A simple and effective synthesis of activated vinylphosphonates from 3-methoxy-2-diethoxyphosphorylacrylate

Article abstract of DOI:10.1016/j.tetlet.2010.02.108

A facile, efficient and general one-step procedure for the synthesis of 3-substituted 2-diethoxyphosphorylacrylates from 3-methoxy-2-diethoxyphosphorylacrylate 1b and nitrogen, carbon and phosphorus nucleophiles is presented. Reaction of 1b with 3,5-dimethoxyphenol in the presence of trifluoromethanesulfonic acid yields 3-diethoxyphosphoryl-5,7-dimethoxychromen-2-one.

Full text of DOI:10.1016/j.tetlet.2010.02.108

Tetrahedron Letters 51 (2010) 2274–2276
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A simple and effective synthesis of activated vinylphosphonates
from 3-methoxy-2-diethoxyphosphorylacrylate
*
Tomasz Janecki , Anna Albrecht, Jacek F. Koszuk, Jakub Modranka, Dominika Słowak
_
´
´
Institute of Organic Chemistry, Technical University of Łódz, 90-924 Łódz, Zeromskiego 116, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile, efficient and general one-step procedure for the synthesis of 3-substituted 2-diethoxyphospho-
rylacrylates from 3-methoxy-2-diethoxyphosphorylacrylate 1b and nitrogen, carbon and phosphorus
nucleophiles is presented. Reaction of 1b with 3,5-dimethoxyphenol in the presence of trifluoromethane-
sulfonic acid yields 3-diethoxyphosphoryl-5,7-dimethoxychromen-2-one.
Received 28 December 2009
Revised 10 February 2010
Accepted 19 February 2010
Available online 23 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Vinylphosphonates are a well known class of organophosphorus
compounds which have proved to be very useful reagents in organ-
ic synthesis. They are frequently used as intermediates in the syn-
thesis of many important acyclic, carbocyclic and especially
heterocyclic compounds.1–3 They are also excellent substrates for
the synthesis of 1,2-epoxyalkylphosphonates—compounds of great
synthetic and biological significance.4 The presence of an electron-
withdrawing substituent, such as an alkoxycarbonyl group at the
Finally, reaction of 2b with guanidine hydrochloride yielded 2-
amino-5-diethoxyphosphoryl-4-hydroxypyrimidine.10 In this Let-
ter, we report that the reaction of 3-methoxy-2-diethoxyphospho-
rylacrylate (1b) with various nucleophiles proved to be an efficient
synthetic route to diverse activated vinylphosphonates.
Acrylate 1b was efficiently synthesized from ethyl diet-
hoxyphosphorylacetate, methyl formate and methyl iodide by
modifying the method described for the synthesis of 3-methoxy-
2-dimethoxyphosphorylacrylate (1a).8 Phosphorylacrylate 1b was
then tested in reactions with various nitrogen and carbon nucleo-
philes. In all cases, the corresponding crude substitution products
were purified by distillation or column chromatography to give
pure 6a–p in moderate to high yields (Table 1). Reactions with
amines proceeded smoothly in methanol or ethanol as solvent
according to the conditions given in Table 1 (entries 1–12).11 Benz-
amide, t-butyl carbamate and carbon nucleophiles also reacted
smoothly with 1b in the presence of butyllithium or sodium hy-
dride, to give products 6m–p in moderate to high yields (entries
a-position greatly enhances the synthetic utility of vinylphospho-
nates by both, facilitating Michael-type additions and enabling
