Synthesis of Terminal Vinylphosphonates Via Dbu-Promoted Tandem Phospha-Michael/Elimination Reactions

Article abstract of DOI:10.1080/10426507.2014.906422

The terminal vinylphosphonates were prepared from various β-nitroolefins and phosphites through tandem phospha-Michael/elimination reactions. In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), a variety of new vinylphosphonates were obtained in

Full text of DOI:10.1080/10426507.2014.906422

This article was downloaded by: [Heriot-Watt University]
On: 02 January 2015, At: 10:22
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis of Terminal Vinylphosphonates
Via Dbu-Promoted Tandem Phospha-
Michael/Elimination Reactions
Hui-Xuan Chena, Lin-Jie Huanga, Jin-Biao Liua, Jiang Wenga & Gui
Luab
a Institute of Drug Synthesis and Pharmaceutical Process, School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006,
P.R. China
b Institute of Human Virology, Sun Yat-sen University, Guangzhou
510080, P.R. China
Click for updates
Accepted author version posted online: 26 Jun 2014.Published
online: 13 Dec 2014.
To cite this article: Hui-Xuan Chen, Lin-Jie Huang, Jin-Biao Liu, Jiang Weng & Gui Lu (2014)
Synthesis of Terminal Vinylphosphonates Via Dbu-Promoted Tandem Phospha-Michael/Elimination
Reactions, Phosphorus, Sulfur, and Silicon and the Related Elements, 189:12, 1858-1866, DOI:
10.1080/10426507.2014.906422
To link to this article: http://dx.doi.org/10.1080/10426507.2014.906422
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 189:1858–1866, 2014
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2014.906422
SYNTHESIS OF TERMINAL VINYLPHOSPHONATES
VIA DBU-PROMOTED TANDEM
PHOSPHA-MICHAEL/ELIMINATION REACTIONS
Hui-Xuan Chen,1 Lin-Jie Huang,1 Jin-Biao Liu,1 Jiang Weng,1
and Gui Lu1,2
1Institute of Drug Synthesis and Pharmaceutical Process, School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China
2Institute of Human Virology, Sun Yat-sen University, Guangzhou 510080, P.R.
China
GRAPHICAL ABSTRACT
Abstract The terminal vinylphosphonates were prepared from various β-nitroolefins and
phosphites through tandem phospha-Michael/elimination reactions. In the presence of 1,
8-diazabicyclo[5.4.0]undec-7-ene (DBU), a variety of new vinylphosphonates were obtained
in moderate to high yields under simple and mild condition. These new compounds were
characterized by HRMS, 1H, 13C, and 31P NMR techniques.
Keywords Vinylphosphonates; Michael addition; β-elimination
INTRODUCTION
Vinylphosphonates have received considerable attention in the past few decades both
in synthetic organic chemistry and medicinal chemistry.1 On one hand, they are versa-
tile synthetic intermediates owing to the various transformations of the vinyl group and
the phosphonate group, and have been used in miscellaneous reactions such as reduc-
tion,2 epoxidation,3 Michael addition,4 cycloaddition,5 HWE olefination,6 etc. On the other
hand, vinylphosphonates are important structural motifs frequently found in natural prod-
ucts and pharmaceutical molecules,7 such as the broad-spectrum antibiotic fosfomycin,8
the neuraminidase inhibitor tamiphosphor,9 the sphingosine kinase 1 inhibitors FTY720-
vinylphosphonate.10
Hence, several methods for the synthesis of vinylphosphonates have been devel-
oped,11 and very insightful reviews of their relative merits have also been published.1,12
Received 4 January 2014; accepted 17 March 2014.
Address correspondence to Prof. Gui Lu and Dr. Jiang Weng, Institute of Drug Synthesis and Pharmaceutical
Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China. E-mail:
lugui@mail.sysu.edu.cn (G. Lu) and wengj2@mail.sysu.edu.cn (J. Weng)
1858

TERMINAL VINYL PHOSPHONATES
1859
However, only a few methods have been reported for the synthesis of terminal vinylphos-
phonates.13–17 These classical methods are often limited by a number of drawbacks: harsh
conditions, expensive metals, limited scope, and multi-step transformation. For example,
the vinylphosphonates were prepared from phosphonite and paraformaldehyde in two steps
(Scheme 1, eq. 1)13; The transition-metal catalyzed addition reaction (eq. 2)14 and Arbuzov
reaction (eq. 3)15 suffered from high temperature; Additional esterification was required
after phosphorylation of acetylarenes with phosphorus trichloride in the presence of glacial
acetic acid (eq. 4).17 Therefore, a convenient and mild method for the preparation of terminal
vinylphosphonates is still highly desirable.
