A quaternary ammonium salt [H-dabco][AcO]: As a recyclable and highly efficient catalyst for the one-pot synthesis of β-phosphonomalonates

Article abstract of DOI:10.1039/c5ra02743h

A simple, green and highly efficient approach for the one-pot three-component synthesis of β-phosphonomalonates has been developed. In the presence of the quaternary ammonium salt catalysts, the β-phosphonomalonates were obtained in excellent yields within short times via tandem Knoevenagel-phospha-Michael reaction. The reaction of aldehydes/ketones, active methylene compounds, and diethyl phosphite performed at room temperature under solvent-free conditions. No column purification is required and the products can be purified by simple crystallization. The catalysts can be easily recovered and reused several times without significant activity loss. This journal is

Full text of DOI:10.1039/c5ra02743h

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Graphical Abstract
recyclable catalyst for oneꢀpot synthesis of βꢀphosphonomalonates via tandem
Knoevenagel–phosphaꢀMichael reaction.
A
OEt
P OEt
[H-dabco][AcO]
(3 mol%)
O
O
CN
O
OEt
OEt
+
+
H P
R1
R2
R1
X
CN
neat. r.t.
R2
X

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A quaternary ammonium salt [H-dabco][AcO]: as a recyclable and highly efficient catalyst
for the one-pot synthesis of β-phosphonomalonates
Ya-Qin Yu,b Da-Zhen Xu*,a
a
National Pesticide Engineering Research Center (Tianjin), Collaborative Innovation Center of Chemical
Science and Engineering (Tianjin), Nankai University, Tianjin 300071, People’s Republic of China
Fax: +86 22 2350 5948; E-mail: xudazhen@nankai.edu.cn
b
Key Laboratory for Water Environment and Resources, Tianjin Normal University, Tianjin, 300387, People’s
Republic of China
Keywords
β-phosphonomalonates, multicomponent reactions, quaternary ammonium salts, recycling, green chemistry
Abstract
A simple, green and highly efficient approach for the one-pot three-component synthesis of β-phosphonomalonates
has been developed. In the presence of the quaternary ammonium salt catalysts, the β-phosphonomalonates were
obtained in excellent yields within short times via tandem Knoevenagel–phospha-Michael reaction. The reaction of
aldehydes/ketones, active methylene compounds, and diethyl phosphite performed at room temperature under
solvent-free conditions. No column purification is required and the products can be purified by simple
crystallization. The catalysts can be easily recovered and reused several times without significant activity loss.
Introduction
The multi-component coupling reactions (MCRs), which enable the facile, automated and high throughput
generation of small organic molecules, are a powerful synthetic tool to access complex structures from simple
precursors via one-pot procedure.1 MCRs are highly important reactions and have been widely used in
pharmaceutical chemistry for the production of structural scaffolds and combinatorial libraries for drug discovery.2
The synthesis of phosphonates and their derivatives have attracted considerable attention over the last few years
due to their wide range of applications in material chemistry,3 catalysis4 and medicinal chemistry as enzyme
inhibitors,5 peptide mimics,6 antibiotics7 and pharmacological agents.8 As a result, various synthetic methods have
been developed for the preparation of phosphonates. One of the most promising tools for the synthesis of
β-phosphonomalonates involves the phosphorus–carbon (P–C) bond formation by phospha-Michael addition.9
These methods are mainly focused on the two-pot procedures in which the α, β-unsaturated malonates should be
prepared first in a separate step.10 The reports for one-pot synthesis of β-phosphonomalonates via tandem
Knoevenagel–phospha-Michael reaction are rare in the literature.11 However, there are still a lot of disadvantages
associated with these procedures, such as low yields, long reaction times, elevated temperature, special reaction
conditions, using hazardous organic solvents or unrecyclable catalysts. Even though, nearly all the methods were
based on the substrate of triethyl phosphite and few example employed diethyl phosphite,11d, 11e which fulfills the
criteria of atom economy, as the phosphorous component in this transformation. Therefore, a simple and green
procedure employing diethyl phosphite as the phosphorous component for one-pot synthesis of
β-phosphonomalonates with an efficient and reusable catalyst remains a major challenge in synthetic organic
chemistry.