further functionalization of the adduct, for example, Horner–
Wadsworth–Emmons olefination.1,3 Many synthetic methods lead-
ing to vinylphosphonates have been described so far.1–3 We
envisioned that the reaction of 3-alkoxy or 3-dimethylamino-2-
dialkoxyphosphorylacrylates 1 or 2 with nucleophiles, to yield sub-
stitution products 3 via an addition/elimination mechanism, would
have great synthetic potential as a simple and general method for
the synthesis of activated vinylphosphonates (Fig. 1). Acrylates 1
and 2 can be regarded as phosphonate analogs of alkoxymethylid-
enemalonates 45 or dimethylaminomethylidenemalonates 5,6
respectively, a well known group of organic reagents which under-
go substitution reactions with various nitrogen, sulfur, oxygen and
carbon nucleophiles, and which have proved to be excellent start-
ing materials for the synthesis of many biologically important clas-
ses of compounds, including 4-oxochromene-, 4-oxoquinoline- and
4-oxonaphthyridine-3-carboxylic acids.5–7
Surprisingly, in contrast to the wide synthetic applications of
malonates 4 and 5, only a few reactions of acrylates 1 or 2 with
nucleophiles have been reported so far. Phosphonoacrylates 1a
and 2a were employed in reactions with arylhydrazines to give
intermediate substitution products which cyclized to 2-aryl-3-hy-
droxy-4-dimethoxyphosphorylpyrazoles.8 Similar reaction of 2b
with hydrazine gave 3-hydroxy-4-diethoxyphosphorylpyrazole.9
O
O
(R1O)2P
COOR2
Nu
(R1O)2P
COOR2
X
Nu
1a R1 = R2 = Me, X = OMe
3
1
R = R2 = Me, X = NMe2
2a
2b R1 = R2 = Et, X = NMe2
ROOC
COOR
X
4 X = OR
5
X = NMe2
* Corresponding author. Tel.: +48 42 6313220; fax: +48 42 6365533.
E-mail address: tjanecki@p.lodz.pl (T. Janecki).
Figure 1. Synthesis of activated vinylphosphonates from 3-alkoxy or 3-dimethyl-
amino-2-dialkoxyphosphorylacrylates and the structures of malonates 4 and 5.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.108

T. Janecki et al. / Tetrahedron Letters 51 (2010) 2274–2276
2275
Table 1
Scope of the reaction of 1b with various nitrogen and carbon nucleophiles
O
O
O
(EtO)2P
COOEt
OMe
(EtO)2P
COOEt
COOEt
(EtO)2P
COOEt
Nu
NuH
or
COOEt
1b
6p
6a-o
Entry
Product
NuH
Conditions
Yielda (%)
E/Zb
Purification methodc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
NH3
PrNH2
EtOH/H2O, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
EtOH, rt, 20 h
71
82
89
73
72
74
70
80
75
90
76
80
75/25
65/35
70/30
60/40
70/30
>99/1
>99/1
>99/1
65/35
60/40
70/30
>99/1
50/50
40/60
70/30
—
185–190 °C/0.04 Torr
175 °C/0.5 Torr
CHCl3/acetone = 99/1
225 °C/0.4 Torr
225 °C/0.4 Torr
185–190 °C/0.5 Torr
190–200 °C/0.6 Torr
220–225 °C/0.6 Torr
215–220 °C/0.4 Torr
CHCl3
CHCl3/acetone = 98/2
CHCl3/acetone = 98/2
CHCl3/acetone = 98/2
CHCl3
CyclohexylNH2
BnNH2
PhCH(Me)NH2
Pyrrolidine
Piperidine
Morpholine
PhNH2
2-Aminopyridine
PhNHNH2
PhNHNHBoc
Ph(CO)NH2
BocNH2
(EtO)2P(O)CH2COOEt
CH2(COOEt)2
EtOH, rt, 2 h
EtOH, rt, 20 h
MeOH, reflux, 1 h
n-BuLi, THF, rt, 20 h
NaH, Et2O, rt, 16 h
NaH, THF, rt, 4 h
NaH, THF, rt, 4 h
50
36/53d
56
CHCl3/acetone = 98/2
CHCl3/acetone = 98/2
88
a
b
c
Yield of pure, isolated products based on 1b.
Determined from the 31P NMR spectrum of the crude product.
Distillation (bp/pressure) or column chromatography on silica gel (eluent).