Scheme 1
With an interest in synthesizing potentially bioactive terminal vinylphosphonates, we
have been trying to find a convenient synthetic method of vinylphosphonates under mild
conditions. We envisioned that terminal vinylphosphonates could be obtained through the
tandem phospha-Michael addition/β-elimination reaction of β-nitroolefin and phosphites

1860
H.-X. CHEN ET AL.
promoted by organic base (Scheme 1). To the best of our knowledge, there are few examples
involving the synthesis of terminal vinylphosphonates through this kind of tandem reactions.
Ono and co-works synthesized 4-phosphorylchromenes from 3-nitro-chromenes and dialkyl
phosphite in the presence of triethyl amine.18 Recently, Sobhani and coworkers developed
a three-component synthesis of terminal vinylphosphonates from aldehydes, nitromethane
and trialkylphosphites through an addition-elimination sequence in ionic liquid.19 However,
the scope of these methods is limited with respect to nitroolefins and phosphites.
Herein, we report an efficient and general synthesis of terminal vinylphosphonates
through the tandem phospha-Michael addition/β-elimination reaction of β-nitroolefin and
dialkyl phosphite (or diaryl phosphite) promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU). This reaction is carried out at room temperature and completed within 0.5–1.0 h.
This method is simple, practical, and high rapid in terms of time and yield. These noteworthy
advantages make the present methodology a very valuable complement to the existing
methods available for the synthesis of terminal vinylphosphonates.
RESULTS AND DISCUSSION
We first investigated the model reaction of β-nitrostyrene with diphenyl phos-
phite in the presence of DBU in dichloromethane at ambient temperature. The reaction
proceeded smoothly to give the desired product in 83% isolated yield in less than 30
mins (Table 1, entry 1). Encouraged by this promising result, we screened several com-
mon organic and inorganic bases as triethylamine, diisopropylethylamine (DIPEA), 1,1,3,
3-tetramethyl guandine (TMG), K2CO3, NaOH and Cs2CO3, but none of them was more
efficient than DBU for the desired transformation (entries 2–7). Evaluation of the solvent
was also carried out, other solvents as MeOH, THF, toluene, and chloroform (entries 8–11)
Table 1 Optimization of reaction conditions
Entrya
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11c
12
13d
DBU
Et3N
DCM
DCM
DCM
DCM
DCM
DCM
DCM
MeOH
PhMe
THF
83
14
5
18
41
9
50
trace
46
33
45
50
64
K2CO3
Cs2CO3
DIPEA
NaOH
TMG
DBU
DBU
DBU
DBU
DBU
DCM
CHCl3
DCM
DBU
aReaction condition: 2a (0.54 mmol), 1a (0.67 mmol) base (0.67 mmol), solvent (5 mL), 30 min, r.t. bYield of
isolated product. c DBU (0.27 mmol) was used. d DBU (1 mmol) was used.

TERMINAL VINYL PHOSPHONATES
1861
gave lower yields. Reducing the DBU loading to 40 mol% led to a remarkable decrease in
the yield (entry 12), but a higher DBU loading did not improve the yield (entry 13).
Under the optimal reaction conditions, the substrate scope and limitations of our
method were investigated, the results were summarized in Table 2. In most cases, substi-
tuted β-nitrostyrene with either electron-donating or electron-withdrawing groups on the
phenyl ring were able to generate the corresponding products in good yields. The reaction
conditions were compatible with alkyl, alkoxy, and halogen groups on the phenyl ring
(Table 2, entries 1–9), while no desired product was obtained when using hydroxyl-
substituted β-nitrostyrene 2j as substrate (entry 10). Furthermore, electron-donating and
electron-withdrawing groups on the ortho position of the phenyl ring resulted in lower
yields due to steric effects (entries 3 and 7). Besides phenyl substituted β-nitroalkenes,
heteroaryl-substituted nitroalkenes, such as 2k and 2l, were also good substrates for this
reaction, and the corresponding products were obtained in good yields (74% and 75%
yield respectively, entries 11–12). However, It should also be noted that the use of alkyl-
substituted nitroalkene, such as 2n did not afford the desired product 3n (entry 14).