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Ionic liquids (ILs) have attracted significant attention as ecofriendly media for many chemical and biochemical
transformations due to their unique physicochemical properties, such as non-inflammability, negligible vapour
pressure, reusability and high thermal stability.12 The functional ILs have also been synthesized and utilized as
recyclable catalysts for different reactions with good to excellent performance.13-17 Recently, We have reported a
series of ionic liquid catalysts based on the skeleton of 1,4-diazobicyclo [2.2.2] octane (DABCO) and they shown
to be very effective catalysts for the Michael addition reaction18 and Knoevenagel condensation.19 Other kinds of
functionalized ILs based on DABCO were also designed and invested in different reactions.20 As our continuing
interests in ionic liquid mediated organic reactions, here, we wish to disclose our study on using of the
DABCO-base quaternary ammonium salts (QASs) as highly efficient catalysts for the multi-component one-pot
synthesis of β-phosphonomalonates via tandem Knoevenagel–phospha-Michael reaction.
Results and discussion
The quaternary ammonium salts [H-dabco][AcO], [H-dabco]Cl, [C4-dabco]Br and [C8-dabco]Br were synthesized
according to the literature.[14(a)]
Fig. 1. Structures of the DABCO-base quaternary ammonium salts.
As can be seen from the results summarized in Table 1, the reaction of 4-methylbenzaldehyde (1a), malononitrile
(2a) and diethyl phosphite (3) was performed in THF at room temperature with 10 mol% of DABCO-base QASs
as the catalyst. All the catalysts tested exhibited good catalytic activity with the corresponding products obtained in
good to excellent yields (Table 1, entries 1-4). The QAS catalyst [H-dabco][AcO] promoted the tandem
Knoevenagel–phospha-Michael reaction for synthesis of β-phosphonomalonate 4a with better yield under the same
conditions (Table 1, entry 1 vs entries 2-4). The other QASs catalysts also gave good yields, but longer reaction
times were needed (Table 1, entries 2-4). Catalyst [H-dabco][AcO] was used as the catalyst of choice and
evaluated in different solvents. No better results were observed when the reaction performed in other solvent such
as CH2Cl2, CH3CN, Toluene or C2H5OH (Table 1, entries 5-8). It was found that, under neat conditions, the yield
of the corresponding β-phosphonomalonate 4a was obtained in 95% yield at room temperature within only 30
minutes (Table 1, entry 9). Without any solvents added, allowed the reactions to be performed in a very simple,
cheap and green manner. After completion of the reaction, the crude products solidified when water was added,
filtered and washed with cold water to remove the catalyst. The desired products could be purified by
crystallization, and no chromatographic technique was used for product purification. This procedure avoids using
large quantities of volatile organic solvents which is generally the main source of waste, and required less time for
this transformation. Then we tried to reduce the amount of the catalyst [H-dabco][AcO], the product 4a was
formed in nearly the same yields within 30 minutes when 5 mol% and 3 mol% catalyst were used (Table 1, entries
10 and 11). When we reduced the amount of the catalyst to 1 mol%, β-phosphonomalonate 4a could be also
obtained in high yield in 2 hours (Table 1, entry 12). The loading of diethyl phosphite could be reduced to 1 eq, but

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reaction time was changed to 4 hours (Table 1, entry 13). This reaction, performed under condition without anVyiew Article Online
DOI: 10.1039/C5RA02743H
catalyst, led to the formation of product 4a in a very low yield even after a long reaction time (Table 1, entry 14).
Table 1. One-pot reaction of benzaldehyde, malononitrile and diethyl phosphite under different conditionsa
Entry
1
Cat. (mol %)
Solvent (mL)
THF (1)
THF (1)
THF (1)
THF (1)
CH2Cl2 (1)
CH3CN (1)
Toluene (1)
C2H5OH (1)
neat
T (h)
2.5
6
Yieldb (%)
[H-dabco][AcO] (10)
[H-dabco]Cl (10)
[C4-dabco]Br (10)
[C8-dabco]Br (10)
[H-dabco][AcO] (10)
[H-dabco][AcO] (10)
[H-dabco][AcO] (10)
[H-dabco][AcO] (10)
[H-dabco][AcO] (10)
[H-dabco][AcO] (5)
[H-dabco][AcO] (3)
[H-dabco][AcO] (1)
[H-dabco][AcO] (3)
-
95
87
82
80
94
90
72
51
95
94
95
94
94
<5
2
3
6
4
6
5
2
6
2
7
4
8
6
9
0.5
0.5
0.5
2
10
11
12
13c
neat
neat
neat
neat
4
14
neat
24
a
Conditions: aromatic 4-methylbenzaldehyde (1a, 1 mmol), malononitrile (2a, 1 mmol), diethyl phosphite (3, 2
mmol), room temperature (25°C).
b Isolated yield.
c 1 mmol Diethyl phosphite was used.