Yield of pure E and Z isomers respectively, separated by column chromatography.
d
13–16).12 Substitution products 6a–o were obtained as pure E iso-
mers or as mixtures of E and Z isomers in the ratios shown in Table
1. Reaction with ethyl malonate (entry 16) gave allylphosphonate
6p. Vinylphosphonate 6n was separated into individual E and Z iso-
mers but no efforts were undertaken to separate the other isomeric
mixtures.
acid effectively promotes the Friedel–Crafts reaction of phenol 11
with acrylate 1b yielding intermediate phosphonate 12. Subse-
quent spontaneous lactonization and elimination of methanol
gives the final chromenone 13.
O
To explore further the reactivity of 1b, additional experiments
were performed (Scheme 1). Reaction of 1b with 2 equiv of phthal-
imide in the presence of NaH, gave adduct 7 in 75% yield, as a mix-
ture of two diastereomers in a 95:5 ratio. No substitution product
could be detected. Our efforts to eliminate methanol from this ad-
duct by heating it in toluene or xylene in the presence of acidic cat-
alysts (p-toluenesulfonic or trifluoromethanesulfonic acids) failed.
Reaction of 1b with indole (1 equiv) and NaH (1.1 equiv) afforded a
mixture of 3-indolyl-3-methoxy- and 3,3-bis(indolyl)-2-diethoxy-
phosphorylpropanoates which were difficult to separate. Interest-
ingly, the same reaction performed with two equivalents of
indole and 2.1 equiv of NaH gave bis(indolyl)propanoate 8 in 68%
yield as the only product. In turn, the reaction of 1b with 1.2 equiv
of diethyl phosphite and NaH gave adduct 9. Pleasingly, when
crude 9 was heated in toluene in the presence of p-toluenesulfonic
acid, followed by low pressure (Kugelrohr) distillation of the
solvent and volatile by-products, and further purification of the
residue by column chromatography on silica gel (CHCl3/acetone =
95:5), (E)-2,3-di(diethoxyphosphoryl)acrylate (10) was obtained
in 56% overall yield.13
O
(EtO)2P
COOEt
OMe
O
N
i
1b +
NH
O
O
7
O
(EtO)2P
COOEt
N
ii
1b +
N
N
H
8
O
(EtO)2P
COOEt
iii
1b + (EtO)2P(O)H
MeO
P(OEt)2
O
Finally, 3,5-dimethoxyphenol 11 proved to be an effective C-
nucleophile in the reaction with 1b. Initially, the reaction was per-
formed in the presence of two equivalents of methanesulfonic acid
as catalyst at room temperature. The progress of the reaction was
monitored by 31P NMR spectroscopy. Under these conditions the
reaction was very slow and conversion of 1b was only 24% after
18 days. However, we were pleased to observe that when trifluoro-
methanesulfonic acid was used as the catalyst14 the reaction was
complete in 6 days at room temperature. After purification of the
crude product, 3-diethoxyphosphorylchromen-2-one 13 was ob-
tained in 88% yield (Scheme 2).15 Clearly, trifluoromethanesulfonic
9
O
(EtO)2P
iv
COOEt
P(OEt)2
O
10
Scheme 1. Reagents and conditions: (i) phthalimide (2 equiv), NaH (2.1 equiv),
THF, rt, 16 h, 75%; (ii) indole (2 equiv), NaH (2.1 equiv), THF, rt, 16 h, 68%; (iii)
(EtO)2P(O)H (1.2 equiv), NaH (1.3 equiv), THF, À20 °C, 4 h; (iv) TsOH (0.5 equiv),
toluene, reflux, 4 h, 56%.

2276
T. Janecki et al. / Tetrahedron Letters 51 (2010) 2274–2276
OMe
OMe
O
OMe O
OMe
i
P(OEt)2
P(OEt)2
1b
+
MeO
OH
COOEt
OH
MeO
O
O
MeO
11
12
13
Scheme 2. Reagents and conditions: (i) CF3SO3H (2 equiv), CH2Cl2, rt, 6 d, 88%.