The reaction of β-nitrostyrene with various dialkyl phosphites (diethyl/dibutyl/
diisopropyl phosphites) was also studied. Dialkyl phosphites showed lower reactivities
than diaryl phosphite, which was demonstrated by the fact that the yield was apparently
lower than using diaryl phosphite even when prolonging the reaction time to 1 h (Table 3
vs. Table 2). Meanwhile, it was also found that the yield decreased with increasing the alkyl
chain in the dialkyl phosphites. These results demonstrated that the reactivity sequence of
phosphites spices in this reaction is diphenyl phosphite > diethyl phosphite > diisopropyl
phosphite > dibutyl phosphite. The relative reactivity of the reaction using these dialkyl
phosphites (1a–d) might be due to the drastic variation of its pKa values.20
Table 2 The substrate scope of nitrostyrene
Entrya
Product
R1
Yield (%)b
1
2
3
4
5
3a
3b
3c
3d
3e
3f
Ph
4-Me-Ph
2-MeO-Ph
3-MeO-Ph
4-MeO-Ph
4-F-Ph
83
64
59
68
62
6
61
7
8
9
10c
11
12
13
14
3g
3h
3i
3j
3k
3l
2-Cl-Ph
4-Cl-Ph
4-Br-Ph
56
57
73
NRd
74
75
29
NRd
4-OH-Ph
furan-2-yl
thiophen-2-yl
naphthalen-1-yl
i-Pr
3m
3n
aReaction condition: 1a (100 mg, 0.67 mmol), 2 (0.54 mmol), DBU (0.67 mmol), DCM (5 mL), 30 min to 1 h,
r.t. bYield of isolated product. cDBU (1.34 mmol). dNR = No Reaction

1862
H.-X. CHEN ET AL.
Table 3 The substrate scope of phosphites
Entry
product
R2
Yield
1
2
3
3o
3p
3q
Et
i-Pr
n-Bu
61
49
43
aReaction condition: 2a (0.54 mmol), 1 (0.67 mmol), DBU (0.67 mmol), DCM (5 mL), 30 min to 1 h, r.t. bYield
of isolated product.
On the basis of literatures,21 a plausible mechanism for this reaction was proposed in
Scheme 2. In the presence of DBU, conjugate addition of phosphites to nitroalkenes gives
Michael adduct II. Subsequently, the elimination of nitrous acid was promoted by DBU to
afford the desired product III.
Scheme 2
CONCLUSION
In summary, we have described a new method for the synthesis of terminal vinylphos-
phonates fromβ-nitroolefins and phosphites through tandem phospha-Michael/elimination
reactions. In the presence of DBU, a variety of new vinylphosphonates were obtained in
moderate to high yields under simple and mild condition.
EXPERIMENTAL
Unless otherwise stated, commercial reagents purchased from Alfa Aesar, Energy
and Aladdin chemical companies were used without further purification. Purification of
reaction products was carried out by flash chromatography using Qing Dao Sea Chemical
1
Reagent silica gel (200–300 mesh). H NMR spectra were recorded on a Bruker Avance
III 400 (400 MHz) spectrometer and referenced internally to the residual proton resonance
in CDCl3 (δ: = 7.26 ppm), or with tetramethylsilane (TMS, δ: = 0.00 ppm) as the internal
standard. Chemical shifts were reported as parts per million (ppm) in the δ: scale down-
field from TMS. Multiplicity is indicated as follows: s (singlet), d (doublet), t (triplet), q
(quartet), quint (quintet), m (multiplet), dd (doublet of doublet), bs (broad singlet). 13C
NMR spectra were recorded on Bruker spectrometer with complete proton decoupling, and
chemical shifts were reported in ppm from TMS with the solvent as the internal reference

TERMINAL VINYL PHOSPHONATES
1863
(CDCl3, δ: = 77.0 ppm). 31P NMR spectra were recorded on Bruker spectrometer and
chemical shifts were reported in ppm. High resolution mass was recorded on an ESI-ion
trap mass spectrometer (Shimadzu, LCMS-IT-TOF). Analytical TLC was performed using
EM separations percolated silica gel 0.2 mm layer UV 254x fluorescent sheets. Selected 1H,
13C, and 31P NMR spectra are presented in the Supplemental Materials (Figures S1–S36)
General Procedures
To a stirred solution of (E)-β-nitroalkenes (0.67 mmol) in CH2Cl2 (5 mL) was added
HPO(OR)2 (0.54 mmol) and DBU (0.67 mmol) dropwise. The mixture was stirred for
30–60 min at room temperature. The process was monitored by TLC. After the starting
material was comsumed, the solution was concentrated in vacuo. The residue was purified
by column chromatography with petroleum ether/ethyl acetate as eluent to afford the
corresponding vinylphosphonate.