To confirm the generality of the present method, next, the reactions of a variety of aldehydes (1) with active
methylene compounds (2) and diethyl phosphite (3) were examined in the presence of catalyst [H-dabco][AcO] (3
mol%) under neat conditions at room temperature. The results are summarized in Table 2. The reactions of
different substituted benzaldehydes containing electron withdrawing groups or donating groups with malononitrile
and diethyl phosphite were converted to the corresponding β-phosphonomalonates in good to excellent yields
(91–98%) within 15 to 100 minutes (Table 2, entries 1-18). Heteroaromatic aldehydes, such as
thiophene-2-carbaldehyde (1s) was also effective substrates to execute the tandem Knoevenagel–phospha-Michael
reaction in the presence of [H-dabco][AcO] (Table 2, entry 19). This catalytic system was successfully applied for
the reaction of aliphatic ketone 1t with malononitrile (2a) and diethyl phosphite (3) and produced the desired
products 4t in good yields (Table 2, entry 20). Ethyl cyanoacetate (2b), although the methylene group is less
activated than malononitrile, was readily reacted with different substituted benzaldehydes (1e, 1f, 1j) and diethyl
phosphite (3), and afforded the corresponding products (4u, 4v, 4w) in 90-97% yields (Table 2, entries 21-23).
OEt
P OEt
[H-dabco][AcO]
(3 mol%)
CN
O
R
O
OEt
OEt
+
+
R CHO
H P
X
CN
neat. r.t.
1
2
3
X
4

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Table 2. One-pot synthesis of different β-phosphonomalonates catalyzed by [H-dabco][AcO]a
Entry
1
R
X
Product
4a
4b
4c
T (min) Yieldb (%)
4-MeC6H4
4-t-BuC6H4
C6H5
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
30
35
45
60
25
40
15
20
30
15
20
35
35
25
15
40
40
100
20
120
95
93
97
91
95
95
96
93
98
91
95
93
97
96
93
95
97
94
96
91
2
3
4
4-MeOC6H4
4-ClC6H4
4d
4e
5
6
3-ClC6H4
4f
7
2-ClC6H4
4g
4h
4i
8
4-FC6H4
9
3-FC6H4
10
11
12
13
14
15
16
17
18
19
20
4-NO2C6H4
3-NO2C6H4
4-BrC6H4
4j
4k
4l
4-CNC6H4
3-Br-4-FC6H3
2,5-(MeO)2C6H3
2,4-Cl2C6H3
3,5-Br2C6H3
naphthalen-1-yl
thiophen-2-yl
4m
4n
4o
4p
4q
4r
4s
4t
O
21c
22d
23e
4-ClC6H4
3-ClC6H4
4-NO2C6H4
CO2Et
CO2Et
CO2Et
50
90
97
91
4u
4v
4w
18
160
a
Conditions: carbonyl compound (1, 1 mmol), active methylene compound (2, 1 mmol), diethyl phosphite (3, 2
mmol), room temperature (25°C), solvent-free conditions.
b Isolated yield.
c e d.r. = 2:1, according to NMR.
d d.r. = 3:2, according to NMR.
When diethyl phosphite (3) was replaced by triethyl phosphite (5) and reacted with aldehydes and malononitrile
under the same reaction conditions, affording a mixture of products 4g and 6 in a ratio of 2:1 (Scheme 1).
Compound 6 is probably formed via a five-member ring transition state between (EtO)2P-O-CH2CH3 and C=C
bond, in which P and Et are inclined to add on the double bond simultaneously by a concerted process.

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Scheme 1.
The reusability of the catalyst was also examined for the synthesis of β-phosphonomalonates 4a. The catalyst
could be recycled after removing the products and more diethyl phosphite. The reaction of 4-methylbenzaldehyde,
malononitrile and diethyl phosphite gave the corresponding product 4a in similar yields over six cycles (Fig. 2).
Fig. 2. Recycling of the catalyst [H-dabco][AcO] for the synthesis of β-phosphonomalonate 4a.
We have developed an improved process for one-pot synthesis of β-phosphonomalonates which offered several
advantages over this procedure. This process performed at room temperature without any organic solvent, and the
catalyst was a quaternary ammonium salt, which was easily recovered and could be reused more than six times.
This is a simple and very mild reaction, which is readily amenable to large-scale synthesis. Using this procedure,
we tried this reaction out on a 0.1-mol scale, and 31.04 g of 4e was prepared in 95% yield. Therefore, this is an
easy access to these β-phosphonomalonates on a large scale via tandem Knoevenagel–phospha-Michael reaction,
using DABCO-base QASs as catalysts.
