Synthesis of vinylphosphonates and its first exploration of bioactivity

Article abstract of DOI:10.2174/157017811796064467

Phosphonation of β-nitro-alkene with triethyl phosphite was achieved under microwave irradiation using CH₂Cl₂ as the solvent in the absence of catalyst with moderate to high yields (up to 90%). This method of formation of carbonphosphor bonds is simple, mild, convenient and effective. Synchronously, a number of vinylphosphonates derivatives were synthesized and evaluated biologically preliminary.

Full text of DOI:10.2174/157017811796064467

416
Letters in Organic Chemistry, 2011, 8, 416-422
Synthesis of Vinylphosphonates and its First Exploration of Bioactivity
Sheng-Nan Lia, Lan-Ting Xu a, Yue Chenb, Ju-Lian Lia and Ling He*,a
aKey Laboratory of Drug-Targeting and Drug-Delivery Systems of the Ministry of Education, Department of Medicinal
b
Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, P.R. China; Department
of Nuclear Medicine, Affiliated Hospital, Luzhou Medical College, No. 25 Taiping Street, Luzhou, Sichuan, 646000,
P.R. China
Received December 18, 2010: Revised April 13, 2011: Accepted April 13, 2011
Abstract: Phosphonation of ꢀ-nitro-alkene with triethyl phosphite was achieved under microwave irradiation using CH2Cl2
as the solvent in the absence of catalyst with moderate to high yields (up to 90%). This method of formation of carbon-
phosphor bonds is simple, mild, convenient and effective. Synchronously, a number of vinylphosphonates derivatives
were synthesized and evaluated biologically preliminary.
Keywords: Vinylphosphonate, phosphonation, triethyl phosphite, B-nitro-alkene.
INTRODUCTION
RESULTS AND DISCUSSION
The development of efficient and convenient procedures
to construct various organophosphorus compounds,
particularly the formation of phosphorus-alkene bonds, is a
very attractive process. Phosphorus-alkene bonds, such as
those in vinylphosphonates, have been widely used in
organic synthesis, especially in asymmetric synthesis. First,
we can use the vinylphosphonates as a building block to
synthesize a large number of enantioselective compounds
through asymmetric Michael addition [1, 2]. Second,
vinylphosphonates can also be used as intermediates for the
synthesis of biologically active compounds [3, 4].
Additionally, vinyl-phosphonates play an important role in
asymmetric hydrogenations [5-8]. Moreover, it also can be
used in cycloaddition reactions [9, 10]. And, many other
chemical synthesis use vinylphosphonates to react [11-16].
Therefore, chemical synthesis research as part of the
development of new pharmacologically active compounds is
of great significance for the preparation of vinylphos-
phonates.
With an interest in synthesizing potentially bioactive
nitrogenous compounds, we focused on the application and
prolongation of active nitrogen sources and development of
the catalyzed amidation. Although a series of studies on
catalyzed amidation reactions by transition-metals have
demonstrated that the method could effectively form carbon-
nitrogen bonds in the presence of oxidant [28], the amidation
reactions of using nitro-compound as a nitrogen source under
the presence of deoxidant are sparse in the literature. As part
of our continuing interest in catalyzed amidation and
continuation of substrate, we would like to establish an
effective reaction system for the amidation of sp2 C-H and
sp3 C-H using nitro-compound as a nitrogen source. Initially,
we investigated the reaction of (E)-ꢀ-nitro-styrenes with
(EtO)3P in CH2Cl2 under microwave irradiation. We hoped
that the inter- or intra-molecular amidation of the alkenes or
arenes catalyzed by the transition metal using triethyl
phosphite as deoxidizer would form carbon-nitrogen bonds
(Scheme 2). However, only the carbon-phosphor bond was
formed (Scheme 1). This prompted us to undertake further
investigation, and it was finally found that organophosphorus
compounds were produced with high yield via a one pot
reaction of (E)-(2-nitrovinyl)benzene and (EtO)3P under
microwave irradiation using CH2Cl2 as the solvent without
catalyst. The yield of this reaction was 84% yield (Table 2,
entry 1).
