Synthesis of [1-(Dimethylamino)alkyl]phosphonates from (1-Hydroxyalkyl) phosphonates: Transformation of allylic hydroxyphosphonates into allylic aminophosphonates

Article abstract of DOI:10.1055/s-0029-1218713

A noncatalyzed reaction of (1-hydroxyalkyl)phosphonates with N,N-dimethylformamide diethyl acetal for the synthesis of novel [1-(dimethylamino)alkyl]phosphonates is described. Treatment of allylic (1-hydroxyalkyl)phosphonates with N,N-dimethylformamide diethyl acetal without any catalyst and under reflux in xylene gives novel allylic [1-(dimethylamino) alkyl]phosphonates. By using this method, a series of [1-(dimethylamino)alkyl] phosphonates was synthesized in good yields. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218713

1736
PAPER
Synthesis of [1-(Dimethylamino)alkyl]phosphonates from (1-Hydroxy-
alkyl)phosphonates: Transformation of Allylic Hydroxyphosphonates into
Allylic Aminophosphonates
(
1-Aminoalkyl)ph
a
osphonate
b
s
from (1-H
y
a
droxyalkyl
k
)phosphonate
s
Kaboudin,* Mohammad Reza Faghihi
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran
Fax +98(241)4214949; E-mail: kaboudin@iasbs.ac.ir
Received 10 February 2010; revised 17 February 2010
phonates into 1-aminophosphonates. Replacement of the
Abstract: A noncatalyzed reaction of (1-hydroxyalkyl)phospho-
nates with N,N-dimethylformamide diethyl acetal for the synthesis
of novel [1-(dimethylamino)alkyl]phosphonates is described.
Treatment of allylic (1-hydroxyalkyl)phosphonates with N,N-di-
hydroxy group in (1-hydroxyalkyl)phosphonates by an
azide group, followed by reduction, has given the amino
function by way of the Mitsunobu reaction.15 Yuan and Li
methylformamide diethyl acetal without any catalyst and under reflux have reported the conversion of (1-hydroxyalkyl)phos-
in xylene gives novel allylic [1-(dimethylamino)alkyl]phospho-
phonate into (1-hydrazinoalkyl)phosphonates by nucleo-
nates. By using this method, a series of [1-(dimethylami-
philic substitution of hydrazine by mesylated (1-
no)alkyl]phosphonates was synthesized in good yields.
hydroxyalkyl)phosphonates.16 Recently, we have reported
a novel method for the synthesis of 1-aminophosphonates
Key words: 1-aminophosphonates, 1-hydroxyphosphonates, N,N-
dimethylformamide diethyl acetal, allylic alcohols, allylic amines
by the reaction of 1-hydroxyphosphonates with amines by
means of microwave irradiation.17
N,N-Dimethylformamide dialkyl acetals have been used
Organophosphorus compounds have found a wide range
widely as alkylating agents of various compounds.18
of applications in the areas of industrial, agricultural, and
These reagents have also been reported to be efficient in
medicinal chemistry owing to their biological and physi-
some organic transformations. Recently, an efficient
cal properties as well as their utility as synthetic interme-
method for the synthesis of arylpropargyl aldehydes from
diates. a-Functionalized phosphonic acids are valuable
arylacetylenes and amide acetals was reported by Kim et
intermediates for the preparation of medicinal compounds
al.19
and synthetic intermediates.1–4 Among a-functionalized
A wide variety of allylic alcohols were transformed into
b,g-unsaturated amides when heated to approximately
160 °C with N,N-dimethylacetamide dialkyl acetals. The
proposed mechanism for this transformation appears in
Scheme 1.20 We were interested in examining the treat-
ment of allylic (1-hydroxyalkyl)phosphonates with N,N-
dimethylformamide diethyl acetal (Scheme 2).
phosphonic acids, 1-aminophosphonic acids make up an
important class of compounds that exhibit a variety of in-
teresting and useful properties. 1-Aminophosphonic acids
are important substitutes for the corresponding a-amino
acids in biological systems.5 On the other hand, methyl-
amino acids containing peptide natural products have
found clinical use, due, in part, to the physical properties
and chemical stability conferred by the methylamino
acids present in their structures.6 A number of potent anti-
biotics,7 enzyme inhibitors,8 and pharmacological agents9
are, indeed, 1-aminophosphonic acids or peptide ana-
logues.