Scheme 2. Synthesis of β-phosphonomalonate 4e on 0.1-mol scale.
A plausible mechanism for the formation of β-phosphonomalonates in the presence of [H-dabco][AcO] is shown in

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Scheme 3. The process represents a typical tandem reaction by double-activation. In the initiation step of the
catalytic cycle, double-activation of the carbonylgroup of aldehydes and malononitrile by the catalyst
([H-dabco][AcO]) occurred to formation of Knoevenagel product. After that, the catalyst may activate both the
cyanogroup and diethyl phosphite, and take the H+ from diethyl phosphite by the top N and give the H+ attaching
to bottom N to –CN. Then a tautomerzation via H [1, 3] shift takes place to produce target product.
N
N
H
O
AcO
H
H
CN
CN
Ar
H
-H2O
O
CN
CN
O
P
Ar
H
+
CN
CN
H
Ar
EtO
EtO
OEt
OEt
H
N
N
O
H
P
AcO
N
N
CN
N
Ar
OEt
OEt
O
P
H
AcO
CN
Ar
CN
Scheme 3. A plausible mechanism for [H-dabco][AcO] catalytic synthesis of β-phosphonomalonates.
In order to show the unique catalytic behavior of [H-dabco][AcO] in the reactions, other catalysts like L-proline,
FeCl3 and catalysts (3 mol%) from reported literatures, including sodium sterarate,11(b) ZnO9(c), HClO4-SiO2,10(b)
NH4SO3H,11(b) I2,11(k) and pyridine,10(c) were also employed in the one-pot reaction of benzaldehyde, malononitrile
and diethyl phosphite. As shown in Table 3, [H-dabco][AcO] is the most effective catalyst for this tandem reaction,
leading to the formation of β-phosphonomalonate 4c in an excellent yield within very short time.
Table 3. Comparison of the catalytic activity of [H-dabco][AcO] with various reported catalysts for the synthesis
of β-phosphonomalonate 4c. a
Entry Catalyst
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
[H-dabco][AcO]
0.75
24
12
12
12
12
6
95
<5
62
27
51
43
78
19
59
L-proline
FeCl3
Sodium stearate
ZnO
HClO4-SiO2
NH4SO3H
I2
12
Pyridine
6
a Conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), diethyl phosphite (2 mmol) and catalyst (3 mol%),
room temperature (25°C), solvent-free conditions.
b Isolated yield.
Conclusion
In summary, it was demonstrated that the readily available, economic DABCO-base quaternary ammonium salts
(QASs) could behave as recyclable and highly efficient catalysts for the multi-component one-pot synthesis of

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β-phosphonomalonates via tandem Knoevenagel–phospha-Michael reaction. The reactions, performed under
solvent-free conditions at room temperature, allowed a very simple, clean synthesis of β-phosphonomalonates with
good to excellent yields in short times. The quaternary ammonium salts could be easily recovered and reused at
least for seven times without activity loss. The desired products could be easily separated and purified without any
requirement of column chromatographic purification. It is a simple route to large scale synthesis of
β-phosphonomalonates.
Experimental
General procedure for the synthesis of β-phosphonomalonates (4)
A 10-mL round bottomed flask was charged with aldehyde (1, 1 mmol), active methylene compound (2, 1 mmol),
diethyl phosphite (3, 2 mmol) and [H-dabco][AcO] (5.2mg, 0.03 mmol). The reaction mixture was stirred at room
temperature under air. After completion of the reaction (monitored by TLC), cold water (5 mL) was added, the
mixture was solidified in the round bottomed flask, filtered and washed with cold water to remove the catalyst and
diethyl phosphite. The crude products were purified by the crystallization technique and no column purification
was followed. The filtrate was extracted with ethyl acetate to remove diethyl phosphite, the quaternary ammonium
salt [H-dabco][AcO] was left, more water were evaporated from the salt under vacuum, and reused in the next
recycling run. The catalyst could be recovered and reused in the reaction for six times at least.
[1-(p-Tolyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4a)11(h)
1H NMR (400MHz, CDCl3): δ = 1.13 (3H, t, J = 6.8 Hz), 1.34 (3H, t, J = 6.8 Hz), 2.35 (3H, s), 3.59 (1H, dd, J1 =
8.0 Hz, J2 = 21.2 Hz), 3.72-3.82 (1H, m), 3.95-4.03 (1H, m), 4.09-4.18 (2H, m), 4.61 (1H, t, J = 8.8 Hz), 7.22 (2H,
d, J = 8.0 Hz), 7.36 (2H, d, J = 6.4 Hz).