CH3CH2OC(O), (CH3CH2O)2P(O)), 3.45–3.60 (m, 4H, 2 Â H2), 3.65–3.80 (m, 4H,
2 Â H2), 3.93–4.30 (m, 6H, CH3CH2OC(O), (CH3CH2O)2P(O)), 7.43 (d, J = 15.4 Hz,
1H, H-3); 13C NMR (62.9 MHz, CDCl3): d = 12.5 (s, CH3CH2OC(O)), 14.5 (d,
J = 6.9 Hz, (CH3CH2O)2P(O)), 21.1 (s, CH2), 21.9 (s, CH2), 27.1 (s, CH2), 28.5 (s, CH2),
57.9 (s, CH3CH2OC(O)), 59.7 (d, J = 5.1 Hz, (CH3CH2O)2P(O)), 80.8 (d, J = 197.4 Hz,
C-2), 154.0 (d, J = 18.8 Hz, C-3), 163.7 (d, J = 10.1 Hz, C-1); 31P NMR (101 MHz,
CDCl3): d = 24.21; Anal. Calcd for C13H24NO6P: C, 48.60; H, 7.53. Found: C, 48.46;
H, 7.59.
The structures and stereochemistry of products 6a–p, 7–10, and
13 were confirmed by IR, 1H, 13C and 31P NMR spectroscopy as well
as by elemental analysis.
We also tested the reaction of ethyl 3-dimethylamino-2-dieth-
oxyphosphorylacrylate (2b) with several nucleophiles or pronucleo-
philes, for example, simple amines, benzamide, phthalimide, indole
and diethyl phosphite, but no advantage over the use of 1b was
found. Typically, these reactions were less effective or failed.
In conclusion, a simple, highly effective and general method for
the synthesis of b-substituted vinylphosphonates from easily acces-
sible 3-methoxy-2-diethoxyphosphorylacrylate (1b) and nitrogen,
carbon and phosphorus nucleophiles, has been demonstrated. Cur-
rently we are studying the scope of this method with respect to other
nucleophiles. Also, further studies directed towards the application
of the obtained substitution products in the synthesis of phosphoryl
substituted heterocycles are underway.
12. Typical procedure for the reactions with amides, indole, and carbon
nucleophiles: to a solution of tert-butyl carbamate (0.825 mmol, 97 mg) in
Et2O (5 mL), NaH (0.825 mmol, 20 mg) was added in one portion, under an
argon atmosphere, at 0 °C and the mixture was stirred for 1 h, at rt. After this
time, a solution of 1b (0.750 mmol, 200 mg) in Et2O (5 mL) was added at 0 °C.
The mixture was stirred for 16 h, at rt, then H2O (20 mL) was added. Extraction
with CH2Cl2 (3 Â 10 mL), drying (Na2SO4) and evaporation of the solvent gave
the crude product as a mixture of E/Z isomers in a 40/60 ratio, which was
purified by column chromatography (eluent: CHCl3) to yield pure (E)- and (Z)-
6n. Ethyl (E)-3-(tert-butoxycarbonylamino)-2-(diethoxyphosphoryl)acrylate (E)-
6n: (95 mg, 36%); oil; IR (film, cmÀ1): 1745, 1603, 1231, 1020; 1H NMR
(250 MHz, CDCl3): d = 1.31 (t, J = 7.1 Hz, 9H, CH3CH2OC(O), (CH3CH2O)2P(O)),