Diphenyl 1-phenylvinylphosphonate (3a) 22
Diphenyl 1-p-tolylvinylphosphonate (3b). Yellow oil. 1H NMR (400 MHz, CDCl3)
δ: 7.51 (d, J = 7.6 Hz, 2H), 7.28 (t, J = 7.6 Hz, 4H), 7.21 (d, J = 7.6 Hz, 2H), 7.15 (d,
J = 6.3 Hz, 6H), 6.50 (d, J = 23.4 Hz, 1H), 6.28 (d, J = 49.9 Hz, 1H), 2.38 (s, 3H).13C
NMR (101 MHz, CDCl3) δ: 150.3, 150.2, 139.5, 138.6, 137.7, 133.7, 133.6, 133.1, 133.0,
129.7, 129.3, 127.6, 127.5, 125.1, 120.6, 120.6, 21.2. 31P NMR (162 MHz, CDCl3) δ: 10.2
(s). HRMS (ESI): m/z [M+H]+ calculated for [C21H20O3P]+: 351.1145, found: 351.1134.
Diphenyl 1-(2-methoxyphenyl)vinylphosphonate (3c). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.35–7.26 (m, 6H), 7.18-7.10 (m, 6H), 6.96 (t, J = 7.5 Hz, 1H), 6.89
(d, J = 8.1 Hz, 1H), 6.62 (dd, J = 23.6, 1.0 Hz, 1H), 6.20 (dd, J = 50.8, 1.2 Hz, 1H), 3.65
(s, 3H). 13C NMR (101 MHz, CDCl3) δ: 156.9, 156.9, 150.7, 150.7, 137.1, 136.5, 136.4,
135.3, 130.4, 130.4, 129.8, 129.8, 129.5, 125.7, 125.6, 124.8, 120.5, 120.5, 120.5, 111.0,
55.3. 31P NMR (162 MHz, CDCl3) δ: 9.0 (s). HRMS (ESI): m/z [M+H]+ calculated for
[C21H20O4P]+: 367.1094, found: 367.1086.
Diphenyl 1-(3-methoxyphenyl)vinylphosphonate (3d). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.34–7.24 (m, 5H), 7.21–7.11 (m, 8H), 6.92 (dd, J = 8.2, 1.6 Hz,
1H), 6.55 (d, J = 23.4 Hz, 1H), 6.31 (d, J = 49.5 Hz, 1H), 3.80 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ: 159.6, 150.3, 150.2, 139.6, 137.9, 137.4, 137.3, 134.6, 134.5,
129.7, 129.6, 125.2, 125.2, 120.6, 120.6, 120.2, 120.1, 114.3, 113.4, 113.3, 55.3. 31P NMR
(162 MHz, CDCl3) δ: 9.7 (s). HRMS (ESI): m/z [M+H]+ calculated for [C21H20O4P]+:
367.1094, found: 367.1087.
Diphenyl 1-(4-methoxyphenyl)vinylphosphonate (3e). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.62–7.52 (m, 2H), 7.28 (dd, J = 14.7, 6.7 Hz, 4H), 7.14 (dd, J =
6.0, 2.4 Hz, 6H), 6.93 (d, J = 8.8 Hz, 2H), 6.46 (d, J = 23.4 Hz, 1H), 6.24 (d, J = 49.9 Hz,
1H), 3.84 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 160.0, 150.3, 150.2, 138.9, 137.1, 132.,
132.8, 129.7, 129.0, 128.9, 128.3, 125.2, 120.6, 120.6, 114.0, 55.3. 31P NMR (162 MHz,
CDCl3) δ: 10.4 (s). HRMS (ESI): m/z [M+H]+ calculated for [C21H20O4P]+: 367.1094,
found: 367.1084.