[1-(4-(tert-Butyl)phenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4b)
1H NMR (400MHz, CDCl3): δ = 1.09 (3H, t, J = 7.2 Hz), 1.31 (9H, s), 1.32 (3H, t, J = 7.2 Hz), 3.66 (1H, dd, J1 =
8.0 Hz, J2 = 21.2 Hz), 3.73-3.83 (1H, m), 3.94-4.02 (1H, m), 4.10-4.20 (2H, m), 4.70 (1H, dd, J1 = 8.0 Hz, J2 = 8.8
Hz), 7.42 (4H, s). 13C NMR (100MHz, CDCl3): δ = 15.95 (d, 3JCP = 5.7 Hz), 16.19 (d, 3JCP = 5.8 Hz), 25.53, 31.15,
34.61, 43.91 (d, JCP = 143.4 Hz), 63.23 (d, 2JCP = 7.3 Hz), 64.15 (d, 2JCP = 7.0 Hz), 111.70, 126.20, 127.28, 129.05,
152.45. 31P NMR (162 MHz, CDCl3): δ 19.73. Anal. Calcd. for C18H25N2O3P: C, 62.06; H, 7.23; N, 8.04. Found:
C, 62.17; H, 7.15; N, 8.09.
[1-Phenyl-2,2-dicyanoethyl] phosphonic acid diethyl ester (4c)11(h)
1H NMR (400MHz, CDCl3): δ = 1.07 (3H, t, J = 7.2 Hz), 1.30 (3H, t, J = 6.8 Hz), 3.64 (1H, dd, J1 = 8.0 Hz, J2 =
21.2 Hz), 3.70-3.78 (1H, m), 3.91-4.01 (1H, m), 4.08-4.17 (2H, m), 4.69 (1H, t, J = 8.4 Hz), 7.37-7.40 (3H, m),
7.45-7.47 (2H, m).
[1-(4-Methoxyphenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4d)11(h)
1H NMR (400MHz, CDCl3): δ = 1.14 (3H, t, J = 6.8 Hz), 1.34 (3H, t, J = 6.8 Hz), 3.60 (1H, dd, J1 = 7.6 Hz, J2 =
21.2 Hz), 3.74-3.78 (1H, m), 3.81 (3H, m), 3.96-4.06 (1H, m), 4.11-4.20 (2H, m), 4.63 (1H, t, J = 8.4 Hz), 6.94
(2H, d, J = 8.8 Hz), 7.41 (2H, d, J = 7.2 Hz).
[1-(4-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4e)11(h)
1H NMR (400MHz, CDCl3): δ = 1.13 (3H, t, J = 7.2 Hz), 1.31 (3H, t, J = 7.2 Hz), 3.64 (1H, dd, J1 = 7.6 Hz, J2 =
21.6 Hz), 3.78-3.88 (1H, m), 3.96-4.06 (1H, m), 4.09-4.19 (2H, m), 4.68 (1H, t, J = 7.6 Hz), 7.38 (2H, d, J = 8.8
Hz), 7.43 (2H, d, J = 7.2 Hz).
[1-(3-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4f)11(h)
1H NMR (400MHz, CDCl3): δ = 1.16 (3H, t, J = 7.2 Hz), 1.33 (3H, t, J = 6.8 Hz), 3.75 (1H, dd, J1 = 8.0 Hz, J2 =
21.6 Hz), 3.83-3.93 (1H, m), 4.00-4.10 (1H, m), 4.14-4.23 (2H, m), 4.84 (1H, t, J = 7.6 Hz), 7.34-7.40 (2H, m),
7.42-7.45 (1H, m), 7.52 (1H, s).

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[1-(2-Chlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4g)11(h)
1H NMR (400MHz, CDCl3): δ = 1.11 (3H, t, J = 7.2 Hz), 1.36 (3H, t, J = 6.8 Hz), 3.76-3.86 (1H, m), 3.96-4.03
(1H, m), 4.17-4.26 (2H, m), 4.50 (1H, dd, J1 = 8.4 Hz, J2 = 21.6 Hz), 4.86 (1H, t, J = 8.8 Hz), 7.32-7.39 (2H, m),
7.46-7.50 (1H, m), 7.79-7.82 (1H, m).
[1-(4-Fluorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4h)11(j)
1H NMR (400MHz, CDCl3): δ = 1.15 (3H, t, J = 7.2 Hz), 1.34 (3H, t, J = 6.8 Hz), 3.70 (1H, dd, J1 = 7.6 Hz, J2 =
21.2 Hz), 3.80-3.90 (1H, m), 3.98-4.06 (1H, m), 4.15-4.22 (2H, m), 4.73 (1H, t, J = 7.6 Hz), 7.13 (2H, t, J = 8.4
Hz), 7.52 (2H, t, J = 6.4 Hz).
