hz), 64.5 (d, J = 6 Hz), 63.4
2
= 26.8 Hz, 1H), 4.22–4.34 (m, 3H), 4.12–4.19 (m,
1
13
Colorless oil (59 mg, 91%, dr = 1 : 1). H NMR (CDCl
3
3
, 100 MHz) d = 137.1,
0
2
1
1
.5H), 4.53–4.58 (m, 1H), 4.25–4.29 (m, 1H), 4.08–4.15 (m, 3H), (d, J = 7 Hz), 62.8, 53.1, 51.5, 16.3 (dd, J = 6 Hz, J = 11 Hz).
1 2
3
1
.52–2.63 (m, 1H), 2.17–2.32 (m, 1H), 1.40 (t, J = 7.2 Hz, 1H), 1.29–
P NMR (CDCl , 162 MHz) d = 14.63. HRMS m/z (ESI): calcd for
3
13
+
.35 (m, 5H). C NMR (CDCl , 100 MHz) d = 137.1, 129.0, 128.7, C H Cl PO ([M + H] ): 406.9899, found 406.9908.
3
14 20
4
3
28.4, 128.0, 126.5, 65.7 (d, J = 11 Hz), 62.3, 60.0, 33.2, 31.8, 16.4.
(E)-Diisopropyl(1,2-dichloro-2-phenylvinyl)phosphonate (4b).
3
1
1
P NMR (CDCl
PNaO
3
, 162 MHz) d = 25.57. HRMS m/z (ESI): calcd for Colorless oil (58 mg, 86%, dr = 3 : 1). H NMR (CDCl
([M + Na] ): 347.0341, found 347.0357.
3
, 400 MHz)
+
C
13
H
19Cl
2
3
d = 7.39–7.42 (m, 2H), 7.31–7.35 (m, 3H), 4.54–4.62 (m, 2H), 1.18
13
(
trans)-Diethyl(1,2-dichloro-2-phenylethyl)phosphonate (2q). (d, J = 6.4 Hz, 6H), 1.14 (d, J = 6.4 Hz, 6H). C NMR (CDCl
3
,
1
Colorless oil (61 mg, 90%, dr = 6 : 1). H NMR (CDCl
3
, 400 MHz) 100 MHz) d = 145.9 (d, J = 21 Hz), 137.0, 129.9, 129.0 (d, J = 2 Hz),
d = 7.42–7.45 (m, 2H), 7.30–7.35 (m, 3H), 5.42 (t, J = 5.2 Hz, 1H), 127.9, 123.7, 72.7 (d, J = 7 Hz), 23.8 (d, J = 4 Hz), 23.4 (d, J = 8 Hz).
3
1
4
.77–4.82 (m, 1H), 4.58–4.66 (m, 1H), 4.18–4.23 (m, 1H), 1.28
P NMR (CDCl , 162 MHz) d = 3.95. HRMS m/z (ESI): calcd for
3
+
(
d, J = 6.0 Hz, 6H), 1.23 (d, J = 7.2 Hz, 3H), 1.15 (d, J = 6.4 Hz, 3H). C H Cl PO ([M + H] ): 337.0522, found 337.0535.
1
4
20
2
3
1
3
C NMR (CDCl
3
, 100 MHz) d = 138.2 (d, J = 8 Hz), 128.9, 128.4,
(E)-(1,2-Dichloro-2-phenylvinyl)diphenylphosphine oxide (4c).
1
1
5
1
27.9, 73.3 (d, J = 7 Hz), 72.4 (d, J = 3 Hz), 62.5 (d, J = 3 Hz), 59.4, White solid (78 mg, 91%, dr = 7 : 1). H NMR (CDCl
3
, 400 MHz) d =
7.66–7.71 (m, 4H), 7.40–7.48 (m, 4H), 7.32–7.39 (m, 5H), 7.10–7.24
3
1
7.9, 23.7 (dt, J
1
= 6 Hz, J
2
= 13 Hz, J
3
= 42 Hz). P NMR (CDCl
3
,
13
62 MHz) d = 13.49. HRMS m/z (ESI): calcd for C14
H
21Cl
2
PnaO
3
(m, 2H). C NMR (CDCl
J = 2 Hz), 132.1 (d, J = 2 Hz), 131.7 (d, J = 10 Hz), 130.0, 129.4, 128.3 (d,
3
, 100 MHz) d = 148.1 (d, J = 21 Hz), 136.0 (d,
+
([M + Na] ): 361.0498, found 361.0503.
31
(
trans)-Dibutyl(1,2-dichloro-2-phenylethyl)phosphonate (2r). J = 13 Hz), 127.8. P NMR (CDCl , 162 MHz) d = 25.88. HRMS m/z
Colorless oil (68 mg, 92%, dr = 10 : 1). H NMR (CDCl , 400 MHz) (ESI): calcd for C H Cl PO ([M + H] ): 373.0310, found 373.0322.
3
1
+
3
20 16
2
1
1b
d = 7.46–7.49 (m, 2H), 7.34–7.39 (m, 3H), 5.46 (t, J = 5.2 Hz, 1H),
4
3
(
Diphenylselenium dichloride (5) . Light yellow solid (289 mg,
1
.30 (dd, J
1
= 6.0 Hz, J
2
= 13.2 Hz, 1H), 4.10–4.21 (m, 2H), 3.92– 95%). H NMR (CDCl
3
, 400 MHz) d = 7.99 (s, 4H), 7.53–7.69 (m, 6H).
13
.99 (m, 1H), 3.78–3.84 (m, 1H), 1.61–1.65 (m, 2H), 1.41–1.50
C NMR (CDCl
3
, 100 MHz) d = 133.6, 131.8, 131.4, 129.8. HRMS m/z
+
2
m, 2H), 1.35–1.39 (m, 2H), 1.27–1.32 (m, 2H), 0.87–0.95 (m, (ESI): calcd for C12H11Cl Se ([M + H] ): 304,9398, found 304.9400.
1
3
6
H). C NMR (CDCl
3
, 100 MHz) d = 137.8 (d, J = 8 Hz), 129.0,
128.4, 127.8, 68.2 (d, J = 8 Hz), 66.9 (d, J = 7 Hz), 62.4 (d,
J = 3 Hz), 59.0, 57.4, 32.3 (dd, J = 6 Hz, J = 16 Hz), 18.5 (d, J =
1
2
Acknowledgements
3
1
6
Hz), 13.4 (d, J = 6 Hz). P NMR (CDCl , 162 MHz) d = 15.45.
3
+
HRMS m/z (ESI): calcd for C H Cl PO ([M + H] ): 367.0991, Financial support from the Jiaxing Science Project (No.
1
6
26
2
3
found 367.1002.
trans)-(1,2-Dichloro-2-phenylethyl)diphenylphosphine oxide 70513022) and the National Natural Science Foundation of
2s). White solid (64 mg, 86%, dr = 8 : 1), mp 113–114 1C. China (No. 21371078 and 21401077) is gratefully acknowledged.
2015AY11014), a Start-up Grant of Jiaxing University (No.
(
(
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