Diphenyl 1-(4-fluorophenyl)vinylphosphonate (3f). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.58 (dd, J = 7.3, 5.4 Hz, 2H), 7.29 (dd, J = 15.5, 7.6 Hz, 4H),
7.21–7.04 (m, 8H), 6.54 (d, J = 23.3 Hz, 1H), 6.27 (d, J = 49.3 Hz, 1H). 13C NMR

1864
H.-X. CHEN ET AL.
(101 MHz, CDCl3) δ: 163.2, 160.8, 149.2, 149.1, 137.8, 136.0, 133.3, 133.2, 128.7, 128.6,
128.6, 128.5, 128.5, 124.2, 119.5, 119.5, 114.7, 114.5. 31P NMR (162 MHz, CDCl3) δ:
9.4 (s). HRMS (ESI): m/z [M+H]+ calculated for [C20H17O3FP]+: 355.0894, found:
355.0905.
Diphenyl 1-(2-chlorophenyl)vinylphosphonate (3g). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.50–7.40 (m, 2H), 7.27 (dd, J = 6.8, 3.0 Hz, 6H), 7.13 (d, J =
6.2 Hz, 6H), 6.81 (dd, J = 23.8, 2.9 Hz, 1H), 6.23 (dd, J = 50.5, 2.9 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ: 150.4, 150.3, 137.9, 137.8, 137.5, 135.6, 135.0, 134.9, 133.3, 133.2,
130.8, 130.8, 130.0, 129.7, 129.6, 126.5, 125.1, 120.5, 120.4. 31P NMR (162 MHz, CDCl3)
δ: 7.4 (s). HRMS (ESI): m/z [M+H]+ calculated for [C20H17O3PCl]+: 371.0598, found:
371.0593.
Diphenyl 1-(4-chlorophenyl)vinylphosphonate (3h). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.54 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.29 (t, J =
7.6 Hz, 4H), 7.15 (dd, J = 14.5, 7.5 Hz, 6H), 6.56 (d, J = 23.3 Hz, 1H), 6.29 (d, J =
49.2 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ: 150.2, 150.1, 138.8, 137.0, 134.7, 134.6,
134.6, 134.4, 129.8, 129.1, 129.0, 128.8, 125.3, 120.5, 120.5. 31P NMR (162 MHz, CDCl3)
δ: 9.1 (s). HRMS (ESI): m/z [M+H]+ calculated for [C20H17O3PCl]+: 371.0598, found:
371.0600.
Diphenyl 1-(4-bromophenyl)vinylphosphonate (3i). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.50 (dd, J = 21.8, 8.4 Hz, 4H), 7.30 (t, J = 7.8 Hz, 4H), 7.15 (dd,
J = 14.9, 7.5 Hz, 6H), 6.56 (d, J = 23.3 Hz, 1H), 6.30 (d, J = 49.2 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ: 150.2, 150.1, 138.9, 137.1, 134.8, 134.7, 131.8, 129.8, 129.4, 129.3,
125.3, 123.1, 120.5, 120.5. 31P NMR (162 MHz, CDCl3) δ: 9.0 (s). HRMS (ESI): m/z
[M+H]+ calculated for [C20H17O3PBr]+: 415.0093, found: 415.0100.
1
Diphenyl 1-(furan-2-yl)vinylphosphonate (3k). Yellow oil. H NMR (400 MHz,
CDCl3) δ: 7.45 (s, 1H), 7.34–7.24 (m, 4H), 7.23–7.12 (m, 6H), 6.87 (d, J = 3.3 Hz, 1H),
6.60–6.45 (m, 2H), 6.33 (d, J = 24.0 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ: 150.1, 150.1,
149.0, 148.7, 143.2, 129.8, 129.4, 129.1, 129.0, 128.3, 126.5, 125.4, 120.6, 120.5, 112.0,
115.4, 111.8, 111.1. 31P NMR (162 MHz, CDCl3) δ: 8.1 (s). HRMS (ESI): m/z [M+H]+
calculated for [C18H16O4P]+: 327.0781, found: 327.0744.