[1-(3-Fluorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4i)
1H NMR (400MHz, CDCl3): δ = 1.16 (3H, t, J = 6.8 Hz), 1.33 (3H, t, J = 7.2 Hz), 3.73 (1H, dd, J1 = 8.0 Hz, J2 =
21.6 Hz), 3.82-3.92 (1H, m), 4.00-4.10 (2H, m), 4.79 (1H, t, J = 8.8 Hz), 7.12 (1H, t, J = 8.4 Hz), 7.29 (2H, t, J =
3
3
8.0 Hz), 7.38-7.44 (1H, m). 13C NMR (100MHz, CDCl3): δ = 16.00 (d, JCP = 5.7 Hz), 16.12 (d, JCP = 5.9 Hz),
25.27, 43.83 (d, JCP = 143.2 Hz), 63.64 (d, 2JCP = 7.3 Hz), 64.46 (d, 2JCP = 7.0 Hz), 111.42, 116.64, 125.27, 131.05,
132.85, 161.55, 162.78 (d, JCF = 246.5 Hz). 31P NMR (162 MHz, CDCl3): δ 18.81. Anal. Calcd. for C14H16FN2O3P:
C, 54.20; H, 5.20; N, 9.03. Found: C, 54.31; H, 5.16; N, 9.11.
[1-(4-Nitrophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4j)9(c)
1H NMR (400MHz, CDCl3): δ = 1.22 (3H, t, J = 6.4 Hz), 1.37 (3H, t, J = 6.4 Hz), 3.88 (1H, dd, J1 = 6.8 Hz, J2 =
21.6 Hz), 3.94-4.00 (1H, m), 4.08 -4.14 (1H, m), 4.20-4.24 (2H, m), 4.81 (1H, t, J = 8.0 Hz), 7.76 (2H, d, J = 8.0
Hz), 7.73 (2H, d, J = 8.0 Hz).
[1-(3-Nitrophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4k)11(j)
1H NMR (400MHz, CDCl3): δ = 1.23 (3H, t, J = 6.8 Hz), 1.37 (3H, t, J = 6.4 Hz), 3.90 (1H, dd, J1 = 7.2 Hz, J2 =
21.6 Hz), 3.98-4.04 (1H, m), 4.10 -4.18 (1H, m), 4.21-4.24 (2H, m), 4.84 (1H, t, J = 8.0 Hz), 7.68 (1H, t, J = 8.4
Hz), 7.93 (1H, d, J = 7.2 Hz), 8.31 (1H, d, J = 8.0 Hz), 8.43 (1H, s).
[1-(4-Bromophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4l)11(h)
1H NMR (400MHz, CDCl3): δ = 1.17 (3H, t, J = 7.2 Hz), 1.33 (3H, t, J = 7.2 Hz), 3.65 (1H, dd, J1 = 7.6 Hz, J2 =
21.6 Hz), 3.81-3.91 (1H, m), 3.99-4.07 (1H, m), 4.12-4.21 (2H, m), 4.71 (1H, t, J = 8.4 Hz), 7.39 (2H, d, J = 7.2
Hz), 7.73 (2H, d, J = 8.4 Hz).
[1-(4-Cyanophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4m)11(e)
1H NMR (400MHz, CDCl3): δ = 1.17 (3H, t, J = 7.2 Hz), 1.33 (3H, t, J = 7.2 Hz), 3.75 (1H, dd, J1 = 7.6 Hz, J2 =
21.6 Hz), 3.85-3.95 (1H, m), 4.01-4.11 (1H, m), 4.11-4.22 (2H, m), 4.71 (1H, dd, J1 = 7.6 Hz, J2 = 8.8 Hz), 7.64
(2H, d, J = 6.8 Hz), 7.73 (2H, d, J = 8.0 Hz).
[1-(3-Bromo-4-fluorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4n)11(j)
1H NMR (400MHz, CDCl3): δ = 1.21 (3H, t, J = 7.2 Hz), 1.36 (3H, t, J = 7.2 Hz), 3.68 (1H, dd, J1 = 7.6 Hz, J2 =
21.6 Hz), 3.91-3.98 (1H, m), 4.06-4.12 (1H, m), 4.16-4.25 (2H, m), 4.72 (1H, dd, J1 = 7.6 Hz, J2 = 9.2 Hz), 7.21
(1H, t, J = 8.4 Hz), 7.48-7.52 (1H, m), 7.74 (1H, d, J = 6.4 Hz).