R2
R2
OR
OR
R1
R3
140 °C
xylene
R1
R3
H
NMe2
+
O
OH
C
NMe2
These important compounds have been synthesized by
various routes: (a) the addition of a P–H function to
imines and enamines,10 (b) the addition of a P–H function
to nitriles,11 (c) Arbuzov and Michaelis–Beacker reac-
tions,12 (d) the condensation of X–NH2 with acyl phos-
phorus species,13 (e) Curtius and Hoffmann
rearrangement of substituted phosphonoacetic esters, and
(f) alkylation of nucleophilic precursors such as Schiff
bases.14 Despite this wide range of synthetic methods for
the synthesis of 1-aminophosphonates, little attempt has
been made to convert readily accessible 1-hydroxyphos-
R2
R2
O
R1
R3
R1
R3
[2,3]
O
NMe2
C:
NMe2
Scheme 1
R2
O
R2
O
OEt
OEt
R1
O
P(OEt)2
xylene
reflux
R1
P(OEt)2
H
NMe2
+
SYNTHESIS 2010, No. 10, pp 1736–1740
x
x.
x
x
.
2
0
1
0
OH
NMe2
Advanced online publication: 26.03.2010
DOI: 10.1055/s-0029-1218713; Art ID: Z03210SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

PAPER
(1-Aminoalkyl)phosphonates from (1-Hydroxyalkyl)phosphonates
1737
O
As part of our efforts in exploring novel reactions for the
synthesis of organophosphorus compounds,17,21–23 the
method we report herein is for the preparation of [1-(di-
methylamino)alkyl]phosphonates by the reactions of (1-
hydroxyalkyl)phosphonates with N,N-dimethylform-
amide diethyl acetal in the absence of any catalyst under
reflux in xylene.
OEt
OEt
O
xylene
reflux
Ph
P(OEt)2
+
H
NMe2
Ph
P(OEt)2
OH
1a
NMe2
2a
Scheme 3
3
3.44 (2JHP = 21.5 and JHH = 9.5 Hz) and 6.56 (4JHP = 2.8
and 3JHH = 15.8 Hz), along with a singlet peak at d = 2.40.
The 13C NMR spectrum exhibited a doublet peak at
d = 66.0 (JCP = 158.4 Hz) and one singlet peak at d = 43.0,
which corresponds to the resonances for the methyl
groups (NMe2). The absence of a carbonyl group in the
13C NMR spectrum also confirmed the structure of com-
pound 2a.
Treatment of diethyl (1-hydroxy-3-phenylallyl)phospho-
nate (1a), chosen as a model compound and prepared by
our previously reported method,24 was studied in the pres-
ence of N,N-dimethylformamide diethyl acetal in xylene,
and the progress of the reaction was monitored by TLC
(Scheme 3).
Treatment of 1a with N,N-dimethylformamide diethyl
acetal in xylene gave 2a in 56% yield after 18 hours under
reflux (Scheme 3). The structure of 2a was confirmed by
NMR data and elemental analysis. In the 31P NMR spec-
trum, a singlet peak appeared at d = 23.94. The 1H NMR
spectrum had two sets of doublet of doublet peaks at d =
To study the scope and limitations of the reaction, various
(3-aryl-1-hydroxyallyl)phosphonates 1 were treated with
N,N-dimethylformamide diethyl acetal in refluxing xy-
lene (Table 1). The reactions of diethyl (3-aryl-1-hy-
Table 1 Conversion of Allylic (1-Hydroxyalkyl)phosphonates 1 into Novel Allylic [1-(Dimethylamino)alkyl]phosphonates
Entry Alcohol
1
Product
Time (h)
18
Yielda (%)
31P NMR (d) of
product
O
O
1
1a
2a
2b
2c
2d
65
23.94
23.87
24.71
24.42
P(OEt)2
P(OEt)2
NMe2
OH
O
O
2
1b
1c
1d
1e
24
24
24
24
60
63
54
–
P(OEt)2
P(OEt)2
PhO
MeO
PhO
NMe2
OH
O
O
3
P(OEt)2
P(OEt)2
MeO
NMe2
OH
O
O
4
5
P(OEt)2
P(OEt)2
NMe2
OH
NO2
O
b
–
–
–
–
P(OEt)2
OH
O
P(OEt)2
b
6
1f
–
–
24
–
OH
Me2N
Me2N
O
O
7
1g
1h
3
18
24
71
–
18.87
–
P(OEt)2
P(OEt)2
NMe2
OH
O
P(OBn)2
b
8
–
–
OH
a Yield of isolated, pure product after column chromatography.
b Unknown mixture.