Diphenyl 1-(thiophen-2-yl)vinylphosphonate (3l). Yellow oil. 1H NMR (400 MHz,
CDCl3) δ: 7.55 (s, 1H), 7.30 (t, J = 7.2 Hz, 5H), 7.17 (dd, J = 12.9, 7.3 Hz, 6H), 7.08
(d, J = 3.5 Hz, 1H), 6.41 (d, J = 8.0 Hz, 1H), 6.32 (d, J = 17.2 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ: 150.2, 150.1, 138.3, 138.1, 132.6, 131.7, 131.6, 130.8, 129.7, 127.9,
127.7, 127.7, 126.2, 125.3, 120.6, 120.6. 31P NMR (162 MHz, CDCl3) δ: 8.3 (s). HRMS
(ESI): m/z [M+H]+ calculated for [C18H16O3PS]+: 343.0552, found: 343.0537.
Diphenyl 1-(naphthalen-1-yl)vinylphosphonate (3m). Yellow oil. 1H NMR
(400 MHz, CDCl3) δ: 7.97 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 7.6 Hz, 2H), 7.53–7.40 (m,
4H), 7.22 (t, J = 7.3 Hz, 4H), 7.09 (t, J = 7.2 Hz, 2H), 7.04 (d, J = 7.6 Hz, 4H), 6.96
(d, J = 23.9 Hz, 1H), 6.24 (d, J = 51.1 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ: 150.5,
150.4, 138.9, 137. 5, 137.5, 137.1, 133.8, 133.8, 133. 7, 131.7, 131.7, 129.6, 128.8, 128.8,
128.3, 126.8, 126.8, 126.3, 126.0, 125.6, 125.0, 125.0, 120.4, 120.4. 31P NMR (162 MHz,
CDCl3) δ: 8.2 (s). HRMS: C24H20O3P for [M+H]+, calcd. 387.1145, found 387.1129.
HRMS (ESI): m/z [M+H]+ calculated for [C24H20O3P]+: 387.1145, found: 387.1129.
Diethyl 1-phenylvinylphosphonate (3o) 19
Diisopropyl 1-phenylvinylphosphonate (3p) 19
.
.
Dibutyl 1-phenylvinylphosphonate (3q). Colorless oil. 1H NMR (400 MHz, CDCl3)
δ: 7.55–7.48 (m, 2H), 7.34 (q, J = 5.5 Hz, 3H), 6.33 (dd, J = 21.9, 1.3 Hz, 1H), 6.16 (dd,

TERMINAL VINYL PHOSPHONATES
1865
J = 45.7, 1.3 Hz, 1H), 4.03 (tdd, J = 10.0, 6.9, 3.3 Hz, 4H), 1.63–1.56 (m, 4H), 1.33 (dd,
J = 15.0, 7.5 Hz, 4H), 0.88 (t, J = 7.4 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ: 140.7,
138.9, 136.8, 136.7, 131.6, 131.5, 128.4, 128.2, 127.5, 127.4, 65.9, 65.9, 32.4, 32.3, 18.7,
13.5. 31P NMR (162 MHz, CDCl3) δ: 17.14 (s). HRMS (ESI): m/z [M+H]+ calculated for
[C16H26O3P]+: 297.1614, found: 297.1621.
This work was financially supported by the European Commission through the
project FP7-201431(CATAFLU.OR), the Introduction of Innovative R&D Team Program
of Guangdong Province (No. 2009010058), the Guangdong Natural Science Foundation
(No. S2013040012409) and the Fundamental Research Funds for the Central Universities
(No. 12ykpy10).
SUPPLEMENTAL MATERIAL
Supplementary data for this article can be accessed on the publisher’s website, www.
tandfonline.com/gpss
REFERENCES
1. (a) Dembitsky, V. M.; Al Quntar, A. A. A.; Haj-Yehia, A.; Srebnik, M. Mini-Rev. Org. Chem.
For reviews, see: 2005, 2, 91-109. (b) Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2008,
3601-3613. (c) Maffei, M. Curr. Org. Synth. 2004, 1, 355-375. (d) Minami, T.; Motoyoshiya, J.
Synthesis 1992, 333-349.