[1-(2,5-Dimethoxyphenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4o)11(i)
1H NMR (400MHz, CDCl3): δ = 1.15 (3H, t, J = 7.2 Hz), 1.34 (3H, t, J = 7.2 Hz), 3.76 (3H, s), 3.82 (3H, s),
3.84-3.92 (1H, m), 3.98-4.07 (1H, m), 4.10-4.22 (1H, m), 4.35 (1H, dd, J1 = 8.4 Hz, J2 = 21.6 Hz), 4.76 (1H, t, J =
9.2 Hz), 6.90 (2H, s), 7.18 (1H, s).
[1-(2,4-Dichlorophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4p)
1H NMR (400MHz, CDCl3): δ = 1.10 (3H, t, J = 7.2 Hz), 1.29 (3H, t, J = 7.2 Hz), 3.77-3.87 (1H, m), 3.91-4.03
(1H, m), 4.11-4.20 (2H, m), 4.35 (1H, dd, J1 = 8.0 Hz, J2 = 22.0 Hz), 4.69 (1H, t, J = 8.0 Hz), 7.29 (1H, dd, J1 = 2.4
Hz, J2 = 8.8 Hz), 7.45 (1H, t, J = 1.2 Hz), 7.69 (1H, dd, J1 = 1.6 Hz, J2 = 8.4 Hz). 13C NMR (100MHz, CDCl3): δ =
16.10 (d, 3JCP = 5.6 Hz), 16.22 (d, 3JCP = 5.8 Hz), 24.80, 38.94 (d, JCP = 144.4 Hz), 63.87 (d, 2JCP = 7.0 Hz), 64.49

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(d, 2JCP = 7.1 Hz), 111.02, 111.12, 127.33, 128.23, 130.18, 130.60, 135.92, 136.05. 31P NMR (162 MHzD, CODI: 1C0l.31)0:3Vδ9ie/wC5ARrtAic0le2O74nl3inHe
18.28. Anal. Calcd. for C14H15Cl2N2O3P: C, 46.56; H, 4.19; N, 7.76. Found: C, 46.49; H, 4.13; N, 7.69.
[1-(3,5-Dibromophenyl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4q)
1H NMR (400MHz, CDCl3): δ = 1.23 (3H, t, J = 6.8 Hz), 1.36 (3H, t, J = 6.8 Hz), 3.61 (1H, dd, J1 = 8.0 Hz, J2 =
21.6 Hz), 3.91-4.01 (1H, m), 4.06-4.14 (1H, m), 4.17-4.23 (1H, m), 4.69 (1H, t, J = 7.6 Hz), 7.60 (2H, s ), 7.74 (1H,
s). 13C NMR (100MHz, CDCl3): δ = 16.18 (d, 3JCP = 5.9 Hz), 16.26 (d, 3JCP = 6.0 Hz), 25.17, 43.54 (d, JCP = 142.7
2
2
Hz), 63.95 (d, JCP = 7.2 Hz), 64.66 (d, JCP = 7.0 Hz), 111.04, 123.75, 131.14, 134.36, 135.32. 31P NMR (162
MHz, CDCl3): δ 17.98. Anal. Calcd. for C14H15Br2N2O3P: C, 37.36; H, 3.36; N, 6.22. Found: C, 37.29; H, 3.31; N,
6.21.
[1-(Naphthalen-1-yl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4r)11(j)
1H NMR (400MHz, CDCl3): δ = 0.80 (3H, t, J = 6.8 Hz), 1.33 (3H, t, J = 6.8 Hz), 3.34-3.44 (1H, m), 3.76-3.85
(1H, m), 4.08-4.26 (2H, m), 4.70 (1H, dd, J1 = 9.2 Hz, J2 = 21.6 Hz), 4.91 (1H, t, J = 8.8 Hz), 7.50-7.60 (3H, m),
7.88 (3H, d, J = 8.0 Hz), 8.04 (1H, d, J = 8.4 Hz).
[1-(Thiophen-2-yl)-2,2-dicyanoethyl] phosphonic acid diethyl ester (4s)11(e)
1H NMR (400MHz, CDCl3): δ = 1.23 (3H, t, J = 7.2 Hz), 1.34 (3H, t, J = 7.2 Hz), 3.95-4.01 (2H, m), 4.04-4.20
(3H, m), 4.68 (1H, d, J1 = 4.8 Hz), 7.34-7.39 (2H, m).