1.49 (s, 9H, C(CH3)3), 4.01–4.17 (m, 4H, (CH3CH2O) 2P(O)), 4.26 (q, J = 7.1 Hz,
2H, CH3CH2OC(O)), 8.16 (dd, J = 14.9 Hz, J = 12.5 Hz, 1H, @CH–NH), 10.21 (d,
J = 12.5 Hz, 1H, NH); 13C NMR (62.9 MHz, CDCl3): d = 13.8 (s, C(O)CH2CH3), 16.1
(d, J = 6.4 Hz, P(O)(OCH2CH3)2), 27.7 (s, C(CH3)3), 60.6 (s, C(O)OCH2CH3), 61.9
(d, J = 5.6 Hz, P(O)(OCH2CH3)2), 83.8 (s, C(CH3)3), 94.0 (d, J = 202.6 Hz, P(O)C@),
150.7 (s, NHC(O)O), 152.0 (d, J = 18.2 Hz, @CH–N), 167.1 (d, J = 10.6 Hz, CO2Et);
31P NMR (101 MHz, CDCl3): d = 22.04; Anal. Calcd for C14H26NO7P: C, 47.86; H,
7.46. Found: C, 47.71; H, 7.53. Ethyl (Z)-3-(tert-butoxycarbonylamino)-2-
(diethoxyphosphoryl)acrylate (Z)-6n: (140 mg, 53%); oil; IR (film, cmÀ1): 1745,
1603, 1231, 1020; 1H NMR (250 MHz, CDCl3): d = 1.29 (t, J = 7.1 Hz, 3H,
CH3CH2OC(O)), 1.33 (t, J = 7.1 Hz, 6H, (CH3CH2O)2P(O)), 1.50 (s, 9H, C(CH3)3),
4.01–4.20 (m, 4H, (CH3CH2O)2P(O)), 4.22 (q, J = 7.1 Hz, 2H, CH3CH2OC(O)), 8.64
(dd, J = 39.5 Hz, J = 12.7 Hz, 1H, @CH–NH), 10.39 (d, J = 12.7 Hz, 1H, NH); 13C
NMR (62.9 MHz, CDCl3): d = 14.0 (s, C(O)CH2CH3), 15.9 (d, J = 6.5 Hz,
P(O)(OCH2CH3)2), 27.7 (s, C(CH3)3), 60.3 (s, C(O)OCH2CH3), 62.4 (d, J = 5.4 Hz,
P(O)(OCH2CH3)2), 82.7 (s, C(CH3)3), 93.0 (d, J = 187.2 Hz, P(O)C@), 151.0 (s,
NHC(O)O), 153.0 (d, J = 4.6 Hz, @CH–N), 165.0 (d, J = 11.8 Hz, CO2Et); 31P NMR
(101 MHz, CDCl3): d = 22.87; Anal. Calcd for C14H26NO7P: C, 47.86; H, 7.46.
Found: C, 47.98; H, 7.53.
Acknowledgements
This work was financed by the Ministry of Science and Higher
Education (Project No. NN204 005736).
References and notes
1. Minami, T.; Okauchi, T.; Kouno, R. Synthesis 2001, 349.
2. Dembitsky, V. M.; Quntar, A. A. A.; Haj-Yehia, A.; Srebnik, M. Mini-Rev. Org.
Chem. 2005, 2, 91.
3. Janecki, T.; Ke˛dzia, J.; Wa˛sek, T. Synthesis 2009, 1227.
4. Iorga, B.; Eymery, F.; Savignac, P. Synthesis 1999, 207.
5. Milata, V. Aldrichim. Acta 2001, 34, 20.
6. Hermecz, I.; Kereszturi, G.; Vasvari-Debreczy, L. In Aminomethylenemalonates
and Their Use in Heterocyclic Chemistry; Katritzky, A. R., Ed.; Academic Press Inc.:
San Diego, 1992; Vol. 54.
7. Milata, V.; Claramunt, R. M.; Elguero, J.; Zalupsky, P. In Targets in Heterocyclic
Systems; Attanasi, O. A., Spinelli, D., Eds.; Italian Society of Chemistry: Rome,
2000; Vol. 4, p 167.
8. Miller, P. C.; Molyneaux, J. M. Org. Prep. Proced. Int. 1999, 31, 295.
9. Aboujaoude, E. E.; Collignon, N.; Savignac, P. Tetrahedron 1985, 41, 427.
10. Aboujaoude, E. E.; Collignon, N.; Savignac, P. Phosphorus, Sulfur Relat. Elem.
1987, 31, 231.