At present, several methods for the preparation of
vinylphosphonates have been developed. As reported in the
literature, the preparation of these compounds is mainly done
using the Horner-Wadsworth-Emmons reaction [16],
Oxidative addition [17-19], Substitution reactions [20-22],
Ivanov reaction [23], the catalytic reaction with metal
catalysts [24-26] and other methods [27]. For example, in
[24], they used platinum as catalyst at high temperature for a
long time. For these metal catalyst reactions [7], some
expensive metal catalysts are used. As a result, we have been
trying to find a convenient method of vinylphosphonates
synthesis that is simple, can be completed under mild
experimental conditions and gives a high yield.
Next, we began to turn our attention to our substrates
coupling with (EtO)3P that for the vinylphosphonates. As a
model, we focused on the coupling of (E)-(2-nitrovinyl)
benzene with (EtO)3P. First, the phosphonation of alkenes
was investigated under microwave irradiation or by
traditional heating. From the experimental results, we found
that longer reaction times were needed to achieve a similar
yield with conventional refluxing. Thus, the results reveal
that microwave irradiation has the evident advantage of a
short reaction time over traditional heating. Second, we
investigated the effect of the solvent on the reaction (Table 1,
*Address correspondence to this author at the Key Laboratory of Drug-
Targeting and Drug-Delivery Systems of the Ministry of Education,
Department of Medicinal Chemistry, West China School of Pharmacy,
Sichuan University, Chengdu, Sichuan, 610041, P.R. China; Tel: +86 28
85503365; Fax: (+86)28 85502940; E-mail: lhe2001@sina.com
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

Synthesis of Vinylphosphonates
Letters in Organic Chemistry, 2011, Vol. 8, No. 6
417
O
O
O
P
NO2
(EtO)3P
CH2Cl2 / MWI
1
2
Scheme 1. Synthesis of Vinylphosphonates.
NO2
NH
R
R
R
R
N
N
H
O
Scheme 2. Hypothetical Intra-molecular Amidation of Alkenes and Arenes.
Table 1. Optimization of Reaction Conditionsa
entry
solvent
catalyst
Equiv
Yieldb [%]
1
2
-
-
3
3
3
3
3
3
3
3
3
3
40
84
CH2Cl2
DMF
-
3
-
-
trace
trace
0
4
THF
5
CH3CH2OH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
-
6
CuCl
FeCl2
FeC2O4
Cu(CF3SO4)2
SnCl2
84
7
84
8
-
9
trace
20~30
10
aReactions were performed under microwave irradiation (325 W) for 10 min ~30 min with a substrate to (EtO)3P ratio of 1:3. bIsolated yield.
entries 1-3). As a result, we discovered that we only obtain
the target molecule in CH2Cl2. The reactions carried out in N,
N-dimethyl formamide (DMF) or tetrahydrofuran (THF)
resulted in the formation of a trace amount of product after a
long reaction time. Finally, to evaluate the catalytic
efficiency of various catalysts, the reaction of (E)-(2-nitro
vinyl) benzene with (EtO)3P was studied using different
catalysts, including CuCl, FeCl2, and Cu(CF3SO4)2 (Table 1,
entries 4-6). When using CuCl or FeCl2 or when not using
catalyst, the same product yield was obtained. When using
Cu(CF3SO4)2 as the catalyst, we did not obtain the target
product.
entry 14). The reason for the poor conversion of 2d may be
the p-electrophilic substituent. The reason for the poor
conversion of 2n may be that the methyl-N causes steric
hindrance. Furthermore, as evident from the reactions of 2a-
k and 2o-p, when there is no substituent on the benzene ring,
the yield is the highest. On the whole, if there were
substituents on the benzene ring and the substituents were
electron-donating groups, the yield was higher, and when the
substituents were electron-withdrawing groups, the yield was
lower. In addition, the yield of the heterocyclic compounds
and linear compounds was higher than that of the benzenes.