Synthesis 2010, No. 10, 1736–1740 © Thieme Stuttgart · New York

1738
B. Kaboudin, M. R. Faghihi
PAPER
droxyallyl)phosphonates 1a–d with N,N-dimethyl- allylic [1-(dimethylamino)alkyl]phosphonates by using
formamide diethyl acetal in refluxing xylene afforded the N,N-dimethylformamide diethyl acetal without any cata-
corresponding [3-aryl-1-(dimethylamino)allyl]phospho- lyst under reflux in xylene. By using this method, a series
nates 2a–d in good yields (entries 1–4). Treatment of [1- of [1-(dimethylamino)alkyl]phosphonates was synthe-
hydroxy-3-(o-nitrophenyl)allyl]phosphonate 1e and (1- sized in good yields. The main advantages of this protocol
hydroxy-1-methyl-3-phenylallyl)phosphonate 1f, a tertia- are that it is a simple procedure, involving easy workup,
ry allylic hydroxyphosphonate, with N,N-dimethylform- leading to good yields, and proceeds under catalyst-free
amide diethyl acetal in refluxing xylene gave mixtures of reaction conditions.
unknown products (entries 5 and 6). The reaction also
gave a mixture of unknown products when the dibenzyl
All the chemicals that were used were commercially available and
derivative of a (3-aryl-1-hydroxyallyl)phosphonate 1h
was used (entry 8). An interesting result was obtained
from the reaction of diethyl {3-[4-(dimethylamino)phe-
nyl]-1-hydroxyallyl}phosphonate (1g) with N,N-dimeth-
ylformamide diethyl acetal in refluxing xylene (entry 7):
{3-(dimethylamino)-3-[4-(dimethylamino)phenyl]prop-1-
enyl}phosphonate 3 was obtained as the major product.
distilled or recrystallized before use. NMR spectra were recorded
on a 250 Bruker Avance instrument. The chemical shift data are re-
ported relative to the solvent resonances (d = 7.26 ppm, CHCl3, 1H
NMR; d = 77.0 ppm, CDCl3, 13C NMR). Column chromatography
was carried out on silica gel 100 (Merck No. 10184). Merck silica
gel 60 F254 plates (No. 5744) were used for preparative TLC.
Allylic (1-Hydroxyalkyl)phosphonates 1; General Procedure
Allylic (1-hydroxyalkyl)phosphonates 1 were obtained according to
the method described in our previously published article.24
It has been suggested that, in the reaction of a diethyl (1-
hydroxyallyl)phosphonate 1, a trace amount of ethoxide
ion can deprotonate the (1-hydroxyalkyl)phosphonate, the
product of which is subsequently quenched by iminium
salt in the reaction mixture (Scheme 4). The product 2 is
obtained by intramolecular nucleophilic substitution of
the amine residue (Scheme 4).
Diethyl (1-Hydroxy-3-phenylallyl)phosphonate (1a)
White solid;24 mp 105 °C (n-hexane–EtOAc).
1H NMR (250 MHz, CDCl3): d = 1.22–1.38 (m, 6 H), 4.03–4.30 (m,
4 H), 4.68 (dd, J = 6.0 Hz, JHP = 12.7 Hz, 1 H), 5.22 (br, 1 H, OH),
6.27–6.38 (m, 1 H), 6.75–6.81 (m, 1 H), 7.25–7.39 (m, 5 H).
13C NMR (63 MHz, CDCl3): d = 16.5 (d, JPC = 5.7 Hz), 63.2 (d,
JPC = 6.9 Hz), 63.4 (d, JPC = 6.9 Hz), 69.4 (d, JPC = 161.0 Hz), 123.7
(d, JPC = 4.4 Hz), 126.6, 127.9, 128.6, 132.2 (d, JPC = 13.2 Hz),
136.4.
OEt
Me
H
NMe2
N C OEt +
EtO
H
Me
OEt
31P NMR (101 MHz, CDCl3–H3PO4): d = 22.32.