13. Spectral data for (E)-Ethyl 2,3-di(diethoxyphosphoryl)acrylate (10): oil, IR (film,
cmÀ1): 1732, 1598, 1254, 1013; 1H NMR (250 MHz, CDCl3): d = 1.25–1.42 (m,
15H,
CH3CH2OC(O),
2 Â (CH3CH2O)2P(O));
4.05–4.25
(m,
8H,
2 Â (CH3CH2O)2P(O)); 4.34 (q, J = 7.1 Hz, 2H, CH3CH2OC(O)); 6.82 (dd,
J = 18.4 Hz, J = 24.8 Hz, 1H, H-3); 1H NMR{31P} (CDCl3): d = 1.25–1.42 (m,
15H,
CH3CH2OC(O),
2 Â (CH3CH2O)2P(O)),
4.05–4.25
(m,
8H,
2 Â (CH3CH2O)2P(O)), 4.34 (q, J = 7.1 Hz, 2H, CH3CH2OC(O)), 6.80 (s, 1H, H-3);
13C NMR (62.9 MHz, CDCl3): d = 11.9 (s, CH3CH2OC(O)), 14.1 (d, J = 7.3 Hz,
(CH3CH2O)2P(O)), 14.2 (d, J = 6.9 Hz, (CH3CH2O)2P(O)), 60.2 (s, CH3CH2OC(O)),
60.6 (d, J = 4.5 Hz, (CH3CH2O)2P(O)), 61.4 (d, J = 4.2 Hz, (CH3CH2O)2P(O)), 133.2
(dd, J = 179.3 Hz, J = 38.8 Hz, C-2), 141.3 (dd, J = 168.5 Hz, J = 39.3 Hz, C-3),
162.3 (dd, J = 12.7 Hz, J = 2.2 Hz, C-1); 31P NMR (101 MHz, CDCl3): d = 9.91 (d,
11. General procedure for the reactions of 1b with amines: a solution of 1b (2 mmol,
532 mg) and the corresponding amine (2.2 mmol) in an appropriate solvent
(5 ml) was stirred under the conditions given in Table 1. Evaporation of the
solvent and purification (Table 1) gave 6a–l. Sample data: (E,Z)-Ethyl 3-
(benzylamino)-2-(diethoxyphosphoryl)acrylate (E,Z)-6d: (498 mg, 73%); oil; IR
(film, cmÀ1): 1656, 1609, 1213; 1H NMR (250 MHz, CDCl3):16 d = 1.28 (t,
J = 7.1 Hz, 3H, C(O)OCH2CH3), 1.31 (t, J = 7.1 Hz, 6H, P(O)(OCH2CH3)2), 3.96–
4.11 (m, 4H, P(O)(OCH2CH3)2), 4.19 (q, J = 7.1 Hz, 2H, C(O)OCH2CH3), 4.44 (d,
J = 6.2 Hz, 0.4H, NHCH2Ph (Z)-isomer), 4.47 (d, J = 6.2 Hz, 0.6H, NHCH2Ph (E)-
isomer), 7.20–7.40 (m, 5H, CAr-H), 7.81 (dd, J = 12.7 Hz, J = 13.9 Hz, 0.6H, @CH–
NH (E)-isomer), 8.19 (dd, J = 14.3 Hz, J = 37.3 Hz, 0.4 H, @CH–NH (Z)-isomer),
9.10–9.36 (m, 1H, NH); 13C NMR (62.9 MHz, CDCl3):16 d = 13.8 (s, C(O)CH2CH3
(E)-isomer), 13.9 (s, C(O)CH2CH3 (Z)-isomer), 15.6 (d, J = 6.6 Hz, P(O)(OCH2CH3)2
(Z)-isomer), 15.7 (d, J = 6.9 Hz, P(O)(OCH2CH3)2 (E)-isomer), 52.3 (s, NHCH2Ph
(Z)-isomer), 52.6 (s, NHCH2Ph (E)-isomer), 58.9 (s, C(O)OCH2CH3), 60.9 (d,
J = 5.2 Hz, P(O)(OCH2CH3)2 (E)-isomer), 61.2 (d, J = 5.0 Hz, P(O)(OCH2CH3)2 (Z)-
isomer), 79.3 (d, J = 194.0 Hz, P(O)C = (Z)-isomer), 80.8 (d, J = 208.0 Hz,