Anyway, we found that the reaction gives the product with a
high yield when (E)-(2-nitrovinyl) benzene and (EtO)3P were
reacted under microwave irradiation in CH2Cl2. The
Moreover, we determined whether these reaction
conditions can be applied to other substrates. The results are
shown in Table 2. At this point, we have found a convenient
preparation method for vinylphosphonates. As shown in the
results, this approach was extensive. It can be applied to the
compounds such as, benzenes (Table 2, entries 2a-k, and 2o-
p) and heterocycles (Table 2, entries 2l-n). Second, almost
all of the substrates could produce their corresponding
product with high conversion and good yield by this method
except for substrates 2d (Table 2, entry 4) and 2n (Table 2,
1
structure of the product was confirmed by H-NMR, 13C-
NMR, 31P-NMR, and HRMS (specific data is shown in the
experimental section).
We then test the bioactivity of the vinylphosphonates
(include: Table 2, entry 1,2,5,6,8,9). The results are shown in
Table 3. We found that the vinylphosphonates really have
antitumor activity, includes anti-uterine cervix cancer (hela

418 Letters in Organic Chemistry, 2011, Vol. 8, No. 6
Li et al.
Table 2. Phosphonation of ꢀ-Nitro-Alkenes with (EtO)3P
O
O
O
NO2
P
(EtO)3P
MWI
R
CH2Cl2 /
R
3
4
Entry
R
Conversion [%]
Yield [%]
1
2
Ph
99
99
99
99
90
90
90
85
99
99
99
99
90
25
84
52
50
25
69
61
52
50
59
48
36-
42
74
54
p-ClC6H4
3
p-CH3C6H4
P-BrC6H4
4
5
p-HOC6H4
6
p-CH3OC6H4
m-ClC6H4
7
8
m-BrC6H4
9
3,4-(CH3O)2C6H3
3-CH3O-4-HOC6H3
3-CH3O-4-NO2C6H3
6-quinoline
10
11
12
13
14
3-indole
N-CH3-3-indole
O
15
16
77
90
99
90
O
O
O
Br
aAll reactions were carried out under microwave irradiation (325 W) with a molar ratio of compound 3 to (EtO)3P =1 3. bYield of isolated product.
cell), anti-breast cancer (MCF-7 cell) and anti-lung cancer
(A549 cell).
EXPERIMENTAL
General Procedures
NMR spectra were obtained on Bruker AVANCE 400
spectrometers (1H at 400MHz,13C at 400MHz and 31P at
400MHz). Chemical shifts are reported in ppm,using TMS as
an internal standard and CDCl3 as a solvent. 13C NMR
spectra are reported in ppm relative to the center line of a
triplet at 77.0 ppm of CDCl3. The mass spectra (ESI /
HRMS) were recorded on a Bruker Daltonics Data analysis
3.2 mass spectrometer. Column chromatography was carried
out using silica gel H (300-400 mesh). Aldehydes,
nitromethane, (EtO)3P, bases, CH2Cl2 are all analytical pure.
And (EtO)P3 was atmospheric distillated at its boiling
point,CH2Cl2 was redistillated by P2O5 before experimented.
CDCl3 was purchased from the Merk Company.
CONCLUSIONS
In summary, we have established a convenient and
effective method for the preparation of vinylphosphonates
based on the coupling of (EtO)3P with nitroethylene
derivatives under microwave irradiation without the addition
of a catalyst. This method is simple, is completed under mild
experimental conditions, and has a moderate to high yield.
We will work in the future to study whether this approach
can be applied to other more specific compounds. Further
investigation into the pharmacological activity of these
vinylphosphonates compounds is underway and will be
reported in due course.