R2
O
R2
O
R1
P(OEt)2
Diethyl [1-Hydroxy-3-(m-phenoxyphenyl)allyl]phosphonate
(1b)
Colorless oil.
R1
P(OEt)2
NMe2
EtO
OH
R2
O
P(OEt)2
1H NMR (250 MHz, CDCl3): d = 1.22–1.40 (m, 6 H), 4.09–4.24 (m,
4 H), 4.30 (br, 1 H), 4.66 (dd, J = 6.3, 13.0 Hz, 1 H), 6.30 (dt,
J = 5.25, 10.5 Hz, 1 H), 6.74 (dd, J = 3.75, 16.0 Hz, 1 H), 6.80–7.40
(m, 9 H).
13C NMR (63 MHz, CDCl3): d = 16.4 (d, JPC = 5.7 Hz), 63.1 (d,
JPC = 6.9 Hz), 63.2 (d, JPC = 6.9 Hz), 69.2 (d, JPC = 161.0 Hz),
116.8, 118.2, 118.8 121.6, 123.3, 124.7 (d, JPC = 4.4 Hz), 129.8,
131.4, 131.5 (d, JPC = 13.2 Hz), 138.3 (d, JPC = 2.5 Hz), 157.0,
157.5.
R1
R2
O
O
R1
P(OEt)2
Me
N
C OEt
O
H
Me
Me2N
H
OEt
Scheme 4
31P NMR (101 MHz, CDCl3–H3PO4): d = 21.99.
Anal. Calcd for C19H23O5P: C, 62.96; H, 6.35. Found: C, 62.80; H,
6.30.
Treatment of diethyl [(hydroxy)(phenyl)methyl]phospho-
nate as a nonallylic 1-hydroxyphosphonate with N,N-di-
methylformamide diethyl acetal in refluxing xylene gave
a mixture of unknown products (Scheme 5).
Diethyl [1-Hydroxy-3-(m-methoxyphenyl)allyl]phosphonate
(1c)
Colorless oil.
1H NMR (250 MHz, CDCl3): d = 1.20–1.38 (m, 6 H), 3.76 (s, 3 H),
4.04–4.21 (m, 4 H), 4.54 (br, 1 H, OH), 4.65 (dd, J = 6.3, 13.5 Hz,
1 H), 6.28 (dt, J = 5.25, 15.75 Hz, 1 H), 6.72 (dd, J = 4.75, 15.5 Hz,
1 H), 6.75 (d, J = 6.75 Hz, 1 H), 6.89 (s, 1 H), 6.95 (d, J = 7.75 Hz,
1 H), 6.75 (t, J = 7.75 Hz, 1 H).
O
OEt
OEt
xylene
reflux
24 h
mixture of
unknown products
P(OEt)2
H
NMe2
+
OH
Scheme 5
13C NMR (63 MHz, CDCl3): d = 16.4 (d, JPC = 5.7 Hz), 55.1, 63.1
(d, JPC = 7.5 Hz), 63.2 (d, JPC = 7.5 Hz), 69.1 (d, JPC = 162.3 Hz),
111.9 (d, JPC = 1.9 Hz), 113.3, 119.2, 124.5 (d, JPC = 4.4 Hz), 129.5,
131.9 (d, JPC = 13.2 Hz), 137.9 (d, JPC = 2.5 Hz), 159.7.
In summary, we have presented a novel procedure for the
conversion of allylic (1-hydroxyalkyl)phosphonates into
31P NMR (101 MHz, CDCl3–H3PO4): d = 22.29.
Synthesis 2010, No. 10, 1736–1740 © Thieme Stuttgart · New York

PAPER
(1-Aminoalkyl)phosphonates from (1-Hydroxyalkyl)phosphonates
1739
Anal. Calcd for C14H21O5P: C, 55.98; H, 7.05. Found: C, 56.12; H,
7.18.
Dibenzyl (1-Hydroxy-3-phenylallyl)phosphonate (1h)
White solid; mp 138 °C (n-hexane–EtOAc).
1H NMR (250 MHz, CDCl3): d = 3.00 (br, 1 H, OH), 4.70 (dd,
J = 6.5 Hz, JHP = 12.5 Hz, 1 H), 5.05–5.30 (m, 4 H), 6.30 (dt,
J = 6.0, 16.0 Hz, 1 H), 6.65 (dd, J = 4.8, 15.8 Hz, 1 H), 7.20–7.35
(m, 15 H).