[1-Cyclohexyl-2,2-dicyanoethyl] phosphonic acid diethyl ester (4t)11(e)
1H NMR (400MHz, CDCl3): δ = 1.35 (6H, t, J = 7.2 Hz), 1.47 (4H, s), 1.73-1.81 (4H, m), 2.00-2.10 (2H, m),
3
3
4.09-4.29 (5H, m). 13C NMR (100MHz, CDCl3): δ = 16.29 (d, JCP = 5.5 Hz), 16.15 (d, JCP = 6.5 Hz), 24.47,
28.48, 28.77, 41.05 (d, JCP = 145.3 Hz), 61.78 (d, 2JCP = 5.5 Hz), 63.33 (d, 2JCP = 7.3 Hz), 111.20.
[1-(4-Chlorophenyl)-2-cyano-2-ethylcarboxylic acid ethyl ester] phosphonic acid diethyl ester (4u)11(h)
1H NMR (400MHz, CDCl3): δ = 1.15-1.29 (6H, m), 1.30-1.38 (3H, m), 3.95-4.24 (7H, m), 4.37 (1H, dd, J1 = 5.6
Hz, J2 = 8.8 Hz), 7.74 (2H, d, J = 7.2 Hz), 8.25 (2H, d, J = 8.4 Hz).
[1-(3-Chlorophenyl)-2-cyano-2-ethylcarboxylic acid ethyl ester] phosphonic acid diethyl ester (4v)
1H NMR (400MHz, CDCl3): δ = 1.09-1.15 (3H, m), 1.18-1.36 (6H, m), 3.78-3.87 (1H, m), 4.00-4.22 (6H, m), 4.33
(1H, dd, J1 = 1.5 Hz, J2 = 2.1 Hz), 7.29-7.33 (2H, m), 7.42-7.48 (2H, m). 13C NMR (100MHz, CDCl3): δ = 13.69,
16.08 (d, 3JCP = 4.7 Hz), 16.13 (d, 3JCP = 4.4 Hz), 39.08, 43.01 (d, JCP = 143.0 Hz), 63.31, 63.69 (d, 2JCP = 6.8 Hz),
2
63.73, 64.01 (d, JCP = 7.0 Hz), 114.52, 127.96, 128.77, 130.04, 133.58, 134.35, 163.97. 31P NMR (162 MHz,
CDCl3): δ 21.18. Anal. Calcd. for C16H21ClNO5P: C, 51.41; H, 5.66; N, 3.75. Found: C, 51.49; H, 5.73; N, 3.71.
[1-(4-Nitrophenyl)-2-cyano-2-ethylcarboxylic acid ethyl ester] phosphonic acid diethyl ester (4w)
1H NMR (400MHz, CDCl3): δ = 1.07-1.56 (3H, m), 1.19-1.37 (6H, m), 3.77-3.87 (1H, m), 4.05-4.21 (6H, m), 4.31
(1H, dd, J1 = 6.0 Hz, J2 = 8.8 Hz), 7.35 (2H, d, J = 8.0 Hz), 7.47 (2H, d, J = 6.8 Hz). 13C NMR (100MHz, CDCl3):
3
3
2
δ = 13.76, 16.06 (d, JCP = 5.9 Hz), 16.18 (d, JCP = 5.6 Hz), 39.16, 42.79 (d, JCP = 143.5 Hz), 63.15 (d, JCP = 5.6
Hz), 63.37, 63.74 (d, 2JCP = 6.9 Hz), 114.52, 114.60, 128.99, 130.70, 131.17, 134.72, 164.19. 31P NMR (162 MHz,
CDCl3): δ 21.47. Anal. Calcd. for C16H21N2O7P: C, 50.00; H, 5.51; N, 7.29. Found: C, 50.10; H, 5.58; N, 7.23.
[1-(2-Chlorophenyl)-2,2-dicyanobuthyl] phosphonic acid diethyl ester (6)21
1H NMR (400MHz, CDCl3): δ = 1.10 (3H, t, J = 7.2 Hz), 1.21-1.28 (6H, m), 1.91-2.00 (1H, m), 2.16-2.25 (1H, m),
3.82-3.92 (1H, m), 3.95-4.05 (1H, m), 4.08-4.17 (2H, m), 4.30 (1H, d, J = 23.2 Hz), 4.86 (1H, t, J = 8.8 Hz),
7.26-7.33 (2H, m), 7.41-7.43 (1H, m), 7.95 (1H, dt, J1 = 2.4 Hz, J2 = 7.2 Hz).
Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (grant no. 21302101).
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