Synthesis of Vinylphosphonates
Letters in Organic Chemistry, 2011, Vol. 8, No. 6
419
Table 3. The Cytotoxicity Test of the Vinylphosphonates
R
Concentration
(ug/ml)
hela cell (%)
48h
MCF-7 cell (%)
A549 cell (%)
48h
24h
72h
24h
48h
72h
24h
72h
Ph
10
50
no
no
no
no
no
no
no
no
no
no
no
33
no
no
no
no
no
11
no
no
no
12
no
no
15
30
10
27
5
no
no
no
20
no
no
12
10
20
4
6
no
11
15
no
10
5
12
no
18
13
no
1
17
no
14
20
no
11
13
8
22
no
10
7
8
no
no
No
10
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
5
100
10
p-ClC6H4
p-HOC6H4
p-CH3OC6H4
m-BrC6H4
6
50
no
11
no
no
no
20
5
no
4
100
10
4
no
no
no
8
50
9
23
10
4
100
10
11
14
13
4
21
15
12
27
10
7
50
10
13
no
no
no
no
no
17
15
20
2
16
4
100
10
20
no
no
no
no
no
70
17
20
23
6
10
6
no
no
no
no
no
no
50
15
12
8
100
10
7
18
1
9
13
21
25
3,4-
(CH3O)2C6H3
50
6
17
11
2
100
13
11
General Procedures for Synthesis of (E)-ꢀ-nitroethylenes
General Procedures for Cytotoxicity Test of the
Vinylphosphonates by CCK-8
To a stirred solution of corresponding aldehyde (10
mmol), CH3COONH4 (10mmol) in CH3COOH (8.4 mL) was
added nitromethane (30 mmol) dropwise. The mixture was
refluxing over a period of 2h. Then it was cooled to room
temperature and added ice water in the mixture. A
suspension began to form, and then filtered with suction on a
Büchner funnel, and the filter cake washed with ice water
until it began to be yellow. Finally, the yellow solid was
recrysted to give about 75-85% of pure product.
Preparation of Cancer Cells
Uterine cervix cancer Hela, breast carcinoma MCF-7,
lung cancer A549 cells lines (obtained from The Experiment
Center of Luzhou Medical College Affiliated Hospital) were
incubated in incubator (Thermo Eletron Corporation) at
37°C in a humidified atmosphere (95%) with 5% CO2., Hela
cells were cultured in DMEM (GIBCO). MCF-7 and A549
cells were cultured in PRMI1640 (GIBCO). Above of two
culture media were supplemented with 10% heat-inactivated
FBS (Lanzhou National HyClone Bio-Engineering Co., Ltd),
and 50 mg/ml penicillin/streptomycin. Growth and
morphology were monitored and cells were passaged when
they had reached 90% confluence. Cells were harvested in
logarithmic growth phase, and diluted with medium to a final
concentration of 7ꢁ104/ml.
General Procedures for Synthesis of Vinylphosphonates
To a stirred solution of corresponding (E)-ꢀ-nitrostyrenes
(3mmol) in CH2Cl2 (10 mL) was added (EtO)3P (15 mmol)
dropwise. The mixture was refluxed under microwave
irradiation (325W) for 5~30 min. The mixture was cooled to
room temperature and H2O2 was added in it until there was
no bubble. Then the reaction mixture was extracted with
EtOAc (3ꢀ10 mL) and saturated NaCl. The combined
organic layers were dried over Na2SO4 and concentrated
under reduced pressure to give orange oil. This crude
product was purified by column chromatography on silica
gel with petroleum ether/ethyl acetate as eluent to give
alkenylphosphonates.
Preparation of Prescreen Vinylphosphonate
The prescreen vinylphosphonate compounds were
dissolved by DMSO (Sigma), and diluted by serum-free
DMEM to concentration of 10ug/ml,50ug/ml,100ug/ml. The
final concentration of prescreen vinylphosphonate were
administered filtration sterilization through 0.22um bacteria
proof filter (MILLEX).

420 Letters in Organic Chemistry, 2011, Vol. 8, No. 6
Li et al.
Test of CCK-8 Method
Diethyl(1-(p-tolyl)vinyl)phosphonate
3
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.28 (t, JP-H
=
The CCK-8 method was performed flowering as
instruction of kits (Cells Counting Kit, Beyotime Institute of
Biotechnology, Shanghai). 100ul/well of cells suspensions
were seeded in 96 well polypropylene microplates (Corning)
at 7000cells/well, and incubated in a humidified incubator at
37°C with 5% CO2 for 24 hours to adherence. Added 10ul of
various concentrations (10ug/ml, 50ug/ml, and 100ug/ml) of
prescreen anticancer pharmacon into the plate well, which
containing 3 kind of cancer cells, respectively. Incubated the
plate for an appropriate length of time (24, 48, 72h) in the
incubator. Then, 10ul of CCK-8 solution were added to each
well of the 96 well plates. The plates were incubated at 37°C
with 5% CO2 for 3 hours. The absorbances at 450 nm were
determined using a microplate reader (Multiskan VAC,
Thermo Electron Corporation). DMEM containing 10%
CCK-8 was used as a cells control group. Paclitaxel injection
(Sichuan pharmaceutical Co. Ltd, Taiji Group) with
concentration of 5ug/ml, 20ug/ml was used as a positive
group. All of the concentration level of a variety of prescreen
vinylphosphonate has three parallel well. The growth
inhibiting ratio of each vinylphosphonate was calculated as
following formula.