13C NMR (63 MHz, CDCl3): d = 68.5 (d, JPC = 3.1 Hz), 68.6 (d,
JPC = 3.1 Hz), 71. 4 (d, JPC = 161.7 Hz, 1 H), 123.3 (d, JPC = 4.8 Hz),
126.7, 128.1, 128.6 (d, JPC = 4.4 Hz), 128.6, 128.6, 132.3, 134.9,
136.3.
Diethyl (1-Hydroxy-2-methyl-3-phenylallyl)phosphonate (1d)
Colorless oil.
1H NMR (250 MHz, CDCl3): d = 1.29 (t, JHP = 7.5 Hz, 3 H), 1.30 (t,
JHP = 7.5 Hz, 3 H), 2.00 (d, JHP = 2.3 Hz, 3 H), 4.11–4.23 (m, 4 H),
4.54 (dd, J = 5.3 Hz, JHP = 12.3 Hz, 1 H), 4.85 (dd, J = 5.7 Hz,
JHP = 9.8 Hz, 1 H, OH), 6.67 (d, JHP = 4.5 Hz, 1 H), 7.19–7.34 (m,
5 H).
13C NMR (63 MHz, CDCl3): d = 15.4 (d, JPC = 2.1 Hz), 16.4 (d,
JPC = 5.7 Hz), 62.9 (d, JPC = 7.3 Hz), 63.2 (d, JPC = 7.3 Hz), 73.7 (d,
JPC = 157.8 Hz), 126.6, 127.8, 128.1, 128.9 (d, JPC = 2.5 Hz), 133.9
(d, JPC = 4.0 Hz), 137.3 (d, JPC = 3.0 Hz).
31P NMR (101 MHz, CDCl3–H3PO4): d = 22.67.
Anal. Calcd for C23H23O4P: C, 70.02; H, 5.88. Found: C, 69.85; H,
5.60.
31P NMR (101 MHz, CDCl3–H3PO4): d = 22.82.
[1-(Dimethylamino)allyl]phosphonates 2; General Procedure
N,N-Dimethylformamide diethyl acetal (4 mmol) was added to a
mixture of compound 1 (2 mmol) in xylene (10 mL) and the soln
was stirred for 18–24 h at reflux. Evaporation of the solvent and
chromatography (silica gel, EtOAc–n-hexane, 5:5) gave the pure
products as colorless oils. All products gave satisfactory spectral
data in accord with the assigned structures.
Anal. Calcd for C14H21O4P: C, 59.13; H, 7.45. Found: C, 59.41; H,
7.35.
Diethyl [1-Hydroxy-3-(o-nitrophenyl)allyl]phosphonate (1e)
Yellow solid; mp 99 °C (n-hexane–EtOAc).
1H NMR (250 MHz, CDCl3): d = 1.30 (t, JHP = 7.5 Hz, 3 H), 1.31 (t,
JHP = 7.5 Hz, 3 H), 4.10–4.30 (m, 4 H), 4.65–4.82 (m, 1 H), 5.20 (t,
J = 5.8 Hz, 1 H, OH), 6.31 (dt, J = 5.3, 15.7 Hz, 1 H), 7.15–7.30 (m,
1 H), 7.35–7.63 (m, 3 H), 7.87 (d, J = 7.8 Hz, 1 H).
13C NMR (63 MHz, CDCl3): d = 16.4 (d, JPC = 5.7 Hz), 63.2 (d,
JPC = 7.5 Hz), 63.6 (d, JPC = 7.5 Hz), 69.1 (d, JPC = 161.0 Hz),
124.4, 127.1 (d, JPC = 13.2 Hz), 128.2, 128.3, 128.9 (d, JPC = 2.5
Hz), 129.9 (d, JPC = 4.4 Hz), 132.1 (d, JPC = 3.1 Hz), 147.7.
Diethyl [1-(Dimethylamino)-3-phenylallyl]phosphonate (2a)
Colorless oil.
1H NMR (250 MHz, CDCl3): d = 1.17–1.30 (m, 6 H), 2.40 (s, 6 H),
3.44 (dd, J = 9.5 Hz, JHP = 21.5 Hz, 1 H), 4.00–4.18 (m, 4 H), 6.21–
6.34 (m, 1 H), 6.56 (dd, J = 2.8 Hz, JHP = 15.8 Hz, 1 H), 7.18–7.36
(m, 5 H).