P(O)C = (E)-isomer), 126.5 (s, C2Ar (Z)-isomer), 126.7 (s, C2Ar (E)-isomer), 127.0
(s, C4Ar (Z)-isomer), 127.2 (s, C4Ar (E)-isomer), 127.4 (s, C3Ar (Z)-isomer), 128.3 (s,
C3Ar (E)-isomer), 136.3 (s, C1Ar (E)-isomer), 136.5 (s, C1Ar (Z)-isomer), 161.5 (d,
J = 18.2 Hz, @CH–N(E)-isomer), 161.9(d, J = 8.6 Hz, @CH–N(Z)-isomer), 166.7(d,
J = 11.7 Hz, CO2Et (Z)-isomer), 168.2 (d, J = 10.5 Hz, CO2Et (E)-isomer); 31P NMR
(101 MHz, CDCl3):16 (E)-isomer d = 22.04, (Z)-isomer d = 22.87. Anal. Calcd for
C16H24NO5P: C, 56.30; H, 7.09. Found: C, 56.16; H, 7.18. (E)-Ethyl 2-
(diethoxyphosphoryl)-3-morpholinoacrylate (E)-6h: (514 mg, 80%); oil; IR (film,
cmÀ1): 1679, 1586, 1273, 1020; 1H NMR (250 MHz, CDCl3): d = 1.21–1.50 (m, 9H,
3JP-P = 10.3 Hz, P); 10.73 (d, JP–P = 10.3 Hz, P); Anal. Calcd for C13H26O8P2: C,
3
41.94; H, 7.04. Found: C, 41.87; H, 7.18.
14. Krawczyk, H.; Albrecht, Ł.; Wojciechowski, J.; Wolf, W. M. Tetrahedron 2007, 63,
12583.
15. 3-Diethoxyphosphoryl-5,7-dimethoxy-2H-chromen-2-one (13): To a solution of
1b (0.750 mmol, 20 mg) and 3,5-dimethoxyphenol (11) (0.820 mmol, 102 mg)
in CH2Cl2 (5 mL), TfOH (0.750 mmol, 113 mg) was added in one portion. The
mixture was stirred for 6 d at rt. Next, a saturated solution of NaHCO3 (10 mL)
was added. Extraction with CH2Cl2 (3 Â 10 mL), drying (Na2SO4) and
evaporation of the solvent gave
a crude product, which was purified by
crystallization from Et2O to yield pure 13 (226 mg, 88%) as orange crystals, mp
97 °C (Et2O); IR (film, cmÀ1): 1732, 1600, 1256, 1136, 1032, 784; 1H NMR
(250 MHz, CDCl3): d = 1.35–1.50 (m, 6H, (CH3CH2O)2P(O)), 3.88 (s, 3H, CH3O),
3.91 (s, 3H, CH3O), 4.00–4.45 (m, 4H, (CH3CH2O)2P(O)), 6.20–6.50 (m, 2H,
2 Â CH-Ar), 8.77 (d, J = 17.4 Hz, 1H, H-3); 13C NMR (62.9, MHz, CDCl3):
d = 16.15 (d, J = 6.3 Hz, (CH3CH2O)2P(O)), 55.83 (s, CH3O), 55.90 (s, CH3O),
62.77 (d, J = 5.8 Hz, (CH3CH2O)2P(O)), 92.57 (s, 2 Â C-Ar), 94.75 (s, 2 Â C-Ar),
103.40 (d, J = 14.3 Hz, C-4), 110.05 (d, J = 200.8 Hz, C-3), 148.64 (d, J = 8.2 Hz, C-
2), 158.15 (s, C-Ar), 165.97 (s, C-Ar); 31P NMR (101 MHz, CDCl3): d = 13.39;
Anal. Calcd for C15H19O7P: C, 52.64; H, 5.60. Found: C, 52.32; H, 5.74.
16. Values for specific isomers were obtained from the spectra of the mixture of
isomers.