2. Cheruku, P.; Paptchikhine, A.; Church, T. L.; Andersson, P. G. J. Am. Chem. Soc. 2009, 131,
8285-8289.
3. Ono, Y.; Han, L-B. Tetrahedron Lett. 2006, 47, 421-424.
4. Sulzer-Mosse, S.; Tissot, M.; Alexakis, A. Org. Lett. 2007, 9, 3749-3752.
5. Rabasso, N.; Fadel, A. Tetrahedron Lett. 2010, 51, 60-63.
6. Ishikawa, H.; Honma, M.; Hayashi, Y. Angew. Chem. Int. Ed. 2011, 50, 2824-2827.
7. (a) Lu, X.; Sun, C.; Valentine, W. J.; E, S.; Liu, J.; Tigyi, G.; Bittman, R. J. Org. Chem. For
the biologically important alkenylphosphonates, see: 2009, 74, 3192-3195. (b) Kuemin, M.; van
der Donk, W. A. Chem. Commun. 2010, 46, 7694-7696. (c) Delomenede, M.; Bedos-Belval, F.;
Duran, H.; Vindis, C.; Baltas, M.; Negre-Salvayre, A. J. Med. Chem. 2008, 51, 3171-3181.
8. Giordano, C.; Castaldi, G. J. Org. Chem. 1989, 54, 1470-1473.
9. Shie, J.-J.; Fang, J.-M.; Wang, S.-Y.; Tsai, K.-C.; Cheng, Y.-S. E.; Yang, A.-S.; Hsiao, S.-C.; Su,
C.-Y.; Wong, C.-H. J. Am. Chem. Soc. 2007, 129, 11892-11893.
10. Liu, Z.; MacRitchie, N.; Pyne, S.; Pyne, N. J.; Bittman, R. Bioorg. Med. Chem. 2013, 21,
2503-2510.
11. (a) Thielges, S.; Bisseret, P.; Eustache, J. Org. Lett. 2005, 7, 681-684. (b) Quntar, A. A. A.;
Rosenthal, D.; Srebnik, M. Tetrahedron 2006, 62, 5995-5999. (c) Quntar, A. A. A.; Melman, A.;
Srebnik, M. J. Org. Chem. 2002, 67, 3769-3772. (d) Aboujaoude, E. E.; Lietje´, S.; Collignon,
N.; Teulade, M. P.; Savignac, P. Tetrahedron Lett. 1985, 26, 4435-4438. (e) Al-Quntar, A. A.
A.; Srebnik, M. J. Organomet. Chem. 2005, 690, 2504-2514. (f) Pergament, I.; Srebnik, M.
Tetrahedron Lett. 2001, 42, 8059-8062. (g) Gil, J. M.; Oh, D. Y. J. Org. Chem. 1999, 64, 2950-
2953. (h) Cristau, H. J.; Mbianda, X. Y.; Beziat, Y.; Gasc, M. B. J. Organomet. Chem. 1997, 529,
301-311. (i) Huang, X.; Xiong, Z. C. Synth. Commun. 2003, 33, 2511-2517. (j) Bhattacharya, A.
K.; Rana, K. C. Bioorg. Med. Chem. 2011, 19, 7129-7135. (k) Holt, D. A.; Erb, J. M. Tetrahedron
Lett. 1989, 30, 5393-5396. (l) Bessie`res, B.; Schoenfelder, A.; Verrat, C.; Mann, A.; Ornstein,
P.; Pedregal, C. Tetrahedron Lett. 2002, 43, 7659-7662. (m) Attolini, M.; Bouguir, F.; Iacazio,
G.; Peiffer, G.; Maffei, M. Tetrahedron 2001, 57, 537-543. (n) Rostamnia, S.; Alizadeh, A.;
Zhu, L. G. J. Comb. Chem. 2009, 11, 143-145. (o) Cristau, H. J.; Gasc, M. B.; Mbianda, X.

1866
H.-X. CHEN ET AL.
Y. J. Organomet. Chem. 1994, 474, C14-C15. (p) Evano, G.; Tadiparthi, K.; Couty, F. Chem.
Commun. 2011, 47, 179-181. (q) Blaszczyk, R.; Gajda, T. Heteroat. Chem. 2007, 18, 732-739.