13C NMR (63 MHz, CDCl3): d = 16.4, 16.5, 43.0, 62.2, 62.5, 66.0
(d, JPC = 158.4 Hz), 119.8, 126.5, 127.9, 128.6, 136.2, 136.5.
31P NMR (101 MHz, CDCl3–H3PO4): d = 21.53.
Anal. Calcd for C13H18NO6P: C, 49.51; H, 8.76; N, 4.44. Found: C,
49.32; H, 8.55; N, 4.40.
31P NMR (101 MHz, CDCl3–H3PO4): d = 23.94.
Anal. Calcd for C15H24NO3P: C, 60.58; H, 8.14; N, 4.71. Found: C,
60.35; H, 8.15; N, 4.45.
Diethyl (1-Hydroxy-1-methyl-3-phenylallyl)phosphonate (1f)
Colorless oil.
Diethyl [1-(Dimethylamino)-3-(3-phenoxyphenyl)allyl]phos-
phonate (2b)
Colorless oil.
1H NMR (250 MHz, CDCl3): d = 1.24–1.35 (m, 6 H), 1.60 (d,
JHP = 15.5 Hz, 3 H), 4.00–4.30 (m, 4 H), 4.21 (br, 1 H, OH), 6.34
(dd, J = 4.25, 16.0 Hz, 1 H), 6.78 (dd, J = 5.0, 16.0 Hz, 1 H), 7.19–
7.38 (m, 5 H).
13C NMR (63 MHz, CDCl3): d = 16.4 (d, JPC = 5.0 Hz), 23.9, 63.1
(d, JPC = 7.5 Hz), 63.4 (d, JPC = 7.5 Hz), 72.5 (d, JPC = 161.6 Hz),
126.6 (d, JPC = 1.6 Hz), 124.5, 128.5, 129.5, 129.7 (d, JPC = 10.4
Hz), 136.7 (d, JPC = 3.1 Hz).
1H NMR (250 MHz, CDCl3): d = 1.26–1.37 (m, 6 H), 2.47 (s, 6 H),
3.50 (dd, J = 9.3 Hz, JHP = 21.3 Hz, 1 H), 4.06–4.25 (m, 4 H), 6.25–
6.38 (m, 1 H), 6.60 (dd, JHP = 3.0 Hz, J = 15.8 Hz, 1 H), 6.90–7.38
(m, 9 H).
13C NMR (63 MHz, CDCl3): d = 16.5, 16.6, 43.1, 62.3, 62.5, 66.1
(d, JPC = 157.3 Hz), 117.0, 118.3, 118.9, 120.9, 121.5, 123.4, 129.8,
138.2, 157.0, 157.8.
31P NMR (101 MHz, CDCl3–H3PO4): d = 24.66.
Anal. Calcd for C14H21O4P: C, 59.13; H, 7.45. Found: C, 59.00; H,
7.28.
31P NMR (101 MHz, CDCl3–H3PO4): d = 23.87.
Anal. Calcd for C21H28NO4P: C, 64.75; H, 7.25; N, 3.60. Found: C,
64.35; H, 7.15; N, 3.40.
Diethyl {3-[p-(Dimethylamino)phenyl]-1-hydroxyallyl}phos-
phonate (1g)
Yellow solid; mp 99 °C (n-hexane–EtOAc).
Diethyl [1-(Dimethylamino)-3-(3-methoxyphenyl)allyl]phos-
phonate (2c)
Colorless oil.
1H NMR (250 MHz, DMSO-d6): d = 1.17–1.23 (m, 6 H), 2.88 (s, 6
H), 3.95–4.09 (m, 4 H), 4.46 (dd, J = 6.7 Hz, JHP = 13.5 Hz, 1 H),
5.76 (br, 1 H, OH), 5.95 (dt, J = 5.5, 15.7 Hz, 1 H), 6.54 (dd, J = 4.5,
16.0 Hz, 1 H), 6.66 (d, J = 8.5 Hz, 2 H), 7.24 (d, J = 8.5 Hz, 2 H).
13C NMR (63 MHz, DMSO-d6): d = 16.4 (d, JPC = 3.8 Hz), 38.8,
62.5 (d, JPC = 6.9 Hz), 62.8 (d, JPC = 6.9 Hz), 68.8 (d, JPC = 165.4
Hz), 112.7, 120.6 (d, JPC = 3.8 Hz), 124.5 (d, JPC = 2.5 Hz), 127.8,
132.1 (d, JPC = 13.2 Hz), 150.5.