7.2Hz, 6H), 2.35 (s, 3H), 4.10 (q, J = 6.8Hz, 4H), 6.13 (dd,
2JH-H = 1.0Hz, JP-H = 45.8Hz, 1H), 6.29 (dd, JH-H = 1.0Hz,
3JP-H = 21.8Hz, 1H), 7.16 (d, J = 8.0Hz, 2H), 7.42 (d, J =
7.6Hz, 2H); 13C-NMR (CDCl3, 100MHz) ꢁ (ppm): 15.1 (JP-C
= 24Hz), 20.1, 62.6 (JP-C = 24Hz), 126.2 (JP-C = 24Hz), 128.0,
129.9 (JP-C = 32Hz), 132.6 (JP-C = 48Hz), 137.3, 139.2.
3
2
Diethyl(1-(4-bromophenyl)vinyl)phosphonate
3
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.27 (t, JP-H
=
=
2
3
7.8Hz, 6H), 4.09-4.14 (m, 4H), 6.15 (dd, JH-H = 1.2, JP-H
2
3
45.4Hz, 1H), 6.34 (dd, JH-H = 1.2, JP-H = 22.0Hz, 1H), 7.41
(d, J = 7.6Hz, 2H), 7.49 (d, J = 8.4Hz, 2H); 13C-NMR
(CDCl3, 100MHz) ꢁ (ppm): 16.2 (JP-C = 24Hz), 62.4 (JP-C
24Hz), 122.6 (JP-C = 4Hz), 129.1 (JP-C = 24Hz), 131.6, 135.6
(JP-C = 60Hz), 138.0, 139.8.
=
Diethyl(1-(4-hydroxphenyl)vinyl)phosphonate
3
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.30 (t, JP-H
=
=
2
3
7.0Hz, 6H), 4.08-4.15 (m, 4H), 6.08 (dd, JH-H = 1.4, JP-H
2
3
46.2Hz,1H), 6.20 (dd, JH-H = 1.6Hz, JP-H = 22.0Hz, 1H),
6.78 (d, J = 8.4Hz,2H), 7.40 (dd, J = 1.2, 8.6Hz, 2H); 13C-
NMR (CDCl3, 100MHz) ꢁ (ppm): 16.1 (JP-C = 24Hz), 63.6
(JP-C = 24Hz), 114.3, 127.4 (JP-C = 24Hz), 128.3 (JP-C
=
The growth inhibiting ratio %=(1-OD of pharmacon / OD
of cells control group) ꢀ100%
64Hz), 131.6 (JP-C = 32Hz), 136.8, 140.6; HRMS (ESI):
Calcd. for: C12H1704P ([M+H]+): 257.0941, found: 257.0937.
Meanwhile, the growth and morphology, including form,
size, quantity, cells granulations of cancer cells of each well
were monitored and recorded by inverted microscope (Leica
DM IRB S70), with magnification of 10ꢀ20.
Diethyl(1-(4-methoxyphenyl)vinyl)phosphonate
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.23 (t, JP-H
=
=
3
7.2Hz, 6H), 3.78 (s, 3H), 4.00-4.10 (m, 4H), 6.07 (dd, 2JH-H
1.2, 3JP-H = 46.0Hz, 1H), 6.21 (dd, 3JH-H = 1.4, 3JP-H = 21.8Hz,
1H), 6.85 (d, J = 8.8Hz, 2H), 7.45 (dd, J = 1.2, 8.8Hz, 2H);
13C-NMR (CDCl3, 100MHz) ꢁ (ppm): 16.3 (JP-C = 24Hz),
55.3, 62.2 (JP-C = 24Hz), 113.8, 128.7(JP-C = 35Hz), 130.1 (JP-
C = 32Hz), 138.0, 139.7, 159.7; HRMS (ESI): Calcd. For:
C13H1904P ([M+H]+): 271.1101, found: 271.1093.