(r) Gulykina, N. S.; Dolgina, T. M.; Bondarenko, G. N.; Beletskaya, I. P. Russ. J. Org. Chem.
2003, 39, 797-807. (s) Tavs, P.; Weitkamp, H. Tetrahedron 1970, 26, 5529-5534. (t) Shin, C.;
Yonezawa, Y.; Katayama, K.; Yoshimura, J. Bull. Chem. Soc. Jpn. 1973, 46, 1727-1729.
12. (a) Gaumont, A. C.; Gulea, M. In: Science of Synthesis: Houben-Weyl Methods of Molecular
Transformations, Molander, G. A. (Ed.). Thieme: Stuttgart, 2006, 33, pp. 665-694. (b) Wang,
H.-Q.; Liu, Z.-J. Chin. J. Org. Chem. 2003, 23, 321-330. (c) Minami, T.; Okauchi, T.; Kouno, R.
Synthesis 2001, 349-357.
13. (a) Krawczyk, H.; Albrecht, L.; Wojciechowski, J.; Wolf, W. M. Tetrahedron 2008, 64, 5051-
5054. (b) Biju, A. T.; Padmanaban, M.; Wurz, N. E.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50,
8412-8415.
14. (a) Ananikov, V. P.; Ivanova, J. V.; Khemchyan, L. L.; Beletskaya, I. P. Eur. J. Org. Chem. 2012,
3830-3840. (b) Goulioukina, N. S.; Dolgina, T. M.; Beletskaya, I. P.; Henry, J. C.; Lavergne, D.;
Ratovelomanana-Vidal, V.; Genet, J. P. Tetrahedron: Asymmetry 2001, 12, 319-327. (c) Han, L.
B.; Tanaka, M. J. Am. Chem. Soc. 1996, 118, 1571-1572.
15. Kalek, M.; Ziadi, A.; Stawinski, J. Org. Lett. 2008, 10, 4637-4640.
16. (a) Wang, D. Y.; Hu, X. P.; Deng, J.; Yu, S. B.; Duan, Z. C.; Zheng, Z. J. Org. Chem. 2009, 74,
4408-4410. (b) Bailey, P. L.; Jackson, R. F. W. Tetrahedron Lett. 1991, 32, 3119-3122. (c) Li, S.
N.; Xu, L. T.; Chen, Y.; Li, J. L.; He, L. Lett. Org. Chem. 2011, 8, 416-422.
17. Gulyukina, N. S.; Dolgina, T. M.; Bondarenko, G. N.; Beletskaya, I. P.; Bondarenko, N. A.;
Henry, J. -C.; Lavergne, D.; Ratovelomanana-Vidal, D.; Genet, J.-P. Russ. J. Org. Chem. 2002,
38, 573-587.
18. Ono, N.; Banshou, N.; Ito, S.; Murashima, T.; Ogawa, T. J. Heterocycl. Chem. 1997, 34, 1243-
1246.
19. Sobhani, S.; Honarmand, M. During preparation of this munascript, Sobhani and coworkers also
developed a method to synthesize terminal vinylphosphonates through a tandem reaction in ionic
liquids (5-HPAA). See: Synlett 2013, 24, 236-240.
20. Li, J.-N.; Liu, L.; Fu, Y.; Guo, Q. X. Tetrahedron For the pKa ꢁs values of different phosphorus
nucleophiles, see: 2006, 62, 4453-4462.
21. (a) Alcaine, A.; Marques-Lopez, E.; Merino, P.; Tejero, T.; Herrera, R. P. Org. Biomol. Chem.
2011, 9, 2777-2783. (b) Terada, M.; Ikehara, T.; Ube, H. J. Am. Chem. Soc. 2007, 129, 14112-
14113. (c) Ballini, R.; Rinaldi, A. Tetrahedron Lett. 1994, 35, 9247-9250. (d) Ballini, R.; Bosica,
G. Tetrahedron 1995, 51, 4213-4222. (e) Zhu, Y.; Malerich, J. P.; Rawal, V. H. Angew. Chem.
Int. Ed. 2010, 49, 153-156.
22. Nurtdinov, S. Kh.; Khairullin, R. S.; Tsivunin, V. S.; Zykova, T. V.; Kamai, G. Kh. Zh. Obsh.
Khim. 1972, 42, 123-125.