1H NMR (250 MHz, CDCl3): d = 1.19–1.34 (m, 6 H), 2.47 (s, 6 H),
3.50 (dd, J = 9.3 Hz, JHP = 21.3 Hz, 1 H), 3.82 (s, 3 H), 4.08–4.39
(m, 4 H), 6.22–6.39 (m, 1 H), 6.82 (dd, JHP = 3.8 Hz, J = 16.0 Hz, 1
H), 6.89–7.38 (m, 4 H).
13C NMR (63 MHz, CDCl3): d = 16.5, 16.6, 41.9, 55.4, 62.3, 62.5,
66.1 (d, JPC = 158.4 Hz), 114.4, 117.7, 122.1, 123.4, 129.9, 130.2,
138.2, 155.8.
31P NMR (101 MHz, CDCl3–H3PO4): d = 22.98.
31P NMR (101 MHz, CDCl3–H3PO4): d = 24.71.
Anal. Calcd for C15H24NO4P: C, 57.48; H, 7.72; N, 4.47. Found: C,
57.35; H, 7.55; N, 4.63.
Anal. Calcd for C16H26NO4P: C, 58.69; H, 8.01; N, 4.28. Found: C,
58.55; H, 8.15; N, 4.35.
Synthesis 2010, No. 10, 1736–1740 © Thieme Stuttgart · New York

1740
B. Kaboudin, M. R. Faghihi
PAPER
Diethyl [1-(Dimethylamino)-2-methyl-3-phenylallyl]phospho-
nate (2d)
(6) Aurelio, L.; Brownlee, R. T. C.; Hughes, A. B. Chem. Rev.
2004, 104, 5823.
Colorless oil.
(7) Atherton, F. R.; Hassall, C. H.; Lambert, R. W. J. Med.
Chem. 1986, 29, 29.
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J. Med. Chem. 1989, 32, 1652.
(9) Hassal, C. H. In Antibiotics, Vol. VI; Hahn, F. E., Ed.;
Springer: Berlin, 1983, 1.
(10) (a) Kukhar, V. P.; Hudson, H. R. In Aminophosphonic and
Aminophosphinic Acids; Wiley: Chichester, 2000.
(b) Bhagat, S.; Chakraborti, A. K. J. Org. Chem. 2007, 72,
1263. (c) Kaboudin, B. Phosphorus, Sulfur Silicon Relat.
Elem. 2002, 177, 1749.
(11) Gancarz, R.; Wieczorek, J. S. Synthesis 1978, 625.
(12) Seyferth, D.; Marmor, R. S.; Hilbert, P. J. Org. Chem. 1971,
36, 1379.
(13) Worms, K. H.; Schmidt-Dunker, M. In Organic Phosphorus
Compounds, Vol. 7; Kosolapoff, G. M.; Marier, L., Eds.;
Wiley: New York, 1976, 1.
(14) Barycki, J.; Mastalerz, P.; Soroka, M. Tetrahedron Lett.
1970, 36, 3147.
(15) Gajda, T.; Matusiak, M. Synthesis 1991, 367.
(16) Yuan, C.; Li, C. Synthesis 1996, 507.
1H NMR (250 MHz, CDCl3): d = 1.26–1.35 (m, 6 H), 1.99 (d,
JHP = 2.0 Hz, 3 H), 2.78 (s, 6 H), 3.59 (d, JHP = 15.5 Hz, 1 H), 4.07–
4.22 (m, 4 H), 6.66 (d, JHP = 4.5 Hz, 1 H), 7.19–7.33 (m, 5 H).
13C NMR (63 MHz, CDCl3): d = 13.2, 16.5, 16.6, 44.8, 62.4 (d,
JPC = 6.9 Hz), 62.7 (d, JPC = 6.9 Hz), 65.9 (d, JPC = 176.1 Hz),
126.7, 128.1, 129.0, 130.1, 137.2.
31P NMR (101 MHz, CDCl3–H3PO4): d = 24.42.
Anal. Calcd for C16H26NO3P: C, 61.70; H, 8.42; N, 4.50. Found: C,
61.58; H, 8.35; N, 4.30.