The Criterion of Selected
The growth inhibiting ratio exceed zero, and
corresponding with concentration level of prescreen
vinylphosphonate, and combined with the cancer cells’
growth inhibited, quantity decreased, normal form could not
be identified and so on.
Diethyl(1-(3-chlorophenyl)vinyl)phosphonate
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.28-1.35 (m, 6H),
4.07-4.14 (m, 4H), 6.15 (d, 3JP-H = 45.2Hz, 1H), 6.35 (d, 3JP-H
= 22.0Hz, 1H), 7.28 (dd, J = 8.0, 10.8Hz, 2H), 7.42 (d, J =
6.4Hz, 1H), 7.50 (s, 1H); 13C-NMR (CDCl3, 100MHz) ꢁ
Characterization of Compounds
Diethyl(1-phenylvinyl)phosphonate
1H-NMR(CDCl3, 400MHz) ꢁ (ppm):1.28 (t,3JP-H = 7.2Hz,
(ppm): 16.2 (JP-C = 16Hz), 62.4 (JP-C = 16Hz), 125.7 (JP-C
16Hz), 127.5 (JP-C = 16Hz), 128.3, 129.6, 132.5 (JP-C
25Hz), 134.3, 138.4 (JP-C = 60Hz), 139.4.
=
=
3
6H), 4.07-4.14 (m,4H),6.16 (d, JP-H = 45.6Hz, 1H),6.34
(d,3JP-H = 22.0Hz, 1H),7.35 (d, J=6.8Hz, 3H),7.53 (d,
J=6.8Hz, 2H); 13C-NMR (CDCl3, 100MHz) ꢁ (ppm): 16.3
(JP-C = 24Hz), 62.2 (JP-C = 24Hz), 127.7 (JP-C = 24Hz), 128.4
(JP-C = 64Hz), 131.7 (JP-C = 32Hz), 136.7 (JP-C = 48Hz),
138.9, 140.7; MS: Calcd. for: C12H1703P ([M+Na]+): 263.1,
found: 263.1; 31P-NMR (CDCl3, 400MHz) ꢁ (ppm): 16.9.
Diethyl(1-(3-bromophenyl)vinyl)phosphonate
3
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.30 (d, JP-H
=
=
2
3
6.8Hz, 6H), 4.09-4.16 (m, 4H), 6.16 (dd, JH-H = 1.2, JP-H
2
3
45.2Hz, 1H), 6.36 (dd, JH-H = 1.2, JP-H = 21.6Hz, 1H), 7.48
(td, J = 1.2, 10.4Hz, 3H), 7.66 (d, J = 1.6Hz, 1H); 13C-NMR
Diethyl(1-(4-chlorophenyl)vinyl)phosphonate
(CDCl3, 100MHz) ꢁ (ppm): 16.1 (JP-C = 16Hz), 63.6 (JP-C
=
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.29 (t, JP-H
=
=
3
16Hz), 122.4, 126.2 (JP-C = 16Hz), 130.0 (JP-C = 16Hz),
131.3, 132.6 (JP-C = 20Hz), 137.4, 138.7 (JP-C = 16Hz), 139.3;
HRMS (ESI M+): Calcd. for: C12H16Br03P ([M+H]+):
320.0126, found: 320.0171.
2
3
6.8Hz, 6H), 4.08-4.15 (m, 4H), 6.15 (dd, JH-H = 1.2, JP-H
2
3
45.4Hz, 1H), 6.34 (dd, JH-H = 1.2, JP-H = 22.0Hz, 1H), 7.33
(d, J = 8.0Hz, 2H), 7.48 (dd, J = 1.2, 8.6Hz, 2H); 13C-NMR
(CDCl3, 100MHz) ꢁ (ppm): 16.3 (JP-C = 24Hz), 62.3 (JP-C
=
Diethyl(1-(3,4-dimethoxyphenyl)vinyl)phosphonate
24Hz), 128.8 (JP-C = 24Hz), 131.8 (JP-C = 32Hz), 134.4, 135.2
(JP-C = 44Hz), 138.1, 139.8.