Diethyl {3-(Dimethylamino)-3-[4-(dimethylamino)phe-
nyl]prop-1-enyl}phosphonate (3)
Colorless oil.
1H NMR (250 MHz, CDCl3): d = 1.23–1.31 (m, 6 H), 2.18 (s, 6 H),
2.93 (s, 6 H), 3.47–4.26 (m, 5 H), 5.81 (dd, J = 17.3 Hz, JHP = 26.5
Hz, 1 H), 6.67 (d, J = 8.8 Hz, 2 H), 6.85 (ddd, J = 8.0, 17.3 Hz,
JHP = 21.8 Hz, 1 H), 7.11 (d, J = 8.8 Hz, 2 H).
13C NMR (63 MHz, CDCl3): d = 16.5, 16.6, 43.6, 60.6, 61.6, 73.9
(d, JPC = 22.0 Hz), 112.9, 117.3 (d, JPC = 182.4 Hz), 128.00, 128.7,
150.25, 154.20.
31P NMR (101 MHz, CDCl3–H3PO4): d = 18.87.
(17) Kaboudin, B. Tetrahedron Lett. 2003, 44, 1051.
(18) Paquette, L. A. In Encyclopedia of Reagents for Organic
Synthesis; Wiley: New York, 1995, 2075–2078.
(19) Lee, K. Y.; Lee, M. J.; GowriSankar, G.; Kim, J. N.
Tetrahedron Lett. 2004, 45, 5043.
Anal. Calcd for C17H29N2O3P: C, 59.97; H, 8.59; N, 8.23. Found: C,
59.80; H, 8.63; N, 8.13.
(20) Büchi, G.; Cushman, M.; Wüest, H. J. Am. Chem. Soc. 1974,
96, 5563.
(21) Kaboudin, B.; Moradi, K. Tetrahedron Lett. 2005, 46, 2689.
(22) (a) Kaboudin, B. Chem. Lett. 2001, 880. (b) Kaboudin, B.;
Nazari, R. Tetrahedron Lett. 2001, 42, 8211. (c) Kaboudin,
B.; Nazari, R. Synth. Commun. 2001, 31, 2245.
(d) Kaboudin, B.; Balakrishna, M. S. Synth. Commun. 2001,
31, 2773. (e) Kaboudin, B.; Rahmani, A. Synthesis 2003,
2705. (f) Kaboudin, B.; Saadati, F. Synthesis 2004, 1249.
(g) Kaboudin, B.; Rahmani, A. Org. Prep. Proced. Int. 2004,
36, 82. (h) Kaboudin, B.; Moradi, K. Tetrahedron Lett.
2005, 46, 2989.
(23) (a) Kaboudin, B.; Haghighat, H. Tetrahedron Lett. 2005, 46,
7955. (b) Kaboudin, B.; Haghighat, H.; Yokomatsu, T.
J. Org. Chem. 2006, 71, 6604. (c) Kaboudin, B.; Karimi, M.
Bioorg. Med. Chem. Lett. 2006, 16, 5324. (d) Kaboudin, B.;
Farjadian, F. Beilstein J. Org. Chem. 2006, 2, 4.
(e) Yamagishi, T.; Kusano, T.; Kaboudin, B.; Yokomatsu,
T.; Sakuma, C.; Shibuya, S. Tetrahedron 2003, 59, 767.
(f) Kaboudin, B.; Haruki, T.; Yamaghishi, T.; Yokomatsu,
T. Tetrahedron 2007, 63, 8199. (g) Kaboudin, B.; Haruki,
T.; Yamagishi, T.; Yokomatsu, T. Synthesis 2007, 3226.
(h) Kaboudin, B.; Haghighat, H.; Yokomatsu, T.
Tetrahedron: Asymmetry 2008, 19, 862. (i) Kaboudin, B.;
Saadati, F. Tetrahedron Lett. 2009, 50, 1450.
(24) Sardarian, A. R.; Kaboudin, B. Synth. Commun. 1997, 27,
543.
Acknowledgment
The authors gratefully acknowledge support by the Institute for Ad-
vanced Studies in Basic Sciences (IASBS) Research Council under
grant no. G2009IASBS120.
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Synthesis 2010, No. 10, 1736–1740 © Thieme Stuttgart · New York