3
1H-NMR (CDCl3, 400MHz) ꢁ (ppm): 1.29 (t, JP-H
=
=
7.0Hz, 6H), 3.90 (s, 6H), 4.05-4.17 (m, 4H), 6.12 (dd, 2JH-H

Synthesis of Vinylphosphonates
Letters in Organic Chemistry, 2011, Vol. 8, No. 6
421
1.4, 3JP-H = 45.8Hz,, 1H), 6.25 (dd, 2JH-H = 1.4, 3JP-H = 21.8Hz,
1H), 6.85 (d, J = 8.0Hz, 1H), 7.11 (t, J = 1.6Hz, 1H), 7.13 (d,
J = 2.0Hz, 1H); 13C-NMR (CDCl3, 100MHz) ꢀ (ppm): 16.3
(JP-C = 28Hz), 55.9 (JP-C = 12Hz), 62.2 (JP-C = 24Hz), 110.8
(d, J = 8.4Hz, 1H), 7.03 (dt, J = 1.4, 4.52Hz, 2H) 13C-NMR
(CDCl3, 100MHz) ꢀ (ppm): 15.1 (JP-C = 24Hz), 61.2 (JP-C
24Hz), 62.6 (JP-C = 24Hz), 100.1, 106.9 (JP-C = 24Hz), 107.1,
120.3 (JP-C = 24Hz), 129.5 (JP-C = 32Hz), 137.3, 139.0, 146.6
(JP-C = 24Hz).
=
(JP-C = 24Hz), 120.1 (JP-C = 28Hz), 124.4, 129.3 (JP-C
48Hz), 130.2 (JP-C = 32Hz), 138.2, 139.9, 148.6.
=
Diethyl(1-(6-bromobenzo[d][1,3]dioxol-5-
Diethyl(1-(4-hydroxy-3-methoxyphenyl)vinyl)phosphonate
yl)vinyl)phosphon- ate
3
1H-NMR (CDCl3, 400MHz) ꢀ (ppm): 1.30 (t, JP-H
=
=
3
1H-NMR (CDCl3, 400MHz) ꢀ (ppm): 1.31 (t, JP-H
=
2.8Hz, 6H), 3.91 (s, 3H), 4.07-4.14 (m, 4H), 6.09 (dd, 2JH-H
3
6.8Hz, 6H), 4.13 (t, J = 7.2Hz, 4H), 5.97 (d, JP-H = 32Hz,
1.4, 3JP-H = 45.8Hz, 1H), 6.23 (dd, 2JH-H = 1.6, 3JP-H = 21.6Hz,
1H), 6.90 (d, J = 0.8Hz, 1H), 7.05 (dd, J = 1.6, 6.4Hz, 1H),
7.15 (s, 1H); 13C-NMR (CDCl3, 100MHz) ꢀ (ppm): 16.3 (JP-C
= 24Hz), 55.9, 62.3 (JP-C = 20Hz), 110.3 (JP-C = 24Hz, 114.6,
120.7 (JP-C = 28Hz), 128.5 (JP-C = 48Hz), 130.0 (JP-C = 32Hz),
138.1, 139.9, 146.4 (JP-C = 84Hz); HRMS (ESI M+): Calcd.
for: C13H1903P([M+H]+): 287.1053, found: 287.1043.
3
1H), 6.03(d, J = 4.0Hz, 2H), 6.54 (d, JP-H = 22.0Hz, 1H),
6.85 (s, 1H), 7.06 (s, 1H); 13C-NMR (CDCl3, 100MHz) ꢀ
(ppm): 16.1 (JP-C = 24Hz), 54.0 (JP-C = 24Hz), 63.5 (JP-C
24Hz), 101.9, 102.4 (JP-C = 24Hz), 110.1 (JP-C = 24Hz), 112.8
(JP-C = 32Hz), 135.6, 147.0, 148.0, 149.0 (JP-C = 24Hz).
=
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7.0Hz, 6H), 4.08-4.17 (m, 4H), 6.33 (dd, JH-H = 1.4, JP-H
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3
2
3
1.2, JP-H = 22.8Hz,1H), 6.40 (dd, JH-H = 1.2, JP-H = 48.2Hz,
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2
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